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abstract: 'We examine the conditions under which a signed graph contains an edge or a vertex that is contained in a unique negative circle or a unique positive circle. For an edge in a unique signed circle, the positive and negative case require the same structure on the underlying graph, but the requirements on the signature are different. We characterize the structure of the underlying graph necessary to support such an edge in terms of bridges of a circle. We then use the results from the edge version of the problem to help solve the vertex version.'
address: 'Department of Mathematics, Binghamton University, Binghamton, NY 13902'
author:
- Richard Behr
title: Edges and Vertices in a Unique Signed Circle in a Signed Graph
---
signed graph ,balance ,negative circle ,positive circle ,bridge
Introduction {#introduction .unnumbered}
============
A *signed graph* is a graph in which each edge is assigned either a positive or negative sign. The sign of a circle (a connected, $2$-regular subgraph) in a signed graph is defined to be the product of the signs of its edges. In many cases, the most important feature of a signed graph is the sign of each of its circles. A signed graph that contains no negative circle is said to be *balanced*, while a signed graph that contains at least one negative circle is *unbalanced*. The purpose of this paper is to determine when a signed graph contains an edge or a vertex that is contained in a unique negative circle or a unique positive circle.
Signed graphs were invented by Harary in 1953 in order to help study a question in social psychology [@harary]. In 1956, Harary observed that an edge of a signed graph lies in some negative circle if and only if the block (maximal $2$-connected subgraph) containing it is unbalanced [@harary2]. Similarly, an edge lies in some positive circle if and only if it is not a balancing edge in its block (see Lemma \[negativebalance\]). Our problem is related to these facts, but the added uniqueness condition creates many additional restrictions on both the structure of the underlying graph and the signature.
Definitions
===========
Graphs
------
A *graph* $G = (V(G),E(G))$ consists of a finite vertex set $V(G)$ and finite edge set $E(G)$. Each edge has a pair of vertices as its *endpoints*, and we write $e{:}uv$ for an edge with endpoints $u$ and $v$. A *link* is an edge with two distinct endpoints, and a *loop* has two equal endpoints. We write $K_n$ for the complete graph on $n$ vertices.
Let $H$ be a subgraph of $G$. Then for $v \in V(G)$, the *degree of* $v$ *in* $H$, denoted $\deg_H(v)$, is the number of edges in $H$ that are incident with $v$ (a loop counts twice).
A *circle* $C$ is a connected $2$-regular subgraph. An edge $e \in E(G){\setminus}E(C)$ connecting two different vertices of $C$ is a *chord*.
A *path* $P=v_0,e_0,v_1,e_1,...,e_{n-1},v_n$ is a sequence of adjacent vertices and connecting edges that never repeats an edge or a vertex. We call $v_0$ and $v_n$ the *endpoints* of $P$, while the other vertices are *interior vertices*.
We *subdivide* an edge by replacing it with a path that has at least one edge. A *subdivision* of $G$ is a graph obtained by subdividing some of the edges of $G$.
Given a circle $C$ of $G$, a *bridge* of $C$ is either a connected component $D$ of $G{\setminus}V(C)$ along with all edges joining $D$ to $C$, or a chord of $C$. The *vertices of attachment* of a bridge $D$ are the vertices in $V(D) \cap V(C)$. A path contained in $D$ that has different vertices of attachment for its endpoints is a *path through $D$*.
A *cutpoint* of $G$ is a vertex $v$ with the property that there exist subgraphs $H_1$ and $H_2$ each with at least one edge, such that $G=H_1 \cup H_2$ and $H_1 \cap H_2 = \{v\}$. An *isthmus* is an edge whose removal increases the number of connected components. A *block* of $G$ is a maximal subgraph that contains no cutpoint. Each edge is contained in exactly one block.
Signed Graphs
-------------
A *signed graph* $\Sigma$ is a pair $(G, \sigma)$, where $G$ is a graph (called the *underlying graph*), and $\sigma : V(G) \rightarrow \{+,-\}$ is the *signature*.
The *sign* of a circle $C$ in $\Sigma$ is defined to be the product of the signs of its edges. Thus, a signed circle can be either positive or negative. A signed graph is *balanced* if all of its circles are positive, and *unbalanced* if it contains at least one negative circle.
A *theta graph* consists of three paths with the same endpoints and no other vertices in common. The most useful thing about theta graphs in our context is the *theta property*: every signed theta graph has either $1$ or $3$ positive circles. If two circles $C_1$ and $C_2$ intersect in a path with at least one edge, then $C_1 \cup C_2$ is a theta graph with third circle $C_1 \Delta C_2$ (we use $\Delta$ for symmetric difference). By the theta property, if $C_1$ and $C_2$ have the same sign then $C_1 \Delta C_2$ is positive, and otherwise $C_1 \Delta C_2$ is negative.
A *switching function* on $\Sigma=(G,\sigma)$ is a function $\zeta : V(G) \rightarrow \{+,-\}$. We can use $\zeta$ to modify $\sigma$, obtaining a new signature given by $\sigma^{\zeta}(e):=\zeta(v) \sigma(e) \zeta(w)$, where $v,w$ are the endpoints of $e$. The switched signed graph is written $\Sigma^{\zeta}:=(G,\sigma^{\zeta})$. If $\Sigma '$ is obtained from $\Sigma$ via switching, we say $\Sigma'$ and $\Sigma$ are *switching equivalent*, written $\Sigma' \sim \Sigma$. Switching is useful for us because of the following fact.
\[sw2\]Let $\Sigma_1$ and $\Sigma_2$ be signed graphs on the same underlying graph. Then, $\Sigma_1 \sim \Sigma_2$ if and only if $\Sigma_1$ and $\Sigma_2$ have the same collection of positive circles. In particular, $\Sigma$ is balanced if and only if it switches to an all-positive signature.
If $\Sigma$ can be switched so that it has a single negative edge $b$, we call $b$ a *balancing edge*. The deletion of a balancing edge yields a balanced signed graph. Moreover, if $b$ is a balancing edge, the negative circles of $\Sigma$ are precisely those that contain $b$.
Assume an edge $e$ is contained in at least one circle. Then $e$ is contained in only positive circles if and only if the block containing it is balanced, and $e$ is contained in only negative circles if and only if it is a balancing edge in its block (Lemma \[negativebalance\]). In other words, $e$ is contained in some negative circle if and only if the block containing $e$ is unbalanced (as discovered by Harary [@harary2]), and $e$ is contained in some positive circle if and only if $e$ is not balancing in the block containing it.
Batteries
=========
Let us give a name to the main object of study in this paper. A *battery* is an edge of $\Sigma$ that is contained in a unique negative or positive circle $C$. An edge $e$ may be a *negative battery* or a *positive battery*, depending on the sign of $C$. We write $[e,C,-]$ for a negative battery $e$ that is contained in the unique negative circle $C$, and similarly $[e,C,+]$ for a positive battery. The advantage of this notation is that it enables us to keep track of both $C$ and its sign.
We wish to determine when a given edge $e$ is a battery. This problem is uninteresting when $e$ is an isthmus of $\Sigma$ ($e$ is not contained in a circle), so throughout we assume $e$ is contained in at least one circle. Since the block $B$ containing $e$ is the union of all circles containing $e$, we will focus only on $B$. If $B$ consists of a single circle, it is trivially true that all edges of $B$ are batteries. Thus, for the rest of this section we assume that the underlying graph of $\Sigma$ is a block $B$ containing $e$ such that $B$ is neither an isthmus, nor a circle.
Layering
--------
In this section we introduce the structure of the underlying block $B$ that is necessary for $e$ to be a battery.
First, we need some terminology to help describe the chords of a circle $C$. We say that chords $c_1$ and $c_2$ of $C$ *cross* if $C \cup c_1 \cup c_2$ is a subdivision of $K_4$. Chords that do not cross are *noncrossing*. Let $\mathcal{E}$ be the set of all vertices of $C$ that are endpoints of some chord of $C$. The vertices of $\mathcal{E}$ partition $C$ into paths, called *segments*. A segment of $C$ whose endpoints have a chord between them is called a *handle*. We say that $C$ is *$2$-handled* if any two of its chords are noncrossing and it contains exactly two handles. Thus, the property of being $2$-handled is a stronger version of having noncrossing chords (noncrossing chords may create many handles). If $C$ is $2$-handled, edges $e$ and $f$ contained in separate handles are said to be *separated*.
We will now define the appropriate structure on $B$, and then explain how to reduce this structure to a $2$-handled circle. Let $C$ be a circle of $B$, and suppose every bridge of $C$ has exactly two vertices of attachment. The graph obtained by replacing each of these bridges with a single chord between its vertices of attachment is denoted $C^*$. If $C^*$ is $2$-handled, we say that $B$ is *$C$-layered*. See Figure \[f1\] for an example of a $C$-layered graph.
![On the left, we have a $C$-layered graph. On the right, we have replaced all bridges of $C$ with chords to obtain the $2$-handled circle $C^*$. In each picture, the handles are labeled $H_1$ and $H_2$, while the other $4$ segments of $C$ are unlabeled. \[f1\]](UNEa)
Assuming that each bridge of $C$ has two vertices of attachment, it is extremely convenient to use $C^*$ to deduce things about $B$. For example, suppose $C^*$ has a theta graph containing chords $c_1$, $c_2$, and $c_3$, and suppose $c_1$, $c_2$, and $c_3$ correspond to the bridges $D_1$, $D_2$, and $D_3$. Then, we can deduce that $B$ contains at least one theta graph whose three constituent paths go through $D_1$,$D_2$, and $D_3$ (this occurs in Figure \[f1\]—pick any three chords). The following lemma makes this example concrete.
\[subd\] Let $H$ be a subgraph of $C^*$. Then, $B$ contains a subdivision of $H$.
To obtain the subdivision of $H$ in $B$, first take $H \cap C$. Then, for each chord in $H$, take a path through the corresponding bridge.
We will frequently make use of Lemma \[subd\] by finding configurations of circles in $C^*$ and then pulling them up to $B$.
Negative and Positive Batteries
-------------------------------
We are now ready to describe when a certain fixed edge is a battery. As a reminder, we assume that $\Sigma=(B, \sigma)$ is a signed graph such that $B$ is a block that is not an isthmus, nor circle. Also, $e$ is an edge of $\Sigma$, and $C$ is a circle containing $e$. Our main theorem concerning edge batteries is as follows.
\[battery1\] The edge $e$ is a battery if and only if $B$ is $C$-layered, $e$ is contained in a handle of $C$, and either:
1. The other handle of $C$ contains a balancing edge, in which case $[e,C,-]$ is a negative battery.
2. Every path through a bridge of $C$ makes a negative circle with either half of $C$, in which case $[e,C,+]$ is a positive battery.
First, we need a lemma. The author thanks Thomas Zaslavsky for suggesting this lemma, which helps simply our proof method.
\[tomk4\] Every edge in a signed subdivision of $K_4$ lies in an even number of negative circles and an even number of positive circles.
Let $\Sigma$ be a signed subdivision of $K_4$, and let $e$ be an edge of $\Sigma$. Then, $e$ is contained in exactly four circles, denoted $C_1, C_2, C_3$, and $C_4$. The labeling is chosen so that $C_1 \Delta C_2 = C_3 \Delta C_4$. If $C_1 \Delta C_2$ is a positive circle, then $C_1$ and $C_2$ must have the same sign, as well as $C_3$ and $C_4$ (here we are using the theta property). If $C_1 \Delta C_2$ is a negative circle, then $C_1$ and $C_2$ have different signs, as do $C_3$ and $C_4$. In either case, there are an even number of both positive and negative circles containing $e$.
The reverse direction of the proof is easy. If $B$ is $C$-layered and $e$ is contained in a handle, then clearly either of the two signature properties listed imply that $e$ is a negative or positive battery respectively.
It remains to show the forward direction. Suppose $e$ is a battery contained in the unique signed circle $C$. If there exists some bridge $D$ of $C$ that has three or more vertices of attachment, then $D \cup C$ contains a subdivision of $K_4$ (containing all of $C$). By Lemma \[tomk4\], $e$ is contained in at least two circles that have the same sign as $C$ in this subdivision—impossible by assumption that $e$ is a battery in $C$. Thus, each bridge of $C$ must have precisely $2$ vertices of attachment (they can’t have $1$, since $G$ is a block).
Replace each bridge of $C$ with a single chord between its vertices of attachment to form $C^*$. We will find configurations of circles in $C^*$ and repeatedly use Lemma \[subd\] without mention to pull them up to $B$. If $C$ has two chords $c_1$ and $c_2$ that are crossing, then $C \cup c_1 \cup c_2$ is a subdivision of $K_4$ containing $C$, once again impossible by Lemma \[tomk4\]. So we assume that $C^*$ is a circle with noncrossing chords. Now we want to prove that $C$ has exactly two handles and that $e$ must be in one of them.
First, suppose that $e$ is contained in a segment of $C$ that is not a handle. Thus, the segment of $C$ containing $e$ meets two different chords at its endpoints, $c_1$ and $c_2$. Consider $C \cup c_1 \cup c_2$. This graph has six circles, denoted $C, C_1, C_2, C_3, C_4$, and $C_5$. We choose the labeling so that $e \in C,C_3,C_4,C_5$ and $C_1 \Delta C_2 \Delta C_3 = C$ and $C_2 \Delta C_3 = C_4$, and $C_1 \Delta C_3 = C_5$. This situation is illustrated in Figure \[f2\]. If $C$ is negative, then $C_3$, $C_4$, and $C_5$ must be positive (they contain $e$). Since $C_3 \Delta C_5 = C_1$ and $C_4 \Delta C_5 =C_2$, both $C_1$ and $C_2$ are positive. This implies that $C=C_1 \Delta C_2 \Delta C_3$ is positive, a contradiction. Similarly, if $C$ is positive, then $C_3$, $C_4$ and $C_5$ are negative. This implies that $C_1$ and $C_2$ are positive, but then $C_1 \Delta C_4 =C$ implies that $C$ is negative, a contradiction. Thus, this case is impossible—$e$ must be contained in a handle.
![The edge $e$ is not contained in a handle of $C$. The circles $C_2 \Delta C_3 = C_4$, and $C_1 \Delta C_3 = C_5$ are not labeled. \[f2\]](UNEc)
Now, we have $C^*$ with non-crossing chords and we know $e$ is in a handle of $C$. All that remains is to show that there are exactly two handles. Suppose there are (at least) three handles, and let their corresponding chords be $c_1$, $c_2$, and $c_3$. Each handle along with its chord forms a circle, and we denote these $C_1$, $C_2$, and $C_3$, respectively. We choose labeling so that $e \in C_1$, and we write $C_4:= C \Delta C_1 \Delta C_2 \Delta C_3$. This situation is illustrated in Figure \[f3\]. If $C$ is negative, then $C_1$ and $C_1 \Delta C_4$ and $C_1 \Delta C_4 \Delta C_3$ are positive, which means $C_3$ (and similarly $C_2$) are positive. However, $(C_1 \Delta C_4 \Delta C_3) \Delta C_2 = C$ which implies that $C$ is positive, a contradiction. Similarly, if $C$ is positive then $C_1 \Delta C_4 \Delta C_3$ is negative and $C_2$ and $C_3$ must again be positive. Therefore, the equality $(C_1 \Delta C_4 \Delta C_3) \Delta C_2 = C$ contradicts the fact that $C$ is positive. Consequently, there must be no more than two handles present. Note that under the assumption that $B$ is not a single circle, less than two handles are also impossible.
![The edge $e$ is contained in a handle, and there are two other handles. \[f3\]](UNEd)
Now that we have confirmed the structure of $B$, we will examine the signature of $\Sigma$. We break this into two cases. First, suppose $C$ is negative (so that $e$ is a negative battery). Delete the handle of $C$ not containing $e$ (denoted $H$), destroying the only negative circle containing $e$. The resulting $\Sigma {\setminus} H$ is still a block (clearly deleting a handle from a $C$-layered graph with at least one bridge does not create a cutpoint), and hence balanced (it contains $e$). Thus, we can switch $\Sigma$ so that the only negative edge is contained in $H$ (Lemma \[sw2\]). This is the balancing edge described in the theorem.
If $C$ is positive, we observe that every path through a bridge of $C$ between its vertices of attachment makes a negative circle with either half of $C$. To see this, it is convenient to switch $\Sigma$ so that $C$ is all-positive. Then, any path through a bridge of $C$ between vertices of attachment must have a negative sign, otherwise this path along with $C$ forms an all-positive theta graph containing $e$ (and hence two positive circles containing $e$).
Consider a negative battery $[e,C,-]$ separated from a balancing edge $b$, and let $H$ be the handle containing $b$. Clearly, every edge in $H$ is a balancing edge. Moreover, no edge outside of $H$ is a balancing edge. This is because $G {\setminus} H$ is a block, and thus $e$ is contained in a circle besides $C$ with any given edge in $G{\setminus}H$. Thus we call $H$ the *balancing handle*, since it contains all balancing edges of $\Sigma$. The presence of a single negative battery fixes $H$, and as a consequence, we are able to describe the location of all other negative batteries at the same time.
\[allbat\] Suppose $\Sigma$ has a negative battery $[e,C,-]$ separated from a balancing handle $H$. Let $f$ be an edge contained in $\Sigma{\setminus}C$ and let $D$ be the bridge of $C$ containing $f$. Then $f$ is a negative battery if and only if there is exactly one path through $D$ that contains $f$.
If $f$ is a negative battery there must only be one path through $D$ containing it, since each path through $D$ can be extended to a circle containing $H$. Conversely, if there is exactly one path through $D$ that contains $f$, this path extends uniquely to a circle containing $H$.
![Here, $H$ is the balancing handle. The batteries are labeled $e_1,...,e_8$. Each battery outside of $C$ is contained in a unique path through the bridge containing it. Notice that $G$ is $C$-layered with respect to any circle $C$ that contains a negative battery. \[f4\]](UNEb)
Theorem \[allbat\] is illustrated in Figure \[f4\]. As seen in the figure, the presence of a negative battery allows for the presence of many other negative batteries. Interestingly, the presence of a positive battery severely restricts the possible locations of other positive batteries.
As an easy application of Theorem \[battery1\] we notice that if $[e,C,+]$ is a positive battery, every edge contained in either handle of $C$ is a positive battery, and no other edge of $C$ is a positive battery. We will now study edges that are contained in $\Sigma{\setminus}C$.
\[balbridge\] If $[e,C,+]$ is a positive battery and $D$ is a bridge of $C$, then $D$ is balanced.
Suppose $A$ is a negative circle contained in $D$. Let $P_0$ be a path through $D$ that intersects $A$ in a path $A_0$ with at least one edge. Then, define $A_1$ so that $A = A_0 \cup A_1$. Since $A$ is negative, $A_0$ and $A_1$ have opposite sign. Define $P_1$ to be the path obtained by replacing $A_0$ with $A_1$ in $P_0$. Then, $P_0$ and $P_1$ have opposite sign—impossible by Theorem \[battery1\].
\[3bridge\] Suppose $[e,C,+]$ is a positive battery. If $C$ has 3 or more bridges, no edge outside of $C$ is a positive battery.
Let $f$ be an edge of $\Sigma$ not contained in $C$. Since $[e,C,+]$ is a positive battery, $\Sigma$ is $C$-layered and hence all bridges of $C$ have two vertices of attachment and are pairwise non-crossing. Let $D_1, D_2$, and $D_3$ be three bridges of $C$ with labeling chosen so that $f \in D_1$. For convenience, we switch $\Sigma$ so that $C$ is all-positive. By Theorem \[battery1\], performing this switch makes all paths through $D_1, D_2$, and $D_3$ negative. Let $P_1$ be such a path through $D_1$ that contains $f$, and let $P_2$ and $P_3$ be paths through $D_2$ and $D_3$ respectively. Then, $P_1$ and $P_2$, together with two (possibly trivial) paths through $C$ between the vertices of attachment of $D_1$ and $D_2$, form a positive circle containing $f$. Similarly, $P_1$ and $P_3$ are contained in a positive circle containing $f$. Thus, we have found two positive circles containing $f$—it is not a positive battery.
If $C$ has less than $3$ bridges it is possible to have positive batteries outside of $C$, though specific types of bridges are required.
\[2bridge\] Suppose $[e,C,+]$ is a positive battery and $C$ has exactly $2$ bridges. If both bridges are paths, every edge contained in either bridge is a positive battery. Otherwise, no edge in either bridge is a positive battery.
Let $D_1$ and $D_2$ be the bridges of $C$. Once again we switch so that $C$ is all-positive. If $D_1$ and $D_2$ are paths, then they are negative paths by Theorem \[battery1\]. In this case, $D_1$ and $D_2$ along with the (possibly trivial) paths in $C$ between their vertices of attachment form a positive circle. The fact that this is the only positive circle containing $D_1$ and $D_2$ is a matter of inspection.
Now, suppose that one of the bridges, say $D_1$, is not a path. Since we are working within a block, $D_1$ must contain a circle $A$. By Lemma \[balbridge\], $A$ is a positive circle. As in the proof of Lemma \[balbridge\], let $P_0$ be a path through $D_1$ that intersects $A$ in a path $A_0$ that contains at least one edge. Define $A_1$ so that $A = A_0 \cup A_1$. Let $P_1$ be the path obtained by replacing $A_0$ with $A_1$ in $P_0$. Let $P_2$ be a path through $D_2$. Then, $P_0, P_1$, and $P_2$ along with the appropriate paths through $C$ form a theta graph with three positive circles, forcing every edge in $P_0, P_1$ and $P_2$ to be in at least $2$ positive circles. Clearly for any edge $f$ outside of $C$, a choice of $P_0,P_1$, and $P_2$ can be found containing $f$.
Finally, we investigate the case where $C$ has only one bridge.
Suppose $[e,C,+]$ is a positive battery and $C$ has exactly $1$ bridge $D$. An edge $f$ of $D$ is a positive battery if and only if it is contained in a single circle in $D$.
Since $D$ is balanced (Lemma \[balbridge\]), any positive battery contained in $D$ is contained in a single circle in $D$. In the other direction, suppose $f$ is contained in a single (positive) circle in $D$. Then, any other circle containing $f$ must consist of a path through $D$ and a path through $C$. This will form a negative circle by Theorem \[battery1\].
Vertex Batteries {#sec3}
================
Now let us examine a similar question to the one discussed in the previous section—when does a vertex of $\Sigma$ lie in a unique signed circle $C$? We will call such a vertex a *vertex battery*, written $[v,C,-]$ or $[v,C,+]$ for the negative and positive varieties, respectively. We cannot assume that $G$ is a block, since a vertex, unlike an edge, may be contained in many blocks at once (if the vertex is a cutpoint). However, an acyclic block is of no interest to us. Thus, for the rest of this section we assume that every block containing $v$ contains a circle.
First, we will study the problem of determining if $v$ is a negative vertex battery. It is clear that if $v$ is a negative vertex battery, it is contained in one and only one unbalanced block $B$. Moreover, there is a restriction on $\deg_B(v)$, the degree of $v$ in $B$.
\[vertdeg\] Let $B$ be an unbalanced block of $\Sigma$. If $\deg_B(v) \geq 3$, then $v$ is not a negative vertex battery.
Certainly $v$ is contained in some negative circle $C$ in $B$. Thus, consider the two edges incident to $v$, say $e_1$ and $e_2$, that are contained in $C$. There is a third edge $e_3 \in B$ incident with $v$, and therefore there must be some theta graph $\Theta \subseteq B$ such that $C \subset \Theta$ and also $e_3 \in \Theta$. Therefore, $v$ is contained in all three circles of $\Theta$. Since $C$ is negative, $\Theta$ contains an additional negative circle which contains $v$.
Assuming $v$ is a negative vertex battery, let $B$ be the single unbalanced block containing $v$, and let $C$ be the negative circle of $B$ containing $v$. By Lemma \[vertdeg\], $\deg_B(v)=2$, so let $v_1$ and $v_2$ be the two neighbors of $v$ in $B$. We can *suppress* $v$—that is, replace the edges $v_1v$ and $v_2v$ with the single edge $e_v{:}v_1v_2$, setting $\sigma(e_v)=\sigma(v_1v)\sigma(v_2v)$. We write the result of the suppression as $B {\downarrow} v$. Thus, there is a bijective correspondence between the signed circles of $B$ and the signed circles of $B {\downarrow} v$. Therefore, we have the following theorem, which reduces the vertex problem to the edge problem.
\[uniquecharvtx\] Let $\Sigma$ be a signed graph, and let $v$ be a vertex of $\Sigma$. Then $[v,C,-]$ is a negative vertex battery if and only if
1. The block $B$ of $\Sigma$ containing $v$ and $C$ is the only unbalanced block containing $v$, and $\deg_B(v)=2$.
2. $[e_v,C{\downarrow}v,-]$ is a negative edge battery in $B {\downarrow} v$.
We will now turn our attention to the problem of determining if a given vertex is a positive vertex battery. Our characterization of positive vertex batteries is analagous to our characterization of negative vertex batteries, though slightly more complicated. Just as a negative vertex battery may be contained in many blocks in which it is contained in only positive circles (balanced), but only one block in which it is contained a negative circle, a positive vertex battery may be contained in many blocks in which it is contained in only negative circles, but only one block in which it is contained in a positive circle.
We will first describe when an edge is contained in only negative circles and then convert this to a description of vertices.
\[negativebalance\] An edge of $\Sigma$ is contained in only negative circles if and only if it is a balancing edge in the block containing it.
Let $e$ be an edge of $\Sigma$ and let $B$ be the block contaning it. First, if $e$ is a balancing edge in $B$, then $e$ is clearly contained in only negative circles (switch so that $e$ is the only negative edge).
In the other direction, suppose that $e$ is contained only in negative circles. Consider $B{\setminus}e$. Suppose there is a negative circle $C$ contained in $B{\setminus}e$. Then, since $B$ is a block, there is a theta graph containing both $C$ and $e$, forcing $e$ to be in a positive circle—impossible. Thus, $B{\setminus}e$ is balanced and can hence be switched to all-positive by a switching function $\zeta$. However, applying $\zeta$ to $B$ instead will leave $e$ as a negative edge, since $e$ is contained in only negative circles. Thus, $e$ is a balancing edge in $B$.
We can now characterize the type of block in which $v$ is contained only in negative circles.
\[vertonlyneg\] A vertex $v$ is contained only in negative circles in $B$ if and only if $v$ is degree $2$ in $B$, and $e_v$ is a balancing edge in $B{\downarrow}v$.
If $v$ is degree $2$ in $B$ and $e_v$ is a balancing edge, then clearly $v$ is contained in only negative circles by Lemma \[negativebalance\].
Conversely, if $v$ is contained in only negative circles, then $B$ is not balanced. If $\deg_B(v)\geq 3$, then $v$ is contained in a negative circle $C$ and furthermore $v$ is a degree $3$ vertex in a theta graph containing $C$. Hence, $v$ is contained in a positive circle—impossible. Thus, $\deg_B(v)=2$, and we can suppress $v$ to obtain the result.
Now we will describe the blocks in which $v$ is contained in exactly one positive circle. This along with Lemma \[vertonlyneg\] will complete the description of positive vertex batteries.
\[vertonepos\] A vertex $v$ is contained in a unique positive circle $C$ in a block $B$ if and only if either:
1. $B=C$ is a balanced circle.
2. $B$ is unbalanced, $\deg_B(v)=2$, $B{\downarrow}v$ is $C$-layered, and $e_v$ is a positive edge battery in $B{\downarrow}v$.
3. $B$ is unbalanced, $\deg_B(v)=3$, $B$ is $C$-layered with exactly one bridge, $v$ is a vertex of attachment of the bridge, and all edges of $C$ are positive edge batteries.
If $B$ and $v$ satisfy either of the first two conditions above, then clearly $v$ is contained in a unique positive circle in $B$. If $B$ and $v$ satisfy the third condition, observe that any circle besides $C$ that contains $v$ must consist of a path through the single bridge and a handle of $C$—a negative circle.
In the other direction, suppose $v$ is contained in a unique positive circle in $B$. If $B$ is balanced, it consists of only a single positive circle or else $v$ is contained in multiple positive circles.
So, suppose that $B$ is unbalanced and consider the case where $\deg_B(v) \geq 4$. Let $e_1,...,e_4$ be four edges incident with $v$, so that $e_1$ and $e_2$ are contained in $C$. Since $B$ is a block, we can find a theta graph $\Theta$ that contains $C$, and $e_3$ (up to choice of labels). Furthermore, there is a path $P$ containing $e_4$ starting at $v$ and ending at a vertex of $\Theta$ (besides $v$). It is easy to see that $\Theta \cup P$ contains at least two positive circles that contain $v$.
Now we consider the case where $B$ is unbalanced and $\deg_B(v)=3$. Find a theta graph $\Theta \subseteq B$ that contains $C$ such that $\deg_{\Theta}(v)=3$. Observe that $\Theta$ is $C$-layered, with a single bridge $P$ consisting of a path. There can be no path connecting an internal vertex of $P$ to an internal vertex of a handle of $C$, or else we create a subdivision of $K_4$, forcing $v$ to be in more than one positive circle. There can be no path besides $P$ connecting two vertices of $C$, or else there is a second positive circle containing $v$. Thus, any path besides $P$ connecting two vertices of $\Theta$ must have both its endpoints in $P$ and be otherwise disjoint from $\Theta$. Since $\deg_{\Theta}(v)=3$, no such path will contain $v$. The union of all such paths forms a single bridge of $C$, of which $v$ is a vertex of attachment.
Finally, we combine the results of this section to give a complete description of whether or not $v$ is a positive vertex battery. As a reminder, we assume that each block containing $v$ contains at least one circle.
Let $\Sigma$ be a signed graph, and let $v$ be a vertex of $\Sigma$. Then $[v,C,+]$ is a positive vertex battery if and only if:
1. The block containing $v$ and $C$ is the unique block of the form described in Lemma \[vertonepos\].
2. In any other block $B$ containing $v$, $v$ is degree $2$ and $e_v$ is a balancing edge in $B{\downarrow}v$.
A positive vertex battery must be contained in exactly one block in which it is contained in a unique positive circle. It must be contained in no positive circles in all other blocks containing it. Thus, the proof is a combination of Lemma \[vertonepos\] and Lemma \[vertonlyneg\].
[99]{} F. Harary, *On the notion of balance of a signed graph*, Michigan Math. J. 2 (1953), no. 2, 143–146. F. Harary, *On local balance and $N$-balance in signed graphs*, Michigan Math. J. 3 (1955–1956), 37–41. T. Soza[ń]{}ski, *Enumeration of weak isomorphism classes of signed graphs*, J. Graph Theory 4 (1980), 127–144. T. Zaslavsky, *Signed graphs*, Discrete Appl. Math. 4 (1982), 47–74.
| null | minipile | NaturalLanguage | mit | null |
1. Introduction {#sec1-jcm-08-01617}
===============
Chronic rhinosinusitis (CRS) is defined as a chronic inflammation of the mucosal lining of the nose and paranasal sinuses and is associated with chronic relapsing infections. It is one of the most common diseases for which antibiotics are prescribed \[[@B1-jcm-08-01617]\]. CRS is divided into two subtypes, CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP), based on the absence or presence of nasal polyps. Though the pathophysiological mechanisms of CRS are unclear, many studies suggest a dysbiotic microbiome associated with the pathological process \[[@B2-jcm-08-01617],[@B3-jcm-08-01617],[@B4-jcm-08-01617],[@B5-jcm-08-01617],[@B6-jcm-08-01617]\]. *S. aureus* infections and biofilms have been associated with CRS disease recalcitrance \[[@B7-jcm-08-01617]\] and *S. aureus* can enter the pseudostratified columnar respiratory epithelium of the sinuses, affecting the inflammatory process \[[@B8-jcm-08-01617],[@B9-jcm-08-01617]\]. *S. aureus* secreted proteins, particularly enterotoxins, have been identified in CRSwNP mucus \[[@B10-jcm-08-01617],[@B11-jcm-08-01617]\] and are thought to induce T-cell activation and Th2 polarisation with increased production of immunoglobulins including IgE, IgG/IgG4 and IgA \[[@B12-jcm-08-01617],[@B13-jcm-08-01617]\]. CRS patients exhibiting *S. aureus* enterotoxin-specific IgE frequently have comorbid asthma and high mucosal Interleukin 5 (IL5) levels \[[@B14-jcm-08-01617]\].
Steroids, oral antibiotics and nasal irrigations are included in the non-surgical and post-surgery treatments for CRS based on European position paper on rhinosinusitis and nasal polyps (EPOS) 2012 guidelines \[[@B15-jcm-08-01617]\]. Macrolide antibiotics, including clarithromycin and azithromycin, are frequently used for the treatment of CRS infectious exacerbations. They act by binding to the 50S ribosomal subunit of bacteria affecting the bacterial protein synthesis \[[@B16-jcm-08-01617]\]. Macrolides have been shown to reduce proinflammatory cytokine production and have been proposed for the long-term treatment of a number of chronic inflammatory diseases such as diffuse panbronchiolitis, bronchiectasis, CRS and cystic fibrosis \[[@B15-jcm-08-01617],[@B16-jcm-08-01617],[@B17-jcm-08-01617],[@B18-jcm-08-01617]\]. Notably, doses that are much lower than the Minimum Inhibitory Concentration (MIC) are effective at reducing the inflammation, even when bacteria are resistant or persist in the post-treatment sputum \[[@B15-jcm-08-01617],[@B16-jcm-08-01617],[@B17-jcm-08-01617],[@B18-jcm-08-01617]\].
Clindamycin is a classical broad-spectrum antibiotic that is used as well for the treatment of CRS exacerbations---particularly in cases of penicillin allergy or when infected with methicillin-resistant staphylococci or anaerobes. Similar to macrolide antibiotics, clindamycin binds to the 50S ribosomal subunit and inhibits the peptide chain synthesis \[[@B19-jcm-08-01617]\]. Sub-inhibitory concentrations of clindamycin can affect *S. aureus* protein production as well \[[@B20-jcm-08-01617]\]. Here, we tested the effect of sub-inhibitory clindamycin and azithromycin treated *S. aureus* planktonic and biofilms on the production of exoproteins and the resulting effect on attenuating their toxic, pro-inflammatory and barrier disrupting effects.
2. Experimental Section {#sec2-jcm-08-01617}
=======================
2.1. Cells, Bacteria and Antibiotics {#sec2dot1-jcm-08-01617}
------------------------------------
This study was performed in accordance with guidelines approved by the Human Research Ethics Committee of the Queen Elizabeth Hospital and the University of Adelaide. All patients gave written informed consent (reference HREC/15/TQEH/132) and all samples obtained were anonymised and coded before use. All methods were carried out in accordance with the relevant guidelines and regulations. Primary Human Nasal Epithelial Cells (HNECs) were from patients undergoing endoscopic skull base procedures without clinical or radiological evidence of sinus disease. Exclusion criteria included active smoking, age less than 18 years, pregnancy, and systemic diseases (immunosuppressive disease). *S. aureus* clinical isolates (CIs) were obtained from the sinonasal cavities of chronic rhinosinusitis patients without nasal polyps (CRSsNP; 1 with asthma (CI4) and one without asthma (CI2)). *S. aureus* ATCC51650 was obtained from the American Type Culture Collection (ATCC, Manassas, USA). Clindamycin and azithromycin were purchased from Sigma-Aldrich (St. Louis, USA).
2.2. Bacterial Cell Culture Supernatant Collection and Protein Concentration {#sec2dot2-jcm-08-01617}
----------------------------------------------------------------------------
A single colony of *S. aureus* ATCC51650 and CIs were cultured on 1.5% Tryptic Soy Agar (TSA) plates at 37 °C overnight. For each isolate, a 0.5 MacFarland Unit (MFU) suspension was created in 0.9% NaCl. The suspension was subsequently diluted 1:100 in Tryptic Soy Broth (TSB) and incubated for 24 h at 37 °C. Optical density at 600 nm (OD600) was tested to monitor bacterial growth. The culture was then centrifuged at 3000 g for 10 min, the supernatant collected and filtered using a 0.22 μm filter and the filtered supernatant was used in cell culture experiments. The protein concentration was measured using NanoOrange protein quantitation kit (Invitrogen, Carlsbad, CA, USA) following the manufacturer's instructions. The bacterial pellet was resuspended in 0.9% NaCl and used for intracellular infection experiments.
2.3. Antibiotic Sensitivity Test {#sec2dot3-jcm-08-01617}
--------------------------------
The minimum inhibitory concentration (MIC) of clindamycin and azithromycin was tested following the previously described broth microdilution method \[[@B21-jcm-08-01617]\]. Briefly, overnight cultured bacterial colonies were collected from 1.5% TSA plates, adjusted to 0.5 MacFarland Units (MFU) with normal saline, and the bacterial suspension was 1:100 diluted in serially diluted antibiotics in 96 well plates. After a growth of 16 to 20 h at 37 °C, the MIC value was read. One, ½, ¼, ⅛ MIC of the different antibiotics were used for the bacterial treatments.
2.4. Primary HNECs Culture and Treatment {#sec2dot4-jcm-08-01617}
----------------------------------------
Primary HNECs were harvested from nasal mucosa from at least three control donors by gentle brushing in a method described by Ramezanpour et al. \[[@B22-jcm-08-01617]\]. Extracted cells were suspended in PneumaCult^TM^- Ex Plus medium (StemCell Technologies, Vancouver, Canada). The cell suspension was depleted of macrophages using anti-CD68 (Dako, Glostrup, Denmark) coated culture dishes, and HNECs were maintained with PneumaCult^TM^-Ex Plus medium in collagen coated flasks (Thermo Scientific, Walthman, MA, USA) in a cell incubator at 37 °C with 5% CO~2~ until confluence. 5 × 10^5^ cells for each well were then transferred to collagen coated 24 well plates (Corning, New York, NY, USA) and eight well chamber slides (Corning), cultured for a further 24 h followed by application of bacterial exoproteins into the cell culture media at a concentration of 5%. HNECs were incubated for 24 h, followed by collection of the cell culture supernatant for IL6 and IL8 ELISA and Lactate Dehydrogenase (LDH) test.
2.5. Air Liquid Interface (ALI) Culture and Treatment {#sec2dot5-jcm-08-01617}
-----------------------------------------------------
HNECs were maintained at an Air Liquid Interface (ALI) medium, following the PneumaCult^TM^-ALI culture technique (StemCell Technologies). Briefly, Transwells (BD Biosciences, San Jose, USA) were treated with collagen (Stemcell Technologies), 7 × 10^4^ HNECs were seeded in a volume of 100 μL PneumaCult^TM^-EX plus medium into the apical chamber of Transwell plates with 500 μL of the medium in the basal chamber of each well. After three days of incubation, the apical media was disposed and 500 μL of PneumaCult^TM^-ALI medium was added into the basal chamber. The medium was changed every alternate day and HNECs at ALI (HNEC-ALI) were maintained for 21 days for development of Apical Junctional Complexes. At three weeks, the filtered *S. aureus* exoproteins from planktonic cultures were added to the apical chamber of HNEC-ALI cells at a concentration of 1:2 diluted in PneumaCult^TM^-EX plus medium to test the effect on cytotoxicity and mucosal barrier structure.
2.6. Cytotoxity Assay {#sec2dot6-jcm-08-01617}
---------------------
Cytotoxicity of HNECs was measured using an LDH release kit (Promega, Madison, WI, USA) following the manufacturer's instructions. Briefly, 50 μL of the media from each well was transferred to a new plate, and 50 μL of LDH reagent was added to the supernatant and incubated for 30 min in the dark at room temperature (RT). 10% Triton X-100 in medium was used as positive control and 5% tryptic soy broth in medium was used as negative control. The absorbance of prepared samples was recorded at 490 nm on a FLUOstar Optima plate reader (BMG Labtech, Ortenberg, Germany), and relative viability was calculated relative to the LDH levels of negative controls (untreated cells) and positive controls. Absorbance from each well was read using a microplate reader at 490 nm.
2.7. IL6 and IL8 ELISA Assay {#sec2dot7-jcm-08-01617}
----------------------------
Interleukin-6 (IL6) and Interleukin-8 (IL8) protein levels were determined with an IL6 and IL8 enzyme-linked immunosorbent assays (ELISA) kit (BD Biosciences, Franklin Lakes, NJ, USA), according to the manufacturer's instructions. All measurements were performed in duplicate. Poly (I:C) Low Molecular Weight (LMW) (Invivogen, San Diego, CA, USA) was added at a concentration of 10 μg/mL to induce inflammation and used as positive control \[[@B23-jcm-08-01617],[@B24-jcm-08-01617]\]. The optical density (OD) was measured at 450 nm and protein content determined using the standard curve prepared for each assay.
2.8. SDS Page {#sec2dot8-jcm-08-01617}
-------------
After 24 h culture, 15 μL of filtered bacterial culture supernatant was run on a NuPAGE 4% to 12% Bis-Tris SDS gel (Invitrogen, Carlsbad, CA, USA) for 50 min at 200 volts. The gel was stained with colloidal blue staining kit (Invitrogen, California, USA) according to the manufacturer's instructions and imaged on Gel Doc EZ system (Bio-Rad Hercules, CA, USA). Images were analyzed with image lab software (Bio-Rad).
2.9. Biofilm Culture, Treatment and Minimum Biofilm Eradication Concentration (MBEC) Assay {#sec2dot9-jcm-08-01617}
------------------------------------------------------------------------------------------
A 1.0 MFU *S. aureus* culture suspended in TSB was added to 96-well Biofilm inoculators (Innovotech, Edmonton, Canada). Following the manual, plates were incubated for 48 h at 37 °C on an orbital shaker at 110 rpm to allow biofilm formation. The pegs were subsequently washed with phosphate buffered saline (PBS) and dose ranges of clindamycin (50, 20, 10, 5, 2, 1, 0.5, 0.2 and 0.1 μg/mL) and azithromycin (500, 200, 100, 50, 20, 10, 5, 2 and 1 μg/mL) were added into the wells. Pegs were treated for 24 h at 37 °C with gentle shaking. After antibiotic challenge, the pegs were washed and sonicated on high for 30 min to dislodge the biofilm. The recovery plates with collected biofilm were incubated for 24 h at 37 °C to determine the MBEC (the minimum concentration of antibiotic that eradicates the biofilm). Concurrently, the AlamarBlue (Invitrogen) viability assay was then used as previously described to determine biofilm viability and anti-biofilm activity of the treatment \[[@B25-jcm-08-01617]\]. Fluorescence was measured in a microplate reader (FLUOstar Optima, BMG Labtech) and percent reduction of biofilm after treatment calculated.
2.10. S. aureus Biofilm Protein Collection and Protein Concentration {#sec2dot10-jcm-08-01617}
--------------------------------------------------------------------
A measurement of 0.5 MFU of overnight-cultured *S. aureus* isolates were diluted 1:100 and cultured in TSB medium in 50 mL Falcon tube for 48 h to form biofilms. Then, the media and bacteria were disposed, and the biofilms were washed with PBS twice gently, followed by adding fresh TSB with ½ MIC and 1 MIC clindamycin and azithromycin. After 48 h incubation, the media was disposed and biofilms were washed with PBS, followed by collection of the biofilm after sonication for 30 min and centrifugation at 4000 rcf for 10 min. The collected samples were diluted in sterile milliQ water. The protein content was tested using NanoOrange protein quantitation kit (Invitrogen) following the manufacturer's instructions.
2.11. Transepithelial Electrical Resistance (TEER) {#sec2dot11-jcm-08-01617}
--------------------------------------------------
Transepithelial electrical resistance (TEER) was measured by using an EVOM volt-ohmmeter (World Precision Instruments, Sarasota, FL, USA) after adding 100 µL of PBS to the apical chamber of HNEC-ALI cultures. Only readings more than 800 Ω/cm^2^ were used for the treatments. PneumaCult^TM^-Ex Plus medium and 2% Triton X-100 in medium were used as negative and positive control, respectively, and TEER readings were carried out at 0 h, 15 and 30 min.
2.12. Permeability Assay {#sec2dot12-jcm-08-01617}
------------------------
FITC-dextran 4kDa (Sigma-Aldrich, Saint Louis, CA, USA) was used to measure the paracellular permeability of HNEC-ALI. After 30 min of TEER measurement, the media in the apical chamber was changed with 3 mg/mL FITC-dextran in PneumaCult^TM^-Ex Plus medium. After 2 h of incubation at 37 °C, 40 μL samples from the basolateral compartment chamber of the Transwell was collected and transferred to 96-well plates (Corning, Cambridge, UK), and the fluorescence was measured using a microplate fluorometer (FLUOstar Optima, BMG Labtech). Relative permeability of treatments was expressed as treatment fluorescence/medium control fluorescence.
2.13. Immunofluorescence Staining {#sec2dot13-jcm-08-01617}
---------------------------------
HNEC-ALI were fixed with 2.5% formaldehyde, permeabilized with 0.1% Triton X-100 in PBS for 10 min and blocked with serum-free blocker for 1 h (Dako, Glostrup, Denmark). HNEC-ALI was incubated with 1:100 dilution of mouse monoclonal anti-human Zonula occludens-1 (ZO-1) antibody (Invitrogen) at 4 °C overnight. After washing with TBST three times, 1:200 diluted anti-mouse Alexa Fluor-488 conjugated secondary antibody (Jackson Immunoresearch Laboratories, West Grove, PA, USA) was added and incubated 1 h at RT followed with DAPI (Sigma-Aldrich, St. Louis, USA) staining for 15 min. Then, membranes were transferred to a glass slide and a drop of anti-fade mounting medium (Dako, Glostrup, Denmark) was added before cover slipping. Samples were visualized by using LSM700 confocal laser scanning microscope (Carl-Zeiss, Oberkochen, Germany).
2.14. Intracellular S. aureus Infection {#sec2dot14-jcm-08-01617}
---------------------------------------
The bacterial pellet from the bacterial cell culture supernatant collection protocol was resuspended to 3.0 McFarland unit in 0.9% NaCl, diluted 1:12.5 in PneumaCult^TM^-Ex Plus medium and co-cultured with HNECs for 3 h (37 °C, 5% CO~2~). To remove extracellular bacteria after treatment, the cells were washed with PBS three times, treated with 4 μg/mL lysostaphin (Sigma-Aldrich, St. Louis, MO, USA) for 30 min and washed with PBS a further three times. HNECs were then lysed with sterile milliQ water for 30 min and lysates 1:10 serially diluted before plating on 1.5% TSA plates. Plates were incubated for 24 h at 37 °C to allow growth before colonies were enumerated and colony forming units per mL (CFU/mL) were determined. Concurrently, HNECs grown on chamber slides were fixed with purified methanol for 7 min at RT and Giemsa stained to assess the bacterial infection status.
2.15. Statistical Analysis {#sec2dot15-jcm-08-01617}
--------------------------
Microsoft Excel 2010 (Microsoft Corp, Redmond, WA, USA) and SPSS v.22 (IBM Corp, Armonk, NY, USA) were used for statistical analysis. Half MIC antibiotics and no-antibiotic bacterial supernatant treatments were compared using t-test; multi-MIC antibiotics treatments were analyzed using analysis of variance (ANOVA) followed by Least Significant Difference (LSD) post hoc comparison. All treatments were repeated three times separately using cells from three donors. Data is presented as mean ± standard error of the mean (SEM). *p* \< 0.05 was considered as statistically significant.
3. Results {#sec3-jcm-08-01617}
==========
3.1. S. aureus MIC and Bacterial Growth with Subinhibitory Clindamycin and Azithromycin {#sec3dot1-jcm-08-01617}
---------------------------------------------------------------------------------------
To determine the effect of sub-inhibitory concentrations of clindamycin and azithromycin on bacterial growth, the MIC's of *S. aureus* ATCC 51650 and two *S. aureus* clinical isolates were first determined ([Table 1](#jcm-08-01617-t001){ref-type="table"}). Bacteria were then treated with ½, ¼ and ⅛ MIC antibiotics for 24 h before measuring OD600 absorbance values. Compared to non-treated samples, bacteria treated with sub-inhibitory clindamycin or azithromycin had similar OD600 values indicating low antibiotic concentrations, which did not significantly affect the growth of those bacteria ([Figure 1](#jcm-08-01617-f001){ref-type="fig"}, *p* \> 0.05). This allowed for a more direct comparison of antibiotic treated and untreated exoproteins in subsequent experiments without confounding issues of variable bacterial density.
3.2. Sub-Inhibitory Clindamycin and Azithromycin Reduced S. aureus Exoprotein Secretion {#sec3dot2-jcm-08-01617}
---------------------------------------------------------------------------------------
The effect of sub-inhibitory clindamycin and azithromycin *on S. aureus* exoprotein production was assessed measuring protein concentrations and using SDS-page of the bacterial culture exoproteins. Sub-inhibitory clindamycin and azithromycin consistently reduced *S. aureus* exoprotein production in a dose-dependent way for all three isolates tested; however, the effect of clindamycin was more pronounced compared to azithromycin ([Figure 2](#jcm-08-01617-f002){ref-type="fig"} and [Table 2](#jcm-08-01617-t002){ref-type="table"}).
3.3. Sub-Inhibitory Clindamycin Reduced S. aureus Biofilm Protein Content {#sec3dot3-jcm-08-01617}
-------------------------------------------------------------------------
As *S. aureus* often forms persistent biofilm states with reduced sensitivity to antibiotics, we wanted to assess whether sub-inhibitory antibiotics had a similar effect on biofilms. We first tested the clindamycin and azithromycin minimal biofilm eradiation concentration (MBEC) for ATCC 51650, CI1 and CI2. The clindamycin (MBEC \>50 μg/mL) and azithromycin (MBEC \>500 μg/mL) MBEC were more than 250-fold times higher than the MIC. We then treated biofilms of ATCC 51650, CI1 and CI2 with ½ MIC and 1 MIC of clindamycin and azithromycin for 48 h and collected and quantified the biofilm proteins. Results showed ½ MIC and 1 MIC clindamycin and 1 MIC azithromycin significantly reduced biofilm protein content (*p* \< 0.05) ([Figure 3](#jcm-08-01617-f003){ref-type="fig"} and [Table 3](#jcm-08-01617-t003){ref-type="table"}).
3.4. Sub-Inhibitory Clindamycin Reduced Bacterial Exoprotein-Induced Cytotoxicity of HNECs {#sec3dot4-jcm-08-01617}
------------------------------------------------------------------------------------------
Exoproteins from the three planktonic *S. aureus* strains left untreated or treated with sub-inhibitory clindamycin or azithromycin for 24 h were applied to HNECs for 24 h, followed by measuring cell viability using LDH assays. Compared with negative control (5% tryptic soy broth in cell culture medium), the addition of non-treated exoproteins (5% in cell culture medium) from *S. aureus* ATCC 51650 and two clinical isolates significantly reduced the cell viability to 37.67 ± 5.44% for ATCC 51650, 41.43 ± 7.50% for CI1 and 41.86 ± 9.36% for CI2 (*p* \< 0.05). Half MIC clindamycin or azithromycin reduced the *S. aureus* exoprotein-induced HNEC toxicity for 3/3 and 2/3 isolates, respectively (*p* \< 0.05). Direct application of ½ MIC antibiotics at respective concentrations did not affect cell viability compared to negative control ([Figure 4](#jcm-08-01617-f004){ref-type="fig"}).
3.5. Sub-Inhibitory Clindamycin Reversed S. aureus Exoprotein Induced IL6 And IL8 Secretion by HNECs {#sec3dot5-jcm-08-01617}
----------------------------------------------------------------------------------------------------
We harvested *S. aureus* ATCC 51650, CI1 and CI2 exoproteins after treatment with ½, ¼, ⅛ MIC clindamycin or azithromycin for 24 h and added exoproteins into HNEC culture media at a concentration of 5%. We used 10 μg/mL Poly I:C (LMW) as a positive control to induce inflammation and 5% bacterial growth medium in PneumaCult^TM^-EX plus medium as negative control. After 24 h culture, IL6 and IL8 concentration were tested using ELISA assays. *S. aureus* ATCC 51650, CI1 and CI2 exoproteins significantly enhanced the IL6 secretion in HNECs compared to negative control (*p* \< 0.05). Compared to those, exoproteins harvested from ½ MIC clindamycin treated *S. aureus* significantly reduced the bacterial exoprotein induced IL6 secretion back to background levels for all three isolates (*p* \< 0.5). However, ½ MIC azithromycin did not show the same effect ([Figure 5](#jcm-08-01617-f005){ref-type="fig"}a, *p* = 0.99 for ATCC51650, *p* = 0.97 for CI1 and *p* = 0.38 for CI2). In contrast, compared with negative control, *S. aureus* supernatant reduced the basal IL8 secretion of HNECs for all three isolates (*p* \< 0.05). ½ MIC clindamycin and azithromycin treatment reversed this reduction to the control level in 3/3 and 2/3 isolates, respectively (*p* \< 0.05) ([Figure 5](#jcm-08-01617-f005){ref-type="fig"}b).
3.6. Sub-Inhibitory Clindamycin Treatment of S. aureus Reduced Intracellular Infection Rate of HNECs {#sec3dot6-jcm-08-01617}
----------------------------------------------------------------------------------------------------
*S. aureus* can invade mammalian cells, which is thought to contribute to the chronic relapsing nature of *S. aureus* infections in the context of CRS \[[@B8-jcm-08-01617],[@B26-jcm-08-01617]\]. To test the effect of sub-inhibitory clindamycin and azithromycin on intracellular infection rate, we first treated *S. aureus* with ½ MIC clindamycin or azithromycin for 24 h before co-culturing the bacteria with HNECs for 3 h. To test the bacterial infection rate, Giemsa staining of HNECs was performed and colony forming units (CFUs) were counted after removal of extracellular bacteria and cell lysis. Giemsa staining showed ATCC 51650 and CI1 positive control cells had infection rates of 49 ± 9.8% and 26.9 ± 3.3%, whilst CI2 had a very low infection rate of 4 ± 0.6%. Cells treated with ½ MIC clindamycin, but not azithromycin, significantly reduced intracellular infection rate of ATCC 51650 and CI1 ([Figure 6](#jcm-08-01617-f006){ref-type="fig"}a and [Table 4](#jcm-08-01617-t004){ref-type="table"}). There was a significant reduction of CFUs in HNECs infected with ½ MIC clindamycin treated bacteria compared with control and azithromycin treated bacteria ([Figure 6](#jcm-08-01617-f006){ref-type="fig"}b, *p* \< 0.01).
3.7. ½ MIC Clindamycin Reversed Bacterial Exoprotein Induced Mucosal Barrier Disruption of HNEC-ALI {#sec3dot7-jcm-08-01617}
---------------------------------------------------------------------------------------------------
Our previous studies found *S. aureus* exoproteins could severely disrupt the mucosal barrier structure and function of HNEC-ALI cultures \[[@B27-jcm-08-01617],[@B28-jcm-08-01617],[@B29-jcm-08-01617]\]. To explore the effect of sub-inhibitory clindamycin and azithromycin on *S. aureus* exoprotein induced barrier dysfunction, *S. aureus* was cultured with and without ½ MIC clindamycin or azithromycin, exoproteins filtered and added to the apical chamber of HNEC-ALI cultures. Non-treated bacterial exoproteins reduced the TEER after 15 min exposure ([Figure 7](#jcm-08-01617-f007){ref-type="fig"}a, *p* \< 0.01) and increased the permeability of FITC-dextrans after 30 min ([Figure 7](#jcm-08-01617-f007){ref-type="fig"}b, *p* \< 0.01). Compared with the no antibiotic treated group, ½ MIC clindamycin, but not azithromycin, completely reversed the TEER reduction with TEER values similar to negative control. Both antibiotics reduced the increased FITC-dextran permeability of positive control samples, however, the effect was more pronounced with ½ MIC clindamycin treated samples, reducing permeability to background levels ([Figure 7](#jcm-08-01617-f007){ref-type="fig"}b). Immunofluorescence showed that *S. aureus* exoproteins in the presence or absence of ½ MIC azithromycin disrupted ZO-1 immunolocalisation of HNEC-ALI cultures. In contrast, ½ MIC clindamycin treated exoproteins induced no alteration in the localization of ZO-1 compared with negative control ([Figure 7](#jcm-08-01617-f007){ref-type="fig"}c).
4. Discussion {#sec4-jcm-08-01617}
=============
This study showed that sub-inhibitory clindamycin effectively blocked *S. aureus* exoprotein production, thereby inhibiting exoprotein induced toxicity, reversing its detrimental effects on mucosal barrier structure and function and modulating its pro-inflammatory properties. Sub-inhibitory azithromycin had similar effects on affecting these processes---albeit to a lesser extent. Furthermore, clindamycin---but not azithromycin---treated *S. aureus* lost its invasive capacity of primary human nasal epithelial cells. Importantly, whilst up to 250-fold higher concentrations than MIC values were required to kill *S. aureus* biofilms, subinhibitory clindamycin or azithromycin was sufficient to significantly reduce protein production of *S. aureus* biofilms.
Clindamycin, which belongs to the lincosamide class of antibiotics and azithromycin, is a macrolide antibiotic. Unlike antibiotics such as beta-lactam antibiotics, which act on the bacterial cell wall, both clindamycin and azithromycin have a similar mechanism of action and inhibit bacterial protein synthesis by binding to the 50S subunit of the bacterial rRNA \[[@B20-jcm-08-01617],[@B30-jcm-08-01617]\]. As expected, dose-dependent reductions in exoprotein production were seen for both antibiotics---even at concentrations as low as ⅛ MIC values. However, differences between both antibiotics were observed where exoprotein quantities in the presence of subinhibitory clindamycin were consistently lower than in the presence of azithromycin. These differences could account for the variability seen in the attenuation of exoprotein-induced cell toxicity and inflammation in the presence of both antibiotics. Interestingly, whilst the effect of subinhibitory azithromycin on attenuation of exoprotein dependent inflammation was evident for IL8, no differences were observed in HNEC IL6 production between exoproteins treated or untreated with subinhibitory azithromycin. Furthermore, whereas subinhibitory clindamycin completely reversed exoprotein induced barrier disruption and manifestly reduced intracellular infection rate of all three isolates, subinhibitory azithromycin had no effect on these processes. It is hypothesized that apart from the overall reduction in the amount of exoproteins that is produced in the presence of those antibiotics, qualitative differences in expression of proteins might occur where some specific proteins might be induced or suppressed as well. This phenomenon has been demonstrated for clindamycin where changes at transcriptional and protein level are observed, resulting in an overall suppression of exoprotein production, except for an induction of expression of specific proteins such as coagulase and fibronectin binding protein B \[[@B20-jcm-08-01617]\]. A more detailed gene expression and proteomics analysis would be required to define which genes and proteins are induced or repressed by both antibiotics and how that might affect invasiveness, inflammation and mucosal barrier disruption.
*S. aureus* is one of the most commonly identified bacteria in the sinonasal cavities of CRS patients and *S. aureus* mucosal biofilms are often found in those patients with more severe recalcitrant disease \[[@B4-jcm-08-01617],[@B7-jcm-08-01617],[@B31-jcm-08-01617],[@B32-jcm-08-01617],[@B33-jcm-08-01617]\]. In line with our findings of up to 250-fold MIC concentrations of clindamycin and azithromycin needed to kill *S. aureus* biofilms, *S. aureus* biofilms are known to be significantly less sensitive to bacterial killing by antibiotics than their planktonic counterparts. Regardless, our study indicates that treatment with low concentrations of ½ MIC of clindamycin and azithromycin was sufficient to significantly reduce the bacterial exoprotein production in *S. aureus* biofilms. This has important clinical implications and indicates that MIC level antibiotic concentrations, used to treat acute infectious exacerbations, might reduce *S. aureus* biofilm exoprotein induced inflammation and toxicity, in addition to reducing the bacterial burden by killing planktonic cells. Further in vivo experiments would be required to assess this hypothesis.
This study showed that *S. aureus* exoproteins of all three isolates exerted significant cytotoxic effects when applied to HNECs. In fact, 10% *S. aureus* exoproteins induced similar toxicity as 10% Triton X-100, one of the most widely used non-ionic surfactants for lysing cells. Numerous virulence factors are secreted by *S. aureus* that could contribute to this toxicity, including cytolysins and proteases, which are known to cause cell damage \[[@B34-jcm-08-01617],[@B35-jcm-08-01617]\]. These same factors could also be the cause of the mitigation of inflammation and the acute detrimental effects on the mucosal barrier function. It is postulated that exoproteins secreted by the bacteria might significantly contribute to the inflammation observed in the context of *S. aureus* infection and that low concentrations of azithromycin and clindamycin might reduce exoprotein induced inflammation in vivo as well. Low concentrations of macrolides are often used as anti-inflammatory agents for the management of a number of severe chronic inflammatory diseases of the airways \[[@B15-jcm-08-01617],[@B16-jcm-08-01617],[@B17-jcm-08-01617],[@B18-jcm-08-01617]\]. In line with our findings where such low concentrations of antibiotics did not affect *S. aureus* growth, bacteria remain present in the sputum of patients---despite the reduction of inflammation upon long-term treatment with subinhibitory macrolides \[[@B15-jcm-08-01617],[@B16-jcm-08-01617],[@B17-jcm-08-01617],[@B18-jcm-08-01617]\]. In view of our findings, it is reasonable to hypothesise that at least part of the anti-inflammatory effect of subinhibitory macrolide antibiotics might be secondary to reduced exoprotein production.
This study showed reciprocal effects on inflammatory cytokine production with increased and decreased IL6 and IL8 production by HNECs upon application of *S. aureus* exoproteins. Different proteins within *S. aureus* supernatants could influence the inflammatory process and resulting inflammatory cytokine production. IL6 and IL8 protein levels were increased in mucosal explants exposed to *S. aureus* biofilms \[[@B36-jcm-08-01617]\], whilst IL6 can be degraded by specific *S. aureus* proteases as well \[[@B29-jcm-08-01617]\]. Similar to this study, Tajima et al. showed that *S. aureus* β-hemolysin inhibited the human umbilical vein endothelial cell IL8 production \[[@B37-jcm-08-01617]\]. Taken together, these findings indicate a balancing act where bacterial exoproteins might be responsible for inducing inflammation, whilst at the same time reducing specific inflammatory cytokine levels as well, thereby preventing the recruitment of specific immune cells that would be needed to kill the bacteria. Normalizing cytokine levels with the use of subinhibitory clindamycin might therefore reduce inflammation and at the same time help the immune system to eliminate the infection.
5. Conclusions {#sec5-jcm-08-01617}
==============
This study indicates that *S. aureus* exoproteins incite severe cytotoxicity, disrupt the mucosal barrier structure and function and attenuate inflammation. These processes are blocked by subinhibitory clindamycin and to a lesser extent azithromycin---indicating the potential use of these antibiotics to reduce the inflammatory cascade in severe *S. aureus* infections. Additionally, clindamycin could reduce *S. aureus* invasiveness of HNEC, further reducing the potential of this organism to cause chronic relapsing infections.
H.H. conducted experiments and drafted the manuscript; M.R., A.J.H., S.L. conducted experiments; A.J.P., P.-J.W. edited manuscript and helped with study design; S.V. edited manuscript, designed the study.
This work is supported by grants from The Hospital Research Foundation and The Garnett Passe and Rodney Williams Memorial Foundation to P.-J.W. and S.V.
The authors declare no conflicts of interest that are relevant to this study.
{#jcm-08-01617-f001}
######
Protein content of *S. aureus* exoproteins after sub-inhibitory clindamycin and azithromycin treatment. (**a**) Protein content measured by NanoOrange (μg/mL) or (**b**) gel electrophoresis of ATCC 51650, CI1 and CI2 24-h planktonic cultures in the absence (no antibiotic, grey bar) or presence of ½, ¼ or ⅛ MIC clindamycin (blue bars) or azithromycin (green bars). *n* = 3. \* *p* \< 0.05, \*\* *p* \< 0.01, one-way ANOVA followed LSD post hoc comparison.
{#jcm-08-01617-f003}
{#jcm-08-01617-f004}
{#jcm-08-01617-f005}
{#jcm-08-01617-f006}
######
Transepithelial electrical resistance, relative permeability and immunofluorescence staining of *S. aureus* exoproteins treated HNEC-ALI cultures. (**a**,**b**) ½ MIC clindamycin significantly reversed the TEER decrease (**a**) and the increased HNEC-ALI permeability of FITC-dextrans induced by *S. aureus* ATCC 51650, CI1 and CI2 (**b**). (**c**) Immunofluorescence staining of ZO-1 (green) in HNEC-ALI cultures treated with medium (control) or exoproteins from ATCC 51650, CI1 and CI2 left untreated or treated with ½ MIC clindamycin or ½ MIC azithromyxin. DAPI stains nuclei blue. \* *p* \< 0.05, \*\* *p* \< 0.01. *n* = 3.
jcm-08-01617-t001_Table 1
######
*S. aureus* minimal inhibitory concentration for clindamycin and azithromycin (μg/mL) for ATCC51650, Clinical Isolate 1 (CI1) and 2 (CI2).
Antibiotic ATCC51650 CI1 CI2
---------------------- ----------- ----- -----
Clindamycin (μg/mL) 0.2 0.2 0.2
Azithromycin (μg/mL) 2 2 2
jcm-08-01617-t002_Table 2
######
Gray scale analysis of the sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) with Image J. (compared with no antibiotic treatment, \* *p* \< 0.05, one-way analysis of variance (ANOVA) followed by Least Significant Difference (LSD) post hoc comparison.). CI= clinical isolate, MIC = minimum inhibitory concentration.
Antibiotic ATCC51650 CI1 CI2
-------------------- ----------------- ----------------- ----------------
No antibiotic 41.31 ± 2.36 37.91 ± 2.48 10.74 ± 2.60
½ MIC clindamycin 12.22 ± 0.58 \* 9.18 ± 0.53 \* 1.51 ± 1.56 \*
¼ MIC clindamycin 18.31 ± 0.90\* 11.79 ± 1.08 \* 3.96 ± 1.10 \*
⅛ MIC clindamycin 21.45 ± 1.82 \* 16.99 ± 1.23 \* 8.51 ± 1.85
½ MIC azithromycin 18.48 ± 0.70 \* 25.06 ± 1.89 \* 3.94 ± 2.28 \*
¼ MIC azithromycin 23.82 ± 2.27 \* 31.03 ± 3.68 \* 9.46 ± 1.94
⅛ MIC azithromycin 28.66 ± 0.65 \* 32.97 ± 2.14 10.46 ± 1.99
jcm-08-01617-t003_Table 3
######
Gray scale analysis of the SDS-page of 48-h biofilms with Image J. (compared with no antibiotic treatment, \* *p* \< 0.05, one-way ANOVA followed by LSD post hoc comparison).
Antibiotic ATCC51650 CI1 CI2
-------------------- ---------------- ---------------- ----------------
No antibiotic 11.54 ± 1.85 38.85 ± 1.90 15.60 ± 1.04
1 MIC clindamycin 3.80 ± 0.43 \* 1.57 ± 0.12 \* 1.79 ± 0.49 \*
½ MIC clindamycin 10.27 ± 1.09 7.51 ± 0.68 \* 1.57 ± 0.88 \*
1 MIC azithromycin 7.20 ± 0.49 \* 6.35 ± 0.68 \* 1.86 ± 0.58 \*
½ MIC azithromycin 10.15 ± 2.09 7.43 ± 0.64 \* 7.22 ± 2.07 \*
jcm-08-01617-t004_Table 4
######
*S. aureus* intracellular infection rate. Cells were Giemsa stained and % of HNECs infected by *S. aureus* quantified and the average of three independent infection rates expressed as mean ± SEM. Compared with no antibiotic treatment, ½ MIC clindamycin significantly reduced intracellular infection rate of ATCC 51650 and CI1 (\*\* *p* \< 0.01).
Antibiotic ATCC51650 CI1 CI2
-------------------- ------------------ ----------------- ------------
No antibiotic 49 ± 9.8% 26.9 ± 3.3% 4 ± 0.6%
½ MIC Clindamycin 6.3 ± 0.76% \*\* 5.6 ± 3.8% \*\* 2.9 ± 2.6%
½ MIC Azithromycin 42.8 ± 10.7% 27.4 ± 19.7% 3.6 ± 2.3%
| null | minipile | NaturalLanguage | mit | null |
Apparently this wasn’t just an isolated incident: a second federal agency is also having trouble finding emails that a congressional committee is demanding in order to fulfill its oversight responsibilities:
The Environmental Protection Agency (EPA) and the IRS share a problem: officials say they cannot provide the emails a congressional committee has requested because an employee’s hard drive crashed. EPA Administrator Gina McCarthy confirmed to the House Oversight Committee Wednesday that her staff is unable to provide lawmakers all of the documents they have requested on the proposed Pebble Mine in Alaska, because of a 2010 computer crash. “We’re having trouble getting the data off of it and we’re trying other sources to actually supplement that,” McCarthy said. “We’re challenged in figuring out where those small failures might have occurred and what caused them occur, but we’ve produced a lot of information.”
More details:
The committee suspects that Phillip North, who worked for the EPA in Alaska, decided with his colleagues to veto the proposed Pebble Mine near Bristol Bay in 2009, before the agency even began researching its potential impacts on the environment. Committee staffers have been trying for about a year to interview North, but he has been in New Zealand and refuses to cooperate, they said. “We have tried to serve a subpoena on your former employee and we have asked for the failed hard drive from this Alaskan individual who now is in New Zealand, and seems to never be returning,” Rep. Darrell Issa (R-Calif.), the committee’s chairman, said Wednesday. Emails provided by the committee show that EPA told congressional investigators about the hard drive crash months ago. But McCarthy said she only told the National Archives and Records Administration (NARA) about the problem Tuesday.
Ah, so the guy Issa’s been trying to subpoena for alleged criminal wrongdoing is living in a foreign country and ignoring his inquires. Meanwhile, the hard drive that might have stored potentially incriminating emails on it has conveniently “crashed.”
Any takers on what the third federal agency will be to accidentally “lose” relevant and potentially damaging internal emails? It’s only a matter of time. | null | minipile | NaturalLanguage | mit | null |
In vivo and in vitro ADMET profiling and in vivo pharmacodynamic investigations of a selective α7 nicotinic acetylcholine receptor agonist with a spirocyclic Δ2-isoxazoline molecular skeleton.
(±)-3-Methoxy-1-oxa-2,7-diaza-7,10-ethanospiro[4.5]dec-2-ene sesquifumarate (±)-1 was previously characterized as the most selective agonist at α7 neuronal nicotinic acetylcholine receptors in a series of spirocyclic quinuclidinyl-Δ2-isoxazoline derivatives. In this study, we performed different in vitro biological assays aimed at characterizing the ADMET properties of (±)-1. Then, we tested the compound in vivo in behavioral studies including classical novel object recognition and inhibitory avoidance tests in the rat, and a spatial memory assay in zebrafish involving a rapid T-maze task. The results indicated an overall favorable profile for (±)-1 in view of potential therapeutic applications targeting the central nervous system. | null | minipile | NaturalLanguage | mit | null |
Q:
Arithmetic Calculations in PHP for other region
I am doing project for Brazil Country in PHP Language.
there comma (,) and decimal will be interchanged ,for example
Type India Brazil
Decimal 10.34 10,34
Big Value 10,234 10.234
when i do add or multiply in php it works fine for India,but for brazil it won't change formats.
is there any class i need to call ? i am very fresh for this kind of project
The code i tired,
$number = "29346.99"; //value
echo "$" .number_format($number, 2, '.', ',');
function strtonumber( $str, $dec_point=null, $thousands_sep=null )
{
if( is_null($dec_point) || is_null($thousands_sep) ) {
$locale = localeconv();
if( is_null($dec_point) ) {
$dec_point = $locale['decimal_point'];
}
if( is_null($thousands_sep) ) {
$thousands_sep = $locale['thousands_sep'];
}
}
$number = (float) str_replace($dec_point, '.', str_replace($thousands_sep, '', $str));
if( $number == (int) $number ) {
return (int) $number;
} else {
return $number;
}
}
Output:$29,346.99
A:
Use this to parse locale strings to number:
http://php.net/manual/en/numberformatter.parse.php
Then do your calculations.
