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Hotel Rezia**** is located just a few minutes from Bormio town centre and the thermal baths; it is a charming and elegant hotel characterized by a cosy and relaxing atmosphere. The hotel and the nearby chalet (a wonderful building created in 17th century) were renovated in 2005, on the occasion of the FIS Alpine Ski World Championships. They are both 100% furnished with natural wood, stone and attention to details. The rooms available are hotel singola, classic, superior, deluxe and chalet basic, classic, deluxe; they all feature services such as WiFi, Sky TV, room service and general services. Hotel Rezia offers traditional and Italian dishes made with high quality, fresh food; the cellar is stocked with the best wines produced in Italy and France, and the Lounge Bar is the best place to enjoy a good coffee or a drink. Hotel Rezia is a wellness oasis too, with sauna, Turkish bath, Finnish shower, gym, and a beauty salon offering facial and body treatments, massage rituals, hair removal and tanning salon. | 2019-04-19T00:54:45 | http://www.bormioonline.com/en/hotel-rezia/ |
“Dear Mom”… I want to say Thank you.
Thank you for making me feel special during Christmas time and always, for remembering to help me bake cookies for Santa and leaving them under the Christmas Tree with milk. Thank you for reminding Dad that he needs to leave fake footprints leading to the Christmas Tree to keep the magic alive for a little while longer and that he needs to dress up as Santa no matter how much that suit itches!
Thank you for always making sure I had presents waiting for me on Christmas morning. Thank you for all the hard work and love you put into every Christmas, making sure family came around and making the best four course meal we have ever had in our lives! Thank you for cleaning up after all of the mess we left behind after Christmas pudding, sticky sweet fingers and bits of wrapping paper left all over the house.
Thank you for all of the sweet memories you have given us over the years. Thank you from the bottom of my heart.
There are so many reasons and memories to Thank our Mom’s for, so remember to Thank your mom this Christmas.
Give Mom the opportunity to find that “book” within her… and give you a story that you will treasure and pass down through the generations with our “Dear Mom” journal from the “Journal of a Lifetime” range. | 2019-04-20T20:15:13 | http://www.reflectionsinmotion.co.za/dear-mom-i-wanted-to-say-thank-you/ |
the surveillance champions during last year.
French prison authority and ministry of justice.
European agreement of human rights, are most of the time not fully respected.
suburban district mostly populated by immigrants.
beneficiaries of the minimum welfare to allow them free transport tickets.
2 others are Lisbon and Prague.
Special prize to the french governement and parliament for the LSQ law.
terrorism, immigration, civil protest, political opposition and petty crimes. | 2019-04-26T10:21:27 | http://bigbrotherawards.eu.org/BBA-2001-Final-Press-release |
my laptop screens are waaay off. i recently viewed my photos on someone who has a calibrated screen and the grass in my pictures is NEON green.
can someone please recommend a good calibration system I can buy?
I have Colorvision Spyder, the lower end version and it is great.
Color Munki if you need to calibrate more than one machine.
If you're still looking, hope this is helpful. I have all three of Datacolor Spyder Elite 3, Xrite iOne Display Pro and Xrite Color Munki Photo. I use the XR-CMP for printer calibration although it will do deplays as well. But, my go-to display (monitory and projetor) is the XR-iOne, It is slightly higher priced than the others, but I love it. It (and its software) have features the others don't have, in particular the ability to measure and factor in ambient (room) light for different conditions. I don't use the Spyder anymore. I've converted completely to Xrite systems. BTW, once you decide, be sure you spend some time getting comfortable with soft-proofing, then printing to a printer that uses ICC profiles specific to your printer/paper combination(s).
but here's to a great new year, and accurate color! | 2019-04-25T18:03:48 | http://www.equinephotographers.org/4um/viewtopic.php?p=170619 |
INSCRIPCIÓ ART AL VENT 2018- XVª ED.
NO LA VULL RECUPERAR. LA DONE A L'AJUNTAMENT - No la quiero recuperar. La dono al Ayuntamiento - I don't want to recover it. I donate it to the Town Hall.
HE LLEGIT I ACCEPTE LES BASES - He leído y acepto las condiciones - I read the terms and conditions and I am agree. | 2019-04-26T15:42:19 | https://docs.google.com/forms/d/e/1FAIpQLScMN-pz8O9lHArs7jYb2sXX1UlYxvRPunD6UGtjRDfaQj1MrQ/viewform?c=0&w=1 |
A major study has found that unhealthful eating is responsible for more deaths worldwide than any other risk factor, including smoking.
A diet low in nutrients may cause more deaths worldwide than smoking or other unhealthful habits, suggests new research.
The Global Burden of Disease Study looked at dietary consumption between 1990 and 2017 in 195 countries, focusing on 15 types of food or nutrients.
In a paper that features in The Lancet, the study investigators conclude that, due to its contribution to noncommunicable diseases, poor diet accounted for 1 in 5, or 11 million, adult deaths in 2017.
The vast majority of those deaths, around 10 million, were from cardiovascular disease. The rest were mainly from cancer and type 2 diabetes.
Ranking the countries from lowest to highest rates of diet-related deaths puts Israel first, with 89 deaths per 100,000 people, and Uzbekistan last, with 892 per 100,000.
The United States, with 171 deaths per 100,000, comes in at 43rd place and the United Kingdom at 23rd, with 127 deaths per 100,000. India is in 118th place, and China is in 140th.
In their analysis of global diets, the researchers looked at 15 items: fruits, vegetables, nuts and seeds, legumes, whole grains, fiber, calcium, milk, omega-3 fatty acids from seafood, polyunsaturated fats, trans fats, red meat, processed meat, sugary drinks, and sodium.
They found that the global diet in 2017 contained less than the ideal amounts of nearly all healthful food items. The biggest deficiency was in nuts and seeds, milk, and whole grains.
Consumption of nuts and seeds, for instance, was on average only 3 grams (g) per day, or around 12 percent of the optimal intake.
Consumption of milk was only 16 percent of optimal intake and whole grains was only 23 percent.
Alongside these, daily intakes of unhealthful dietary items “exceeded the optimal level globally.” Sugary drink consumption, for example, “was far higher than the optimal intake,” followed by the consumption of processed meat and sodium. Red meat consumption was just above the optimal level.
An important finding of the study was that insufficient intake of healthful foods could be just as, if not more, damaging than eating too many unhealthful foods.
In addition, just three of these — whole grains, fruits, and sodium — accounted for more than half of the diet-related deaths and two-thirds of the years lost to diet-related ill health and disability.
Dr. Murray says that these results contrast with the fact that, over the last 20 years, policy discussions have tended to focus more on restricting unhealthful foods.
He and his colleagues suggest that campaigns should concentrate on rebalancing diets. They also urge that any changes to food production and distribution aimed to achieve this must consider the environmental impact on the climate, land, water, and soil.
In a linked editorial, Prof. Nita G. Forouhi and Prof. Nigel Unwin, both of the Medical Research Council Epidemiology Unit at the University of Cambridge in the U.K., agree with the authors in that “in a global context,” and despite its limitations, the study offers “evidence to shift the focus” from restricting unhealthful food items to increasing healthful ones.
They suggest that it confirms a need to emphasize foods rather than nutrients. However, they also highlight some of the challenges of shifting the global diet toward a more healthful one, such as the “prohibitive” costs of fruits and vegetables.
For example, in low-income countries, “Two servings of fruits and three servings of vegetables per day per individual accounted for 52 percent of household income,” compared with just 2 percent in high-income nations. | 2019-04-24T02:16:36 | http://medicalnews.me/cancer/poor-diet-biggest-risk-factor-for-early-deaths-worldwide/ |
A multimillion-rand logistics and retail park being developed by M&F Giuricich Developments and Fortress Property Fund, in KwaZulu-Natal, will be built this year.
The logistics park, located between the King Shaka International Airport and Durban, will form part of the N2 Business Estate, located on the northern edge of the Cornubia development.
Once completed, the total estate could create 2 400 permanent jobs and generate R45-million a year in rates income for the city.
“A logistics park of this size and nature is a perfect fit for the vision that we had of establishing the Cornubia N2 Business Estate as a prime commercial location,” said Tongaat Hulett Developments director Karen Petersen, noting that it met the criteria needed to attract tenants with specific needs, adding considerably to establishing the business estate as a prime commercial site.
M&F Giuricich Developments cofounder Florian Giuricich noted that, of the 200 000 m2 of space available, half would be allocated for logistics warehousing facilities and the remainder for retail.
“We believe the opportunity exists for this facility to meet the needs of logistics companies or major brands with significant warehousing needs. There is very little infrastructure of this nature in existence along the N2 that exploits proximity to the airport and Dube TradePort, as well as access to Durban, so we are expecting ready interest in these facilities,” he said.
Further, Giuricich pointed out that the retail component of the development would be equally attractive given the visibility from the highway, noting that there was considerable interest from large retail destination-based tenants who enjoy the prominent exposure and easy access to site from the N2 motorway.
This included some international retail tenants that are entering the South African market. Access provided by the flyover bridge network that links to the Umhlanga town centre and the amenities being developed within Cornubia itself add to the site’s retail suitability. | 2019-04-25T01:54:18 | http://www.tongaat.com/kwazulu-natal-to-get-another-retail-logistics-park/ |
Debra Ann Buckler, 59, passed away on November 21, 2018 while she was being sung “Great is Thy Faithfulness” at the Comfort House in Pella, Iowa. She was born in Fayette, Missouri on August 29, 1959. Her parents, Ron and Wanda (Kitchen) Buckler, raised her on a farm house. She was the second oldest out of her three siblings: Tim Buckler, Diane Mueller, and Lisa Buckler. Her secondary and beyond education was at Fayette High School, Hannibal-LaGrange University, Kirksville College of Osteopathic Medicine, and Sinai Samaritan Medical Center.
Despite her not being married, she found another way to give her love by adopting her two daughters, Aneese Lu-Juan Buckler and Tori Jie-Ron Buckler. She was known for being generous, selfless, loving, and so much more. She was an Internal Medicine and Geriatric physician in several states. Her favorite hobbies were making puzzles, listening to music, and spending time with her friends and family. She served the Lord faithfully ever since she dedicated her life as a child.
Deb was preceded in death by her parents, Ron and Wanda; and is survived by her siblings, Tim Buckler, Diane Mueller, and Lisa Buckler; her daughter, Aneese Buckler and her fiancé Denton Williams, and other daughter, Tori Buckler. She is also survived by many individuals as close as family.
The funeral arrangements are under Garden Chapel Home in Pella, Iowa. In lieu of flowers Deb would appreciate donations to go to Smile Train, American Cancer Society, and Bethany Christian Services. | 2019-04-19T15:06:56 | https://www.gardenchapel.com/notices/Debra-Buckler |
Multi ani fericiti si multa sanatate!
Happy one year anniversary! (we celebrated ours last month!). | 2019-04-21T18:02:31 | http://www.toytulip.com/2012/12/1-year-old-wife.html |
Your ideas how AoC2 forum should looks like!
By Lonathan, January 19 in Your ideas how AoC2 forum should looks like!
I HATE THEM!! I HATE THEM I HATE!!!! THEM!!!!!!!
I would like to know with which versions of android is AoC2 cross-compatible because on my Tablet ( SM-T113) which is quite good device, I can't play your game. Is your game avalaible for 4.4+ Android users ? Can you fix this ? My device is compatible with even latest strategy games (like Kingdom Rush Vengeance for example). I also have uploaded image on which is written that my device is incompatible.
I hope that you will read my message ! | 2019-04-22T06:33:58 | http://www.ageofcivilizationsgame.com/topic/1474-delete-attachment-quotas/?tab=comments |
From skin cleansing to make-up removal, Evonik’s Micellar concept offers inspiring solutions that aim to simplify the beauty routine of consumers. A range of no-rinse cleanser formulations has been extensively tested in order to provide the best possible solutions for facial cleansing.
An exceptionally clear and flawless skin is not surprisingly a new desire within the Personal Care Market. However, micellar cleansers now offer consumers a simple solution for skin cleansing, representing a new era in facial skin care. While face washes, tonics and wipes have been the dominant cleansing formats for decades, newer formats such as micellar cleansers have become a major trend across the globe, and still have more potential to grow. The numerous benefits that these formulations provide, range from skin cleansing to the easy removal of (even water-proof) make-up as well as skin hydration. These are very good reasons why many consumers have already incorporated micellar cleansers into their daily beauty routine.
With micellar cleansers less is more. First, because their formula is usually less complex and consists of fewer ingredients which is highly valued by 'safety conscious' consumers. Second, micellar cleansers meet the current environmental trend of water conservation as they do not need to be rinsed-off, and therefore provide an opportunity for consumers to lower their water usage. Convenient and easy to use, micellar cleansers appear to be the best all-in-one solution for facial skincare these days and are easy to use on the go.
The challenge for micellar cleanser formulations lies within the high demands placed on the ingredient’s properties as they need to be able to easily remove long-lasting and waterproof make-up, whilst being mild enough at the same time to be left on the skin. Evonik´s most recent launch, RHEANCE® One, is a very unique all-natural multifunctional ingredient that’s fully biodegradable, with an outstanding cleansing performance and offers excellent skin compatibility that when used in micellar water formulations efficiently removes long-lasting and waterproof make-up. Evonik’s high performing PEG-free solubilizer TEGOSOFT® PC 41 MB is another prime example that meets the most challenging requirements of micellar cleanser formulations. With its range of TEGO® Solve products, Evonik offers other highly effective PEG-free solubilizers that provide a superior skin feel and are 100% based on renewable raw materials. TEGO® Betain 810, an extremely mild and preservative-free / non-irritant surfactant, is especially suitable for mild but effective cleansing formulations such as micellar water. The base formula can be easily expanded with TEGO® Cosmo C 100, a nature identical amino acid that adds additional energizing and revitalizing properties to the regular cleansing formulation, and helps to support the protection of the skin.
With this micellar concept, Evonik provides an inspiring selection of formulations for different types of micellar cleansers, including a micellar water, micellar oil, micellar gel as well as a micellar wipes that have all been extensively tested and proven to outperform most market benchmark products. | 2019-04-26T04:35:00 | https://personal-care.evonik.com/product/personal-care/en/products-solutions/concepts/pages/micellar-concept.aspx?productId=16782 |
In Ephesians, Paul tells us not to exasperate our children. In Colossians, he admonishes us not to embitter them or they will become discouraged. We are warned against making our children “very angry” or creating a “bitter spirit.” Many good and faithful parents master the discipline and miss the connection. And that child will go into a self-protection mode that keeps people at a safe distance. No amount of discipline will bring him back. HE NEEDS CONNECTION!