To get the result of your calculations back to a locale string use:
http://php.net/number_format
There are other options to do this, too.
| null | minipile | NaturalLanguage | mit | null |
Introduction {#Sec1}
============
The previous guidelines for MR imaging of the sonographically indeterminate adnexal mass suggested a basic examination involving T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) to determine the nature and key signal characteristics of the mass, supplemented by additional oblique T2W imaging, fat-suppressed T1W (FST1W) or contrast-enhanced T1W (CET1W) imaging, depending on the key characteristic of the mass \[[@CR1]\].
Recently, much effort has been invested in improving pre-surgical diagnosis of adnexal tumours by developing risk models and scoring systems using sonography \[[@CR2]--[@CR4]\]. In clinical routine, 5--25 % of adnexal lesions will remain indeterminate after sonography \[[@CR2]\]. Even using the International Ovarian Tumour Analysis group (IOTA) simple rules, 22 % of lesions remained indeterminate on ultrasound (US) \[[@CR4]\]. Most of these turn out to be common benign entities such as haemorrhagic lesions, fat-poor mature teratomas, uterine leiomyomas and ovarian fibromas \[[@CR5]\]. The clinical impact of defining whether an indeterminate mass is benign or malignant is enormous. Women believed to have ovarian cancer may require radical cytoreductive surgery by a specialist surgeon in gynaecological oncology \[[@CR6]--[@CR8]\]. Furthermore, women with suspected malignancy may require transfer to a specialist institution. Conversely, benign adnexal masses may either be managed conservatively or undergo simple resection by a general gynaecologist.
In addition, with the increasing use of pelvic MRI, adnexal masses may also be identified as an incidentaloma. In our original guidelines, we suggested that where radiologist supervision of the examination was possible, an algorithmic approach could be used in order to tailor the examination, and that in most cases an accurate diagnosis could be achieved using one or two 'problem-solving' sequences in addition to the compulsory sequences. We have reconsidered these guidelines in light of recent clinical and imaging developments, and present our updated recommendations in Table [1](#Tab1){ref-type="table"}.Table 1MR imaging protocol (2016)Patient preparationIntravenous smooth muscle relaxant\
Placement of intravenous cannulaBasic MR sequencesSagittal T2W of the pelvis\
Pair of T1W, T2W through the indeterminate mass\
±T2W sequence in the long axis of the uterus^1^Problem-solving sequencesT1 'bright' mass---FST1W\
T2 'dark' solid mass (site of origin)---oblique T2W^a^\
T2 'dark' solid mass (nature)---DWI^b^\
T2 solid mass---DWI^b,c^ and CET1W^d^\
Cystic-solid mass---DWI^b,c^ and CET1W^d^*Note*: Modifications to the previous recommendations are highlighted in grey*FST1W* fat-suppressed T1-weighted, *DWI* diffusion-weighted imaging, *DCET1W* dynamic contrast- enhanced T1-weighted^a^In many cases, this oblique T2W sequence along the long axis of the uterus ('ovarian axis') suffices. In other cases, a plane selected across the maximum point of contact of the mass and uterus is required to determine whether it is ovarian or uterine in origin and to look for bridging vessels^b^A solid mass which has low signal on DWI sequences with b values of ≥ 800 s/mm^2^ can be regarded as benign, and CET1W imaging is unnecessary^c^As T2 solid masses with intermediate to high DWI signal may be benign or malignant, additional CET1W imaging is required^d^Ideally, with DCE MRI, where a type 3 curve is highly predictive of malignancy
New imaging techniques {#Sec2}
======================
Diffusion-weighted imaging (DWI) {#Sec3}
--------------------------------
There are now several studies confirming that DWI has a valuable role in MR imaging of the adnexal mass \[[@CR9]--[@CR14]\].
The correct DWI technique is ensured by using a high enough b value to suppress any high signal intensity (SI) from freely diffusing water molecules, whilst keeping sufficient signal-to-noise ratio to identify pathology that has restricted water diffusion. For the female pelvis, we use the urine in the bladder as internal reference to guarantee that the chosen high b value is satisfactory. The urine is high in SI at b0, and decreases as the b value increases. When the bladder SI is fully suppressed, the optimal b value for adnexal mass characterization is achieved. For gynaecological imaging characterization, the optimal b value is usually 800--1000 s/mm^2^, but may be increased up to 1200 or 1400 s/mm^2^ \[[@CR10]\]. Once the DWI sequence has been optimized, the lesion can then be evaluated (Table [2](#Tab2){ref-type="table"} and Fig. [1](#Fig1){ref-type="fig"}).Table 2How to integrate DWI in diagnostic algorithmDiagnostic stepsDWI signal at high b valueBackgroundDiagnosis1. Check urine in bladderUrine remains high in SINeed to increase the high b valueCannot evaluate adnexal mass DWIVery low SIAdequate high b valueCan now evaluate adnexal mass DWI2. Characteristics of T2WI and DWI in adnexal massLow T2WI SI\
Low DWI SIHighly likely benignFibroma\
Cystadenofibroma\
Benign solid componentAny T2WI SI\
Residual signal on DWINon-specificMature teratoma\
Endometrioma\
Cancer\
Metastases3.Compare DWI with ADC SIHigh SI on high b and high SI on ADCT2WI shine throughMay be seen in cystsHigh SI on high b value and low ADCRestricted diffusion---non-specificMature teratoma\
Endometrioma\
Cancer4. ADC measurementCharacterization of lesion is not possible based on ADC quantificationCancer tissue has low ADC but this is non-specificOverlap between benign and malignant lesions*SI* signal intensity, *DWI* diffusion-weighted imaging, ADC apparent diffusion coefficient, *T2WI* T2-weighted imaging Fig. 1Characterization of adnexal masses by combining T2WI and DWI
The key points for the interpretation of DWI are as follows:DWI SI of water (i.e. urine in the bladder) is dark.The DWI SI of the mass must be compared with that on T2WI and ADC.Due to considerable overlap, ADC quantification is not useful for assessing adnexal masses \[[@CR13]\]. In view of this, there is---up to now---no indication to perform multi-b value diffusion.
The presence of 'diffusion restriction' is evidenced by high DWI SI on high-b-value images with corresponding low SI on the ADC map (Fig. [2](#Fig2){ref-type="fig"}). This differs from those tissues in which the water molecules are not highly restricted, where the DWI SI may be low on the high b value and high on ADC or, in the presence of very high T2 SI lesions, the lesion may be high and high (T2 shine-through effect).Fig. 2Ovarian carcinoma confined to the right ovary (*arrow*) displaying intermediate SI on T2WI and restricted diffusion characterized by high SI on the high-b-value (b1200) image and loss of signal on ADC
Initial studies evaluating DWI in adnexal masses reported high SI in mature cystic teratomas and endometriomas as well as in malignant masses, whilst the majority of fibromas and other benign masses had low DWI signal \[[@CR9], [@CR14]\]. These authors rightly cautioned against using DWI as a 'standalone' technique, due to the overlap in common benign and malignant masses \[[@CR9]\]. DWI should not be applied in the diagnosis of mature ovarian teratomas and endometriomas. In practice, the great majority of these lesions can be accurately diagnosed by simply observing their T2W features and the characteristics on T1W and FST1W imaging.
Rather, the added value of DWI is in assessing non-fatty, non-haemorrhagic pelvic masses that are entirely solid, or complex masses that are either septate cysts or complex solid and cystic masses. Diagnostic confidence is increased by about 15 % when DW images are added to conventional images \[[@CR12]\]. If the solid component of an indeterminate adnexal mass is of low SI on T2WI, and the entire mass displays low signal on DWI obtained with a b value of 800--1000 s/mm^2^, there is a very high likelihood of benignity \[[@CR11]\].
DWI is thus diagnostic in the majority of predominantly solid benign adnexal masses, such as ovarian fibroma or cystadenofibroma, and in most pedunculated uterine leiomyomas. Moreover, a low T2W solid mass with low DWI signal is highly likely to be benign, irrespective of its pattern of contrast enhancement \[[@CR12]\].
In these circumstances, DWI can thus replace CET1W MRI as a confirmatory sequence for benignity of a solid or partly solid indeterminate mass. This is of particular relevance in pregnant women in whom contrast administration is contraindicated but complementary imaging to US is warranted.
Conversely, when an indeterminate adnexal mass is solid or has a solid component with high signal on the high-b-value DWI, it may be benign or malignant, and CET1W MRI should be performed.
Dynamic contrast-enhanced (DCE) MR imaging {#Sec4}
------------------------------------------
Two European centres have done pioneering work on DCE MRI of complex adnexal lesions \[[@CR15]--[@CR20]\]. It is well known that factors related to tumour biological processes, such as VEGFR-2 expression and pericyte coverage index (PCI), are related to maximum uptake of gadolinium by the tumour \[[@CR18]\].
Using semi-quantitative multiphase contrast-enhanced MRI, the predominant finding by both groups was that in adnexal masses where solid components demonstrate a rapid rate and high level of enhancement, there is a very high likelihood of malignancy, whereas a slow rate and low level of enhancement is associated with a high likelihood of a benign lesion \[[@CR15]--[@CR17], [@CR20]\].
The analysis of dynamic contrast enhancement is based on the comparison of the time--intensity curve of the solid component in an adnexal mass with that of the external myometrium which serves as internal reference. Thus, a DCE MR sequence must be acquired in a plane that involves the solid component of the adnexal mass (i.e. solid papillary projections, thickened irregular septa or solid portion) and the myometrium (Fig. [3](#Fig3){ref-type="fig"}). Either the plane is selected by the radiologist and a 2D T1W sequence is performed, or better, a 3D T1W sequence may be acquired. Technical details for optimizing DCE MRI (Fig. [3](#Fig3){ref-type="fig"}) are provided in the [technical appendix](#Sec15){ref-type="sec"}.Fig. 3Technical assessment of DCE MR imaging in complex adnexal masses. This example shows a complex right ovarian mass with a solid component in intermediate T2W signal (**a**) that heterogeneously enhances after gadolinium injection. Parametric map (maximal slope) helps to determine the most suspicious location (hot spot) where the region of interest should be placed to build the time--intensity curve (**b**). To compare this curve with the myometrial curve, 3D T1W sequence must be reformatted in the coronal plane to place the two ROI (solid component and external myometrium) (**c**). Comparison of time--intensity curves shows that the solid component enhances according to a time--intensity curve type 3 (curve steeper than that of myometrium)
Review process {#Sec5}
==============
The ESUR guidelines for MRI of sonographically indeterminate adnexal masses were published in 2010. In 2015, a re-evaluation of the current practice was initiated by the expert members. Questionnaires analysing recent clinical practice in imaging of sonographically indeterminate adnexal masses, notably the integration of DWI and DCE imaging, and the type of clinical protocol were collected from 13 European institutions and one centre in Japan. In addition, the literature published between 1999 and 2015 was reviewed. In two consensus meetings in 2015, a draft of the current update was developed and discussed, and was ultimately approved after distribution among the subcommittee members.
Updates {#Sec6}
=======
Indications for MRI in a sonographically indeterminate mass {#Sec7}
-----------------------------------------------------------
The complementary use of MRI is most beneficial in the following clinical scenarios:A complex adnexal mass with equivocal malignant featuresA large pelvic mass of indeterminate originA mass adjacent to the uterus with equivocal originA solid adnexal mass
Patient preparation {#Sec8}
-------------------
There are no new data. It is recommended that a smooth muscle relaxant is administered intravenously or intramuscularly.
Diagnostic algorithm (Fig. [4a--c](#Fig4){ref-type="fig"}) {#Sec9}
----------------------------------------------------------
Fig. 4Flow charts with revised algorithm for T1 'bright' masses (**a**), T2 solid masses (**b**), and complex cystic or cystic-solid masses (**c**)
There are no new data regarding this, and the recommendation remains that it requires basic and problem-solving imaging sequences. The basic imaging technique, as a minimum, comprises the following:A T2W sagittal sequence of the pelvisA pair of T1W and T2W sequences covering the adnexal mass and its relationship to the uterus in the same orthogonal (axial or coronal or oblique) plane with identical slice thickness
The choice of which plane is used is at the discretion of the supervising radiologist. The key is the identical position of the pair of T1W and T2W and---if performed---DWI and DCE/CET1W images to allow direct comparison of the entire mass.
For the 2010 guidelines \[[@CR1]\], the decision tree divided indeterminate masses into three groups on the basis of their key characteristic on the basic T1W and T2W sequences. For the purposes of that algorithm, solid material had SI similar to muscle on T1-weighted sequences, and cyst contents had SI on T2W sequences similar to the urinary bladder. The three categories of mass were as follows:T1 'bright' masses containing T1 high SIT2 solid masses with predominant signal either similar to skeletal muscle (T2 'dark' solid masses) or higher than muscle (T2 'intermediate' or mixed-signal solid masses)Complex cystic or cystic-solid masses
T1 'bright' masses (Fig. [4a](#Fig4){ref-type="fig"}) {#Sec10}
=====================================================
There are no new data to guide assessment of such masses. These masses require FST1W imaging using chemical pre-saturation to distinguish fat from blood. The FST1W sequence should be performed in exactly the same plane as the T1W sequence to allow direct comparison.
Whilst haemorrhagic masses may have low signal on T2WI, it is their T1W 'bright' characteristic---a reflection of T1 shortening from extracellular methaemoglobin---that distinguishes them.
When there is concern for a solid nodule within a T1 bright mass, additional assessment as for a complex cystic or cystic-solid mass is required. An enhancing nodule within an endometrial cyst is a finding suggesting endometriosis-associated cancer \[[@CR21]\]. It is recommended that the post-contrast appearance is reviewed on subtracted images to improve reporting accuracy.
As mature cystic teratomas rarely undergo malignant change, all portions of T1 bright masses should be carefully analysed for signs of such transformation as capsular breach or a large heterogeneous solid component.
Caution is warranted regarding application of DWI and DCE and overreliance on their findings for assessment of T1 bright masses. Both may yield positive findings with benign cystic teratomas. Epidermoid components of teratomas show diffusion restriction similar to malignant lesions, and components of benign teratomas may also rarely rapidly enhance or show type 3 time--intensity curves \[[@CR9], [@CR16], [@CR22]--[@CR24]\]. DWI of haemorrhagic lesions may have a confusing appearance, and offers no additional diagnostic value \[[@CR10]\].
Our recommendation is for no change in the evaluation of T1 bright masses. Their fat or blood content can be determined simply and effectively using a combination of T1W, T2W and FST1W imaging. However, if these masses have solid aspects, or if a teratoma displays a large heterogeneous solid component, further assessment with gadolinium injection is advised.
T2 solid masses (Fig. [4b](#Fig4){ref-type="fig"}) {#Sec11}
==================================================
Well-delineated, sonographically indeterminate solid adnexal masses raise concerns for ovarian metastases, yet in practice almost all of these will turn out to be benign fibrous or fibromuscular masses such as uterine leiomyomas or ovarian fibromas \[[@CR5]\].
The first consideration is defining their anatomic site of origin, ovarian or uterine (Fig. [5](#Fig5){ref-type="fig"}). An ovarian fibroma is separate from the uterus, and often only the contralateral normal ovary is seen. In a uterine leiomyoma, there may be normal uterine tissue draped around the solid mass, holding it like a 'claw' (Fig. [5](#Fig5){ref-type="fig"}c and d). Uterine leiomyoma may also be attached to the uterus by a stalk which contains the 'bridging vessels' that supply it (Fig. [5](#Fig5){ref-type="fig"}e and f). The conspicuity of this pedicle and the bridging vessels is made more obvious using an oblique T2W sequence through the maximum point of contact between the mass and the uterus.Fig. 5Differentiation of ovarian versus uterine origin. Beak sign indicating ovarian origin in a benign teratoma (*arrows* and *outlined* in **a** and **b**). The most important differential diagnosis of a solid adnexal mass includes uterine leiomyoma, which can be differentiated by the claw sign (*arrow* and *outlined* in **c** and **d**) or in broad-based leiomyomas by bridging vessels (*arrow* in **e** and **f**)
From feedback through personal communication, we are aware that in clinical practice, many radiologists feel more comfortable confirming the diagnosis of ovarian fibroma with CET1W imaging. Ovarian fibroma is typically slowly and minimally enhancing, and displays a type 1 curve on DCE MRI \[[@CR14], [@CR25]\]. DCE MRI may also be useful in differentiating pedunculated subserosal leiomyomas from ovarian fibromas. Studies have shown that enhancement of pedunculated subserosal leiomyomas parallel those of the adjacent myometrium, whereas contrast uptake in fibromas is more delayed \[[@CR14], [@CR25]\].
We now recommend DWI in T2W low-signal solid ovarian adnexal masses, which are most likely to be an ovarian fibroma or a Brenner tumour. Such a solid mass having entirely low signal on DWI sequences with high b values can be regarded as benign, and CET1W imaging is unnecessary.
It is our recommendation that a solid adnexal mass with T2 intermediate SI or a T2 dark mass showing other than low DWI signal be further assessed by CET1W imaging, ideally with DCE MRI when this is available.
Complex cystic or cystic-solid masses (Fig. [4c](#Fig4){ref-type="fig"}) {#Sec12}
========================================================================
In our previous guidelines \[[@CR1]\], we recommended CET1W imaging for assessment of masses which raised concerns for malignancy: some solid masses (as discussed above), solid components within cystic masses, and nodular or irregular thickening of internal septa or of the inner or outer aspects of the wall of a mass. CET1W imaging remains the benchmark technique to look for malignant features, and is the one most widely available \[[@CR26]\].
However, both DWI and DCE MRI, when available, are recommended as adjunct investigations. Persistent high signal using b values \> 800 s/mm^2^, with corresponding low ADC signal indicating diffusion restriction, is found in ovarian cancer (Fig. [2](#Fig2){ref-type="fig"}). However, several benign lesions, including benign cystic teratomas, endometrial cysts, some fibrothecomas, degenerating leiomyomas, and Brenner tumours, may also display such signal characteristics on DWI. Furthermore, ADC quantification shows too much overlap to confidently allow prediction of malignancy. Conversely, low DWI signal using a high b value is highly predictive of a benign lesion \[[@CR11]\]. Recent data underscore the value of including DCE in the routine work-up of indeterminate adnexal masses. A retrospective analysis in 87 women with complex adnexal masses demonstrated a correct change in 16--24 % of lesion characterization when both DWI and DCE were used \[[@CR12]\]. In addition to peritoneal implants, the presence of a time--intensity curve type 3 is the best predictor of malignancy, and this enhancement pattern was found in no benign but in 58 % of malignant tumours \[[@CR17]\]. Of note, the benign sclerosing stromal tumour of the ovary may display early contrast enhancement; however, the centripetal enhancement pattern may suggest a specific diagnosis in this extremely rare tumour among women of childbearing age \[[@CR27]\].
A time--intensity curve type 1, a weak and progressive enhancement after gadolinium injection, predicts benignity and may be especially helpful in recognizing benign stromal tumours and cystadenofibroma that may display a high DW signal \[[@CR14], [@CR28]\].
Our recommendations for complex cystic or cystic-solid masses are that DWI and DCE MRI be used, if available, as adjuncts to CET1W imaging.
Tubo-ovarian inflammatory disease commonly causes complex cystic masses, with more indolent or chronic forms typically presenting as sonographically indeterminate masses. Complex folds and other mural abnormalities within tubal disease may mimic neoplastic features \[[@CR29]\]. Caution is warranted in using DWI, as the high signal in these masses is produced mainly by the liquid purulent component and not the solid aspect. Thus, DWI must be carefully analysed in combination with T1W and T2W images. CET1W imaging can increase the conspicuity and improve the diagnosis of tubal disease, and may provide some clues as to disease activity and to complications such as abscess formation.
New developments {#Sec13}
================
An MRI scoring system based on standard T1WI and T2WI appearances supplemented by DWI and DCE MRI features---the ADNEX MR scoring system---has been proposed \[[@CR17]\]. A prospective multicentre study is being conducted in conjunction with the female pelvic imaging working group of the ESUR (EURAD-MR Classification) in order to analyse the potential impact of this model on therapeutic strategy and to test its reproducibility. First results are expected in 2016.
18-FDG PET/CT can provide additional information to transvaginal ultrasound (TVUS) in the differential diagnosis of benign from malignant pelvic lesions. However, in the assessment of sonographically indeterminate lesions, it is currently not recommended, due to its adherent limitations, including physiological uptake in normal ovaries, uptake in common benign lesions, and its potential lack of uptake in cystic or in necrotic tumours. Furthermore, with reported sensitivity of 52--58 % and specificity of 76--78 % for characterization of ovarian masses, it is inferior to MRI \[[@CR30]\]. Increased uptake of FDG in an ovarian mass in women of post-menopausal age is indicative of a malignant tumour \[[@CR30]\]. However, caution is warranted in benign teratomas in both pre-and postmenopausal women \[[@CR31]\].
The added value of the integration of PET/MRI for characterization of ovarian lesions has yet to be validated \[[@CR32]\].
Summary of new recommendations {#Sec14}
==============================
An algorithmic MRI approach using basic and problem-solving sequences under radiologist supervision will ensure a specific diagnosis in the vast majority of sonographically indeterminate adnexal masses.
We do not recommend any change in the evaluation of T1 'bright' masses (Fig. [4a](#Fig4){ref-type="fig"}). Their fat or blood content can be determined simply and effectively using a combination of T1W, T2W and FST1W imaging. When there is concern for a solid nodule within such a mass, it requires additional assessment as for a complex cystic or cystic-solid mass.
We now recommend that DWI be applied for low T2 solid adnexal masses (Fig. [4b](#Fig4){ref-type="fig"}). Such masses with low DWI signal can be regarded as benign. Any solid adnexal mass which shows intermediate or high DWI signal requires further assessment by CET1W imaging, ideally with DCE MRI. This technique may also be useful in the differentiation of uterine from ovarian origin in such a mass.
We now recommend that for complex cystic or cystic-solid masses, both DWI and DCE MRI are used, if available (Fig. [4c](#Fig4){ref-type="fig"}). Otherwise, such masses are appropriately examined using CET1W imaging.
Our recommendations are shown in new algorithms and summarized in Table [1](#Tab1){ref-type="table"}. These ESUR guidelines now supersede those from 2010.
Electronic supplementary material
=================================
{#Sec15}
Below is the link to the electronic supplementary material.ESM 1(DOCX 14 kb)
John A. Spencer is deceased.
The original version of this article was revised: The name of the author Gabriele Masselli was rendered wrongly.
An erratum to this article is available at <http://dx.doi.org/10.1007/s00330-016-4656-0>.
Open access funding provided by Paracelsus Medical University. The scientific guarantor of this publication is Rosemarie Forstner. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. The authors state that this work has not received any funding. No complex statistical methods were necessary for this paper. Institutional Review Board approval was not required because this is an expert consensus paper.
Methodology: recommendation paper, experts from multiple European and one Japanese institution involved.
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Q:
Angular CORS simple request triggers preflight with Authorization header in POST
The preflight is not supposed to happen for simple requests as per the documentation: https://developer.mozilla.org/en/docs/Web/HTTP/Access_control_CORS).
This is indeed the case if I don't put the additional "Authorization" header in the request:
"Content-Type": "application/x-www-form-urlencoded",
"Authorization": "Basic _base64_string_"
Without "Authorization" header:
:authority:www.target.com
:method:POST //<----------------This is correct
:path:/oauth2/access_token?client_id=xxx-xxx
:scheme:https
accept:application/json, text/plain, */*
accept-encoding:gzip, deflate, br
accept-language:en-US,en;q=0.8,fr;q=0.6
content-length:79
content-type:application/x-www-form-urlencoded//<----------------This is correct
origin:http://source.com:4200
referer:http://source.com:4200/
With "Authorization" header, OPTIONS method is automatically set:
:authority:www.target.com
:method:OPTIONS //<----------------This is NOT correct, caused by Authorization header
:path:/oauth2/access_token?client_id=xxx-xxx
:scheme:https
accept:*/*
accept-encoding:gzip, deflate, sdch, br
accept-language:en-US,en;q=0.8,fr;q=0.6
access-control-request-headers:authorization
access-control-request-method:POST
origin:http://source.com:4200
referer:http://source.com:4200/
Because of this issue, I am unable to authorize my app, the server response is :
HTTP method 'OPTIONS' is not allowed. Expected 'POST'
So it seems that the "Authorization" header triggers the preflight in CORS.
Can anyone shed some light on this please?
A:
Because of this issue, I am unable to authorize my app, the server response is :
HTTP method 'OPTIONS' is not allowed. Expected 'POST'
If you have admin access to the server the request is being sent to, then you need to configure that server to allow HTTP OPTIONS requests, and to respond to them with the Access-Control-Allow-Headers and Access-Control-Allow-Methods response headers that browsers need to see in order to allow the actual GET or POST or whatever you’re trying to make (in addition to the Access-Control-Allow-Origin response header browsers need to see for the actual request).
If you don’t have admin access to that server to configure it to send that CORS-enabled response to OPTIONS requests, then your only option for getting requests from frontend JavaScript code to work with it is to set up a CORS proxy and make the request through that. The answer at "No 'Access-Control-Allow-Origin' header is present on the requested resource" has how-to details.
Your only other option beyond that is to not make the request from your frontend JavaScript code but to instead make it from your own backend code instead, which bypasses the cross-origin restrictions that browsers impose).
So it seems that the "Authorization" header triggers the preflight in CORS. Can anyone shed some light on this please?
Yeah, when you add the Authorization header, that makes it no longer a “simple request”.
https://developer.mozilla.org/en-US/docs/Web/HTTP/Access_control_CORS#Preflighted_requests explains this; it says that one of the conditions that triggers the browser to do a preflight is:
If, apart from the headers set automatically by the user agent (for
example, Connection, User-Agent, or any of the other header with
a name defined in the Fetch spec as a “forbidden header name”),
the request includes any headers other than those which the Fetch
spec defines as being a “CORS-safelisted request-header”, which
are the following:
Accept
Accept-Language
Content-Language
Content-Type
DPR
Downlink
Save-Data
Viewport-Width
Width
The Authorization is not in that list, so it triggers a preflight.
| null | minipile | NaturalLanguage | mit | null |
Alistair Darling
Alistair Maclean Darling, Baron Darling of Roulanish, (born 28 November 1953), is a British Labour Party politician who served as Chancellor of the Exchequer in the Labour Government from 2007-2010 and as a Member of Parliament (MP) from 1987 until he stepped down in 2015, most recently for Edinburgh South West. He was one of only three people to have served in the Cabinet continuously from Labour's landslide victory at the 1997 general election until their defeat at the 2010 general election; the other two were Gordon Brown and Jack Straw.
Darling was first appointed as Chief Secretary to the Treasury by Prime Minister Tony Blair in 1997, and was promoted to Secretary of State for Work and Pensions in 1998. After spending four years at that department, he spent a further four years as Secretary of State for Transport, while also becoming Secretary of State for Scotland in 2003. Blair moved Darling for a final time in 2006, making him President of the Board of Trade and Secretary of State for Trade and Industry, before new Prime Minister Gordon Brown promoted Darling to replace himself as Chancellor of the Exchequer in 2007, a position he remained in until 2010.
From 2012-14, Darling was the chairman of the Better Together Campaign, a cross-party group that successfully campaigned for Scotland to remain part of the United Kingdom in the 2014 independence referendum. On 3 November 2014, Darling announced that he was standing down at the 2015 general election. He was nominated for a life peerage in the 2015 Dissolution Honours and was created Baron Darling of Roulanish, of Great Bernera in the County of Ross and Cromarty, on 1 December 2015.
Darling was a vocal advocate for the Remain campaign for the EU referendum on 23 June 2016.
Early life
Alistair Darling was born in London the son of a civil engineer, Thomas, and his wife, Anna MacLean. He is the great-nephew of Sir William Darling, a Conservative/Unionist Member of Parliament for Edinburgh South (1945–1957) who had served as Lord Provost of Edinburgh during the Second World War. He was educated at Chinthurst School, in Tadworth, Surrey, then in Kirkcaldy, and at the private Loretto School, in Musselburgh. He attended the University of Aberdeen, from where he graduated as a Bachelor of Laws (LL.B). He became the President of Aberdeen University Students' Representative Council.
Darling joined the Labour Party aged 23, in 1977. He became a solicitor in 1978, then changed course for the Scots bar and was admitted as an advocate in 1984. In 1982 he was elected to the Lothian Regional Council, where he supported large rates rises in defiance of Margaret Thatcher's rate-capping laws, and even threatened not to set a rate at all. He served on the council until he was elected to the House of Commons. He was also a board member for the Lothian and Borders Police and became a governor of Napier College in 1985, until his election as an MP two years later.
Member of Parliament
He first entered Parliament at the 1987 general election in Edinburgh Central, defeating the incumbent Conservative MP, Sir Alexander Fletcher, by 2,262 votes; and remained an Edinburgh MP until he stood down in 2015.
After the creation of the devolved Scottish Parliament, the number of Scottish seats at Westminster was reduced, and the Edinburgh Central constituency he represented was abolished. After the 2005 general election he represented the Edinburgh South West constituency. The Labour Party was so concerned that Darling might be defeated, that several senior party figures, including Deputy Prime Minister John Prescott and Chancellor Gordon Brown, made encouragement trips to the constituency during the campaign. Despite being a senior Cabinet Minister, Darling was hardly seen outside the area, as he was making the maximum effort to win his seat. In the event, he won it with a majority of 7,242 over the second-placed Conservative candidate, a 16.49% margin on a 65.4% turnout.
Shadow Cabinet
As a backbencher he sponsored the Solicitors (Scotland) Act 1988. He soon became an Opposition Home Affairs spokesman in 1988 on the front bench of Neil Kinnock.
After the 1992 general election, he became a spokesman on Treasury Affairs, but was promoted to Tony Blair's Shadow Cabinet as the Shadow Chief Secretary to the Treasury in 1996.
In government
Following the 1997 general election, he entered Cabinet as the Chief Secretary to the Treasury. In 1998, he was appointed Secretary of State for Social Security, replacing Harriet Harman who had been dismissed. After the 2001 general election, the Department of Social Security was abolished and replaced with the new Department for Work and Pensions, which also took employment away from the education portfolio. Darling fronted the new department until 2002 when he was moved to the Department for Transport, after his predecessor Stephen Byers resigned.
Secretary of State for Transport
Darling was given a brief to "take the department out of the headlines". He oversaw the creation of Network Rail, the successor to Railtrack, which had collapsed in controversial circumstances for which his predecessor was largely blamed. He also procured the passage of the legislation – the Railways and Transport Safety Act 2003 – which abolished the Rail Regulator and replaced him with the Office of Rail Regulation. He was responsible for the Railways Act 2005 which abolished the Strategic Rail Authority, a creation of the Labour government under the Transport Act 2000. Darling was also responsible for the cancellation of several major Light Rail schemes, including a major extension to Manchester Metrolink (later reversed) and the proposed Leeds Supertram, citing rising costs of £620m and £486m respectively.
Darling gave the government's support to the Crossrail scheme for an East-West rail line under London, whose £10,000,000,000 projected cost later rose to £15,000,000,000.
Although he was not at the Department for Transport at the time of the collapse of Railtrack, Darling vigorously defended what had been done in a speech to the House of Commons on 24 October 2005. This included threats that had been made to the independent Rail Regulator that if he intervened to defend the company against the government's attempts to force it into railway administration – a special status for insolvent railway companies – the government would introduce emergency legislation to take the regulator under direct political control. This stance by Darling surprised many observers, because during his tenure at the Department for Transport, he had made several statements to Parliament and the financial markets assuring them that the government regarded independence in economic regulation of the railways as essential.
Secretary of State for Scotland
In 2003, when the Scotland Office was folded into the Department for Constitutional Affairs, he was appointed Scottish Secretary in combination with his Transport portfolio.
Secretary of State for Trade and Industry
In the Cabinet reshuffle of May 2006, he was moved to be Secretary of State for Trade and Industry; Douglas Alexander replaced him as both Secretary of State for Transport and Secretary of State for Scotland. On 10 November 2006 in a mini-reshuffle, Malcolm Wicks, the Minister for Energy at the Department of Trade and Industry, and thus one of Darling's junior ministers, was appointed Minister for Science. Darling took over day-to-day control of the Energy portfolio.
Chancellor of the Exchequer
In June 2007, the new Prime Minister Gordon Brown appointed Darling Chancellor of the Exchequer, a promotion widely anticipated in the media. Journalists observed that three of Darling's four junior ministers at the Treasury (Angela Eagle, Jane Kennedy and Kitty Ussher) were female and dubbed his team, "Darling's Darlings".
In September 2007, for the first time since 1860, there was a run on a British bank, Northern Rock. Although the Bank of England and the Financial Services Authority have jurisdiction in such cases, ultimate authority for deciding on financial support for a bank in exceptional circumstances rests with the Chancellor. The 2007 subprime mortgage financial crisis had caused a liquidity crisis in the UK banking industry, and Northern Rock was unable to borrow as required by its business model. Darling authorised the Bank of England to lend Northern Rock funds to cover its liabilities and provided an unqualified taxpayers' guarantee of the deposits of savers in Northern Rock to try to stop the run. Northern Rock borrowed up to £20 billion from the Bank of England, and Darling was criticised for becoming sucked into a position where so much public money was tied up in a private company.
In March 2008, Darling's Budget was criticised in a media campaign spread by a social networking site. Amid anger at the rise in alcohol duties, James Hughes, a landlord in Edinburgh (where Darling's constituency was based) symbolically barred Darling from his pub, and a passing reporter from the Edinburgh Evening News ran the story. A Facebook group was created, leading dozens of pubs across Britain to follow Hughes, barring Darling from their pubs. The story was eventually picked up by most national press and broadcast media in Britain, and David Cameron, Leader of the Opposition at the time, cited the movement at Prime Minister's Questions on 26 March.
Child benefit data scandal
Darling was Chancellor when the confidential personal details of over 25 million British citizens went missing while being sent from his department to the National Audit Office. A former Scotland Yard detective stated that with the current rate of £2.50 per person's details this data could have been sold for £60,000,000. The acting leader of the Liberal Democrats, Vince Cable, put the value at £1.5bn, or £60 per identity.
Storm warning
In an interview in The Guardian published 30 August 2008, Alistair Darling warned, "The economic times we are facing... are arguably the worst they've been in 60 years. And I think it's going to be more profound and long-lasting than people thought." His blunt warning led to confusion within the Labour Party. However, Darling insisted that it was his duty to be "straight" with people.
In October 2008 the government bailed out the Royal Bank of Scotland as part of the 2008 bank rescue package; Darling said in 2018 that the country was hours away from a breakdown of law and order if the bank had not been bailed out.
Budget 2008
On 12 March 2008, Darling gave his first budget in the House of Commons.
10% income tax band
Darling's predecessor, Gordon Brown, just before he became Prime Minister, had abolished the 10% starting rate on income tax and reduced the basic rate of income tax from 22% to 20% in his final budget on 21 March 2007; this was to come into effect in the tax year starting 6 April 2008. This was not amended in Darling's 2008 budget. Although the majority of taxpayers would be marginally better off as a result of these changes, around 5,100,000 low earners (including those earning less than £18,000 annually) would have been worse off. On 18 October 2007, the Treasury released statistics which established that childless people on low incomes could lose up to £200 a year as a result of the changes, while parents and those earning more than £20,000 would gain money.
Increasing political backlash about the additional tax burden for some put immense pressure onto the government; including Darling with Gordon Brown facing criticism from his own Parliamentary Labour Party.
In May 2008 Darling announced he would help low-paid workers hit by the scrapping of the 10p rate, by raising that year's personal tax allowance by £600 funded by borrowing an extra £2.7 billion.
Stimulus spending
To boost falling demand, the government announced an additional £20bn spending package. Subsequently, Mervyn King, governor of the Bank of England, warned the government against further stimulus spending, due to insecure public finances.
Budget 2009
On 22 April 2009, Darling delivered his second budget speech in the House of Commons. To stimulate the motor industry, a £2,000 allowance was announced for a car more than 10 years old, if it was traded in for a new car. A 50% tax band was announced for earners of over £150,000 to start the following tax year.
Darling also announced that Personal allowance would be tapered down by £1 for every £2 earned above £100,000 until it reached zero. This resulted in an anomalous effective marginal tax rate of 60% above £100,000, with the marginal tax rate returning to 40% for incomes above £112,950.
Budget 2010
Gordon Brown confirmed on 10 March 2010 that Alistair Darling would deliver his Third budget before the general election, which was delivered on 24 March 2010.
Later activities
Following the defeat of the Labour Party at the 2010 general election, Darling announced that he intended to leave frontbench politics. On 17 May 2010, it was reported that he stated: "It has been an honour and a tremendous privilege but I believe it is time for me to return to the backbenches from where I shall look after, with great pride, the constituents of Edinburgh South West."
Darling suggested on 7 September 2010 on The Daily Politics show that he was only intending to take a "year out" and may possibly reconsider his future.
Expenses claims
In May 2009, The Daily Telegraph reported that Darling changed the designation of his second home four times in four years, allowing him to claim for the costs of his family home in Edinburgh, and to buy and furnish a flat in London including the cost of stamp duty and other legal fees. Darling said that "the claims were made within House of Commons rules".
Nick Clegg, Leader of the Liberal Democrats, criticised him by saying: "given that very unique responsibility that [Darling] has [as Chancellor], it's simply impossible for him to continue in that role when such very major question marks are being raised about his financial affairs". A former Chairman and treasurer of the Scottish Labour Party described Darling's position as "untenable" and said that "[Darling] certainly shouldn't be in the Cabinet".
On 1 June 2009, Darling apologised "unreservedly" about a mistaken claim for £700, which he had agreed to repay. He was supported by the Prime Minister, who referred to the incident as an inadvertent mistake.
In 2010, he resigned from the Faculty of Advocates as they were investigating his financial affairs.
Better Together campaign
Darling was the Chairman and one of the directors of the Better Together campaign, which campaigned for a "No" vote in the 2014 referendum on Scottish independence. He was involved in the campaign's launch in June 2012, delivered a speech on the subject in the annual John P Mackintosh lecture in November 2012, and addressed a fringe meeting at the Scottish Conservative Conference in June 2013. In August 2014, Darling took part in Salmond & Darling: The Debate and Scotland Decides: Salmond versus Darling, televised debates with First Minister Alex Salmond on the pros and cons of Scottish Independence.
Darling was criticised by some Scottish Labour MPs and supporters who believed that working with Conservatives on the Better Together campaign might damage Labour's prospects in Scotland. At the general election a year after the referendum, Labour lost all but one of their seats in Scotland to the SNP, with swings of over 30% in several seats, including a UK record swing of 39.3% against Labour in Glasgow North East.
Personal life
Darling had a brief previous marriage when young, but has been married to former journalist Margaret McQueen Vaughan since 1986; the couple have a son (Calum, born 1988) and daughter (Anna, born 1990). Margaret Vaughan worked for Radio Forth, the Daily Record and Glasgow Herald until Labour's election victory in 1997. Darling's media adviser, the former Herald political journalist, Catherine MacLeod, is a close friend of Vaughan and Darling, as well as being a long-standing Labour Party supporter. A sister Jane works as a cook and lives in Edinburgh. Darling has admitted to smoking cannabis in his youth.
He enjoys listening to Pink Floyd, Coldplay, Leonard Cohen and recently to the American rock band The Killers.
References
Further reading
External links
Rt Hon Alistair Darling, Chancellor of the Exchequer HM Treasury (archived)
Kaupthing Controversy theukgovernment.com
BBC Radio 4 Profile
Lord Darling of Roulanish
Alistair Darling | Politics | The Guardian
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Category:1953 births
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Category:Presidents of the Board of Trade | null | minipile | NaturalLanguage | mit | null |
---
abstract: 'We apply the finite-temperature renormalization-group (RG) to a model based on an effective action with a short-range repulsive interaction and a rotation invariant Fermi surface. The basic quantities of Fermi liquid theory, the Landau function and the scattering vertex, are calculated as fixed points of the RG flow in terms of the effective action’s interaction function. The classic derivations of Fermi liquid theory, which apply the Bethe-Salpeter equation and amount to summing direct particle-hole ladder diagrams, neglect the zero-angle singularity in the exchange particle-hole loop. As a consequence, the antisymmetry of the forward scattering vertex is not guaranteed and the amplitude sum rule must be imposed by hand on the components of the Landau function. We show that the strong interference of the direct and exchange processes of particle-hole scattering near zero angle invalidates the ladder approximation in this region, resulting in temperature-dependent narrow-angle anomalies in the Landau function and scattering vertex. In this RG approach the Pauli principle is automatically satisfied. The consequences of the RG corrections on Fermi liquid theory are discussed. In particular, we show that the amplitude sum rule is not valid.'
address:
- ' Centre de Recherche en Physique du Solide et Département de Physique,'
- 'Université de Sherbrooke, Sherbrooke, Québec, Canada J1K 2R1.'
author:
- 'Gennady Y. Chitov and David Sénéchal'
title: 'The Fermi Liquid as a Renormalization Group Fixed Point: the Role of Interference in the Landau Channel'
---
===
epsf.tex
Introduction
============
In 1956-1957 L.D. Landau formulated his theory of Fermi liquids.[@Landau57] The original phenomenological formulation of this theory is based on an expansion near the ground state of the energy functional in terms of variations of the distribution function (bosonic variables). Later, Pomeranchuk derived the thermodynamic stability conditions for this functional.[@Pomeran] Much effort has been dedicated, including by Landau himself,[@Landau59] to vindicate some intuitive assumptions of Landau and elucidate the foundations of the phenomenological Fermi Liquid Theory (FLT). The field-theoretic interpretation of the Landau FLT has reformulated the key notions and basic results of the phenomenological theory entirely in terms of the fermionic Green functions technique.[@Landau59; @Lutt60; @AGD; @Nozieres] The demonstration of the equivalence of the field-theoretic results obtained from the solution of the Bethe-Salpeter equation with the results obtained from the functional expansion and from the Boltzmann transport equation describing the collective modes, has become a textbook topic.[@AGD; @Nozieres; @Lifshitz80; @PinesNoz; @Baym91] The field-theoretic approach provided not only a solid basis to phenomenology, but also a potentially efficient method to calculate the phenomenological parameters of FLT from first principles.
Current interest in non-Fermi Liquids in $d>1$ inspired a new wave of efforts aimed at clarifying the foundations of the Landau FLT and the mechanisms of its breakdown. Let us mention only two approaches, which can be seen as sophisticated modern counterparts of the two classic formulations of the Landau FLT. A bosonized treatment of Fermi liquids has recently been developed[@Boson] in the framework of Haldane’s formulation of higher-dimensional bosonization.[@Haldane] At about the same time, the Renormalization Group (RG) technique has been applied to interacting fermions in $d>1$ with models based on fermionic field effective actions (see Refs and references therein). It both approaches it has been established, for models with reasonable fermion-fermion effective interactions, that the Fermi liquid phase is stable, whereas adding gauge-field interactions may drive the system towards a Non-Fermi-Liquid regime, or may result in a Marginal Fermi Liquid phase, like for composite fermions at the half-filled Landau level.
The RG analysis of FLT presented here and in our previous work,[@GD95] like other such analyses already published, starts from a low-energy effective action with a marginal (in the RG sense) short-range interaction. However, contrary to other works on the subject, our finite-temperature RG approach revealed that, in the Landau channel of nearly forward scattering quasiparticles, the effective interaction flows with successive mode eliminations towards the Fermi surface, even in the absence of singular or gauge interactions. In other words, the action’s interaction (coupling function) does not stay as a purely marginal under the RG transformation, since its $\beta$-function is not identically zero. From the RG flow equations the standard FLT results have been recovered.[@GD95]
It was also pointed out, and elaborated later in more detail by one of us together with N. Dupuis in Ref., that the bare interaction function of the low-energy fermion effective action cannot be identified with the Landau interaction function. The latter, along with other observable parameters of a Fermi liquid, should be calculated as a fixed point of the RG equations.[@NG96] Let us briefly give two arguments for this. First, identifying the Landau function with the effective action’s bare interaction is inconsistent with other standard FLT results, due to the role of Fermi statistics. Indeed, in a stable Fermi liquid, the well-known relationship between components of the scattering amplitude ($\Gamma_l$) and of the Landau interaction function ($F_l$), i.e., $\Gamma_l= F_l/(1+F_l)$, cannot satisfy the Pauli principle for the amplitude (the amplitude sum rule) if $F$ has the symmetry properties of the action’s bare interaction. (For the explanation of this point see Sect. \[deficientS\] below). Second, identifying the Landau function with the bare interaction is inconsistent with the low-energy effective action method itself, in the way it is applied to condensed matter problems. Namely, at the starting point of the analysis, the bare parameters of the effective action, including the interaction, are regular functions of their variables.[@Polchinski93; @Shankar94] It is known, however, that this is not the case even for parameters of a normal Fermi liquid. For instance, the scattering amplitude and the Landau function are two distinct limits of the four-point vertex in the Landau channel when energy-momentum transfer goes to zero. The non-analyticity of the forward scattering vertex appears in its dependence both on the small energy-momentum transfer and, due to the antisymmetry (crossing symmetry), on the small angles between incoming (outgoing) particles lying near the Fermi surface. This contradiction becomes flagrant if one couples the fermionic action with gauge fields since, as shown by other methods,[@Stern] the Landau function for the marginal Fermi Liquid of composite fermions at the half-filled Landau level develops a delta-function singularity in the forward direction ($\t=0$). Such behavior of the Landau function is related to the divergence of the quasiparticle’s effective mass, according to the theory of Halperin, Lee and Read for the half-filled Landau level[@HLR] (see also Ref). So, coming back to our arguments, the Landau function cannot be a regular interaction in the effective action at the starting point of the RG analysis.
The aim of the present study is twofold. Once the classic FLT results have been recovered by the RG approach,[@GD95] the latter would loose its appeal if it did not provide a constructive method for calculating the Fermi liquid’s parameters. This is especially important goal in the long-term prospective of applying this powerful method to more complex strongly correlated fermion systems. In this work we explicitly derive the Landau function and the forward scattering vertex from the short-range effective bare interaction. We do it in the one-loop RG approximation which takes into account contributions of the direct ($ZS$) and exchange $(ZS')$ graphs. This enables us to reveal singular features of the Landau function and scattering vertex in the forward direction ($\theta =0$).
An equally important goal of this work is to resolve the old problem of FLT with the Pauli principle. In its treatment of FLT, the field-theoretic approach encountered a very subtle problem caused by Fermi statistics of one-particle excitations and by the necessity to provide both stability for the Fermi liquid and a solution for the two-particle vertex that meets the Pauli principle.[@Mermin67; @Lifshitz80] The problem was “settled” by imposing the amplitude sum rule on the components of the Landau quasiparticle’s interaction function. The phenomenological FLT is spared from this problem partially by the way it is formulated, partially because it says nothing about the quasiparticle scattering amplitudes. (A detailed discussion of this problem, which lies at the heart of the present study, is postponed until Sec.\[deficientS\], where it will be put in contact with the present RG approach.) The same problem arose in our previous work[@GD95] in the form of a “naturalness problem”[@Polchinski93] of the effective action: the effective action had to be “fine tuned” in order for the scattering amplitude to meet the Pauli principle. We will show that if quantum interference of the direct and exchange processes is taken into account, this problem is eliminated in a natural manner.
The paper is organized as follows. Sections \[modelS\] and \[couplingS\] are introductory: we define the effective action of the model and the coupling functions (the bare interaction) and vertices to be calculated in the Landau interaction channel. In Section \[RGeqS\], which is rather technical, the one-loop RG equations for the two-dimensional case are derived. Section \[deficientS\] explains some of the weak points of the standard FLT results and argues for their partial revision. In Section \[solutionS\] we give a numerical and approximate analytical solution of the coupled RG equations for spinless fermions. In Section \[discussionS\] we present and discuss our results for the Landau function and the scattering vertex calculated at different temperatures. In Section \[contactS\] we relate this study to the standard treatment of Fermi liquid Theory. The consequences of the RG corrections on FLT results are discussed.
The Model {#modelS}
=========
We apply the Wilson-Kadanoff renormalization scheme in the framework developed earlier for a model with $SU(N)$-invariant short-range effective interaction and rotation invariant Fermi surface in spatial dimensions $d\leq3$ at finite temperature.[@GD95] In order to make the discussion as clear as possible, we concentrate in this work on $2D$ spinless ($N=1$) fermions. This simple model has nevertheless all the necessary qualities to illustrate our key points and to demonstrate the new features brought by the RG analysis of a Fermi liquid. In this case the RG equations take their simplest form, since only the antisymmetric momentum-frequency dependent parts of the interaction and vertices are present (they were labeled by A in Ref.).
The partition function in terms of Grassmann variables is given by the path integral \[Z\] Z = | e\^[S\_0 + S\_[int]{}]{}wherein the free part of the effective action[@Polchinski93; @Shankar94; @Weinberg] is \[S0\] S\_0 =\_[([**1**]{})]{}|([**1**]{})([**1**]{}) .We introduced the following notation: \[notation\] \_[([**i**]{})]{} [1]{}\_[\_i]{}([**i**]{}) ([**K**]{}\_i,\_i), where $\beta$ is the inverse temperature, $\mu$ the chemical potential, $\omega_i$ the fermion Matsubara frequencies. We set $k_B=\hbar=1$. The interacting part of the action is \[Sint\] S\_[int]{} = -14\_[([**1**]{},[**2**]{},[**3**]{},[**4**]{})]{} |([**1**]{})|([**2**]{})([**3**]{})([**4**]{}) \^[\_0]{}([**1**]{},[**2**]{};[**3**]{},[**4**]{}) (2)\^2 ([**1**]{}+[**2**]{}-[**3**]{}-[**4**]{}) ,where $\delta(\cdots)$ stands for a Dirac delta function for the momenta and a Kronecker delta for the Matsubara frequencies. The function $\Gamma^{\La_0}$ is antisymmetric under the exchange $({\bf
1} \leftrightarrow {\bf 2})$ and $({\bf 3} \leftrightarrow {\bf 4})$. The bare cutoff $\La_0$ of the action is introduced such that each vector ${\bf K}_i$ in the effective action lies in a shell of thickness $2\La_0$ around the Fermi surface. We denote this shell, i.e., the support of the effective action in the momentum space, as $C^2_{\La_0}$. The Matsubara frequencies are allowed to run over all available values. We presume that the density of particles in the system is kept fixed.
The one-particle excitations are linearized near the Fermi surface, and therefore the bare one-particle Green’s function for the free part of action $S_0$ is: \[G0\] G\_0\^[-1]{}([**K**]{}\_1,\_1) = i\_1+-([**K**]{}\_1) i\_1-v\_F(K\_1-K\_F) i\_1-v\_Fk\_1 .In the integration measure only the relevant part is kept: \[measure\] d[**K**]{} = \_[-\_0]{}\^[\_0]{} \_0\^[2]{}[(K\_F+k)]{}dkd K\_F\_[-\_0]{}\^[\_0]{}\_0\^[2]{} dkdThe temperature $T$ is restricted by the condition \[TCond\] T v\_F\_0 .
The relevant physical information can be obtained by studying interactions of particles scattering with small momentum and energy transfer (we call it the [*Landau channel*]{}), and those with nearly opposite incoming (outgoing) momenta (the BCS channel). Since we are interested in the repulsive case, we presume that stability conditions against Cooper pairing are fulfilled, and we concentrate on the Landau channel.
Coupling functions and vertices in the Landau channel {#couplingS}
=====================================================
Let us clarify the meaning of the quantities entering the effective action. Consider the vertex function $\Gamma({\bf 1},{\bf 2};{\bf 3},{\bf 4})$, constructed from the connected two-particle Green’s function ${ G}_2^c({\bf 1},{\bf 2};{\bf 3},{\bf 4}) =
-\langle\psi({\bf 1})\psi({\bf 2})
\bar\psi({\bf 3})\bar\psi({\bf 4})\rangle_c$ by amputation of the external legs. Here $\langle ...\rangle$ means an average with the effective action (\[S0\],\[Sint\]) which contains only “slow” modes, lying in the support $C^2_{\La_0}$. Once auxiliary source fields (with momenta inside the shell $C^2_{\La_0}$) coupled to the action’s Grassmann fields $\{\psi$, $\bar\psi \}$ have been introduced, such connected $n$-particle Green’s functions can be defined as functional derivatives of the source-dependent generating functional.[@Metzner] At tree-level, $\Gamma({\bf 1},{\bf 2};{\bf 3},{\bf 4})|_{\rm tree} =
\Gamma^{\La_0}({\bf 1},{\bf 2};{\bf 3},{\bf 4})$. The bare vertex $\Gamma^{\La_0}$ (in the sense of the effective action (\[S0\],\[Sint\])) can be defined in the same fashion as $\Gamma$, with the difference that $\Gamma^{\La_0}$ is the result of averaging over the “fast” modes (those [*outside*]{} $C^2_{\La_0}$) with the [*microscopic*]{} action. Contrary to $\Gamma$, the vertex $\Gamma^{\La_0}$ is not a physical observable, since it is not the result of an integration over all degrees of freedom.
Taking into account momentum and frequency conservation, we use the following notation for the nearly forward scattering vertex: \[GammaTr\] ([**1**]{},[**2**]{};[**1**]{}+[Q]{},[**2**]{}-[Q]{}) ([**1**]{},[**2**]{};[Q]{}) ,with the transfer vector \[Transfer\] [Q]{} = [**3**]{}-[**1**]{} ([**Q**]{},) such that $Q \ll K_F$ ($\Omega $ is a bosonic Matsubara frequency). We write the momentum ${\bf K}_i$ as ${\bf K}_i={\bf K}_F^i+{\bf k}_i$ where ${\bf K}_F^i$ lies on the Fermi surface and ${\bf k}_i$ ($|{\bf k}_i| \leq \La_0$) is normal to the Fermi surface at the point ${\bf K}_F^i$.
In order to calculate physical quantities, we must perform an average with the effective action (\[S0\],\[Sint\]), i.e., we must integrate out the “slow” modes, which lie inside $C^2_{\Lambda_0}$, in the corresponding path integrals. This is done in Wilson’s RG approach by successively integrating the high-energy modes in $C^2_{\La_0}$, i.e., by progressively reducing the momentum cutoff from $\La_0$ to zero. We define a RG flow parameter $t$ such that the cutoff at an intermediate step is $\La(t)=\La_0 e^{-t}$. Integrating over the modes located between the cutoffs $\La(t)$ and $\La(t+dt)$, a recursion relation (in the form of a differential equation) can be found for the various parameters of the action. This equation (or set of equations) is then solved from $t=0$ to $t\to\infty$ and this yields the fixed-point value of the parameters of the action. The physical quantities are then obtained from these parameters, e.g. by functional differentiation if they are source fields.
A considerable simplification of this problem comes from the scaling analysis of the low-energy effective action using the smallness of the scale $\La/K_F$.[@Shankar94] A tree-level analysis shows that the only part of the coupling function $\Gamma^\La$ which is not irrelevant couples two incoming and two outgoing particles with the same pairs of momenta $({\bf K}_F^1,{\bf K}_F^2)$ lying on the Fermi surface. The dependence of the coupling function on ${\bf k}_i$ and on the frequencies $\omega_i$ is irrelevant and can be omitted. When the initial cutoff $\La_0$ satisfies condition (\[TCond\]), we can unambiguously define a [*bare*]{} coupling function which depends [*only*]{} on the angle between the incoming (or outgoing) momenta. This bare coupling function is given by the vertex $\Gamma^{\La_0}({\bf 1},{\bf 2};{\cal Q})$ in the zero transfer limit (${\cal Q}=0$) where the two external momenta are put on the Fermi surface and the external frequencies are $\omega_{\rm min}\equiv\pi T$ (the latter will be dropped from now on). \[Fdef\] U([**K**]{}\_F\^1,[**K**]{}\_F\^2) 12\_F \^[\_0]{}([**K**]{}\_F\^1,[**K**]{}\_F\^2; 0) ,where $\nu_F = K_F/ \pi v_F$ is the free density of states at the Fermi level. Each vector ${\bf K}_F^i$ may be specified by a plane polar angle $\t_i$. The function $U$ is an even function of the relative angle $\t_{12}$ between ${\bf K}_F^1$ and ${\bf K}_F^2$. The only remnant of the antisymmetry of $\Gamma^{\La_0}$ (the Pauli principle) is the condition:[@GD95] \[Pauli\] U(0)=0 .
As shown earlier,[@GD95] the tree-level picture becomes more complicated when we carry out the mode elimination inside $C_\La^2$. It turns out that simply discarding the frequency dependence of $\Gamma^{\La}$ and identifying the momenta ${\bf K}_F^1 \rightleftharpoons {\bf K}_F^3$, ${\bf K}_F^2 \rightleftharpoons {\bf K}_F^4$ is an ill-defined procedure when the running cutoff $\La$ becomes of the order of the temperature ($v_F \La \sim T$). The ambiguity arises when calculating the one loop-contribution from, say, the $ZS$ graph, since this contribution is not an analytic function of the transfer $\cal Q$ at ${\cal Q}=0$.[@AGD; @Lifshitz80; @Mermin67] To describe correctly the parameters of the Fermi liquid, one should retain the dependence of the coupling function $\Gamma^{\La}({\bf K}_F^1,{\bf K}_F^2;{\cal Q})$ on the energy-momentum transfer ${\cal Q}$. Retaining this ${\cal Q}$-dependence allows the calculation of response functions or collective modes of the Fermi liquid.[@Dupuis96] For the purpose of the present study we define two coupling functions ($\Gamma^Q$ and $\Gamma^\Omega
$), depending on the order in which the limits of zero momentum- ($\bf Q$) and energy-transfer ($\Omega$) are taken: \[two-limits\] \^Q(\_[12]{}) = \_[Q0]{} (\_[12]{},[Q]{}) \_[=0]{} , \^(\_[12]{}) = \_[0]{} (\_[12]{},[Q]{}) \_[Q=0]{} We use dimensionless vertices, by including in their definition the factor $\frac12 \nu_F$, like in Eq. (\[Fdef\]). The functions $\Gamma^{Q, \Omega}(\t)$ are even functions of the angle $\t$. We will not explicitly indicate their dependence on the cutoff $\La$, unless necessary. We will indiscriminately call these functions (running) vertices.
Let us summarize: The effective action is defined on the support $C^2_{\La_0}$ with the bare coupling function $\Gamma^{\La_0}$, which is presumably an analytic function of its variables and is marginal at tree level. While performing the mode elimination within $C^2_{\La_0}$, we need to calculate the flow of the two vertices $\Gamma^Q$ and $\Gamma^\Omega$. The bare coupling $\Gamma^{\La_0}$ has an unambiguous meaning only as the common initial point of the RG flow trajectories of $\Gamma^Q$ and $\Gamma^\Omega$. The fixed point values $\Gamma^{Q*} \equiv \Gamma^Q(t=\infty)$ and $\Gamma^{\Omega *} \equiv \Gamma^\Omega(t=\infty)$ are physical observables: the first one is the $Q$-limit of the vertex $\Gamma$ (as defined at the beginning of this section) and is the scattering amplitude of quasiparticles with all four external momenta lying on the Fermi surface. The second one is the unphysical limit ($\Omega$-limit) of the vertex $\Gamma$ and is identified with the Landau function.[@Landau59]
The RG equations in the Landau channel {#RGeqS}
======================================
There are three Feynman diagrams contributing to the RG flow at the one-loop level (see Fig. 1), denoted $ZS$ (zero sound), $ZS'$ (Peierls), and $BCS$. The $BCS$ graph contribution preserves the antisymmetry of the vertex, while those of the $ZS$ and $ZS'$ graphs separately do not: only their combined contribution ($ZS+ZS'$) is antisymmetric under exchange of incoming (or outgoing) particles. To respect the Pauli principle, it is therefore necessary to take into account both the $ZS$ and $ZS'$ contributions to the RG flow. In this work we discard the symmetry-preserving contribution of the $BCS$ graph to the RG flow of the vertices in the Landau channel. Thus, we leave out the interference near $\t=\pi$ of the Landau channel with the BCS channel, which leads to the Kohn-Luttinger effect.[@Shankar94]
The formal analytic expression of the $ZS$ graph is \[ZS\] ZS = -\_[([**5**]{})]{}([**1**]{}, [**5**]{};[**1**]{}+[Q]{},[**5**]{}-[Q]{}) ([**5**]{}-[Q]{},[**2**]{};[**5**]{},[**2**]{}-[Q]{}) G([**5**]{})G([**5**]{}-[Q]{}) ,wherein the transfer vector ${\cal Q}$ is given by (\[Transfer\]). To calculate the contribution of this graph to the RG flow of $\Gamma^Q$ and $\Gamma^\Omega$, we only need to keep the dependence on the momenta ${\bf K}_F^i$ and on the transfer ${\cal Q}$ in the vertices on the r.h.s. of (\[ZS\]). Momentum and energy conservation is already taken into account in (\[ZS\]). The phase space restrictions are satisfied automatically for any ${\bf K}_5 \in C^2_{\La}$ in the limit ${\cal Q}
\to 0$. When ${\bf K}_1$ and ${\bf K}_2$ lie on the Fermi surface and ${\cal Q} \to 0$, the r.h.s. of (\[ZS\]) contains both vertices of type (\[two-limits\]) with ${\bf K}_F^5$ running freely around the Fermi surface during the angular integration. Thus, for this graph, all the phase space is available for integration. The summation over $\omega_5$ of the Green’s functions product on the r.h.s. of (\[ZS\]) when ${\cal Q} \to 0$ gives zero in the $\Omega$-limit, and thus \[GammaOmZS\] [[\^]{} (\_1 -\_2) ]{} \_[ZS]{}=0 .The ${\bf Q}$-limit of the same product gives a factor $\frac14 \beta \cosh^{-2}(\beta v_Fk_5/2)$, and accordingly[@GD95] \[GammaQZS\] [\^Q(\_1 -\_2)t]{} \_[ZS]{}= [\_R \^2(\_R)]{} \_[- ]{}\^ \^Q (\_1-) \^Q(-\_2) ,where we introduced a dimensionless temperature flow parameter: \[Br\] \_R(t) 12 v\_F (t) .
We now turn our attention to the $ZS'$ graph. Its analytic form is \[ZS’\] ZS’ = \_[([**5**]{})]{} ([**1**]{}, [**5**]{};[**1**]{}+[Q]{}’,[**5**]{}-[Q]{}’) ([**5**]{}-[Q]{}’,[**2**]{};[**5**]{},[**2**]{}-[Q]{}’) G([**5**]{})G([**5**]{}-[Q]{}’) , wherein ${\cal Q}' \equiv {\bf 2}-{\bf 1}-{\cal Q}$ can be thought of as an “effective” transfer vector for this graph. For $|{\bf K}_2-{\bf K}_1| \not=0$ the limit ${\cal Q} \to 0$ of the r.h.s. of (\[ZS’\]) is single-valued and equivalent to the $Q$-limit.[@Mermin67] The Green’s functions contribution to this graph is \[GProduct\] [1]{}\_[\_5]{} G([**5**]{})G([**5**]{}-[Q]{}’) \_[[Q]{} = 0]{}= -[12]{} [[(([**K**]{}\_5)-) - (([**K**]{}\_5-[**K**]{}\_2-[**K**]{}\_1)-) ]{} ]{} .If $|\t_1-\t_2| \ll {T /v_F K_F}$ the r.h.s. of Eq.(\[GProduct\]) becomes $-\frac14 \beta \cosh^{-2}(\beta
v_Fk_5/2)$. The calculation of the $ZS'$ contribution is more subtle, since even in the zero-transfer limit ${\cal Q} \to 0$ (in any order), the vector ${\bf Q}' \vert_{{\cal Q} \to 0} = {\bf K}_2-{\bf
K}_1$ is free to take any modulus in the interval $\lbrack 0, 2K_F \rbrack$ as the angle $\t_1-\t_2$ varies. A large ${\bf Q}'$ kicks the vertex momenta on the r.h.s. of (\[ZS’\]) outside of $C^2_{\La}$, even if ${\bf K}_5 \in C^2_{\La}$. In such cases the contribution of the $ZS'$ graph is cut off, except for special positions of the vector ${\bf K}_5$ running over the Fermi surface. Thus, for an arbitrary angle $\t_1-\t_2$, not all the phase space is available for integration.
To understand where this elimination of the $ZS'$ contribution comes from, we must keep in mind that our effective action has support $C^2_{\La}$ in momentum space. Let us consider the $ZS'$ graph (see Fig. 1) when all external momenta satisfy momentum conservation and lie in $C^2_{\La}$. It suffices then to check whether the internal momenta (${\bf K}_5$ and ${\bf K}_5-{\bf Q}'$) lie in $C^2_{\La}$ when ${\bf K}_F^5$ runs around the Fermi surface during the integration. From Fig. 2A we see that if $|{\bf Q}'| >2 \La$, the loop momenta lie both in $C^2_{\La}$ only at special values of ${\bf K}_F^5$ (the shaded regions), i.e., only small fragments of phase space are available for integration. At smaller ${\bf Q}'$ (cf. Fig. 2B) these intersections form a connected region and ${\bf K}_F^5$ is free to run around the Fermi surface. If we completely neglect the $ZS'$ graph when the intersection is disconnected (in Fig. 2A), the contribution of this graph to the RG flow at $|{\bf Q}'| < 2 \La$ is calculated in the same way as that of the $ZS$ graph. Since $|{\bf
K}_1|=|{\bf K}_2|=K_F$ and ${\bf Q}' \vert_{{\cal Q} \to 0} = {\bf K}_2-{\bf K}_1$, the condition $|{\bf Q}'| < 2 \La$ is equivalent to the condition $|\sin((\t_1-\t_2)/2)| < \La / K_F$ for the angle between ${\bf K}_1$ and ${\bf K}_2$.
Taking into account both the contributions of the ZS and ZS$'$ graphs, the RG equations for $\Gamma^{Q,\Omega }$ can be written in [*implicit form*]{}:[@NG96] = [\^Q t]{}\_[ZS]{} + [\^Q t]{}\_[ZS’]{} = [\^t]{}\_[ZS’]{} = [\^Q t]{}\_[ZS’]{} .Summing up all formulas, we obtain the following system of RG equations: \[RGangle\] = [\_R \^2\_R]{} \_[-]{}\^ \^Q(-) \^Q(+ ) +[\^(2)t]{} = -\_R (\_c- ||) \_[-]{}\^ \^Q(-) \^Q(+) Y(,;\_R) .To simplify those formulas we parametrized the angular dependence of the vertices in Eqs. (\[RGangle\]) by the angle $\phi$ between ${\bf
K}_F^1$ and $({\bf K}_F^1+{\bf K}_F^2) $, $| \phi| \in [0, \pi/2]$. The small $ZS'$ contribution coming from $|\sin\phi|>\La(t)/K_F$ (Fig. 2A) was neglected, which is accounted for by the Heaviside step function $\Theta$, wherein $\t_c \equiv \arcsin( \La(t) /K_F)$. We also defined the function \[Ybetax\] Y(, ; \_R) \_[Q\^]{}\_F, \_Fv\_F K\_F .which arises in the calculation of the $ZS'$ contribution (\[GProduct\]). Notice that \[limY\] \_[\_[Q\^]{}0]{} Y(,;\_R) = [1\^2\_R]{} .From Eqs. (\[RGangle\]a,\[Ybetax\],\[limY\]) we see that at small angles $(|\phi|\lesssim {T /v_F K_F})$ there is a strong interference between the $ZS$ and $ZS'$ contributions. This interference depletes the RG flow of $\Gamma^Q (\phi)$ at small angles. Moreover, at $\phi=0$ the flow is exactly zero, for the two contributions have the same thermal factor $\beta_R\cosh^{-2}(\beta_R)$:[@note0] \[Gamma0\] [\^Q (=0, t) t]{} = 0 , t .
The initial conditions for the flow equations (\[RGangle\]) are: \[Init\] \^Q (, t=0)= \^(, t=0)=U() .Recall that the fixed points $\Gamma^{Q*}$ and $\Gamma^{\Omega *}$ of the vertices $\Gamma^Q$ and $\Gamma^\Omega$ are the forward scattering vertex and the Landau interaction function, respectively. From Eqs. (\[Gamma0\],\[Init\],\[Pauli\]) we conclude that the RG equations for the forward scattering vertex preserve the Pauli principle at any point of the RG flow trajectory \[GPauli\] \^Q (=0 , t)=0 , t ,while the “uncompensated” RG flow generated by the $ZS'$ graph drives the vertex $\Gamma^\Omega$ to a fixed point value (the Landau function), which does not satisfy the Pauli principle, i.e., $\Gamma^{\Omega*}(\phi=0) \not=0$.
Deficiencies of the decoupled approximations in the Landau channel {#deficientS}
==================================================================
Before finding a solution (exact or approximate) to the flow equations (\[RGangle\]) which fully takes into account the coupling of $\Gamma^Q$ and $\Gamma^\Omega$, we will comment on approximate solutions in which this coupling is neglected. The Landau channel, as defined in this paper, includes, at one-loop RG, both the direct ($ZS$) and exchange ($ZS'$) quasiparticle-quasihole loops with a small transfer $\cal Q$. We will call [*decoupled*]{} any treatment of the Landau channel which does not explicitly take into account both the direct and exchange contributions. It is shown below that solutions for the forward scattering vertex provided by decoupled methods fail to meet the requirements of the Fermi statistics. Tackling the Pauli principle by imposing additional constraints on the solutions (sum rules) leads to conceptual difficulties discussed below.
To shorten notation we drop upper labels ($ Q, \Omega$), and define $\Gamma$ ($F$) as the running vertex whose fixed point is the forward scattering vertex (resp. the Landau function).
Let us first solve the RG equations in the decoupled approximation. If we neglect completely the $ZS'$ contribution in Eqs. (\[RGangle\]) and perform a Fourier transformation, we recover a familiar system of equations,[@GD95] with its RPA-like solution in which all harmonics are decoupled: \[RGRPA\] = \_l\^2 \_l\^[RPA]{} ()= [\_l(\_0)1+(\_0-) \_l(\_0)]{} =0 F\_l\^[RPA]{} ()= [cst]{} . We introduced the auxiliary parameter $\tau \equiv \tanh \beta_R$ ($\tau \in [0, \tau_0]$), with $\tau_0 \equiv\tanh \beta_0$ and $\beta_0 \equiv \frac12 v_F \beta \La_0$. Since the temperature in the effective action is restricted by the condition (\[TCond\]), we can set $\tau_0=1$ for all practical purposes.
With the initial conditions $\Gamma_l(\tau_0)=F_l(\tau_0)=U_l$ (cf Eq. (\[Init\])), the fixed points of Eqs.(\[RGRPA\]) are \[RPAFP\] [(a)]{} \_l\^\* = [U\_l1+U\_l]{} F\_l\^\* = U\_l ,with the following stability conditions for the fixed point: \[Stab1\] U\_l > -1 , l ,which are the Stoner criteria well-known from the RPA approach. The bare interaction satisfies the Pauli principle (cf. Eq.(\[Pauli\])) \[Pauli2\] \_[l=-]{}\^U\_l = 0 .If the vertex $\Gamma$ is to satisfy the Pauli principle, the condition \[SR\] \_[l=-]{}\^ =0 must be imposed on the r.h.s. of (\[RPAFP\]a). However, it has been known for a long time that conditions (\[SR\]) and (\[Pauli2\]) are incompatible, unless the stability conditions (\[Stab1\]) are broken.[@Mermin67] Indeed, subtracting (\[Pauli2\]) from (\[SR\]), we find \[BrSt\] \_[l=-]{}\^ =0 ,which cannot be satisfied without violation of (\[Stab1\]).