So what is connection? Simply stated, connection with a parent is the certain knowledge of a parent’s unfailing accessibility and acceptance. Psychology refers to this as attachment. Your child needs to know beyond a shadow-of-a-doubt that they are valued, protected, and worthy of your love. Then you have established an emotional and relational connection to withstand the tests of life.
Connection is the bond that communicates to the child what Phillip Yancey described about God in his book, What’s So Amazing About Grace: “There is nothing I can do to make God love me any more or any less.” That is what we want for our children. Though we will allow them to experience the consequences of their decisions, we want them to lay down at night knowing there is nothing they can do to make us love them any more or any less. What can you do with your children to establish and maintain an emotional connection that will empower your child for their future?
Time is the first strategy. To connect with your child you must spend time with them. Let me suggest that quality time cannot occur without quantity. You and I have one shot with each of our children. There are no “do-overs.” One childhood experience is all we have with that young heart and mind. Spending time with your children communicates volumes about your values. Follow anyone around for six months and you can accurately state what is most important to that person based on the amount of time invested in certain activities. Your children live with you. They know how valuable they are to you by the amount of time you spend with them.
How do you spend your discretionary time? I am not talking about the time you must give to career and household responsibilities. There are some things that have to be done. I am referring to that time in your schedule when you can choose to be with your children.
We spend hours playing ping pong now that we have a table. Three years ago it was foosball. I lift weights with all three of my boys. If they are in the front yard playing soccer, guess what, dad crashes the party. This is it! This moment is all I have with them. We eat as a family. We go to movies as a family. We have created a climate in our home that being together is a good thing. And when your 18 year old still likes to do things with you, connection exists. Whatever your lifestyle is like, make the time to be with your children beginning at an early age.
Touch is the second valuable tool. Non-sexual, physical touch is so important. It’s said that kids need, on average, 11 touches per day. Noted Christian psychiatrist Grace Ketterman believes kids need at least 100 touches per day! Non-sexual touching is linked to the release of oxytocin, a chemical also released during those tender moments of breast feeding. Hugs, high fives, holding hands, rocking in the chair, etc. are all examples of non-sexual touch. Without touch, connection cannot happen. In our home, everyone is touched every day. Even if you are having a bad day, you are touched.
I am amazed at the number of families I work with that don’t hug each other. These are stable, Christian homes void of physical affection. If you truly want to connect with your child, practice non-sexual touch on a daily basis. The connection is real and tangible.
The third tool for creating connection with your children is validation. Every child is asking the question, “Am I worthy of your affection and time?” Parents have the power to stamp “valid” on their child. And this stamp will carry that child into adulthood. Even God the Father validated Jesus. After Jesus’ baptism, God descended from heaven and spoke these words, “This is my Son, whom I love; with him I am well pleased.” (Matthew 3:17) Jesus experienced the same validation again at the Mount of Transfiguration. These are powerful words of acceptance and affirmation.
Imagine the heart of a child when they hear words like these coming from their parents. That child will begin to open his heart to his parents and connect. Praising your child when they accomplish a goal is good. Communicating praise to your child for just being there goes deep into the heart. I often tell my boys I am so proud to be their father just because of them, not for what they have done. Of course we reward performance. But they need to know that my love and acceptance of them is not dependent on how well they do in life.
Spending time with your children is invaluable. Touching them on a consistent basis will soften their hearts. And validating them will empower their spirits. When all three are combined with discipline and structure, you will connect with your child and create the emotional attachment necessary to propel them into a healthy adulthood. Take the risk and connect with your children.
Kent Hughes has a private practice focusing on marital and family issues in Clarksville, Tennessee.
Read 582 times | Like this? Tweet it to your followers! | 2019-04-18T15:22:14 | http://readjourneymagazine.com/index.php?option=com_k2&view=item&id=1059:connecting-with-your-children&Itemid=104 |
If you’ve ever needed an X-ray or an MRI, you know that getting a glimpse inside the human body can be uncomfortable, time consuming, and expensive. However, one researcher at the Research Institute for Aging has developed a way to make some of that monitoring much easier.
“You can infer so much of your health status through how your heart and how your blood is working throughout these systems,” he said. According to Amelard, being able to monitor the entire body at once provides more useful information than single point monitoring with a finger clip. Similarly, he explained that since CHIS relies on light, it also poses no risk to the patient.
Amelard explained that one of the major functions he foresees for this device is improving health care for seniors. Falls due to dizziness can be very serious, so the device, upon noticing decreased bloodflow to the head, could send an advance warning that the patient is at risk.
In addition to helping seniors, it may be valuable for monitoring patients where the familiar finger clip monitors are a problem, such as burn victims and premature infants. These special cases aside, Amelard said the device is useful for any patient undergoing long-term monitoring.
“If we were to wear a finger clip … for an extended period of time, it’s going to be cutting off circulation. If you have delicate skin it might be causing some rashes or abrasions,” Amelard said. According to him, since CHIS is touchless, “you don’t have to be worrying about elongated stresses” that contact-based devices cause.
“I think that our healthcare system is top notch in terms of treatment plans. It’s just that acute care, treating a [blood vessel] blockage after it’s already blocked, it’s very expensive, it’s very timely, [and] the recuperation period is often quite lengthy. The big question then is can we be mitigating these, or preventing these in the first place?” he asked. | 2019-04-20T21:05:08 | http://uwimprint.ca/article/shining-a-light-on-blood-flow-research/ |
Three peach growers observed new peach cultivars for production in Piedmont area of North Carolina. Potentially several new growers could start growing peaches in this area once they evaluate these newer cultivars.
In Cabarrus and nearby piedmont counties there is limited peach production despite a heavy direct market demand. The peach cultivars available in past years were very susceptible to frost. There are newer cultivars with increased chilling hours that are less susceptible to frost/freeze events during bloom. The commonly available Lovell rootstock used in the past showed stress and reduced growth due to heavy wet soils. In one observation during a recent rainy season, trees on the Halford rootstock outperformed trees on the Lovell rootstock. Demonstrating the newer cultivars will show farmers the current potential for peach production in piedmont soils in areas with limited climatic advantages. Comparing the rootstocks may help farmers make buying decisions.
24 trees were planted alternating Halford and Lovell rootstocks. Cultivars included Challenger, Glactica, Intrepid, Contender and Carolina Gold. These were planted in red clay soil. The trees grew normally until July. During July there were several 3 inch rain events with about 8 inches of rain the week of July 26. The excessive rain drowned several trees. On August 9 a visual comparison of the planting was made to evaluate the survivability and quality of the trees.