This proves that the antisymmetric bare interaction $U$ cannot be at the same time a fixed point of the RG flow and the Landau function, unless the classic FLT formulas are unapplicable. The accepted cure to this paradox is to give up the Pauli principle on the Landau function, because of the neglected $ZS'$ contribution.[@Mermin67] In the RG approach, this may be accomplished (in the decoupled approximation) by letting the $ZS'$ contribution drive the bare interaction $U$ towards the Landau function $F^*$ during an earlier stage of mode elimination, and then by solving the RG equations (\[RGRPA\]) with $F^*$ as a new renormalized “bare” interaction.[@GD95; @NG96] This leads to the well-known relationship between the scattering vertex and the Landau function \[RPALandau\] \_l\^\* = [F\_l\^\* 1+F\_l\^\*]{} Because of the $ZS'$ contribution, the Pauli principle does not apply to $F^*$ (a), while it is enforced on the vertex $\Gamma^*$ through a sum rule (b): \[SRLandau\] [(a)]{} \_[l=-]{}\^F\_l\^\*0 \_[l=-]{}\^ = 0 .In doing so, the stability conditions (\[Stab1\]) are modified as follows \[StabPom\] F\_l\^\* >-1 , l ,i.e., they become Pomeranchuk’s stability conditions for the Fermi liquid, originally obtained on thermodynamic grounds.[@Pomeran] Such a decoupled RG treatment of the direct and exchange loops makes Eqs. (\[SRLandau\]) compatible with the conditions (\[StabPom\]).
However, the sum rule (\[SRLandau\]b) is “unnatural”, in the following sense. The bare interaction can in principle be traced from a microscopic Hamiltonian. For instance, let us consider the spinless extended Hubbard Hamiltonian on a square lattice (with lattice spacing $a$) at low filling, with nearest-neighbor repulsive interaction ($U^{\rm nn}$). Fourier-transforming and antisymmetrizing the interaction, we end up with the following coupling function of the microscopic Hamiltonian: $U^A_{\rm mic} ({\bf K}_1,{\bf K}_2;{\bf K}_3,{\bf K}_4) ~\simeq~ -\frac14 a^2
U^{\rm nn}\cdot ({\bf K}_1-{\bf K}_2)\cdot
({\bf K}_3-{\bf K}_4)$.[@Shankar94] Let us choose this interaction as a trial bare dimensionless coupling function: \[Ubare\] U(\_1-\_2)=[U]{} \^2([\_1-\_2 2]{}) ,wherein all parameters are hidden within a single coefficient ${\cal U}$. The only nonzero Fourier components $U_l$ of the interaction are: \[UbareF\] U\_0= 12 [U]{} , U\_[1]{}=- 14 [U]{} .The interaction (\[Ubare\]) satisfies the Pauli principle (\[Pauli\],\[Pauli2\]). The RPA sum rule (\[SR\]) imposes an additional constraint, which the interaction (\[Ubare\]) does not satisfy. If we suppose that the “improved” results (\[RPALandau\],\[SRLandau\]b) are always true, then, starting from any kind of microscopic interaction (e.g., the bare interaction (\[Ubare\])) and integrating “fast modes” outside the immediate vicinity of the Fermi surface, we have to end up with a “fine tuned” interaction, for any interaction has to be “fine tuned” in order to satisfy (\[SRLandau\]b). The integral of the flow (\[GPauli\]) (or, equivalently the sum rule (\[Gsumrule\]) below) is not a fine tuning, since firstly, the bare interaction at the initial point can be always antisymmetrized, and, secondly, we have an exact cancellation of the RG flow for the vertex $\Gamma$ at zero angle due to direct and exchange contributions, thus preserving (\[GPauli\]). On the contrary, there is no reason for any bare interaction to satisfy (\[SR\]) at the beginning, nor is there a mechanism to provide the fine tuning (\[SRLandau\]b) on other parts of the RG trajectory.
These difficulties are not specific to the decoupled RG approximation, since the latter is strictly equivalent to the diagrammatic microscopic derivation of FLT[@Landau59; @AGD; @Lifshitz80] leading to the same results (\[RPALandau\],\[SRLandau\],\[StabPom\]). The decoupled RG treatment is equivalent to applying the Bethe-Salpeter equation with the particle-hole $ZS$ loop singled out, $F$ being the vertex irreducible in this loop. There are no [*a priori*]{} reasons in that approach to demand this vertex to satisfy the Pauli principle. The rearrangment of diagram summations in the Bethe-Salpeter equation leading to (\[RPALandau\]) is based on the assumption that the vertex irreducible in the direct particle-hole loop ($ZS$) is a regular function of its variables, neglecting the zero-angle singularity (at $T=0$[@note0]) in the $ZS'$ loop. As a consequence, the Pauli principle for the scattering vertex ${ \Gamma}^*$ is not guaranteed in the final result and “the amplitude sum rule” (\[SRLandau\]b) must be imposed by hand. The solution (\[RPALandau\]) of the Bethe-Salpeter equation is tantamount to the summation of the ladder diagrams built up from the $ZS$ loops, wherein the Landau function stands as the bare interaction. For this reason, the solution (\[RPALandau\]) we will call the “[*the $ZS$-ladder approximation*]{}” in the following. We refer the reader to a paper of A. Hewson[@Hewson] wherein a “generalized” Bethe-Salpeter equation for Fermi liquids, which explicitly takes into account both the $ZS$ and $ZS'$ loops, is derived. For further discussion on this issue, see also Ref..
Solution of the coupled RG equations {#solutionS}
====================================
Exact Numerical Solution
------------------------
The coupled integro-differential flow equations (\[RGangle\]) may be solved numerically. The functions $\Gamma(\t)$ and $F(\t)$ are then defined on a discrete grid of angles, and simple linear interpolation is used to represent them between the grid points. The grid spacing is not uniform: it has to be very small near $\t=0$, where the flow is singular, but may be larger elsewhere. The RG equations then reduce to a large number of coupled nonlinear differential equations, which are solved by a fourth-order Runge-Kutta method with adaptive step-size. Typically, a grid of a few hundred points is sufficient (we take advantage of the symmetry of the functions). Of course, the numerical solution was checked to be indistinguishable from the (exact) RPA solution when the $ZS'$ contribution is discarded.
An example of solution for the spinless case with the interaction function (\[Ubare\]) is shown on Fig. 3(A), at various temperatures. The interaction function $U(\t)$ and the RPA solution $\Gamma^{\rm RPA}(\t)$ are also shown. This solution will be discussed in Sect. \[discussionS\].
Approximate Analytical Solution
-------------------------------
The flow equations (\[RGangle\]) may also be solved analytically, albeit only approximately. In this section we give the approximate solution for the fixed points $\Gamma^*$ and $F^*$ both in terms of Fourier components and in terms of angular variables. (See Eqs. (\[ApGam\],\[Gamang\]) below.)
The Fourier transform of Eqs. (\[RGangle\]) is \[GFex\] = [1\^2\_R]{}\_n\^2 + [F\_n\_R]{} = -\_[l,m=-]{}\^\_[n-m,2l-2m]{}(\_R) \_l \_[l-2m]{} \_[n’,m’]{}(\_R) \_0\^[/2]{} d \_0\^d (2n’) (m’) (\_c-||)Y(,;\_R) .On the plane $(\phi,\t)$, the function $Y(\phi,\t;\beta_R)$ has a maximum on the line $\t=\pi/2$, which moves from the position $(\pi/2,\pi/2)$ at the beginning of renormalization procedure (when $\beta_R
\sim\beta_F$) towards the position $(0,\pi/2)$ when approaching the fixed point $(\beta_R\to 0)$. Elsewhere, $Y(\phi,\t;\beta_R)$ is either quite flat, or its contribution is eliminated by the cutoff factor $\Theta(\t_c-|\phi|)$ during the renormalization flow. Therefore, we approximated the function $Y(\phi,\t;\beta_R)$ on the plane $(\phi, \t )$ by its value on the line $(\phi,\pi/2)$. This approximation, simplifying considerably our equations, allows an analytical treatment and a qualitative insight harder to find in purely numerical results. The approximate analytical solution of the RG equations given below justifies that simplification [*a posteriori*]{}, when compared with the direct numerical solution of Eqs. (\[RGangle\]).
The approximate RG equations are: \[RGFNew\] = \_[m=-]{}\^\_m\^2 = -\_[m=-]{}\^Y\_[n-m]{}(\_R) \_m\^2 ,wherein \[FY\] Y\_n(\_R) = [2 ]{} \_0\^[(2 \_R/\_F)]{} d Y(,[2]{}; \_R) (2n ) .The key difference between Eqs.(\[RGRPA\]) and (\[RGFNew\]) is that the former do not generate new harmonics since all harmonics are decoupled, whereas the latter couple all harmonics (because of the $ZS'$ contribution) in such a way that an infinite number of new harmonics are generated by the RG flow, even if only a finite number of harmonics are nonzero at the start. For instance, the trial interaction (\[UbareF\]) has only three nonzero components, but according to Eqs.(\[RGFNew\]) the fixed points $\Gamma^*$ and $F^*$ will possess an infinite number of them. The generation of new harmonics is not an artefact of the approximation which was used to go from Eqs. (\[RGangle\]) to Eqs. (\[RGFNew\]), but is a generic consequence of the interference in the Landau channel (cf. Eqs. (\[GFex\])).
Let us start the analysis of Eqs.(\[RGFNew\]) with a heuristic observation. Whereas the component $Y_0(\beta_R)$ is a nonnegative function of $\beta_R$, the others $(Y_n(\beta_R),~~n \geq 1)$ are increasingly oscillating functions of $\beta_R$ when $n$ increases. These oscillations along the whole RG trajectory $[0,\beta_0]$ will effectively decrease the contributions from the harmonics $\Gamma_m$ $(m\neq n)$ to the flow of $\Gamma_n$. Because of this, we expect the diagonal terms ($m=n$) of Eqs.(\[RGFNew\]) to be more important, and this justifies a perturbative approach, in which the nondiagonal terms are ignored at zeroth order. Let $\gamma_n(\beta_R)$ be the zeroth order solution: \[QuasiRPA\] [\_n \_R]{} = \_n\^2 .The solution is \[gamQRPA\] \_n(\_R)= [U\_n ]{} ,with \[In\] I\_n(\_R) && \_0\^[\_R]{} d\_R’ Y\_n(\_R’) = [1\_F]{}\_0\^[(2 \_R/\_F)]{} d\
&& .The fixed point $\gamma_n^*$ is \[gamast\] \_n\^\*= [U\_n 1+ U\_n]{} .The integrals $I_n(\beta_0)$ can be evaluated analytically, since $(\beta_F, \beta_0) \gg 1$ according to condition (\[TCond\]). In the following we shall need the first two components only: \[I0\] I\_0(\_0) && [\_0 K\_F]{}[1 ]{}\
&&+[1]{}(2 - ) + [T v\_F K\_F]{} [(2)(3)]{} I\_1(\_0) && [\_0 K\_F]{}[1 ]{} +[Tv\_F K\_F]{} [(2)(3)]{} .(The next term in the temperature dependence, omitted in Eqs. (\[I0\]), is of the order $(T/v_FK_F)^3$). Treating the off-diagonal terms ($n \neq m$) on the r.h.s. of (\[RGFNew\]a) as perturbations, we obtain the following approximate solution at first order: \[ApGam\] \_n(\_R) \_n(\_R) + \_[m n]{} \_[\_R]{}\^[\_0]{} d\_R’ Y\_[n-m]{}(\_R’) \_m\^2 (\_R’) F\_n(\_R) = \_n(\_R) + \_[\_R]{}\^[\_0]{} d\_R’ .It is straightforward to check that the solution (\[ApGam\]a) satisfies the sum rule (i.e., the Pauli principle (\[Gamma0\],\[GPauli\])): \[Gsumrule\] \_[n]{} \_n(\_R)=0 , \_R .The solution (\[ApGam\]) can be converted back in terms of the relative angle $\t\in [-\pi,\pi]$ with a little help from Eq. (\[QuasiRPA\]): \[Gamang\] \^\*() &=& U() - \_0\^[\_0]{} [d\_R \^2\_R]{} \_[n=-]{}\^(n) \_n\^2 (\_R)\
&&+(\_0-||) \_[12 \_F |(/2)|]{}\^[\_0]{}d\_R Y([2]{},[2]{}; \_R) \_[n=-]{}\^(n) \_n\^2 (\_R) F\^\*() = \^\*() + \_0\^[\_0]{} [d\_R \^2\_R]{} \_[n=-]{}\^(n) \_n\^2 (\_R) ,wherein $\t_0 \equiv 2 \arcsin(2 \beta_0/\beta_F)$. A comparison of Eqs. (\[Gamang\]a) and (\[RGangle\]a) shows that – with the aforementioned approximation of the angular dependence of the function $Y$ – the approximate solution (\[ApGam\]a) may be obtained by replacing the vertex components $\Gamma_n$ on the r.h.s. of Eq. (\[RGangle\]a) by the “renormalized” RPA ansatz (\[gamQRPA\]). It would be a mistake, however, to conclude that the $ZS'$ diagram contributes only to the third term on the r.h.s. of Eq. (\[Gamang\]a) since the $\gamma_n$-s partially include its contribution. It is worth noting that Eqs. (\[ApGam\]b,\[Gamang\]b) are not approximations in the sense of Eqs. (\[ApGam\]a) or (\[Gamang\]a), but they are exact relations for $F$, derived from the basic RG equations (\[RGFNew\]).
Extension of the Effective Action
---------------------------------
In the numerical and analytical results presented in the following sections the initial cutoff $\La_0$ of the effective action is extended to $K_F$, i.e., $\beta_0 =\beta_F/2$. This point should be clarified. Notice first that the $ZS$ contribution is not sensitive to the bandwidth cutoff $\La_0$ – provided condition (\[TCond\]) is satisfied – since $\tanh\beta_0$ is unity with exponential accuracy. On the other hand, the angular cutoff of the $ZS'$ contribution (cf. Eqs. (\[RGangle\],\[GFex\],\[FY\],\[In\])) comes from a cutoff imposed on the momentum transfer in this graph (cf. Eq. (\[ZS’\])). It is $\t_c=\arcsin(2\beta_R/\beta_F)$ (with $2\beta_R/\beta_F \equiv\La/K_F$) if $\La_0 \leq K_F$, and $\t_c=\pi/2$ otherwise. The specific choice $\beta_0 =\beta_F/2$ ($\La_0 = K_F$) means that at the initial point of the RG flow the angle $\phi$ is allowed to take all values (i.e., the momentum transfer ${\bf Q}'$ is not cut off), while the bandwidth is extended to the full depth of the Fermi sea. It can be checked that the results are not sensitive to the choice of a bigger cutoff $\La_0\gtrsim K_F$, since then not only is the $ZS$ contribution to the flow is exponentially small, but that of $ZS'$ as well, until the cutoff decreases to $\La \sim K_F$ (this was also confirmed by direct numerical tests). The formulas for the approximate analytic solution are derived for $\Lambda_0 \leq K_F$.
Such an extension of the low-energy cutoff to large values is analogous to what is routinely done in $1D$ models (e.g., the Tomonaga-Luttinger model[@Voit]). In that context, deviations of the real excitation spectrum from linearity and the approximated integration measure are expected to affect only the numerical values of the renormalized physical parameters.
Choosing $\Lambda_0 \sim K_F$ renders the RG fixed points (observables) sensitive only to the two independent physical scales present in the model: $T$ and $v_FK_F=2E_F$, and not to the arbitrary scale $\La_0$, which divides fast and slow modes. Lowering the running cutoff until it reaches some intermediate scale $\Lambda_X$ (such that $\Lambda_X\ll K_F$ and $v_F\Lambda_X\gg T$) provides us with $\Lambda_X$-dependent parameters for the action. We regard $\La_X$ as the scale of the low-energy effective action. However, the observable quantities (the fixed points) do not depend on a particular choice of $\La_X$.
Analysis and Discussion of the RG Results {#discussionS}
=========================================
We will now discuss the main novelties brought by quantum interference in the Landau channel and compare with the results of decoupled approximations. The solutions $\Gamma^*(\t)$ and $F^*(\t)$ at different temperatures and for the interaction (\[UbareF\]) are shown on Fig.3 (A: direct numerical solution of Eqs. (\[RGangle\]); B: solution (\[Gamang\])). For this interaction the sum in the second and third terms on the r.h.s. of Eq. (\[Gamang\]a) is $\gamma_0^2 (\beta_R)+2 \gamma_1^2 (\beta_R)\cos\t$. The curves were calculated for ${\cal U}=1$ (cf. Eq. (\[Ubare\])), which is four times smaller than the critical value ${\cal U}_{cr}^{\rm RPA}=4$ at which the instability appears in the RPA solution (\[RGRPA\]a) for $\Gamma_1^*$. Comparison of the approximate solutions (\[ApGam\],\[Gamang\]) with the direct numerical solution shows good agreement.
In Fig. 3 the differences between the RG solution and the RPA solution (\[RGRPA\]a) are minor at large angles, but they become especially striking at small angles $\t$, where the interference between the $ZS$ and $ZS'$ contributions is very strong. The RG solution gives $\Gamma^*(\t=0)=0$ (the Pauli principle), while $\Gamma^{\rm RPA}(\t=0)=-1/3$ for this interaction strength. The Landau interaction function $F^*(\t)$ differs from the bare interaction $U(\t)$, and $F^*(\t=0) \neq 0$. If the $ZS'$ contribution is neglected (the RPA solution (\[RGRPA\]b)), these two quantities coincide.
An interesting feature of the RG result is the temperature dependence of the vertices $\Gamma^*(\t)$ and $F^*(\t)$. As $T$ decreases, the “beak” of $\Gamma^*(\t)$ in the region of strong interference becomes narrower. The characteristic angular width of this “beak” is $|\t| \sim T/v_FK_F$. A similar narrowing is noticeable in the temperature dependence of $F^*(\t)$. One can also see from the figures a weakening of the interference effect at lower temperatures, for then the RG solutions lie closer to the RPA curves, but the distinctions between them do not disappear as $T \to 0$, and the RG never reproduces the RPA result.[@noteT0]
In terms of Fourier components this behavior manifests itself in a linear temperature dependence of $\Gamma^*_n$ and $F^*_n$. This linearity is found both in the direct numerical solution of Eqs. (\[RGangle\]), and from the solution of Eqs.(\[FY\],\[gamQRPA\],\[In\],\[ApGam\]). This temperature dependence can be revealed analytically. Integrating by parts and using Eq. (\[QuasiRPA\]), we can rewrite Eq. (\[ApGam\]a) at the fixed point as \[GBP\] \_n\^\* =\_n\^\* + \_[m n]{}I\_[n-m]{}(\_0)U\_m\^2 -2 \_0\^[\_0]{} d\_R \_[m n]{} I\_[n-m]{}(\_R) \_m\^3(\_R) .The leading term on the r.h.s. of Eq. (\[GBP\]) is $\gamma_n^*$. Using then Eq. (\[gamast\],\[I0\]a), we obtain for $n=0,1$: \[Gamas\] \_n\^\*(T) \_n\^\*(T) \_n\^\*(0) + [T v\_F K\_F]{} [(2)(3)]{} \[\_n\^\*(0)\]\^2 , (n=0,1) ,wherein \[gamT0\] \_n\^\*(0) = [U\_n ]{} .For the interaction (\[UbareF\]) $U_n=0$ and so $\gamma_n^*=0$ for $n>1$. Thus, the higher harmonics $\Gamma_{n>1}^*$, are entirely generated by the RG flow. To leading order, we obtain from Eq. (\[GBP\]): \[Gam2\] \_2\^\* I\_1(\_0)U\_1\^2 .This component also has a linear temperature dependence, according to Eqs. (\[I0\]). To estimate the components of the Landau function, we first rewrite Eq. (\[ApGam\]b) in another, equivalent form (cf. Eqs. (\[RGFNew\])): \[Feq\] F\_n(\_R) = U\_n + \_[m=-]{}\^ \_[\_R]{}\^[\_0]{} d\_R’ Y\_[n-m]{}(\_R’) \_m\^2 (\_R’) .Proceeding in the same fashion as above, we obtain the linear temperature-dependent components $F_n^*$: \[Fnas\] F\_n\^\* U\_n +I\_0(\_0)U\_n\^2+ (|n-1|+1)I\_1(\_0)U\_[|n-1|]{}\^2 , (n=0,1) F\_2\^\* I\_1(\_0)U\_1\^2 .We should emphasize that simple formulas like (\[Gamas\],\[Gam2\],\[Fnas\]) serve only to illustrate how the temperature dependence comes about, and give only the order of magnitude of the higher harmonics ($n > 2$). The latter should rather be calculated numerically. The temperature dependence of the lowest harmonics (e.g., $F^*_0$ and $F^*_1$) does not seem to be a relevant issue in the calculation of quantities such as the compressibility, effective mass and heat capacity, since, in the total $ZS'$ contribution, the temperature corrections, of the order of $T/v_FK_F$, are very small in comparison with the main corrections of order $\Lambda_0 /K_F$. As a consequence, the actual values of the lowest harmonics vary within a few percent at most, even in the entire temperature interval $0 \leq T/v_FK_F \leq 0.1$ (the maximum temperature studied is really high: $T=0.2 E_F$).
The temperature dependence is more pertinent as a “collective” effect of the higher harmonics generated by the RG flow. Let us explain this point with the example of the interaction (\[UbareF\]). The “improved” RPA ansatz (\[gamQRPA\]) renormalizes the bare components $U_n$ into $\gamma_n$ ($n=0, \pm 1$). The latter form almost perfectly the function $\Gamma^*(\t)$, except at small angles. For those three components $\gamma_n$ the sum rule (\[Gsumrule\]) is less violated than for the “pure” RPA components (\[RPAFP\]a). The generation of the new harmonics by the second term on the r.h.s. of Eq. (\[ApGam\]a) gives “a final touch” to the curve $\Gamma^*(\t)$, resulting mostly in the formation of a temperature-dependent feature near $\t=0$. The actual calculation of the components $\Gamma^*_n$ showed that, in order to obtain with acceptable accuracy the right form of $\Gamma^*(\t)$ provided by Eq. (\[Gamang\]a) via the Fourier transformation of Eq. (\[ApGam\]a), at least $N_{\rm max} \sim v_FK_F/T$ components are necessary. So, the lower the temperature is, the more harmonics are needed for the formation of the vertex $\Gamma^*(\t)$. The same conclusion can be drawn from a numerical solution of the equations, but since it is carried out in terms of angles on a discrete grid, a reliable calculation of higher harmonics is difficult.
Another physical consequence of the quantum interference in the Landau channel is the increased robustness of the system against instabilities induced by strong interactions. Even from the approximate solution (\[ApGam\]), we see that the maximum interaction strength allowed is now larger than the one provided by the RPA solution (cf. (\[RPAFP\],\[Stab1\])). From Eq. (\[gamast\]) we obtain the stability conditions for the approximate solution (\[ApGam\]): $U_l >
-[1-I_0(\beta_0)]^{-1}, ~\forall~ l$ with $0<I_0(\beta_0)<1$ according to (\[I0\]a). Since $I_0(\beta_0)$ grows with temperature, larger values of $|U_l|$ are allowed as $T$ increases: the higher the temperature, the more stable the system is, as it should be from physical grounds. At the optimal choice of the initial cutoff ($\La_0 = K_F$), $I_0(\beta_0)$ grows from 0.255 at $T=0$ to 0.27 at $T/v_FK_F=0.1$. This value of temperature is the largest we can try without violating the condition of applicability of our model (\[TCond\]). Thus, within this approximate solution, the effect of interference increases the critical coupling by 40% compared the the RPA critical value (\[Stab1\]). Since we are retaining only two one-loop diagrams, linearized excitation spectrum and integration measure, we cannot be more conclusive on the role of the modes deep into the Fermi sea in screening a microscopic interaction of arbitrary strength, and in stabilizing the Fermi liquid phase.
Contact with the Landau FLT and Discussion {#contactS}
==========================================
In this section we explain how the present RG theory is related to the standard results of the Landau FLT.[@Landau57; @Landau59] This will also allow us to relate this study to previous work on this RG approach to the Fermi liquid.[@GD95; @NG96]
It is important to notice that the two contributions to the RG flow, coming from the $ZS$ and $ZS'$ graphs, behave quite differently as the flow parameter $\beta_R$ runs from $\beta_0 \gg 1$ towards $\beta_R=0$. At large $\beta_R$ the $ZS$ contribution to the flow, which gives the term proportional to $\cosh^{-2} \beta_R$ on the r.h.s. of Eq. (\[GFex\]), is virtually negligible, up to $\beta_R \sim 1$. On this part of the RG trajectory, the main contribution to the renormalization of $\Gamma$ and $F$ comes from the $ZS'$ graph. On the other hand, closer to the fixed point ($\beta_R \lesssim 1$), the $ZS$ contribution grows since $\cosh^{-2}\beta_R \sim 1$ for all harmonics, while $Y_n(\beta_R)$ decreases for the lower-order harmonics. At $\beta_R \ll 1$: \[Yas2\] Y\_n(\_R) . Using the approximated form (\[FY\]) is justified here, since at $\beta_R\ll 1$ there is no difference between the exact form of the RG equations (\[GFex\]) and Eqs. (\[RGFNew\]). Indeed, when $\beta_R \ll 1$, the largest allowed $\phi$ is roughly $ 2 \beta_R / \beta_F$, so in Eq.(\[Ybetax\]) ${\rm max} | \beta_{Q^\prime} | \approx 2 \beta_R \ll 1$ and the limit (\[limY\]) of the function $Y$ can be taken. The Kronecker delta appearing after the integration over $\t$ removes one summation, and we recover exactly Eqs. (\[RGFNew\]) with $Y_n(\beta_R)$ given by (\[Yas2\]). It should be also kept in mind that the $ZS'$ flow is localized within the angle $|\phi| \sim 2 \beta_R /
\beta_F$.
Such different behavior of the two contributions ($ZS$ and $ZS'$) to the total RG flow explains why approximations based on the decoupling of these two contributions (RPA, $ZS$-ladder[@AGD; @Lifshitz80; @GD95; @NG96]) are reasonable. To clarify to what extent the standard results of FLT (\[RPALandau\],\[SRLandau\]) can be corroborated by RG, we will make a two-step approximation of our RG equations. In doing so we will follow exactly the “recipe” of the $ZS$-ladder approximation discussed in Sec.V, but now we can check each step by direct comparison with the RG solution of Eqs. (\[RGangle\]).
In the first step we neglect the contribution of the $ZS$ graph above an intermediate flow parameter $\beta_X$. As one can see from the RG equations (\[GFex\]), this removes the exponentially small difference between $\Gamma_n( \beta_R)$ and $F_n( \beta_R)$ at $\beta_R > \beta_X$. This approximation is asymptotically exact as $T \to 0$.[@note0] Neglecting, in the second stage of this approximation, the $ZS'$ flow for $\beta_R < \beta_X$, localized by that time within the angle $\t_X = 2 \arcsin(2 \beta_X / \beta_F)$, we recover the exactly solvable equations (\[RGRPA\]) with the new initial point $\beta_R =
\beta_X$, instead of $\beta_R = \beta_0$. Then according to Eqs. (\[RGRPA\]), $F_n^{X} \equiv F_n(\beta_X)$ is the (approximate) fixed point value of the Landau function, while $\Gamma_n(\beta_R)$ flows towards the (approximate) fixed point $\Gamma_n^{\rm ph}$ from the new bare value $\Gamma_n^X \equiv \Gamma_n(\beta_X) = F_n^{X}$. This second step of approximation violates the Pauli principle, no matter how close we are to the Fermi surface (cf. Eq.(\[Gamma0\]) and Ref.). Afterwards the theory says nothing about the values of the functions $\Gamma(\t)$ and $F(\t)$ inside the interval $2 \t_X$ and, of course, there are no more correlations between these functions.
To preserve the correct zero-temperature limit and to minimize the angle within which the approximation gives completely wrong results for $\Gamma^*$ and $F^*$, the intermediate cutoff $\La_X$ corresponding to $\beta_X=v_F \La_X /2T$ should be chosen such that $\tanh \beta_X \approx
1$ (cf. Eqs. (\[RGRPA\],\[RPAFP\]) and Ref.) and $2\beta_X / \beta_F =\La_X / K_F \ll 1$. Summing up what is said above, we obtain: \[Lappr\] \_n\^[ph]{} = [\_n\^X ]{} = [F\_n\^[X]{} ]{} \_n\^X=F\_n\^[X]{} = U\_n + \_[l, m=-]{}\^\_[\_X]{}\^[\_0]{} d\_R’ [Y]{}\_[n-m, 2l-2m]{}( \_R’) \_l (\_R’) \_[l-2m]{}(\_R’) .
In Fig. 4 we illustrated all this by the direct numerical calculation of $F^{X}$, $\Gamma_n^X$ from Eqs. (\[RGangle\]) for the interaction (\[Ubare\]), followed by a calculation of $\Gamma^{\rm ph}$ from Eqs. (\[Lappr\]). The RG solutions for $\Gamma^*$ and $F^*$ are also presented. The function $F^{X}(\t)$ follows almost perfectly the Landau function (the real fixed point $F^*(\t)$), except within $2 \t_X$ of $\t=0$. In the part of the RG trajectory $\beta_X \leq \beta_R \leq \beta_0$ ($\beta_0=100$, $\beta_X=5$, $T/v_FK_F =0.005$), not only is the $ZS$ flow exponentially weak, but the central part of the $ZS'$ flow as well (cf. Eq. (\[limY\])). So, the evolution of both vertices is due mostly to the “tail” $\t > \t_X$ of the function $Y$ at $\beta_R \gtrsim 1$. That is why $\Gamma^X(\t)$ and $F^{X}(\t)$ are virtually identical. Only the slowing down of the $ZS'$ flow almost everywhere at $\beta_R \lesssim 1$ – except on the central part (cf. Eq. (\[Yas2\])) wherein it is always as strong as the other one ($ZS$) – results in the drastic differences between the two limits of the four-point vertex at the fixed point. The function $\Gamma^{\rm
ph}(\t)$ is featureless and looks like a corrected RPA solution. The differences between $\Gamma_n^*$ and $\Gamma_n^{X}$ ($F_n^*$ and $F_n^{X}$) are negligible, i.e. less than 1%, only for the components $n=0,1$.
As it should be clear by now, there is no real incompatibility of the stability conditions with the Pauli principle, since this is a mere artefact of the ZS-ladder approximation. It is pointless to impose the sum rule either to $\Gamma_n^{\rm ph}$ in the form (\[Gsumrule\]), or to $F_n^{X}$ in the form (\[SRLandau\]). Both sums would give the value of the “uncorrelated” function $\Gamma^{\rm ph}(\t)$ at $\t =0$. This function goes smoothly from the right patch $[\t_X, \pi]$ towards $\t=0$ (cf. Fig. 4) – or, equivalently, from the left, because of parity . Actually, it can be proved exactly, turning the arguments of Sec.V around, that in a stable Fermi liquid, it is impossible to obtain $\Gamma^{\rm ph}(\t=0)=0$, even by chance. Thus, there is no need for the Landau function $F^*$ to be “fine tuned” in the sense of the sum rule (\[SRLandau\]), since only the relation (\[Lappr\]) – between the approximate vertex $\Gamma^{\rm ph}$ and $F^X$ – is an exact relationship (more precisely, asymptotically exact when $T\to 0$), not (\[RPALandau\]), which relates the physical quantities $F^*$ and $\Gamma^*$.
In the context of our discussion at the end of Sect. \[solutionS\], notice that the cutoff $\La_X$ ($v_F \La_X/T \gg 1$, $ \La_X/K_F \ll 1$) corresponds to the initial cutoff of the [*low-energy*]{} effective action wherein $\Gamma^X$ is the bare interaction function (coupling) of that action. The equality of the functions $\Gamma^{X}$ and $F^{X}$ illustrates the point of Sect. \[couplingS\] that, at the beginning, the action’s coupling function can be defined independently of the order in which the zero-transfer limit is taken.
When the RG flow reaches the scale $\La_X$, the contribution of the $ZS'$ graph to the flow of $\Gamma_n$ and $F_n$ is strictly irrelevant in the RG sense, and could have been neglected in a model with a finite number of couplings (e.g., the $\varphi ^4$ theory, 1D g-ology models, and so on), keeping only marginal terms (cf. Eqs. (\[RGRPA\])). But, as pointed out by Shankar,[@Shankar94] in the vicinity of the Fermi surface we are dealing with coupling [*functions*]{}, i.e., with an [*infinite*]{} set of couplings. Our RG solution provides a curious example of a finite deviation of the RG trajectory at the fixed point due to an infinite number of irrelevant terms. The [*right*]{} fixed point ($\Gamma^{*}(\theta =0)=0$) cannot be reached if those terms are neglected, since $\Gamma^{\rm ph}(\t_X\to0) \ne \Gamma^*(\t=0)$ (even at $T=0$[@noteT0]) and we would return to the problems caused by the solution $\Gamma^{\rm ph}$ (the $ZS$-ladder approximation) discussed in Sec.V. To put it differently, neglecting those irrelevant terms at some part of the flow (solution (\[Lappr\])) violates the invariance of the RG trajectory at the point $\theta=0$, expressed by Eqs. (\[Gamma0\],\[Init\],\[GPauli\]).
The $ZS$-ladder approximation seems acceptable in the normal Fermi liquid regime with moderate interaction ($F_n \lesssim
10$), when the narrow-angle features of vertices revealed by the RG theory are not too large,[@noteT0] because the forward ($\t=0$) singularity has little effect on the first components ($\Gamma_n^* \approx \Gamma_n^{\rm
ph}$, $F_n^* \approx F_n^{X}$ for $n=0,1$ and, in the case of a weak interaction, for $n=2$). This singularity affects mostly the higher Fourier components. So, the relationship (\[RPALandau\]) is valid only for small $n$. It should not be used for $F_n^*$ ($n \geq 2$) neither directly, nor via the sum rule from the scattering vertex provided experimentally. For the physical vertex $\Gamma_n^*$ the sum rule (\[Gsumrule\]) is always valid, but this study indicates that its angular shape may require a large number of harmonics to adequately represent it. The existence of a finite solution for $\Gamma^{\rm ph}(\t)$ under conditions \[stabNum\]\_n\^X > -1, n guarantees not only finite RG solutions for $\Gamma^*$ and $F^*$, but also the fulfillment of the thermodynamic Pomeranchuk conditions (\[StabPom\]) by $F^*$.
The major consequence of this study on the standard results of the Landau FLT is reducing the relationship (\[RPALandau\]) between the components of the scattering vertex and the Landau function to the rank of approximation and invalidating of the sum rule (\[SRLandau\]). The rest of results for normal Fermi liquids would not be affected seriously by the RG corrections. For example, the temperature dependence of the vertices would give a weak correction to the leading terms. These conclusions are neither related to the specific choice model considered, nor to the spatial dimension. Including spin doubles the number of vertices involved, changing nothing essentially. (The derivation of the RG equations with spin is straightforward using the $N$-flavor formalism of Ref .) The differences for the case $d=3$ are only quantitative (e.g., the type of the temperature dependence) because of different angular functions and solid angle integrations.
Summary
=======
In studying the Fermi-liquid regime of interacting fermions in $d>1$ with the model of the $\psi^4$-Grassmann effective action as starting point of the analysis, one must distinguish between three quantities: ([*i*]{}) the bare interaction function of the effective action; ([*ii*]{}) the Landau interaction function; ([*iii*]{}) the forward scattering vertex. We have derived the RG equations for the Landau channel which take into account both contributions of the $ZS$ and $ZS'$ graphs at one-loop level. The basic quantities of the Fermi liquid theory, the Landau function and the scattering vertex, are calculated as fixed points of the RG flow in terms of effective action’s interaction function.
The classic derivation of Fermi liquid theory using the Bethe-Salpeter equation for the four-point vertex at $T=0$ is based on the approximation that the vertex irreducible in the direct particle-hole loop ($ZS$) is a regular function of its variables, neglecting the zero-angle singularity in the exchange loop ($ZS'$). This approach is equivalent to our earlier decoupled RG approximation[@GD95; @NG96], and they are both tantamount to summation of the direct particle-hole ladder diagrams, wherein the Landau function stands as the bare interaction (the $ZS$-ladder approximation).
One of the major deficiencies of the $ZS$-ladder approximation is that the antisymmetry of the forward scattering vertex related by the RPA-type formula to the Landau interaction function, is not guaranteed in the final result, and the amplitude sum rule must be imposed by hand on the components of the Landau function. This sum rule, not indispensable in the original phenomenological formulation of the Landau FLT[@Landau57], from the RG point of view is equivalent to fine tuning of the effective interaction.
The strong interference of the direct and exchange processes of the particle-hole scattering near zero angle invalidates the $ZS$-ladder approximation in this region, resulting in temperature-dependent narrow-angle anomalies in the Landau function and scattering vertex, revealed by the RG analysis. In the present RG approach the Pauli principle is automatically satisfied. As follows from the RG solution, the amplitude sum rule being an artefact of the $ZS$-ladder approximation, is not needed to respect statistics and, moreover, is not valid.
Stimulating conversations with C. Bourbonnais, N. Dupuis and A.-M. Tremblay are gratefully acknowledged. In particular we thank A.-M. Tremblay for careful reading of the manuscript. This work is supported by NSERC and by F.C.A.R. (le Fonds pour la Formation de Chercheurs et l’Aide à la Recherche du Gouvernement du Québec).
L.D. Landau, Sov. Phys. JETP [**3**]{}, 920 (1957); [**5**]{}, 101 (1957). I.Ia. Pomeranchuk, Zh. Eks. Teor. Fiz. [**35**]{}, 524 (1958), (English Transl.: Sov. Phys. JETP, [**8**]{}, 361 (1959)). L.D. Landau, Sov. Phys. JETP [**8**]{}, 70 (1959). J.M. Luttinger, Phys. Rev. [**119**]{}, 1153 (1960). A.A. Abrikosov, L.P. Gorkov, and I.E. Dzyaloshinski, 1963, [*Methods of Quantum Field Theory in Statistical Physics*]{} (Dover, New York). P. Nozières, 1964, [*Interacting Fermi Systems*]{} (Benjamin, New-York). E.M. Lifshitz, L.P. Pitayevskii, 1980, [*Statistical Physics II*]{} (Pergamon Press, Oxford). D. Pines, P. Nozières, 1966, [*The Theory of Quantum Liquids: Normal Fermi Liquids*]{} (Addison-Wesley, New York). G. Baym and C. Pethick, 1991, [*Landau Fermi-liquid theory*]{} (John Wiley and Sons, New-York). A. Houghton and B. Marston, Phys. Rev. B, [**48**]{}, 7790 (1993); H.-J. Kwon, A. Houghton, and B. Marston, Phys. Rev. B, [**52**]{}, 8002 (1995); A.H. Castro Neto and E. Fradkin, Phys. Rev. Lett. [**72**]{}, 1393 (1993); Phys. Rev. B, [**51**]{}, 4048 (1995). See also references therein. F.D.M. Haldane, in [*Proceedings of the International School of Physics “Enrico Fermi”, 1992*]{}, ed. R.A. Broglia and J.R. Schrieffer (North Holland, Amsterdam, 1994). G. Benfatto and G. Gallavotti, J. Stat. Phys. [**59**]{}, 541 (1990); , 9967 (1990). R. Shankar, Physica A [**177**]{}, 530 (1991). J. Polchinski, in [*Proceedings of the 1992 Theoretical Advanced Studies Institute in Elementary Particle Physics*]{}, ed. J. Harvey and J. Polchinski (World Scientific, Singapore, 1993). R. Shankar, Rev. Mod. Phys. [**66**]{}, 129 (1994). S. Weinberg, Nucl. Phys. [**B413**]{} \[FS\], 567 (1994). C. Nayak, F. Wilczek, Nucl. Phys. [**B417**]{} \[FS\], 359 (1994); [*ibid.*]{} [**B430**]{} \[FS\], 534; cond-mat/9507040. A. C. Hewson, Adv. Phys. [**43**]{}, 543 (1994). G.Y. Chitov and D. Sénéchal, Phys. Rev. B [**52**]{}, 13487 (1995). N. Dupuis and G.Y. Chitov, Phys. Rev. B, [**54**]{}, 3040 (1996). A. Stern and B.I. Halperin, Phys. Rev. B [**52**]{}, 5890 (1995). B.I. Halperin, P.A. Lee and N. Read, Phys. Rev. B [**47**]{}, 7312 (1993) The latter point is challenged in some studies predicting a finite effective mass, like, e.g., the bosonization approach of P. Kopietz and G.E. Castilla, Phys. Rev. Lett. [**78**]{}, 314 (1997). This question deserves further study. N.D. Mermin, Phys. Rev. [**159**]{}, 161 (1967). For a comprehensive introduction into the effective action formalism in the present context of fermion systems and other useful issues we recommend a recent review of W. Metzner, C. Castellani and C. Di Castro, cond-mat/9701012. N. Dupuis, cond-mat/9604189. Both the $ZS$ contribution and the zero-angular part of the $ZS'$ contribution become singular in the limit $T \to 0$ since $\lim_{\beta\to \infty }
(\beta /4)\cosh^{-2}(\beta x/2)=\delta (x)$. See, for instance, J. Voit, Rep. Prog. Phys. [**58**]{}, 977 (1995). At exactly zero temperature the angular features of the vertices reduce to finite discontinuities at zero angle, accompanied by finite-angle deviations from the RPA curve depending on the parameters of the effective action, e.g., the radius of Fermi surface, the strength of the interaction, etc. The zero-temperature limit is, however, mostly an academic question since the effect of interference between the Landau and the BCS channels, neglected in this study, would result in a Kohn-Luttinger instability in the $V$-interaction function[@Shankar94] and destroy the regime of Fermi liquid before the system attains $T=0$. Due to this second interference our results are not reliable near $\theta =\pi$, since $\Gamma( \pi)=V(0)$.[@Shankar94; @GD95]
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Virtual Reality and Mystical Maturity
Summary:
Development in virtual reality technologies, and increasing interest in technologies that directly transform conscious experience, or help users train conscious experience, bring up very
interesting parallels with common tenets of some mystical traditions. Mystical claims point toward where VR will most likely go in the future and what some of the implications will be. VR
and consciousness hacking technologies will lead to classical mystical insights and powers, but what's really interesting is what happens then…
For decades technologists had tried and failed to create significantly believable, immersive virtual realities that didn't make people nauseous with extended use. VR technologies
progressed, but the holy grail of a Star Trek Holodeck style virtual environment seemed much harder to achieve than expected.
But in the last few years VR has been having a momentous revival. Mostly this has been because of Oculus Rift, a VR headset developed by 23 year old Palmer Luckey (who was recently featured on the cover of TIME) with the assistance of an extended community of professional
and amateur VR engineers. Oculus seemed to break the code and create 360 degree VR landscapes that are immediately compelling and exciting. Oculus eventually raised $2.4 million
dollars on Kickstarter to develop their prototype. (A tactic that later became controversial when Oculus was bought by Facebook for $2 billion. None of the Kickstarter supporters received equity
in the company, as early stage investors would have if Oculus had raised their initial funding that way.) The ability to create experiences or put VR users into faraway places is exciting to,
well, pretty much every industry, from gaming and porn, VR's most obvious initial applications, to religious ministry. But there are major steps still to take. Let's imagine where VR is going and then we'll see how this links up with
mysticism.
Right now VR experiences are primarily visual and auditory, and obviously, no matter how good the sights and sounds get they will never be enough to recreate our full multisensory experience.
People are working on including our other senses. Several companies are bringing touch to VR. Taste is still missing of course, and so is smell, which is
very important for creating meaningful emotional experiences and lasting memories.
These all may be pretty hard to crack, but I expect us to do it eventually. So let's assume that we have already created fully immersive VR that's like real life in every sensory way.
What would people want next? The next huge step, even bigger in fact, would be being able to influence our sense of identity and narrative memory of our lives. When I enter VR I still know
that I am "me" in real life having a VR experience. Every VR experience would be a lucid dream by default. We wouldn't yet be able to "forget" ourselves in the dream. But, we’ll overcome
this too, because people will want to literally become the character in the dream, to change their identities, their histories, their character traits, and their behaviors, and to forget whoever
it was they were before. And they'll want to do it over and over again to experience many different kinds of lives - lives that are better than their real lives, and sometimes worse as well, or
just different, to see what it's like. It will be exactly like Alan Watt’s famous Dream of Life talk.
It will also be a lot like the vision of reincarnation of Hinduism and Buddhism, both of which hold that all creatures are moving through many many lives. Over the course of these infinite
numbers of lives, beings are presented with challenges and opportunities to learn and grow and, specifically, to become more wise and compassionate. In both Hinduism and Buddhism the last goal of
all beings is to exit this cycle of birth and death, because all lives, no matter what kind, are seen to be replete with unavoidable suffering. Virtue, logic, and the intrinsic desire for
happiness all overlap in the motivation to end one's own and others' suffering by gaining enough o cut through the mechanics that maintain the cycle, which requires developing mystical insight
into the nature of identity (presented differently in each tradition). Once this is done the mystic just isn't born again.
But, ending the cycle of lives and experience isn’t going to be the goal for VR users. It may be that some people get tired of life, have no more interest in new experiences, and would just
like to fade out peacefully. (Two interesting side questions this brings up is whether people will still want to die if they can create a VR experience in which they are a person who loves
living; and how VR might be utilized to help people die in particularly interesting ways.) Others, however, may not tire. They may enjoy living different lives infinitely and enjoy the
creative work they get to do in each of these lives. It does not seem likely to me that all people will come to the conclusion which serves as the foundation of Buddhism and Hinduism: that
all life has suffering in it and is ultimately not worth living. This is certainly a topic for another blog (or blogs or books!), but the main reason for this is that, at worst, some people
appreciating creativity and beauty more than simple peace, even if it necessarily includes suffering, and, at best, life can get good enough that we end up disproving the original premise of
Buddhism and Hinduism after all. It may be that VR offers an opportunity for infinite creativity.
This leads to the last great obstacle: duration. There may be physical limitations on the time that someone can stay in VR. Perhaps VR experiences will be expensive, or the user will need to
emerge to eat or pee, or the computer itself will not be able to run continuously. Like the other obstacles, demand from users to overcome this problem will be so high that we will
undoubtedly do it. Users will then be able to fully immerse themselves in any sensorially and mentally realistic environment and character they want indefinitely. They would be able to
choose whether to be themselves or be someone new. And they will be able to choose to stay in these lives for as long as they want.
At this point people will be able to literally create their own lives, which is an idea more New Agey than classically Buddhist or Hindu, though some subtraditions of contemplative Hinduism do
view the world as a kind of projection out of one’s essential Self, and both traditions see what you experience in any one life as a causal consequence of your actions in previous lives). And
they’ll see that the sense of identity is fluid, undetermined, and mutable, rather than fixed, which is a decidedly Buddhist insight. But more than this too, pleasure, insight, beauty, diversity,
challenge, experimentation, stability, any existential ache or craving to have something, to be someone, to finish it all off - all of that will be available to us in true abundance.
What’s most interesting though - yes more interesting than being able to create whatever life you want - is how that will change our sense of values. In part because I've been influenced by
the contemplative traditions' thoughts on multiple lives I imagine that one consequence of VR will be that people will become more mature, more insightful, and more empathetic by living through
the great diversity of experiences that VR will make possible. Moreover, what will be demanded of us is a new way to relate to desires and their satisfaction in the first place. When even
the most wondrous experiences are at our fingertips, I think we’ll be surprised to find something even more wondrous set in on its own: a way of relating to experience that will feel
simultaneously deeply safe yet fully enlivened, a kind of awe and wonder at the plenitude of reality, a mature relaxation into watching what new potentials unfold for us as we continue to develop
even further, which is also a love of creating new goals but without any longer any individual or collective naive or despairing hope that there will ever be a final end to things, unless as a
matter of personal choice.
This maturity is what I am most looking forward to for us as a species and collective presence on this planet (and potentially beyond). This relaxation away from thinking that any kind of
experience is going to solve all of our problems, and yet enjoying every experience we have, makes me feel safe, makes me feel that at that point we will be making decisions out of collective
enjoyment of life much more than collective fear, which feels more common now. Fully immersive VR will end up being a fast track to world awakening in a classically mystical sense, but of
course we don’t have to wait for immersive VR. The same way of living I’ve laid out is at least in principle available to all of us now through both traditional and more contemporary means.
In any case, the first step is simply recognizing it as a desirable and realistic way to live. And for those of us who weren’t already aware, VR is hinting at the possibility.
Hey I see what your saying about the vast new range of experiential opportunities that this technology will open up but won't users still have to undergo old age and death? Perhaps VR could also
create a schism between the virtual and physical world that would hinder our ability to care for one another as we go through the inevitable processes of human existence. It sounds like you may be
hinting at a kind of "omega point" of infinite creativity, which you don't think people will ever tire of?
Thanks
Evan
#2
Zach(Thursday, 11 February 2016 15:26)
Hey Evan, thanks for the comment. Yeah, I think people will still age and die unless we solve those problems separately. However, there's lots of ways in which VR could address our death anxiety and
help us come to peace with it, or even come to enjoy! or at least appreciate it, and appreciate change and endings of all kinds more broadly. One way would be to have the experience of many more
endings of relationships and even of whole lives in VR, a kind of phobia-desensitization like process.
Will VR create a decrease in care? I think it's a risk. In fact, there is a certain amount of increased objectification of life, and of other people, that will almost certainly happen as VR users
gain more control of their VR experiences. However, I don't think we should underestimate our love of surprise and of other people having their own interests. I don't think that VR experiences in
which the behavior of the VR characters is fully known and programmed by the user will ever get as popular as VR experiences in which the characters surprise us and behave in ways that don't
automatically conform to our will and our desires. And if VR characters surprise and have their own interests then they will be more like real life, and offer more like a training ground and play
space for alternative realities and choices, than worlds in which we have utter dominion over what happens. These kinds of VR experiences will probably build empathy and care on average over time,
rather than decrease it, in the same way that reading literature is a powerful way to build empathy, but even more effective.
An "omega point" of infinite creativity? Well, if we're talking infinite creativity, which can never be reached, then we are already there. But, I do think that we have the opportunity to liberate
ever greater creativity. Unlike some interpretations of (the) omega point(s) though, this will also lead to greater diversity, rather than uniformity.
#3
Evan(Friday, 12 February 2016 13:03)
That's true, haha, there already are infinite possibilities of creativity, however limited our means of communicating them are, so VR could be a deep well of possibility in that regard beyond paper
and pen, or linear visual entertainment.
About the phobia desensitization process: I have actually been doing that recently, and am thinking of another (fiction) novel that I could read to better come to grips with the future. Actually, I
read "The Death of Ivan Ilyich" in one night after opening to the possibility of death a few months ago. This may seem tangential:
He sought his former accustomed fear of death and did not find it. "Where is it? What death?" There was no fear because there was no death.
In place of death there was light.
"So that's what it is!" he suddenly exclaimed aloud. "What joy!"
Also Yongey Mingyur Rinpoche's account of his 4 years as a wandering yogi, where he almost died on the street in India, inspired me a lot. But this is all just fodder for conceptual understanding,
which must be fully integrated with the "heart" to truly liberate us from fear. I'm optimistic about technology and the incredible vistas it could open for humanity, but how far do you think it could
potentially go in improving our lives? I'm cautious about the unbridled optimism we have in our inventions. Aldous Huxley's idealism inspired him to believe in a Godhead accessible by means of
psychedelics (the wondrous novelty of his era) but on his deathbed, accompanied by his wife who documented their talks and his state, described him as seemingly confused and bewildered, and only
after administering a high dose of LSD did he pass away. So it's just that I don't know if we can wholeheartedly, if not recklessly, idealize the novelties of this generation, however wondrous they
may be.
So let me know what you think
Also there's this book I'm reading called "The Master and his Emmisary" right now which you may like, it's a kind of feedback on our striving to encapsulate the world in thought and manipulation,
i.e. the left hemisphere of the brain.
What caused you to lean away from "mysticism" too if you want to answer?
#4
Zach(Monday, 29 February 2016 16:30)
Hey Evan.
You say, "I'm cautious about the unbridled optimism we have in our inventions." I agree. You might want to check out my most recent writing, Three Principles to Do Consciousness Hacking better, here
I'm my blog. It's something I've written for the new website for the consciousness hacking community (consciousnesshacking.org). Mostly they are engineers interested in using technology to improve
our wellbeing directly. I think it's a well intentioned bunch, but of course good intentions are only the beginning. I lay out a few principles that will make positive technologists work more
beneficial.
I don't think I've leaned away from mysticism really. I love that doorway, those practices, and those ideas, and I think mystical practice and philosophies hold a great number of gems that will
become increasingly relevant. It's just that I got clear that what I actually care about is flourishing, and then mysticism is just one piece of that puzzle.
Thanks for the recommendation, that sounds like something I should read, it's certainly an issue I often find myself grappling with.
#5
Evan(Saturday, 19 March 2016 01:35)
Thanks for that answer it sounds like there really is promise there, and whatever endeavors alleviate suffering are worthwhile in the end. | null | minipile | NaturalLanguage | mit | null |
Letter to the Editor:
We present responses from migrant-sending households in rural western Odisha from interviews conducted during the lockdown.[i](#fn1){ref-type="fn"} Odisha has a significant indigenous population (referred to as Scheduled Tribes or STs in India), with over 9 million STs calling it home ([@b0020], [@b0015]).[ii](#fn2){ref-type="fn"} Studies show that seasonal, informal migrants---a common feature among Odisha's STs---are the most vulnerable among India's internal migrants ([@b0030], [@b0020], [@b0025], [@b0010]).
From our interviews, we find that most migrants had gone for few months---leaving family members at home---to other Indian states, where they often did not speak the local language. They had little or no formal education or marketable skills. The majority of households have official Below Poverty Line (BPL) status.[iii](#fn3){ref-type="fn"} Lack of local employment alternatives, cited as the primary reason behind migration, left migrants susceptible to manipulation and mistreatment, and made them acquiescent of dangerous, informal, odd jobs at low wages (about INR 275/day or USD 3.6/day on average).[iv](#fn4){ref-type="fn"}
Given the uncertainty behind reopening of worksites, many migrants are returning home. But their main reason behind migrating---lack of local employment opportunities---still stands. In the absence of local employment options and income from migration, migrants and their households hope to earn a livelihood locally with assistance from a more effective [National Rural Employment Guarantee Act](http://www.nrega.nic.in){#ce.inter-ref_mzl_brl_mmb} (NREGA), India's flagship public works program.[v](#txtfn7){ref-type="fn"}
[@b0005] discuss how during previous epidemics, public works programs in regions with poor infrastructure successfully combined employment with building infrastructure. Since the survey districts are characterized by poor physical and health infrastructure ([@b0020]), in the short-run, NREGA can provide employment and income while building infrastructure to improve access to patients by first responders and connectivity for health workers. New medical infrastructure could also enable access to treatment of other pressing medical issues. NREGA can also provide assistance for constructing community assets, such as facilities for irrigation, rainwater harvesting and plantations and *anganwadi* centres (child-care centers, under India's Integrated Child Development Services (ICDS) program). This can improve health, education levels and livelihoods of STs in the long-run, addressing not only the immediate need for local employment but also distress migration in the future.
Conflict of interest {#s0005}
====================
No conflict of interest.
The interviews were conducted in May 2020 with the help of the indigenous development NGO [Agragamee](http://www.agragamee.org/){#ce.inter-ref_mnz_xql_mmb} in Rayagada, Koraput, Nabarangpur, Balangir and Kandhamal. These districts all have significant indigenous populations. Because of the lockdown, urban worksites were closed and migrants were returning home. However, since most migrants had not arrived home and were not contactable at the time the survey started, their households were interviewed. Purposive sampling was used to select sample households.
In India, STs number 104 million, and comprise about 9% of total population. Among social groups, the ST group ranks at the bottom for all development indicators.Although the share of STs in total population in Odisha and the survey districts is much higher than the India average, the pattern of very low levels of socio-economic development is the same. Almost all the survey districts are in what is commonly referred to as the [KBK region](http://www.kbk.nic.in/){#ce.inter-ref_yss_jrl_mmb}, after the former district names, Koraput, Balangir, Kalahandi. This region has the poorest districts of Odisha ([@b0020]).
Since BPL status in India is very restrictive, it indicates that a household is very poor.
The World Bank's cutoff for extreme poverty before adjusting for Purchasing Power Parity (PPP) is USD 1.90/day. For monthly wage reports, daily wages were calculated by dividing these by 30. We assume 30 workdays in a month and no holidays, as is the case for these temporary workers. We use INR (Indian Rupees) 75 equivalent to 1 US dollar as the exchange rate.
Under NREGA (commonly referred to as MNREGA or MGNREGA, given the full form of the program-the Mahatma Gandhi National Rural Employment Guarantee Act), the national government guaranteed a wage of INR 182/day for 100 days/year in 2019-20. To address [distress migration, the Odisha government](https://indianexpress.com/article/india/odisha-announces-steps-to-check-distress-migration-from-four-districts-6218730/){#ce.inter-ref_ntg_4rl_mmb} increased NREGA wages to INR 286 for 200 days in 4 districts in January 2020. However, poor livelihood options and delayed NREGA payments have led to continuing distress migration from these and other districts in Odisha with a high proportion of ST migrants. Effective from April 2020, as part of the COVID-19 relief package, the Indian government increased NREGA wages to INR 202.
| null | minipile | NaturalLanguage | mit | null |
Q:
Screen dims after xrandr
I have an old P3 laptop with an 800x600 screen on which I've installed WattOS 7.5. I know it is now on 10 but 7.5 is the latest one that will fit on a CD. The later ones will only fit on DVD. This is an old machine - it only has a CD reader, it will not boot off USB and it doesn't like microWatt (which still fits on a CD). There is something wrong with the microWatt drivers - the entire screen appears as a 0.25" bar. Anyway, it has WattOS 7.5.
My login screen is very reddish. If I run it from my desktop it is greenish - which is the correct colour. Also, for some reason, the system thinks it has a 1024x768 screen. After logging in, all the colours are OK.
The obvious answer would have been to ask the WattOS site but it is a chicken and egg situation. It wants me to sign in and in order to sign in, I need an invite key. I've got no idea what one of those is. To find out, I'd have to login and ask but I can't login because I haven't got an invite key.
Before committing the settings in stone, I decided to try them out. First, I set the screen size
xrandr -s 800x600
The screen size changes and I can now see the taskbar but the brightness has also changed to half. When I type xrandr -q, I get
xrandr: Failed to get size of gamma for output default
Followed by the resolutions
I suspect it is assuming I have 24 or 32-bit colour but this is an old system so at most 16-bit colour, which possibly explains why it has all gone dim and why my login screen seems to have lost its blue/green component.
The questions
I must be looking up the wrong keywords - I can't find how to set the number of colours to 65536 or to tell the system that it has 16-bit colour. All the hits I am getting are how to set console window colours.
Another lot of searches says gedit /etc/X11/xorg.conf This file doesn't exist on my system. Again, I think I'm looking up the wrong keywords. Almost all the hits tell me where it is, none of them tell me what has replaced it.
How do I make these settings permanent so that my login screen appears in the correct colour and the system knows what size my screen is.
Edit I've found https://ubuntuforums.org/showthread.php?t=1493835 Apparently xorg.conf will be used if created. I'll give that a try later today. The laptop can only stray from a power supply for 5 minutes: after that it shuts down.
Edit This question is now purely academic - the machine just died.
A:
Finally got to the bottom of this. WattOS has an on screen utility called arandr. I've never been successful in pasting pictures so I'll do a sort of diagram. On some systems, it is called the Screen layout editor. On WattOS, it is called arandr. I used it because I thought it had something to do with xrandr.
________________
|____menu________|
|____icons_______|
| | |
| default | |
|____________|___|
What I was doing was going through all the menu options and icons and not finding anything to do with resolution. The help doesn't tell you how to use it - all it has is the about screen.
What I should have done is right click on the area marked Default, select Resolution and then pick the resolution.
It is as simple as that: it has only taken me 7 years to figure out this one.
| null | minipile | NaturalLanguage | mit | null |
Oh, once upon a midnight eerie
I woke with something in my head
I couldn't escape the memory
Of a phone call and of what you said
Like a game show contestant with a parting gift
I could not believe my eyes
When I saw through the thoughts of a trusted friend
Who needs to humor me and tell me lies, yeah humor me and tell me lies
And I'll lie too and say I don't mind
And as we seek so shall we find
And when you're feeling open I'll still be here
But not without a certain degree of fear
Well, what will be with you and me
I still can see things hopefully
But you
Why you wanna give me a run-around?
Is it a sure-fire way to speed things up?
When all it does is slow me down
Shake me and my confidence
About a great many things
But I've been there I can see it cower
Like a nervous magician waiting in the wings
Of a bad play where the heroes are right
And nobody thinks or expects too much
And Hollywood's calling for the movie rights
Singing "Hey babe, let's keep in touch", hey baby, let's keep in touch
But I want more than a touch I want you to reach me
And show me all the things no one else can see
So what you feel becomes mine as well
And soon if we're lucky we'd be unable to tell
What's yours and mine, the fishing's fine
And it doesn't have to rhyme, so don't you feed me a line
But you
Why you wanna give me a run-around?
Is it a sure-fire way to speed things up?
When all it does is slow me down
Tra la la la la bombardier, this is the pilot speaking
I've got some news for you
It seems my ship still stands no matter what you drop
And there ain't a whole lot that you can do
Oh sure the banner may be torn and the wind's gotten colder
Perhaps I've grown a little cynical
But I know no matter what the waitress brings
I shall drink it and always be full, yeah I will drink it and always be full
Oh I like coffee and I like tea
I'd like to be able to enter a final plea
I still got this dream that you just can't shake
I love you to the point you can no longer take
Well all right okay, so be that way
I hope and pray that there's something left to say
But you
Why you wanna give me a run-around?
Is it a sure-fire way to speed things up
When all it does is slow me down?
Oh you
Why you wanna give me a run-around?
Is it a sure-fire way to speed things up
When all it does is slow me down?
Four (styled as four) is the breakthrough album by American jam band Blues Traveler, released on September 13, 1994.
Four peaked at #8 on the Billboard 200 albums chart (North America) and is most known for its hit "Run-Around". According to the RIAA, the album has six Platinum certifications.
"Run-Around" peaked at #2 in the Adult Top 40 in 1995, and "Hook" peaked at #8 in the Mainstream Top 40 in 1996.
* The song "Hook" shares the same harmonic structure as Johann Pachelbel's Canon in D.Read Full BioFour (styled as four) is the breakthrough album by American jam band Blues Traveler, released on September 13, 1994.
Four peaked at #8 on the Billboard 200 albums chart (North America) and is most known for its hit "Run-Around". According to the RIAA, the album has six Platinum certifications.
"Run-Around" peaked at #2 in the Adult Top 40 in 1995, and "Hook" peaked at #8 in the Mainstream Top 40 in 1996.
* The song "Hook" shares the same harmonic structure as Johann Pachelbel's Canon in D. * "The Mountains Win Again" was used in advertisements for Busch Beer. * The Black Cat logo was created by Darren Greene. | null | minipile | NaturalLanguage | mit | null |
Company: 002909 Arng: 39229-09137 Eff Date: 2001-06-06
----- Receipt ----- ----- Delivery -----
Quantity Cut CD Quantity Cut CD
Nominated 0 67
Working 0 67
Capacity Allocation 0 67
Confirmed 0 24 CBL | null | minipile | NaturalLanguage | mit | null |
Characterization of a stearoyl-acyl carrier protein desaturase gene from potential biofuel plant, Pongamia pinnata L.
A new full length cDNA clone encoding stearoyl-ACP desaturase (SAD) was isolated from seeds of Pongamia pinnata, an oil yielding legume plant. The cDNA clone (PpSAD) contained a single open reading frame of 1182-bp coding for 393 amino acids with a predicted molecular mass of 45.04 kDa, and shares similarity with SAD from other plants. Characteristics of the deduced protein were predicted and analyzed using molecular homology modeling; its three dimensional structure strongly resembled the crystal structure of Ricinus communis (RcSAD). Southern blot analysis indicated that 'sad' is a multiple copy gene and was a member of a small gene family. Expression analysis using quantitative real-time PCR revealed that the gene showed marked distinct expression during different stages of seed developments. The results of the expression analysis in this study, combined with existing research, suggest that 'sad' gene may be involved in the regulation of plant seed growth and development. | null | minipile | NaturalLanguage | mit | null |
1. Technical Field
The present invention relates to vibration isolation systems, and more particularly, an assembly which isolates a gyroscope from mounting surface vibratory heat expansion, and/or contraction-induced rotational displacements.
2. Background Art
A wide variety of torque-producing devices make use of spinning rotor elements mounted on low-friction bearings. Among such devices are gyroscopes which have many applications in the aerospace industry. Gyroscopes are used, for example, in airplanes, torpedoes, and missiles as a basic element in automatic steering systems to "remember" the orientation of the horizon and the direction of north during maneuvers. Such torque-producing devices are generally mounted on a support structure. It has been found that for many applications, it is desirable to isolate the gyroscopes and the support structure from the vibrations and other extraneous dynamic motions of the base on which it is mounted so as to help reduce potential rotational discrepancies.
In many systems and devices in current use, it is desirable to isolate a support structure from vibrations as well as to help ensure that the support structure maintains a constant angular orientation with respect to a predetermined reference surface. For example, the support structure of an inertial navigation system often is mounted within a vehicle whose position is to be determined in such a manner that vibrations of the vehicle which may be transmitted to the support structure do not adversely affect gyro operation and also in such a manner that the support structure experiences no rotational movement with respect to the vehicle, or, in other words, the angular orientation of the support structure with respect to the vehicle is continually maintained. The isolating requirements of a support structure becomes clear when it is realized that the gyroscopes in the accelerometer which are mounted on the platform rectify high frequency vibration applied thereto so that an output signal is generated by these components in response to vibratory displacement whereby the accuracy of the navigational system is affected. Further, unless the angular orientation for the support structure is maintained, inaccurate rotation rates will be sensed, thereby severely limiting the accuracy of the system.
Several exemplary isolation and mounting assemblies are disclosed in U.S. Pat. Nos. 3,057,592 issued to Thrasher; U.S. Pat. No. 3,151,833 issued to Thrasher; U.S. Pat. No. 4,099,696 issued to Toome; U.S. Pat. No. 4,270,393 issued to Osborne et al; U.S. Pat. No. 4,531,701 issued to Treu; U.S. Pat. No. 4,618,111 issued to Sherwood et al; U.S. Pat. No. 4,688,909 issued to Smith; U.S. Pat. No. 4,771,644 issued to Meron; U.S. Pat. No. 4,890,812 issued to Chechile et al; and U.S. Pat. No. 5,138,903 issued to Grossenbacher, Jr., et al. | null | minipile | NaturalLanguage | mit | null |
BrushUI theme
Description
It is a theme studied in detail, inspired by brushed metal or even the "brushed" to offer any type of brush. From this comes the name "BrushUI". Attention: Theme compatible with all roms that support the team chooser of CyanogenMod 12 / 12.1. Please restart after you apply it if you notice any particular graphical glitches. | null | minipile | NaturalLanguage | mit | null |
Q:
PHP/PDO/MySQL: inserting into MEDIUMBLOB stores bad data
I have a simple PHP web app that accepts icon images via file upload and stores them in a MEDIUMBLOB column.
On my machine (Windows) plus two Linux servers, this works fine. On a third Linux server, the inserted image is corrupted: unreadable after a SELECT, and the length of the column data as reported by the MySQL length() function is about 40% larger than the size of the uploaded file.
(Each server connects to a separate instance of MySQL.)
Of course, this leads me to think about encoding and character set issues. BLOB columns have no associated charsets, so it seems like the most likely culprit is PDO and its interpretation of the parameter value for that column.
I've tried using bindValue with PDO::PARAM_LOB, to no effect.
I've verified that the images are being received on the server correctly (i.e. am reading them post-upload with no problem), so it's definitely a DB/PDO issue.
I've searched for obvious configuration differences between the servers, but I'm not an expert in PHP configuration so I might have missed something.
The insert code is pretty much as follows:
$imagedata = file_get_contents($_FILES["icon"]["tmp_name"]);
$stmt = $pdo->prepare('insert into foo (theimage) values (:theimage)');
$stmt->bindValue(':theimage', $imagedata, PDO::PARAM_LOB);
$stmt->execute();
Any help will be really appreciated.
UPDATE: The default MySQL charset on the problematic server is utf8; it's latin1 on the others.
The problem is "solved" by adding PDO::MYSQL_ATTR_INIT_COMMAND => "SET NAMES latin1 COLLATE latin1_general_ci" to the PDO constructor.
This seems like a bug poor design to me: why should the charset of the connection have any effect on data for a binary column, particularly when it's been identified as binary to PDO itself with PARAM_LOB?
Note that the DB tables are defined as latin1 in all cases: it's only the servers' default charsets that are inconsistent.
A:
This seems like a bug to me: why should the charset of the connection have any effect on data for a binary column, particularly when it's been identified as binary to PDO itself with PARAM_LOB?
I do not think that this must be a bug. I can imagine that whenever the client talks with the server and says that the following command is in UTF-8 and the server needs it in Latin-1, then the query might get re-encoded prior parsing and execution. So this is an encoding issue for the transportation of the data. As the whole query prior parsing will get influenced by this re-encoding, the binary data for the BLOB column will get changed as well.
From the Mysql manual:
What character set should the server translate a statement to after receiving it?
For this, the server uses the character_set_connection and collation_connection system variables. It converts statements sent by the client from character_set_client to character_set_connection (except for string literals that have an introducer such as _latin1 or _utf8). collation_connection is important for comparisons of literal strings. For comparisons of strings with column values, collation_connection does not matter because columns have their own collation, which has a higher collation precedence.
Or on the way back: Latin1 data from the store will get converted into UTF-8 because the client told the server that it prefers UTF-8 for the transportation.
The identifier for PDO itself you name looks like being something entirely different:
PDO::PARAM_LOB tells PDO to map the data as a stream, so that you can manipulate it using the PHP Streams API. (Ref)
I'm no MySQL expert but I would explain it this way. Client and server need to negotiate which charsets they are using and I assume they do this for a reason.
| null | minipile | NaturalLanguage | mit | null |
Ian Christian
Key Details
Biography
I am a medical negligence partner and deal with a wide variety of claims for individuals who have received substandard medical treatment.
I am an expert in all birth injury and neonatal claims, including cerebral palsy, erb’s palsy, hypoglycaemia, hyperbilirubinaemia, and retinopathy of prematurity cases.
I have conducted a number of high profile multiparty actions, including:
Representing families whose cases were considered in the Health Care Commission’s 2006 report into maternal deaths at Northwick Park Hospital
Representing 9 families at inquests and with civil claims following the outbreak of endocarditis at the Trent Cardiac Centre in 2009
Concluding the civil claims arising from the deaths of residents at the Orchid View Care Home run by Southern Cross in November 2014. I had previously conducted the 8-week inquest and campaigned for a public inquiry.
I have advised the Care Quality Commission on the content of the Care Act 2014 and I am now an invitee to Public Policy events associated with improving care in the social and healthcare arena.
I also have a sports practice specialising in treatment provided by medical staff in elite sport.
I am currently representing a number of professional rugby players and am a panel member for the Rugby Players Association. I advised the RPA on the concussion protocol which was implemented by the RFU at the start of the 2014/15 season.
In December 2016, I lectured to the Faculty of Sports and Exercise Medicine at the Royal College of Surgeons on the World Anti Doping Code. Download a copy of the lecture.
Testimonials
"He is hard-working, with very good client skills." – Chambers & Partners 2018
Cases I've Been Involved With
Read My Comments On The Latest News
“The vast majority of babies born in the UK suffer no serious problems but there are a growing number who are not so fortunate and suffer injuries at birth which can be devastating.
“Birth injuries can be catastrophic. Many babies injured at birth suffer cerebral palsy and severe brain injuries which leaves them disabled for the rest of their lives. They will often need 24-hour care for life and will never work or be able to live independently.
“From our experience investigating maternity care on behalf of the families affected, many birth injuries are wholly avoidable and there are several common factors that keep occurring: failures in interpreting CTG heartbeats, incorrect use of the syntocinon drug, delays in decisions to undertake caesarean sections and not having consultants present at high risk births. Better training, safer staffing levels and more robust procedures could help reduce the risk of these issues.
“It’s often only because of medical negligence cases that some of these issues come to light and reoccurring issues become known. It’s therefore crucial that lessons are learnt to improve patient safety for others.”
“It’s hugely disappointing to see that Northampton have not been held to account for the handling of George North’s injury as it was an chance to make a statement and remind clubs, players and fans how serious an issue it is.
“The concussion protocol can only be effective if the doctor's decision to allow the player to return to play stands up to scrutiny. Which is why the findings and lack of punishment in today’s report feel like a backwards step, with the experts stating that Northampton could and should have done more to prevent North returning to the playing field.
“After a billion dollar court battle in America, the NFL has finally introduced the type of rules around concussion that rugby may need to adopt. In the NFL, if a concussion is identified then the player is removed from play and cannot return until the team physician and an unaffiliated consultant reviews both the video of the play and performs an examination.
“Surely it is now time for all suspected concussions to be reviewed by an independent doctor, without time pressures, which will allow a balanced decision to be made. If that affects the outcome of the game, so be it. Long-term health is more important than winning a game.
“This isn’t the first time George North has played on when all those watching thought he should be off the pitch and it proves that players need protecting from themselves. This was an opportunity for the panel to make a statement about concussion and the importance of a safety first approach and it has been wasted.”
“As a result of this terrible error, this boy, who as a young teenager should be finding his independence, instead needs the support of doctors, pharmacists, physiotherapists, occupational therapists, carers, educational services, a professional deputy and much more.
“The last five years have been incredibly difficult for the family who have cared for their son with limited support. We hope that this settlement will enable them to now look forward and make plans for the future and hope that our young client will now be able to access the services that he needs to live a full and happy life.
“It is encouraging the University Hospitals of Leicester NHS Trust conducted their own investigations and were able to make an early admission of fault. It is our hope that they and other NHS Trusts will continue to learn from the mistakes made and ensure that their practices are improved in the hope that no other family will have to endure what this family has been through.”
“It is imperative that Brighton NHS Trust continue to take the findings of the CQC seriously and take swift action to make the necessary improvements which could potentially save lives.
“We see the impact these kind of failings can have on patients and their families and it is vital that patient safety is the number one priority.
The trust also needs to address the long-standing issues surrounding its people policies and implement an immediate programme of change to improve the culture of the organisation and the service to its patients.” | null | minipile | NaturalLanguage | mit | null |
Automated detection of many-particle solvation states for accurate characterizations of diffusion kinetics.
Discrete-space kinetic models, i.e., Markov state models, have emerged as powerful tools for reducing the complexity of trajectories generated from molecular dynamics simulations. These models require configuration-space representations that accurately characterize the relevant dynamics. Well-established, low-dimensional order parameters for constructing this representation have led to widespread application of Markov state models to study conformational dynamics in biomolecular systems. On the contrary, applications to characterize single-molecule diffusion processes have been scarce and typically employ system-specific, higher-dimensional order parameters to characterize the local solvation state of the molecule. In this work, we propose an automated method for generating a coarse configuration-space representation, using generic features of the solvation structure-the coordination numbers about each particle. To overcome the inherent noisy behavior of these low-dimensional observables, we treat the features as indicators of an underlying, latent Markov process. The resulting hidden Markov models filter the trajectories of each feature into the most likely latent solvation state at each time step. The filtered trajectories are then used to construct a configuration-space discretization, which accurately describes the diffusion kinetics. The method is validated on a standard model for glassy liquids, where particle jumps between local cages determine the diffusion properties of the system. Not only do the resulting models provide quantitatively accurate characterizations of the diffusion constant, but they also reveal a mechanistic description of diffusive jumps, quantifying the heterogeneity of local diffusion. | null | minipile | NaturalLanguage | mit | null |
The premier of the Canadian province of Quebec, Philippe Couillard, has temporarily halted the approval of new mining operations partnering with the province’s state-owned power company, Hydro-Quebec.
Also Read: Dutch Court Rules That Bitcoin Has “Properties of Wealth”
Hydro-Quebec Halts Approval of New Mining Operations From Offshore Applicants
The company states that “Although [it has] a large volume of electricity to meet the different needs of customers in the territory,” it will not be able to accept all mining applicants, adding that “In recent months, we have received [proposals for] projects representing several thousand megawatts.”
“Hydro-Quebec Distribution will not be able to supply the totality of the installations targeted by the projects which have been presented to it. currently being analyzed, in particular, because of their impact on demand during winter peaks.”
The company states that it is currently “working to develop guidelines to determine which of the projects received in the blockchain sector can be accepted, as well as the tariffs and conditions applicable to this sector.”
Hydro-Quebec’s decision to temporarily halt new partnerships with offshore mining companies has been met with surprise, as the company had recently made efforts to double its revenues to $30 billion by 2030 – with commercial strategies targeting the blockchain and cryptocurrency industries comprises a major source of the anticipated revenue.
According to local media citing an anonymous source close to company, “Hydro-Québec had the management of the cryptocurrency market confiscated” and received “an order to wait quietly for new instructions from the government.”
Quebec cabinet member, Pierre Moreau, addressed the clampdown on new large-scale mining operations, stating that “The objective of the government is to assure all Quebecers that during winter peaks, Hydro-Quebec does not say, ‘well, listen, I can not provide because we are in the process of mining cryptocurrency.‘”
Domestic Mining Operations Proliferate
The founder of a Montreal-based bitcoin consulting firm, Jonathan Hamel, has stated that the Couillard administration’s decision “is not surprising considering the government’s hostility to technological change.” Mr. Hamel states that the Couillard government previously “attempt[ed] to ban Uber,” and has pushed for stronger “taxation of the giants of the web,” adding “Mr. Couillard seems to be inspired by regulatory surges in the European Union, a strategy that has the effect of scare investors.”
The number of local mining operations in the province appears to have rapidly proliferated, with Hydro-Quebec indicating that it has received supply requests from individuals consuming 5,000% more power than the average home.
Do you think that Hydro-Quebec will again accept applications for new mining operations from offshore companies? Share your thoughts in the comments section below! | null | minipile | NaturalLanguage | mit | null |
Massa positive after strong start to season
22 March 2013
Felipe Massa went some way to laying to rest the ghosts of the past few seasons, where he has struggled to match Fernando Alonso through the first few races, with fourth place in the Australian Grand Prix, and is confident that his rediscovered form can continue in Malaysia this weekend.
The Brazilian has out-qualified Alonso at each of the last three races, although results have not necessarily gone his way on Sunday, and he was a contender for the podium in Melbourne until an ill-timed pit-stop not only dropped him back, but also behind his team-mate, who he had been leading for the first half of the race. The reason for his ability to match Alonso at this point in the season is clear to Massa, who has found himself under pressure to perform after slow starts to the past few seasons.
“The car is much better and we have already showed throughout the Australian weekend - practice, qualifying and the race - that it is more competitive than last year,” he commented, “The car is ten times better and I feel happy and more comfortable than I did at this time last year, when I struggled to understand the car. This year, I can be much more consistent and the car is easier to drive, which is pretty good for the team and also for me.”
Like Scuderia team principal Stefano Domenicali, it is Massa's perception that Red Bull continues to have an edge when it come to out-and-out speed, but the Brazilian is equally confident that the F138 is easier on its tyres come raceday.
“Remember, in qualifying, we were one second slower, but track conditions were not consistent, so it is hard to judge where we really are,” he mused, “The situation could be completely different at [Sepang], so we need to wait and see. Maybe we will have a clearer picture of what is really the gap between us and the others in qualifying, either negative or positive.
“In the [Australian] race, our pace was excellent, maybe the best, when our tyres were in good shape. Our level of tyre degradation was higher than [race winner] Kimi [Raikkonen]'s, but it was reasonable when compared to the other cars and that is definitely positive.
“Overall, Australia went well for us, [but] we need to make sure we progress race by race now. It is true we had a good race pace when compared to the Red Bull, after it had been quicker than us on Saturday, but we need to work to get better in both qualifying and the race. This will be an important weekend to understand as much as possible about the car and the tyres.” | null | minipile | NaturalLanguage | mit | null |
Apoptosis has a vital role in regulating cell numbers during haemopoiesis and failure to remove damaged, superfluous or potentially dangerous cells can lead to malignancy or autoimmunity. Many critical life-or-death checkpoints, particularly during lymphopoiesis, are governed by opposing factions of the Bcl-2 protein family, which regulate the 'intrinsic\' apoptosis pathway.^[@bib1],\ [@bib2]^ Bcl-2, discovered via the t(14;18) chromosome translocation typical of human follicular lymphoma,^[@bib3],\ [@bib4],\ [@bib5]^ inhibits apoptosis,^[@bib6]^ as do its closest homologues (Bcl-x~L~, Bcl-w, A1/Bfl1, Mcl-1 and, in humans, Bcl-B). Other close homologues (Bax and Bak) instead promote apoptosis, as do distant relatives known as BH3 (Bcl-2 homology region 3)-only proteins because they share only an ∼26 amino-acid motif with the wider Bcl-2 family. During cellular stress, BH3-only proteins are induced and bind with high avidity via their amphipathic BH3 *α*-helix to the hydrophobic groove on the surface of pro-survival Bcl-2-like proteins,^[@bib7],\ [@bib8],\ [@bib9]^ thereby preventing them from restraining any activated Bax or Bak molecules. Certain BH3-only proteins (particularly Bim and cleaved Bid) can also bind weakly and transiently to Bax and/or Bak, triggering their conformational change and subsequent homo-oligomerisation on the outer mitochondrial membrane. As a consequence, cytochrome *c* is released into the cytoplasm, leading to the activation of the proteases (caspases) that provoke cellular demolition by cleaving vital proteins.
Although Bax and Bak are both widely expressed and functionally redundant,^[@bib10]^ recent studies suggest Bak may have particular importance in certain cell types. Thus, loss of Bak results in thrombocytosis, whereas loss of Bax does not, indicating that Bak has the more important role in regulating platelet life span.^[@bib11],\ [@bib12]^ Furthermore, loss of Bak was able to partially rescue thymic defects caused by conditional deletion of Mcl-1, whereas neither overexpression of Bcl-2 nor loss of Bax was able to do so.^[@bib13]^ Specificity of interactions may account for these observations: Bak binds tightly to Mcl-1 and Bcl-x~L~ but only poorly to Bcl-2, whereas Bax binds avidly to all the pro-survival proteins.^[@bib14],\ [@bib15],\ [@bib16]^ Presumably, therefore, Bax activation can be thwarted by all pro-survival proteins, including Bcl-2, whereas Bak is kept in check by Mcl-1 and Bcl-x~L~.
To further explore the role of Bak-specific cell death during haemopoiesis, we have investigated whether loss of Bak or increased expression of Mcl-1 enhances the impact of pan-haemopoietic overexpression of Bcl-2. To do so, we crossed vavP-*BCL-2* transgenic (hereafter *BCL-*2tg) mice^[@bib17]^ with *Bak*^−*/*−[@bib10]^ or vavP-*Mcl-1* transgenic (hereafter *Mcl-1*tg) mice^[@bib18]^ and compared the phenotypes of single and doubly mutant offspring. This study also enabled us to undertake further analysis of the puzzling thymic and platelet phenotype of *BCL-2*tg mice.
Results
=======
Impact of overexpression of Mcl-1 and loss of Bak on haemopoiesis in *BCL-2tg* mice
-----------------------------------------------------------------------------------
Overexpression of Bcl-2 via the haemopoietic cell-specific vavP-driven transgene^[@bib19]^ enhances the survival of T- and B-lymphoid cells, which accumulate in excessive numbers in the periphery.^[@bib17],\ [@bib20]^ In addition, *BCL-2*tg mice have a distinctive thymic phenotype: a reduced proportion of pre-T cells (CD4^+^CD8^+^ double positive; hereafter DP) and elevated proportions of the other three major populations (CD4^−^CD8^−^ double negative, hereafter DN; CD4^+^CD8^−^ single positive, hereafter CD4SP; and CD4^−^CD8^+^ single positive, hereafter CD8SP).^[@bib17]^ This is referred to as the 'low DP\' thymic phenotype of *BCL-2*tg mice (see further below).
To assess whether overexpression of Mcl-1 exacerbates the *BCL-2*tg phenotype, we compared the composition of blood and haemopoietic tissues in 6-week-old neonates. Despite a minor (*P*≤0.05) increase in the total number of DP thymocytes in *Mcl-1/BCL-2* bi-transgenic compared with *BCL-2*tg mice, the *proportion* of DP thymocytes was comparably low (lower left panel in [Supplementary Figure 1B](#sup1){ref-type="supplementary-material"}) and there was little impact on the *BCL-2*tg-induced lymphocytosis in the other lymphoid organs ([Supplementary Figure 1](#sup1){ref-type="supplementary-material"} and [Supplementary Table 1](#sup1){ref-type="supplementary-material"}).
To assess the impact of loss of Bak, we first analysed haemopoietic tissues in young adult (12- to 14-week-old) mice. Loss of Bak had little impact alone, but did increase lymphocytosis in *BCL-2*tg mice ([Figure 1](#fig1){ref-type="fig"} and [Supplementary Table 2](#sup1){ref-type="supplementary-material"}). This was most apparent in the spleen where cellularity, already elevated approximately fivefold in *BCL-2*tg mice, increased to nearly sevenfold in *Bak*^−*/*−^ *BCL-2*tg animals, due primarily to a further elevation in the number of immunoglobulin (Ig) isotype-switched (B220^+^IgM^−^IgD^−^) B-lymphoid cells and mature T cells (CD4^+^ and CD8^+^; [Figure 1a](#fig1){ref-type="fig"}). A comparable cross of *Bax*^−/−^ and *BCL-2*tg mice revealed no comparable differences between *BCL-2*tg and *Bax*^−*/*−^ *BCL-2*tg animals ([Supplementary Table 3](#sup1){ref-type="supplementary-material"}).
Lack of Bak did not notably alter the low proportion of DP thymocytes in the *BCL-2*tg thymus ([Figure 1b](#fig1){ref-type="fig"} and [Supplementary Table 2](#sup1){ref-type="supplementary-material"}). *BCL-2*tg thymocytes have very high levels of the pro-apoptotic BH3-only protein Bim, most being sequestered by BCL-2,^[@bib21]^ and Bim levels were unchanged in either *Bak*^−/−^ *BCL-2*tg or *Mcl-1*tg*/BCL-2*tg mice ([Figure 1c](#fig1){ref-type="fig"} and [Supplementary Figure 1C](#sup1){ref-type="supplementary-material"}).
To explore the perturbation of T lymphopoiesis more closely, we compared the thymus and spleen of *BCL-2*tg and *Bak*^−/−^ *BCL-2*tg mice at three time points: 6--8, 12 and 24 weeks ([Figure 2](#fig2){ref-type="fig"} and [Supplementary Table 4](#sup1){ref-type="supplementary-material"}). The decrease in the number of DP thymocytes was not as marked at 6--8 weeks (∼80 % that in wild-type (WT) littermates) as at 12 and 24 weeks (∼46% and ∼47%, respectively), although mature thymocytes (CD4SP and CD8SP) were already significantly elevated at 6--8 weeks, as were T cells in the spleen. Strikingly, there was an approximately fourfold increase in the DN population in 6- to 8-week-old *BCL-2*tg and *Bak*^−/−^*BCL-2*tg mice, and this was almost entirely due to T-cell receptor *β*^+^ (TCR*β*^+^) DN cells (elevated 16-fold; [Figure 2a](#fig2){ref-type="fig"}). These cells are probably mature T cells (TCR*β* is highly expressed) that have downregulated their co-receptors (CD4 or CD8) because they are autoreactive and have escaped negative selection.^[@bib22]^ The early increase in these 'pseudo DN\' cells may inhibit the production of *bona fide* DN thymic progenitor cells (see Discussion).
Loss of Bak increases resistance of *BCL-2*tg thymocytes to certain apoptotic stimuli
-------------------------------------------------------------------------------------
To compare the resistance of thymocytes of the different genotypes to apoptosis, we first performed *in vitro* tests. In the absence of cytokines, the *Mcl-1* and *BCL-2* transgenes provided comparable protection, but in the presence of cytotoxic agents, the *BCL-2* transgene provided greater protection, consistent with previous observations,^[@bib23]^ and co-expression of both conferred no additional advantage ([Supplementary Figure 2](#sup1){ref-type="supplementary-material"}).
By itself, loss of Bak did not protect DP thymocytes from spontaneous death in culture or from apoptosis induced by dexamethasone or phorbol 12-myristate-13-acetate (PMA), but it did enhance resistance to ionomycin at low (1 *μ*g/ml) concentration and, at early time points, to DNA damage (*γ*-irradiation and etoposide; [Figure 3a](#fig3){ref-type="fig"} and [Supplementary Figure 3](#sup1){ref-type="supplementary-material"}). Furthermore, loss of Bak enhanced the resistance of DP thymocytes expressing the *BCL-2* transgene to apoptosis induced by etoposide treatment and, modestly, to *γ*-irradiation ([Figure 3a](#fig3){ref-type="fig"}). DP thymocytes are exquisitely sensitive to CD3 antibody, which triggers apoptosis by aggregating the TCR-CD3 complex.^[@bib24],\ [@bib25]^ As a further test, therefore, we injected mice of all four genotypes with an optimal dose of CD3*ɛ* monoclonal antibody (mAb) or with an Ig isotype-matched control antibody, and determined thymus weight and cellularity after 40 h ([Figure 3b](#fig3){ref-type="fig"}). Following CD3 antibody treatment, thymus weight dropped substantially in both WT and *Bak*^−*/*−^ mice, due primarily to a reduction in DP thymocytes. As reported previously,^[@bib26]^ expression of the *BCL-2* transgene provided DP thymocytes with only partial protection against this insult (65%). Of note, however, protection in the *Bak*^−*/*−^ *BCL-2*tg mice was considerably more robust (\>90%), suggesting that TCR-activated apoptosis involves a Bak-specific component.
Pathology
---------
*BCL-2*tg mice are predisposed to the development of autoimmune kidney disease and, in later life, follicular lymphoma.^[@bib20]^ To determine whether overexpression of Mcl-1 or loss of Bak increased the risk of morbidity, cohorts of mice were monitored for 12 months. Most mice that became ill during this period showed evidence of autoimmune kidney disease: weight loss, blood in the urine and pale, often speckled, kidneys.
The overall survival of *Mcl-1*tg*/BCL-2*tg mice over 12 months was comparable to that of *BCL-2*tg mice and serum Ig levels were similarly elevated in both cohorts ([Supplementary Figure 4](#sup1){ref-type="supplementary-material"}). The autoimmune kidney disease was most likely due to overexpression of Bcl-2 as *Mcl-1*tg mice do not develop comparable symptoms.^[@bib18]^
Loss of Bak resulted in a trend towards earlier morbidity in *BCL-2*tg mice, although the difference between *Bak*^−/−^*BCL-2*tg and *BCL*-2tg animals did not achieve statistical significance ([Supplementary Figure 5A](#sup1){ref-type="supplementary-material"}). The elevation in IgM, IgG and IgA antibody-secreting cells (ASCs) in the spleen and bone marrow was similar between these cohorts ([Supplementary Figures 5B and C](#sup1){ref-type="supplementary-material"}).
Although a few lymphomas developed in transgenic mice of each genotype, neither overexpression of Mcl-1 nor loss of Bak enhanced the susceptibility of the *BCL-2*tg mice to follicular lymphoma during the time period analysed. Like *Mcl-1*tg mice,^[@bib18]^ certain *Mcl-1*tg*/BCL-2*tg mice developed other lymphomas, at comparable frequency.
Impact on platelets
-------------------
Both *Bak*^−*/*−^ and *BCL-2*tg mice have platelet abnormalities: loss of Bak causes thrombocytosis,^[@bib11],\ [@bib12]^ but Bcl-2 overexpression results, surprisingly, in thrombocytopaenia.^[@bib17]^ We therefore determined platelet levels in the blood of *Bak*^−*/*−^*BCL-2*tg mice. Unexpectedly, loss of Bak did not elevate platelets in the blood of *BCL-2*tg mice; rather, *Bak*^−*/*−^ *BCL-2*tg mice, like *BCL-2*tg mice, were thrombocytopaenic ([Figure 4a](#fig4){ref-type="fig"}). Thus, Bcl-2 overexpression is dominant over loss of Bak in regard to this phenotype.
At steady state, platelets circulate in the blood for up to 5 days in mice, 10 days in humans^[@bib27],\ [@bib28]^ and the elevated platelet count in *Bak*^−*/*−^ mice is due to increased platelet life span.^[@bib11]^ To determine the impact of overexpression of BCL-2 on platelet life span, we injected *BCL-2*tg, *Bak*^−*/*−^*BCL-2*tg and *Bak*^−/−^ mice with NHS-biotin and tracked the disappearance of labelled platelets from the circulation ([Figure 4b](#fig4){ref-type="fig"}). Consistent with previous reports,^[@bib11]^ platelet life span was significantly extended in *Bak*^−*/*−^ mice, with a half-life of 100 h compared with 60 h in WT littermates. Importantly, *BCL-2*tg animals showed an intermediate platelet half-life of 75 h. Thus, overexpression of Bcl-2 enhances the life span of platelets, albeit more modestly than loss of Bak. Underlining the fundamental importance of Bak in regulating platelet life span, there was no additive effect in *Bak*^−/−^*BCL-2*tg mice; platelet survival in these animals was indistinguishable from that seen in the *Bak*^−*/*−^ cohort.
Megakaryocyte (not shown) and platelet counts were normal in young *Mcl-1*tg mice^[@bib18]^ ([Supplementary Figures 6A and B](#sup1){ref-type="supplementary-material"}) and platelet life span was also normal ([Supplementary Figure 6C](#sup1){ref-type="supplementary-material"}), suggesting that the modest increase in platelet Mcl-1 levels in this model ([Supplementary Figure 6D](#sup1){ref-type="supplementary-material"}), coupled with its short half-life,^[@bib29]^ is not sufficient to have any measurable effect on overall survival times. Like *BCL-2*tg mice, *Mcl-1*tg/*BCL-2*tg mice were thrombocytopaenic, although the deficit in mature platelets was not quite as profound ([Supplementary Figures 6A and B](#sup1){ref-type="supplementary-material"}).
Why does haemopoietic overexpression of Bcl-2 cause thrombocytopaenia?
----------------------------------------------------------------------
The thrombocytopaenia in *BCL-2*tg and *Bak*^−/−^*BCL-2*tg mice ([Figure 4a](#fig4){ref-type="fig"}) is at odds with the enhanced platelet life span in these animals ([Figure 4b](#fig4){ref-type="fig"}). To clarify this conundrum, we decided to investigate the *BCL-2*tg platelet phenotype in more detail.
Megakaryocyte frequency was normal in the bone marrow of *BCL-2*tg mice, as in *Bak*^−/−^ mice, albeit somewhat increased in *Bak*^−/−^*BCL-2*tg mice ([Figure 4c](#fig4){ref-type="fig"}). Although the percentage of reticulated (newly formed) platelets was unchanged in *BCL-2*tg compared with WT mice, their absolute number was significantly reduced ([Figure 4d](#fig4){ref-type="fig"}), implying a defect in platelet production from megakaryocytes. We therefore tested the ability of megakaryocytes from WT and *BCL-2*tg mice to produce pro-platelets *in vitro*. Consistent with a previous report,^[@bib30]^ Bcl-2 overexpression did not decrease proplatelet formation by fetal liver-derived megakaryocytes but, rather, caused a small but significant increase ([Figure 4e](#fig4){ref-type="fig"}). These data indicate that, at least in culture, *BCL-2*tg megakaryocytes exhibit no obvious defects in maturation and proplatelet formation. Nevertheless, when we analysed the ability of mice to recover from acute thrombocytopaenia induced by injection of anti-platelet serum (APS), we found that platelet rebound was significantly impaired in *BCL-2 versus* WT mice ([Figure 4f](#fig4){ref-type="fig"}).
To further clarify the basis for the platelet defect, we examined whether thrombocytopaenia in *BCL-2*tg mice is platelet-intrinsic or -extrinsic ([Figure 5](#fig5){ref-type="fig"}). Bone marrow chimaeric mice were generated by injecting lethally irradiated Ly5.1 mice with 2 × 10^6^ Ly5.2 bone marrow cells from *GFP*tg mice^[@bib31]^ (in which GFP expression is ubiquitous) or *BCL-2*tg mice, or with a 50 : 50 mixture of both. Analysis at 9 weeks post-transplantation showed that the red blood cell count was comparable in all three classes of reconstituted mice but, as expected, the white blood cell count was higher and the platelet count was lower in mice reconstituted with *BCL-2*tg cells than in those reconstituted solely with *GFP*tg cells ([Figures 5a--c](#fig5){ref-type="fig"}). In the *GFP*tg/*BCL-2*tg chimaeras, where the proportion of GFP^+^ platelets was around 40% ([Figure 5d](#fig5){ref-type="fig"} and [Supplementary Table 5](#sup1){ref-type="supplementary-material"}), total platelet counts were equivalent to those seen in mice reconstituted solely with *BCL-2*tg cells ([Figure 5c](#fig5){ref-type="fig"}). By 12 weeks, there were 24% GFP-positive platelets and the proportion of GFP-positive megakaryocytes was similar (22% [Supplementary Table 5](#sup1){ref-type="supplementary-material"}). We infer that (i) the *BCL-2*tg-driven thrombocytopaenia derives from bone marrow cells; (ii) WT (*GFP*tg) haemopoietic cells cannot compensate for the defect; and (iii) the defect in platelets is cell extrinsic.
Ten weeks post-reconstitution, mice were injected with APS and platelet numbers assessed daily for 5 days ([Figure 5e](#fig5){ref-type="fig"}). In all mice, APS reduced circulating platelet numbers to \<10% within 24 h. In the chimaeric *GFP*tg/*BCL-2*tg mice, the rebound was more robust than that seen in *BCL-2*tg-reconstituted mice, but still significantly impaired relative to *GFP*tg-reconstituted counterparts ([Figure 5e](#fig5){ref-type="fig"}). If the rate of production of platelets had been slower only in cells expressing the *BCL-*2 transgene, then the proportion of GFP-positive (i.e., *BCL-2*tg negative) platelets would have been expected to increase over time in the chimaeric *GFP*tg/*BCL-2*tg mice. However, it remained constant over the 5 days ([Figure 5f](#fig5){ref-type="fig"}), again suggesting that megakaryocyte- and platelet-extrinsic factors underlie the thrombocytopaenia observed in *BCL-2*tg animals.
Role of the spleen
------------------
As the spleen can increase or decrease the pool of platelets that it sequesters,^[@bib32]^ and *BCL-2*tg (and *Bak*^−/−^*BCL-2*tg) mice have enlarged spleens ([Supplementary Table 2](#sup1){ref-type="supplementary-material"}), we determined platelet counts before, and 4 weeks post, splenectomy in both WT and *BCL-2*tg mice. Although platelet numbers increased in both cohorts, the relative increment was equivalent: 1.4-fold increase in WT and 1.5-fold in *BCL-2*tg mice ([Figure 6a](#fig6){ref-type="fig"}). Furthermore, when acute thrombocytopaenia was induced in splenectomised mice, *BCL-2*tg animals mounted a significantly impaired response, with platelet counts very significantly lower than those seen in WT littermates 5 days post induction ([Figure 6b](#fig6){ref-type="fig"}). Although the degree of thrombocytopaenia in the splenectomised *BCL-2*tg animals is modest, when the increase in platelet life span in these animals is taken into account, it indicates a significant residual defect, which is amplified under conditions of emergency thrombopoiesis ([Figure 6b](#fig6){ref-type="fig"}).
Role of lymphocytes
-------------------
Having established that the thrombocytopaenia in *BCL-2*tg mice was due to environmental factors involving bone marrow-derived cells but extrinsic to megakaryocytes and platelets, we reasoned that a non-myeloid cell might be playing a role. We therefore crossed the *BCL-2*tg mice with *Rag1*^−/−^ mice, which lack mature B and T lymphocytes.^[@bib33]^ Circulating lymphocytes were greatly reduced in *BCL-2*tg *Rag1*^−/−^ compared with *BCL-2*tg mice ([Figure 6c](#fig6){ref-type="fig"}), as expected, but blood platelet counts were elevated 1.7-fold ([Figure 6d](#fig6){ref-type="fig"}). Indeed, platelet counts in *BCL-2*tg *Rag1*^−/−^ mice were comparable to those in WT and *Rag1*^−/−^ mice. Thus, the absence of mature lymphocytes prevents thrombocytopaenia in *BCL-2*tg mice. Given the increased platelet life span conferred by overexpression of BCL-2, however, the increase is not as much as might be expected, suggesting that additional (unknown) factors might contribute to the *BCL-2*tg phenotype.
Discussion
==========
Bax and Bak are the critical effectors of apoptosis. Although both are widely expressed and functionally redundant, genetic and biochemical data suggest that Bak is held in check primarily by Mcl-1 and Bcl-x~L~, whereas Bax activation is inhibited by all five pro-survival Bcl-2 homologues.^[@bib14],\ [@bib15],\ [@bib16]^ Recent studies have suggested that Bak activation is the principal trigger for apoptosis in platelets^[@bib11]^ and in certain thymic populations.^[@bib13]^ To test whether Bak is critical at other stages of haemopoietic development, we crossed vavP-*BCL-2*tg mice with mice lacking Bak. We also crossed vavP-*BCL-2*tg mice with vavP-*Mcl-1*tg mice, in which Bak activation in haemopoietic cells should be more difficult to achieve than in WT mice.
Constitutive overexpression of Bcl-2 during haemopoiesis results in many changes: thymic abnormalities, most notably a low proportion of DP thymocytes; striking peripheral lymphocytosis involving both B- and T-lymphoid cells; elevated ASCs and serum Ig; poorly understood thrombocytopaenia; and predisposition to autoimmune kidney disease and late onset follicular lymphoma.^[@bib19],\ [@bib20]^
Our analysis of young *Mcl-1*tg/*BCL-2*tg mice suggested that overexpression of Mcl-1 did not significantly modulate the *BCL-2tg* phenotype ([Supplementary Figure 1](#sup1){ref-type="supplementary-material"}), probably because the level of Mcl-1, albeit significantly higher than normal,^[@bib18]^ was insufficient to effectively reduce Bak activation.
In contrast, *Bak*^−/−^*BCL-2*tg mice developed a more severe lymphocytosis than *BCL-2*tg littermates, primarily due to a further elevation in the numbers of mature B- and T-lymphoid cells ([Figure 1a](#fig1){ref-type="fig"}), changes that were not seen in *Bax*^−/−^*BCL-2*tg mice ([Supplementary Table 3](#sup1){ref-type="supplementary-material"}). The implication is that Bak can have a non-redundant role in maintaining homeostasis within these populations. Bak must be less critical in regulating ASCs, however, because their frequency was comparable in *BCL-2*tg and *Bak*^−/−^*BCL-2*tg mice, as was the risk of autoimmune kidney disease ([Supplementary Figure 5](#sup1){ref-type="supplementary-material"}).
Lack of Bak had no impact on the low proportion of DP thymocytes characteristic of *BCL-2*tg mice ([Figure 1b](#fig1){ref-type="fig"}), which kinetic analysis suggested was preceded by an accumulation of DN cells expressing high levels of TCR*β* ([Figure 2a](#fig2){ref-type="fig"}). Also notable in *Bim*^−*/*−^ and *Bim*^−/−^*Puma*^−/−^ mice, these TCR*β*+DN cells are thought to be thymocytes that have downregulated their co-receptors^[@bib26],\ [@bib34]^ after escaping negative selection at the DP stage.^[@bib22]^ The 'pseudo\' DN cells may inhibit the expansion and maturation of *bona fide* DN progenitor cells to DP (pre-T) cells,^[@bib22]^ perhaps due to competition for niche cells or cytokines.
DP thymocytes, normally highly sensitive to apoptosis, are rendered significantly resistant to most cytotoxic agents by overexpression of Bcl-2.^[@bib24]^ Loss of Bak modestly enhanced the resistance of DP thymocytes from *BCL-2*tg mice to apoptosis induced by DNA-damaging agents *in vitro* ([Figure 3a](#fig3){ref-type="fig"}) and significantly increased their resistance to CD3 antibody treatment *in vivo* ([Figure 3b](#fig3){ref-type="fig"}). Thus, Bak may be non-redundant for effecting apoptosis of certain lymphoid populations, perhaps because of kinetic differences in the activation of Bak *versus* Bax and/or a Bak-specific component of certain apoptosis-inducing signals. Ca^+^ flux (which is induced by TCR/CD3 ligation) may have an important role in the Bak activation, as, by itself, loss of Bak provided significant protection against apoptosis induced by ionomycin ([Figure 3a](#fig3){ref-type="fig"}). We have shown previously that loss of the pro-apoptotic BH3-only protein Bim also provides greater resistance to CD3 antibody than the *BCL-2* transgene and that Bim is the critical downstream apoptosis effector.^[@bib26],\ [@bib35]^ Bim can activate both Bak and Bax as well as inhibit all pro-survival Bcl-2 family members.^[@bib36],\ [@bib37],\ [@bib38]^
Our most unexpected finding involved platelets. The observation that *BCL-2*tg mice are thrombocytopaenic^[@bib17]^ led to conjecture that platelet shedding by megakaryocytes involves activation of apoptosis,^[@bib39]^ and a considerable body of subsequent work supported that notion (reviewed in White and Kile^[@bib32]^). However, counter to this proposal, we and others recently demonstrated that deletion of Bak and Bax does not impair platelet production.^[@bib12],\ [@bib40],\ [@bib41]^ Thus, an explanation for the thrombocytopaenic phenotype of *BCL-2*tg mice has remained elusive.
Platelet survival is primarily dependent on Bcl-x~L~, which is required in ageing platelets to restrain Bak, the principal mediator of their apoptosis.^[@bib11],\ [@bib12],\ [@bib42]^ We found that platelet life span is extended in *BCL-2*tg mice ([Figure 4b](#fig4){ref-type="fig"}), demonstrating for the first time that overexpression of a Bcl-2 family pro-survival protein can positively influence the survival of platelets in the circulation. BCL-2 may be able to partly restrain Bak at these high, non-physiological concentrations, as well as inhibit normal targets Bax and Bad, which also influence platelet life span,^[@bib12],\ [@bib43]^ albeit not to nearly the same extent as loss of Bak.^[@bib12]^ In any event, the thrombocytopaenia in *BCL-2*tg animals must actually be more severe than suggested by the platelet count alone -- were this not the case, the extended platelet life span conferred by the *BCL-2* transgene would have provoked mild thrombocytosis.
Consistent with Kozuma and colleagues,^[@bib30]^ megakaryocyte numbers were normal in *BCL-2*tg mice, and their ability to form pro-platelets *in vitro* was unimpaired. However, contrary to that study, removal of the spleen did not raise their platelet counts to that found in splenectomised WT mice, either at steady state or during emergency thrombopoiesis ([Figures 6a and b](#fig6){ref-type="fig"}), ruling out increased splenic sequestration as the principal cause. Instead, we believe the thrombocytopaenia is underpinned by a defect in platelet shedding caused by extrinsic factors in the *BCL-2*tg haemopoietic microenvironment. Analysis of bone marrow chimaeras supported this notion, as WT megakaryocytes in a *BCL-2*tg environment were unable to produce platelets at the same rate as those in a WT environment ([Figure 5e](#fig5){ref-type="fig"}). Our data suggest that the lymphocytosis induced by the *BCL-2* transgene is a major contributing factor, as platelet counts increased to WT levels in a *Rag1*^−/−^ background ([Figure 6d](#fig6){ref-type="fig"}). Other as yet unidentified haemopoietic cells must also have a role, however, as platelet counts were not elevated above WT levels, as would be expected from the increased platelet life span conferred by overexpression of BCL-2. As vavP-*BCL-2* transgene expression also elevates levels of bone marrow macrophages and monocytes ([Supplementary Table 2](#sup1){ref-type="supplementary-material"}), these cells may contribute. However, whether the impairment of platelet production is mediated directly by lymphoid and other haemopoietic cell types or indirectly, via effects on other tissues, remains to be determined. Furthermore, it remains formally possible that, in addition, BCL-2 overexpression does have a subtle intrinsic impact on megakaryocyte function. Specific overexpression of BCL-2 in the megakaryocyte lineage *in vivo* would enable this to be assessed in the absence of extrinsic factors.
Materials and Methods
=====================
Mice
----
All mice used were on a C57BL/6J background and bred at the Walter and Eliza Hall Institute (WEHI). Experimental protocols were approved by Animal Ethics Committee of WEHI. Transgenic mouse lines were vavP-*Mcl-1*(33)^[@bib18]^ and vavP-*BCL-2*(69),^[@bib17],\ [@bib20]^ which, respectively, express FLAG-tagged mouse Mcl-1 protein and human BCL-2 protein in haemopoietic cells.^[@bib19]^ To generate *Mcl-1*tg/*BCL-2*tg mice, *Mcl-1*tg males were mated with *BCL-2*tg females. To generate *Bak*^−*/*−^*BCL-2*tg mice, *BCL-2*tg males were crossed with *Bak*^−*/*−[@bib10]^ females, then *Bak*^+/−^ *BCL-2*tg males were mated with *Bak*^+/−^ females. Crosses were also performed with *Rag1*^−/−^,^[@bib44]^ *Bax*^+/−[@bib45]^ and Tg(UBC-GFP)30Scha/J mice (*GFP*tg mice).^[@bib31]^
Haemopoietic analysis
---------------------
Single-cell suspensions were prepared from spleen, lymph nodes, bone marrow and thymus and viable leukocytes enumerated using a haemocytometer and trypan blue exclusion or with a CASY Cell Counter (Scharfe System GmbH, Reutlingen, Germany). An ADVIA 2120 haematology analyser (Siemens, Erlangen, Germany) was used for obtaining blood cell counts. The remaining blood was depleted of red cells by treatment with 0.168 M ammonium chloride before fluorescence-activated cell sorting (FACS) analysis. Cell composition was determined by staining with fluorochrome-labelled surface marker-specific monoclonal antibodies followed by FACS analysis using an LSRI (BD Biosciences, Franklin Lakes, NJ, USA). Data were processed using FlowJo Version 9.3.2 (TreeStar, Ashland, OR, USA) and Weasel Version 3.0 software (Walter and Eliza Hall Institute, Melbourne, VIC, Australia). The monoclonal antibodies, produced and labelled with fluorescein isothiocyanate, R-phycoerythrin or allophycocyanin (APC) at WEHI unless otherwise indicated, were: RB6-8C5, anti-Gr1; MI/70, anti-Mac1; H129.19, anti-CD4; YTS169, anti-CD8; Ter119, anti-erythroid marker; ID3, anti-CD19; RA3-6B2, anti-CD45R-B220; 5.1, anti-IgM; 11-26C, anti-IgD; S7, anti-CD43; T24-31, anti-Thy1; H57-59, anti-TCR*β*; Jo2, anti-Fas/CD95 (BD Biosciences); anti-PNA (Vector Laboratories, Cambridgeshire, UK).
Blood platelet counts were determined using an ADVIA 2120 analyser (Siemens) or by flow cytometry, as follows: 5 *μ*l of tail vein blood was diluted 40-fold in PBS in an EDTA tube and stained with CD41 antibody (clone MWReg30, BD Biosciences) labelled with APC; 10 *μ*l was then added to PBS (980 *μ*l) containing 10 *μ*l beads (ProSciTech, Townsville, QLD, Australia; 3.5--4 *μ*m beads, 1 × 10^7^/ml) and 1000 events were acquired by flow cytometry; platelet frequency was calculated as dilution factor (4000) × number of events in platelet gate (CD41^+^) × 1 × 10^5^. Reticulated platelet numbers were determined by staining with thiazole orange and CD41-APC antibody^[@bib11]^ followed by analysis on a FACSCalibur flow cytometer (BD Biosciences). Platelet life span was investigated by *in vivo* labelling with biotin.^[@bib11]^ Induction of thrombocytopaenia with APS, culture of fetal liver megakaryocytes, proplatelet formation assays and platelet preparation were performed as described.^[@bib11],\ [@bib12]^
CD3 antibody treatment
----------------------
Mice were injected intraperitoneally with 30 *μ*g hamster mAb to mouse CD3*ɛ* (145-2C11) or, as a control, isotype-matched antibody to TCR*γ* (GL3) and killed after 40 h for analysis of thymic cellularity and composition by flow cytometry.
Survival assays
---------------
Thymocyte populations isolated by flow cytometry were cultured at 0.2--0.5 × 10^6^ cells/ml in high-glucose Dulbecco\'s Modified Eagle\'s medium supplemented with 10% fetal calf serum (Bovogen, Melbourne, VIC, Australia), 50 *μ*M 2-mercaptoethanol (Sigma-Aldrich, St. Louis, MO, USA) and 100 *μ*M asparagine (Sigma-Aldrich) without additional cytokines in the presence or absence of 10 *μ*g/ml etoposide (Pfizer, Sydney, NSW, Australia), 10 *μ*M dexamethasone phosphate (Hospira, Lake Forest, IL, USA), 10 ng/ml PMA (Sigma-Aldrich), 10 *μ*g/ml ionomycin (Sigma-Aldrich) or following treatment with 10 Gy *γ*-irradiation. Cell viability was determined by flow cytometry after staining with fluorescein isothiocyanate-conjugated Annexin V and propidium iodide. Specific viability was calculated at each time point as (viability of treated cells/viability of untreated cells) × 100%. Alternatively, apoptotic cells were identified by active caspase-3 staining. Cells were fixed and permeabilised using the BD Cytofix/Cytoperm Kit for 20 min, then washed with BD Perm/Wash buffer and stained with phycoerythrin rabbit anti-active caspase-3 antibody (clone C92-605, BD Biosciences), then washed again in BD Perm/Wash buffer before analysing by flow cytometry.
Haemopoietic reconstitutions
----------------------------
The *GFP*tg/*BCL-2*tg haemopoietic chimaeras were generated using bone marrow collected from *GFP*tg and *BCL-2*tg mice. Bone marrow (2 × 10^6^) cells suspended in phosphate-buffered saline were injected into lethally irradiated (2 × 5.5 Gy spaced by 2 h) C57BL/6-CD45.1 (Ly5.1) mice. To prevent infections, transplanted animals were initially provided with water containing neomycin (Sigma-Aldrich). After stable reconstitution of their haemopoietic system (9 weeks later), blood was collected from the retro-orbital plexus for ADVIA and FACS analysis (see above).
Western blot analysis
---------------------
Thymocyte lysates were prepared using RIPA buffer (300 mM NaCl, 2% octylphenoxypolyethoxyethanol (IGEPAL CA-630; Sigma-Aldrich), 1% deoxycholic acid, 0.2% SDS, 100 mM Tris-HCl pH 8.0) containing protease inhibitors (Roche, Basel, Switzerland) and platelet lysates with NP40 lysis buffer (1% octylphenoxypolyethoxyethanol, 150 mM NaCl, 50 mM Tris-HCl, pH 7.4) containing protease inhibitors. Proteins were separated on NuPAGE Bis-Tris gels (Life Technologies, Carlsbad, CA, USA) according to manufacturer\'s instructions. Blots were probed with: anti-Mcl-1 (clone 19C4-15; WEHI mAb facility), anti-human Bcl-2 (clone Bcl-2-100;^[@bib46]^ WEHI mAb facility), anti-Bcl-2 (clone 7; BD Biosciences), anti-Bim (polyclonal; Enzo Lifesciences, Farmingdale, NY, USA), anti-Bcl-x~L~ (polyclonal; BD Biosciences), anti-Bak (polyclonal; Sigma-Aldrich) and anti-*β*-actin (clone AC-74; Sigma-Aldrich).
ELISA and enzyme-linked immunospot (ELISPOT)
--------------------------------------------
ASCs were enumerated by ELISPOT. MultiScreen-HA filter plates (Merck Millipore, Billerica, MA, USA ) were coated with 2 *μ*g/ml anti-mouse total Ig (DA, Silenus Laboratories, Boronia, VIC, Australia) or 10 *μ*g/ml anti-mouse IgA (Southern Biotech, Birmingham, AL, USA). Red cell-depleted spleen or bone marrow cells were added at 1 × 10^4^ or 1 × 10^5^ per well in RPMI/5% FCS/5 *μ*M 2-mercaptoethanol and incubated for 18--19 h. The plates were washed and incubated with secondary antibodies: anti-mouse IgA-biotin, anti-mouse IgG1-HRP/IgG2a-HRP/IgG2b-biotin/IgG3-HRP or anti-mouse IgM-HRP (Southern Biotech). For biotinylated antibodies, plates were washed again and incubated with streptavidin-HRP (Southern Biotech). ELISPOTs were revealed by the addition of substrate solution: 250 *μ*g/ml 3-amino-9-ethylcarbazole (Sigma-Aldrich) in 0.05 M sodium acetate (pH 5.0) and 0.03% H~2~O~2~. ELISPOTs were counted on an ELISPOT reader (Autoimmun Diagnostika GMBH, Strasburg, Germany).
Serum Ig levels were determined by ELISA. Plates were coated with specific anti-mouse Ig antibodies (Southern Biotech). Purified mouse monoclonal IgM*κ* (TEPC 183), IgG1*κ* (MOPC31c), IgG2a*κ* (UPC 10), IgG2b*κ* (MOPC 141), IgG3*λ* (Y5606) and IgA*λ* (MOPC315; Sigma-Aldrich) were used to quantify Ig concentration. Biotinylated or HRP-conjugated isotype-specific antibodies were as for ELISPOT assay (with streptavidin-HRP, if required). The assay was developed with 0.54 mg/ml diammonium 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (Sigma-Aldrich) in 0.1 M citric acid (pH 4.4) and 0.03% H~2~O~2~. Absorbance at 492 nm was measured in a microplate reader.
Statistical analysis
--------------------
GraphPad Prism (Version 5.0a; GraphPad Software, La Jolla, CA, USA) was used to graph and statistically analyse data. The Mann--Whitney test was used to determine statistical significance when samples had a clear difference in S.D., otherwise, an unpaired two-tailed *t*-test was performed. For analysis of Kaplan--Meier mouse survival curves, significance was determined using the log-rank (Mantel--Cox) test.
We thank our colleagues Andreas Strasser, Warren Alexander, Daniel Gray and David Tarlinton for useful discussions; Giovanni Siciliano, Jessica Mansheim, Kelly Trueman, Krystal Hughes, Sophie Allan, Marion Lebois and Katya Henley for excellent technical assistance; and A Strasser and D Tarlinton for reagents. This work was supported by the NHMRC (Australia) program grants 461221; 1016647; NHMRC project grant 575535; NCI grant CA43540; Leukemia and Lymphoma Society Specialized Center for Research Grant 7015-02; Australian Cancer Research Foundation (Centre for Therapeutic Target Drug Discovery); Fellowships from the Sylvia and Charles Viertel Foundation (BTK), Leukemia and Lymphoma Society (ECJ), NHMRC Career Development Award (CJV); NHMRC/INSERM (CJ), EMBO (CJ, KJC), Human Frontier in Science Program (KJC) and infrastructure support to WEHI from the NHMRC Independent Research Institute Infrastructure Support Scheme (IRISS) and the Victorian State Government Operational Infrastructure Support(OIS).
**Author Contributions**
CJV and SC conceived the studies, planned experiments, analysed data. BTK and ECJ provided advice and designed the platelet experiments. CJV, ECJ, KJC, CJ and KEL performed the experiments. CJV, SC, ECJ and BTK wrote the manuscript.
APS
: anti-platelet serum
ASC
: antibody-secreting cell
BH
: Bcl-2 homology
DN
: double negative
DP
: double positive
FACS
: fluorescence-activated cell sorting
Ig
: immunoglobulin
mAb
: monoclonal antibody
PMA
: phorbol 12-myristate-13-acetate
SP
: single positive
TCR
: T-cell receptor
tg
: transgenic
WT
: wild type
[Supplementary Information](#sup1){ref-type="supplementary-material"} accompanies this paper on Cell Death and Differentiation website (http://www.nature.com/cdd)
Edited by C Borner
The authors declare no conflict of interest.
Supplementary Material {#sup1}
======================
######
Click here for additional data file.
{ref-type="supplementary-material"}. Statistical significance is shown only for *BCL-2*tg *versus Bak*^−*/*−^*BCL-2*tg; \**P*\<0.05, \*\**P*\<0.01, Mann--Whitney test. (**c**) Expression of the indicated Bcl-2 family proteins in sorted DP thymocytes determined by western blot analysis of cells from two independent mice for each genotype](cdd2013201f1){#fig1}
{ref-type="supplementary-material"}. Statistical significance is shown only for *BCL-2*tg *versus Bak*^−*/*−^*BCL-2*tg; \**P*\<0.05, Mann--Whitney test](cdd2013201f2){#fig2}
{#fig3}
{#fig4}
{#fig5}
{#fig6}
[^1]: Current address: Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, UK
[^2]: Current address: Laboratoire d\'Hématologie du CHU de Bordeaux, Bordeaux, France; Université Bordeaux Segalen, Bordeaux, France; INSERM U1034, Pessac, Bordeaux, France
| null | minipile | NaturalLanguage | mit | null |
Midfielder Sergio Pena was the unlucky player to miss out as Peru finalised their 23-man squad for the World Cup on Monday.
Pena was forced to make way for captain Paolo Guerrero, who has been freed to take part at the tournament after the Swiss Federal Tribunal agreed to temporarily lift a 14-month doping ban pending an appeal.
Guerrero, who tested positive for a cocaine byproduct contained in a tea and which he said he ingested unknowingly, was freed to take part on Thursday and scored twice in the 3-0 win over Saudi Arabia on Sunday.
Peru, making their first appearance at the World Cup since 1982, face Denmark, France and Australia in their group.
"This is the most difficult moment of my career and I feel I did not do enough to take part in the best competition in the world and represent my country as well as possible," Pena said on Instagram.
"Tomorrow, I will wake up with more strength than ever and continue what I love doing," added the 22-year-old, who plays for Spanish second division side Granada.
Peru squad:
Goalkeepers: Pedro Gallese (Veracruz), Carlos Caceda (Deportivo Municipal), Jose Carvallo (UTC).
Defenders: Aldo Corzo (Universitario), Luis Advincula (Lobos Buap), Christian Ramos (Veracruz), Miguel Araujo (Alianza Lima), Alberto Rodriguez (Atletico Junior), Anderson Santamaria (Puebla), Miguel Trauco (Flamengo), Nilson Loyola (Melgar).
Midfielders: Renato Tapia (Feyenoord), Pedro Aquino (Lobos Buap), Yoshimar Yotun (Orlando City), Paolo Hurtado (Vitoria Guimaraes), Christian Cueva (Sao Paulo), Edison Flores (Aalborg), Andy Polo (Portland Timbers), Wilder Cartagena (Veracruz).
Forwards: Andre Carrillo (Watford), Raul Ruidiaz (Morelia), Jefferson Farfan (Lokomotiv Moscow), Paolo Guerrero (Flamengo). | null | minipile | NaturalLanguage | mit | null |
VICOLUNGO Many jobs, no one accepts them, arriving immigrants, hundreds of immigrants and fear begins to serpeggiare Lower. This has been debated in the evening "Security and immigration-issues of our current society. How to ensure security in the territory in the light of current legislation on immigration ", held in the hall of the castle, on Friday 26 October, organized by administrators and Vicolungo Commons. We see the historical background: all this stems from the recent presence on the territory of the town of Biandrate an important logistical hub as the Esselunga, which will serve the entire North ItaGlia, and the fact that it has raised among the local residents, considerable apprehension for the consequences of social impact of a planned presence of non-citizens (mostly Pakistani Muslims) quantifiable between 1,500 and 2,000 units. In fact, the jobs were, as the mayor of Biandrate, Sandra Zanaria: "I delivered personally 700 curricula, but many refuse to do work humble and work in cold rooms ».(...) | null | minipile | NaturalLanguage | mit | null |
Who is the lead role in this? Naturally I haven't seen it because I cant find where to buy it but after reading Eli Wallach's book he was offered the role in this movie but the producers said no use steiger. But I thought it was James Coburn who ended up playing in the role.
the revolution steiger and colburn get into reminds me of the civil war blondie & tuco get caught up in w/ a big difference . AE's, blondie & tuco avoided the war with disgust. so many men wasted so badly.
th civil war was about slavery, cotton, and southern "pride". the revolution was different.there was a real cause to take up arms....and dynamite | null | minipile | NaturalLanguage | mit | null |
Contents: The Sir! No Sir! blog is an information clearing house, drawing on a wide variety of sources, to track the unfolding history of the new GI Movement, and the wars that brought the movement to life.
Where applicable, parallels will be drawn between the new movement and the Vietnam era movement which was the focus of the film Sir! No Sir!
Disclaimer: In accordance with title 17 u.s.c. section 107, this material is distributed without profit for research and educational purposes.
The Sir! No Sir! Blog has no affiliation whatsoever with the originator of this article nor is the Sir! No Sir! Blog endorsed or sponsored by the originator. Links are provided to allow for verification of authenticity.
US Military - National Guard
March 11, 2009
This article, by William H. McMichael, was originally published by The Army Times, March 5, 2009
A Maryland state senator is pushing a bill that would require the governor to prevent the mobilization of the state’s National Guard for federal duty unless Congress has authorized the use of military force or issued a declaration of war.
The bill also would authorize the governor to ask for the return of deployed units in certain circumstances.
But unlike initiatives such as the multi-state “Bring the Guard Home” campaign that are rooted in anti-war sentiment, State Sen. Richard Madaleno Jr.’s bill aims to influence national policy and practice. Madaleno said he wants Congress to play a larger role in future troop deployment decisions, including determining whether the Guard truly needs to be part of any overseas military action.
“I think one of the lessons — certainly, of Iraq — is, ‘We gave this authority to the president,’ ” Madaleno said after a March 4 committee hearing on the bill in Annapolis, Md.
After the successful invasion, public awareness waned, which “allowed a policy drift,” Madaleno said. “And if you put in place certain additional checks, ... you potentially provide the framework for Congress to do something and remain engaged in the oversight of the conflict.”
The debate over which branch of government has the authority to declare war has continued for decades. World War II was the last conflict initiated by a formal declaration of war. Congress in 2001 gave President George W. Bush blanket authority to deploy troops in response to terrorist attacks or threats, clearing the way for Operation Enduring Freedom, and in 2002 authorized the use of military force in Iraq.
But many of the conflicts or military strikes of the past 60 years have been fought, at least initially, without the approval of the body with the constitutional authority to “declare war” — most famously in Korea, but also in Libya, Grenada, Panama, Operation Desert Shield, Somalia, Haiti, Bosnia, Sudan, the former Yugoslavia, Bosnia and Kosovo.
Madaleno, a Democrat, said he supported the Iraq invasion, although he said hebelieves there were “serious gaps in how the war was prosecuted after ... the first six months.”
At the same time, he argued, “If we are actually going to be actively engaged in conflicts around the world for a variety of reasons, how do we create a political process that makes sure that the people remain engaged and supportive of the conflicts that we’re in? It shouldn’t just be the executive branch that is solely responsible for that decision-making. We have to create a political process that keeps the public engaged, informed, through their elected representatives.”
State Sen. George Edwards, a Republican, said he wasn’t familiar with Madaleno’s bill, but he indicated he would not be inclined to support it.
“Maybe there’s going to be times when something needs to be done without a declaration of war,” he said. “We’re part of the United States of America. We take things from the federal government, [like] when they want to give us this stimulus package money. The federal government buys most of our military equipment. When people join the Guard, they know the potential of being called up to active duty to protect the interests of the United States. I think it’s working fine just the way it is.”
The Maryland National Guard is staying out of the debate. “We have no position on this bill,” said Army Lt. Col. Charles Kohler, spokesman for the Maryland Guard. “Our job in the military is to follow the orders” of civilian leadership.
The Maryland Guard has about 300 troops mobilized and deployed to Iraq, Afghanistan, Kosovo and Bosnia, Kohler said. Over the 2007-08 timeframe, some 1,200 troops were deployed to Iraq, most with the 58th Infantry Brigade Combat Team, in what Kohler said was the Maryland Guard’s largest combat-zone deployment ever.
About 5,000 troops serve in the Maryland Army National Guard, with another 1,500 in the state’s Air National Guard, according to Kohler.
Currently, 34,851 Army National Guard and Air National Guard troops, and 24,717 members of the four Reserve forces, are deployed to Iraq, Afghanistan and other areas considered part of Operation Enduring Freedom, according to the Pentagon.
Maryland is also home to a Bring the Guard Home campaign, which argues that the National Guard is unlawfully deployed because the aims of the war in Iraq outlined in the 2002 congressional authorization for use of force have been achieved and that the authorization did not provide for “an indefinite assignment of State Guard members to the National Guard of the United States.”
Despite the differing emphasis in his bill, Madaleno — whose photo and bill are displayed on the campaign’s Web page — said he wouldn’t mind if the Maryland group’s and others’ initiatives were also successful, as they would have the same effect.
“By doing it this way, I’m trying to take a slightly different tack than several other states, where they’ve focused solely on the resolution to bring the Guard home from Iraq now,” Madaleno said. “And I’m trying to refocus and broaden the debate a little bit: What are the lessons of this conflict that inform us for the next conflict?”
February 13, 2009
This article, by Joseph B. Frazier, was distributed by the Associated Press, February 11, 2009
PORTLAND, Ore. — The Oregon National Guard has written to 433 of its soldiers to say they may have been exposed to a toxic, carcinogenic chemical at an Iraqi water pumping plant shortly after the war began.
Guard spokesman Maj. Mike Braibish said three companies of the 162nd Infantry Battalion were deployed in Kuwait, and the troops were sent, about 50 at a time, into Iraq to escort employees of Houston-based KBR, which was inspecting oil facilities.
He said no symptoms indicating exposure have been reported to the Oregon Guard.
“That doesn’t mean they won’t be,” Braibish said Wednesday. “Some may have been treated by the Veterans Administration, and we don’t know about it. It’s a possibility.”
U.S. Sens. Evan Bayh of Indiana and Byron Dorgan of North Dakota say there are unanswered questions about the exposure of U.S. troops to the chemical hexavalent chromium at the Basra water plant in 2003.
Bayh first raised concerns about the Indiana Guard. In a letter to the Pentagon on Tuesday, the senators mentioned Oregon troops.
They say KBR allowed soldiers to be exposed to the chemical for more than two months even though KBR knew the site was contaminated. KBR has denied it knowingly harmed troops or was responsible for an unsafe condition.
The senators also say that Indiana National Guard troops didn’t learn of possible exposure until they saw KBR workers wearing special clothing and that Guard troops from Oregon, South Carolina and West Virginia haven’t been told they may have been exposed.
Braibish said 433 letters were sent earlier this year. He said 18 were returned as undeliverable.
“We have the responsibility to let the soldiers know what we know,” he said.
He said Oregon troops did the guard duty for six to eight weeks in 2003, and then the Indiana National Guard took it over.
Each Oregon soldier may have gone into the area four times but not necessarily to the water treatment facility at Basra, Braibish said.
They would go into Iraq and return to Kuwait each night, he said.
He said Indiana troops went to the same locations each day and may have stayed at the facility at times.
The company closed the site in summer 2003 for “remediation,” or to fix problems, he said.
In October 2003, the Army started studying hexavalent chromium levels at the site.
Braibish said a key to determining exposure would be concentrations of the chemical before “remediation,” which KBR may know but which the Army does not.
“There are three factors,” Braibish said. “Time, or duration, frequency and concentration.”
“We know the duration and frequency,” but not the concentration levels before KBR tried to fix the problem by covering the area with gravel and asphalt, he said.
He said KBR did not report concentration levels and was not required to do so in its contract.
Based on the data they could get, Braibish said, Department of the Army investigators concluded that exposure levels did not exceed OSHA levels and were not substantial.
“I believe we made a good faith effort,” Braibish said. “The challenge is that we don’t know the concentration. Does KBR know?”
He said symptoms can include respiratory problems, torn nasal membranes and, in severe cases, various forms of cancer.
Hexavalent chromium is used, among other things, as an additive to dyes, paints, inks and plastics, and as an anticorrosive surface coating.
January 14, 2009
The following report, was originally filed by CBS Nwews, December 22, 2008
The military contractor Kellogg Brown and Root, known as KBR, has won more than $28 billion in U.S. military contracts since the beginning of the Iraq war. KBR may be facing a new scandal. First, accusations its then-parent company Halliburton was given the lucrative contract. And later, allegations of shoddy construction oversight that resulted in Americans getting electrocuted. Now, some other American soldiers say the company knowingly put their lives at risk, CBS News chief investigative correspondent Armen Keteyian exclusively reports.
In April of 2003, James Gentry of the Indiana National Guard arrived in Southern Iraq to take command of more than 600 other guardsmen. Their job: protect KBR contractors working at a local water plant.
"We didn't question what we were doing, we just knew we had to provide a security service for the KBR," said Battalion Cmdr. Gentry.
Today James Gentry is dying from rare form of lung cancer. The result, he believes, of months of inhaling hexavalent chromium - an orange dust that's part of a toxic chemical found all over the plant.
At least one other Indiana guardsman has already died from lung cancer, and others are said to be suffering from tumors and rashes consistent with exposure to the deadly toxin.
"I'm a nonsmoker. I believe that I received this cancer from the southern oil fields in Iraq," he said.
Now CBS News has obtained information that indicates KBR knew about the danger months before the soldiers were ever informed.
Depositions from KBR employees detailed concerns about the toxin in one part of the plant as early as May of 2003. And KBR minutes, from a later meeting state "that 60 percent of the people … exhibit symptoms of exposure," including bloody noses and rashes.
Gentry says it wasn't until the last day of August in 2003 - after four long months at the facility - that he was told the plant was contaminated.
"We would never have been there if we would have known," Gentry said.
A new internal Army investigation obtained exclusively by CBS News says the Army's medical response was "prompt and effective." But even after a briefing Monday, Indiana Sen. Evan Bayh says that KBR has a lot to answer for.
"Look, I think the burden of proof at this point is on the company," Bayh said. "To come forward and very forthrightly explain what happened, why we should trust them, and why the health and well-being of our soldiers should continue to be in their hands."
In a statement, the company told CBS News: "We deny the assertion that KBR harmed troops and was responsible for an unsafe condition."
The company says it notified the Army as soon as it identified the toxin.
Still, some Indiana guardsmen say they only just learned of the risk.
"I didn't know I was exposed to a deadly carcinogen until five years later when I received a letter," said Indiana National Guardsman Jody Aistrop.
This is far from the first time the multi-billion dollar contractor has been accused of questionable conduct at Iraq. In addition to convictions for bribery, it's alleged KBR provided contaminated water to troops. The company denies all charges.
"It's going to cost American lives, I'm afraid," Gentry said. "I love them. I love my men so much."
So much so Gentry says he will urge each and every one of them get tested for the cancer that he fears is taking his life.
July 03, 2008
This report, by Libby Lewis, was originally broadcast on National Public Radio's All Things Considered, June 18, 2008
Men have been going off to war and coming home since time began. Every veteran must reckon in one way or another with the gulf between what he's experienced and what the rest of us have not. That gulf has meant the ruin for a lot of men, and also for some women.
Well, now a group of Iraq veterans is trying to bridge the divide. They're talking to communities, colleges and police about what it's like to come home from war. NPR's Libby Lewis has this report.
LIBBY LEWIS: These were Michael Hawley's first days out of Iraq.
Mr. MICHAEL HAWLEY (Iraq War Veteran): The first night, I caught the clap. The second night, I got in a fight with a white rapper and his posse. My friends and I got clubbed. Third night, nothing happened, but I was still out. And the fourth night, I impregnated a 38-year-old grandmother.
LEWIS: Hawley's at the police station in Granby, Connecticut with four other war veterans. They're talking to officers around here who work together as crises negotiators. The instigator here is Jay White. He's a counselor at the VA's Hartford Vet Center. He served two tours in Iraq. He wants to reach the people on Main Street who deal with trouble - like police and emergency rescue people - because trouble is the way many war veterans have dealt with the gulf between them and us. Jay White looks out at the police officers in Granby.
Mr. JAY WHITE (Counselor, VA's Hartford Vet Center): As you'll hear from these guys, it's a volatile crowd. And the varying ages, varying degrees of what people saw in Iraq or Afghanistan, and they're coming back to Connecticut.
LEWIS: Why should police and the rest of us need to know what's in these guy's heads and what happened to them so far away in the past? Author William Faulkner knew. He put it this way: The past isn't dead. It isn't even past.
Take Jesse Cohen's first encounter in combat in Iraq. It keeps coming back in the middle of the night here in suburban Connecticut. Cohen's telling these police officers, these strangers, what he hasn't told anybody else before.
Mr. JESSE COHEN (Iraq War Veteran): My girlfriend, she hears me talking at night. And often I have to wake up, change my clothes, take a shower, 'cause I'm drenched in sweat. And it's like I'm there again.
LEWIS: In his dream, there's a line of white dots that grow larger and turn into trucks, then a firefight, and brain matter on a windshield.
Mr. COHEN: And this time, it's more traumatic than it was the first time. 'Cause the first time, it was like a video game. I'm like, oh, wow. Cool. This happened. And it doesn't hit you until you're back here, and you're just like, wow, everything just downloaded and you're just trying to process it.
LEWIS: These are regular guys. They went to Iraq for the same reasons men have always gone to war: to do the right thing for their country, or to get ahead in life, or to prove themselves to themselves. Three of them served together in the Connecticut National Guard. Before they went, their idea of war was from the movies or video games.
Aaron Jones is a beefy guy with tattoos all over his arms. He takes the police officers back to his first day in Iraq after training. He hears a noise...
Mr. AARON JONES (Iraq War Veteran): I walked outside, and there's my platoon sergeant laying with a hole in his shoulder. Turns out he had one his head, too. I didn't notice that, the way he had fallen. And he pretty much died in my arms as I was dragging him to the bunker.
LEWIS: Patrick Montes helped Jones pull their sergeant's body inside. Two days later, they lost their buddy Felix Delgreco in an attack. He was 22.
Mr. PATRICK MONTES (Veteran of Iraq and Afghanistan): I did the math in my head. I was like, wait a minute. There's 120 of us, and there's 365 days. And we've been here three days, and we're down two, and we have two wounded. And so, you know, you kind of do the math, and you're like, yeah. What's the point? I'm not going to make it.
LEWIS: Montes was lead gunner for their team. He made it, and he served a second tour in Afghanistan. Here in Granby, his eyes are constantly scanning the room, the windows, the door.
Brian Bartman was there, too. He looks like preppy in a buttoned-down shirt and sports jacket. But every now and then, he holds his pen like it's a weapon. He talks about the ways they dealt with war, like playing video games just after an ambush.
Mr. BRIAN BARTMAN (Iraq War Veteran): I can't wait to go back and play Halo. Let's go. Well, it's life saving over there, because you can get through these traumatic events and then go back to talking about insignificant stuff again. It doesn't work well with normal life.
LEWIS: Normal life? Talk about a mind warp. Here's Jesse Cohen.
Mr. COHEN: For us to come back into civilization, where everyone's just driving along, not a care in the world, just oh, I got to make to work on time or I got pick up my kids and this and that...
LEWIS: Cohen says he couldn't deal with it.
Mr. COHEN: I'm, like, driving around like a maniac. I had a heavy foot for a while. I was - I had a lot of road rage.
LEWIS: Police around the country said they're seeing more dangerous driving and road rage by Iraq veterans who've come back. Connecticut crises negotiator Brian Callany(ph) says it's important for law officers to understand these guys, especially for worst-case scenarios, like a hostage situation.
Mr. BRIAN CALLANY (Crises Negotiator): With the Iraq war and the horrors that these - a lot of these young men are seeing without any life experience, the chances of becoming a target group for us to have to deal with as a negotiator is probably better than 50-50.
LEWIS: Aaron Jones came home injured and alone, without his buddies. First thing, he found out his wife was with another guy. He had to move back in with his parents to help him through back surgery.
Mr. JONES: I came from a very religious family, where what's PTSD? Go to church and pray. I just wasn't really - I wasn't really willing to do that. I got back to being religious when I was in Iraq, and I probably would've stayed that way, except for when I came home, it felt like the whole world just fell out from underneath me.
LEWIS: Jones had a lot of guns, and he clung to them when he got back. One day, he pulled a .45 on a guy who was bugging him for change. He didn't pull the trigger, but he got a huge rush.
Mr. JONES: And it sounds messed up, but I wanted so bad to kill somebody when I came home. And I don't know why that is. I'm not a psychologist. But I didn't do it over there, my guys had. And I wanted to prove I could do it.
LEWIS: And Jones said he really gets how some guys fall into domestic violence. His wife leaving him chewed him up on the inside.
Mr. JONES: One of the things that you hear a lot about is domestic, with guys coming home. I can see how very easy it was, 'cause I wanted to just destroy her, and definitely wanted destroy the guy that she was with.
LEWIS: Jones didn't explode. That's because he stumbled on counselor Jay White at the Vet Center, when he was looking for a VA home loan. He's been going there ever since. All of these guys drank like crazy when they came home. They talked of benders that lasted weeks, lots of bar fights and driving drunk, and a constant train of abnormal thoughts. Patrick Montes got locked up for assault and public drunkenness and other charges. He says he mouthed off to a Hartford police officer who told him to move his car.
Mr. MONTES: I think I said the f-word, too. I can't remember - not at him, just saying like all right, right, we'll F-ing move.
LEWIS: At the police station lockup, Montes handed over his wallet and keys. He was taking his laces out of his shoes when one of the officers saw his military ID and said...
Mr. MONTES: This is not Baghdad anymore. There's no dead babies here. And I - it took every ounce of strength in me to not clock him. I continued to take my laces out of my shoes...
(Soundbite of laughter)
Mr. MONTES: ...and I was like, here you go.
LEWIS: Montes can laugh about it now. A prosecutor threw the charges out. And he's back with his buddies in Connecticut.
March 12, 2008
The Winter Soldier, Iraq and Afghanistan hearings organized by the Iraq Veterans Against the War (IVAW) will begin on March 13th. During the four day event, scholars and most importantly, veterans and civilians with personal experiences of war, will attempt to educate the American public about the nature and the reality of the Bush Administration's alleged war against terrorism. There will be those, no doubt, some veterans themselves, who will be offended by these hearings and will regard the testimony given by these courageous individuals as unpatriotic, un-American, unsupportive of the troops, perhaps even as treasonous. Such condemnation and opposition to Winter Soldier, Iraq and Afghanistan is unwarranted and misguided, perhaps, for some, a remnant of a deep seated resentment regarding earlier Winter Soldier hearings in which veterans testified regarding their experiences fighting the war in Vietnam.
It is not the purpose of Winter Soldier to malign or disparage America, but to begin a dialogue regarding the morality, legality, and necessity of the war in Iraq and Afghanistan. To tell the truth about war does not diminish this nation. If anything, it affirms America's greatness, and the commitment of its citizens to truth and justice. With the war in Iraq entering it's sixth year with no end in sight, it is time, long past time, that all Americans at least become aware of the nature of war and of its cost in human lives and national treasure.