Observations in this demonstration matched a previous observation that Halford is a preferred rootstock for heavy clay soils for survivability and growth the first year. Unfortunately, all the dead trees had to be replaced with Lovell rootstock, so meaningful rootstock data can’t be collected in future years. Once these peaches start producing, local farmers will be able to evaluate the various cultivars for reliability and quality. | 2019-04-25T11:53:21 | https://newcropsorganics.ces.ncsu.edu/specialty-crops/specialty-crops-research/piedmont-peach-production/ |
Excellent post. I was checking constantly this blog and I’m impressed! Very useful info specifically the last part 🙂 I care for such info much. I was seeking this certain information for a long time. Thank you and good luck. | 2019-04-26T15:40:46 | https://university.genakirby.net/product/apprentice-collection/ |
HELLFIRE NITRATE is a stimulant-free pre-workout product that takes Nitric Oxide production to the next level with its blend of NO enhancers. Arginine Nitrate and Arginine AKG form the base of the complex and are further enhanced by Pine Bark Extract which stimulates the enzyme that produces nitric oxide in the body. HELLFIRE NITRATE is stimulant free and was developed to be stacked with HELLFIRE CONCENTRATE Pre-workout for a synergistic effect.
Take 5 capsules 30 minutes before training. Need only be taken on training days. For best results stack with HELLFIRE CONCENTRATE. | 2019-04-26T06:06:01 | https://xtremenutrition.co.za/product/supplements-sa-hellfire-nitrate-90-caps/ |
Looking for a delicious meal to enjoy while camping under the stars? This Sweet Thai chicken with vegetables & noodles is the perfect thing to keep you full and ready for the next adventure!
Open pouch and remove oxygen absorber.
Prepare in pouch or other suitable container.
Add 2 cups (16oz) boiling water to ingredients or you may crease / fold pouch at water line 8 then fill to water line 8.
Stir completely and cover. Let stand 10-12 minutes. | 2019-04-20T20:12:08 | https://yourgearclub.com/products/freeze-dried-thai-style-chicken-w-noodles |
It is not known when Peter was born. But the date of his death is about the year 64 C.E. He died by being nailed to a cross in Rome. This type of death is called crucifixion. There is a legend that Peter asked to be crucified upside down, as he felt unworthy to die as Jesus did. Most historical sources only say he was crucified.
The Roman Catholic Church, Eastern Orthodox, Oriental Orthodox, Lutheran Church and Anglican Communion, consider Simon Peter a saint. Roman Catholics believe that the Pope is Peter's successor. For this reason, he is the rightful head of all other bishops. Eastern and Oriental Orthodox also recognise the Bishop of Rome as the successor to Saint Peter and the Ecumenical Patriarch sends a delegation each year to Rome to participate in the celebration of his feast.
In the Ravenna document of 13 October 2007 representatives of the Eastern Orthodox Church agreed that "Rome, as the Church that 'presides in love' according to the phrase of St Ignatius of Antioch (To the Romans, Prologue), occupied the first place in the taxis (order), and that the bishop of Rome was therefore the protos (first) among the patriarchs. They disagree, however, on the interpretation of historical evidence from this era regarding the rights of the bishop of Rome as protos, a matter that was already understood in different ways in the first millennium."
↑ ""Ravenna Document" of 13 October, 2007".
This page was last changed on 4 April 2019, at 00:41. | 2019-04-18T23:16:54 | https://simple.wikipedia.org/wiki/St._Peter |
If your are a UK taxpayer, we can make your donation go further by reclaiming the tax you have paid on your donation. Click to download the Gift Aid declaration.
Donations made through Virgin Money Giving may be made by clicking on the gift aid button on their website.
It costs about £15 a month to keep a child at Unity School.
As well as direct financial support, we are always looking for volunteers to help with fundraising activities. Either by assisting at organised events or by coming up with new ideas or projects.
Sometimes people arrange an event for their friends or neighbours such as a coffee morning or garage sale, a church lunch, sponsored walk. One school has raised a lot of money through bag packing at a local supermarket. Cake sales always go down well!Obviously, the Charity Trustees will give you all the help and encouragement they can and advertise your event through our website, facebook page etc if you require it. Others volunteer to assist at our fundraising events such as our Christmas Sale, exhibitions etc. If you would like to help at such events contact Karyn on 01903 236921 or email the us by scrolling down to Contact Us.
You might like to scroll down and look at The activities of our Fundraising Group.
Rustington Methodist Church – Both the Methodist and Parish Churches in Rustington have provided major support for our charity since we started.
St. Peter & St Paul Church, Rustington – Both the Methodist and Parish Churches in Rustington have provided major support for our charity since we started.
St. Andrew’s Church of England School, Worthing – St. Andrew’s School continues to fundraise for us and supports us. Our Treasurer, Chris Azzaro, was previously Deputy Head at the school and our Trustee, Ian Straw, is a teacher at the school and leads groups of young people out to volunteer in Mombasa.
ISE – International School Eindhoven – the ISE is a major supporter of our school and charity. They send volunteers to our school and through their fundraising efforts, support our much-needed medical programme.
Bishop Luffa school, Chichester – Bishop Luffa has done fundraising for our charity over the last few years and continues to support us. | 2019-04-19T19:28:56 | http://www.mombasachildren.org.uk/support-us/ |
Mean, mean winters and too long.
Ninety days of frost free weather.
I know you don’t believe it but . . .
Got to get outside and get together!
Now I said, ninety days is all we get.
Ninety days of summer weather.
Just got to get outside and get together.
We got to get OUTSIDE!
Corn, squash, cucumbers and thyme.
And go skinny-dippin’ in the pond.
Ow! Ninety days is all we get.
Just ninety days of frost free weather.
Get outside and get together.
And have a cookout on the lawn.
Billion, billion stars come out to shine.
We just got to get OUTSIDE!
From Happy Life, forthcoming from Copper Canyon Press in September 2011.
love this. Sent it to my Michigan sister who definitely related to it! (and I used to live there too).
As a transplant Floridian who sleeps naked under a ceiling fan much of the year, I DO remember camping in Vermont in August, and being grateful for our Coleman tent heater at night! Great poem, great memory-maker.
Kind of irrepressible, that intentionally-formless energy. Pshew!
love the poem, and i'll drink to all of that! | 2019-04-23T14:50:33 | http://yourdailypoem.com/listpoem.jsp?poem_id=753 |
Silver Falls farm has been continuously operated by the Dewey family since 1817. Although they are not certified organic, they do use organic farming practices. They are a diversified dairy farm and have many exciting plans for further expansion in the future. They grow vegetables, herbs, flowers, fruit, fall decorations, and corn for cornmeal depending on the growing season.
Please come meet the family in person at the South Dayton Farmers' Market on Saturdays 9am to 1pm from June 20th to Oct 17th. | 2019-04-22T09:25:15 | http://ccaghelp.com/place/silver-falls-farm-221 |
[Update 1/15/2014] While the old link expired a while ago, there is another new link that gives exactly the same 50K upon signup. Click on this link to apply.
[Original Post] This offer has been on and off in the past several years. So the bottom line is if you miss it just be patient and wait a fee months.
Earn up to 15,000 additional bonus miles upon anniversary (you need to spend up to $25K within a year).
The other interesting thing is that Virgin Atlantic Black is now a World Elite MasterCard instead of Amex. | 2019-04-20T05:12:03 | http://www.drcreditcard.net/blog/bofa-brings-back-50000-points-bonus-for-its-virgin-atlantic-black-card |
Darwin doubters have sometimes questioned evolutionary theory by asserting that no “missing link” exists between humans and other primates. But the fossil record shows that there was no instant leap to humanity: rather our species’ physical hallmarks appeared gradually over the past several million years. “Humans did not suddenly come into existence, but we share features with many other [species],” John G. Fleagle, an anatomist at Stony Brook University, has said. Fingernails evolved 54 million years ago (mya) and the opposable thumb 25 mya, for instance. The pelvis shape needed for walking upright as well as the knee appeared more than 3.5 mya, and the foot arch arose around 1.8 mya. Although skull construction was set around 35 mya, brains only ballooned in size between 2 and 1 mya, and the chin dates from around 200,000 years ago. With apologies to Shakespeare’s Hamlet: what a patchwork is a man.
One feature that visibly separates us from most other mammals is our lack of fur. As Nina G. Jablonski explains in our cover story, “The Naked Truth,” the transition of hirsute to hairless helped to set the stage for the emergence of large brains and symbolic thought. The appearance of bare skin was one of a suite of adaptations that allowed our ancestors to thrive on the savanna as grasslands expanded in Africa starting about three million years ago.
Our forebears abandoned their easier foraging habits, traveling longer distances through a tropical landscape to acquire sufficient food to survive. Adding meat to their diets meant more calories, but finding prey also took more work. Their activity level increased and with it their need to dissipate body heat to avoid tissue damage. By 1.6 mya, protohumans had long legs for sustained walking and running. Along with that trait came naked skin and a large number of eccrine sweat glands, which produce moisture that removes body heat through evaporative cooling. The hairs on our head also help to combat overheating, by shielding our big brain from direct sun.
Although the board of editors didn’t plan it this way, many of the other feature articles in this issue also examine changes over time. The connection is most direct in “The Art of Bacterial Warfare,” by B. Brett Finlay, which describes the ancient battle between infectious agents and their human hosts. But other articles also describe “evolution” in various areas.
Whereas Finlay’s article focuses on inner space, for instance, “Cloudy with a Chance of Stars,” by Erick T. Young, looks at outer: how stars arise and change over time, a seemingly simple question that has long puzzled astronomers. “The Prolific Afterlife of Whales,” by Crispin T. S. Little, explores how sunken whale carcasses today—and dinosaurs millions of years ago—support a series of ecosystem oases on the seafloor. Even “Better Mileage Now,” by Ben Knight, looks at how internal-combustion engines are changing, creating improved performance. By explaining such advances, Scientific American strives to fulfill its mission of demystifying a changing world. | 2019-04-23T09:10:55 | https://www.scientificamerican.com/article/continuum-of-change/?error=cookies_not_supported&code=d6236bdf-96bd-406d-8155-e1fbddc7c979 |
A huge wave hit, scattering passengers on the vessel, known as a duck boat, into Table Rock Lake near Branson, Coleman said, recounting the ordeal from a hospital bed.
When the Indianapolis woman came up for air, she was alone, Coleman told television station KOLR on Saturday.
Coleman’s husband and three children, ages nine, seven and one; her 45-year-old sister-in-law and two-year-old nephew; her mother-in-law and father-in-law and her husband’s uncle all died on Thursday night in the deadliest accident of its kind in nearly two decades.
Others killed included a Missouri couple who had just celebrated a birthday; another Missouri couple who was on what was planned as their last extended vacation; an Illinois woman who died while saving her granddaughter’s life; an Arkansas father and son; and a retired pastor who was the boat’s operator.
State and federal investigators were trying to determine what sent the vessel, originally built for military use in World War II, to its demise.
An initial assessment blamed thunderstorms and winds that approached hurricane strength, but it wasn’t clear why the amphibious vehicle even ventured into the water.
Coleman said the crew told passengers they were going into the water first, before the land-based part of their tour, because of the incoming storm.
Fourteen people survived, including two adults who remained hospitalised on Saturday.
Coleman and her 13-year-old nephew were the only two of the 11 members of her family who boarded the boat to make it out alive.
Another survivor was 12-year-old Alicia Dennison, of Illinois, who says her grandmother, 64-year-old Leslie Dennison, saved her from drowning.
Alicia’s father, Todd Dennison, told the Kansas City Star that his daughter recalled feeling her grandmother below her, pushing her upward after the boat capsized.
Another young survivor was 14-year-old Loren Smith of Osceola, Arkansas.
She suffered a concussion, but her father, 53-year-old retired maths teacher Steve Smith, and her 15-year-old brother, Lance, died.
Others killed included 65-year-old William Bright and his 63-year-old wife, Janice.
The couple had recently celebrated their 45th wedding anniversary and had talked about Branson being one of their last big trips, recalled neighbour Barbara Beck.
Another Missouri couple killed in the accident were 69-year-old William Asher and 68-year-old Rosemarie Hamann.
The St Louis-area couple had been celebrating Hamman’s birthday earlier in the week.
Chance brought the Colemans aboard the doomed vessel.
Tia Coleman said her family initially lined up for the wrong tour so they had to switch out their tickets for the 6:30pm ride. | 2019-04-23T15:30:32 | https://www.yahoo.com/news/survivor-lost-nine-relatives-duck-boat-sinking-recalls-final-words-230334110.html |
Nepali young leg spin prodigy Sandeep Lamichhane bid a grand farewell to his debut Indian Premier League (IPL) after the bowler starred in the last two victories of Delhi Daredevils. Sandeep was included for Daredevils in the last three matches of the tournament after the franchise was knock out of the playoff contention. But those three inconsequential games for Daredevils proved a good exposure platform for Sandeep who not only picked up five wickets but also showed a great amount of maturity in contrast to his age.
After picking up 1-25 against Royal Challengers Bangalore in the debut game and 1-21 against Chennai Super Kings, Sandeep came up with another spell-binding performance picking up three wickets against Mumbai Indians at the Feroze Shah Kotla Stadium in New Delhi on Sunday.
Although Sandeep was hit for 36 runs – the most expensive match for the 17-year old in IPL – he took the wickets of Surya Kumar Yadav, Keiron Pollard and Krunal Pandya enticing all three batsmen cunningly. Sandeep now returns from Delhi with five wickets and good economy of 6.833, a perfect figure for a leg spinner in his debut IPL. | 2019-04-18T14:41:37 | https://cricketingnepal.com/articles/453363/sandeeps-grand-farewell-in-ipl-debut |
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Over the past week, we've been quite literally drilling down on the last few tasks that must be accomplished prior to our steel working teams arriving on site. Our team has been priming and drilling pier holes and lining them with sleeves to provide additional stability if soil conditions are ever to unsettle and create any instability.
Soon after the sleeves are all in place, we'll see QTS Ashburn rapidly take shape. With our foundation secured, we can continue to press forward on an aggressive delivery schedule and quickly offer high-demand, high-quality inventory in one of the nation's premiere data center markets. | 2019-04-18T13:28:56 | https://www.qtsdatacenters.com/resources/construction-blog/2017/08/31/securing-our-foundation |
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Current treatments for AIDS are ineffective at eradicating the virus because; they are unable to detect mutant forms of the HIV virus. At the moment, HIV AIDS has afflicted 60 million people worldwide and a staggering 16,000 new infections occur each day. The current treatment options use antiretroviral drugs consisting of protease inhibitors and reverse transcriptase inhibitors, but these current treatments are unable to permanently destroy the virus. We first performed research to understand how HIV viruses infect human cells using information obtained from sources like the Cell Digest Journal. We then investigated the current treatment drugs for HIV AIDS patients using information obtained from the Database AIDS and Cancer Research Abstract, and from molecular genetics textbooks.