Neither is it the purpose of Winter Soldier to diminish the efforts and sacrifices of members of the military. To tell the truth about war, though difficult and disconcerting, will ultimately prove uplifting and curative as the legacy, dignity, self-respect, and integrity of our servicemen and women, rests not upon fantasy, lies, and fabrications but upon their commitment to America and to freedom. Though veterans must accept some personal responsibility for their actions, all who supported the war or did nothing to stop it must share culpability. Most blameworthy, of course, are those political leaders, whose misguided policies, incompetence, and paranoia ultimately makes killing, dying, and grieving inevitable.
Winter Soldier is a wakeup call to all Americans that our nation is in peril and that what threatens the fabric and foundations of our way of life in these dangerous times is not some amorphous, enigmatic horde of bloodthirsty terrorists. Rather it is the assault upon truth, individual freedom, and the values of justice and morality we hold sacred. Further, Winter Soldier is an admonition that to avoid hypocrisy, we must have the moral courage to look at and to judge our own behavior with at least as much honesty and scrutiny as we view and judge the behavior of others.
Unfortunately and tragically, perhaps war is a reality that will not soon go away and sacrifices on the field of battle will again be required. However, by demanding truth and recognizing war as it truly is, we will begin to resolve the divisiveness that plagues our nation, and provide veterans and devastated families the opportunity to heal and to achieve some semblance of normalcy in their lives. Further, we will ensure that war remains a means of last resort, that no other person will again have to kill, die, or grieve the loss of their son or daughter for a cause that is misguided, and, perhaps, most important, that those who dare to initiate such wars and connive to use deception and myth to encourage participation and support are held responsible for their crimes against humanity.
Is it truly support, therefore, to remain silent when our troops are placed in harm's way unnecessarily, to kill and be killed subject to the whims and ineptitudes of our political leaders? Who can dispute that sending inadequately prepared National Guard troops into combat and then failing to provide them with body and vehicle armor is unconscionable and criminally negligent. The fact that so many of our heroic sons and daughters are languishing abandoned, their emotional and psychological injuries untreated, and their needs ignored, is a national tragedy and disgrace. The fact that America has become isolated in the world, respected no longer for its ideals, but feared for its brutality, no longer admired for its values of justice and freedom, but hated for its hypocrisy and intolerance, should bring a tear to the eye and anger to the heart of anyone who truly loves America. Such outrage requires, no demands, the true patriot, the Winter Soldier, to embrace truth and to cry out in condemnation and protest against this corrupting and disgracing of America by those political leaders and their coconspirators who cherish not our values and way of life but only wealth and power. | null | minipile | NaturalLanguage | mit | null |
Use of radial artery grafts in extracranial-intracranial revascularization procedures.
Cerebral revascularization procedures have been used in the clinical management of actual or threatened cerebral ischemic states and unclippable cerebral aneurysms. An alternative to a low-flow bypass graft (for example, with the superficial temporal artery) is the use of high-flow grafts created using the saphenous vein (SV) or radial artery (RA). These high-flow grafts are particularly useful when otherwise adequate collateral flow is insufficient to enable sacrifice of the parent vessel without the risk of cerebral ischemia. In their clinical series of 13 patients who underwent high-flow bypass with an RA graft, the authors describe 8 women and 5 men whose ages ranged from 44 to 69 years (mean 57.84 +/- 9.05 years). Indications for RA graft bypass were unclippable aneurysms in 10 patients and occlusive cerebrovascular disease in 3 patients. The authors review the properties of the 2 most common conduits, the SV and RA grafts. They present the technique of high-flow extracranial-intracranial bypass produced using RA grafts in the management of occlusive atherosclerotic disease and complex intracranial aneurysms that are not otherwise amenable to either clip ligation or coil occlusion. | null | minipile | NaturalLanguage | mit | null |
Who we are
The Canadian Foundation for Healthcare Improvement (CFHI) supports partners to accelerate the identification, spread and scale of proven healthcare innovations. We work shoulder-to-shoulder with you to improve health and care for everyone in Canada.
Please note: The posting of our email address on our website does not signify our consent to receiving commercial electronic messages. Do not send us commercial electronic messages unless we have provided you with our express consent to do so.
The Canadian Foundation for Healthcare Improvement is a not-for-profit organization funded by Health Canada. The views expressed herein do not necessarily represent the views of Health Canada. | null | minipile | NaturalLanguage | mit | null |
Q:
Right hand side also gets assigned
Directly stating the problem; I assign the 'temp' as *TEMP* in the let statement. When I do so, *TEMP* gets assigned exactly what 'temp' had been assigned at each iteration. And I am ending up pushing the same value of 'temp's at the end. Don't have a clue why, do you guys have any idea about how things go wrong in here?
(defparameter *TEMP* `((key value)(key2 value2)(key3 x))
(defparameter *SYNS* NIL)
(defparameter *PUSH-HERE* NIL)
(dolist (i *matrix*)
(dolist (j i)
(if (equal 'keyword (first j))
(foo (second j)))) ;fills *SYNS*
(let ((temp *TEMP*))
;(print *TEMP*) prints temps last assigned value?
(set-key temp (get-key i)) ;gets key's value
(set-key2 temp (get-key2 i)) ;gets key2's value
(loop while (not (equal 0 (length *SYNS*)))
do (set-key3 temp (pop *syns*))
(push temp *PUSH-HERE*))))
Resulting value becomes like this;
((key last-assigned-value)(key2 last-assigned-value)(key3 last-assigned-value)
(key last-assigned-value)(key2 last-assigned-value)(key3 last-assigned-value)
(key last-assigned-value)(key2 last-assigned-value)(key3 last-assigned-value))
instead of;
((key first-assigned-value)(key2 first-assigned-value)(key3 first-assigned-value)
(key second-assigned-value)(key2 second-assigned-value)(key3 second-assigned-value)
(key last-assigned-value)(key2 last-assigned-value)(key3 last-assigned-value))
I have tried printing, and just before push line, temp is printed as I want, but after the whole iteration is completed, I got the unintentional list I put above.
A:
You are binding the address of *temp* to temp. I assume set-key updates temp as with rplaca or (setf (car place) value). Thus you are modifying *temp* also since it is the same value as temp. Every round you are overwriting temp which is the same address you have been pushing to the neew list and thus it results in 3 sub lists of the same since they are the same. This is also in violation of Common Lisp since *temp*is quoted literal, and thus constant, data. It might behave differently in different implementations.
Instead of destructive operation you could do non destructive operation that crates a new value, eg. with substitute-if, then update the binding:
(setf temp
(substitute-if (cons 'key 'new-value)
(lambda (e) (eq e 'key))
temp
:key #'car))
If you still want mutation you can get away with it by using copy-alist:
(let ((temp (copy-alist *temp*)))
...)
| null | minipile | NaturalLanguage | mit | null |
2014–15 Grand Prix of Figure Skating Final
The 2014–15 Grand Prix of Figure Skating Final was an international figure skating competition in the 2014–15 season, held together with the ISU Junior Grand Prix Final. The competition was held from December 11 to 14, 2014 in Barcelona, Spain — the first time it took place on the Iberian Peninsula.
The combined event was the culmination of two international series — the Grand Prix of Figure Skating and the Junior Grand Prix. Medals were awarded in the disciplines of men's singles, ladies' singles, pair skating, and ice dancing on the senior and junior levels.
Records
The following new ISU best scores were set during this competition:
Schedule
(Local time):
Thursday, December 11
14:00 - Junior: Ladies' short
15:05 - Junior: Short dance
16:20 - Junior: Men's short
17:25 - Junior: Pairs' short
19:45 - Opening ceremony
20:45 - Senior: Pairs' short
21:30 - Senior: Ladies' short
Friday, December 12
14:30 - Junior: Ladies' free
15:40 - Junior: Free dance
17:00 - Junior: Men's free
18:15 - Junior: Pairs' free
19:45 - Senior: Short dance
21:00 - Senior: Men's short
Saturday, December 13
16:00 - Senior: Pairs' free
17:25 - Senior: Ladies' free
19:25 - Senior: Free dance
20:45 - Senior: Men's free
Awards ceremony
Sunday, December 14
12:00 - Exhibition
Qualifiers
Senior-level qualifiers
Changes to initial lineup
Gracie Gold withdrew due to a foot injury. She was replaced by Japan's Rika Hongo.
Junior-level qualifiers
Medalists
Senior
Junior
Medals table
Overall
Senior
Junior
Senior-level results
Men
Ladies
Pairs
Ice dancing
Junior-level results
Men
Ladies
Pairs
Ice dancing
References
External links
2014–15 Grand Prix Final at the International Skating Union
Entries: Junior Grand Prix Final, Grand Prix Final
Starting orders and result details
Category:2014 in Spanish sport
Category:2014 in figure skating
Category:Grand Prix of Figure Skating Final
Category:ISU Junior Grand Prix
Category:International figure skating competitions hosted by Spain
Category:2014 in youth sport
Category:2015 in youth sport | null | minipile | NaturalLanguage | mit | null |
A faraway movie shoot brought the actress up close and personal with her own beauty myth.
When I was growing up in Tulsa, the kids called me "bubble lips" and "frog eyes." My mama always said, "Oh, you're such a pretty girl," and I believed I was, thanks to her encouragement. Still, this was before the "black is beautiful" era of the 1970s, and everything around me seemed to negate my particular look—especially the movies. The screen is one of the most influential tools in our lives, and if you don't see yourself represented, it's almost as if you don't exist. As I got older, I was drawn to the power and possibility for healing that cinema and the theater offered the world, and even though I didn't resemble the typical actress—or maybe because of it—I moved to Hollywood. At auditions I was constantly told that I looked too much like an African and not enough like an African-American. I thought, 'This is as African-American as you get—my family has been here for 400 years!' The hues of America were not being celebrated. Instead, everybody was trying to fit a homogeneous image.
Then in 1986, I traveled to Zimbabwe for the first time to shoot the TV movie Mandela. I felt as if I'd been given a pure shot of oxygen. Suddenly, I was part of the dominant culture. I saw people like me. They had round faces and large eyes, with skin so warm and lips so full that I almost wanted to kiss strangers. I'd been living in Los Angeles, a world full of cubic zirconias, and here I was in the land of deep, rich-colored, genuine gemstones. I felt organically beautiful for the first time in my life. It may sound immodest, but I realized that my presence in movies gives that same validation to other young black women. They can feel free to walk their walk, swing their hips, and flash their smiles because they see themselves up on the screen. Everybody has a part of her body that she doesn't like, but I've stopped complaining about mine because I don't want to critique nature's handiwork. There's no such thing as imperfection. My job is simply to allow the light to shine out of the masterpiece. | null | minipile | NaturalLanguage | mit | null |
Locally made terra cotta is helping to shape UB’s new medical school building at the Medical Campus. According to UB|MD, each of the panels weighs in at 60 pounds, and measures 1×5 feet. It was HOK (designers) that contracted with Boston Valley Terra Cotta on the project, after Boston Valley beat out a couple of German companies for the work.
“HOK contacted us during the conceptual design stage,” explained Willard Pottle, international sales and marketing manager at Boston Valley Terra Cotta, which won the bid to manufacture the panels over two German firms. “They made it very clear that they wanted to use terra cotta to acknowledge Buffalo’s architectural history.” – UB|MD
Below is a video that show the manufacturing process behind the panels:
Altogether, there will be 28,006 panels used for the project, making the order one of the biggest for the family owned company.
Once complete, the building will house the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo. Check out the video below to learn about the BNMC – Imagine Progress 2017. Also refer to the new BNMC website. | null | minipile | NaturalLanguage | mit | null |
Although fostering transdisciplinary research is CGREAL's first mission, its most important contributions to scholarship are not its research products themselves. Instead, that honor goes to the products of our training program; the new investigators that we are able to bring to ELSI research and policy analysis in order to expand the range of voices at the table in society's complex negotiations with genomics. Our trainees are CGREAL's most important contribution to ELSI research because they will be shaping genomics' translational trajectory as ELSI researchers well beyond the life of CGREAL itself. If our first five years' experience holds true over the next five, this impact will be significant. As Table D in Appendix A shows, CGREAL's graduates to date have done extraordinarily well. Over the next five years, the CGREAL training program will continue to focus on preparing advanced trainees who can have an immediate impact on policy and practice in translational genomic research and genomic medicine. To maintain our momentum, CGREAL is fortunate to have enlisted the services of Drs. Mark Aulisio and Anne Matthews as co-directors of our training program. Aulisio already serves as Director of the M.A. in Bioethics graduate program within the CWRU Department of Bioethics, and Matthews is the Director of Graduate Studies for the Department of Genetics, with special responsibility for CWRU's M.S. in Genetic Counseling Program. Together, they will help us improve the four kinds of training opportunities we have offered to date; 1) Seed Grant mentored research opportunities for junior faculty; 2) post-doctoral fellowships for American professionals; 3) pre-doctoral dissertation research opportunities through existing graduate and professional programs at CWRU; 4) trainee exchange and visiting scholar programs with minority-serving institutions. In addition, Aulisio and Matthews will help CGREAL expand the scope of its training program to include genetic counseling trainees and dual-degree professional students (JD, MD, MPH, ND) pursuing their MA in Bioethics; this will include the development of a new joint MA/MS degree concentrating on Genetics, Ethics, and Policy. The program will also develop more formal opportunities for CGREAL trainees to interact regularly with advanced scientific trainees from the Department of Genetics, and with ELSI research trainees from other CEERs. This section details these opportunities and developments. | null | minipile | NaturalLanguage | mit | null |
Anyone who's ever watched a horror film will know that the sound of two clashing notes evokes a visceral response in most people. Among Western listeners there's a strong preference for consonance, which exists even from infancy; consonance is the pleasing mixture of two tones, while dissonance is their clashing. (For a good example of both, see this video.) It's controversial whether the same preferences exist in other cultures, but new research indicates the preferences might be wired in our brains. The prevailing theory of music in the brain is that dissonant combinations share frequencies that are a bit too close. When these frequencies are perceived by the cochlea, the part of the inner ear that translates sounds to nerve impulses, they can't be well distinguished. Because similar frequencies are processed next to one another on the cochlea, their nerve signals can interfere with one another. The perception is a grating effect, called "beating." But neuroscientists have found that beating is not actually what we dislike when we hear discordant tones, as they reported this week in PNAS. Their approach was to study a unique subset of people called amusics. Amusia is a congenital disorder; people with the condition have a hard time detecting the direction of pitch changes and can't tell some notes apart. Thus, many of the sensations of music are lost on people with this condition. The researchers played various combinations of tones to the amusics, many of which normal listeners would find quite unpleasant, but the subjects reported no displeasure. The one exception, however, was beating. Amusics could indeed detect beating and found it grating, just as other people do. When two notes of close frequency were played to the same ear, subjects rated that as jarring; when, in contrast, they were separated one note to one ear, the beating was lessened and so too was the subjects' dislike of the sound. Thus beating is unpleasant to all of us, but doesn't appear to have anything to do with our appreciation for music, since amusics dislike it, too. That appreciation appears instead to be hardwired in our brains, reliant on our ability to accurately detect the gaps in frequency between two notes, rather than just the dislike of beating. The finding helps resolve a key question of how and why we appreciate pleasing sounds. And that should be music to your ears.
Photo courtesy of jeanbaptisteparis via Flickr | null | minipile | NaturalLanguage | mit | null |
Q:
AJAX/JQUERY - Split the returned data and place in two seperate divs
I am currently using the following code to run an AJAX query every 10 seconds to populate <div id="datacontainer"></div>
setInterval(function(){
$.ajax({
url: "ajax.php",
type: "GET",
cache: false}
).done(function(html) {
$( '#datacontainer' ).html( html );});},10000
);
I have now setup the ajax.php file to return a string that now contains the delimiter '----' that I want to split and populate two div's.
I want to split into data[] when split data[0] goes into <div id="nummessages"></div> and data[1] goes to <div id="datacontainer"></div>
How would this code need to be modified to achieve this?
A:
setInterval(function(){
$.ajax({
url: "ajax.php",
type: "GET",
cache: false}
).done(function(html) {
var divs = html.split('----');
$( '#nummessages' ).html( divs[0] );
$( '#datacontainer' ).html( divs[1] );
});
},10000);
| null | minipile | NaturalLanguage | mit | null |
Zinc Pocket-Hole Screws Washer Head Fine No.7 x 1-1/4" 1200pk
High quality pocket-hole screws for use in softwoods and plywood, on a wide variety of exterior projects. Designed to sit flush in the bottom of the pocket, eliminating pull through. Use with Kreg jigs. | null | minipile | NaturalLanguage | mit | null |
Q: I keep reading about Zoysia grass. Stories say it grows sideways and doesn't need to be mowed as often or watered as often, and only needs to be fertilized once a year. Is this true or all hype? I live in north Pinellas on a corner lot. The side of the house that has the most yard faces south with no trees. The front of the house faces east. I don't have a lot of money, but I want to fix up this house as much as possible. Would you also recommend some ground covers that are fast growing, with or without flowers?
Darlene Smith, Palm Harbor
A: Those colorful ads look good, but they are mostly hype. Zoysia will grow here and it doesn't need to be mowed as often because it is a slower grower. However, it needs water and fertilizer and it won't cover from a plug; because of its slow growth, it can't compete with weeds. A Zoysia called "Empire" can be purchased as sod, but it is maintained like St. Augustine grass.
Some tough, full-sun ground covers to consider are sunshine mimosa (Mimosa strigillosa), a great creeping native with purple flowers, and perennial peanut (Arachis spp.), another creeper with golden yellow flowers. You may also want to consider Bahia grass, our most drought-tolerant turf, with some plant beds and lots of mulch. Keep in mind that any plantings will require water to get established. Another suggestion it to do your landscape in stages.
Florida red maple grows all over state
Q: Here is a photo from a tree in our neighborhood that I wasn't able to identify. It's a mature tree about 20 feet tall, and the entire canopy is covered with these red seed clusters. Just like a jacaranda when it's in flower, there are no leaves on the tree. It's absolutely outstanding with that bright red color!
Judy VanNess, Clearwater
A: Your lucky find is a Florida red maple, Acer rubrum. The seed that you have pictured, from the tree, is called a samara. As they fall from the tree, they look like little helicopters. The red maple prefers wet swampy areas but will grow upland; it's a good tree for retention ponds. It is native all over the state and grows to 40 feet.
Orange tree has signs of terminal virus
Q: We have a 30-plus-year-old orange tree that has been well taken care of. The fruit is great and plentiful. Last year and again this year, surface bark on the trunk and main branches is coming off in patches (3 by 6 inches), exposing a white layer that looks almost like corduroy. The tree pruner and the sprayer said to paint the areas with copper sulfate (a fungicide?). Do you agree? We have tried to find copper sulfate with no luck with the exception of one nursery that could get copper crystals or copper sulfate in 50-pound bags.
Carl and Judy Graber, Largo
A: I have some sad news regarding your orange tree. Based on the age of the tree and the patches of sluffing bark, your tree has psorosis, one of five viruses that attack citrus. Unfortunately, there is no cure, so copper applications will be of no help. Copper helps with fungus and bacterial infections, not viruses. Psorosis is not contagious and over time will cause a slow decline of the tree. As the disease progresses, parts of the tree will die out and fruit size and fruit set will diminish. Plant a new tree now and by the time your current tree is ready for burial, your new tree will have you back in juice.
Free mulch
All those oak leaves and pine needles in your yard make excellent mulch for plant beds. It doesn't make sense to rake up this material, throw it in the trash and replace with bagged cypress. In the case of leaves, nutrients are stored there. As they fall and decompose, the nitrogen cycle starts all over again. If you have more than you need, share with your neighbors or add to your compost pile.
Need help?
Enter Greg "Dr. Hort" Charles, who for more than 30 years educated gardeners through the Pinellas Technical Education Centers. He answers questions about landscape and garden pests. E-mail your questions to [email protected] or to [email protected] (put Dr. Hort in the subject line). Mail questions to HomeLink, Features Department, St. Petersburg Times, P.O. Box 1121, St. Petersburg, FL 33731. Describe your problem in full, and include your name and contact information. If possible, include a photo. We will print his advice on Saturdays in HomeLink. | null | minipile | NaturalLanguage | mit | null |
---
abstract: 'We illustrate properties of guided waves in terms of a superposition of body waves. In particular, we consider the Love and $SH$ waves. Body-wave propagation at postcritical angles—required for a total reflection—results in the speed of the Love wave being between the speeds of the $SH$ waves in the layer and in the halfspace. A finite wavelength of the $SH$ waves—required for constructive interference—results in a limited number of modes of the Love wave. Each mode exhibits a discrete frequency and propagation speed; the fundamental mode has the lowest frequency and the highest speed.'
author:
- 'David R. Dalton[^1], Michael A. Slawinski[^2], Theodore Stanoev[^3]'
bibliography:
- 'DSSS\_arXiv.bib'
title: '**Guided waves as superposition of body waves**'
---
Introduction
============
Let us consider Love wave and the $SH$ waves to examine the concept of a guided wave within a layer as an interference of body waves therein. In the $x_1x_3$-plane, the nonzero component of the displacement vector of the Love wave is [e.g., @Slawinski Section 6.3] $$\begin{aligned}
u_2^\ell(x_1,x_3,t)
=&\,\,
C_1\exp{\left(-\iota\,\kappa\,s_\ell\,x_3\right)}\exp\left[\iota\,(\kappa\,x_1-\omega\,t)\right]\\
&+C_2\exp{\left(\iota\,\kappa\,s_\ell\,x_3\right)}\exp\left[\iota\,(\kappa\,x_1-\omega\,t)\right]\,,\end{aligned}$$ where $s_\ell:=\sqrt{(v/\beta_\ell)^2-1}$, with $v$ being the speed of the Love wave and $\beta_\ell$ the speed of the $SH$ wave; $\omega$ and $\kappa$ are the temporal and spatial frequencies, related by $\kappa=\omega/v$. The $SH$ waves travel obliquely in the $x_1x_3$-plane; different signs in front of $x_3$ mean that one wave travels upwards and the other downwards. Their wave vectors are ${\bf k}_{\pm}:=(\kappa, 0, \pm\,\kappa\,s_\ell)$. Considering their magnitudes, $$\|{\bf k}_\pm\|=\sqrt{\kappa^2+(\kappa\,s_\ell)^2}\,,$$ we have $$\|{\bf k}_\pm\|=\kappa\sqrt{1+(s_\ell)^2}=\kappa\,\dfrac{v}{\beta_\ell}\,;$$ from which it follows that $$\label{eq:LoveRestrict}
\dfrac{\beta_\ell}{v}=\dfrac{\kappa}{\|\bf k_\pm\|}=\sin \theta\,,$$ where $\theta$ is the angle between ${\bf k}_{\pm}$ and the $x_3$-axis. Thus, $\theta$ is the angle between the $x_3$-axis and a wavefront normal, which means that—exhibiting opposite signs—it is the propagation direction of upward and downward wavefronts.
Total reflection
================
A necessary condition for the existence of a guided wave is a [*total reflection*]{} on either side of the layer; the energy must remain within a layer. For the Love waves, this is tantamount to no transmission of the $SH$ waves through the surface or the interface. The former is ensured by the assumption of vacuum above the surface; hence, total reflection occurs for all propagation angles, $\theta$. The latter requires $\beta_\ell<\beta_h$, where $\beta_h$ is the speed of the $SH$ wave within the halfspace. This inequality results in the existence of a critical angle, $\theta_c=\arcsin(\beta_\ell/\beta_h)$, which is required for a propagation at postcritical angles, $\theta>\theta_c$.
In view of expression (\[eq:LoveRestrict\]), the lower limit of $v$ is $\beta_\ell$, for which $\sin\theta=\beta_\ell/\beta_\ell=1$; hence, $\theta=\pi/2$. It corresponds to the $SH$ waves that propagate parallel to the $x_1$-axis, and can be viewed as the Love wave.
The upper limit, $v=\beta_h$, is a consequence of the critical angle, for which $\sin\theta_c=\beta_\ell/\beta_h$. If $\beta_h\to\infty$—which corresponds to a rigid halfspace—$\theta_c\to 0$; hence, the $SH$ waves within the layer can propagate nearly perpendicularly to the interface and still exhibit a total reflection. This means that $v\to\infty$, as can be also inferred from Figure \[fig:GuideTwo\].
These limits, $\beta_\ell<v<\beta_h$, are a consequence of total reflection. Also, the upper limit needs to be introduced to ensure an exponential amplitude decay in the halfspace [e.g., @Slawinski Section 6.3.2].
Constructive interference
=========================
Guided waves—as superpositions of body waves—require a [*constructive interference*]{} of body waves. A necessary condition of such an interference is the same phase among the wavefronts of parallel rays. In Figure \[fig:GuideOne\], this condition means that the difference between $\|AB\|$ and $\|AB'\|$ must be equal to a positive-integer multiple of the wavelength, $\lambda$, taking into account the phase shift due to reflection. A reflection at the surface results in no phase shift [@Udias Sections 5.4 and 10.3.1], and the $SH$-wave postcritical phase shift at the elastic halfspace is presented by @Udias [equation (5.74)].
![[]{data-label="fig:GuideOne"}](FigGuideOne){width="11cm"}
To illustrate the constructive interference—without discussing the phase shift as a function of the incidence angle—let us consider an elastic layer above a rigid halfspace, on which a transverse wave undergoes a phase change of $\pi$ radians for any angle. In such a case, the propagation angle is [e.g., @SalehTeich Section 7.1] $$\label{eq:ConstInterQ}
\theta_n=\arcsin\left(n\frac{\lambda}{Z}\right)\,,\qquad n=1,2,\ldots\,,$$ where $\lambda$ is the wavelength of the $SH$ wave, $Z$ is the layer thickness and $n$ is a mode of the guided wave; $n=1$ is the fundamental mode.
Thus—as a consequence of constructive interference—for a given $SH$ wavelength and layer thickness, the propagation angles, $\theta_n$, form a set of discrete values; each $n$ corresponds to a mode of the guided wave. As illustrated in Figure \[fig:GuideTwo\], each mode has its propagation speed, which—in accordance with expression (\[eq:LoveRestrict\])—is $$\label{eq:vnspeed}
v_n=\dfrac{\beta_\ell}{\sin\theta_n}\,,$$ where, as a consequence of total reflection, $\theta_n\in(\theta_1,\pi/2)$, where $\theta_1>\theta_c$. The specific value of $\theta_1$ depends on $Z$ and $\lambda$; it corresponds to the first postcritical value for which $\|AB\|-\|AB'\|=2\,\|AB\|\cos^2\theta=2\,Z\,\cos\theta$ is a multiple integer of $\lambda$.
Examining Figure \[fig:GuideTwo\], we distinguish the upgoing and downgoing wavefronts, which compose the guided wave. Its longest permissible wavelength is twice the layer thickness, $\lambda_1=2Z$, which corresponds to the fundamental mode; $\lambda_2=Z$, $\lambda_3=2Z/3$, and, in general, $\lambda_n=2Z/n$.
Frequencies of body and guided waves
====================================
$\lambda$, referred to in the caption of Figure \[fig:GuideOne\] and used in expression (\[eq:ConstInterQ\]), corresponds to the $SH$ wave; $\lambda_n$, where $n=1,2,\ldots$, corresponds to the guided wave. They are related by the propagation angle, $\theta_n$, and by the layer thickness, $Z$.
![[]{data-label="fig:GuideTwo"}](FigGuideTwo){width="11cm"}
The radial frequency of a monochromatic $SH$ wave is constant, $\omega=2\pi\,\beta_\ell/\lambda$. The radial frequencies of the Love wave are distinct for distinct modes, $\omega_n=2\pi\,v_n/\lambda_n$. For a given model, $\beta_\ell$, $\beta_h$ and $Z$, the relations between $\omega$ and $\omega_n$, as well as among $\omega_n$, where $n=1,2,\ldots$, are functions of $n$ and $\theta_n$; explicitly, $\omega_n=n\,\pi\,\beta_\ell/(Z\,\sin\theta_n)$, and, in general, its behaviour as a function of $n$ cannot be examined analytically. However, in an elastic layer above a rigid halfspace, in accordance with expression (\[eq:ConstInterQ\]), $$\label{eq:omegan}
\omega_n=n\,\pi\,\dfrac{\beta_\ell}{Z\,\sin\theta_n}=\pi\,\dfrac{\beta_\ell}{\lambda}=\dfrac{\omega}{2}\,,$$ which is constant for all modes, and depends only on the radial frequency of the $SH$ wave.
The constructive interference, illustrated in Figure \[fig:GuideOne\], requires that $$\|AB\|-\|AB'\|=a\,\lambda-b\,\lambda=(a-b)\,\lambda\,,$$ where—in contrast to $a=\|AB\|/\lambda$ and $b=\|AB'\|/\lambda$—$a-b$ is a positive integer; $\lambda$ is the $SH$ wavelength. Following trigonometric relations, we write $$\begin{aligned}
\|AB\|-\|AB'\|=&~\|AB\|-\|AB\|\cos(\pi-2\theta)=\|AB\|\left(1-\cos(\pi-2\theta)\right)\\=&~2\,\|AB\|\cos^2\theta\,. \end{aligned}$$ Since $\|AB\|=Z/\cos\theta$, where $\theta$ is the $SH$-wave propagation angle, it follows that $2\|AB\|\cos^2\theta=2Z\cos\theta$, and the constructive interference requires that $2\,Z\cos\theta=(a-b)\,\lambda$, where ${(a-b)\in{\mathbb N}}$; in other words, $$\cos\theta=\dfrac{a-b}{2\,Z}\,\lambda\,,$$ where $\theta\geqslant\theta_c$, to ensure the total reflection, and $(a-b)\,\lambda\leqslant2Z$, for $\theta\in\mathbb R$.
Using this result and the inverse trigonometric function, we write the first equality of expression (\[eq:omegan\]) as $$\label{eq:omega2}
\omega_n=n\,\pi\,\dfrac{\beta_\ell}{Z\,\sqrt{1-\left(\dfrac{a_n-b_n}{2\,Z}\right)^2\,\lambda^2}}\,,$$ which corresponds only to a given value of $n$ and, hence, of $\theta_n$, since $a_n-b_n$ changes with the propagation angle, and needs to be restricted to integer values for each $n$.
Following expression (\[eq:omega2\]), we obtain $$\label{eq:omega/omega}
\dfrac{\omega_n}{\omega_{n+1}}=
\dfrac{n}{n+1}
\dfrac{\sqrt{1-\left(\dfrac{a_{n+1}-b_{n+1}}{2\,Z}\right)^2\,\lambda^2}}{\sqrt{1-\left(\dfrac{a_n-b_n}{2\,Z}\right)^2\,\lambda^2}}
\,.$$ Since $\theta_{n+1}>\theta_n$, examining Figure \[fig:GuideOne\] and considering given values of $\lambda$ and $Z$, we see that—as $\theta$ increases—$\|AB\|-\|AB'\|$ decreases. Hence, $(a_n-b_n)>(a_{n+1}-b_{n+1})$, and the root in the numerator is greater than in the denominator. Consequently, the ratio of roots is greater than unity. However, $n/(n+1)<1$.
We cannot, in general, determine analytically if the radial frequency of the $n$th mode is higher or lower than the frequency of the $n+1$ mode. To determine it, we need not only to specify $Z$ and the model parameters, which result in $\theta_c$, but also $\lambda$ and $n$, to obtain $\theta_n$ and $\theta_{n+1}$, with integer values of $\|AB\|-\|AB'\|$.
Numerical example
=================
To obtain specific values, we let $Z=1000$, $\beta_\ell=2000$, $\beta_h=3000$ and $\lambda=50$, which means that $\theta_c\approx 0.73$, in radians, and ${\omega=2\pi\,\beta_\ell/\lambda\approx 251}$. For the guided wave, in accordance with Figure \[fig:GuideOne\], we obtain—numerically—${\theta_1\approx 0.76}$, which corresponds to $(a_1-b_1)=29$. To include higher modes, using expression (\[eq:omega/omega\]), we obtain $\omega_1/\omega_2\approx 0.52$, $\omega_2/\omega_3\approx 0.69$ and $\omega_3/\omega_4\approx 0.77$, which corresponds to, respectively, $(a_{n+1}-b_{n+1})=29-n=28$, $27$ and $26$, and to $\omega_2=17.60$, $\omega_3=25.55$ and $\omega_4=33.07$.
We might infer that the Love-wave fundamental mode, $n=1$, exhibits the lowest radial frequency—which, following expression (\[eq:omega2\]), is $9.123$—and that the frequency increases monotonically with $n$. The highest allowable mode corresponds to $n=29$, since, for that value, $(a_n-b_n)=1$. For this mode, $\omega_{29}\approx 182.27$; also, $\omega_{28}/\omega_{29} \approx 0.966$. Frequencies of distinct modes are shown in the left-hand plot of Figure \[fig:GuideThree\].
![[]{data-label="fig:GuideThree"}](FigGuideThree "fig:"){width="8cm"} ![[]{data-label="fig:GuideThree"}](FigGuideFour "fig:"){width="8cm"}
Examining expression (\[eq:omega/omega\]), in view of these results, we conclude that—as $n$ increases—both $n/(n+1)$ and the ratio of roots tend to unity; the former from below, the latter from above. The ratio of successive frequencies approaches the ratio of successive overtones for a vibrating string, $\tfrac{1}{2}\,,\tfrac{2}{3}\,,\tfrac{3}{4}\,,\ldots\,, \tfrac{28}{29}$.
Furthermore, using expression (\[eq:vnspeed\]) and the computed values of $\theta_n$, we can obtain the corresponding propagation speeds of the Love-wave modes. For the fundamental mode, $$v_1=\dfrac{\beta_\ell}{\sin\theta_1}=\dfrac{2000}{\sin(0.76)}=2903.09\,,$$ which is the highest speed of this Love wave; it is smaller than $\beta_h=3000$, as required. The lowest speed corresponds to $\theta_{29}=1.55$, which is nearly $\pi/2$; hence, the $SH$ waves propagate almost parallel to the layer. The speed of the resulting Love wave is $v_{29}=\beta_\ell/\sin\theta_{29}=2000.63$, which is greater than $\beta_\ell=2000$, as required. Speeds of distinct modes are shown in right-hand plot of Figure \[fig:GuideThree\].
Conclusions
===========
Superposition of body waves allows us to examine several properties of guided waves. Body-wave propagation at postcritical angles—required for a total reflection—results in the speed of the Love wave being between the speeds of the $SH$ waves in the layer and in the halfspace. A finite wavelength of the $SH$ waves—required for constructive interference—results in a limited number of modes of the Love wave. Each mode exhibits a discrete frequency and propagation speed; the first mode has the lowest frequency and the highest speed.
Acknowledgments {#acknowledgments .unnumbered}
===============
We wish to acknowledge the graphic support of Elena Patarini. This research was performed in the context of The Geomechanics Project supported by Husky Energy. Also, this research was partially supported by the Natural Sciences and Engineering Research Council of Canada, grant 202259.
[^1]: Department of Earth Sciences, Memorial University of Newfoundland, Canada; [[email protected]]{}
[^2]: Department of Earth Sciences, Memorial University of Newfoundland, Canada; [[email protected]]{}
[^3]: Department of Earth Sciences, Memorial University of Newfoundland, Canada; [[email protected]]{}
| null | minipile | NaturalLanguage | mit | null |
CRISPR savior siblings
Two prominent scientists, Robin Lovell-Badge and George Daley, have been amongst the most outspoken proponents of leaving the door open to heritable human genetic modification via CRISPR. While they each have articulated their reasons in somewhat different ways at times, […] | null | minipile | NaturalLanguage | mit | null |
CCGPS History
Two outstanding Christian leaders helped to create and shape the growth of what is now the Campolo College of Graduate and Professional Studies: the College’s namesake, Dr. Tony Campolo, and its first Dean, Dr. Harold Howard. It is their vision and commitment to social justice that has empowered the College to change the lives of so many people through better job opportunities and better lives for their families, all from a firm foundation of faith.
Tony Campolo
Dr. Tony Campolo, who graduated from Eastern in 1956, served his alma mater for nearly 35 years as a professor of sociology, after earning his PhD from Temple University. An advocate for social justice, renowned motivational speaker, and a prolific author, Dr. Campolo has appeared on Nightline, Larry King Live and CNN News. He hosts a program on the Premier Radio Network in England and has written more than 35 books, including Red Letter Christians.
Dr. Campolo is an ordained minister who serves as the associate pastor of Mount Carmel Baptist Church in West Philadelphia. It was his vision for economic development that created a unique graduate program in development at Eastern. He says, “Recognizing the need for job creation among the poor, the Campolo College has developed specialized graduate programs in urban economic development and nonprofit leadership that equip students to empower indigenous people to develop and own faith-based microbusinesses and industries, and to manage community-based organizations.” His passion for social justice and boundless energy in serving God’s people motivate everyone at the Campolo College to try to emulate his example of Christian leadership.
Harold C. Howard
It is rare when an individual displays gifts that span a multitude of disciplines and vocations. It is even more unique when they offer their talents to the world with cheerful and Christ-like humility. Such a man was the late Dr. Howard. At the beginning of his career, Dr. Howard was a pastor and evangelist, crossing North America with his wife, Gladys, and ministering in tents and church revivals. After obtaining his Ph.D. in history at Loyola University, he joined the Eastern faculty as a history professor and was soon chosen vice president and academic dean. Blessed with a diplomatic temperament, sense of humor and passion for strategic planning, Dr. Howard left Eastern and began his own transatlantic consulting business. Needing his gifts in a time of transition, Eastern asked him to return to help shape the plans that would transform Eastern College into Eastern University. Dr. Howard later served as Provost, and became well-known on and off campus for his “Provost's Perspectives” columns on topics like trends in higher education, leadership, ethics and the Christian worldview. One of his lasting legacies to Eastern was the Degree Completion program, a pioneer initiative for adult students. Now evolved into the Campolo College of Graduate and Professional Studies, it has been emulated by schools across the Delaware Valley and elsewhere. In addition to his name adorning the University’s Learning Center on the St. Davids campus, the Campolo College continues to honor the vibrant memory of Dr. Howard, a man of deep wisdom and of even more profound faith, by awarding the Harold C. Howard Servant Leader Award to students who display similar vision, compassion and leadership abilities. | null | minipile | NaturalLanguage | mit | null |
The news that "Kiwi" software company Right Hemisphere now has German owners should make us rethink the role of corporate welfare.
The former Helen Clark government lavished taxpayer funds on this company, seeing it as a successful example of the New Zealand digital economy that her government once pushed.
Now, some years after receiving an interest-free NZ$14 million from the government, the company has been bought by SAP.
When it comes to government funding, corporate welfare can be every bit as insidious as that given to the shirkers, the breeders and the bludgers. Seriously, the tech sector is top of the troughers!
Just last month, at a time of government cutbacks, the tech sector received NZ$50 million in government research grants.
The biggest financial booty, NZ$5.9 million, went to NextWindow, now owned by Canadians!
It certainly does make you wonder how much New Zealand actually benefits from such taxpayer funding, when overseas interests benefit, too.
Adding more fuel to the fire was a fine post from blogger Cactus Kate, a Hong Kong-based Kiwi lawyer, who singled out one government beneficiary, Rod Drury, who, according to the latest Rich List, is worth around NZ$72 million.
Cactus, real name Cathy Odgers, believes that it is unfair for the taxpayer to subsidise successful entrepreneurs. Drury has the successful Xero software business, which recently took over an Australian payroll firm, and he has interests in the trans-Tasman Pacific Fibre, too.
But Drury revealed why a successful businessman, even if he doesn't believe in corporate welfare, applied for such grants.
He said that rival businesses applied for and got grants, too, so Xero needed such cash to maintain competitive advantage.
"If it's on offer, we have to take it," Drury said, adding that such funding also helped create jobs and exports.
Indeed, he says that if the money is on offer, it is the duty of companies to their shareholders to take what support they can, and more fool the government for making such funding available!
But wouldn't it be better to — instead of trying to pick winners — which creates nice photo ops for government ministers, make life easier for all businesses, by keeping taxes and regulations as low and simple as possible? That is, give business help, not hand-outs.
Isn't this also more honest than "crony capitalism", where companies seek the favours of government?
Perhaps governments should take a share in businesses that they fund, so that the taxpayer gets a fair share of the business' later success, especially when the business is sold to overseas interests.
Yet that may be too much effort. That NZ$50 million per year is chicken feed in the context of government spending. Maybe we have to accept that in the name of jobs and exports, some tech troughing will happen, and is OK. | null | minipile | NaturalLanguage | mit | null |
TV Show
All Hail King Julien season 1, 2, 3, 4, 5 complete tv series safe download without torrents.
TV Show All Hail King Julien season 1, 2, 3, 4, 5 all seasons with full episodes available for free download, no torrents and Ads, only direct download links for mobile and tablet support. Episodes are uploaded in mp4 | avi | mkv formats. Quality: 480p | 720p | 1080p Full HD
King Julien is shaking his booty and back! Discover Madagascar’s world takes around the craziest adventures of the jungle within this humor series. With his loyal side kicks Maurice and Mort, they match a whole new cast of animals, for example demanding head of security Clover as well as also the Foosa. Nobody will stop this king out of judgmentin the air…wavin’ enjoy he doesn’t attention. | null | minipile | NaturalLanguage | mit | null |
- Maho is a construction zone. Steel framing still at the resort; stucco work and paint are finished at the casino.
- The usual crowd of idiots at the end of the runway.
- Divi Resort at Little Bay has invested in lots of new landscaping, and the place is looking sharp. A snorkeling investigation revealed a big drop in the number of black urchins, but most of the usual fish species were well represented.
- The dump behind Philipsburg isn't burning. One monster cruise ship in port -- looked like it was 14 stories high, but I may be exaggerating.
- There was a relaxed and friendly crowd at Club Orient. Perch Lite now defines Happy Hour as 1:30 to 2:30. Unfortunately there is a 2- or 3-foot wide band of sargassum along the entire beach. Yesterday was windy, and the man who rents chairs and umbrellas says this is the third windy day in a row. Waves were high, and floating sargassum made swimming a little unpleasant. Snorkeling along the reef was a little challenging due to waves and current.
- Bikini Restaurant has a cheerful group of new green beach umbrellas. The beach crowd was quite small. Customers were drinking at the bar, and a few were having meals at the restaurant. Three or four guys were taking advantage of the windy conditions to kite-surf.
- Roofers are working at some of the buildings facing the beach.
- At Cul-de-Sac, the smell of rotting sargassum, which is piled in 6-foot hills, is almost overpowering. Still, the usual crowd of people were sitting on benches at the pier, and the ferry to Ile Pinel seemed to be operating. I inquired about Vanou -- he's the fisherman who sells fish at the market in Marigot, and takes people out to Tintamarre on Sundays. We were told that Vanou is fine, still fishing, and that his boat survived the hurricane just fine.
- No signs of runway extension work at the Grand Case airport.
- Grande Case was hit hard. Three or four restaurants are open, amid the shattered buildings. The Catholic Church still has no roofing - just exposed plywood sheathing.
- The solar panels on the roof of the fire station between Grande Case and Marigot were damaged during Irma -- about 20% of the panels are missing or damaged. The solar system hasn't been repaired.
- At the house between Grande Case and Marigot, the one which has year-round Christmas decorations - near the intersection of the road to Anse Aux Peres - there are no longer any Christmas decorations.
- As usual, the traffic from Grande Case to Marigot is the most congested on the island.
- In Marigot, the T-shirt and souvenir stands in the square were open. Both bakeries across from the market are closed.
- Sandy Ground has damaged houses, of course, but retail establishments are open, and street life looked as usual.
- Baie Nettle is different -- Sands and Dreams are totally gone.
- The French authorities installed brand new utility poles for electricity from Baie Nettle to Basses Terres.
My reports of the physical conditions here fail to convey my emotions. Anyone who has been absent from St. Maarten for many months, like my wife and I, is likely to feel an overwhelming sense of joy and relaxation upon returning to this island. It is absolutely good to be here.
Most locations don't smell of sargassum -- they smell of clean ocean air. The sand at Mullet is white, and this morning a small stingray was swimming in the waves, almost at the beach. Ribs and chicken still fall off the bone, and a cold Carib still tastes the way it should, especially when sand is between one's toes.
My reports of the physical conditions here fail to convey my emotions. Anyone who has been absent from St. Maarten for many months, like my wife and I, is likely to feel an overwhelming sense of joy and relaxation upon returning to this island. It is absolutely good to be here.
Most locations don't smell of sargassum -- they smell of clean ocean air. The sand at Mullet is white, and this morning a small stingray was swimming in the waves, almost at the beach. Ribs and chicken still fall off the bone, and a cold Carib still tastes the way it should, especially when sand is between one's toes.
We can so concur with this. It felt great to get back to the island last month and we are very much looking forward to our return in November. While many things were destroyed, the elements we so love are still there -- sunshine, beaches, turquoise water, good food, and some of the friendliest people around.
Agreed, that was our thoughts too. It seems pretty universal, that anyone who has been recently has been just to happy to have been on island, and happy to see that what we love about the island is still there. She is tattered in a lot of places, still, but overall, still beautiful.
Thank you for the informative report. I think Baie Nettle hit me the hardest when I was there in June. No guard at the Nettle Bay Beach Club and many units without roofs. I've been told that Ma Ti Beach next door to Dreams owns the land and will be expanding to at least where Dreams was.
I heard from the chair rental guy that before the latest batch of sargassum, they paid for a tractor -- not a cheap step -- to clean the beach. Then the winds picked up, and the latest batch of sargassum came ashore. "That's nature," he said philosophically.
Thanks for the update. I guess we've been spoiled over the year as there were enough people visiting Orient beach to hire the staff to keep on top of the sargassum. In years pass it usually didn't travel much south of Pedro's while we were on the island. Enjoy the rest of your trip. | null | minipile | NaturalLanguage | mit | null |
Rainbow Hair: the Craziest Experiments
No matter how hard our mothers and grandmothers protest, modern young beauties will check if colorful hair suits them. It all started with blue and pink strands which looked rather modest. Eventually, the dyed area increased, the colors became more and more bright.
And now rainbow hair is a new trend. To those who can’t decide what color to choose, the stylists suggest just to use all of them. What is rainbow hair? This is hair dyed in 5-8 different bright colors, imitating the rainbow. Bold, isn’t it? Yes! Bold, beautiful, original and bright!
Our authors followed attentively the trends of dyeing hair in unusual colors. The experts published their valuable advice about how to color your hair in blue colorbeautifully. Then we collected an fascinating gallery of photos of girls with lavender hair.
And, finally, we suggested to the most courageous experimenters how to choose one of 10 shades ofpink hair, which is the most suitable for their skin tone.
And today you will see the original forms of creating multi-colored locks, an unusual rainbow in your hair. Enjoy!
Rainbow-colored hair: the craziest variants
Colorful squares
The whole area of the hair is divided in 4 parts and every part is dyed in different colors. If some strands are lifted to comb your hair, there will be an interesting combination: the colors weave and mix with each other. It’s not very difficult to make such a rainbow. Even a novice hairdresser can cope with this task.
Hidden rainbow in your hair
Are you hesitating? You want to change your hair color now radically but the next day you worry about looking too bold? How will your boss, colleagues and relatives react? What will happen if after a week you will become bored of being a rainbow-haired girl?
The best variant for you is a rainbow under the top layer of your hair. The hidden rainbow will be visible only if you want to. However, the top layer of your hair will remain the usual light, sometimes dark shade. Rainbow hair inside will be visible only if you lift the unpainted top and release the colorful madness.
The layers of rainbow hair
This variation is performed in a similar technique. In the process of dyeing, the upper layer of hair is lifted, fixed with a clip. A thin layer on the back of the head is dyed in a chosen color. Then another layer is separated in the same way and colored with another bright shade. The number of color layers may be different. Thus, the loose falling hair has one color, and in the hairstyle there will be a multi-colored madness.
Shaving
The more radical solution combines a bright palette of shades and relief patterns or just ornaments. The favorite theme of rebel-dreamers is cats on the back of the head. Moreover, there are spider lines, longitudinal lines, zigzags, etc.
Rainbow strands
One more bold interpretation is long and colorful strands. You can dye your hair in bright colors from the roots to the ends, as it’s on the photo. Vertical rainbow looks perfectly on the long colorful hair, especially on curly.
Girls who want only to try on the rainbow can start with dyeing only some locks not form the roots. This can be performed in an ombre technique. It’s a smooth transition of colors. This is a perfect variant for young girls, students and teachers.
Rainbow pastel
Hairstyle in pastel rainbow colors looks very cute and gentle, it emphasizes the youth of the girl. This color doesn’t offend the eyes of the people around, it looks beautifully in a braid, in a clump, and on flowing hair. Most often, experts advise their clients to use the blue-violet gamut as a basis.
Colorful highlights in the hair
It’s very difficult to create colorful highlights. Only a professional hairdresser can handle this. But this hairstyle looks gorgeous, original and unusual. Short strokes of different colors are applied with a thin brush and thus the hairdresser has to be careful and accurate.
Rainbow hair on top of the head
It’s one more original form. Only the top of the head is dyed in bright colors. Look how beautifully ombre looks on the top of the head! If the bright «hat» is created by a professional, it can look originally and brightly even when the hair start to grow.
Hologram
How do you like a colorful hologram on your hair? A slight rainbow hair 3D effect is in line with the latest fashion trends. Unusually colored throughout the length in the technique of rainbow ombre, your hair will definitely surprise all friends and acquaintances.
If you like the stylish variations, collected by our authors, then save these extremely beautiful and bold ideas to your networks just with the touch of the button. See more interesting options for how to dye your hair in unusual star colors: Avril Lavigne, Rihanna, Nicole Richie, Gwen Stefani and many others.
Subscribe to articles with valuable tips about creating stylish outfits immediately after publication. | null | minipile | NaturalLanguage | mit | null |
Let My People Go
As I write this, the Egyptian state seemingly totters on the brink of collapse. One last push from what appears to be a genuine, spontaneous popular uprising may be all it takes to send “president for life” Hosni Mubarak into exile or to a wall with (perhaps) a blindfold and final cigarette.
That’s how it looks, anyway. Predicting the future of developments like this is always risky, but with the army apparently operationally neutral and its troops openly fraternizing with the revolutionary masses, I’d strongly advise against buying Egyptian government bonds at the moment.
The question, as always at times like this, is “what next?”
From an anarchist standpoint, the early stages of the Egyptian revolution are encouraging. It’s been, to all appearances, an essentially leaderless uprising aimed at the destruction of state power. That’s a good thing — but of course it scares the bejabbers out of governments everywhere, so much so that the Chinese Communist regime has taken to censoring the subject on the Internet.
The US foreign policy mandarins who’ve actively worked to keep Mubarak in power for lo on thirty years continue, still obviously trapped in the alternate reality they’ve inhabited since the end of World War II, to imagine that they can exert substantial influence over the outcome. But in the real world that outcome, from the US government’s frame of reference, will almost certainly measure out in units of “how bad can it get?” As with Iran in 1979, “blowback” is virtually inevitable. Three decades of malign interventionism can’t be made up for in a week, a month or even a year.
The usual suspects have, over the last few days, changed the chorus of their never-ending tune. “Stability” (i.e. keeping Mubarak in power) has given way to “democracy” (i.e. installing a new regime equally beholden to Washington). Neither outcome is likely.
The focal figure, so far, of the move to harness Egypt’s revolution to perpetuation of the state is former government functionary Mohamed ElBaradei. ElBaradei isn’t much to Washington’s liking, having disputed the US line on Iran’s nuclear ambitions as Director General of the UN’s International Atomic Energy Agency … but they’ll take him six days a week and twice on Sunday over the other major pro-state force lurking in the background, the Muslim Brotherhood.
According to The Guardian, ElBaradei claims a mandate from the Muslim Brotherhood and other “opposition” groups to form a “national salvation government.”
Any lasting coalition between secularist and Islamist statists seems unlikely. Eventually they’ll duke it out. But they’re pulling together for the moment to combat the specter of anarchy. It remains to be seen whether they can fool “the street” into selling its freedom for a mess of politics and co-opt the masses as instruments of their own re-enslavement. I’m deeply sorry to report that historically that’s the most common outcome.
But we can hope — and agitate — for the best.
Citations to this article: | null | minipile | NaturalLanguage | mit | null |
‘Los Suns’ Dominate!
My brother and I were in the nose-bleed seats last night – did you catch us in the crowd? Probably not. But you definitely should have caught the outrageous fandemonium at the second game of the Suns-Spurs playoffs matchup last night. It was the most intensely energized crowd, with seas of orange shirts, ear-shattering boos at the Spurs, and creative noisemakers to add to the fiesta. And a fiesta it was – in honor of Cinco de Mayo, the team dressed in their Los Suns jerseys. The game itself was fierce – we were neck and neck with the Spurs all night. We tied it at a halftime, and surprisingly had a very strong second half of the game, but there were no solid leads the entire game, and no guarantees. But Los Suns really got it together, and we won 110-102, bringing the tally to 2-0 in our run against the notorious Spurs. I can’t tell you enough about how fun the game was.
Earlier in the day, I heard that Steve Nash and Steve Kerr had made their stance against SB-1070, Arizona’s new controversial, muchly-debated immigration bill. They added that they were also wearing the Los Suns jerseys as protest of the bill. Amar’e Stoudemire also took to his twitter to protest against the bill. Here’s a snippet of what they said:
Nash: “I think the law is very misguided. I think it is unfortunately to the detriment of our society and our civil liberties and I think it is very important for us to stand up for things we believe in.”
Kerr: “We want to celebrate the diversity that exists in our state and exists in the NBA. We know what’s going on and we don’t agree with the law itself.”
Amar’e (in a tweet): We support the Latin community. They are part of the 12 tribes of Israel. It 1 nation under YAH (god). Let’s come together. Shalom! 1love”
Now, I can see both sides of this situation – they are in fact exercising their freedom of speech. They have every right to do so, and I applaud them for standing up for Latinos.
The flipside, however, is that people rely on sports entertainment as an escape from the everyday politics and strife of our society. Thus, the team should’ve just stuck to the game, and not the politics.
However, consider this. The Suns weren’t the ones who let politics infiltrate sports – they are responding to national endeavors to boycott Arizona and everything associated with it. The Suns were standing up against this in their own way – their team shouldn’t be boycotted solely because of their state’s offensive legislature. They’re standing up against the bill and standing up for Arizona – there are dissenting voices in this state, and lumping everyone into one racist group is unfair.
As much as I’m conflicted about this bill, I don’t think boycotting the state is the answer. It’s a very strong message, yes, but it pains me because I live here, and I don’t want my state to suffer on account of this bill. | null | minipile | NaturalLanguage | mit | null |
Q:
C# - Undeclared Prefix in XML
So I am trying to make a standard xml in C# but receive the error, 'xmii' is an undeclared prefix. I have researched the problem but nothing has seemed to work. Any suggestions?
XmlDocument doc = new XmlDocument();
doc.LoadXml("<xmii:Request/>");
docFrag.InnerXml = "<xmii:Name>" + name + "</xmii:Name>";
doc.DocumentElement.AppendChild(docFrag);
docFrag.InnerXml = "<xmii:PWord>" + pword + "</xmii:PWord>";
doc.DocumentElement.AppendChild(docFrag);
Here is an example of what the xml should look like
<xmii:Request>
<xmii:Name>John</xmii:Name>
<xmii:PWord>Monkey</xmii:PWord>
</xmii:Request>
A:
Just to summarize the comments. Credit to @MichaelCoxon with his answer. The code works if this is included
XmlDocument doc = new XmlDocument();
doc.LoadXml("<xmii:Request xmlns:xmii=\"http://my.namespace.com/xmii/namespace\"/>");
docFrag.InnerXml = "<xmii:Name xmlns:xmii=\"http://my.namespace.com/xmii/namespace\">" + name + "</xmii:Name>";
doc.DocumentElement.AppendChild(docFrag);
docFrag.InnerXml = "<xmii:PWord xmlns:xmii=\"http://my.namespace.com/xmii/namespace\">" + pword + "</xmii:PWord>";
doc.DocumentElement.AppendChild(docFrag);
| null | minipile | NaturalLanguage | mit | null |
Adsorption of gemini surfactants with partially fluorinated chains at three different surfaces: neutron reflectometry results.
The adsorption of six symmetrical cationic (dimethylammonium bromide) gemini surfactants with four different partially fluorinated chains at three different surfaces--the air/water, the hydrophilic silica/water, and the hydrophobic (octadecyltricholorosilane (OTS))/water--has been investigated by neutron reflectometry. The corresponding single chain trimethylammonium bromides have also been studied at the two solid surfaces. Four of the geminis with a C(6) spacer and chains with differing amounts of fluorocarbon have identical limiting areas per molecule at the air/water interface (106 ± 5 Å(2)). This is similar to the value for the corresponding hydrocarbon gemini with a C(6) spacer and C(12) side chains, but unlike the hydrocarbon gemini, it is significantly more than twice the area per molecule of the corresponding single chain cationic. In adsorbed aggregates on hydrophilic silica the area per molecule decreases from the air/water value by an average of about 25%, indicating a substantial improvement in the packing of these geminis in the aggregate, which can be attributed to the stronger interaction between the hydrophobic chains in the interior of the aggregates. On the hydrophobic OTS surface the area per molecule in the adsorbed monolayer for three partially fluorinated geminis decreased by about 15% from the air/water value, again indicating much more favorable packing next to the hydrophobic OTS, but for one of the geminis, fC(8)C(6)-C(6)-C(6)fC(8), the change in area was reversed. This reversal is accompanied by a marked thinning of the layer, which is attributed to a shift in the balance between the interactions of the hydrocarbon spacer and fluorocarbon chain fragments and the OTS surface. | null | minipile | NaturalLanguage | mit | null |
Armand-Jean du Plessis, better known to history as Cardinal Richelieu (1585–1642), spent most of his career contending for and then exercising control over a deeply divided, indebted, and dysfunctional superpower. His country’s politics were vicious, and its government paralyzingly complex. In short, if he were dropped into Washington today, he might feel right at home.
French historians have long hailed Richelieu as the architect of the absolute monarchy that dominated Europe throughout the seventeenth and eighteenth centuries. Henry Kissinger, in Diplomacy, dubbed him “the father of the modern European state system.” Even critics, such as Alexandre Dumas, who made him the villain of The Three Musketeers, often cannot help admiring Richelieu’s icy savoir-faire, which is captured in the famous portrait by Philippe de Champaigne that adorns the cover of Jean-Vincent Blanchard’s new biography. As Richelieu intended, it shows a master political player with the ruthlessness necessary to achieve his goals, chief among them raising France to greatness.
Richelieu was indeed a model statesman, but not for the reasons usually given. Despite his long-standing reputation (which Blanchard largely endorses), the cardinal was not really a great institution builder, still less someone bent on making France what Blanchard calls “a modern administrative state.” Nor do Kissinger’s claims about Richelieu inaugurating an international order based on raison d’état hold up. The cardinal was hardly the first European statesman to place national interest above moral or religious imperatives, and the modern European state system, with its power balancing and alliances, did not really take firm shape until the Peace of Westphalia, six years after Richelieu’s death. Richelieu was, however, one of the greatest examples in history of the politician as high-stakes gambler, notable less for what he did than for how he did it.
Richelieu’s qualities as a statesman emerge most sharply when he is compared with other leaders of the period -- particularly his great rival, Spain’s chief minister, the Count-Duke of Olivares, who lacked both the cardinal’s keen foresight and his taste for risk but nonetheless came close to defeating him on many occasions. For this reason, the single best recent treatment of Richelieu remains the British historian J. H. Elliott’s brilliant 1984 study Richelieu and Olivares. Blanchard’s biography is engaging and well written but has a more sprawling and somewhat thinner feel. As a specialist in seventeenth-century literature, Blanchard has trouble situating Richelieu in the broader sweep of European history, particularly when it comes to the complex dynamics of ancien régime administration and diplomacy. Still, he has read the most important primary sources carefully and has a good eye for colorfully illustrative passages, along with a genuine sensitivity to his subject’s personal strengths and weaknesses. Those who know Richelieu only from the movies will find in Blanchard’s pages a very human character who triumphed in a setting far more frightening than anything Hollywood has recently devised.
ORBITING JUPITER
The tone of Richelieu’s career was set by the savage and unpredictable political culture into which he emerged. The first two kings of France in his lifetime, Henry III and Henry IV, were both assassinated. The next king, Louis XIII, had his chief minister, Concino Concini, shot in the street, after which the man’s naked body was ripped to pieces on the Pont Neuf. (Some reports claimed that members of the frenzied crowd even cooked and ate Concini’s heart.) Several other leading figures of the period ended their days on the executioner’s block, including the unhappy Comte de Chalais, whose headsman bungled the job and ended up frantically chopping away at his screaming victim with a small hatchet.
Richelieu himself was regularly in danger of meeting a similar fate. Chalais had plotted to have him stabbed to death, and another enemy tried to put a bomb under the seat of his carriage. Richelieu was Concini’s protégé, and himself escaped from the angry Parisian crowds only because he had the presence of mind to order his retainers to start shouting, “Vive le roi!” (Long live the king!). Surviving in such a milieu, to say nothing of flourishing, required brilliant timing, courage, an uncanny ability to read and manipulate others, and a willingness to take dramatic risks -- all qualities Richelieu had in abundance.
Richelieu rose to national prominence during a particularly perilous time, the years following the assassination of Henry IV in 1610. The popular monarch’s successor, Louis XIII, was just eight years old when he took the throne and grew into an awkward, insecure youth with a bad stutter, psychologically overwhelmed by his ferociously ambitious mother, Marie de Médicis, who served as his regent. Sensing an opportunity to claw back some power from the monarchy, French nobles staged a series of revolts, and eventually Louis rebelled against his mother and sought to take control of the government in his own right. (One step in this process was the killing of Concini, who had been Marie’s favorite adviser.)
It was Marie who originally saw the potential in Richelieu -- at the start of this period, a relatively minor noble from western France who had joined the clergy merely to secure his family’s rights to the revenues of a bishopric. She quickly brought him into the inner circles of power, placing him in charge of French foreign policy in 1616. In 1618, after war broke out between mother and son, Louis banished Richelieu to Avignon. But the young bishop managed to convince the king of his loyalty and proved instrumental in bringing about a family reconciliation of sorts. Following the 1621 death of Louis’ chief adviser, the Duc de Luynes, Richelieu came to the fore, eventually becoming the king’s most trusted and important councilor. In 1622, the pope agreed to make him a cardinal.
For the next two decades, Richelieu was a crucial player in French and European politics, but with his position resting on his ability to please and manipulate his vain, stubborn, and temperamental royal master -- whom Blanchard nicely describes as “worn out by inner torments, military battles, and furious hunting.” As a Spanish diplomat of the time put it, Richelieu had come “closer to Jupiter, but also to his thunder.” Blanchard might have dwelt somewhat more on this fascinating relationship, in which Richelieu not only flattered the king endlessly but also made sure the monarch was surrounded by attractive young men. Above all, Richelieu became a mentor to Louis, someone able to scold the king for his shortcomings, sometimes even in public.
As Richelieu’s star and influence rose, Marie grew resentful of her former protégé, and a showdown became inevitable. On November 11, 1630, Marie exploded at the cardinal in front of the king, showering him with insults and forcing him to beg for mercy on his knees. Louis, apparently struck dumb by the outburst, left without acknowledging Richelieu, and Marie’s supporters rejoiced that their nemesis the cardinal had fallen. That evening, the king summoned Richelieu to his hunting lodge at Versailles -- for his execution, the cardinal thought, assuming he had finally lost the high-stakes poker game of court politics. Overcoming his urge to flee, Richelieu obeyed the king’s command and discovered that he was in fact being restored to royal favor, in an episode that would become known as the Day of the Dupes, with Marie’s leading allies arrested instead the next morning. By 1642, Louis could write to Richelieu, “I have never loved you so much. We have been together for too long ever to be separated.”
THE GAMBLER
Richelieu’s statecraft involved as much dangerous risk taking as his domestic political career. In 1618, what would become known as the Thirty Years’ War broke out -- Europe’s last great spasm of religious warfare, in which a furious conflict between a series of Protestant states, on one side, and the House of Hapsburg and its Catholic allies, on the other, tore the center of the continent apart. France, a Catholic state itself, nevertheless intervened on the Protestant side, hoping to supplant the Austrian and Spanish Hapsburgs as the strongest power in Europe.
Richelieu initially felt that France could do no more than subsidize Protestant efforts and engage in strictly limited military campaigns. Ironically, he feared treachery from the Huguenots, France’s own small Protestant minority, who had lingering grievances against the French state and control of several strategic towns, including the Atlantic port of La Rochelle. Realizing that he had to address the Huguenot threat before intervening seriously abroad, in 1627 Richelieu laid siege to La Rochelle and starved the city into submission. (By the end of the operation, even the rats had disappeared, and the starving locals were reduced to eating boiled shoe leather.)
Then, Richelieu made one of his boldest moves. With France exhausted and indebted, he quickly raised another army and sent it on the dangerous route across the Alps into northern Italy, where an unstable political situation offered France the chance to break the Hapsburgs’ extended supply lines. The gamble paid off, and a few months after the fall of La Rochelle, Richelieu and Louis watched French forces storm in triumph across the northern Italian plains.
After its victory in Italy, France continued to encourage and subsidize Protestant powers, such as the Netherlands and Sweden, without committing fully to the broader war. A series of Catholic victories in the early 1630s, however, finally convinced Richelieu to go all in, and in May 1635, he sent a gaudily dressed herald across the border to Spanish-ruled Brussels to issue a formal declaration of war.
At first, the gambit seemed to go terribly wrong. Spanish forces invaded France’s northern provinces in the summer of 1636, capturing several strategic fortresses and coming within a day’s ride of the capital. Panicky crowds flooded the streets of Paris calling for Richelieu’s head. The cardinal fell into a deep despair. Yet François-Joseph le Clerc du Tremblay, the so-called Gray Eminence, who stayed at Richelieu’s side throughout much of his career, managed to rouse him, and recovering his nerve, France’s chief minister walked out onto the Pont Neuf to much the same spot where his predecessor, Concini, had been butchered two decades earlier. Admiring his nerve, the crowd cheered the man it had just been cursing. Meanwhile, the French armies held, then gained a respite when the Spanish broke off their offensive to rebuff an attack from the Dutch. Over the next six years -- the last six years of Richelieu’s life -- France seized large new territories and established itself as a leading power in Europe.
THE CARDINAL’S VIRTUES
Many today might dismiss Richelieu’s brand of leadership as archaic, something with little relevance to the far more ponderous process of modern statecraft, with its armies of bureaucratic functionaries analyzing all policy options in mind-numbing detail. Yet from Munich to the Cuban missile crisis to nuclear proliferation, recent history is replete with instances of international politics resembling nothing so much as a poker game. And was not the 2003 invasion of Iraq very much a gamble, with the Bush administration having its own, not-entirely-un-Richelieu-like power behind the throne, manipulating an inexperienced young leader struggling to emerge from the shadow of his powerful parent? In this sense, the survival skills that politicians develop in their rise to power at home may serve them surprisingly well when they take on responsibility for international affairs, and Richelieu may offer a model of sorts.
As for his historical significance in France’s long-term development, the record is less clear. Richelieu won important victories over his country’s great rivals, Hapsburg Austria and Spain, but he did not consolidate those triumphs. He raised tax revenues manyfold, allowing France to fight effectively in the Thirty Years’ War, but in the process he squeezed the peasantry and provincial elites so brutally that he provoked a series of ruinous revolts that culminated, soon after his death, in outright civil war. And although Richelieu improvised brilliantly, as when he sent out agents called intendants, armed with new powers, to help collect taxes and control the army in the provinces, he did not design permanent new administrative structures.
It would take another monarch and another chief minister -- Louis XIV and Jean-Baptiste Colbert -- to take the story further in the decades that followed. They were the ones who secured the French state’s modern borders, who cooperated more closely with provincial elites and extracted even greater sums from the country with considerably less strife (in order to wage even more ambitious wars), and who turned Richelieu’s intendants into established arms of the central state. Richelieu, in short, did not create modern France nor make it the leading force in Europe. But his actions paved the way for his successors to do so, which is no small feat. | null | minipile | NaturalLanguage | mit | null |
Q:
How can I determine why JPA/eclipselink/J2EE is issuing a ROLLBACK to the DB?
I am chasing a problem where I see SQL statements run in my database log in a transaction, then see that transaction rolledback.
This happens on both Oracle and Postgres, but only on some installations. The application itself is a pretty standard J2EE application using JPA and Eclipselink.
I am not seeing any exceptions, nor is the code explicitly giving up and rolling back.
The best I have been able to do so far is find this log statement:
[#|2011-09-26T11:30:56.052-0700|FINER|sun-appserver2.1|org.eclipse.persistence.session.file:/opt/glassfish/domains/domain1/applications/j2ee-apps/myapp/myapp-ejb_jar/_myapp-ejbPU.transaction|_ThreadID=18;_ThreadName=httpSSLWorkerThread-8888-2;ClassName=null;MethodName=null;_RequestID=e78196
09-bf2e-4026-8cbb-87fdd047c5eb;|begin unit of work flush|#]
It occurs at the exact same time as the ROLLBACK in the postgres log:
appuser @ dbname: 102012/7/67486 2011-09-26 18:30:56.052 UTC - LOG: execute S_3: ROLLBACK
Note that the DB is on UTC while the application is on Pacific.
The relevant code is being called using a webservice with @TransactionAttribute(TransactionAttributeType.SUPPORTS)
I am working with both logging levels and the debugger to see if I can find an exception being thrown and swallowed that might cause this.
How can I find out what code is causing the rollback?
A:
You can enable logging on finest with EclipseLink to debug the issue.
Any exception that occurred within EclipseLink will be logged.
See,
http://wiki.eclipse.org/EclipseLink/Examples/JPA/Logging
Also ensure you are not throwing an error to cause your SessionBean to rollback.
| null | minipile | NaturalLanguage | mit | null |
Data Model Translation: A Challenge of Polyglot Persistence
[Editor’s Note:] This Neo4j Lab has been deprecated. The code is available in our GitHub project, but is no longer actively maintained.We’ve previously talked about the concept of polyglot persistence and why it can make sense to use multiple database technologies together.Today, we will examine a possible use case for using Neo4j (a graph database ) and Cassandra (a column store ) together and take a brief look at the alpha version of a new tool to help make working with Cassandra and Neo4j a bit easier.
Figure 1: Converting a column store data model into a property graph. Converting from one data model to another is often the first step of implementing polyglot persistence.
Neo4j + Cassandra: A Possible Use Case
The Neo4j-Cassandra Data Import Tool – Alpha Version
Polyglot persistence is all about taking advantage of the strengths of multiple database technologies to enhance your application. However, this comes at the expense of the added complexity of working with multiple databases.In order to take advantage of polyglot persistence, often the first task is to convert from one data model to another. For example, converting data from a document data model to a property graph model Our goal is to make this process more simple for the developer. For this reason, we have been working on a prototype Neo4j-Cassandra data import tool.Before looking at this tool, let’s examine why we would want to use Cassandra and Neo4j together. Previously , we looked at using MongoDB and Neo4j together in the context of a product catalog use case. In that example, we leveraged Neo4j for generating personalized recommendations while using MongoDB’s strengths to search, filter and populate the view for our product catalog.What are the strengths of each database that we would want to leverage? Because of Cassandra’s masterless clustering model and reliance on eventual consistency, one of its strengths is the ability to handle a very high write throughput. For this reason, Cassandra is often used to store high volume data such as event logs, which don’t require ACID guarantees like what is available with Neo4j.However, depending on how we want to analyze these event logs, we might run into trouble.As Cassandra does not have a rich query language , it is advised to make the columns and column families optimized for reading the data. This can result in data duplication as you end up creating new tables with the same data, but optimized for different queries.What if we want to explore relationships in our data, perhaps for a fraud detection use case?We know that Neo4j is very good at handling relationships , so it might make sense to bring some of our event log data into Neo4j to run some fraud detection Cypher queries Fraud detection using event log data is just one possible use case that might make sense. Do you have a polyglot Neo4j + Cassandra use case in mind? If so we’d love to hear from you about it!