We concluded that currently used drugs are ineffective at suppressing mutant viruses from replicating over a lengthy time frame. To understand the principles, the promises and, the challenges behind the use of RNAi, we investigated articles in PubMed, the Nature Journal, and the Cell Research Journal. From our findings, we concluded that although the siRNAs potential as a potent future treatment lies in its ability to directly cleave RNAs for viral genes rather than proteins, nevertheless, the technology needed to create vectors that effectively deliver the antiviral RNA to host cells has not yet been fully developed. Based on the results and conclusions from our research we cautiously recommend the use of RNAi specifically siRNA as a more effective treatment alternative for AIDS. They are effective because even when the viral genes mutates, siRNAs can be constructed to complementarily bind to specific conserved regions of the HIV’s genome. Using RNAi designed to effectively target these conserved genes means that conserved viral genes will more likely be deactivated thus, inhibiting HIV replication irrespective of its mutant form.
Key words: mutant, protease inhibitor, reverse transcriptase inhibitor, RNAi, genes, nucleotides, conserved, siRNA.
On March 29, 2007, we received approval of our proposal to research whether the use of RNAi, specifically siRNA is a better alternative therapy for HIV treatment. This report presents the findings of our study. We proceeded to first describe how HIV virus infects the human cell and why current treatment options are ineffective at providing a cure. We researched the current treatments available and concluded that it is best to look for an alternative. We then identified and examined the principles behind the use of RNAi to inhibit viral replication, their possible limitations, and the use of siRNA in AIDS treatment.
The HIV virus arose from mutation of a similar virus called the Simian Immunodeficiency Virus (SIV), which is found in primates. It emerged in the human population of Africa in approximately 1930 (Bauman 718). The virus infects the cell by first attaching to membrane receptors of the host cell before it immediately penetrates the host cell. Once in the cell, it makes a copy of its genetic material and inserts it into the host cell DNA. Once inserted the viral DNA directs the host cell to synthesize many HIV viruses, these viruses destroy the host cell when through lysis and are released into the blood stream.
Currently, HIV has infected approximately 60 million people world wide and in fact a staggering 16,000 new infections are reported daily (Bauman 721). Several factors have significantly contributed in increasing the rate of HIV infection around the world, most notably, unprotected heterosexual contact. In addition, male homosexual contact, the use of contaminated injected needles, sharing razors and tooth brushes, and even mouth-to-mouth kissing to a lesser degree have been vital to its rapid spread.
It is estimated that infection through male homosexual contact accounted for 48% of new AIDS cases in the United States in 2002. Even with the use of condom the individual's risk of being infected is only reduced to about 70%; moreover, leading a reckless sexual lifestyle can drastically reduce the protection provided by condom use (Bauman 718).
Current treatment involves the use of highly active antiretroviral therapy (National Institute of Allergy and Infectious Disease 1-6). It contains a mixture of antiviral drugs that target the proteins produced or found in HIV virus. However, these drugs cannot eradicate the virus because the HIV genes coding for the proteins the drugs target either mutates to avoid detection, or undergo transition to a latent phase and stop producing those target proteins (Cohen par 4). As a result, HIV infected individuals currently have no hope for a possible cure. A new drug therapy is desperately needed to directly target the genes and deactivate the gene products coded for by HIV's genetic material; it is believed that use of RNAi could be very effective for this purpose (Yeung et al par 4).
Using secondary sources like the National Institute of Allergy and Infectious Disease website, microbiology and molecular genetics textbooks, and the Science Now online journal, we obtained in-depth analysis on the principles behind RNAi treatment, their efficacy and, their limitations.
We concluded that although more research on RNAi is still needed, however, compared to current treatments it seems more effective at preventing viral replication. Its ability to directly target and complementary bind to sequence specific HIV target RNA rather than viral proteins, makes siRNA better able to overcome HIV viruses that use mutant proteins to evade detection. Furthermore, siRNAs are easy to construct and test.
Despite being a better alternative to current treatments like reverse transcriptase inhibitors and, protease inhibitors, there are still challenges that need to be overcome if the full potential for this new treatment therapy is to be realized. Currently, the technology to create effective transport systems crucial to delivering the antiviral RNAs to target cells is not yet fully developed; furthermore, it is not yet known if using RNAi could inadvertently lead to the unwanted silencing of other genes vital to the cell (Rana, 2007). Nevertheless, we recommend the use of siRNA as a better alternative for HIV treatment.
In the following sections, we provide additional details about our research methods, the results we obtained, the conclusion we drew from our results, and our recommendations.
We investigated the mechanism and process of HIV infection cycle . We conduct ed an interview with an immunology expert Dr. Frauwirth to obtain current understanding of the virus and insight to future studies. We also researched recently published texts such as Kuby’s Immunology and online database from NCBI website. We were able to figure out the detailed process of HIV infection and the viral lifecycle.
We identified the current treatment options for AIDS and their flaws: Using reverse transcriptase inhibitors . By researching the National Institute of Allergy and Infectious Disease website, we identified examples of drugs that fall under the class of reverse transcriptase inhibitors, and analyzed the biochemical pathway used by such drugs to target and prevent HIV viruses from replicating in the human cell. In addition, using information obtained from the Microbiology With Diseases by Taxonomy textbook, we identified the exact mechanism that makes reverse transcriptase inhibitors effectively attack HIV virus. Furthermore, we also researched the major flaw in using reverse transcriptase inhibitor drugs, and how the HIV virus takes advantage of this flaw to avoid being killed by drugs.
Using HIV protease inhibitors. By obtaining information on the types of drugs that fall under the class of HIV protease inhibitors using information obtained from secondary sources like Science Now Online Journal and molecular genetics textbooks, we were able to specifically analyze the reaction mechanism used by such drugs to inhibit the HIV virus from replicating. Also, we looked at the effectiveness of HIV protease inhibitors at eradicating the HIV virus and the main flaw in using such a treatment alternative. Furthermore, we examined how the HIV virus takes advantage of the limitations of using protease inhibitors to avoid being detected and destroyed.
We researched the principles behind RNAi therapy and its use for HIV treatment. We obtained information from various journals such as the Nature Journal, and the Database for AIDS and Cancer Research, and we created a detailed outline of the pathway used during RNA interference. We also examined how such a pathway can be triggered and applied to a HIV infected cell to inhibit viral replication. We then examined the advantages and disadvantages of using RNAi.
We determined the limitations to using RNAi. W e researched several articles from the Journal of Biotechnology and reviewed various research data from the National Institute of Health online database. In addition, I conducted an interview with an expert at the National Institute of Allergy and Infectious Diseases Dr. Frosso V oulgaropoulou to further analyze the application of RNAi to inhibiting HIV replication. We were able to identify and investigate several factors that limit the effectiveness of this technique.
In this section, we present the results of our research. We cover the mechanism of HIV infection, the current treatment options, the principle behind microRNA therapy, and the limitations of microRNA as a drug for HIV treatment. The following results correspond to the tasks described in the research methods section.
Primary binding of HIV. HIV binds to specific cells in the body that express certain surface protein. The specific cells include T-cells and monocytes, which serves very important immunological roles. The primary binding of HIV occurs between CD4 and gp120. CD4 is specific surface protein that is expressed in both T-cells and monocytes, and gp120 is specific surface glycoprotein on HIV that can bind to CD4 (Frauwirth, Interview) .