Figure 2: The Neo4j Cassandra Data Import tool enables data export from Cassandra, translation to a property graph and inserting into Neo4j.
An Overview of the Tool
Step 1: Inspect Cassandra Schema and Config Data Mapping
CREATE TABLE playlist.artists_by_first_letter: first_letter text: {} artist text: {} PRIMARY KEY (first_letter {}, artist {}) CREATE TABLE playlist.track_by_id: track_id uuid PRIMARY KEY: {} artist text: {} genre text: {} music_file text: {} track text: {} track_length_in_seconds int: {} NEO4J CREDENTIALS (url {}, user {}, password {})
To help developers take advantage of polyglot persistence with Neo4j and Cassandra, we’ve put some effort into developing a command-line tool to enable transferring data from Cassandra to Neo4j. Special thanks to Hanneli Tavante who helped develop this project with the use of her Cassandra expertise!Note that this is just an alpha prototype version that demonstrates some of the issues and a possible approach. Community feedback and contributions are much appreciated.The Neo4j-Cassandra data import tool works by inspecting the Cassandra schema and allowing the user to define how the data should be mapped from Cassandra’s column-oriented data model into a Neo4j property graph:The tool will inspect the Cassandra schema and generate a file with placeholders for specifying the configuration mapping.This initial version of the tool provides limited options for translation, the most notable limitation is that every table will be translated into a node in the graph model. See the documentation for more information.
Figure 3: The tool inspects the Cassandra schema of a specified keyspace. The user must then configure the mappings of the data model to specify how the property graph is created.
Step 2: Import Data to Neo4j
Looking Forward
Once the mapping has been specified by the user, the tool provides a mechanism to generate LOAD CSV Cypher queries to automatically import the data set from Cassandra to Neo4j.This is accomplished by writing to CSV files as an intermediate step, then using Neo4j’s LOAD CSV Cypher import tooling to import the data. The Cypher queries are executed using Neo4j’s Python bindings (py2neo) based on the credentials specified as part of the data mapping.An initial version of the tool is available now available on Github here . Note that the tool is rather limited in scope at this point and has only been tested with an example dataset, as explained in the documentation This was a brief look at the challenges of polyglot data modelling and a new tool that makes that process a bit easier (hopefully) when working with transferring data from Cassandra to Neo4j.By no means is this tool a complete and scalable solution for syncing data from Cassandra to Neo4j. This tool is simply the first step toward providing a solution for implementing polyglot persistence using Cassandra and Neo4j.Our goal is to provide a simple example and a use case of what might make sense. If you are interested in providing feedback, please email me or raise an issue on the GitHub project . We’d love to hear from those using Cassandra and Neo4j together. What is your use case? What would help facilitate the polyglot Neo4j and Cassandra experience? We’re also very open to accepting Pull Requests on the GitHub project for those interested in contributing.If you’re interested, you can read the individual steps for running the tool on our developer pages | null | minipile | NaturalLanguage | mit | null |
Printers and copiers often have a photo-sensitive member which receives an image, and an intermediate transfer member, often with a heated blanket, which receives the image from the photo-sensitive member and transfers it to sheet of paper or other printing media on an impression roller. (The printing media will henceforth be referred to as “paper,” but any printing media should be understood.) The intermediate transfer member often has a delicate surface, for example the heated blanket may comprise a release surface with a soft conforming layer underneath, which allows the surface to press against the impression roller with uniform pressure. These characteristics of the intermediate transfer member produce good images on the printing media, but also mean that its surface may be damaged relatively easily, and such damage may require a time-consuming and expensive replacement of the member. Even for different structures, the intermediate transfer member (often in the form of a blanket) is subject to damage from excess pressure and/or from toner that is left on the release surface too long.
One cause of such damage is paper sticking to the blanket. Normally, paper is fed onto the impression roller and held there with grippers. If the paper is misfed for any reason, then the paper may stick to the blanket of the intermediate transfer member after the image is printed. The printer must then be stopped, opened up, the paper removed, and the ink on the blanket (which in normal operation gets completely transferred to the paper) must be cleaned off. Delay in removing the ink from the blanket may result in the ink drying onto the (generally heated) blanket, which must then be replaced. Ink may also remain on the intermediate transfer member if, as a result of the paper misfeeding, at least part of the intermediate transfer member presses directly against the surface of the impression roller, without any paper in between. If the paper is folded or wrinkled as a result of the misfeed, it may dent the blanket, also making it necessary to replace the blanket. If paper is not released on time from the impression roller, then two sheets of paper may end up on the impression roller, which can hurt the blanket.
Because paper misfeeds are potentially so damaging, it would be desirable to prevent any events which could cause a misfeed, even relatively rare events. | null | minipile | NaturalLanguage | mit | null |
Organic milk for heart health
Now there’s even more proof that consumption of conjugated linoleic acid, or CLA, can boost heart health, according to the Harvard School of Public Health. Of the more than 4,000 study participants, those with the highest CLA levels had a 36 percent lower risk of heart attack compared to those with the lowest concentrations. The catch: This study took place in Costa Rica, where grass-grazing cows can produce milk with five times more CLA than the grain-fed cows common in the United States. Want to get the most from your dairy? Look for U.S. organic milk. Thanks to new regulations, it must come from cows that graze pasture for at least four months of the year and get at least 30 percent of their food from pasture during grazing season. | null | minipile | NaturalLanguage | mit | null |
By Glynis Kazanjian
[email protected]
Less than a quarter of Maryland teachers said they were “very familiar” with the Common Core State Standards when asked about it last fall, according to a survey conducted for the Maryland State Department of Education.
The new standards-based education curriculum was adopted by Maryland in 2010 and was supposed to be fully implemented by the 2013-2014 school year.
The survey found that roughly half of teachers, 55%, said they were “somewhat familiar” with Common Core, while 24% said they were not familiar with the standards at all.
State officials tried to put a positive spin on the results but were met with criticism and questions by state Board of Education members. The survey results were presented to board members at the monthly state board meeting on Tuesday, but local school districts had already received the survey results.
“This is a very good start,” said state education department spokesman William Reinhard. “The CAIRE survey is baseline data, and it showed that 70-80 percent of our teachers were either very or somewhat familiar with the new standards. The researchers will follow up that survey with another this spring, and we expect those numbers to go up.”
Survey reached thousands of teachers
Twenty-one of Maryland’s 24 school districts participated in the Center for Application and Innovation Research in Education (CAIRE) survey. The electronic survey took place over a four-week period with 9,232 teachers, 582 principals and 295 superintendents and staff members, participating.
Similar responses were found when teachers were asked how prepared they felt to teach Common Core. Twenty-two percent, 22%, said they were “very prepared,” while 63% said they were “somewhat prepared” and 15% said they were “not at all prepared.”
Discrepancies between teacher preparedness questioned
When board members asked why some teachers felt very prepared while others didn’t at all, Towson University College of Education Dean Raymond Lorion, who co-authored the report, said the answer falls on individual school districts.
Some of those districts did not introduce Common Core materials until right before they had to use them in the classrooms. Others introduced the materials well before the fall of 2013, and that accounts for the discrepancy, he said.
Henry Johnson, assistant state superintendent of schools, said he looked at the preparedness results very positively because it was the first year of implementation.
“In total 85% of the respondents indicated a general level of preparation,” Johnson said. “Our goal is to help all of our teachers move beyond the basic level of preparation to a very prepared level for the 2014 school year.”
Less than one-third of teachers said they had enough professional development
Only 29% of teachers said they received enough professional development support from their school and school districts to have Common Core fully implemented by the 2013-2014 school year. Half, 50%, said they had “some, but not all” the professional development they felt they needed.
Thirty-seven percent of principals said they had received enough professional development from their school districts to meet all the needs to implement Common Core; 56% said they had received “some” professional development, “but not all” that was needed.
“Shouldn’t we be concerned about the disconnect,” state board member Donna Hill Staton asked.
“Yes,” Johnson said, but he also indicated that different school districts carried out state training opportunities different ways. Based on that, Johnson said he felt the aggregate survey responses are good.
“That’s the disconnect,” Hill Staton said.
State Superintendent of Schools Lillian Lowery said that each district now has its own set of data to examine.
State sends out teams to help teachers
State education officials also said they have been sending out teams to individual school districts to get a closer look at what educators need on the local level. Fifteen out of 24 school districts have already been visited by state Common Core teams.
“We’re doing observations within the schools,” said Cecilia Roe, Maryland Department of Education director of instructional assessment and professional development. “We’re meeting with the teachers we’re observing and we’re having open forums with any teacher in the county that wants to meet with us.”
Roe said their purposes are twofold. The teams will try to find out what the teachers’ comfort level with Common Core is, and what support they need.
As of last fall, only 19% of principals surveyed thought Common Core was supposed to be fully implemented by the beginning of the school year. Twenty seven percent thought they had until the end of the 2013-2014 school year.
Thirty two percent of principals didn’t answer the question, 12% thought they had until some next year, and 10% didn’t know. | null | minipile | NaturalLanguage | mit | null |
Q:
Storing images in SQLite android
I have an SQLite Database in which I am storing images as BLOB using this code
URL url = new URL("http://t0.gstatic.com/images?q=tbn:ANd9GcRsaLl3TGB4W2hJFN_Wh0DNVPQEYGtweNsqvTXVtwE8FXR300-Ut-npgS4");
//open the connection
URLConnection ucon = url.openConnection();
//buffer the download
InputStream is = ucon.getInputStream();
BufferedInputStream bis = new BufferedInputStream(is,128);
ByteArrayBuffer baf = new ByteArrayBuffer(128);
//get the bytes one by one
int current = 0;
while ((current = bis.read()) != -1) {
baf.append((byte) current);
}
mydb = openOrCreateDatabase(DBNAME, Context.MODE_PRIVATE,null);
mydb.execSQL("INSERT INTO " + TABLE + "(IMAGE) VALUES('" + baf.toByteArray() + "')");
mydb.close();
When I try to retrive the image, I am getting the following error
Factory returned null
My Select Query is this
mydb = openOrCreateDatabase(DBNAME, Context.MODE_PRIVATE,null);
Cursor allrows = mydb.rawQuery("SELECT * FROM "+ TABLE, null);
if(allrows.getCount() > 0){
allrows.moveToNext();
System.out.println("3333");
ImageView myImage = (ImageView) findViewById(R.id.ImageView01);
byte[] bb = allrows.getBlob(1);
System.out.println("VVV " + bb);
//convert it back to an image
ByteArrayInputStream imageStream = new ByteArrayInputStream(bb);
Bitmap theImage = BitmapFactory.decodeStream(imageStream);
myImage.setImageBitmap(theImage);
//myImage.setBackgroundResource(R.drawable.icon);
System.out.println("3333");
//myImage.setImageBitmap(BitmapFactory.decodeByteArray(bb, 0, bb.length));
}
Please anyone help.
A:
I use decodeByteArray method
byte[] userPic1Blob = cursor.getBlob(cursor.getColumnIndex(SqlConstans.USER_PIC1_BLOB));
if(userPic1Blob != null && userPic1Blob.length > 0){
Bitmap bm = BitmapFactory.decodeByteArray(userPic1Blob, 0, userPic1Blob.length);
imageView.setImageBitmap(bm);
}
| null | minipile | NaturalLanguage | mit | null |
Tuesday, July 29, 2008
Thirty-Three Hours
Ever wonder how much you'd be able to train if you didn't have to go to work every day? I now know my own answer to that question. (Well, sort of ... I worked remotely from Boulder for about 25 hours last week -- so more flexibility than usual but I'm still not a "full-time athlete.")
When I planned out this three week "work part-time while training a lot" trip I envisioned tons of free time -- afternoon naps, social events with the big-name pro triathletes in town, exploring the local restaurants, driving up to the mountains, visiting friends in Fort Collins and Colorado Springs ... but it turns out that training full-time eats up a lot of time! (Especially with the half-time work thrown in.) I've been just as busy as when I'm at home working full-time, perhaps busier... and more tired thanks to the altitude and the heavy training volume.
My first week in Boulder included:
26500 yards of swimming, mostly in a Long-Course Meters pool (so yes, I converted that workout volume to yards for my log b/c I am that obsessive)
300 miles of biking, including a 103-mile Long Ride on Sunday and a 16-mile climb to Ward on Friday
55 miles of running, including a 15-mile long run... 90% on trails or the track
I don't think that the next two weeks will include quite as many miles as I ramp up the intensity a bit more... but it was a fun experiment to see if I could Cram all that Graham. | null | minipile | NaturalLanguage | mit | null |
T-cell receptor V-gene usage in synovial fluid lymphocytes of patients with chronic arthritis.
In this study we analyzed the usage frequencies of the TCR V-gene segments by alpha beta+ T cells present in synovial fluid of 17 patients with chronic arthritis, including rheumatoid arthritis. The results of this study, obtained from semiquantitative PCR analyses, showed that in all patients most of the TCR V alpha- and V beta-gene segments could be detected both in fresh PBMCs and in fresh SFMCs. The relative frequencies of use of these V-region genes were variable between the different patients. Although there was some skewing of increased usage frequencies of particular TCR V alpha and V beta genes among SFMC-derived TCRs when compared with PBMCs, we could not correlate such increased TCR V-gene usage with the inflammation in the joints as a disease-specific marker. | null | minipile | NaturalLanguage | mit | null |
A sandwich enzyme linked immuno-sorbent assay for the determination of rat heart fatty acid-binding protein using the streptavidin-biotin system. Application to tissue and effluent samples from normoxic rat heart perfusion.
An enzyme linked immuno-sorbent assay (ELISA) of the sandwich type for the determination of heart-type fatty acid-binding protein (H-FABPc) was developed, making use of the streptavidin-biotin system. The assay turned out to be virtually disturbance insensitive and showed a detection limit for H-FABPc of 0.2 micrograms/l with an intra- and inter-assay variation of 5% and 14%, respectively. The H-FABPc content of adult rat heart muscle was found to be 0.740 +/- 0.120 mg/g wet weight. The H-FABPc content of a number of skeletal muscles varied from 0.013 to 0.303 mg/g wet weight and was related to the content of type I muscle fibers of these tissues, suggesting a role for H-FABPc in intracellular fatty acid metabolism. The assay was further applied to study the release of H-FABPc from isolated rat heart during normoxic Langendorff perfusion, as compared to that of lactate dehydrogenase (LDH), into fluid derived from the right ventricular cavity (Qrv) and that from the interstitial space (Qi). Total release of H-FABPc per 15 min amounted to 0.015 +/- 0.010% but that of LDH to 0.080 +/- 0.040% of their total tissue content. Furthermore, for both H-FABPc and LDH 80% was released into Qi, which only accounted for 1-2% of total flow. These findings suggest that during normoxic perfusion of rat heart H-FABPc, and LDH are released from different cellular compartments and that the bulk amount of released intracellular proteins is transported via the lymph instead of being directly released into the bloodstream. | null | minipile | NaturalLanguage | mit | null |
Lydia Manley Henry
Lydia Manley Henry DSc (30 June 1891 – 27 March 1985) was the first female graduate in medicine from the University of Sheffield. She served with the Scottish Women's Hospitals for Foreign Service during the First World War. She was awarded the Croix de Guerre by the French government. For her thesis on gangrene, based on her wartime experience, she was awarded the degree of MD, the first woman to graduate with this degree from the University of Sheffield.
Early life
Lydia Henry was born in Macduff, Scotland, the daughter of William Paterson Henry (1853–1894) and his wife Elizabeth Dawson Murdoch (1856–1946). Her father died of tuberculosis when she was two years old. Her mother moved to Sheffield leaving her daughter to be brought up by an aunt in Macduff. At the age of 14 she relocated to Sheffield to join her mother, who had begun work at the Day Training College for Teachers in Sheffield and eventually in 1905 became Vice-Principal of the City Training College. At this time she felt able to care for her daughter again. Henry was educated at the Sheffield High School for Girls. The Sheffield University Medical School had been founded in 1905 and she enrolled in 1909. In June 1916 she graduated with an MB ChB, and along with fellow student Florence Elizabeht Millard, together they were the first women to receive a medical degree from the University. The next day she became the first woman to work as a hospital doctor in Sheffield.
Medical career
Henry had further experience working as a house officer in Sheffield Royal Infirmary and the Sheffield Royal Hospital. During the World War I, it became easier for women doctors to find posts in teaching hospitals, as many male doctors were serving in the armed forces. Her experience included working in the Sheffield Royal Infirmary women's clinic for venereal diseases, the first woman doctor to do so.
The day after finishing as a house officer and becoming fully qualified to practise medicine, Henry enlisted in the Scottish Women's Hospitals for Foreign Service (SWH), working in the hospital set up in Royaumont Abbey, north-east of Paris. She arrived in July 1917 and was the youngest doctor on the staff. There, as an assistant surgeon, she had charge of the Blanche de Castille ward. She later served at the associated SWH hospital at Villers-Cotterêts, which treated French rather than British soldiers. After the war the French government awarded her the Croix de Guerre.
After the war, Henry worked on her MD thesis, which was on gangrene, based on her experiences with the condition at Royaumont. With this thesis, in 1920 she graduated from the University of Sheffield with the degree of MD, the first woman to do so. Appointment as assistant medical officer of health for Blackburn, Lancashire, followed. Her success in this post led to her appointment as head of the Social Services Department at the King's College for Women of the University of London, and she went on to become a member of its Senate.
Later life
Henry emigrated to Canada in 1925 and married, becoming Mrs J. Stewart Henry. She stopped practising as a physician. During the World War II she returned to Scotland, providing assistance onshore for the submarine crews operating out of north-east Scotland. In 1978, the University of Edinburgh medical school awarded her the degree of DSc, on the occasion of its 150th anniversary. She died in Saint John, New Brunswick, Canada, on 27 March 1985. A memorial to her memory was erected in her birthplace, Macduff, Scotland.
References
Category:1891 births
Category:1985 deaths
Category:People from Aberdeenshire
Category:Alumni of the University of Sheffield
Category:British women medical doctors
Category:Scottish Women's Hospitals for Foreign Service
Category:Recipients of the Croix de Guerre 1914–1918 (France)
Category:20th-century Scottish medical doctors
Category:Scottish emigrants to Canada | null | minipile | NaturalLanguage | mit | null |
"I am a huge fan of America's Next Top Model and have watched the show for years," the owner of People's Revolution, 45, enthused to Us Weekly in a statement Wednesday. "Having worked in various aspects of the fashion industry over the course of my career, I am excited for this new opportunity and hope to bring a different perspective to the show."
"We have greatly enjoyed working with Andre Leon Talley and he has been an amazing asset to the America's family," the show's executive producer, Ken Mok, says. "We wish him all the best in his future endeavors."
Cutrone's first appearance on Top Model will air sometime next spring. | null | minipile | NaturalLanguage | mit | null |
Background
==========
Chronic kidney disease (CKD) affects \~10--15% of the adults globally.[@b1-ijnrd-11-093] The prevalence of this debilitating disease is projected to increase further due to the worldwide diabetes epidemic.[@b2-ijnrd-11-093] In stages 1--4 of CKD, treatment (ie, pharmacotherapy and diet) is focused on slowing the progression of kidney disease and preventing or treating complications and comorbid conditions. In the final stage of CKD (ie, stage 5 or end-stage renal disease \[ESRD\]), renal replacement therapy (RRT) such as dialysis or kidney transplantation becomes necessary to maintain life. With increasing number of people developing CKD, patients requiring RRT is set to increase exponentially. This can cause increased burden on health care system.
All chronic diseases are often challenging to adjust to. Patients with CKD are required to make ongoing psychological adjustments over the course of their disease, such as accepting the life-threatening diagnosis and need for lifelong treatment, learning dialysis techniques, integrating treatment into their lives, and coping with treatment transitions/failures, side effects, and complications.[@b3-ijnrd-11-093] In light of such a substantial and sustained disease burden, the management of CKD/ESRD has expanded from strictly clinical end points toward maintenance of quality of life (QoL), from diagnosis through to end of life care. Of paramount importance are psychological concerns related to the disease and associated renal treatment.
A plethora of studies have demonstrated jarring links between depression and anxiety and CKD/ESRD. Concurrently, psychological comorbidities have been documented to also affect treatment.[@b4-ijnrd-11-093]--[@b6-ijnrd-11-093] It is thus important to understand the interaction of such psychological comorbidities and CKD outcomes. In this review article, we provide a selective narrative overview regarding the recent studies on rates of depression and anxiety in various renal treatment modalities, key associative factors, and potential interventions. It is not intended as a systematic literature but as a scoping synthesis of both empirical evidence and prior systematic reviews to highlight what is already known and directions of practice research. Relevant studies and reviews exploring depression and anxiety in patients with CKD were identified by searching the following databases: PubMed, PsycINFO, and Scopus. Search terms that were used included variations of the terms: depression; anxiety; kidney disease; ESRD; and dialysis. A selective set of studies are included to highlight evidence on the spectrum of CKD including early stage CKD and ESRD treated with different RRTs.
Prevalence rates of depression and anxiety
------------------------------------------
Some key questions regarding mood disorders (ie, depression and anxiety) in CKD relate to its prevalence relative to the other conditions and the general population, to various renal treatment modalities, and also relate to the course of CKD. There is wide variability among studies related to aforementioned topics and are mostly attributed to methodological differences in measurement and criteria to define depression and anxiety disorders (eg, self-reported vs diagnostic interviews), which will be discussed next.
Depression is an emotional state characterized by somatic and cognitive symptoms including feelings of sadness, worthlessness, sleeplessness, loss of appetite and sexual desires, and interest in usual activities.[@b7-ijnrd-11-093] A clinical diagnosis of depression, most often major depressive disorder, is performed when symptoms of depression become persistent, often for more than 2 weeks. The assessment of depression is rather challenging in the CKD population, partly because of overlapping physical symptoms of uremia and depression, such as fatigue, loss of appetite, sleep disruption, and so on. Furthermore, other medical comorbidities such as sleep apnea and vascular complications, which are common in CKD/ESRD, might contribute to these symptoms as well.
Depression can be assessed through either structured clinical interviews, or self- or clinician-administered validated rating scales. Structured clinical interviews are generally seen as the "gold-standard" in the diagnosis of depressive disorders as they are based on specific diagnostic criteria (eg, Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders \[SCID\]). However, depressive symptoms are usually assessed by self- or clinician-administered validated rating scales such as the Beck's Depression Inventory (BDI) scale, Patient Health Questionnaire (PHQ), and Hospital Anxiety Depression Scale (HADS). These assessments are generally preferred in clinical settings for screening and in clinical research for pragmatic reasons to reduce time requirements and financial costs.[@b8-ijnrd-11-093] While these screening tools are not diagnostic measures, they are helpful in identifying those who have significant symptoms and may require further evaluation. There are general cutoffs to signify threshold for caseness (as validated in clinical interviews) and proposed renal specific cutoffs for some screening instruments (ie, HADS, BDI).
Some studies have demonstrated higher prevalence rates of depression in patients with CKD/ESRD than that of other chronic diseases.[@b9-ijnrd-11-093],[@b10-ijnrd-11-093] For instance, in a study by Kimmel et al, the rates of hospitalization due to psychiatric illnesses among patients with ESRD aged 65 years and older were significantly higher for those with ESRD than those with ischemic heart disease, cerebrovascular disease, and peptic ulcer disease.[@b11-ijnrd-11-093] As Cukor et al describes, there are unique, psychosocial paradigms of ESRD challenges that patients face which could explain the high prevalence of depression and anxiety as compared to other illnesses.[@b3-ijnrd-11-093] When compared with the general population, patients with ESRD show more than five times the rate of suffering from depression.[@b12-ijnrd-11-093] The reported prevalence rate of depression in patients with CKD ranges from 20% to 30%.[@b13-ijnrd-11-093],[@b14-ijnrd-11-093] Notably, the assessment method used to identify depression can affect the prevalence estimates. This was illustrated in a meta-analysis of 249 studies conducted by Palmer et al.[@b4-ijnrd-11-093] Within patients undergoing dialysis, the prevalence rates of depression were found to be 22.8% using clinical interviews (eg, SCID and Diagnostic Interviews). However, when self- or clinician-rated questionnaires were used (eg, BDI and HADS), the prevalence rates were found to be 39.3%, which was statistically higher than the previous figure.
Anxiety is another commonly co-occurring psychopathology with CKD/ESRD. Anxiety is an emotional state in which the individual experiences intense fear, uncertainty, and dread from the anticipation of a threatening situation. Anxiety disorders, unlike brief anxiety states caused by stressful events, last at least 6 months, are pervasive and can get worse without treatment. Compared to depression, however, the links between anxiety and CKD are relatively less studied. While anxiety disorders can be reliably diagnosed with the SCID or the Mini International Neuropsychiatric Interview (MINI), they are often assessed with much briefer, but well-validated, scales such as the HADS, Beck's Anxiety Inventory (BAI) scale, and Generalized Anxiety Disorder 7 Inventory (GAD-7).
Existing literature points to increased levels of anxiety in patients with CKD. The prevalence rate of anxiety in patients with ESRD was estimated to be around 12% to 52% in a previous study.[@b5-ijnrd-11-093] However, the exact prevalence remains unclear, mostly due to the limited number of studies, different sample population, and different screening methods used. Studies that have used SCID to diagnose anxiety disorders have found prevalence rates ranging from 0% to 45.7%.[@b14-ijnrd-11-093]--[@b16-ijnrd-11-093]
As illustrated, the prevalence rates of depression and anxiety in patients with CKD/ESRD may not be exactly well defined. However, the high levels of anxiety and depression in these patients remain alarming.
The course of depression and anxiety
------------------------------------
Studies have found evidence of persistent symptoms of depression and anxiety over the course of CKD. Longitudinal studies, albeit few, have shown that emotional symptoms are likely to fluctuate considerably over the course of CKD because of life circumstances, illness burden, disease stages, treatment factors, and other psychosocial issues.
A recent, longitudinal study by Ng et al followed up with 159 patients undergoing dialysis over a period of 12 months.[@b17-ijnrd-11-093] According to their results, 63 patients (39.6%) presented with persistent symptoms of depression, whereas 50 patients (31.8%) had persisting anxiety. Around 13% of the patients reported diminished symptoms, but another 13%--18% had new onset of symptoms. Diminishing perceived social support was found to be associated with increased and persisting distress over time. Similar patterns were also observed in other studies.[@b14-ijnrd-11-093],[@b18-ijnrd-11-093] Prospective work hence highlight that depression and anxiety for the majority of patients with CKD is chronic, with symptoms persisting over time and course of disease.
Depression and anxiety and RRT modalities
-----------------------------------------
Few studies have evaluated the prevalence of depression and outcomes in patients with early stage CKD (ie, stages 1--4), patients established on peritoneal dialysis (PD), or patients with kidney transplant. Research on symptoms of anxiety in these patient subgroups is even more scarce.
Evidence indicates that depression rates in patients with early stage CKD not requiring RRT, albeit lower, are not negligible. Several studies have established an association between depression and CKD based on impaired estimated glomerular filtration rate (eGFR). Hedayati et al found a 21% point prevalence of major depression among veterans with eGFR \<90 mL/min/1.73 m^2^.[@b19-ijnrd-11-093] Similarly, the prevalence of at least moderate depressive symptoms was 26% among subjects with hypertensive CKD in the African--American Study of Kidney Disease and Hypertension Cohort Study.[@b20-ijnrd-11-093] The Cardiovascular Health Study found that in their community- based cohort of elderly subjects, those with depressive symptoms had 19% greater odds of impaired eGFR (95% CI=1.01--1.40) compared to those without, after adjustment for demographics, clinical variables, and health behaviors.[@b21-ijnrd-11-093]
Depression in patients with ESRD undergoing PD
----------------------------------------------
PD is a home-based dialysis modality that involves the insertion of dialysis fluid into the patient's peritoneal cavity for the filtration of toxins and water through the peritoneum. The PD process requires patient to do the dialysate exchange either three times a day (for continuous ambulatory peritoneal dialysis \[CAPD\]) or while sleeping (for automated peritoneal dialysis \[APD\]). Although PD affords greater opportunities for control, autonomy, and the convenience of home-based treatment, recent studies have reported disconcertingly high levels of depression in patients maintained on PD regime.[@b22-ijnrd-11-093] The estimated prevalence rates range from 18.7% to 51.5%, depending on the measurement and the criteria used for diagnosis.[@b23-ijnrd-11-093]--[@b25-ijnrd-11-093]
There also seem to be differences across the PD modalities. Griva et al noted that patients performing the PD procedure manually (CAPD) perceived more treatment associated disruption and higher rates of depression relative to patients on the automated APD.[@b24-ijnrd-11-093] This could be due to the more regular daytime exchange of dialysate for patients on the manual CAPD, and thus less time for work, family, and social life as compared to patients on night-time APD.[@b26-ijnrd-11-093]
Whether PD confers better psychological outcomes than HD is still largely contentious. In some studies, it has been reported that patients with HD experience higher symptoms of depression and anxiety than that of patients on PD,[@b27-ijnrd-11-093],[@b28-ijnrd-11-093] in line with dialysis modality differences in QoL.[@b29-ijnrd-11-093] Patients with HD have also been shown to have higher hospitalization rates for depression and affective disorders.[@b11-ijnrd-11-093] Distress in HD may be related to procedural aspects of treatment such as the need to travel to dialysis centers (DCs), transportation issues, spending considerable time in medical environments (ie, dialysis wards), and the prolonged sitting time during dialysis. Whereas the dialysis units may foster social support among patients, issues related to emotional contagion among them or witnessing adverse outcomes in others may trigger distress. Distress may also be related to fear of access complications, dialysis-related symptoms, and side effects, which are common concerns among patients on HD.[@b30-ijnrd-11-093]
In contrast, other studies have noted that depression and anxiety in patients on PD are equal or even higher than those reported for patients on HD.[@b25-ijnrd-11-093],[@b31-ijnrd-11-093] By virtue of PD being a home-based dialysis technique, individuals may feel sustained distress over the daily responsibility of their own health and well-being or medicalization of home environment that may act as constant reminder of their ill health.[@b32-ijnrd-11-093] Compared to patients on HD, patients on PD lack regular contact with hospital staff who can provide reassurance of quality care for each session, and a point of reference for their queries and concerns. Opportunities for patient peer support are limited compared to those afforded for patients on HD in the DCs. Distress may also be triggered by the worry about burden to family due to home-based PD. It is to be noted though that symptoms of depression and anxiety are comparable for patients on self-care PD (i.e. patients administering dialysis unaided) and those on assisted PD (PD administration involving paid or unpaid caregivers), so as reports of burden among family members and caregivers.[@b24-ijnrd-11-093],[@b33-ijnrd-11-093] The continuous nature of PD regimen and increased time requirements compared to intermittent HD may adversely affect emotional adjustment and, over time, may take its toll and manifest as depression and burn out.[@b24-ijnrd-11-093],[@b34-ijnrd-11-093]
Depression and transplantation
------------------------------
Kidney transplantation is the preferred RRT as it affords superior clinical outcomes and QoL but is constrained by the limited availability of grafts. In most settings, there is a long waiting list of kidney transplant candidates.[@b35-ijnrd-11-093]
The process of kidney transplantation can be stressful for patients both before and after receipt of kidney.[@b36-ijnrd-11-093] While at the waitlist, patients undergo medical and psychosocial evaluation to ensure suitability. A systematic review investigating waitlist patients' experiences found that although being put on the waitlist offered hope, it also introduced negative feelings such as anxiety, disillusionment, disappointment, and vulnerability when waiting time was prolonged.[@b37-ijnrd-11-093] After transplant, patients face new challenges such as the need to adhere to immunosuppressive medications, diet restrictions, and the inherent fear of graft rejection, or death.
In a recent review conducted by Veater and East, kidney transplant patients were noted to experience elevated levels of depression as compared to the general population but generally lower rates of depression compared to patients on other RRTs.[@b6-ijnrd-11-093] Thus, despite the ability of kidney transplants to restore an individual's level of functioning, there is evidence of persistent symptoms of psychological distress.
Consequences of depression and anxiety on treatment outcomes
------------------------------------------------------------
In general, the presence of psychiatric disorders has been shown to be associated with a higher likelihood of adverse clinical outcomes in patients with CKD. Longitudinal studies have demonstrated that for patients on HD, those who had a clinician diagnosis of depression have worse clinical endpoints such as higher rates of hospitalization and inpatient days, higher rates of dialysis withdrawal and mortality,[@b19-ijnrd-11-093],[@b38-ijnrd-11-093],[@b39-ijnrd-11-093] and increased use of health care system.[@b40-ijnrd-11-093]
Mapes et al demonstrated that among patients on HD, depression was independently associated with increased mortality and hospitalization.[@b41-ijnrd-11-093] Several other original studies and systematic reviews have confirmed the prognostic association of depression with overall mortality. A recent meta-analysis by Farrokhi et al which included 31 studies and data of more than 67,000 patients undergoing dialysis found that the presence of depressive symptoms in such patients is associated with a 50% increase in the risk of mortality.[@b42-ijnrd-11-093] Notably, the method of measuring depression (self-rating scale vs interview or physician assessment) did not appear to modify the association between depression and mortality.[@b43-ijnrd-11-093]
Of greater clinical relevance are persistent symptoms of depression. One study in which depression was measured at 6-monthly intervals in 917 incident patients undergoing dialysis for 2 years found that persistent or recurrent depression was associated with cardiovascular mortality, whereas depression detected over 6 months previously or at baseline only was not associated with mortality. This indicates that persistent depression may be associated with death but resolved depression may no longer have ongoing prognostic implications.[@b44-ijnrd-11-093]
In patients with CKD not requiring dialysis, depression has been shown to be associated with the rate of progression to ESRD. One prospective observational study concluded that depressive symptoms in CKD predicted increased rate of progression to ESRD, and faster dialysis initiation, death, or hospitalization.[@b45-ijnrd-11-093] The results of this study echoed another landmark study by Hedayati et al which found patients with both a CKD and a clinical diagnosis of depression twice more likely to be hospitalized and more than three times likely to progress to ESRD and dialysis than patients who are non-depressed.[@b46-ijnrd-11-093] This association was found to be independent of disease severity and the presence of other comorbidities such as diabetes.
Depressive symptoms have also been shown to affect kidney transplant outcomes. Patients who had symptoms of depression after kidney transplant were more likely to die than patients without depression. A prospective cohort study of 840 transplanted patients over 5-year period found a higher mortality rate in patients with depression as compared to patients without (21% vs 13%; *p* = 0.004).[@b47-ijnrd-11-093] Psychiatric symptoms could also affect the likelihood of patients who are put on the kidney transplant waiting list. Bayat et al found that the presence of a psychiatric disorder was a strong, independent factor in determining access to the transplant waitlist.[@b48-ijnrd-11-093] Similarly, Szeifert et al found that patients who reported lower levels of depression on the CES-D had a higher likelihood of being placed on the renal transplant waitlist. However, this association was not found for patients already on the waitlist who are waiting to receive a kidney transplant.[@b49-ijnrd-11-093]
In patients undergoing PD, depression and anxiety symptoms have been noted to increase the likelihood of adverse outcomes. As compared to their nondepressed counterparts, patients on PD who are depressed are associated with higher risk of inflammation and cardiovascular disease and higher mortality rates.[@b50-ijnrd-11-093] Depressed patients on PD are also at a higher risk of developing peritonitis, or the infection of the peritoneum, which in severe cases can result in death. Juergensen et al, for instance, have demonstrated that patients on PD who reported higher scores for anxiety and depression were more likely to develop peritonitis within the following 12 months.[@b51-ijnrd-11-093] Likewise, Troidle et al in their prospective study of 162 patients on PD found that patients who had BDI ≥11 at baseline had 2.7 times more likelihood of developing peritonitis as compared to patients with no depression.[@b23-ijnrd-11-093]
Clinical outcomes associated with anxiety have been far less studied than those of depression. The presence of anxiety disorder in patients on HD has been observed to result in a significantly lower QoL than patients with no psychopathology, and an even lower QoL than patients with only a depressive disorder.[@b14-ijnrd-11-093],[@b52-ijnrd-11-093] In terms of clinical outcomes, few small studies have found a trend of anxiety symptoms leading to adverse clinical events. The presence of anxiety symptoms could have an influence on patients with CKD who did not require dialysis at first. For instance, Loosman et al found that among patients with CKD who are not yet on dialysis, the presence of anxiety symptoms shows a trend toward death or dialysis initiation.[@b53-ijnrd-11-093]
Mechanism linking depression to outcomes
----------------------------------------
One of the key concerns regarding the association of depression with outcomes is whether depression itself plays a direct role in adverse clinical outcomes or that the depressive symptoms are merely indicators of increased comorbidity and disease severity. Although not well characterized, two mechanisms by which depression is associated with adverse renal outcomes have also been proposed.
First, the link between depression and adverse outcomes may be due to biological factors. Genetic influences of depression and ischemic heart disease in twin studies and a lower heart rate variability were observed in patients with depression, both of which lead to higher likelihood of mortality. Allostatic dysregulation from depression and CKD progression has also been observed to cause hyperactivity of the hypothalamic--pituitary axis activity, resulting in increased cortisol and norepinephrine excretion.[@b3-ijnrd-11-093],[@b54-ijnrd-11-093] This can lead to alterations in malnutrition, immunity, inflammation, and atherosclerosis states.[@b55-ijnrd-11-093] This theory was also supported by early evidence that depression could be involved in the development of malnutrition, inflammation, and atherosclerosis (MIA) in patients undergoing dialysis.[@b56-ijnrd-11-093]
Second, depression might also be associated with clinical outcomes via behavioral pathways. Depression has been associated with decreased adherence to dialysis, prescribed medications, and dietary restrictions in patients on chronic HD, which in turn are predictive of poor medical outcomes and higher mortality.[@b57-ijnrd-11-093]--[@b59-ijnrd-11-093] In addition to nonadherence, other poor health behaviors, such as physical inactivity, smoking, dietary indiscretions, which tend to cluster together in individuals with depression in general may also be implicated. At this point, it is also useful to note that the risks of self-harm and suicide are elevated in patients with dialysis who have depression.[@b60-ijnrd-11-093]
Factors associated with depression and anxiety
----------------------------------------------
Multiple studies have examined possible social, clinical, and psychological factors associated with depression in patients with CKD/ESRD. For instance, a recent literature review by Veater and East investigating depression in patients undergoing renal transplantation identified several risk factors for developing depression including gender, sleep quality, employment, and financial status.[@b6-ijnrd-11-093]
Several sociodemographic factors have been identified to cause anxiety and depression. Females were observed to have a tendency of developing anxiety, whereas males develop depression.[@b61-ijnrd-11-093] In terms of ethnicity, white patients, as compared to African--American patients, were at higher risk of depression.[@b11-ijnrd-11-093],[@b62-ijnrd-11-093] In a study by Yoong et al in Singapore, Chinese patients were found to be more likely to develop depression than those of Malay and other ethnicities.[@b63-ijnrd-11-093] Evidently, ethnic culture could have an influence on the propensity for psychiatric difficulties in CKD.
Patients who had lower levels of education and those who are unemployed were also observed to be at higher risks. Presumably due to do an overall lower socioeconomic profile, problems in psychological well-being, social relationships, and general health are more prevalent in these subgroups of patients.[@b64-ijnrd-11-093],[@b65-ijnrd-11-093] Finally, those who were divorced or widowed reported higher levels of depression.[@b66-ijnrd-11-093] This is possibly due to the perceived lack of social support and lower QoL as a result of their divorce or widowing.
The risk of depression and anxiety in patients with CKD has also been associated with various clinical parameters. Patients with a history of psychiatric illness were found to be more prone to develop depression after renal transplantation.[@b19-ijnrd-11-093],[@b67-ijnrd-11-093],[@b68-ijnrd-11-093] Comorbidity might also increase the risk of development of depression and anxiety. For instance, patients with depressive symptoms were also found to have other comorbid illnesses such as diabetes mellitus, hypertension, cardiovascular heart disease, hypoalbuminemia, and substance abuse.[@b8-ijnrd-11-093],[@b61-ijnrd-11-093],[@b62-ijnrd-11-093]
An increased risk of depression and anxiety has also been associated with adverse outcomes in kidney transplantation. Kidney graft rejection has been reported to trigger feelings of depression, anxiety, aggression, and loss.[@b69-ijnrd-11-093] In a qualitative study of patients who experienced kidney graft failure, the patients reported periods of grief and loss for the "imagined future." These psychological feelings of loss were unfortunately often under-recognized by health care professionals.[@b70-ijnrd-11-093]
There is mounting evidence of an association between illness perceptions and depression.[@b18-ijnrd-11-093],[@b71-ijnrd-11-093] Illness perceptions are conceptualized within a framework of self-regulation (Common-Sense Model \[CSM\]).[@b72-ijnrd-11-093] CSM posits that a person's illness beliefs and understanding of the health threat (ie, their cognitive illness representation) and parallel emotional responses to illness inform coping behaviors and in turn influence outcomes such as physical and emotional health. Major components include perceptions of how the illness was caused, symptoms experienced, the duration (timeline), the consequences of the illness are for life, the symptoms associated with the illness (identity), and how the condition is controlled or cured by one's own behavior or treatment. The CSM has been extended with "common-sense" beliefs about treatment because treatment is an important facet of the illness trajectory. This is particularly true for CKD/ESRD where dialysis has a major impact on patients' daily life.
The relationship between depression and illness/treatment cognitions has been studied most frequently, whereas studies in relation to anxiety or other mood disorders are scarce. Overall, cognitive illness representations were associated with poor emotional health in the theoretically expected direction. Associations were found for both patients with CKD not requiring RRT and patients with ESRD already on RRT.
In a recent review of studies in CKD patients not requiring dialysis, Clarke et al[@b73-ijnrd-11-093] noted that symptoms of depression and anxiety are more correlated with illness perception than with health status, which supports the CSM.
For patients already on RRT, depression was found to be associated with illness perception in terms of perceived locus of control and illness intrusiveness. In a study by Christensen et al, a strong internal locus of control was associated with less depression in patients who did not experience a failed renal transplant.[@b74-ijnrd-11-093] This association was, however, inversed for patients who previously had a failed renal transplant (ie, high internal locus of control led to greater symptoms of depression). In terms of illness intrusiveness, patients who perceived greater disruption to their lives as a result of the renal disease experienced increased depression and distress.[@b75-ijnrd-11-093],[@b76-ijnrd-11-093]
Management and treatment
------------------------
Given the high prevalence and dire consequences of depression, the nephrology community has long recognized that treatment goals should focus on early identification and remission or improvements of distress symptoms, including depression, anxiety, and general emotional well-being. According to the K/DOQI guidelines, the psychological status of each patient undergoing dialysis should be evaluated by a social worker upon initiation of dialysis and then at least biannually, with specific focus on the presence of depression and anxiety.[@b77-ijnrd-11-093] Qualitative studies have revealed that patients consider the psychosocial aspects and reduction in symptoms of CKD as priorities for social scientific research agendas,[@b78-ijnrd-11-093],[@b79-ijnrd-11-093] thus suggesting that the optimal management of psychiatric symptoms in ESRD is important and necessary.
Yet, there is little evidence available that can guide clinicians about the most effective treatment options for the several mood conditions. Data suggest that depression is highly undertreated and underdiagnosed in patients with ESRD. A Dialysis Outcomes and Practice Patterns Study (DOPPS) by Lopes et al found that antidepressants were prescribed to only 34.9% patients on HD who had a physician diagnosis of depression.[@b80-ijnrd-11-093]
Psychopharmacological interventions are commonly cited as a method to alleviate depressive symptoms of patients with ESRD. However, clinical trials so far have employed small sample sizes, and evidence on benefits and harms of antidepressant therapy in ESRD remains inconclusive. Antidepressant medications, most commonly those in the class of selective serotonin reuptake inhibitors (SSRIs),[@b81-ijnrd-11-093] have been demonstrated to improve symptoms. However, there are concerns as to whether their side effects can be well tolerated.[@b82-ijnrd-11-093] As medication count is high among patients with CKD/ESRD, adherence to pharmacological treatments may be more problematic in this population.
Therefore, pragmatic and evidence-based psychological interventions require evaluation. In this regard targeting unhelpful illness and treatment perceptions and enhancing opportunities for social networking and support might be an effective approach in order to improve symptoms of depression. Recent work indicates that cognitive behavioral therapy (CBT) might be an efficacious, acceptable, and practical treatment option for depressive symptoms in patients undergoing dialysis.[@b83-ijnrd-11-093],[@b84-ijnrd-11-093] Cognitive behavior therapy aims to counteract psychological disorders or problems that arise from dysfunctional thoughts, feelings, and behaviors.[@b85-ijnrd-11-093] In the context of depression, negative perceptions of the "self, experience, and future" are maintained through selective information processing that focuses attention on, and thus recall of, information that reinforces it. Patients are taught to modify thoughts that are not consistent with evidence, change maladaptive behaviors, and develop skills for coping with negative feelings.
However, such programs may be hard to integrate into standard clinical care. To this end, it may be worthwhile to evaluate more feasible ways of providing support, such as nurse or peer-support programs. Clinic integrated, or telephone delivered, CBT that have been shown to be effective in other patient populations can be realistically implemented in clinical practice. Recent developments in telehealth or e-health have seen the integration of psychotherapeutic interventions for distressed patients going online. A recent framework developed by Hudson et al established the feasibility of online CBT treatments for managing comorbid distress and ESRD.[@b86-ijnrd-11-093] The self-help protocol that aims to improve distress worked based on the CSM, which targets patient's illness beliefs and self-efficacy. While future work has to be conducted to establish its efficacy, the proposed framework was found to be feasible and effective.
Other practical approaches such as stress management training (eg, mindfulness meditation) and enhancing communication with staff and social support of patients and caregivers may also be important components of mental health services supporting patients with CKD. Training of renal health care providers, especially nurses who have the most frequent contact with some patient groups in mental health issues and brief interventions may be particularly useful as the first step toward integrated care models and stepped-care approaches.
Overall, there is a clear need to provide a holistic care for patients with ESRD both physically and psychologically. The current National Institute for Health and Care Excellence (NICE) guidelines for depression in adults with a chronic physical health problem, such as CKD/ESRD, recommend collaborative care in a "stepped-care framework" in which to organize health services.[@b87-ijnrd-11-093] Patients with an inadequate response to one or more treatments are "stepped up" from low-intensity care to a more intensive form of management (including lifestyle, psychological, and pharmacological therapies). As Finkelstein et al describes, systematic strategies that involve screening, diagnosing, and treating of patients with CKD and caregivers for depression are important to manage the psychological impacts that this disease have on their lives.[@b88-ijnrd-11-093]
Summary
=======
Patients with CKD often have psychiatric difficulties in the form of depression and anxiety. Existing literature sheds light onto the specific impacts and mechanisms that psychiatric difficulties can influence CKD treatment and outcomes. If overlooked, these psychiatric comorbidities can affect the patient's treatment prognosis and mortality. There is an ever-increasing need for physicians to address and treat patients with CKD that present with psychiatric comorbidities.
The high prevalence rates of depression and anxiety in patients with CKD as compared to other chronic diseases is of an important concern. It is unfortunate that compared to other chronic illnesses such as coronary heart diseases and cancers, the study of CKD and related psychological disorders are far less extensive. Existing epidemiological studies have revealed important insights and factors that contribute to the development of depression and anxiety in patients with CKD. Patients with certain social, psychological, and clinical characteristics were found to be more prone to falling into depression. These associations provide practitioners vital indicators to identify and assess patients for psychiatric disorders more efficiently.
Implementing systematic distress screening in routine clinical care would be an important first step, which should be performed in conjunction with providing appropriate interventions. Treatment modalities for comorbid depression in patients with CKD have shown promising, albeit preliminary, results. Pharmacotherapies and psychotherapies are among the few interventions that can help relieve patients of their symptoms. Pharmacological treatment for patients with depression in the presence of CKD needs additional attention to avoid medical interactions with the already large number of renal medications. Extra care must be given to these patients to promote treatment adherence and address unhelpful illness and treatment perceptions.
It would also be important to more broadly consider the spectrum of emotional experience including anxiety, worrying, fear of progression of kidney disease, and fear of the future in general, demoralization, death and dying, hopelessness, questions around the meaning of life, and the experience of recurrent psychological and physical trauma through the disease trajectory, just to name a few.
**Disclosure**
The authors report no conflicts of interest in this work.
| null | minipile | NaturalLanguage | mit | null |
Islamic finance a boost for USAID's Afghan farm fund
February 07, 2013|Reuters
By Bernardo Vizcaino
SYDNEY, Feb 7 (Reuters) - Economic instability and legalobstacles have slowed the introduction of modern forms ofIslamic finance in Afghanistan. But sharia-compliant loans arebeginning to play a role in the farm sector through aU.S.-funded aid programme.
The Afghan government is using Islamic financial contractsto extend credit to farmers in areas where conventional bankinghas not fully satisfied demand for funds.
The Agricultural Development Fund (ADF), set up in 2010through a $100 million grant from the U.S. Agency forInternational Development (USAID), offers both conventionalcredit and Islamic financing.
About $11 million of its loans approved between May 2011 andApril 2012, or 70 percent of them, were sharia-compliant, theADF says. Islamic finance obeys a religious ban on payment ofinterest and instead pays lenders with returns on real assets.
Demand for such financing has been particularly strong inrural communities because people there tend to be conservative,said Juan Estrada-Valle, acting chief executive of the ADF.
In Afghanistan's conventional banking sector, officiallending rates hover around 15 percent, according to the WorldBank, and farmers have been forced to buy agricultural inputsfrom traders on credit at inflated margins that in some casesexceed 40 percent.
"Credit has the potential to revolutionise Afghanagriculture, enabling commercial farmers and otheragribusinesses to grow at a rapid pace and contribute to thegrowth of rural communities," Estrada-Valle said.
PERCEPTIONS
The ADF has had to overcome perception problems with itsIslamic contracts. Some customers and their religious advisorswere under the incorrect impression that Islamic loans should befree or cheaper than conventional ones.
While customers already knew of Islam's prohibition oninterest, borrowers had to be educated about other principlesincluding the fact that non-payment by a solvent borrower is asin, Estrada-Valle said.
The ADF's loan portfolio includes an all-women saffronassociation in Herat, apple farmers in Wardak province, and anindustrial-scale producer of agricultural machinery inJalalabad.
As of October 2012, the ADF had provided loans to more than15,000 farm households in 30 of Afghanistan's 34 provinces; itsays it expects to reach 60,000 farmers by the end of 2014.
Its Islamic contracts follow the Hanafi school of thought,the predominant version of Islamic law in Afghanistan. The fundhas so far developed five sharia-compliant contracts which caterto specific needs, said Natalie Schoon at British-basedfinancial consultancy Formabb, who was involved in the project.
One contract incorporates a down payment to allow hiring oflabour and tools for the harvest period; others are designedbearing in mind crop cycles.
Estrada-Valle said the ADF initially intended to make fundsavailable to local financial institutions for on-lending toagricultural enterprises, but the financial institutionsappeared not to have any appetite for this.
So the ADF changed its focus to lending throughnon-financial institutions to farmers as well asagriculture-related enterprises; typical intermediaries includeassociations, cooperatives and large-scale farm stores.
A law covering independent Islamic banks has yet to beapproved by Afghanistan's parliament, and this is hindering theoverall development of Islamic finance in the country. But sincethe ADF was set up as a fund, it is not subject to bankingregulations, Schoon said.
Last May, the central bank said it was considering issuingshort-term Islamic bonds, or sukuk, to help the government raisemoney and develop the financial markets. | null | minipile | NaturalLanguage | mit | null |
Q:
Castle Windsor Setting log level when logging to console
I'm new to Castle Windsor and am struggling to setup the initial log level of ConsoleLogger. The documentation gives some hints for log4net but is silent about logging to console.
My code looks as follows:
container.AddFacility<Castle.Facilities.Logging.LoggingFacility>(
f => f.LogUsing(Castle.Facilities.Logging.LoggerImplementation.Console));
Any hints how I can set the default log level of the facility to e.g. LoggerLevel.Warn?
Cheers
A:
I don't think that is supported if you take direct dependency on ILogger rather than ILoggerFactory. Feel free to request this in the issue tracker.
| null | minipile | NaturalLanguage | mit | null |
The Florida Panthers‘ arena in Broward County (I’m not going to go through the trouble of remembering its current corporate name) opened 19 years ago, at public expense, as a way to get the team to stay in the Miami area long-term. So, naturally, it’s time for the county to start thinking about tearing it down:
This week, Broward County embraced a development vision for the land, a potential playbook created by the Urban Land Institute… The institute’s land use experts said the county-owned BB&T Center, a giant venue surrounded by parking spaces, represents “an opportunity lost.’’
The main reason for hiring ULI is to figure out how to develop the land around the arena — which the county bought back for $86 million in 2015 — which would have been a better idea before spending the money, but better late than never. But that deal also handed Panthers owner Vincent Viola an out clause in his lease, so the consultants are also being tasked with figuring out what to do with the land if the team leaves:
The consultants explored three alternatives: the Panthers extend their lease, and a casino is added; the Panthers extend their lease, and office and housing are added; and the Panthers leave, the arena is demolished, and housing, a casino and offices are added. The third option would bring in the most tax revenue and income to the county, at an estimated $391.3 million over 11 years, the report said.
On the one hand, you could probably come up with more economically productive uses for the land than a hockey arena, assuming Broward County has much more time before it’s underwater. Though if the county ends up having to build the Panthers a new arena somewhere else to keep them after they opt out of their lease, that’s less helpful. That out clause really was as bad an idea as it sounded at the time. | null | minipile | NaturalLanguage | mit | null |
As the World Turns star Marie Wilson (ex-Meg Snyder) dishes on “playing detective” to bring her Ladies of the Lake character to life.
They say April showers bring May flowers, but this year, they brought murder and intrigue -- if you tune in to Amazon's upcoming series, Ladies of the Lake, that is.
The dramatic and downright scandalous mini-series co-produced by Kyle Lowder (ex-Brady Black, Days of our Lives) and Emmy-winning producer Michael Caruso, and based on the book of the same name written by DAYS' executive producer, Ken Corday, debuts on Monday, May 15. And series star Marie Wilson (ex-Meg Snyder, As the World Turns; ex-Summer Townsend, Days of our Lives) is thrilled the murder-filled project is finally coming to fans.
"I'm so excited to share this with everyone," she enthuses. "We had such a great time shooting this because there are scenes that are funny and dramatic and romantic. It's a fun ride that I feel everyone will enjoy."
Anyone who has read Corday's book of the same name knows that the four-part miniseries is chock-full of delicious drama that feels as if it could have been pulled from your favorite soap operas. After all, it's about four wealthy women who fantasize about killing their spouses -- and just may go through with their devilish plans.
"Even though the story is a little over the top, I think the core of these characters are relatable to any human being who feels fear, love, anger, pride, lust, or courage. At the center of all of us, we are the same -- making choices based on our feelings," Wilson explains, adding that her character, Morgan Firestone, couldn't help but be swept up in the murderous plot. "Morgan comes from the competitive 'pageant world' where friends are not easy to come by until one night when her whole world changes."
She continues: "All the characters in the story are so colorful and fun to play. I've never played a character like Morgan before, which made it even more enticing. She has a certain image to uphold, which makes her seem cold and standoffish, but there are layers to characters like that that intrigue me. There are so many sides to everyone, and I love playing detective and discovering and creating their story."
Of course, the real draw for Wilson was the incredible cast and crew who signed on to Ladies of the Lake.
"I enjoyed the script, and I wanted to work with all the people involved on the project: Ken Corday, Michael and Barbi Caruso, [Michael's wife]. Every single person on the set made the entire experience a dream job," she says, adding that her costars Jessica Morris (ex-Jennifer Rappaport, One Life to Live), Ari Zucker (Nicole Walker, DAYS), Lilly Melgar (ex-Lily Corinthos, General Hospital), and Martha Madison (ex-Belle Black, DAYS) were also amazing.
"I can't say enough great words about these girls," she gushes. "They were one of the reasons I wanted to work on this project. They are all talented, generous actors, and to have the opportunity to act with them, for me, was an honor. I looked forward to being on set every day, working as a team to create something magical. Love them!"
However, because she's just as much into fashion as the next Hollywood star, Wilson admits that the dazzling look and feel of Ladies of the Lake was also something that intrigued her -- as it's bound to do for fans, as well.
"I felt so glamorous every day, especially when I showed up in the morning in my jeans and T-shirt look, and then the talented hair and makeup artists transformed you into this diva. How fun!" she says of dressing for the part of Morgan each day. "The thought and details that were put into every character was so well done. It's a major part of their world, and it was portrayed perfectly."
For more Ladies of the Lake fun, be sure to tune in to the series when it premieres on Amazon on Monday, May 15. Anyone can watch the series for free on Amazon, and Amazon Prime members will be able to watch without ads. If you are not an Amazon Prime member, click here for a free 30-day trial.
Will you be tuning in to Ladies of the Lake? How much do you miss As the World Turns and Wilson's former character, Meg? We want to hear from you -- and there are many ways you can share your thoughts. | null | minipile | NaturalLanguage | mit | null |
951 P.2d 1283 (1998)
131 Idaho 56
STATE of Idaho, Plaintiff-Respondent,
v.
Adam P. SHERROD, Defendant-Appellant.
No. 22962.
Court of Appeals of Idaho.
January 2, 1998.
Rehearing Denied February 9, 1998.
*1284 E. Scott Paul, Blaine County Public Defender, Twin Falls, for Defendant-Appellant.
Alan G. Lance, Attorney General, Kenneth M. Robins, Deputy Attorney General (argued), Boise, for Plaintiff-Respondent.
LANSING, Chief Judge.
Adam P. Sherrod appeals from a judgment of conviction for aggravated battery, I.C. § 18-907. He argues that the district court gave an erroneous jury instruction which allowed the jury to find Sherrod guilty of a crime with which he was not charged. We find Sherrod's argument to be meritorious, and we hold that the variance between the charging instrument and the jury's instructions was fatal to this conviction.
FACTS
The charge against Sherrod stemmed from an incident that began as a barroom argument between Richard Grammatico and one of Sherrod's friends, Jeremy Riley. When Grammatico left the bar and started walking home, he was followed by Sherrod, Riley, and another of their friends. Grammatico was tackled from behind and, while he lay on the ground, Sherrod and his friends beat him. In the course of the beating, Grammatico was stabbed twice in the back. As a consequence of the beating and stabbing, Grammatico was treated for a punctured lung and other injuries, including numerous abrasions and cuts which required stitches.
Sherrod was arrested and charged with aggravated battery, I.C. §§ 18-903, -907, a felony. Medical testimony at trial established that the stab wounds which punctured Sherrod's lungs were caused by an instrument at least three or four inches long. The trial evidence included a knife that was discovered by police at the scene of the beating. Grammatico was not able to identify the individual who stabbed him, but other testimony indicated that Sherrod had borrowed the knife from a friend several months earlier. The jury found Sherrod guilty of aggravated battery, and a judgment of conviction for that offense was entered.
On appeal, Sherrod asserts that his conviction should be set aside because there was an impermissible variance between the charge alleged against him and the instructions given to the jury. This variance, he contends, allowed the jury to convict him of an offense different from that with which he was charged.
ANALYSIS
The existence of an impermissible variance between a charging instrument and jury instructions is a question of law over which we exercise free review. State v. Colwell, 124 Idaho 560, 565, 861 P.2d 1225, 1230 (Ct.App.1993) [hereinafter Colwell I]; State v. McBride, 123 Idaho 263, 266, 846 P.2d 914, 917 (Ct.App.1992).
Resolution of the issue raised by Sherrod requires close examination of the State's *1285 pleadings. The prosecutor's initial information charged Sherrod with aggravated battery on two alternative theories. It alleged that he had committed a battery "causing great bodily harm and/or permanent disfigurement, to wit: by stabbing Richard Grammatico in the back and/or kicking and beating Richard Grammatico in the head area, and/or splitting the upper and lower lip of Richard Grammatico, in violation of Idaho Code § 18-903(a), 18-907(a) and 18-204," or, in the alternative, "by means of a deadly weapon, to wit: a knife and/or bottle, in violation of Idaho Code § 18-903(a), 18-907(b), and 18-204." Part Two of the information alleged that Sherrod committed the offense with a deadly weapon, a knife, and was therefore subject to an enhanced penalty under I.C. § 19-2520.
Immediately before the trial, however, the State filed an amended information. It charged Sherrod with aggravated battery by alleging that he "did willfully and unlawfully use force or violence upon the person of Richard Grammatico, causing great bodily harm and/or permanent disfigurement, to wit: by stabbing Richard Grammatico in the back, in violation of Idaho Code § § 18-903(a), 18-907(a)." The amended information included the same penalty enhancement allegation that was found in the original information. This amendment thus made two noteworthy changes in the charge against Sherrod. First, it abandoned the allegation, found in the original information, that the battery was "aggravated" due to use of a deadly weapon, I.C. § 18-907(b). Instead, it charged aggravated battery only under I.C. § 18-907(a), which refers to battery that "causes great bodily harm, permanent disability or permanent disfigurement."[1] Second, the amended information limited the injury that was alleged to constitute "great bodily harm or permanent disfigurement" to stabbing in the back.
Sherrod contends that Instruction No. 19, which defined the elements of aggravated battery for the jury, did not limit the jury's consideration to the offense described in the amended information. He also asserts that the jury's written verdict establishes that it did, in fact, find him guilty of an offense different from that charged. Instruction No. 19 informed the jurors as follows:
In order for the defendant to be guilty of Aggravated Battery, the state must prove each of the following:
1. On or about the 18th day of October, 1994;
2. in the state of Idaho;
3. the defendant Adam Sherrod committed a battery upon Richard Grammatico; and
4. when doing so the defendant caused great bodily harm, or permanent disfigurement,
or
used a deadly weapon or instrument.
If any of the above has not been proven beyond a reasonable doubt, then you must find the defendant not guilty. If each of the above has been proven beyond a reasonable doubt, you must find the defendant guilty.
The verdict form asked the jury to determine whether Sherrod was guilty of aggravated battery and, if they responded affirmatively to the first question, whether he used a deadly weapon in the commission of the aggravated battery.[2] According to the responses on the verdict form, the jury found Sherrod guilty of aggravated battery, but also found that he did not use a deadly weapon in committing the crime.
*1286 Sherrod is correct in asserting that Jury Instruction No. 19 was not consistent with the charge alleged in the amended information. The instruction departed from the charged offense in two ways: it allowed the jury to find Sherrod guilty of aggravated battery by use of a deadly weapon pursuant to I.C. § 18-907(b), an allegation which was contained in the original information but not in the amended pleading; and it allowed the jury to find that Sherrod caused great bodily harm or permanent disfigurement based upon any of the injuries that may have been suffered by the victim, whereas the amended information specifically limited the alleged injury to stabbing in the back. Thus, there were two variances between the State's charging instrument and the jury instructions.
We must next determine whether these variances are fatal to the jury's verdict. Whether a discrepancy between a charging instrument and a jury instruction is a harmless imperfection in the trial or prejudicial error that requires reversal is a question of law subject to free review on appeal. Colwell I, 124 Idaho at 565, 861 P.2d at 1230; State v. McBride, 123 Idaho 263, 265, 846 P.2d 914, 916 (Ct.App.1992).
In State v. Windsor, 110 Idaho 410, 716 P.2d 1182 (1985), the Idaho Supreme Court held that a variance between a charging document and a jury instruction requires reversal "only when it deprives the defendant of his right to fair notice or leaves him open to the risk of double jeopardy." Windsor, 110 Idaho at 417-18, 716 P.2d at 1189-90. In the present case, we perceive no risk of double jeopardy, and therefore our analysis focuses on the fair notice prong of this standard. This notice element "requires courts to determine whether the record suggests the possibility that the defendant was misled or embarrassed in the preparation or presentation of his defense." Id. at 418, 716 P.2d at 1190.
As to that portion of Instruction No. 19 which improperly allowed the jury to find that the battery was aggravated by reason of use of a deadly weapon, we conclude that the variance was not prejudicial for two reasons. First, the amended information contained the sentence enhancement allegation that Sherrod had used a deadly weapon in the commission of the offense. Sherrod was thus on notice that the question whether he had wielded the knife in the attack would be a factual issue which he must address at trial. Second, in that portion of the jury verdict pertaining to the sentence enhancement issue, the jury found that Sherrod did not personally use a deadly weapon. From this finding, we can only conclude that the jury found the battery to be "aggravated" based upon the infliction of great bodily harm or permanent disfigurement and not based upon the use of the knife.[3] Therefore, the district court's error in instructing the jury on aggravated battery by use of a deadly weapon did not contribute to the jury's verdict finding Sherrod guilty of aggravated battery and does not require that the conviction be set aside.
We reach a different conclusion, however, with respect to the other error in Instruction No. 19, which allowed the jury to make a finding of great bodily harm based upon injuries other than stab wounds. The amended information charged that Sherrod committed battery and caused great bodily injury by stabbing the victim in the back, not by any other means. As noted above, however, the jury expressly found that Sherrod did not use the knife. It follows that the jury necessarily found that Sherrod committed battery and inflicted great bodily harm or permanent disfigurement based upon injuries other than the stabbing. In sum, the jury's responses to the two questions on the verdict form show that Sherrod was found guilty of an offense different from that with which he was charged under the amended information.
Under Idaho statutes, a criminal defendant is entitled to be apprised by the *1287 charging instrument not only of the name of the offense charged but in general terms of the manner in which it is alleged to have been committed. See I.C. §§ 19-1303, -1409 (charging instrument must contain a statement of the acts constituting the offense); I.C. § 19-1411 (charging instrument must be direct and certain as it regards the particular circumstances of the offense charged); State v. McMahan, 57 Idaho 240, 246-47, 65 P.2d 156, 158 (1937) (An information must not only state the name of the alleged crime but also inform the accused as to how it is claimed he committed the offense.). Further, conviction of a crime different from that charged is a denial of due process guaranteed by the Fourteenth Amendment to the United States Constitution and Art. I, § 13 of the Idaho Constitution. State v. Cariaga, 95 Idaho 900, 902, 523 P.2d 32, 34 (1974); McMahan, 57 Idaho at 250, 65 P.2d at 160; State v. Gilman, 105 Idaho 891, 893, 673 P.2d 1085, 1087 (Ct.App.1983).
It is an inescapable conclusion that the variance between the charging instrument and the jury instructions in this case prejudiced Sherrod in the presentation of his defense. After the amendment of the information, Sherrod was not on notice that he was alleged to have inflicted any of the injuries other than the stab wounds. In particular, he was not on notice of a need to present evidence or argument that the victim's other injuries were of insufficient severity to amount to great bodily harm or permanent disfigurement. However, in view of the jury's answers to both questions on the verdict form, it is apparent that the jury found Sherrod guilty of battery for inflicting those other injuries, and also deemed those injuries to constitute great bodily harm or permanent disfigurement for purposes of elevating the offense from misdemeanor battery to aggravated battery. Hence, we conclude that the variance between the allegations of the amended information and the jury instructions was reversible error.
Ordinarily, the remedy for erroneous jury instructions is to afford the appellant a new trial. See State v. Chapa, 127 Idaho 786, 790, 906 P.2d 636, 640 (Ct.App.1995); Colwell I, 124 Idaho at 567, 861 P.2d at 1232; State v. Pinkney, 115 Idaho 1152, 1154, 772 P.2d 1246, 1248 (Ct.App.1989); State v. Spurr, 114 Idaho 277, 280, 755 P.2d 1315, 1318 (Ct.App.1988). Under the unique circumstances presented here, however, we conclude that collateral estoppel precludes retrial of Sherrod for the offense charged in the amended information.
Collateral estoppel, or issue preclusion, "means simply that when an issue of ultimate fact has once been determined by a valid and final judgment, that issue cannot again be litigated between the same parties in any future lawsuit." Ashe v. Swenson, 397 U.S. 436, 443, 90 S.Ct. 1189, 1194, 25 L.Ed.2d 469 (1970). Such a determination of a factual issue will preclude its relitigation if the resolution of that issue was necessary to support the prior judgment. Schiro v. Farley, 510 U.S. 222, 114 S.Ct. 783, 127 L.Ed.2d 47 (1994). This principle of issue preclusion applies in criminal as well as civil cases. Schiro, supra; Ashe, supra; State v. Powell, 120 Idaho 707, 708, 819 P.2d 561, 562 (1991); State v. Colwell, 127 Idaho 854, 908 P.2d 156 (Ct.App.1995). Indeed, the United States Supreme Court has held that the doctrine of collateral estoppel is embodied in the Fifth Amendment's guarantee against double jeopardy. Ashe, 397 U.S. at 445, 90 S.Ct. at 1195.
Here, the amended information charged Sherrod with committing aggravated battery causing great bodily harm or permanent disfigurement "by stabbing Richard Grammatico in the back." The jury found that Sherrod did not use the knife, the instrument which, according to the prosecution, inflicted the stab wounds in the attack on Grammatico. The issue whether Sherrod "stabb[ed] Richard Grammatico in the back" has thus been decided by a jury adversely to the State. That finding was necessary to support the judgment that Sherrod was not subject to a sentence enhancement for use of a deadly weapon. Therefore, the State is *1288 now collaterally estopped from retrying that issue on an allegation that Sherrod committed aggravated battery by stabbing Grammatico in the back, the sole charge in the amended information.
For the foregoing reasons, the judgment of conviction for aggravated battery is reversed.
PERRY, J., and WALTERS, Acting J., concur.
NOTES
[1] I.C. § 18-907 states:
A person commits aggravated battery who, in committing battery:
(a) Causes great bodily harm, permanent disability or permanent disfigurement; or
(b) Uses a deadly weapon or instrument; or
(c) Uses any vitriol, corrosive acid, or a caustic chemical of any nature; or
(d) Uses any poison or other noxious or destructive substance or liquid.
[2] The jury was not instructed that Sherrod could be found guilty if he aided and abetted others in the commission of the charged offense.
[3] The knife was the only instrument that was asserted by the prosecutor to be a deadly weapon, and the trial evidence suggests no other weapon that could have inflicted the stab wounds.
| null | minipile | NaturalLanguage | mit | null |
DevTools Digest December 2013
A number of updated features have made it into the Chrome DevTools recently, some small, some big. We'll start out with the Element panel's updates and move on to talk about Console, Timeline, and more.
Disabled style rules copy as commented out
Copying entire CSS rules in the Styles pane will now include styles you toggled off, they will exist in your clipboard as commented out. [crbug.com/316532]
Copy as CSS path
‘Copy as CSS path’ is now available as a menu item for DOM nodes in the Elements panel (similar to the Copy XPath menu item).
Generation of CSS selectors do not have to be limited to your stylesheets/JavaScript, they can also be alternatives for locator strategies in WebDriver tests. [crbug.com/277286]
Regex filter for console
Easily remove event listeners
Try getEventListeners(document).mousewheel[0]; in the Console panel to retrieve the first mousewheel event listener on the document. Carrying on from this, try $_.remove(); to remove that event listener ($_ = value of the most recently evaluated expression). [crbug.com/309524]
Removal of CSS warnings
Those "Invalid CSS property value"-style warnings you might have seen are now removed. There are ongoing efforts into making the implementation more robust against real world CSS including browser hacks. [crbug.com/309982]
Timeline operations summarized in pie chart
The Timeline panel now contains a pie chart in the Details pane which visually shows the source of your rendering costs - this helps you identify your bottlenecks at a glance.
You’ll find that much of the information which used to be displayed in popovers has now been promoted to its own pane. To view, start a Timeline recording and select a frame, take note of the new Details pane which contains a pie chart. When in Frames view, you’ll get interesting stats like average FPS (1000ms/frame duration) for the selected frame(s). [crbug.com/247786]
Image resize event details
Image resize and decode events in the Timeline panel now contain a link to the DOM node in the Elements panel.