Secondary binding of HIV. The primary binding between gp120 and CD4 induce secondary binding. The secondary binding occurs differently in T-cells and monocytes. T-cells have specific receptor called CCR5 on the surface, and on the other hand monocytes have another receptor called CXCR4. These two specific receptors can bind to gp41, glycoprotein embedded in the membrane connected to gp120 (Frauwirth, Interview) .
Fusion of host and HIV. The primary and secondary binding of HIV induces fusion of HIV membrane with host membrane. The fusion is mediated mostly by secondary binding causing the fusion mechanism, but primary binding is necessary for secondary binding to occur. The fusion mechanism is triggered when the CCR5 or CXCR4 is activated by gp41 and lead to serious of events in the host to allow HIV to fuse (Frauwirth, Interview) .
Insertion of HIV genome into the host genome. The fusion of host and HIV membrane releases the viral genome and viral proteins into the host. The most important viral protein called reverse transcriptase can make viral RNA into RNA-DNA hybrids, and converted to normal double stranded DNA. Double stranded DNA is required to infect the host, because in order to reproduce and expend, it require the host to make viral protein and more copies of viral RNA, and only double stranded DNA is capable to fulfill the task. After producing double stranded DNA, another type of viral protein called integrase insert the viral double stranded DNA into the host genome at random location and become provirus (Kuby et al 2007) . The figure 2 illustrates all the components described and indicate the anatomical locations of the components to clarify some of the explanation. The term provirus refers to the state of virus infection, which has no significant activity in the host.
Activation of provirus and reproduction. The provirus gets activated when the environmental or internal signal cause the transcription factors stimulate transcription of proviral DNA. The transcription factors promote the process that allows DNA to pass the contained information to produce messenger RNA, which can ultimately produce proteins. The whole process is done by using host cellular machinery (Frauwirth, Interview) . The final outcome of this process is mass production of viral proteins and viral RNA. The products then assembles itself to form immature HIV, then buds out from the host and released HIV complete maturation and infect other cells. The term bud refers to the process of which HIV uses the host membrane containing all the necessary viral proteins such as gp120 and gp41 to form viral membrane and separate itself from the host (Kuby et al 2007) .
Treating AIDS using reverse transcriptase inhibitors drugs . There are two subclasses of drugs that fall under reverse transcriptase inhibitors, nucleotide reverse transcriptase analogs, and non-nucleotide reverse transcriptase inhibitors (Bauman, 2007).
Reverse transcriptase inhibitors act by interfering with a critical step in the HIV viral cycle called reverse transcription. During reverse transcription, an enzyme called reverse transcriptase converts HIV RNA (ribonucleic acid) to HIV DNA (deoxyribonucleic acid). Examples of drugs that are nucleotide reverse transcriptase inhibitors are AZT (Azidothymidine), Retrovir and Zidovudine.
a) Nucleotide reverse transcriptase inhibitors drugs. These drugs are made up of primarily faulty nucleotide (DNA) sequences, when these faulty DNA sequences are embedded into the newly synthesized viral DNA by the reverse transcriptase enzyme, synthesis of the nascent viral DNA is stopped thus preventing the virus from completely replicating its genes (National Institute of Allergy and Infectious Disease, 2006).
b) Non-nucleotide reverse transcriptase inhibitors . These types of drugs can be proteins that attach directly to the active site of the reverse transcriptase enzyme. When bound to the active site, the inhibitor induces a conformational change in the reverse transcriptase that prevents the enzyme from being able to convert the HIV RNA to DNA. Without the HIV’s genetic information being in a DNA format it can’t be integrated into the host cell’s chromosome, thus, the virus cannot direct the human cells to synthesize HIV virions, therefore the virus is unable to replicate. An example of a non-nucleotide reverse transcriptase inhibitor drug is Nevirapine (Hartwell et al., 2004).
Although reverse transcriptase inhibitors effectively inhibit the HIV cycle of growth and replication, nevertheless, these drugs are unable to cure AIDS because they do not completely eliminate the HIV virus from the body (Cohen, 2002). For the nucleotide reverse transcriptase inhibitor drugs, their major flaw comes from the fact that when administered to the patient at high doses it is extremely toxic. As a result, doctors only administer the drugs at low doses that do not destroy all the viral particles (National Institute of Allergy and Infectious Disease, 2006).
For non-nucleotide reverse transcriptase inhibitor drugs, their major flaw is that they are unable to keep up with the high mutation rate of the HIV virus. Because the viral genes coding for the reverse transcriptase enzyme mutates frequently, the HIV virus can produce alternate forms of the same enzyme that are structurally altered in such a way that their active sites cannot be recognized and attached to the inhibitor drugs. Consequently, the non-nucleotide reverse transcriptase inhibitor drugs cannot identify and inactivate these mutant enzymes and so the HIV virus can go on replicating even in the presence of the antiviral drugs.
Treating AIDS using protease inhibitor drugs. These inhibitors act by interfering with the protease enzyme that the HIV uses to produce infectious viral particles, examples of protease inhibitor drugs include, Norvir, Crixivan, Viracept and, Lexiva. During HIV replication, the virus produces two inactive proteins called gag and pol proteins, these proteins need to be cleaved in order to become activated. The cleavage of gag by HIV protease generates the viral coat used by HIV to attach to the human cells, and cleavage of pol generates key HIV components such as reverse transcriptase, capsid, and matrix proteins. The HIV protease inhibitor drugs disrupt HIV viral replication by binding to inactive gag and blocking its active site so that it cannot be activated by protease (Bauman, 2007). Consequently, the inactive gag is unable to generate viral components needed to form a truly functional virus as a result, HIV virus is unable to produce viable new viruses; therefore, it cannot replicate and destroy the human cells.
The major flaw of protease inhibitors results from their inability to keep up with the high rate of mutation of the HIV genes encoding the protease enzymes (Cohen, 2002). As a result, the virus is able to synthesize so many variant forms of the protease enzymes each having slightly altered active sites that are unrecognizable to the protease inhibitors. When drugs like Norvir are administered to patients they are unable to attach to these modified active sites and deactivate the mutant gag proteins (Hartwell et al., 2004), consequently the virus is able to successfully multiply within the patient even though they are on a rigorous treatment regimen.
RNAi (RNA interference) is basically the process of inhibiting a genes expression by using double stranded RNA to cleave the genes RNA transcript or preventing the RNA from being translated to a protein. RNAi is quite ubiquitous in nature and can be found in fungi, animals and, plants (Engels and Hutvagner, 2006). The process of using double stranded RNA was first observed in worms (Caenorhabditis elegans). In plant cells, RNA interference is used to inhibit adenoviral attack; it is a tool used by plants analogous to an animal’s use of immune cells to fight viral infections (Yeung, et.al 2005).
For our research analysis we describe the two major RNAi mechanisms: the use of siRNA (small interference RNA) and, miRNA (microRNA). siRNA are 21 to 23 nucleotides long double stranded RNA that deactivates a target messenger RNA (mRNA) by binding and directly cleaving it (Strachan and Read, 2004). To understand the efficacy of siRNA and the RNAi pathway it induces, it is imperative we first provide a description of how siRNA is generated.