The Image URL link takes you to the corresponding resource in the Resources Panel. [crbug.com/244159]
GPU Frames
Frames occurring on the GPU are now shown at the top, above frames on the main thread. [crbug.com/305863]
Break on popstate listeners
Rendering settings available in the drawer
Opening the drawer now presents a number of panes, one of which is the Rendering panel, use it to show paint rectangles, FPS meter etc. This is enabled by default at Settings > "Show 'Rendering' view in console drawer"
Copy image as data URL
Image assets in the Resources panel can now have their contents copied as a data URI (data:image/png;base64,iVBO...).
To try this out, find the image resource within Frames > [Resource] > Images and right click on the image preview to access the context menu, then select ‘Copy Image as Data URL’. [crbug.com/321132]
Data URI filtering
If you've never thought they belong, Data URIs can now be filtered out of the Network tab. Select the Filter icon to view other resource filter types. [crbug.com/313845]
Network Timing bugs fixed
If you saw your image apparently taking 300,000 years to download, our apologies. ;) These incorrect timings for network resources have now been fixed. [crbug.com/309570]
Network recording behavior has more control
The behavior of recording network is a little different. First, the record button acts just like you would expect from Timeline or a CPU profile. And because you'd expect it, if you reload the page while DevTools is open, network recording will automatically start. It'll then turn off, so if you want to capture network activity after page load, turn it on. This makes it easier to visualize your waterfall without late-breaking network requests skew the results. [crbug.com/325878]
DevTools themes now available through extensions
User stylesheets are now available through DevTools Experiments (checkbox: "Allow custom UI themes") which allows a Chrome extension to apply custom styling to DevTools. See Sample DevTools Theme Extension for an example. [crbug.com/318566]
That’s it for this edition of the DevTools digest, if you haven’t already, check out the November edition. | null | minipile | NaturalLanguage | mit | null |
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Provided courtesy of The Coastal Carolinas Association of REALTORS®. Information Deemed Reliable but Not Guaranteed. Copyright 2019 of the Coastal Carolinas Association of REALTORS® MLS. All rights reserved. Information is provided exclusively for consumers’ personal, non-commercial use, that it may not be used for any purpose other than to identify prospective properties consumers may be interested in purchasing. | null | minipile | NaturalLanguage | mit | null |
After a 2-0 start, the DC Defenders are the hottest team in the XFL and head coach Pep Hamilton's no-nonsense approach is one of the main reasons.
The former NFL coordinator preaches the importance of accountability and leads by example. On Tuesday, Hamilton was seen running side by side with his team post-practice.
“We are a team. Everybody will be held to a certain standard," Hamilton said. "Accountability is the foundation of teamwork. A lack of focus at times is on me, it’s on the coach. We have to come out here everyday and understand that every play can be the difference in a game.“
Quarterback Cardale Jones describes the culture Hamilton is building within the locker room as “a tough one, one that is uncomfortable. A tough hardnose blue collar culture.”
Seeing his coach run with the team, Jones believes, sends a clear message: “We will be held accountable for our actions and everything matters. That's why we run extra after practice. We can’t get complacent as a team.”
The former Ohio State quarterback has not only become one of the faces, if not the face, of the XFL but also a leader on the Defenders, according to Hamilton.
“He’s making plays on gameday. He’s helping the team win, and the guys recognize he’s ultimately going to play a major factor into whether we win or lose a game, and he’s done his job up to this point,” Hamilton said.
Despite the hype surrounding his name, Jones humbly describes himself as “a player trying to get better each and every week.”
This week, the Defenders are aiming to go 3-0 as they head across the country for their first road game against the 0-2 Los Angeles Wildcats on Sunday. LA's record doesn't reflect the kind of team Hamilton is preparing to go up against.
“We are getting ready to play a really good LA Wildcats team," he said. "Their record is not indicative in the leadership they have in their head coach and/or in the players they have on their team. They have a really good team.”
Jones continued, “We have to be able to run the football. We have to continue to challenge ourselves and honor our technique. Doing the little things right.”
Click here to download the MyTeams App by NBC Sports. Receive comprehensive coverage of your teams and stream Capitals and Wizards games easily from your device.
MORE DEFENDERS NEWS: | null | minipile | NaturalLanguage | mit | null |
Mobile gantry cranes are often required to lift loads at four or more lifting points. In these cases, the crane is supplied with a dual trolley and hook block assembly. The typical dual trolley arrangement has an unadjustable fixed distance between the trolleys. This can be a disadvantage if the distance between the lift points on a product to be lifted varies. For this reason, a system that allows for the multiple trolleys to be independently powered so as to allow for an adjustment of the distance between lift points would be an important improvement in the art. | null | minipile | NaturalLanguage | mit | null |
Homeopathic Materia Medica
VACCININUM
(vac)
(Nosode-From vaccine matter)
Vaccine poison is capable of setting up a morbid state of extreme chronicity, named by Burnett Vaccinosis, symptoms like those of Hahnemann's Sycosis. Neuralgias, inveterate skin eruptions, chilliness, indigestion with great flatulent distension (Clark). Whooping-cough.
Mind
Irritable, impatient ill-humored, nervous.
Head
Frontal headache. Forehead and eyes feel as if split. Inflamed and red lids. | null | minipile | NaturalLanguage | mit | null |
diapsid reptile
Diapsid
Diapsids ("two arches") are a group of reptiles that developed two holes (temporal fenestra) in each side of their skulls, about 300 million years ago during the late Carboniferous period. Living diapsids are extremely diverse, and include all crocodiles, lizards, snakes, and tuatara. Under modern classification systems, even birds are considered diapsids, since they evolved from diapsid ancestors and are nested within the diapsid clade. While some diapsids have lost either one hole (lizards), or both holes (snakes), or even have a heavily restructured skull (modern birds), they are still classified as diapsids based on their ancestry. There are at least 7,925 species of diapsid reptile existing in environments around the world today (over 14,600 when birds are included).
Characteristics
The name Diapsida means "two arches", and diapsids are traditionally classified based on their two ancestral skull openings (temporal fenestrae) posteriorly above and below the eye. This arrangement allows for the attachment of larger, stronger jaw muscles, and enables the jaw to open more widely. A more obscure ancestral characteristic is a relatively long lower arm bone (the radius), compared to the upper arm bone (humerus).
Systematics
Diapsids were originally classified as one of four subclasses of the class Reptilia, all of which were based on the number and arrangement of openings in the skull. The other three subclasses were Synapsida (one opening low on the skull, for the "mammal-like reptiles"), Anapsida (no skull opening, including turtles and their relatives), and Euryapsida (one opening high on the skull, including many prehistoric marine reptiles). With the advent of phylogenetic nomenclature, this system of classification was heavily modified. The Synapsids today are often not considered true reptiles, while the Euryapsida was found to be an unnatural assemblage of diapsids that had lost one of their skull openings. Some studies have suggested that this is the case in turtles as well, and that turtles are actually heavily modified diapsids, which would leave only some prehistoric forms in the Anapsida. In phylogenetic systems, birds (descendants of traditional diapsid reptiles) are also considered to be members of this group.
Well known extinct diapsid groups include the dinosaurs, pterosaurs, plesiosaurs, mosasaurs, and many more obscure lineages. The classification of most of the early groups is fluid and subject to change. | null | minipile | NaturalLanguage | mit | null |
Source Filmmaker
I don't know if the title explains better that I will, but I'll try my best:
I'm actually using the Motion Editor as in the SFM tutorial "Pose to pose animation" but the first pose I made is the one "by default" for SFM = When I select a region of time after the first pose and I pose it as I want to, it's okay. But when I get to a region of time AFTER the second one, the "pose by default" appears (that means, the very first pose I made is here again.
My question is; how can I make the last pose I make, being the pose that'll appear when I'll pose in the next region of time?
(Sorry for my english, don't really know how to say that :c If you want to help me but don't understand, I'll try to explain even better ^^")
if you have all time selected (the entire motion editor (ME) green) whatever pose you do will last the entire time. if you make a pose with the entire ME green, then just select a small section ( a little patch of green instead of the entire ME) and change the pose there, as soon as the playhead leaves that part, the pose will automatically switch back to the previous pose.
Nah, I don't have the entire time selected, each poses that I already have are good and they all play correctly. But let's say I have 6 poses. The FIRST one, is also the last one by default. So that means, when I put the playhead after the last pose I set; it's still the first one, and that "asks" me to repose the whole character, from the first of the first pose, not the sixth.It's time for me to go to bed now, but I'll try to put screens here tomorrow x)
When you created the first pose, 0-10, you most likely had all of time selected. So the scout stays in the finish pose forever. When you posed 79-86, you most likely only had that period of time selected, therefore as soon as the 86 seconds is up, the scout snaps back to pose 1. When you did 79-86, you should have picked time from 79 to inifinity.
Depends on what yo want to happen... You can select the broken point of time, scrub the playhead until to find a pose that is close to what you want and zero the playhead. You can do the samething and send him back into his default (load pose), you select the period of time ramp an animation into it... The possibilities are endless.Watch this...http://youtu.be/pwg8m__LzzA
When I go further in the timeline, I gotta see the last pose I made so, I'll be able to pose, select another time region, pose, select another time region.. without having to repose the whole character like the last pose. Just moving what I want to change between frames.But right now, my "default" pose is the one I showed earlier.
I'm so sorry but I still gotta understand more the "talked-English", though I clearly understand the "written" and that's why I'm bothering you right now ^^"
Well, I think I did what you told me to do, but each time I pose, I gotta redo that step: "Or you could select the period of time you need to change then move the playhead to the pose that you want the character in (somewhere on the time line then slide the playhead slider." to get the last pose. That's not automatic ^^"
If you are working left to right on the time line, Each new pose goes to the end of time. So, starting with the first pose, you would select the left edge of time and ramp out your pose, the right side of time goes to infinity. You make your 1st pose. Now you select the left side of time for the 2nd pose. Of course the model will be in it's 1st pose position. The right side of time extends to infinity, Ramp the left of time into your 1st pose to create the transition and make your second pose. anow do the same for your third pose, the character will be in the 2nd pose position, and so on and so on and so on. Understand? Each new pose has the right side of time extended to infinity. | null | minipile | NaturalLanguage | mit | null |
The influence of age and sex on bone resorption of secondary hyperparathyroidism in renal osteodystrophy.
The severity and incidence of subperiosteal and intracortical bone resorption were evaluated from fine-detail hand radiographs at X 8 magnification in relation to age and sex in 239 chronically dialyzed adult renal failure patients. The severity of subperiosteal resorption decreased significantly with advancing age in both sexes and the incidence decreased somewhat more in males than in females; no such trends were apparent for intracortical resorption. Although the mean values for the grades of subperiosteal and intracortical resorption were significantly higher in females than in males, when the effect of age and duration of follow-up were taken into consideration, this sex difference remained significant only for intracortical resorption. It is concluded that when studying certain aspects of renal osteodystrophy, differences due to age, sex, and duration of follow-up should be considered in the final interpretation of data. | null | minipile | NaturalLanguage | mit | null |
(** Formation of conversions *)
open Nucleus_types
let is_term_convert_opt sgn e (EqType (asmp, t1, t2)) =
match e with
| TermConvert (e, asmp0, t0) ->
if Alpha_equal.is_type t0 t1 then
(* here we rely on transitivity of equality *)
let asmp = Assumption.union asmp0 (Assumption.union asmp (Collect_assumptions.is_type t1))
(* we could have used the assumptions of [t0] instead, because [t0] and [t1] are
alpha equal, and so either can derive the type. Possible optimizations:
(i) pick the smaller of the assumptions of [t0] or of [t1],
(ii) pick the asumptions that are included in [t2]
(iii) remove assumptions already present in [t2] from the assumption set
*)
in
(* [e] itself is not a [TermConvert] by the maintained invariant. *)
Some (Mk.term_convert_panic e asmp t2)
else
None
| (TermAtom _ | TermBoundVar _ | TermConstructor _ | TermMeta _) as e ->
let t0 = Sanity.natural_type sgn e in
if Alpha_equal.is_type t0 t1 then
(* We need not include assumptions of [t1] because [t0] is alpha-equal
to [t1] so we can use [t0] in place of [t1] if so desired. *)
(* [e] is not a [TermConvert] by the above pattern-check *)
Some (Mk.term_convert_panic e asmp t2)
else
None
let is_term_convert sgn e (EqType (_, t1, _) as eq) =
match is_term_convert_opt sgn e eq with
| Some e -> e
| None ->
let t0 = Sanity.natural_type sgn e in
Error.raise (InvalidConvert (t0, t1))
let eq_term_convert_opt (EqTerm (asmp1, e1, e2, t0)) (EqType (asmp2, t1, t2)) =
if Alpha_equal.is_type t0 t1 then
(* We could have used the assumptions of [t0] instead of [t1], see comments in [form_is_term]
about possible optimizations. *)
let asmp = Assumption.union asmp1 (Assumption.union asmp2 (Collect_assumptions.is_type t1)) in
Some (Mk.eq_term asmp e1 e2 t2)
else
None
let eq_term_convert (EqTerm (_, _, _, t0) as eq1) (EqType (_, t1, _) as eq2) =
match eq_term_convert_opt eq1 eq2 with
| Some eq -> eq
| None -> Error.raise (InvalidConvert (t0, t1))
| null | minipile | NaturalLanguage | mit | null |
Narita S, Nomura K, Hatakeyama S, et al. Changes in conditional net survival and dynamic prognostic factors in patients with newly diagnosed metastatic prostate cancer initially treated with androgen deprivation therapy. Cancer Med. 2019;8:6566--6577. 10.1002/cam4.2502
**Funding information**
The authors received no specific funding for this work.
1. INTRODUCTION {#cam42502-sec-0005}
===============
Prostate cancer is the most common malignancy in men and the sixth leading cause of cancer‐related death worldwide.[1](#cam42502-bib-0001){ref-type="ref"} The widespread application of prostate‐specific antigen (PSA) screening has resulted in an increase in the identification of early stage prostate cancer and a reduction of metastatic prostate cancer; in Western counties, metastatic prostate cancer is found in approximately 4% of prostate cancer patients at the time of diagnosis.[2](#cam42502-bib-0002){ref-type="ref"}, [3](#cam42502-bib-0003){ref-type="ref"}, [4](#cam42502-bib-0004){ref-type="ref"} Newly diagnosed metastatic prostate cancer is generally an aggressive disease; conventional androgen deprivation therapy (ADT)‐resistant cancer (known as castration‐resistant prostate cancer) can develop, eventually proving lethal. However, patients with metastatic prostate cancer form a very heterogeneous population, with considerable variation in the response, adverse events, and clinical outcomes.[2](#cam42502-bib-0002){ref-type="ref"}
Recently, large randomized trials have demonstrated a significant benefit to the overall survival (OS) of patients with metastatic hormone‐naïve prostate cancer (mHNPC) from the administration of additional upfront docetaxel and abiraterone acetate treatment.[5](#cam42502-bib-0005){ref-type="ref"}, [6](#cam42502-bib-0006){ref-type="ref"}, [7](#cam42502-bib-0007){ref-type="ref"} The treatment strategy for patients with newly diagnosed mHNPC has changed in recent years. Thus, an accurate assessment of prognosis is critical for clinical decision‐making and for providing information to patients with newly diagnosed mHNPC.
Previous studies have reported survival outcomes for patients with mHNPC that were estimated at the time of diagnosis or initial treatment.[8](#cam42502-bib-0008){ref-type="ref"}, [9](#cam42502-bib-0009){ref-type="ref"}, [10](#cam42502-bib-0010){ref-type="ref"} However, the risk of death changes over time, so the survival probability for patients who have survived for several years may change, and cancer‐specific survival (CSS) and OS rates may not be sufficiently informative for these patients. Conditional survival, which assesses the changing hazard rate as survival time increases,[11](#cam42502-bib-0011){ref-type="ref"}, [12](#cam42502-bib-0012){ref-type="ref"} provides a dynamic risk assessment and more accurate survival information for patients who have already survived for several years. Conditional survival analysis has been applied to assess the prognosis for a number of cancers, including metastatic cancers[13](#cam42502-bib-0013){ref-type="ref"}, [14](#cam42502-bib-0014){ref-type="ref"}; however, only a small number of studies have investigated conditional survival for prostate cancer, especially metastatic prostate cancer.[15](#cam42502-bib-0015){ref-type="ref"}, [16](#cam42502-bib-0016){ref-type="ref"} Net survival, which measures the survival that would be observed if the only possible cause of death was the disease of interest, provides the most appropriate method of estimating survival from cancer.[17](#cam42502-bib-0017){ref-type="ref"}, [18](#cam42502-bib-0018){ref-type="ref"} The newly developed Pohar Perme estimator has been shown to provide unbiased net survival estimates that are more accurate than classical relative survival estimates.[19](#cam42502-bib-0019){ref-type="ref"} However, there is little evidence regarding estimates of conditional survival using an unbiased Pohar Perme estimator in cancer populations.[20](#cam42502-bib-0020){ref-type="ref"}, [21](#cam42502-bib-0021){ref-type="ref"}
In this multicenter retrospective cohort study, we evaluated changes in conditional net survival in patients with mHNPC initially treated with ADT, at time points from 1 to 5 years after the initial diagnosis, using the Pohar Perme estimator. We also evaluated the impact of potential prognostic factors on CSS and OS in this study population.
2. MATERIALS AND METHODS {#cam42502-sec-0006}
========================
2.1. Patients {#cam42502-sec-0007}
-------------
This retrospective multicenter study was conducted at nine medical institutions in the Tohoku region of Japan. A consecutive group of adult patients diagnosed with mHNPC between March 2008 and May 2016 was retrospectively identified at each institute; in total, this included 629 patients. All the patients initially received ADT, which comprised orchiectomy and luteinizing hormone‐releasing agonists/antagonists alone or combined with bicalutamide. No patient received upfront docetaxel and/or abiraterone acetate as an initial therapy. Sequential treatments were administered after first‐line ADT at the physician\'s discretion. The study was approved by each institution\'s ethics committee. An opt‐out method for consent was adopted, in which patients were informed of their inclusion in the study and were provided information on the institution\'s website.
2.2. Assessment {#cam42502-sec-0008}
---------------
Continuous variables for the study cohort are presented as mean ± standard deviation or as medians with interquartile ranges (IQRs), and categorical variables as counts and percentages. The variables in the data set comprised the following patient characteristics at the time of diagnosis: age; body mass index (BMI; kg/m^2^); Eastern Cooperative Oncology Group Performance Status score (ECOG‐PS); biopsy Gleason score; site of metastasis (visceral, lymph node, or bone); presence of bone pain; bone metastasis extent of disease (EOD) score; types of initial hormonal therapy; implementation of local treatment; levels of serum biomarker PSA, hemoglobin (Hb), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and date of cause‐specific death or all‐cause death. ECOG‐PS and the presence of bone pain were evaluated by inquiry and physical examination. EOD scores were classified according to the definition of Soloway et al[22](#cam42502-bib-0022){ref-type="ref"} using bone scintigraphy at the time of the initial diagnosis.
Study enrollment is summarized in Figure [1](#cam42502-fig-0001){ref-type="fig"}. Of the initial 629 patients, 24 were excluded because of missing values on survival outcome. The remaining 605 patients comprised the subjects in our analyses.
{#cam42502-fig-0001}
2.3. Statistical analyses {#cam42502-sec-0009}
-------------------------
CSS and OS were calculated as the time from the diagnosis of mHNPC to death from prostate cancer or from any other cause. Patients known to be alive or lost to follow‐up on the date of last contact were censored. To estimate CSS and OS, we used conditional survival, the multiplicative probability, indicating that 5‐year conditional survival represents the probability of surviving an additional 5 years, given that the patient has already survived *x* years (where *x* is the time elapsed since the diagnosis of mHNPC). Net survival, a non‐parametric unbiased estimator, was used as a measure of conditional survival, calculated by using the "stns" command in Stata statistical software.[19](#cam42502-bib-0019){ref-type="ref"}, [23](#cam42502-bib-0023){ref-type="ref"} The Kaplan‐Meier method was applied to depict CSS and OS curves, which were compared using the log‐rank test. We applied Kaplan‐Meier survival analysis to calculate CSS and OS conditional probabilities.[12](#cam42502-bib-0012){ref-type="ref"}, [24](#cam42502-bib-0024){ref-type="ref"}
Factors associated with the CSS and OS were investigated by using Cox multivariate models. Multiple imputations of missing values of covariates (PSA, Hb, ALP, LDH, and BMI, EOD score, the presence of bone pain, ECOG‐PS, Gleason score, local treatment, luteinizing hormone‐releasing treatment) by chained equations (number of imputations, 200) were performed using the "MI" procedures in SAS statistical software, assuming the mechanism of missingness at random.
In the Cox regression models, PSA levels were categorized as high or low according to whether they were above or below the median value of its distribution at baseline (297 ng/mL). The other serum biomarkers were divided into binary groups according to whether they were above or below the following median values of the normal ranges for Japanese men[25](#cam42502-bib-0025){ref-type="ref"}, [26](#cam42502-bib-0026){ref-type="ref"}, [27](#cam42502-bib-0027){ref-type="ref"}: HGB (≤12 g/dL vs \>12 g/dL\<), ALP (\>350 IU vs ≤350 IU), and LDH (\>220 IU vs ≤220 IU). After entering all potential predictors for CSS and OS, we ran backward selection based on type III score[28](#cam42502-bib-0028){ref-type="ref"} chi‐square test statistics to identify the most suitable models. We then checked whether the selected variables satisfied the proportional hazard assumption and calculated the hazard ratio and 95% confidence interval (CI). In the final models, we calculated the hazard ratio and 95% CI of each covariate for conditional net survival.
Statistical analyses were performed using SPSS ver. 19.0, Stata ver. 14, and SAS ver. 9.4. A *P*‐value \< .05 was considered statistically significant.
3. RESULTS {#cam42502-sec-0010}
==========
3.1. Patient characteristics {#cam42502-sec-0011}
----------------------------
Table [1](#cam42502-tbl-0001){ref-type="table"} shows the patients\' characteristics. For the 605 patients analyzed, the mean age was 72 ± 8.6 years. The mean BMI and median baseline PSA level were 22.7 ± 3.6 kg/m[2](#cam42502-bib-0002){ref-type="ref"} and 295.0 ng/mL (IQR 68.1‐854.8 ng/mL), respectively. Regarding metastatic sites, 90.9%, 51.4%, and 11.6% of the patients had bone, lymph node, and visceral metastases, respectively. The percentages of patients with EOD scores of 1, 2, and ≥3 were 34.1%, 26.5%, and 30.3%, respectively. A combined androgen blockade was used for 81.6% of the patients, and 16.1% were treated using luteinizing hormone‐releasing antagonists.
######
Patient characteristics at the time of diagnosis
Variables n = 605
----------------------------------------------------------- ---------------------
Age, y, mean (SD) 72 (8.6)
BMI, kg/m^2^, mean (SD) 22.7 (3.6)
Missing (n = 158)[\*](#cam42502-note-0003){ref-type="fn"} 23.1 (0.5)
ECOG‐PS, n (%)
0 333 (57.9)
≥1 242 (42.1)
Missing[\*](#cam42502-note-0003){ref-type="fn"} 30
Biopsy Gleason score, n (%)
≤8 256 (45.2)
≥9 311 (54.9)
Missing[\*](#cam42502-note-0003){ref-type="fn"} 38
Site of metastasis, n (%)
Bone 550 (90.9)
Lymph node 311 (51.4)
Visceral 70 (11.6)
Presence of bone pain, n (%)
Yes 212 (38.3)
No 341 (61.7)
Missing[\*](#cam42502-note-0003){ref-type="fn"} 52
EOD score, n (%)
0 55 (9.1)
1 206 (34.1)
2 160 (26.5)
3 130 (21.5)
4 53 (8.8)
Missing[\*](#cam42502-note-0003){ref-type="fn"} 1
Serum markers
Baseline PSA level, ng/ml, median (IQR) 295.0 (68.1‐854.8)
Missing (n = 7)[\*](#cam42502-note-0003){ref-type="fn"} 297.3 (68.1‐865.3)
Baseline Hb level, g/dl, median (IQR) 13.4 (11.7‐14.4)
Missing (n = 52)[\*](#cam42502-note-0003){ref-type="fn"} 13.4 (11.7‐14.5)
Baseline ALP level, IU, median (IQR) 351.0 (248.0‐791.0)
Missing (n = 60)[\*](#cam42502-note-0003){ref-type="fn"} 352.0 (238.0‐883.0)
Baseline LDH level, IU, median (IQR) 210.0 (179.0‐262.0)
Missing (n = 116)[\*](#cam42502-note-0003){ref-type="fn"} 213.0 (176.0‐288.0)
Hormone therapy
LHRH antagonist
Yes 97 (16.1)
No 506 (83.9)
Missing[\*](#cam42502-note-0003){ref-type="fn"} 2
Combined with antiandrogen
Yes 492 (81.6)
No 111 (18.4)
Missing[\*](#cam42502-note-0003){ref-type="fn"} 2
Local treatment
Yes 36 (6.0)
No 565 (94.0)
Missing[\*](#cam42502-note-0003){ref-type="fn"} 4
Abbreviations: ALP, alkaline phosphatase; BMI, body mass index; ECOG‐PS, Eastern Cooperative Oncology Group Performance Status; EOD, extent of bone disease; Hb, hemoglobin; IQR, Interquartile range; PSA, prostate‐specific antigen; LDH, lactate dehydrogenase; LHRH, Luteinizing hormone‐releasing hormone
Summary statistics for variables in the imputed datasets (200 imputations).
John Wiley & Sons, Ltd
3.2. Treatment outcome {#cam42502-sec-0012}
----------------------
During the follow‐up period (median, 2.95 years), a total of 208 patients died, 169 from prostate cancer. The 5‐year CSS and OS for all the patients were 65.5% and 58.2%, respectively. In the univariate analyses at baseline, the following were significantly associated with CSS and OS: BMI ≤18.5 kg/m^2^, ECOG‐PS ≥1, biopsy Gleason score ≥9, EOD score ≥2, low Hb level at baseline, high ALP level at baseline, and high LDH level at baseline (See Tables [S1](#cam42502-sup-0005){ref-type="supplementary-material"} and [S2](#cam42502-sup-0006){ref-type="supplementary-material"}). In addition, the presence of lymph node metastasis was significantly associated with CSS, and age ≥73 years was significantly associated with OS. The multivariate analysis showed that biopsy Gleason score ≥9, EOD score ≥2, low Hb level at baseline, and high LDH level at baseline were independent prognostic factors for CSS and OS. BMI ≤18.5kg/m^2^ and ECOG‐PS ≥1 were also independent prognostic factors for OS and the presence of lymph node metastasis was an independent factor for CSS.
3.3. Conditional survival {#cam42502-sec-0013}
-------------------------
Table [2](#cam42502-tbl-0002){ref-type="table"} and Table [S3](#cam42502-sup-0007){ref-type="supplementary-material"} present the conditional 5‐year net CSS and OS rates. The overall conditional 5‐year net CSS rate at baseline was 0.656, and the overall conditional 5‐year net CSS rates (with the difference from baseline) for patients who survived for 1, 2, 3, 4, and 5 years were 0.645 (−0.11), 0.683 (+0.27), 0.652 (−0.04), 0.802 (+1.06), and 0.906 (+2.10), respectively (Table [S3](#cam42502-sup-0007){ref-type="supplementary-material"}). The overall conditional 5‐year net OS rate at baseline was 0.582, and the overall conditional 5‐year net OS rates for patients who survived for 1, 2, 3, 4, and 5 years were 0.566 (−0.16), 0.615 (+3.3), 0.550 (−0.32), 0.702 (+1.2), and 0.811 (+2.29), respectively (Table [2](#cam42502-tbl-0002){ref-type="table"}). Kaplan‐Meier curves of conditional CSS and OS are shown in Figure [2](#cam42502-fig-0002){ref-type="fig"} and Figure [S1](#cam42502-sup-0001){ref-type="supplementary-material"}. These results demonstrated that conditional 5‐year CSS and OS rates gradually improved compared to baseline for at least 5 years after the initial ADT.
######
Conditional 5‐y net overall survival of patients in relation to clinical and tumor characteristics
Baseline 1 y 2 y 3 y 4 y 5 y
--------------------------------------------------------- --------------------------- ---------------------------- ---------------------------- ---------------------------- ---------------------------- ----------------------------
Cohort, n 605 488 341 249 165 112
5‐y CS rates 0.582 (95%CI:0.521‐0.643) 0.566 (95%CI:0.493‐0.639) 0.615 (95%CI:0.525‐0.705) 0.550 (95%CI: 0.429‐0.672) 0.702 (95%CI: 0.554‐0.851) 0.811 (95%CI: 0.648‐0.975)
Age, y
≥73 0.548 (95%CI:0.455‐0.640) 0.573 (95%CI:0.461‐0.684) 0.660 (95%CI:0.518‐0.802) 0.686 (95%CI: 0.492‐0.879) 0.860 (95%CI:0.629‐1.091) 1.062 (95%CI: 0.803‐1.322)
\<73 0.615 (95%CI:0.538‐0.693) 0.556 (95%CI:0.462‐0.649) 0.568 (95%CI: 0.455‐0.682) 0.437 (95%CI: 0.290‐0.585) 0.566 (95%CI: 0.382‐0.749) 0.611 (95%CI: 0.416‐0.805)
BMI, kg/m^2^
\<18.5 0.476 (95%CI:0.369‐0.583) 0.490 (95%CI:0.369‐0.612) 0.589 (95%CI: 0.449‐0.730) 0.596 (95%CI: 0.410‐0.782) 0.868 (95%CI: 0.636‐1.099) 0.987 (95%CI:0.750‐1.225)
18.5‐24.9 0.622 (95%CI:0.532‐0.712) 0.602 (95%CI:0.494‐0.710) 0.592 (95%CI: 0.455‐0.728) 0.504 (95%CI:0.325‐0.683) 0.600 (95%CI: 0.391‐0.810) 0.712 (95%CI: 0.474‐0.951)
\>25 0.659 (95%CI:0.535‐0.782) 0.594 (95%CI:0.437‐0.751) 0.708 (95%CI: 0.531‐0.886) 0.591 (95%CI: 0.353‐0.829) 0.767 (95%CI: 0.475‐1.058) 0.839 (95%CI: 0.528‐1.150)
ECOG‐PS
≥1 0.492 (95%CI:0.400‐0.584) 0.517 (95%CI:0.405‐0.630) 0.566 (95%CI: 0.427‐0.704) 0.541 (95%CI: 0.371‐0.711) 0.753 (95%CI: 0.533‐0.972) 0.899 (95%CI:0.655‐1.143)
0 0.677 (95%CI:0.595‐0.758) 0.622 (95%CI:0.523‐0.720) 0.673 (95%CI: 0.556‐0.790) 0.561 (95%CI: 0.386‐0.737) 0.677 (95%CI: 0.472‐0.882) 0.742 (95%CI: 0.522‐0.961)
Biopsy Gleason score
≥9 0.522 (95%CI:0.440‐0.605) 0.478 (95%CI:0.381‐0.576) 0.547 (95%CI: 0.428‐0.665) 0.503 (95%CI: 0.333‐0.672) 0.656 (95%CI: 0.444‐0.868) 0.766 (95%CI: 0.529‐1.003)
≤8 0.703 (95%CI:0.612‐0.793) 0.709 (95%CI:0.604‐0.815) 0.723 (95%CI:0.585‐0.861) 0.601 (95%CI: 0.411‐0.790) 0.741 (95%CI: 0.517‐0.965) N/A
Site of metstasis
Lymph node
Yes 0.555 (95%CI:0.472‐0.638) 0.515 (95%CI:0.413‐0.617) 0.567 (95%CI: 0.444‐0.691) 0.497 (95%CI: 0.332‐0.662) 0.605 (95%CI: 0.410‐0.800) 0.716 (95%CI: 0.495‐0.937)
No 0.609 (95%CI:0.519‐0.699) 0.623 (95%CI:0.522‐0.724) 0.667 (95%CI: 0.541‐0.793) 0.607 (95%CI: 0.435‐0.779) 0.810 (95%CI:0.596‐1.025) 0.906 (95%CI: 0.678‐1.134)
Visceral
Yes 0.482 (95%CI:0.284‐0.681) 0.568 (95%CI:0.340‐0.797) 0.518 (95%CI: 0.211‐0.825) 0.540 (95%CI: 0.221‐0.859) N/A N/A
No 0.592 (95%CI:0.528‐0.657) 0.565 (95%CI:0.489‐0.642) 0.608 (95%CI:0.512‐0.704) 0.552 (95%CI: 0.422‐0.681) 0.703 (95%CI: 0.545‐0.861) 0.803 (95%CI:0.629‐0.976)
Presence of bone pain
Yes 0.578 (95%CI:0.474‐0.682) 0.556 (95%CI:0.421‐0.690) 0.530 (95%CI: 0.360‐0.699) 0.453 (95%CI: 0.254‐0.651) 0.583 (95%CI: 0.336‐0.830) 0.647 (95%CI:0.381‐0.914)
No 0.599 (95%CI:0.516‐0.682) 0.589 (95%CI:0.494‐0.685) 0.673 (95%CI: 0.559‐0.787) 0.644 (95%CI: 0.497‐0.791) 0.821 (95%CI: 0.648‐0.994) 0.959 (95%CI: 0.773‐1.146)
EOD score
≥2 0.466 (95%CI:0.385‐0.547) 0.429 (95%CI:0.333‐0.525) 0.433 (95%CI:0.313‐0.553) 0.300 (95%CI:0.158‐0.442) 0.394 (95%CI:0.2120.576) 0.478 (95%CI:0.263‐0.692)
≤1 0.732 (95%CI:0.645‐0.819) 0.710 (95%CI:0.612‐0.807) 0.775 (95%CI:0.669‐0.882) 0.779 (95%CI:0.628‐0.929) 0.914 (95%CI:0.751‐1.077) 0.971 (95%CI:0.809‐1.133)
Serum marker at baseline
PSA level, ng/mL
\>295 0.567 (95%CI:0.480‐0.654) 0.550 (95%CI:0.446‐0.655) 0.556 (95%CI: 0.421‐0.692) 0.531 (95%CI: 0.368‐0.694) 0.693 (95%CI:0.491‐0.894) 0.804 (95%CI: 0.581‐1.027)
≤295 0.596 (95%CI:0.510‐0.681) 0.578 (95%CI:0.479‐0.678) 0.668 (95%CI: 0.553‐0.782) 0.531 (95%CI:0.336‐0.726) 0.662 (95%CI: 0.426‐0.899) 0.758 (95%CI:0.496‐1.019)
Hb level, g/dL
≤12 0.516 (95%CI:0.409‐0.623) 0.518 (95%CI:0.382‐0.654) 0.540 (95%CI: 0.346‐0.733) 0.628 (95%CI: 0.407‐0.850) 0.835 (95%CI:0.560‐1.110) N/A
\>12 0.613 (95%CI:0.539‐0.688) 0.588 (95%CI: 0.503‐0.673) 0.641 (95%CI:0.544‐0.739) 0.529 (95%CI: 0.389‐0.669) 0.666 (95%CI:0.497‐0.835) 0.774 (95%CI:0.587‐0.961)
ALP level, IU
\>350 0.478 (95%CI:0.386‐0.570) 0.489 (95%CI:0.378‐0.600) 0.493 (95%CI: 0.348‐0.639) 0.362 (95%CI: 0.192‐0.531) 0.475 (95%CI: 0.259‐0.691) 0.558 (95%CI: 0.313‐0.804)
≤350 0.663 (95%CI:0.583‐0.744) 0.621 (95%CI:0.527‐0.716) 0.701 (95%CI: 0.594‐0.808) 0.709 (95%CI: 0.566‐0.851) 0.884 (95%CI:0.719‐1.049) 1.013 (95%CI: 0.839‐1.186)
LDH level, IU
\>220 0.422 (95%CI:0.319‐0.525) 0.458 (95%CI:0.323‐0.592) 0.403 (95%CI: 0.223‐0.583) 0.297 (95%CI: 0.087‐0.506) 0.428 (95%CI: 0.132‐0.723) N/A
≤220 0.662 (95%CI:0.588‐0.736) 0.612 (95%CI:0.527‐0.698) 0.693 (95%CI:0.595‐0.791) 0.649 (95%CI: 0.514‐0.783) 0.793 (95%CI: 0.639‐0.947) 0.902 (95%CI:0.736‐1.067)
Hormone therapy
LHRH antagonists[a](#cam42502-note-0005){ref-type="fn"}
Used 0.684 (95%CI:0.470‐0.826) 0.260 (95%CI:0.031‐0.593) 0.291 (95%CI:0.031‐0.645) N/A N/A N/A
Not used 0.586 (95%CI:0.519‐0.647) 0.576 (95%CI:0.498‐0.645) 0.629 (95%CI:0.530‐0.713) 0.557 (95%CI: 0.423‐0.671) 0.710 (95%CI: 0.526‐0.833) 0.823 (95%CI: 0.572‐0.935)
Antiandrogen
Used 0.579 (95%CI:0.512‐0.645) 0.574 (95%CI:0.497‐0.652) 0.628 (95%CI: 0.532‐0.725 0.574 (95%CI: 0.444‐0.703) 0.725 (95%CI:0.569‐0.882) 0.844 (95%CI: 0.672‐1.016)
Not used 0.637 (95%CI:0.487‐0.787) 0.512 (95%CI:0.293‐0.731) 0.558 (95%CI: 0.322‐0.793) 0.462 (95%CI: 0.171‐0.754) 0.600 (95%CI: 0.239‐0.962) 0.643 (95%CI: 0.260‐1.026)
Local treatment
Yes 0.613 (95%CI:0.398‐0.827) 0.621 (95%CI:0.404‐0.838) 0.673 (95%CI: 0.441‐0.905) 0.713 (95%CI: 0.473‐0.952) 0.965 (95%CI: 0.695‐1.234) N/A
No 0.587 (95%CI:0.523‐0.651) 0.565 (95%CI:0.487‐0.642) 0.611 (95%CI:0.515‐0.708) 0.542 (95%CI:0.414‐0.670) 0.685 (95%CI:0.531‐0.8400) 0.775 (95%CI: 0.606‐0.943)
Abbreviations: ALP, alkaline phosphatase; BMI, body mass index; CI, confidence interval; CS, conditional survival; ECOG‐PS, Eastern Cooperative Oncology Group Performance Status; EOD, extent of bone disease; Hb, hemoglobin; LDH, lactate dehydrogenase; LHRH, Luteinizing hormone‐releasing hormone; PSA, prostate‐specific antigen
95%CI estimated based on log‐transformation
John Wiley & Sons, Ltd
{#cam42502-fig-0002}
Next, we used multivariate analyses to assess the changing hazard ratios for conditional 5‐year net CSS and OS rates for up to 5 years (Table [3](#cam42502-tbl-0003){ref-type="table"} and Table [S4](#cam42502-sup-0008){ref-type="supplementary-material"}). Several variables were identified as prognostic factors for CSS and/or OS at baseline, including BMI ≤18.5kg/m^2^, ECOG‐PS ≥1, the presence of lymph node metastasis, high PSA levels at baseline, low Hb level at baseline, and high LDH level at baseline; however, after the 2‐year time point, these variables were no longer independent prognostic factors for CSS and OS (Table [3](#cam42502-tbl-0003){ref-type="table"} and Table [S4](#cam42502-sup-0008){ref-type="supplementary-material"}). Only EOD ≥2 remained a prognostic factor for CSS and OS for each year of survival (except for CSS in the cohort that survived 2 years). At baseline, the conditional 5‐year net CSS and OS rates for the patients with EOD ≥2 were 0.541 and 0.466, respectively; for the patients who survived 5 years, they were 0.647 and 0.478, respectively (Table [2](#cam42502-tbl-0002){ref-type="table"}, Figure [3](#cam42502-fig-0003){ref-type="fig"}, Table [S3](#cam42502-sup-0007){ref-type="supplementary-material"}, and Figure [S3](#cam42502-sup-0004){ref-type="supplementary-material"}). Kaplan‐Meier curves for conditional CSS and OS based on the EOD score are shown in Figure [4](#cam42502-fig-0004){ref-type="fig"} and Figure [\[Link\]](#cam42502-sup-0002){ref-type="supplementary-material"}, [\[Link\]](#cam42502-sup-0003){ref-type="supplementary-material"}. The OS hazard ratios associated with EOD ≥2 in the conditional versions of the Cox regression models for 1,2,3,4, and 5 years were 1.83, 1.74, 2.13, 2.57, and 3.82, respectively (Table [3](#cam42502-tbl-0003){ref-type="table"}). Biopsy Gleason score ≥9 remained an independent prognostic factor for CSS or OS at 3 and 2 years after the diagnosis, respectively, but these were subsequently no longer statistically significant. These results suggested that the prognosis for patients with EOD ≥2 remained poor over time and that a higher number of bone metastases remained a durable prognostic factor for CSS and OS at all survival time points up to 5 years.
######
Proportional hazard ratios for conditional 5‐y net overall survival in multivariate Cox regression analyses for the prediction of overall mortality
Baseline (n = 605) 1 y (n = 488) 2 y (n = 341) 3 y (n = 249) 4 y (n = 165) 5 y (n = 112)
---------------------------------------------------------------- -------------------- --------------- --------------- --------------- --------------- ---------------
BMI \< 18.5 kg/m^2^ [\*](#cam42502-note-0007){ref-type="fn"}
*P*‐value .007 .041 .085 .177 .746 .458
HR 2.05 1.85 2.03 1.89 0.72 0.43
95%CI 1.21‐3.45 1.03‐3.32 0.91‐4.55 0.75‐4.80 0.10‐5.24 0.05‐3.96
BMI 18.5‐24.9 kg/m^2^ [\*](#cam42502-note-0007){ref-type="fn"}
*P*‐value .780 .927 .637 .901 .311 .830
HR 1.06 0.98 1.14 1.04 1.55 1.13
95%CI 0.71‐1.57 0.64‐1.50 0.66‐1.97 0.56‐1.91 0.67‐3.59 0.38‐3.39
ECOG‐PS ≥1
*P*‐value .017 .096 .146 .346 .786 .079
HR 1.43 1.32 1.35 1.25 0.91 0.43
95%CI 1.07‐1.93 0.95‐1.83 0.90‐2.03 0.79‐1.98 0.44‐1.85 0.17‐1.10
Biopsy Gleason score ≥9
*P*‐value .001 .002 .009 .088 .198 .576
HR 1.65 1.72 1.76 1.51 1.55 1.27
95%CI 1.22‐2.24 1.23‐2.41 1.15‐2.67 0.940‐2.41 0.80‐3.00 0.54‐2.98
EOD score ≥2
*P*‐value \<.0001 .001 .015 .004 .008 .005
HR 2.07 1.83 1.74 2.13 2.57 3.82
95%CI 1.48‐2.89 1.27‐2.62 1.11‐2.71 1.28‐3.53 1.28‐5.18 1.50‐9.71
PSA level \>295 ng/mL
*P*‐value .013 .191 .586 .604 .942 .697
HR 0.68 0.79 0.89 0.88 0.97 1.20
95%CI 0.50‐0.92 0.56‐1.12 0.57‐1.37 0.53‐1.45 0.48‐1.96 0.49‐2.93
Hb level ≤12 g/dL
*P*‐value .008 .025 .542 .825 .755 .165
HR 1.57 1.55 1.17 1.07 1.14 2.00
95%CI 1.13‐2.19 1.06‐2.26 0.71‐1.94 0.59‐1.93 0.50‐2.58 0.75‐5.31
LDH level \>220 IU
*P*‐value .001 .079 .090 .067 .427 .621
HR 1.75 1.37 1.47 1.60 1.32 1.25
95%CI 1.27‐2.40 0.97‐1.94 0.94‐2.29 0.97‐2.65 0.67‐2.60 0.51‐3.05
Abbreviations: ALP, alkaline phosphatase; BMI, body mass index; 95%CI, 95% confidence interval; ECOG‐PS, Eastern Cooperative Oncology Group Performance Status; EOD, extent of bone disease; Hb, hemoglobin; HR, hazard ratio; LDH, lactate dehydrogenase; PSA, prostate‐specific antigen
Compared to BMI ≥25 kg/m^2^
John Wiley & Sons, Ltd
{#cam42502-fig-0003}
{#cam42502-fig-0004}
4. DISCUSSION {#cam42502-sec-0014}
=============
This study was the first study to investigate conditional net survival in prostate cancer patients using an unbiased novel estimator. We showed that, after the baseline survival estimation, the conditional net CSS and OS rates gradually increased with time. Furthermore, the significance of prognostic factors for the patients with mHNPC changed over time after ADT. Only EOD ≥2 remained an independent factor for CSS and OS, whereas other well‐known prognostic factors had lost their statistical significance as prognostic factors by 5 years after the administration of ADT therapy.
In general, conditional survival gains are limited for patients at low risk, whereas the relationship is stronger for patients with adverse prognostic features.[29](#cam42502-bib-0029){ref-type="ref"}, [30](#cam42502-bib-0030){ref-type="ref"} In a study to assess population‐based 5‐year conditional survival for various cancers, Janssen‐Heijnen et al reported that conditional 5‐year relative survival in patients with prostate cancer decreased from 89% at diagnosis to 81% at 6 years after diagnosis.[31](#cam42502-bib-0031){ref-type="ref"} Conditional relative survival analyses for a large number of cancers based on the Canadian Cancer Registry showed that the conditional survival in prostate cancer did not change 5 years after diagnosis.[32](#cam42502-bib-0032){ref-type="ref"} In the largest population‐based study for conditional survival, which included 204 472 patients with prostate cancer in the United States, Merrill et al reported an increase in CSS after survival for five years, with the probability of remaining disease‐free up to year 5 increasing from 33.1% to 55.9%.[33](#cam42502-bib-0033){ref-type="ref"} Thus, there have been inconsistent results reported for conditional survival rates based on cancer registries in patients with prostate cancer. Further application of unbiased estimators is needed to assess conditional survival and to perform conditional survival analyses targeted at this specific subgroup population to provide more precise information for the patients.
Newly diagnosed metastatic prostate cancer is not a curative disease, and a recent study that evaluated survival in patients with stage IV prostate cancer registered in the SEER database between 2004 to 2010 showed that the 5‐year OS was 22% to 67.4%,[8](#cam42502-bib-0008){ref-type="ref"}, [9](#cam42502-bib-0009){ref-type="ref"} providing rather pessimistic information for patients with mHNPC. Only one study has specifically reported conditional survival in patients with stage IV prostate cancer. Muralidhar et al assessed conditional cancer‐specific mortality in 41 022 M1 patients registered in the SEER database and reported that 5‐year prostate cancer‐specific mortality improved from 57.2% at diagnosis to 41.1% at 5 years, 28.8% at 10 years, and 20.8% at 15 years.[16](#cam42502-bib-0016){ref-type="ref"} Although that study had some limitations, including being based on an old database with patients diagnosed between 1973 and 2011, as well as a lack of detailed background other than age, race, income, married status, and Gleason grading, it showed that the risk of death decreased overtime in patient with advanced stage prostate cancer. This study, which is the first study to assess the conditional net survival specific to metastatic prostate cancer using the unbiased novel Pohar Perme estimator, demonstrated that 5‐year CSS and OS rates significantly increased from 65.5% and 58.2% to 90.6% and 81.1%, respectively. Taken together, conditional survival estimates may provide more appropriate information for patients with mHNPC.
The stratification of conditional survival estimates by prognostic factors provides more relevant clinical information and better estimates of individual patient prognosis.[32](#cam42502-bib-0032){ref-type="ref"}, [34](#cam42502-bib-0034){ref-type="ref"} In line with previous studies that reported baseline risk factors for mHNPC,[10](#cam42502-bib-0010){ref-type="ref"}, [35](#cam42502-bib-0035){ref-type="ref"}, [36](#cam42502-bib-0036){ref-type="ref"} our multivariate analysis confirmed the impact of potential baseline prognostic factors for CSS and OS in mHNPC. Poorer CSS and OS rates at the time of diagnosis were observed for subgroups based on low Hb, high LDH level, BMI ≤18.5kg/m^2^, ECOG‐PS ≥1, and the presence of lymph node metastasis; however, these differences diminished in the following years, suggesting that the prognostic significance of these factors decreases as time elapses after diagnosis. In contrast, the number of bone metastases remained a significant risk factor even after 5 years of follow‐up. These findings could be used to drive a more evidence‐based strategy for post‐treatment follow‐up scheduling that is based on the patient\'s actual current risk rather than simply on baseline probabilities.
Bone metastatic tumor burden is one of the most influential prognostic markers in patients with mHNPC.[10](#cam42502-bib-0010){ref-type="ref"}, [37](#cam42502-bib-0037){ref-type="ref"} In large randomized trials that showed the benefit of upfront therapy using docetaxel and abiraterone acetate with ADT in patients with mHNPC, the number of bone metastases was one of the specific factors used for dichotomizing risk groups for prognosis.[6](#cam42502-bib-0006){ref-type="ref"}, [38](#cam42502-bib-0038){ref-type="ref"} A retrospective study that included 304 Japanese patients with treatment‐naïve castration‐sensitive prostate cancer reported that EOD ≥2 was an independent risk factor, and EOD ≥2 was one of four risk factors used in the study to develop three risk categories.[37](#cam42502-bib-0037){ref-type="ref"} Consistent with these results, this study showed that EOD ≥2 was an independent prognostic factor and showed for the first time that the number of bone metastases continued to influence the CSS and OS of patients with mHNPC over time. The conditional survival rate remained low for patients with EOD ≥2 but generally increased for the entire cohort and the other subgroups. These findings give the intriguing possibility of developing more personalized treatment and/or follow‐up for individual patients with mHNPC and of providing these patients with more accurate information about their prognosis. However, conditional survival rates have not yet been established for patients treated with upfront abiraterone acetate and docetaxel with ADT, which has become a novel standard treatment for high‐risk and high‐volume mHNPC. Among the other prognostic variables considered in the multivariate analysis, biopsy Gleason score ≥9 remained a statistically significant independent prognostic factor for CSS and OS until 3 years and 2 years, respectively. The results of the LATITUDE trial suggested that three risk factors could be used as an indication for the upfront administration of abiraterone: biopsy Gleason score ≥8, the presence of three or more bone lesions, and/or the presence of measurable visceral metastases.[6](#cam42502-bib-0006){ref-type="ref"} Although our results do not provide a definitive assessment, they strongly support these two factors---the number of bone metastases and biopsy Gleason score---as being risk factors for CSS and OS in patients with newly diagnosed mHNPC. However, the present study did not reveal any impact of visceral metastasis on CSS and OS, perhaps because of the small number of patients compared with the numbers included in the previous trials (14.0%‐18%).[6](#cam42502-bib-0006){ref-type="ref"}, [39](#cam42502-bib-0039){ref-type="ref"}
Our study had several limitations. First, the multicenter design resulted in heterogeneity of the patients\' treatment and monitoring. Second, the study did not consider the impact of sequential treatments after the initial ADT. The sequential therapy given after development of CRPC was described in Table [S5](#cam42502-sup-0009){ref-type="supplementary-material"}. Although there was no statistical association of year of diagnosis with CSS and OS in this study, sequential treatments following ADT failure may have played a role in the outcomes for some patients. The retrospective study design and short follow‐up duration were further limitations. Future studies with a longer follow‐up period and a validation dataset are warranted.
In conclusion, the conditional 5‐year net CSS and OS rates in patients with mHNPC gradually increased in the years following ADT treatment, implying that the risk of mortality decreased with increasing length of survival. The patients\' risk profiles changed over time, but the EOD score remained an independent prognostic factor for CSS and OS after 5 years of follow‐up. Conditional net survival can play a role in clinical decision‐making and provides valuable information for cancer survivors.
CONFLICT OF INTEREST {#cam42502-sec-0015}
====================
Tomonori Habuchi has acted as a paid consultant for Janssen and Sanofi for work performed outside the current study.
AUTHOR CONTRIBUTIONS {#cam42502-sec-0016}
====================
Shintaro Narita: Data collection, statistical analysis, manuscript writing. Hiromi Sato, Shingo Hatakeyama, Masahiro Takahashi, Toshihiko Sakurai, Sadafumi Kawamura, Masanori Ishida, Senji Hoshi: Data collection. Toshiaki Kawaguchi, Shigeto Ishidoya, Jiro Shimoda, Koji Mitsuzuka, Kengo Nagashima: supervision. Kyoko Nomura: Statistical analysis, manuscript writing. Tatsuo Tochigi, Norihiko Tsuchiya, Chikara Ohyam, Yoichi Arai, Tomonori Habuchi: manuscript editing, supervision. All authors have read and approved of the final manuscript.
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The authors would like to acknowledge the following investigator of this study: Dr Yuri Ito for her technical advice on conditional survival. The authors also wish to express their appreciation to Yoko Mitobe, Sayaka Fukuda, Saeko Nakamura, and Masako Nagata for their assistance while conducting the study.
| null | minipile | NaturalLanguage | mit | null |
A Regular Commentary on Strategic Affairs from a Leading Commentator and Analyst
2018 book project: Little Europe? Twenty-First Century Strategy for Declining Powers
hms iron duke
Monday, 16 July 2012
Leviathan: The Great European Divide
Alphen, the Netherlands. 16
July.In 1651 English political
philosopher Thomas Hobbes wrote “Leviathan” in which he said prophetically, “The only way to erect…a common power, as may be able to
defend [men] from the invasion of foreigners, and the inquiries of one
another... is to confer all their power and strength upon one man, or upon one
assembly of men...Leviathan”.Hunkered down behind the Eurozone crisis is Europe’s key existential
question; can the future prosperity, stability and, indeed, democracy of
Europeans be afforded by one single super-Leviathan?
The current crisis has painfully
exposed what is the great European divide; those who believe in a greater
‘Europe’ and those suspicious of grand constructs that not only threaten hard
won freedoms but also seek to replace the nation-state.Sadly, friendships have been torn asunder
over this issue; I too have lost a couple.
Many continental Europeans are
used to so-called ‘dirigisme’, diktat
by fiat from above.As an Englishman
grounded in a political culture in which fundamental individual freedoms are
sacrosanct the very idea of a European Leviathan is dangerous political
folly.It would require trust in a European
political caste over which I have no writ.
Later this year I will have the
honour of addressing a meeting of senior French politicians and officials.‘L’Europe’ is very much a concept that France
has championed.Whilst it is a perfectly
honourable creed it, ‘Europe’, begs the ultimate political and economic question;
what is the ‘finalité’?
First, there would need to be a European
head of state, a real European president supported by a real European
government led by a cabinet replete with European ministers, covering all the
many competences of a modern state; a single system of justice and policing, sound
economic governance and all aspects of ‘Home’ Affairs. Second, Europe’s five
hundred million or so very disparate peoples with their myriad of cultures,
traditions, beliefs and languages would need representation via a single
European parliament credibly charged with powers of political oversight and
made up of Europe-wide political parties. Third, there would need to be a real executive
supported by a European ‘civil service’ charged with implementing European
policy and held to account by a functioning parliament.Fourth, there would need to be a European
Finance Ministry supported by a real European Central Bank that would act as a
bank of last resort, much like the US Federal Reserve.Finally, and critically, any such ‘state’
would send European citizens to their deaths in war in the service of a real
European Army, Navy and Air Force.
To make that work France would
need to be scrapped, the French Government in Paris reduced to being little
more than an English county council or more aptly a French departement.Parliamentary
democracy in France would be diluted some tenfold as by ratio of population to
representation the size of European parliamentary constituencies increased in
size some tenfold. French national control over
all main tax-raising powers and indeed all other aspects of sound money would
be handed over to the European finance ministry.The French would also need to abandon their armed
forces, its military traditions, history and glory and subordinate it to a
European Army.
Of course, money is the root of all evil. The Europe on offer today is one of mutual impoverishment, which makes it different to the 'Europe' of yore. For the first
time European integration pre-supposes little or no economic growth.In the past ‘Europe’ has been built on the
transfer of surpluses from the taxpayers of the formerly rich north and west
Europe to those of the poor south and east Europe. How long
can Western European politicians impose such transfers on their newly
impoverished taxpayers in the name of Europe before they revolt?
For me ‘Europe’ can only ever
work as a tight alliance of nation-states in which the political centre of
gravity remains national sovereignty under national parliamentary control ‘harmonised’
into a tool for strategic influence, both within Europe and beyond.To that end the place of Brussels is to serve
the European state, not replace it.I
will never compromise on this point.
Shortly before his death Hobbes said,
“I am about to take my last voyage. A great leap in the dark.”He could well have been speaking of the giant
leap into the political dark that is now taking place in Europe.Ultimately, a European Leviathan would be an
insult to the tradition of English and Scottish political thought that made parliamentary
democracy possible – Hume, Locke, Mill, Smith et al.And, if friendships are lost because I will
not compromise on this fundamental political principle, then so be it.
About Me
Julian Lindley-French is Senior Fellow of the Institute of Statecraft, Director of Europa Analytica & Distinguished Visiting Research Fellow, National Defense University, Washington DC. An internationally-recognised strategic analyst, advisor and author he was formerly Eisenhower Professor of Defence Strategy at the Netherlands Defence Academy,and Special Professor of Strategic Studies at the University of Leiden. He is a Fellow of Respublica in London, and a member of the Strategic Advisory Group of the Atlantic Council of the United States in Washington.
Latest books: The Oxford Handbook on War 2014 (Paperback) (2014; 709 pages). (Oxford: Oxford University Press) & "Little Britain? Twenty-First Strategy for a Middling European Power". (www.amazon.com)
The Friendly-Clinch Health Warning: The views contained herein are entirely my own and do not necessarily reflect those of any institution. | null | minipile | NaturalLanguage | mit | null |
very helpful lioness
Main menu
You are here
An update on Drupal 8.6 pre-feature freeze
Thu, 06/28/2018 - 13:52 -- webchick
Greetings, folks! As we head into feature freeze for Drupal 8.6 (the week of July 18), here's a run-down of the various initiatives, and a hit-list of what they're trying to accomplish in the next two weeks. Patch reviews, testing, design, docs, and many more skills are very welcomed!
A couple of caveats here:
1) This is my own personal best understanding of where this stuff is all at, based on reading issue comments, attending meetings, overhearing things from other people who attended meetings, catching the odd Slack snippet of conversation, carrier piegon, etc. And therefore may not be 100% accurate, or even 80% accurate — there's a lot going on! (please clarify in the comments if you see any errors/omissions)
2) Just because something is listed here, there is absolutely no guarantee that it gets reviewed + (truly) RTBCed + committed in time for feature freeze and makes it into 8.6. As you can see, there are lots of issues in the list below, and we're all doing our best to stay on top of them. Worst-case, there's always 8.7. :)
3) This post gets into nitty-gritty "technical audience" details; if you're interested in a more broad overview of initiatives and their aims for 8.6 and beyond, there's the strategic initiatives overview on Drupal.org. I was also recently on a Lullbabot podcast to that effect.
For 8.6, one of the big accomplishments of this initiative was introducing Nightwatch.js testing framework to core, which allows us to test JavaScript code with (wait for it)... JavaScript (what a concept!). This will be critical in ensuring that the React-ified components work as expected, and our existing JavaScript-rich functionality continues to work solidly as we expand on dynamic functionality in the UI.
Bring JS code up to modern standards
TONS of work has been going on in the JSON API contributed module queue to fix a number of outstanding issues to make it core-worthy. So even if this module doesn't make it in time for 8.6, the entire ecosystem will benefit throughout 8.6's lifecycle by using a much more robust and well-tested contributed module. Additionally, a long-standing gap of file upload support has been added. Huzzah!
For the remainder of 8.6, the team would like to focus on the following:
These two initiatives overlap in that we're aiming to build the automatic update functionality around improving core's underlying Composer support.
The Composer team has compiled an excellent plan of attack for how to provide Composer support without jeopardizing the site builder experience. Most of that work will take place in 8.7.
UPDATE July 3, 2018: The team has proposed some of the concrete tasks needed under here for possible inclusion in 8.6. Needs patches, which then need reviews. Let's git er done! (I'm so, soooo sorry. ;))
However, one of the pre-requisites for Composer to work well, is adding semantic versioning support for contrib. Support for this would also be tremendously helpful to contrib module authors and site builders, regardless if they use Composer to manage their dependencies or not.
New topic-based core help system
For the plan around this initiative to happen, we need to make several adjustments to core's Update Status module, which currently makes several hard-coded assumptions about the last minor release of Drupal expiring immediately once a new minor release is available.
Update Status Improvements
If the next minor version of core has a security release, status still says "Security update required!" even if the site is on an equivalent, secure release already [#2804155]
The Layout team has been hard at work improving upon the experimental Layout Builder functionality that was added to 8.5. The main goal of the team for 8.6 is to gather real-world testing feedback from end users, which they are accomplishing by adding Layout Builder to a new branch of the Lightning distribution. Doing this has uncovered a few holes in the implementation relative to what's possible in contrib right now, and filling those gaps is the focus of the remaining 8.6 time for the team.
Layout Builder gaps
Allow the inline creation of non-reusable Custom Blocks in the layout builder [#2957425]
Allow Custom blocks to be set as non-reusable adding access restriction based on where it was used. [#2976334]
Add a validation constraint to check if an entity has a field [#2976356]
Determine if Layout Builder should replace entity_view_display for all Entity Types [#2936358]
The goal of this initiative for 8.6 is to stabilize the migration system which means marking the experimental Migrate Drupal + Migrate UI modules stable. This was also the goal for 8.5. What's making it tricky is multilingual migrations, which are themselves tricky because there are a multitude of ways one might have set up multilingual functionality prior to it being included in core in Drupal 8, which introduces lots of edge cases around making IDs line up and whatnot.
The Umami profile was committed (albeit marked hidden) in 8.5, and major efforts have been going on to remove all of the "beta blockers" preventing it from being visible in the UI. The last of these—Install profile in settings.php and mismatch check makes re-installs of Drupal hard [#2975328]—just landed earlier this week!
From here to 8.6, the team is working on stability and accessibility improvements.
Last, but certainly not least, is the Workflow initiative, which aims to add the Workspace contributed module to core in 8.6 to facilitate content staging and full-site previews. The module was already committed to 8.6 awhile back, but must be brought up to "beta" level stability to remain in the tagged + shipped release.
Because Workspaces can only stage content that's revisionable, there's also a parallel effort to add revision-ability to more types of data in Drupal core.
MOAR revisionable thingies
Anything else?
Whew! That's QUITE a lot. Are there any issues out there that we're missing that you feel are mission-critical to get into Drupal 8.6? Feel free to suggest them, with the caveat that the longer the list is, the more distributed the community's and core committers' focus is.
Hm. The patch there seems 2+ years old, and not passing tests, so unlikely to get into 8.6 in the next two weeks. However, it'd be a great feature, and a very worthy issue for someone to work on for 8.7!
Thank you for the write up, many interesting and valuable developments going on. I personally perceive that none of these initiatives are as important as rules, which, to me, is an essential module for a cms and I fail to comprehend why it is not added to core - apart from that most of the community seems to disagree with me and thus have other priorities.
Tldr, I am missing rules on the list of being added to 8.6 because too few hands on it.
Thanks, any context around those links? Like cool new capabilities they would unlock, or similar? We need to carefully balance very limited committer availability over the next 2 weeks around those initiatives/issues that have the highest impact.
Having read this I believed it was very informative.
I appreciate you taking the time and energy to put this information together. I once again find myself personally spending a significant amount of time both reading and leaving comments. But so what, it was still worth it!Happy New Year & Merry Christmas | null | minipile | NaturalLanguage | mit | null |
Module 4 is rather straight (pun intended) forward, with a few features, such as the Timber Faced Loading Bank (In a deteriated condition), the platform end, the Watering Facilities Remnants, and the main feature being the Track itself. | null | minipile | NaturalLanguage | mit | null |
Thomas Southcote
Thomas Southcote (c 1622 – 1664) was an English landowner and politician who sat in the House of Commons from 1661 to 1664.
Southcote was the son of George Southcote of Buckland Tout Saints and his wife Frances. He matriculated at Balliol College, Oxford on 2 November 1638, aged 16. He was a student of Lincoln's Inn in 1640. In 1654 he succeeded to the estates of his father. In 1657, he became a J.P. for Devon until his death and a commissioner for assessment for Devon for the year, being commissioner for assessment again from August 1660 until his death. In 1661, he was elected Member of Parliament for Dartmouth in the Cavalier Parliament. He was Deputy Lieutenant from 1661 to his death and commissioner for corporations from 1662 to 1663.
Southcote who was sickly for a long period died at the age of about 42 between 28 March 1664 and 6 April 1664.
Southcote married Alice Petre, daughter of Abraham Petre of Marldon, Devon under a marriage settlement of 15 January 1650. They had two sons and three daughters. His sons died in infancy and his only surviving daughter married Sir William Portman, 6th Baronet.
References
Category:1622 births
Category:1664 deaths
Category:English MPs 1661–1679
Category:Alumni of Balliol College, Oxford
Category:Members of Lincoln's Inn | null | minipile | NaturalLanguage | mit | null |
The impact of HIV testing on blood utilization in the intensive care unit in patients with gastrointestinal bleeding.
To determine whether the AIDS epidemic has influenced physician use of blood products in intensive care unit management of gastrointestinal hemorrhage. Retrospective chart review of 148 patients with gastrointestinal hemorrhage admitted to the intensive care unit. Forty-eight patients were admitted before the onset of HIV testing of the blood supply (group 1) and 100 were admitted after HIV testing was begun (group 2). Of the 148 patients, 18 (eight in group 1, ten in group 2) were not transfused and had higher median hemoglobin levels on admission and higher median hemoglobin nadirs during hospitalization than patients who were transfused. Transfused patients in group 2 did not have significantly lower median hemoglobin levels on admission [7.9(4.2-12.5) g/dl] than transfused patients in group 1 [9.3 (4.1-13.5) g/dl] (p = 0.058). Patients in group 2 had significantly lower median hemoglobin concentrations prior to the first transfusion event [7.4 (4.2-10.3) g/dl] than those in group 1 [8.5 (4.2-12.1) g/dl] (p = 0.016). There were no significant differences between the two groups in terms of the total number of units of packed red blood cells, fresh frozen plasma or platelets transfused. Neither was any significant difference in mortality observed, with 11 patients (22.9%) dying in group 1 and 23 patients (23.0%) dying in group 2. The cause of death in 13 of the 34 patients was related to cardiovascular and hemodynamic complications of gastrointestinal bleeding. There was no significant difference in mean age (group 1: 60.5 years, group 2: 59.4 years) or mean hemoglobin nadir (group 1: 7.0 g/dl, group 2: 7.1 g/dl) among those who died in the two groups. These data indicate that physicians are transfusing patients at lower hemoglobin levels than they did before the beginning of HIV testing. However, there has been no decrease in the total median amount of blood products transfused since that time. This change in practice may be due to increased concern about HIV transmission through blood products and suggests the need for greater awareness of existing transfusion guidelines. | null | minipile | NaturalLanguage | mit | null |
Branched-dextran exo-1,2-alpha-glucosidase
Branched-dextran exo-1,2-alpha-glucosidase (, dextran 1,2-alpha-glucosidase, dextran alpha-1,2 debranching enzyme, 1,2-alpha-D-glucosyl-branched-dextran 2-glucohydrolase) is an enzyme with systematic name (1->2)-alpha-D-glucosyl-branched-dextran 2-glucohydrolase. This enzyme catalyses the following chemical reaction
Hydrolysis of (1->2)-alpha-D-glucosidic linkages at the branch points of dextrans and related polysaccharides, producing free D-glucose
This enzyme does not hydrolyse disaccharides or oligosaccharides containing linear 1,2-alpha-glucosidic linkages.
References
External links
Category:EC 3.2.1 | null | minipile | NaturalLanguage | mit | null |
Homeowners! Avoid These 10 Most Common Home Renovation Mistakes
The good news is, we're not asking you to confess your home renovation slip-ups and goofs here, in public.
But we all make them.
That time you ordered the dishwasher that was too big for the space. The paint that cracked and peeled off in big hunks before it was even dry. The embarrassing trip to the emergency room because you… well, let's not get into it here.
Some home renovation mistakes are so common the experts find themselves talking about them time and time again.
Homeowners, in 2016 and beyond, do your best to avoid these 10 common home renovation mistakes.
Skipping the Prep Work
We know – prep work is boring and you can't wait to see how that Tangerine Dream paint looks in the foyer, so you barge ahead.
But prep work is important. Take the time to do all the steps of your project right from the beginning.
Prep is especially important for painting. Yes, you really do need to dust and clean the walls, scrape any cracked or flaking paint off with a paint scraper and smooth any bumps with sandpaper.
And don't skip the primer – a high-quality primer will help hide any small imperfections on walls. Skip the prep, and your paint job won't have a sleek, smooth finish.
Inaccurate Measurements
Measuring is an exact science. Even a fraction of an inch can mean your counter is crooked, your tile looks sloppy, your refrigerator won't fit.
Norm Abram, the master carpenter for years on “This Old House,” is famous for saying, “Measure twice, cut once.”
It's tempting to rush through the boring measuring part to get to the more exciting stuff. Slow down, measure, then measure again. Are you all thumbs when it comes to measuring?
It's OK to ask a pro to do it for you.
Gutting Everything
Who doesn't love a date with a crowbar or sledgehammer? There's something really satisfying about slamming into that avocado green bathroom tile or the 1970s counter tops with the pattern that looks like it belongs in a science lab.
Whoa, whoa, whoa.
Make sure you have a sensible plan before you start destroying everything. If you can salvage part of your existing room, you'll save money. Don't assume it all has to go.
Using the Wrong Type of Paint
All paint is not the same. And we're not just talking colors. There are different types for different surfaces, and it does make a difference.
Gloss and satin finishes reflect light and make small imperfections show up. In older houses, where the walls likely aren't perfect, a matte finish is better.
The sheen of a satin or gloss paint is easily wiped off, so it's good for trim in areas that might get dirty, like a kitchen or a child's room.
Semi gloss is a good choice for bathrooms, where the moisture level is high. Glossier paint offers more mildew resistance because it's less porous.
Your best bet? Ask the pros at the paint store for advice before you choose your paint.
Ignoring Safety
It's easy to feel invincible when you're working on a home renovation project. You have a plan, you've researched your materials, you took vacation time and you're ready to roll.
Do you have goggles to protect your eyes? Ear protection for loud noise? Sturdy work gloves to protect your hands from splinters and wayward nails? Sturdy boots to protect your feet from sharp objects?
Lots of homeowners don't think about these safety precautions. You can pick up most of these items at the same store where you buy your lumber and paint.
Add them to your list.
And don't forget the first-aid kit.
Buying Cheap Materials
Everybody wants to save a buck. So it's easy to be lured in by cheap materials.
Remember how your dad always says, “You get what you pay for?”
Well, he's right. (He'd love to hear you say that.) If you can't afford to complete your project using high quality materials, wait until you can.
Setting an Unrealistic Budget
Older homes and larger jobs are more likely to have hidden expenses, as are projects involving plumbing, electrical or other work that's hidden behind walls and ceilings.
There could be mold, leaks, corroded pipes, termite damage, fire hazards or asbestos. Maybe you tear out walls and discover your kitchen wiring isn't up to code.
Experts say expect to spend 10 to 15 percent above what you think the project will cost.
Choosing the Cheapest Contractor
The lowest bid is tempting, isn't it? Maybe you can actually save some money on this project.
Resist temptation. Experts say the lowest bid is unlikely to get you the best workmanship. Some contractors may bid low in order to get the job, then cut corners or use low-quality materials to make up the money.
A low bid may mean the contractor doesn't have a realistic grip on the work involved. Get several bids, and really look them over to make sure you know exactly what you're getting for the price.
The written estimates should include details of exact material and installation costs, as well as costs for refuse removal, permits and the general contractor fee. Look for an explanation of how design changes are handled, and a warranty on the work.
These kinds of details show that the contractor has a good grasp of the scope of the project.
Following Trends
When every magazine and home design show sports the same backsplash tile, light fixtures and flooring, you know it's trendy.
That means it's really popular now, but chances are, it won't last. And you'll likely soon tire of it. Choose wisely for your home's key elements, sticking with materials, colors and finishes that will stand the test of time.
Trends are fun, but use them in accessories like pillows and other less expensive home decor.
Trying to Tackle Too Much Yourself
Tackle the painting, a simple backsplash, maybe the flooring. But cabinetry installation, complicated tile work and carpentry require skill and experience.
Mess this stuff up, and it can actually reduce the value of your home.
Make No Mistake — You Need a Dumpster
Chances are, you'll make at least one mistake during your home renovation project.
Don't let that mistake be forgetting to rent a Bin There Dump That dumpster to haul away the mess. That part of your project will go exactly according to plan.
While traditional dumpsters are huge and heavy and could crack your driveway, we place wooden boards under our bins so they never actually touch your property. No damage. Our local dumpster rental operators even sweep up your driveway before they drive off. | null | minipile | NaturalLanguage | mit | null |
1) 17 inch diameter
2) Used to produce the ageing (antique) finish on the marble and granite slab.
3) Design is easy for using on Automatice Polishing Line.
4) Grain size:36#,46#,60#,80#,120#,180#,240#,320#,500#. Wide range of grain makes it possible to achieve from an opaque finishing to a mirror polishing.Read More
) To get antique and sillike effect.
2) High quality polishing
3) Long life time
4) Diamond brush is with strong grinding force ,long lifespan,polishing uniformity and high production efficiency ,environmental protection and so on.Read More
) To get antique and sillike effect.
2) High quality polishing
3) Long life time
4) Diamond brush is with strong grinding force ,long lifespan,polishing uniformity and high production efficiency ,environmental protection and so on.Read More | null | minipile | NaturalLanguage | mit | null |
Teresa Brennan
Teresa Brennan (b. January 5, 1952 – d. February 3, 2003) was an Australian feminist philosopher and psychoanalytic theorist best known for her posthumous book, The Transmission of Affect (2004). Before her death, Brennan was Schmidt Distinguished Professor of the Humanities at Florida Atlantic University, where she founded a PhD program for Public Intellectuals.
Education and career
Brennan graduated with a BA from the University of Sydney and an MA in political theory from the University of Melbourne. Before her PhD at King’s College, Cambridge, Brennan trained as a psychoanalyst at the Tavistock Clinic in London. She taught at The New School, Brandeis University, and Harvard University, and finally as Schmidt Distinguished Professor of Humanities at Florida Atlantic University.
While at Florida Atlantic University from 1998 to 2002, Brennan designed a PhD for Public Intellectuals, intended for training not only scholars but curators and archivists, organizers, and environmentalists.
Publications
Brennan's first two books, Interpretations of the Flesh: Freud and Femininity and History After Lacan, are works of psychoanalytic social theory, while Exhausting Modernity: Grounds for a New Economy and Globalization and Its Terrors draw on Marxist and ecofeminist theories to consider large-scale energetic draining. Her posthumous The Transmission of Affect engages physiological and psychosocial research that challenges the causal framework of sociobiology, with examples such as stress, psychological projection, the introjection of aggression, and the energizing and draining of social interactions.
In addition to these five books, Brennan edited two volumes: Between Feminism and Psychoanalysis and, with co-editor Martin Jay, Vision in Context: Historical and Contemporary Perspectives on Sight. She was General Editor with Susan James of the ‘’Oxford Readings in Feminism’’ series, an extension of ‘’Oxford Readings in Philosophy’’, and also General Editor for the Routledge series ‘’Opening Out: Feminism for Today.’’
Brennan’s colleagues contributed to a posthumous volume on her work Living Attention: On Teresa Brennan. Her papers are housed in the John Hay Library at Brown University, part of the Pembroke Center for Teaching and Research on Women’s Feminist Theory Archive. In 2017, the philoSOPHIA annual conference honored Brennan at Florida Atlantic University, with a keynote by Sara Ahmed.
References
Category:1952 births
Category:2003 deaths
Category:Australian feminist writers
Category:Australian philosophers
Category:Australian women philosophers
Category:Florida Atlantic University faculty
Category:University of Sydney alumni
Category:Alumni of King's College, Cambridge | null | minipile | NaturalLanguage | mit | null |
Disclaimer: I don't own Ace Combat.
"Hey! You!" I hear someone shouted.
I recognised that voice. To say that I'm thrilled to hear it is a bit of a lie. In fact I was hoping I don't have to hear it, ever.
"I know you can hear me!" the voice called out again.
A part of me attempt to persuade me to turn around and be done with this quickly, but another part of me said that dealing with this sort of person is never quick and easy, they bring nothing but trouble and once we dealt with it even more trouble will arise. Naturally the rest of me agree with that one and I decided to just ignore it, hopefully this annoyance will go away.
It wasn't meant to be sadly, as this person instead seem to see this as a sign to be bolder, it seems. I can feel a hand grabbed my shoulder, trying to forcefully turn me around, trying because being bigger and plain stronger, I shrugged their attempt off easily.
This didn't deter them however, they instead decided to directly impede me by getting in the way, forcing me to stop.
"Are you getting kicks from making people angry or something?!" the annoyance asked loudly despite the fact that we're only a feet away from each other at most.
I scan the annoyance in front of me, a short, angry girl around my age looking straight at me.
This girl, we only interacted once and already she act like she can tell me what to do. Any other day, I would've just get her out of the way and move on, but I did the exact same thing last time and look how well it turned out. Taking a deep breath, I decided to just this once listen to what she wanted to say.
"Why didn't you turn around?" she asked.
"Why would I?"
"Because I called you!"
"I—"
"Don't you dare say you didn't hear me because I know you did!"
"Wasn't going to," I said.
"Good," she said, but after a moment something crossed her mind, it seems.
"Wait, if not that then what—, hey!"
I get her out of the way, not waiting for her to finish her question, I said I'll listen but I didn't say anything about hearing the full story. This naturally earned me another scathing look from her, doesn't stop her from following me for some reason.
"Where are you going?" Curious, this one.
I kept quiet, not really feel like telling a stranger about anything. This earned another ire from her. She fall in beside me, angrily.
"Don't ignore me!" she shouted. This girl really likes shouting, it seems.
I glanced around, the nosy creatures around us are starting to take notice. I knew this girl is trouble.
"None of your business," I said.
"Grrr…" She looked like she was about to start another bout of tantrum when she took a deep breath, and then another, and then several more. She's trying to keep her temper in check, it seems. That's nice of her.
"Look, I know you hate being disturbed like this, but I only doing this because I wanted to apologize, all right? So can you please at least listen to what I wanted to say?" Apologise?
"What for?"
"You know, about three days ago." Ahh, three days ago.
I looked at her. She currently has her gaze away from me. She feels guilty about it, it seems.
On one hand, her accusation is baseless and almost got me into trouble. On the other hand, if I was to be in her shoes and see what she saw, I would probably though the same thing.
Well, not really but the thought will cross my mind.
"Forget it," I said, focusing back on the road.
"What?" she asked. She didn't expect me to be flippant about it, it seems.
"You're doing what you think is right, I can't blame you for that."
"But… why?"
"Not sure. Someone taught me that a while ago." Introduce me to the concept more like, but fail to elaborate.
"But, but… because of me, you're almost… I—"
"Nothing happened in the end, so it doesn't matter anymore," I cut her off. Something dramatic might happen if I let her continue.
"Still…."
"You wanted me to be mad at you?" I stopped and asked. Strange how when people seek forgiveness, they tend to try to turn it down when it was presented to them. Maybe because it usually hard to come by and it caught them off guard when it isn't?
"No," she said after some time.
"Then what's with the attempted rebuttal?"
"I… don't know," she said, doubt in her voice. Guess I should have seen this coming.
"Don't worry about it," I said. She looked up at me.
"I don't care about it, you shouldn't too."
"Okay," she said after some time. At least she's not the type to let things drawn out, that's a plus.
I quickened my pace. I have done enough good deeds today, the time has come to get her off my trail.
"Hey, wait up!" she said after she has her emotions in order and realised that I'm already some distance away from her, not waiting around for her.
"Why are you following me?" I asked.
"You got a problem with that?" she asked back.
"You're a stranger."
"So what?"
"It's not safe."
"Why? Are you going to do something dangerous?" she asked, suspicious.
"No."
"Then what's the problem?" This girl… been a while since the last time I saw her kind.
Guess it won't hurt letting her tag along for now, probably safer for her too. Who knows, maybe we'll run into her parents or caretakers.
My silence is all she needed to continue following me.
Scofields Plateau Air Base, Southeast Usea
27 May 2019
Trigger
"Good work you two, dismissed," the Base Commander said.
I stood up from my seat and made for the door when Clown tried to hold me in place by grabbing my shoulder, causing me to almost instinctively throw him over it. Good thing I'm aware of my surrounding enough not to.
"Wait up Leadman, looks like up top got another job for us," he said.
I look over him, sure enough the Base Commander has his adjutant whispering something to him while his eyes locking to our direction. They have received words from upstairs to send us to do more errands for them, it seems.
Of course, why wouldn't they send us on another mission immediately after we finished one? It's not like we're tired after eight days of almost being constantly up in the air fighting for our lives, we've rest enough when listening to debriefing and between missions after all. And our jets, the maintenance crews must have at least checked them out, that should be enough to keep us going even though we're probably got sent out for another job far too soon for them to do anything to our crafts. If we end up getting ourselves killed out there, then we should've pay more attention back at flight school.
Fs.
"What now, sir? Rescue surrounded units? Break the enemy assault? Suicide attack on a 'key position'?" Clown asked after their secret conversation is done, lacking that almost always present cheerfulness. He's more tired about all of these than I thought, it seems.
"Escort mission." Dun dun dun.
"Who's the escorted?" Clown asked.
"If you sit back down, we'll start the briefing," the Base Commander said.
Sit back down, we did. Just like whenever we receive missions like this, the briefing consist of watching a pre-recorded briefing instead of being told by the Base Commander himself.
"The aircraft carrier Vulture alongside several ships and aircrafts belonging to the navy branch of the International Union Peacekeeping Force has been assigned to take part in the operation to take back the space elevator." Thought the force for that are already assembled by now, apparently not.
"IUN, or Osea? Clown snidely asked. For obvious reason, the recording didn't respond.
"As of now the carrier is waiting for the forces and the aircrafts assigned to fill in the gap caused by the surprise attack by Erusea off the southern side of the continent. However, the route taken by this contingent is very close to the enemy territory and we believe that Erusea will most likely try to intercept our allies," the recorded voice said, while the screen is showing the detail of what this contingent are comprised of and their supposed route. There are surprisingly fewer of them than I imagined a task like this would normally require. Tomcats, thought Osea no longer use them, either I was misinformed or these guys just got the short end of the stick.
"The IUN-PKF 508th Tactical Fighter Squadron has been ordered to assist in ensuring the rendezvous a success. First, you will head to the incoming allies position and hold your position there until further orders and then once they've regroup, Mage Squadron will escort them back to Fort Grays or serve as a rear guard if the need arise." As he said that, the screen shows the approximation of what our AO will be like upon our entry.
After some time, the Base Commander turn the screen off, indicating this briefing is over.
"Well, you have your orders. Good luck," he said.
We leave the room to get ready, as usual. It always like this ever since Mage got 'loaned' to the front line, one mission to the next. Stationed on this base today, other base tomorrow. We barely even have time to at least wash our face. I'm amazed that we can still stand and our aircrafts are still in good enough shape to function at all to be honest, but I suppose we're more resilient than I thought.
I glanced over my shoulder to see Clown, who is lagging behind. He didn't show it, but he's probably more tired of all of these missions than I am. It's bad enough that it an almost constant these past days, but it also tend to be futile. A unit that we've rescued will be sent again to their doom, an assault that we repelled would later be followed by an even more fierce assault that we'll be called in again to repel, and the most annoying of all, every time we attack a 'key position' or launch an assault ourselves, it was all a waste of fuel, ammo, and time, and the occasional lives when we work alongside others, because it will either be secured by Erusea before our allies can do anything about it, or even worse those that were supposed to handle things after we secured it is just that incompetent that Erusea would quickly snatch it back. In short, we have to do basically the same thing over and over again, which is annoying.
It almost makes me think they expect us to single-handedly fight and if possible win this war for them, a thought I'm sure also cross Clown's mind. If my experience with them is anything to go by, I believe it actually a possibility. It's not uncommon for me to get sent out to deal with what would be an impossible odds for any other pilots back then. It's less uncommon to be sent out on missions without any chance for respite. Now that I think about it, this really feels like back then, only this time someone occasionally suffer with me.
I almost feel sorry for Clown. I will never say it, but I admit I like the man. It's not every day you get to meet a good-natured opportunists like him. I bet he's hoping things would be easier with me as his wingman. Too bad while I could possibly did make things easier for him, I brought along many cons to outweigh that pros, like the expectations of the Fs back at Osea. Then again, that's what happened if you decided to take chances instead of thinking things through.
Guess it's too late to complain now. At least they don't get clever and try to swindle me out of my pay this time.
When we reached the hangar, the maintenance crews are understandably surprised that we're going up there again this soon. I look at my falcon, it hasn't fail me yet, which is impressive considering who manufacture Osean planes these days.
I got up to the cockpit, will it sturdy enough to get through this mission? Time to find out.
Spring Sea, Southern Usea
27 May 2019
Trigger
"This is Mage, we're in position," Clown said.
"Copy Mage Squadron, keep the airspace secure until our allies arrive," the AWACS assigned with us answered. I just realised I forgot what their TAC name are, we've been through many of them that I fail to see any reason to remember them. They belong to the OADF instead of IUN air force, that much I'm sure.
As ordered we waited, flying around the AO just in case there's something that manage to get through our watcher. We already ran to some opposition on the way here, it's more than likely we'll encounter some more, being close to the enemy territory only ensure it. Being so close to Erusea's territory means if things goes downhill, assistance will take a while if not unlikely. Why they would risk their lives flying this close to the enemy territory would be a mystery only those who decided this is the route they should take can answer. After several minutes of wasting fuel, the AWACS spoke up. Shame, this is the most peaceful that I've been in since we set foot on the front.
"Mage Squadron, Allied forces approaching the operation area."
I look at the radar. Several friendly dots has appeared in it, good to see they at least have the decency to be punctual. The sooner we leave, the less likely we have to deal with interceptors that most likely are already heading our way.
"Roger that," Clown responded, "Allied forces, this is Mage 1. We'll be your escort today," he said to the approaching allies. Quite formal, he really wanted to get this over with, it seems.
"Roger Mage, we have you on radar," they said.
We fall in behind them. It's an odd feeling flying with so many allies like this. Hmm, did I ever do something like this? I don't remember. As we fly, one of the jets is falling behind and take position near us.
"Say, you guys are from Fort Grays right?" someone asked, presumably this pilot.
"That's right," Clown said.
"I knew it. Heard about you guys, they say you're unstoppable."
"Not sure about that. My wingman certainly seems like it."
Unstoppable. It's not even a month yet and already some F are spreading nonsense about us. I suppose a pilot can be unstoppable provided they have the skill and ammo that can last forever. It's a bit silly, but at least it's still believable, even though it's a stretch. I guess I can let it slide this time, so long as that's the only exaggeration them Fs say about us.
"Really? Well, I'll look forward to working you," the pilot said. He then move back to formation with his own squadron and we're once again flying in silence, save for them occasional idle chat the pilots did. That silence is broken for me once again however, when chatterbox pick up an enemy voice.
"Understood, we got them."
I look at my radar, nothing, but that can't be true because chatterbox has caught a voice. Unless it's a ghost, then there has to be some interceptors heading our way. I look around me, these clouds is starting to be quite the inconvenience. I checked my radar once more, one of them will make a mistake and reveal themselves.
Sure enough, I was proven right once more. A single blip appear and quickly disappear, closer than I thought. Thanks experience, you're all right. What's their crafts are, I wonder?
I turned toward the clouds, who knows, maybe I'll crash into one of them.
"Mage 2, stay in formation," the AWACS ordered.
"You got something Trigger?" Clown asked.
I didn't answer, instead letting my action speak for me. Calculating their current possible position based on the information I received, I fire a burst into the clouds and was answered with a hit indicator on my HUD.
"They caught us! All aircraft spread and engage the enemy! Open fire as soon as you come out of the clouds," the enemy said. That's surprising, didn't think they would break that easily.
Enemy signatures is starting to appear into the open as soon as the order are spoken and I finally got a good look at the enemy. Foxhounds, of course, why would I expect anything else?
These guys are fast and annoyingly resilient, but Foxhounds aren't exactly built for close range, and far from being the most manoeuvrable craft in the world, should use that to my advantage.
I open fire on the one right in front of me, from the angle of my approach I should be able to hit the cockpit. It turned out yes, I can hit them and without anyone alive to operate them properly, it was only a matter of giving them an impromptu funeral pyre.
I turned toward the rest of them that has flew past me, ending up on their six. Normally, I would say it's a bit too soon to use my special weapons, what with we've barely a minute from the start of this engagement, but…
I fired my special weapons at the trio of in front of me, and boom they're history. Unfortunately, while I was doing this, two of them attempted to get the best of me. A good plan, but executed poorly.
"Nice kills, Mage 2! Guess they're not wrong about you," someone said.
Strange, here our group consist of fighter jets and several ships down below, but their concern seem to be directed on the aircrafts only.
"All aircrafts, this is Argus. Be advised, multiple bandits carrying long range anti-ship missiles approaching. Mage Squadron, intercept." Ah, there they are.
"We got them," Clown said.
I lower my altitude below the clouds. Su-35, the S variant. Fancy.
"Here they come. Careful with the Hound, he takes on our forces back at Farbanti and come out on top." Who they are talking about, I wonder.
Need to be fast, the ships might ended up in trouble if these guys manage to be within range of their LASM. As I head to greet the new guests, I hear our allies chatting among themselves.
This is why I hate escort duty. Having to worry about someone else's lives, few things are more annoying than that. The fact that silence tend to be unlikely when there are a lot of people only make me hate it even more.
The fighters open fire at us as soon as we're within range, sadly they seem to have forgotten that to hit something, one must make sure the target is right within sight.
I took position on their tail, while Clown is still on the way to assist. I fired a burst at one, turning them from an expensive aircraft into an expensive fireworks. Their reactions are swift, as they're quickly break their formation, two of them are heading for Clown while the rest stay here to deal with me. They wanted to get rid of us first, it seems.
"Take him down. Make him pay for what he did to Erusea!"
Quickly manoeuvre myself behind the closest to me, I open fire as soon as I lined my shot. Can't afford to give them a chance to fight back, I have better things to than humouring a patriot.
Two of them released their missiles at me. Hmm, I wonder…
Turning quickly, I head straight for of them that didn't fire a missile at me. However, I didn't attack it, instead I flew past them, causing the missiles to change target. Huh, it worked, good to know.
I dance around a bit more against the other four. They're good enough, as expected from pilots of one of the best air force in the world. However, good enough is not enough.
They're flying in two-man formation, two of them engage while they each have someone to watch their back just in case I manage to get the better of them. Their reasoning is sound, but not exactly perfect. Outwitting the two designated aggressor, I get behind one of their support and released my missile once I close enough that they don't even have the chance to use their countermeasures. As soon as I took them down, I fired a burst at the aggressor, allowing them to join their wingman. I employ the same tactic on the remaining two.
"Dammit, to think Osea still got pilots like this…" the last of the four said before he disintegrate along with his aircraft. Perhaps if they make more use of the clouds around us, they'll fare much better.
I check how everyone else is holding up. Clown has taken out one of them, I noted, while the last two MiGs have been dealt with. They better give these 'allies' a hard time because if I find these escorted already taken care of them a while ago and content themselves with watching us from a far, then this mission will fail. I head over to where Clown is and take out that last Flanker.
"Thanks, Trigger," he said. Hmm, usually he can take care of himself just fine. If this keeps up, he'll be in serious trouble.
"Area clear. Good work everyone," the AWACS congratulate us. I hear everyone else cheering over our victory. If only it's true.
If the past days is anything to go by, something annoying will happen, like UAVs or something.
"All right, continue the mission. Rendezvous with the carrier ASAP." Any minute now.
We go to where the Vulture is, who been patiently waiting for us quite some distance away from where the engagement took place. Undefended, risky. The Eruseans will kick themselves when they learned that they've let such an easy and expensive prey off their grasp. Still, no complication in sight. Any seconds now.
"Wait. Bogeys inbound." Heh, called it.
"I got them on radar. So many of them!" one of us said.
I checked my own radar. UAVs from the looks of it. Which one, I wonder.
There are some reports about a new type of UAV employed by Erusea. Most of them are rather inconsistent, but so far all reports indicate they have successfully crush any opposition they faced, which means they're possibly better than the 99s. Mage hasn't encounter any of them sadly, though not because of lack of trying.
Need to be careful, I don't know what they are but I'm certain they will be these new types. Lady Luck hate me after all.
Whatever they are, they're fast. Already we can spot them in the distance heading our way.
"Mage Squadron. Intercept and engage, don't let them get close. Everyone else, maintain course and leave the area immediately," the AWACS ordered. These Fs would've told us to get them the sun if they can get away with it. I hear Clown took a big long breath over the radio.
"Well Trigger, guess it's another bout of last stand for us. Let's do this," Clown said.
We turned toward our opposition, just the two of us like these past days. Two overworked, barely alive pilots flying battered aircrafts against at least a whole squadron of fresh, advanced, and fully loaded UAVs.
Command better set us for life after this or someone will kiss a missile, or a bomb, or both.
When we get close, my prediction are proven correct. They are not the 99s. Man Lucy, what did I ever do to you?
"Argus, we have eyes on. Looks like drones, though I never seen them before," Clown said.
"It doesn't matter, hold them off," the AWACS said. Typical, just typical.
It took me quite the effort just to scan their capabilities. Faster, higher manoeuvrability, and lacking in human's inhibition. They're definitely better than the 99s. Still, it appears that at its core, they're just like them. Flying based on what data they're provided with, which could possibly means they suffer from the same flaw and repetitiveness as the 99s.
As I engaged them, I noticed that while yes they're still flawed, they fly better than the 99s, providing less opening than them. Still many of the flaws, especially the bigger ones are still there and they're still as repetitive as ever. Whoever these drones are based on must be one lucky pilot if they're still alive now, what with their glaringly flawed flying style.
Thanks to these disadvantages and their fragility, we managed to one by one take them down, though it's more like only me I noted. Clown is surprisingly quite restrained while engaging them. The fatigue is finally getting to him, it seems. He better snap out of it soon, doubt these drones got any mercy in them.
As I thought, they don't. Slowly, they are starting to overwhelm him, and eventually land some hits on him.
"Dammit, I'm hit!" That shook him awake at least.
"This is Argus. Mage 1, are you all right?"
"I'm fine, for now."
"Dammit." After a few moment of silence, the AWACS spoke up again.
"All right, Mage 1 withdraw and rejoin our allies. Mage 2, hold them off until our allies have left the combat zone." Figures. And they still dare to look down on me.
I looked at what's left of these drones. Only now I realised that these guys receive constant flow of reinforcements. For every one we shot down, more will come to replace it. Them 'allies' better pick up the pace, my ammo supply aren't exactly infinite.
Hold them off I did, regardless of how futile it was. Well, at least my first time engaging them was in a rather fair circumstances. What I learned today will help in keeping me alive in the future, that's always a plus. If this is an RPG, I would've level up quite a lot by now.
But still, that doesn't mean I can do this forever. This aircraft can't run without fuel after all.
"Mage 2, all allies have successfully leaving the operation are. Good work, now get out of there." Finally.
As soon as the orders came out of his mouth, I took the first chance I got to break off. The drones however, either programmed not to let a prey escape or wasn't very keen in letting their brethren die for nothing, give chase. Really, Osea better sculpt a golden statue in my honour for this.
…On second thought, forget the statue. They better give me the gold for the statue and some more for this mess.
I manoeuvre as wildly as I can to throw them off my back, using the clouds for good measure, dodging and weaving to evade their attacks. It worked for the most part, though not exactly enough to completely clear my six. I suppose it can't be helped, they are advanced. The warning alarm's going crazy with their warnings, so does Heather, reminding me that I'm in danger. I can feel my craft protesting against my command every time I manoeuvre. Come on, stay strong just a bit more. We don't endure this long just so you can break when success is within sight.
For what feels like hours I dance with them, trying to get them off my tail and shooting down any that I can shoot down. But there are many of them and my patience is wearing thin. Next time, when the order are no longer to retreat but to kill, I'll kill them so hard they'll independently learn the meaning of regret. But for now, I need to find a way to clear out.
All right, think, there has to be a way. Their numbers are compensating their repetitive movements and looks like the move they take are randomised for each drones, but it still randomised from the same flying style. Just need to wait when most of them do one of their flawed move and rip it open.
…There.
Punching through the opening, I hit the gas as hard as I can. They're quick to caught on, unfortunately, and being faster they rapidly closing in. The lock on warning is blaring once again. You're wasting your missiles, you flying tin can.
However, there are no missile warning that followed it, the warning instead abruptly stopped.
"Bogeys are retreating. That some impressive flying, Mage 2." What?
I checked the radar and looked behind me. As the AWACS said, they are retreating. That's odd.
"You're well behind everyone else, they're waiting for you up ahead," the AWACS said. Right, this mission isn't exactly over yet.
Refocusing myself, I turn back toward the task at hand. I can think of all of the question I had after a bit of a rest.
Fort Grays Air Base, Southeast Usea
27 May 2019
Victoria 'Brownie' Hardy
"Here they come," Knocker said. I look toward the horizon, spotting some ships and aircrafts in the distance. Finally.
It's been eight days since Mage were sent to the front to assist in pushing the Eruseans back. A long and agonising eight days of waiting, worrying, and wondering just why they were sent out without Golem. Bossman and the Base Commander said the request came straight from far up and there is nothing we can do about it.
And so while Golem remained here preparing for the operation to retake the space elevator, Mage is out there, kicking ass and taking names.
I can't say I'm happy about it, why Mage gets to be the hero while Golem stuck with this? Sure it's important, but dammit more than half of the job is just waiting around doing nothing! It might not be so bad if I get to relax in those times, but I can't.
Every time I tried to, my mind would drift to Trigger. I heard all about his exploits back home and I've seen with my own eyes how capable he actually is, but I just can't help it. I can't stop thinking about all the bad things that could happen to him. What if he met his match? What if he finally get himself into a situation he can't handle? What if he's betrayed and the ally become the enemy? I know it's unlikely especially the last one, I mean he takes on squadrons of highly advanced UAVS and one of the best air force in the world by himself and basically won. If they can't bring him down, what chance do we have?
But on the other hand, what if against all odds it happens? What if some guy got lucky and shoot him down? Or he do something stupid like sacrificing himself?
Okay, that last one might be a bit stupid.
In any case, when I heard that Mage Squadron is escorting some allies back to Fort Grays, well, I'm ecstatic. I could at least make sure he's alive.
That is why right now Golem is currently watching the incoming allies from the harbor, hoping to catch an early glimpse of the duo.
"Someone's trailing smoke," Boggard brought me out of my thought.
I look at the one Boggard was talking about and regret it. A lone viper is trailing behind everyone else, smoke trailing him.
Immediately negative thoughts invade my mind. Is that Trigger or Clown? Where's the rest of Mage? What happened to them?
"All right, come on," Knocker said. He didn't show it, but I know he's worried. Clown is his best friend after all.
We head for the hangars. We'll learn what happened later.
We arrived just in time to see Clown or Trigger on a final approach. Hopefully the damage looks worse than it actually is. Thankfully, it does. The falcon land and head for the hangars without much problem.
When we come over, we saw that it was Clown. Fear gripped my heart.
"Hey guys, good to see you again," he said. He looks like he barely had enough rest to pilot, and it shows when he almost fell off the cockpit when he tried to get out of it. Thankfully, Knocker and the maintenance crew is quick to help him.
"What the hell happened to you?" Knocker said.
"Oh you know, the usual sortie and all that." At least he's good enough to joke around. But when he realized Knocker isn't laughing, he took a more serious expression.
"We were attacked by some new type of drones and the AWACS got the bright idea to only have us to hold them off."
"Captain?" I called, a call that took him a bit to respond to.
"Where's Trigger?" This is it, the shots fired. I prepared myself for the worst.
"Sorry but… I'm not sure. He was ordered to watch our back. He's still fine when I got hit though."
Okay, that still leave the possibility that he's okay. He had done the same thing back at Farbanti, if he can survive that, these new drones shouldn't be a problem.
Still, when he do it back then he's in a prime condition, or at least as prime as someone like him can be. If Clown looks like that, then he shouldn't be any better.
I'm overthinking this, he'll be fine. He'll said the same thing if he's here, plus some sarcasm and tactless comments, if he could be bothered to talk at all.
So I waited, letting Knocker deal with his best friend. Thankfully I don't have to wait long.
In the distance, a lone F-16 is approaching. From the way it fly alone, it's obvious who that is. Thank goodness.
He approach from the same direction as everyone. From the look of it, he at least doesn't seem to be damaged.
He landed, in a faster speed than should've been. Thankfully, it didn't damage his landing gear.
When I come over, he's still inside the cockpit. As I expected he look even worse than Clown is, which is saying something. I climb up the ladder.
"Trigger." I shook him. He didn't react.
"Hey, you're all right?" Still no response.
"Axe," I shook him again, a bit harder. Normally, I would've smack him by now, but in this condition I'm worried that I might actually hurt him.
He finally react, looking at me with barely focused eyes. What the hell happened to them?
"Come on, let's get out of here," I told him.
I help him get off his jet. Command better pray I never find out what they have them do while on the front if they knew what is good for them.
I walk as close as I can to him, just in case he abruptly collapsed. He seems to be able to walk just fine, though with a slight limp in every step.
"I think we should get you checked up first."
"No need to bother the doctor," he said.
"It's hardly bothering. Taking care of sick people is their job."
He didn't respond, but continuing to the debriefing.
"I can—" He stopped me with a hand on my shoulder.
"I'm fine," he said. He then walked off, while I stood there like a stump. I quickly catch up when I realized he's leaving me behind.
Debriefing was awkward, to say the least. The Base Commander has to stop every few seconds because the two guys that this debriefing are meant for either lose focus or straight to dozing off. It's a good thing he's patient and understanding enough of their plight and keep it short. Might as well, doubt any of them even register what he was talking about. That is why I made a note for him.
When it's done I was quick to grab hold of him, no way I would let him wander off and doing who knows what while being barely alive like this. Obviously, he's not exactly on board with my idea.
"You need to rest."
"I am going to my room." That caught me off guard. Usually it took a bit of 'convincing' before he would do something sensible like resting when tired.
I let go of him, but remaining close to him. As he said, he went straight for his room, though he's not exactly resting.
"Aren't you going to rest?"
"I am resting," he said.
"You got a different definition of it than me."
He continue writing something on his journal, probably about whatever information his brain manage to memorize, while I spent the rest of it convincing him to take a break.
"You know, I already have a note about what those UAVs if you want." He look away from his book.
"You're persistent." And you're stubborn.
"Only because it matters and I know you don't get enough rest out there."
"What gave it away?"
"Don't try that tone with me, I'm serious right now," I said.
"Come on, just lie in your bed and close your eyes. I don't understand why this is so hard for you."
"Maybe because there is an annoying nag that won't shut up about it."
"Well, that good samaritan can't shut up about it because there is a stubborn mule that doesn't seem to understand how to take care of himself!"
"Hmm? There's a mule here?" he asked, a hint genuine curiosity in his voice.
"No, I mean— ugh! You're really know how to get under someone's skin, you know that?" He tipped his hat.
"Fine, whatever. Just don't go running to me if you ended too tired to do anything."
"I can't run if I'm too tired."
"You know what I meant!"
This dense, stubborn idiot. The nerve of him! Here I was trying to be nice and help him and he repay me by being an insufferable ass. I don't even know why I bother in the first place!
I stopped my line of thought. Dammit, I fell for it again.
For some reason, it's hard for me to control my emotion when around him. That and the fact that he, regardless of what he said, love to mess with people's head means all of those years of practicing to be more patient immediately went down the drain.
"You know what, I'll stop pestering you if you tell me what you're doing at the front."
"You know what I'm doing."
"Only broadly, we both know you've been doing more than that."
And that is, as much as I hate to say it, the truth. All I know is that Mage orders came straight from the top. What's the orders are, I have no idea.
"No."
"Why not?"
"Reasons." This secrecy is starting to get aggravating!
"Because you're secretly still been doing a 'solo flight', didn't you?" He closed his book.
"That's right, I heard about—" He suddenly stood up and close in.
"Don't finish that sentence," he said with a tone that he usually reserved for when he's about to rip someone a new one.
"You heard, but you don't know."
"Then tell me. I thought—" He cut me off with a very sharp pen on my throat, so sharp that all he need to is a bit more push to get some blood out of me.
"If you know what's good for you, you'll get it out of your head and throw it away as far as you can."
"T-Trigger…" He pulled his hand back and get back to sitting spot.
"Some things are better left alone," he said as he's sitting down.
I didn't register what he said, too surprised by what just happened.
When I came to, I look at him still sitting there like nothing happened, his face kept hidden by his hat. He… he just…
As fast as I can, I turned around and ran. I ran, ignoring everyone and everything until I reached my own room.
He just threatened me. He, my best friend, someone I trust the most, someone that I thought will always be there for me just like I'm to him, someone that I love, just threatened to kill me, without even the slightest hint of hesitation.
Why? Why would he do that? All I've done is trying to help him and mention his lack of wingmen back when he's still back at Osea. Why did he suddenly become aggressive? Is it because I reminded him when he's alone? That's very unlikely, but…
Yes, it has to be about that. But why did he mad at that? It's not like flying solo is anything bad. Why, I heard the Ribbon did basically that most of the time.
There has to be something about it. Something more than just him being on his own. Perhaps even something bad. Why would he threatened me if he has nothing to hide?
That's it. With a new found determination, I stood back up. If he in trouble and can't say it then I'll step in myself. Still, I can't do this on my own. Hmm…
I know just the person to help me. | null | minipile | NaturalLanguage | mit | null |
On Cancer: Memorial Sloan Kettering Featured Prominently at Major Cancer Research Meeting
Two Memorial Sloan Kettering studies about targeted cancer therapies received recognition in the press program for one of the nation’s premier cancer research events: the American Association for Cancer Research (AACR) Annual Meeting 2014, held April 5–9 in San Diego. The press program highlights cancer research that a panel of AACR experts considers the most significant of the year and deserving of media attention.
In addition, several Memorial Sloan Kettering investigators received awards and assumed leadership roles.
The AACR meeting brings together roughly 18,000 researchers, patient advocates, and other professionals in the cancer field to present the latest basic, translational, and clinical discoveries. Memorial Sloan Kettering cancer biologist Scott Lowe, who chairs the Geoffrey Beene Cancer Research Center, served as the meeting’s Scientific Program Committee Chairperson.
IDH2 normally makes a protein that plays a critical role in cellmetabolism. However, when the gene is mutated, it can lead to the production of an abnormal protein that is thought to cause some types of cancer — including AML and MDS — by preventing healthy bone marrow cells from maturing.
Dr. Stein presented preliminary results on ten patients who received one of two doses of AG-221 twice daily. Three patients were not able to complete a full cycle of therapy due to complications of their disease, but six of the remaining seven patients had responses, including three complete remissions.
While phase I clinical trials are designed primarily to determine the safety and tolerability of a new drug, Dr. Stein said he is encouraged by the results he’s seen thus far with AG-221 and its implications for the emerging field of targeting cancer metabolism.
Identifying Mechanism by Which Tumors Become Resistant
BYL719 is an investigational drug that targets PI3K-alpha, a gene known to be mutated in a third of breast cancers and to play an important role in the disease. Castel and his colleagues sequenced the DNA of multiple metastatic tumors from a patient who initially responded dramatically to BYL719 but whose cancer eventually returned. Some of these metastatic tumors were sensitive to BYL719 while others proved resistant.
By comparing the DNA of the two tumor types, the researchers found that the resistant tumors had different mutations in the gene PTEN that may have caused the drug to stop working. The responsive tumors contained normally functioning PTEN genes.
Using mouse models, the researchers were able to show that combining BYL719 with a drug that targets another protein responsible for the resistance “reeducated” the cancer to respond to treatment. Castel said that the results stress the importance of developing dynamic therapy so that physicians can adjust treatment as tumors evolve and acquire new mutations that cause drug resistance.
Awards and Appointments for Memorial Sloan Kettering Staff
Several Memorial Sloan Kettering investigators were honored at the meeting.
Maurizio Scaltriti, an Assistant Lab Member in the Human Oncology and Pathogenesis Program (HOPP), was named one of the AACR's “NextGen Stars.” For the first time, the AACR accepted applications from early-career investigators to present their research during selected major symposia. Dr. Scaltriti was chosen as one of five investigators from more than 100 applicants.
Dr. Stein’s research was funded by Agios Pharmaceuticals; Pau Castel’s research was funded by Stand Up To Cancer and the Breast Cancer Research Foundation.
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abnormal (ab-NOR-mul)
Not normal. An abnormal lesion or growth may be cancer, premalignant (likely to become cancer), or benign (not cancer).
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
acute (uh-KYOOT)
Symptoms or signs that begin and worsen quickly; not chronic.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
AML
An aggressive (fast-growing) disease in which too many myeloblasts (immature white blood cells that are not lymphoblasts) are found in the bone marrow and blood. Also called acute myeloblastic leukemia, acute myelogenous leukemia, acute myeloid leukemia, acute nonlymphocytic leukemia, and ANLL.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
blood (blud)
A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
bone marrow (bone MAYR-oh)
The soft, sponge-like tissue in the center of most bones. It produces white blood cells, red blood cells, and platelets.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
cancer (KAN-ser)
A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
cell (sel)
The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
clinical (KLIH-nih-kul)
Having to do with the examination and treatment of patients.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
clinical trial (KLIH-nih-kul TRY-ul)
A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
DNA
The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called deoxyribonucleic acid.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
drug (drug)
Any substance, other than food, that is used to prevent, diagnose, treat or relieve symptoms of a disease or abnormal condition. Also refers to a substance that alters mood or body function, or that can be habit-forming or addictive, especially a narcotic.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
drug resistance (... reh-ZIH-stunts)
The failure of cancer cells, viruses, or bacteria to respond to a drug used to kill or weaken them. The cells, viruses, or bacteria may be resistant to the drug at the beginning of treatment, or may become resistant after being exposed to the drug.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
gene (jeen)
The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
immunotherapy (IH-myoo-noh-THAYR-uh-pee)
Treatment to boost or restore the ability of the immune system to fight cancer, infections, and other diseases. Also used to lessen certain side effects that may be caused by some cancer treatments. Agents used in immunotherapy include monoclonal antibodies, growth factors, and vaccines. These agents may also have a direct antitumor effect. Also called biological response modifier therapy, biological therapy, biotherapy, and BRM therapy.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
investigational (in-VES-tih-GAY-shuh-nul)
In clinical trials, refers to a drug (including a new drug, dose, combination, or route of administration) or procedure that has undergone basic laboratory testing and received approval from the U.S. Food and Drug Administration (FDA) to be tested in human subjects. A drug or procedure may be approved by the FDA for use in one disease or condition, but be considered investigational in other diseases or conditions. Also called experimental.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
investigator (in-VES-tih-gay-ter)
A researcher in a clinical trial or clinical study.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
leukemia (loo-KEE-mee-uh)
Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
medical oncologist (MEH-dih-kul on-KAH-loh-jist)
A doctor who specializes in diagnosing and treating cancer using chemotherapy, hormonal therapy, biological therapy, and targeted therapy. A medical oncologist often is the main health care provider for someone who has cancer. A medical oncologist also gives supportive care and may coordinate treatment given by other specialists.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
melanoma (MEH-luh-NOH-muh)
A form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
metabolism (meh-TA-buh-lih-zum)
The chemical changes that take place in a cell or an organism. These changes make energy and the materials cells and organisms need to grow, reproduce, and stay healthy. Metabolism also helps get rid of toxic substances.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
metastatic (meh-tuh-STA-tik)
Having to do with metastasis, which is the spread of cancer from the primary site (place where it started) to other places in the body.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
myeloid (MY-eh-loyd)
Having to do with or resembling the bone marrow. May also refer to certain types of hematopoietic (blood-forming) cells found in the bone marrow. Sometimes used as a synonym for myelogenous; for example, acute myeloid leukemia and acute myelogenous leukemia are the same disease.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
oncology (on-KAH-loh-jee)
The study of cancer.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
pancreatic (PAN-kree-A-tik)
Having to do with the pancreas.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
protein (PROH-teen)
A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
resistance
Failure of a cancer to shrink after treatment.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
significant (sig-NIH-fih-kunt)
In statistics, describes a mathematical measure of difference between groups. The difference is said to be significant if it is greater than what might be expected to happen by chance alone. Also called statistically significant.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
stress (stres)
The response of the body to physical, mental, or emotional pressure. This may make a person feel frustrated, angry, or anxious, and may cause unhealthy chemical changes in the body. Untreated, long-term stress may lead to many types of mental and physical health problems.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
therapy (THAYR-uh-pee)
Treatment.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
tumor (TOO-mer)
An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)
will (wil)
A legal document in which a person states what is to be done with his or her property after death, who is to carry out the terms of the will, and who is to care for any minor children.
Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary) | null | minipile | NaturalLanguage | mit | null |
Re: Forum Game: Famous people with Bulldogs
Originally Posted by cali baker
I didn't scroll through all the replies to see if Ashton Kutcher was mentioned or not. I just saw this sad story a few minutes ago that he recently had to euthanize his bully due to illness. The article didn't go into further detail. | null | minipile | NaturalLanguage | mit | null |
according to maslow, the psychological need that arises after all other needs have been met is the need for
trait
kelsey is consistently optimistic, talkative, and impulsive. each of these characteristics most clearly represents a :
learned helplessness
reserachers have observed that the experience of repeated uncontrollable traumatic events contributes to:
identify
a psychotherapist is most liekly to use the DSM-IV in order to_______ various psychological disorders
a persistent, irrational fear of a specific object or situation
phobias are most likely to be characterized by:
major depresssive disorder
norby and 18 year old collge freshman has missed almost all his classes in the last month, spends time in his room, many times doesn't dressed or eat meals. he thinks of his life as a failure and blames himself. he is most likely suffering from:
disorganized and fragmented thinking
schizophrenia is most likely to be characterized by:
antisocial personality
a lack of conscience is most characteristic of those who have an______ disorder
major depressive disorder
mood disorder
antisocial type
personality disorder
obsessive compuslive disorder
anxiety disorder
paranoid sub type
schizophrenia
panic disorder
anxiety disorder
narcissistic type
personality disorders
eclectic
a therapitst who uses a variety of psycholical theories and therapeutic methods is said to be:
uncensored reporting of any thoughts that come to mind
free association involves the:
client- centered therapy
carl rogers is known for the develpment of :
behavior therapy
which of the following therapies is more concerned with removing specific troubling symptoms than with providing special insights into the personaliy of the client?
cognitive
training people to stop blaming themselves for failures and negative circumstances beyond their control is of the most direct concern to _______ therapists
establish an emphathetic, caring relationship with their clients
the most effective psychotherapits are those who:
psychopharmacology
the study of the effect of drugs on mind and behavior is called:
preventive mental health
which approach would attempt to minimize psychological disorders by working to reduce the incidence of child abuse and illiteracy in society?
think about, influence, and relate to
the text defines social psychology as the scientific study of how people_____ one another
attitudes
beliefs and feelings that predispose us to respond in particular ways to objects, people and events are called:
cognitive dissonance theory
which theory emphasizes that we adopt certain attitudes in order to justify our past actions
informational social influence
conformity resulting from the acceptance of others' opinions about reality is said to be a response to:
social facilitation
norman triplett observed that adolescents wound a fishing reel faster in the presence of someone working simulataneously on the same tasks. this best illustrates:
the enhancement of a group's prevailing attitudes thruogh group discussion
group polarization refers to
"we have been united on matters by the leader of a group characterized by groupthink?
which of the following comments is most likely to be made by the leader of a group characterized by groupthink?
father care
high rates of violence are most common among those who experience minimal levels of:
physical appearance
our first impressions of those we meet are most likely to be determined by their
the bystander effect
people are less liekly to give aid if an emergency occurs in the presence of many observers. This is known as: | null | minipile | NaturalLanguage | mit | null |
Hospital remoteness and thirty-day mortality from three serious conditions.
Rural U.S. communities face major challenges in ensuring the availability of high-quality health care. We examined whether hospital-specific, all-cause, thirty-day risk-standardized mortality rates (RSMRs) following acute myocardial infarction, heart failure, and pneumonia varied by hospitals' geographic remoteness. We analyzed 2001-2003 Medicare administrative data, comparing RSMRs among hospitals located in urban, large rural, small rural, or remote small rural regions. We found only small mortality differences across remoteness regions for hospitalizations for the three conditions. We examine the implications of these findings for the millions of Americans who rely upon rural hospitals for their care. | null | minipile | NaturalLanguage | mit | null |
Human mitochondrial diseases associated with tRNA wobble modification deficiency.
A growing number of mutations in mitochondrial (mt) tRNA genes have been found to associate with human mitochondrial diseases. Our previous analysis of mutant mt tRNAs isolated from cells derived from patients with mitochondrial diseases revealed the lack of a post-transcriptional taurine-modification at the anticodon wobble uridine in two mt tRNAs bearing typical pathogenic mutations: mt tRNA(Leu(UUR)) with either the MELAS 3243 or 3271 mutation and mt tRNA(Lys) with the MERRF 8344 mutation. We here summarize our recent studies that clarify the molecular basis of the defective mitochondrial translation caused by this wobble modification deficiency. The MERRF mt tRNA(Lys) lacking the wobble modification cannot translate either of its codons (AAA and AAG), while the translational activity of MELAS mt tRNA(Leu(UUR)) lacking wobble modification is more depressed in decoding of UUG codon than UUA codon. These findings suggest that the wobble modification deficiency plays a primary role in the molecular pathogenesis of the MELAS and MERRF mitochondrial diseases. | null | minipile | NaturalLanguage | mit | null |
[Psychological evaluations of operation of patients with mental disorders].
The severe and chronic mental illnesses such as schizophrenia are associated with very complex problems that are not confined to the symptoms but also affect psychosocial functioning and community integration. To evaluate the reliability (in terms of internal consistency) of the WHODAS 2.0 for analyzing the psychosocial functioning of people with schizophrenia living in the community and using mental health services, and report the WHODAS 2.0 results from the same sample. The sample comprised 100 users diagnosed with schizophrenia (F20 to F29 of ICD 10) living in the community and in contact with mental health services in Córdoba, Buenos Aires and San Luis in Argentina. Interviewers were trained in the use of the WHODAS 2.0. For the overall internal consistency of the WHODAS 2.0: Cronbach's alpha = 0.78. WHODAS 2.0 results for these service users were: Domain 1, 57% none, 19.4% mild, 20.4% moderate, 3.2% severe. Domain 2, 60.2% none, 18.3% mild, 17.2% moderate, 3.2% severe. Domain 3, 54.9% none, 23.7% mild, 19.4% moderate, 2.2% severe. Domain 4, 74.2% none, 18.3% mild, 6.5% moderate, 1.1% severe. Domain 5, 82.8% none, 1.8% mild, 4.3% moderate, 1.1% severe. Domain 6, 81.7% none, 15.1% mild, 3.2% moderate. WHODAS 2.0 showed high internal consistency in this population. Most of the service users had no disability or mild disability in all 6 domains. A substantial minority had moderate disability in some domains (D1, D3). In all domains, <5% had severe disability. | null | minipile | NaturalLanguage | mit | null |
- Bottle Retention - There is nothing worse than looking down at your bike and realizing that you have one less water bottle than you started with. Our cages are vigorously lab AND field tested at each stage of the development process to ensure that your water is safely held to the bike.
Details:
- Black Matte is the lightest color/finish combination. Weight may vary up to 3 grams between other colors/finishes.
- Two mounting bolts included | null | minipile | NaturalLanguage | mit | null |
Tarabai Modak
Tarabai Modak (19 April 1892-1973) was born in Mumbai. She graduated from the University of Mumbai in 1914.
She was married to a lawyer from Amravati, Mr. Modak. Later she got a divorce in 1921.
She worked as a principal of a Women's College in Rajkot.
Social worker from Vidarbha region of Maharashtra. Balwadis were first developed her, the first balwadi was started in Bordi a coastal village in Thane district of Maharashtra by Nutan Bal Shikshan Sangh.
She was awarded Padma Bhushan in 1962 for her work in preschool education. Anutai Wagh was her disciple.
She was a member of the Indian National Congress.
Legacy
A play based on her life, Ghar Tighancha Hava, was produced by Ratnakar Matkari.
References
Category:1892 births
Category:1973 deaths
Category:People from Mumbai
Category:University of Mumbai alumni
Category:Indian women social workers
Category:20th-century Indian educational theorists
Category:Recipients of the Padma Bhushan in social work
Category:19th-century Indian women
Category:20th-century Indian women scientists
Category:Women educators from Maharashtra
Category:Educators from Maharashtra
Category:Social workers from Maharashtra | null | minipile | NaturalLanguage | mit | null |
Catholic education in Australia
Catholic education in Australia refers to the education services provided by the Roman Catholic Church in Australia within the Australian education system. From 18th century foundations, the Catholic education system has grown to be the second biggest provider of school-based education in Australia, after government schools. The Catholic Church has established primary, secondary and tertiary educational institutions in Australia. , one in five Australian students attend Catholic schools. There are over 1,700 Catholic schools in Australia with more than 750,000 students enrolled, employing almost 60,000 teachers.
Administrative oversight of Catholic education providers varies depending on the origins, ethos, and purpose of each education provider. Oversight of Catholic systemic schools may rest with a Catholic parish, diocese, or archdiocese; while religious institutes have oversight of Catholic independent schools; and Catholic universities are administered through an academic senate.
Schools
History
The first permanent Catholics in Australia came on the First Fleet to Sydney in 1788. One-tenth of all the convicts who came to Australia on the First Fleet were Catholic and at least half of them were born in Ireland. A small proportion of British marines were also Catholic.
Just as the British were setting up the new colony, French captain Jean-François de Galaup, comte de Lapérouse arrived off Botany Bay with two ships. La Pérouse was six weeks in Port Jackson, where the French, besides other things, held Catholic Masses.
Some of the Irish convicts had been transported to Australia for political crimes or social rebellion in Ireland, so the authorities were suspicious of the minority church for the first three decades of settlement. Catholic convicts were compelled to attend Church of England services and their children and orphans were raised by the authorities as Anglicans. The first Catholic priest colonists arrived in Australia as convicts in 1800 – convicted for "complicity" in the Irish 1798 Rebellion. The Irish led Castle Hill Rebellion of 1804 alarmed the British authorities and the priests permission to celebrate Mass was revoked. Priests were not officially permitted to travel to the colony until 1820.
At first, the Church of England was the established christian church in the colony, and during the early years of transportation all convicts were required to attend Anglican services on Sundays. This included Irish Catholics as well as Jews. Similarly, education in the new settlement was Anglican-controlled until the 1840s.
Free "charity schools" run by other denominations gradually came into existence later.
The absence of a Catholic mission in Australia before 1818 reflected the legal disabilities of Catholics in Britain and the difficult position of Ireland within the British Empire, but by 1833, there were around ten Catholic schools in the Australian colonies. The Church of England lost its legal privileges in the Colony of New South Wales following the Church Act of 1836. Drafted by the Catholic attorney-general John Plunkett, the act established legal equality for Anglicans, Catholics and Presbyterians and was later extended to Methodists.
John Bede Polding, a Benedictine monk, was Sydney's first bishop (and then archbishop) from 1835 to 1877. Polding requested a community of nuns be sent to the colony and five Irish Sisters of Charity arrived in 1838. While tensions arose between the English Benedictine hierarchy and the Irish Ignatian-tradition order from the start, the sisters set about pastoral care in a women's prison and began visiting hospitals and schools and establishing employment for convict women. In 1847, two sisters transferred to Hobart and established a school. The sisters went on to establish hospitals in four of the eastern states.
At Polding's request, the Christian Brothers arrived in Sydney in 1843 to assist in schools but the Irish-English divide proved problematic and the brothers returned to Ireland. In 1857, Polding founded an Australian order of nuns in the Benedictine tradition – the Sisters of the Good Samaritan – to work in education and social work.
Establishing themselves first at Sevenhill, in the newly established colony of South Australia in 1848, the Jesuits were the first religious order of priests to enter and establish houses in South Australia, Victoria, Queensland and the Northern Territory – Austrian Jesuits established themselves in the south and north and Irish in the east. The Australian gold rushes saw a rapid increase in the population and prosperity of the colonies. While the Austrian priests traversed the Outback on horseback to found missions and schools, the Irish priests arrived in the east in 1860 and had by 1880 established the major schools of Xavier College in Melbourne, St Aloysius' College and Saint Ignatius' College, Riverview in Sydney – which each survive to the present.
In 1872, Victoria became the first Australian colony to pass an education act providing for free, secular public education. The other colonies followed over the following two decades. With the subsequent withdrawal of state aid for church schools around 1880, the Catholic Church, unlike other Australian churches, put great energy and resources into creating a comprehensive alternative system of education. It was largely staffed by nuns, brothers and priests of religious orders, such as the Christian Brothers (who had returned to Australia in 1868); the Sisters of Mercy (who had arrived in Perth in 1846); Marist Brothers, who came from France in 1872 and the Sisters of St Joseph, founded in Australia by Mary MacKillop and Fr Julian Tenison Woods in 1867. MacKillop travelled throughout Australasia and established schools, convents and charitable institutions but came into conflict with those bishops who preferred diocesan control of the order rather than central control from Adelaide by the Josephite order. MacKillop administered the Josephites as a national order at a time when Australia was divided among individually governed colonies. She is today the most revered of Australian Catholics, canonised by Benedict XVI in 2010. Catholic schools flourished in Australia and by 1900 there were 115 Christian Brothers teaching in Australia. By 1910 there were 5000 sisters from all orders teaching in schools.
Following the Second Vatican Council of the 1960s, the church experienced huge changes but also began to suffer a decline in vocations to the religious life, leading to a priest shortage. On the other hand, Catholic education under lay leadership has expanded, and about 20% of Australian school students attend a Catholic school. In 1962, Goulburn was the focus of the fight for state aid to non-government schools. An education strike was called in response to a demand for installation of three extra toilets at a local Catholic primary school, St Brigid's. The local Catholic archdiocese closed down all local Catholic primary schools and sent the children to the government schools. The Catholic authorities declared that they had no money to install the extra toilets. Nearly 1,000 children turned up to be enrolled locally and the state schools were unable to accommodate them. The strike lasted only a week but generated national debate. In 1963 the prime minister, Robert Menzies, made state aid for science blocks part of his party's platform. Since the late 1960s, generous funding from state and federal governments has sustained the Catholic education system.
Australia's post-World War II multicultural immigration program has seen a diversification of the Catholic population of Australia away from its predominantly Irish roots – with Catholics arriving from nations like Italy, Lebanon, Malta, Vietnam and Sudan and changing the face of the student population undergoing Catholic education.
Allegations of sexual abuse by staff associated with Catholic education in Australia have involved small fractions of students and staff at Catholic schools and received widespread media and community scrutiny. In 1996, the Australian Church issued a document, Towards Healing, which it described as seeking to "establish a compassionate and just system for dealing with complaints of abuse". Papal apologies followed from John Paul II and Benedict XVI. Outside the church, Broken Rites, a not-for-profit organisation, was formed in 1983 with the aim of researching the cover-up of sexual abuse in the Catholic Church.
, one in five Australian students attend Catholic schools. As with other classes of non-government schools in Australia, Catholic schools receive funding from the Commonwealth government. Church schools range from elite, high cost schools (which generally offer extensive bursary programs for low-income students) to low-fee local schools. Notable schools include the Jesuit colleges of Loyola College Watsonia, St Aloysius, Loyola Senior High School, Mount Druitt and Saint Ignatius' College, Riverview in Sydney, Saint Ignatius' College, Adelaide and Xavier College in Melbourne; the Marist Brothers St Joseph's College, Hunters Hill, and the Marist Brothers St Gregory's College, Campbelltown; the Society of the Sacred Heart's Rosebay Kincoppal School, the Institute of the Blessed Virgin Mary's Loreto Normanhurst and Loreto Kirribilli, the Sisters of Mercy's Monte Sant' Angelo Mercy College, the Christian Brothers' St Edmund's College, Canberra, Waverley College Sydney, St Kevin's College, Melbourne, St Mary Mackillop College, Canberra and Aquinas College, Perth – however, the list and range of Catholic primary and secondary schools in Australia is long and diverse and extends throughout metropolitan, regional and remote Australia: see Catholic schools in Australia.
Administration and funding
In Australia, the state and territory governments have the primary responsibility for funding state government schools and also provide supplementary assistance to non-government schools. However, the Australian federal government is the primary source of public funding for non-government schools (while also providing supplementary assistance to government schools). These public funds subsidise the fees paid by parents for the education of their children at Catholic schools. These provide the overall effect of reducing the numbers and therefore burden on public funding for government schools. Most non-government schools have some religious affiliation, with approximately two-thirds of their students enrolled in Catholic schools. In the final year of secondary schooling, students at both government and non-government schools sit for a government-endorsed certificate that is recognised by all Australian universities and vocational education and training institutions. Thus, Catholic schools may freely teach and encourage religious studies, values and community engagement; and must adhere to the broader requirements of Australia's secular education system.
The National Catholic Education Commission (NCEC), established by the Australian Catholic Bishops Conference through the Bishops Commission for Catholic Education, is tasked with maintaining liaison with the federal government and other key national education bodies and complements and supports the work of the state and territory Catholic education commissions. While some Catholic schools operate independently via religious institutes, the majority of Catholic schools, called systemic schools, operate under the Canon Law jurisdiction of an ecclesiastical public juridic person, such as a bishop. In practice, the bishop assigns a Catholic Education Office (CEO), Catholic Education Commission, Catholic Schools Offices, or a similar body with daily operational responsibility for the leadership, efficient operation, and management of the Catholic systemic schools which educate in parish primary and regional secondary schools in Australia. These diocesan bodies are charged with the implementation and management of the policies of the diocese and the allocation and administration of the funds provided by government and private sources to Catholic systemic schools, as well as the financial responsibilities for administration of salaries for staff members.
Many Catholic schools in Australia are connected to the Internet via Catholic Education Network (CEnet).
Ethos
While Catholic schools must adhere to the broad requirements of Australia's secular education system, they are free to provide a "Catholic" education ethos. The Catholic Education Office of Melbourne outlines this "ethos" as follows:
Catholic view of marriage
With curriculum changes flowing from possible outcomes of the Australian Marriage Law Postal Survey, the NCEC said, without seeing what was proposed, "it is impossible to ... ensure Catholic schools can continue to teach the Catholic view of marriage".
Alumni
Among the millions of Australians who have attended Catholic schools, many have been prominent in public life. In recent years these have included prime ministers Paul Keating, Kevin Rudd, and Tony Abbott, former governor-general Sir William Deane, former deputy prime minister Tim Fischer, the first woman elected to lead an Australian state or territory, Rosemary Follett and serving Lord Mayor of Sydney, Clover Moore. Current parliamentarians include Bill Shorten and Barnaby Joyce.
Prominent indigenous Australians include former senator Aden Ridgeway, Pat Dodson (the first Aboriginal person to become a Catholic priest in Australia), and his brother, Mick, and Kurtley Beale.
In the arts a large number of Catholic educated people have been prominent, from the father of Australian rock and roll, Johnny O'Keefe, to contemporary musicians such as Paul Kelly and Ignatius Jones. In film and television, Catholic educated Australians have included Mel Gibson, David Wenham, Julian Morrow, Antonia Kidman, Anh Do, Santo Cilauro and Tom Gleisner. Contemporary Australian writers who have attended Catholic schools include Robert Hughes, Morris West, Nick Enright, Justin Fleming and Gerard Windsor. Princess Michael of Kent, businesswomen Ita Buttrose, Gai Waterhouse and Lucy Turnbull all attended the Society of the Sacred Heart's Kincoppal School.
A former Chief Justice of the High Court of Australia, Murray Gleeson, attended St Joseph's College, Hunters Hill and his successor, Robert French, attended St. Louis School, Claremont, Western Australia. As of August 2011, a nine members of the 49 member New South Wales Supreme Court were former students of the Jesuit's St Ignatius' College Riverview. Former treasurer and now Ambassador of Australia to the United States, Joe Hockey received a Catholic education.
Universities
The Australian Catholic University opened in 1991, following the amalgamation of four Catholic tertiary institutions in eastern Australia. These institutions had their origins in the 1800s, when religious orders and institutes became involved in preparing teachers for Catholic schools and nurses for Catholic hospitals.
The University of Notre Dame Australia opened in Western Australia in December 1989 and now has over 9,000 students on three campuses in Fremantle, Sydney and Broome.
Campion College, established in 2005, is a liberal arts college located in the suburbs of Sydney.
See also
Public and private education in Australia
Education in Australia
Anglican education in Australia
Christianity in Australia
Catholic Social Services Australia
Catholic Health Australia
List of Catholic schools in Australia
Roman Catholic Church in Australia
References
External links
National Catholic Education Commission
Australian Catholic Bishops Conference official website
Education
Category:Christian education in Australia
*
*
Category:History of education in Australia | null | minipile | NaturalLanguage | mit | null |
Q:
Remove Extra Space around Listbox
I have some extra space around my Listbox. It's 1px wide, but I don't know where it comes from...
I set the padding, margin and BorderThickness of both, the ListBox and the ListboxItem to 0.
This is the XAML:
<!-- NOTEBOX LISTBOX -->
<!-- The Datatemplate for the Notebox - ListboxItem -->
<DataTemplate x:Key="NoteListboxItemTemplate" DataType="ListBoxItem">
<Border Style="{DynamicResource OuterNoteBoxBorder}">
<Border Style="{DynamicResource SecondOuterNoteBoxBorder}">
<StackPanel>
<TextBlock Grid.Column="0" Foreground="#225588" Text="{Binding Title}" Style="{DynamicResource PlayListListBoxTitleLabel}" TextTrimming="CharacterEllipsis" TextWrapping="NoWrap" ></TextBlock>
<ContentPresenter Content="{Binding NoteView}"></ContentPresenter>
<TextBlock Grid.Column="1" Foreground="Black" Text="{local:CultureAwareBinding CreationDate, StringFormat={}{0:F}}" Style="{DynamicResource PlayListListBoxTitleLabel}"></TextBlock>
</StackPanel>
</Border>
</Border>
</DataTemplate>
<!-- The Itemtemplate for the Notebox - ListboxItem -->
<Style x:Key="NoteboxListItemTemplate" TargetType="{x:Type ListBoxItem}">
<Setter Property="Margin" Value="0" />
<Setter Property="Padding" Value="0" />
<Setter Property="Foreground" Value="Black" />
<Setter Property="Background" Value="White" />
<Setter Property="BorderThickness" Value="0" />
<Setter Property="Template">
<Setter.Value>
<ControlTemplate TargetType="{x:Type ListBoxItem}">
<ContentPresenter HorizontalAlignment="{TemplateBinding HorizontalContentAlignment}" VerticalAlignment="{TemplateBinding VerticalContentAlignment}" SnapsToDevicePixels="{TemplateBinding SnapsToDevicePixels}"/>
<ControlTemplate.Triggers>
<Trigger Property="IsSelected" Value="true">
<Setter Property="Foreground" Value="{DynamicResource {x:Static SystemColors.HighlightTextBrushKey}}"/>
<!--<Setter Property="Background" TargetName="Bd" Value="#66000000"/>
<Setter Property="BorderBrush" Value="#000000" />-->
</Trigger>
<MultiTrigger>
<MultiTrigger.Conditions>
<Condition Property="IsSelected" Value="true"/>
<Condition Property="Selector.IsSelectionActive" Value="false"/>
</MultiTrigger.Conditions>
<!--<Setter Property="Background" TargetName="Bd" Value="{DynamicResource {x:Static SystemColors.ControlBrushKey}}"/>-->
<Setter Property="Foreground" Value="{DynamicResource {x:Static SystemColors.ControlTextBrushKey}}"/>
</MultiTrigger>
<Trigger Property="IsEnabled" Value="false">
<Setter Property="Foreground" Value="{DynamicResource {x:Static SystemColors.GrayTextBrushKey}}"/>
</Trigger>
</ControlTemplate.Triggers>
</ControlTemplate>
</Setter.Value>
</Setter>
<Style.Resources>
<SolidColorBrush x:Key="{x:Static SystemColors.HighlightBrushKey}" Color="#88000000"/>
<SolidColorBrush x:Key="{x:Static SystemColors.ControlBrushKey}" Color="Transparent"/>
</Style.Resources>
</Style>
<!-- The Border-Template for our Notebox - ListboxItem -->
<Style x:Key="NoteboxListItemBorderTemplate" TargetType="{x:Type Border}">
<Setter Property="Background" Value="#CCFFFFFF" />
<Setter Property="Margin" Value="0" />
<Setter Property="Padding" Value="0" />
<Style.Resources>
<SolidColorBrush x:Key="{x:Static SystemColors.HighlightBrushKey}" Color="#88000000"/>
<SolidColorBrush x:Key="{x:Static SystemColors.ControlBrushKey}" Color="#44000000"/>
</Style.Resources>
</Style>
<!-- Notebox - Listbox Template -->
<Style x:Key="NoteboxListboxTemplate" TargetType="{x:Type ListBox}">
<Setter Property="Background" Value="Transparent" />
<Setter Property="BorderBrush" Value="Transparent" />
<Setter Property="BorderThickness" Value="0" />
<Setter Property="Padding" Value="0" />
<Setter Property="Margin" Value="0" />
</Style>
<ListBox Grid.Column="1"
Grid.Row="0"
Background="Black"
MouseDoubleClick="ListBox_MouseDoubleClick"
HorizontalContentAlignment="Stretch"
ScrollViewer.HorizontalScrollBarVisibility="Disabled"
ItemContainerStyle="{DynamicResource NoteboxListItemTemplate}"
VirtualizingStackPanel.VirtualizationMode="Recycling"
VirtualizingStackPanel.IsVirtualizing="True"
ItemsSource="{Binding Notes, Mode=TwoWay}"
ItemTemplate="{DynamicResource NoteListboxItemTemplate}"
SelectedItem="{Binding SelectedNote}"
Style="{DynamicResource NoteboxListboxTemplate}">
</ListBox>
What am I missing?
A:
This is the default control template for ListBox:
<ControlTemplate x:Key="ListBoxControlTemplate1" TargetType="{x:Type ListBox}">
<Border x:Name="Bd" BorderBrush="{TemplateBinding BorderBrush}" BorderThickness="{TemplateBinding BorderThickness}" Background="{TemplateBinding Background}" Padding="1" SnapsToDevicePixels="True">
<ScrollViewer Focusable="False" Padding="{TemplateBinding Padding}">
<ItemsPresenter SnapsToDevicePixels="{TemplateBinding SnapsToDevicePixels}"/>
</ScrollViewer>
</Border>
<ControlTemplate.Triggers>
<Trigger Property="IsEnabled" Value="False">
<Setter Property="Background" TargetName="Bd" Value="{DynamicResource {x:Static SystemColors.ControlBrushKey}}"/>
</Trigger>
<Trigger Property="IsGrouping" Value="True">
<Setter Property="ScrollViewer.CanContentScroll" Value="False"/>
</Trigger>
</ControlTemplate.Triggers>
</ControlTemplate>
Notice the Padding="1" on Border named Bd. Since this is harcoded and not template bound, you can either retemplate the ListBox and set the padding to 0, or since Padding on the ScollViewer has a TemplateBinding to the Padding of the ListBox, you can set the Padding on your ListBox to -1 to offset the padding on the border.
A:
The control template of a ListBox looks like this:
<ControlTemplate TargetType="{x:Type ListBox}">
<Border Name="Bd"
Background="{TemplateBinding Background}"
BorderBrush="{TemplateBinding BorderBrush}"
BorderThickness="{TemplateBinding BorderThickness}"
SnapsToDevicePixels="true"
Padding="1"> <!-- This might be the problem -->
<!-- ... -->
| null | minipile | NaturalLanguage | mit | null |
If your medical aid is not listed please feel free to email [email protected] with your medical aid name and we will see if it is feasible to contract in with your medical aid.
Please note that being a member of these medical aids does not necessarily guarantee that Manor Chiropractic will submit the claim directly to medical aid. This will depend on fund availability in your Medical Savings Account (MSA) or if your plan covers Chiropractic treatment. If there are no available funds in your accounts, you will be required to settle the consultation in cash, you will then be issued with an invoice which you can submit directly to your medical aid.
While it is noted that every effort is made at the time of medical aid benefit inquiry to obtain an accurate indication from the medical aid, funds are not reserved and this is not a guarantee of payment from the medical aid. Where the medical aid has not covered in full, the patient/main member is then liable for settlement of the account.
Full medical aid rates apply for submission of claims (please note that these are higher than the standard consultation fees). If Manor Chiropractic is not contracted in with your medical aid, you are then liable for the payment of your account. You will then be issued with an invoice which you can submit to your medical aid for reimbursement (reimbursement may be nil/partial/full depending on your medical aid scheme) | null | minipile | NaturalLanguage | mit | null |
Born in Crumpsall on July 23 1942 and raised in Gorton, then a working class area of Manchester, Hindley lived in a house that was in such poor condition that she and her parents slept in the only available bedroom.
Her parents, Nellie and Bob Hindley, beat her regularly as a young child, and Bob was an alcoholic.
They would regularly read books on philosophy, crime and torture, and Hindley would often hire a van, where the two would plan bank robberies.
She claimed that Brady began talking about ‘committing the perfect murder’ in July 1963, and on July 12 the two murdered their first victim, 16 year old Pauline Reade.
Their next victim, John Kilbride, was killed on November 23 1963.
During the 1990s, Hindley stated that she only took part in the killings because Brady had drugged her, was blackmailing her with pornographic photos he had taken of her, and had threatened to kill her younger sister, Maureen.
Myra Hindley (1942 – 2002), left, circa 1965 (Picture: Getty)
In 2009, a television documentary series on female serial killers was broadcast on ITV3, and Hindley’s solicitor Andrew McCooey reported that she had said to him: ‘I ought to have been hanged. I deserved it.
‘My crime was worse than Brady’s because I enticed the children and they would never have entered the car without my role … I have always regarded myself as worse than Brady.’ | null | minipile | NaturalLanguage | mit | null |
Determinants of Disease Outcome in Patients with Drainage of Aortic Root Abscess Caused by Infective Endocarditis.
The aim of this study was to investigate the factors that determine disease outcome in patients with drainage of aortic root abscess caused by infective endocarditis. Data from 27 patients who were treated for aortic root abscess due to infective endocarditis were analyzed. Nineteen patients survived for more than 3 years after discharge, seven patients died within 1 month after the surgery, and one patient died during the surgery. Based on survival or terminal outcome, patients were divided into two groups. There was no significant difference between surviving or dead patients in terms of age or gender. Other factors, such as disease course, surgery, cardiac function, pathology, pathogenic microorganisms, complications, and nosocomial infections were significantly different between patient groups and appear to be associated with disease outcome. Patients' deaths can be reduced through targeted clinical therapy. | null | minipile | NaturalLanguage | mit | null |
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