A small interfering RNA as shown in Appendix C originates from a linear double stranded RNA (dsRNA). This double stranded RNA is made up of two strands: an antisense strand (guide strand) and a sense strand (passenger strand). The antisense strand contains nucleotide sequences complementary to the target RNA, while the sense strand contains sequences complementary to the guide strand. Once the linear double stranded RNA is formed, it binds to an RNAse II enzyme called DICER (Rana, 2007). The DICER cleaves the dsRNA into a 21 to 23 nucleotide long RNA known as siRNA. Now that the siRNA has been formed, we proceed to examine how it triggers gene silencing. siRNA acts by complementarily binding to a complex called RISC (RNA-Inducing Silencing Complex) through its guide strand to form an siRNA-RISC complex. This complex now binds specifically to the target RNA and cleaves the target RNA thus, preventing the gene product coded by the RNA to be produced, as shown in Appendix C.
MicroRNA on the other hand is generated from a markedly different process. miRNA as seen in figure 2 are 22 nucleotide long RNA molecules coded for within the genome that lead to gene silencing (Strachan and Read, 2004). Unlike siRNA, microRNAs are actually coded for by genes in the cell. The miRNA genes are transcribed by RNA polymerase II in the nucleus, to form a primary miRNA transcript. Just like normal messenger RNAs, the primary miRNA formed has a 5’ cap and a poly-A-tail. Like siRNA, it is double stranded with guide and passenger strands, in addition, it is also looped (Rana, 2007).
The primary miRNA are shortened by a nuclear RNaseII called DROSHA into what is called a premiRNA. The premiRNA are then carried from the nucleus of the cell to the cytoplasm. While in the cytoplasm the premiRNA is cleaved by DICER into the 22 nucleotide mature microRNA. Once formed the microRNA now initiates its RNA interference pathway. It does so by binding the RISC via its guide strand to form a complex. It is this complex that binds to the target RNA albeit with a lower degree of complementarity.
A current view is that miRNAs function to silence gene expression through imperfect base-pairing with transcripts. Due to this imperfect binding by the guide strand, it does not cleave the RNA but rather the loop created as a result prevents translation from occurring. Since RNA silencing mediated by miRNA does not require complete sequence complementarity, one miRNA can target multiply different miRNAs (Engels and Hutvagner, 2006). Thus, miRNA prevents the gene product coded for by the target RNA from forming (Rana, 2007).
Based on our research results from the National Institute of Allergy and Infectious Disease and also from the Nature Journal, current findings support such a notion since several viruses have been found to encode RNAi suppressors, which could function to influence the cell's overall miRNA environment. RNAi, apart from providing an indispensable reverse genetic tool and promising therapeutic approach, regulates gene expression on both transcriptional and post-transcriptional level and it is used to fight against viruses and bacteria (Engels and Hutvagner, 2006).
Now that we have an idea of the gene silencing pathways used by both siRNA and microRNA, let us see how our knowledge of the RNAi process can be specifically applied to inhibit HIV viral replication using siRNA. Studies on the use of siRNA to inhibit HIV-1 replication have shown promise. As seen in figure 3 the HIV viral core consists of several proteins such as reverse transcriptase, capsid and, protease. Scientists have used siRNAs to specifically target RNA transcripts coding for key HIV-1 protein components such as tat protein, reverse transcriptase, and the HIV-1 CD4 co-receptors. Although such studies showed that siRNA was able to significantly suppress HIV-1, nevertheless certain issues remain of concern (Rana, 2007).
NOTE : HIV is a retrovirus with an outer envelope containing proteins, some of which are spikes consisting of gp20 and gp41 proteins. The core of the virus contains RNA genes and copies of reverse transcriptase, the enzyme that makes a DNA copy of RNA. During the reproductive cycle, the DNA copy first becomes integrated into a host chromosome and then is transcribed back into viral RNA.
One of the major concerns about the use of siRNA based therapy is the question of how to effectively deliver the siRNA to the target cells without it being degraded. Recent approaches aimed at tackling this question have not only yielded novel strategies for RNA delivery to cells in vivo, but they have also provided fantastic new strategies to suppress HIV-1. Among strategies used to deliver siRNA to HIV-1 infected cells is the use of lentiviral vectors, and also RNA packaged in micelles (Morris and Rossi, 2006). We found the use of certain lentiviral vectors to be absolutely fascinating especially when you consider how it could also contribute to preventing HIV virions from being produced and released from the infected cell.
For instance, let us consider the use of conditionally replicating HIV vectors (crHIV vectors). In crHIV vectors the antiviral siRNA in addition to the vector RNA are packaged together, unlike a normal HIV virus the crHIV vector lacks the gene and protein for the tat and other structural polyproteins necessary for the formation of nascient viruses in the host cell. Once created, the crHIV vector is targeted to an already infected HIV cell. Like a normal HIV virus it penetrates the host cell and releases its vector RNA along with the antiviral siRNA. The vector RNA is converted to DNA and integrated into the infected cells genome.
However, because the vector RNA lacks the gene for the structural polyproteins necessary for the production of its vector virions, it competes for the tat protein used by the HIV-1 virus already in the host cell for replication. In the mean time, the antiviral RNA introduced into the host cell targets the HIV-1 RNA and cleaves it, consequently reducing the amount of HIV-1 virions that are produced and thus fewer “demand” for the tat polyprotein by the HIV-1(Morris and Rossi, 2006).
As a result, the crHIV vector gains the advantage and out competes the HIV-1 virus for the tat protein therefore the vector virions are predominantly produced and released from the infected cell compared to HIV-1 virions. The use of RNAi to inhibit HIV-1 replication provides significant advantages that make them a very appealing therapeutic strategy. RNA interference using siRNA are easy to construct and test in cells, furthermore, they cost less to create and it takes them less time to elicit their antiviral effects against the HIV-1 virus (Morris and Rossi, 2006).
One of the current major obstacles in the treatment of AIDS has been the fact that the HIV virus is able to evade antiviral drugs such as protease and reverse transcriptase inhibitors through varied mutations on their respective genes (Cassol et al, 2006). The virus also avoids being destroyed by using alternative splicing to try to avoid being targeted via RNAi. To try to overcome this problem, scientists are currently attempting to create siRNAs targeting conserved regions such as the promoters of the HIV-1 that are much less susceptible to mutations. The principle to this strategy is that because the fidelity of such regions of the viral RNA is absolutely crucial to the virus’s ability to code information needed for replication, the HIV-1 virus ensures that very little mutation is permitted in those regions (Morris and Rossi, 2006).
From our research, we found three main limitations of the microRNA techniques in treating HIV: Although RNAi therapy holds great promise nevertheless, like all other drug therapies for HIV treatment it does have some limitations.
Potential for off targeted gene silencing, siRNAs constructed to cleave RNA for a specific gene could lead to the silencing of genes not meant to be targeted. The effect of such inadvertent silencing could lead to unforeseen effects in the host organism (Morris and Rossi, 2006).
Inefficient RNA delivery to host cells. Scientists have made great strides in creating systems especially in the case of HIV treatment, capable of carrying the siRNA in the blood to the target cell. One of the key strategies employed is the use of lentiviral vectors packaged with the antiviral siRNA and delivered to the host cell. As mentioned earlier, the use of conditionally replicating HIV vectors have also been used. However, efficient delivery systems are still sought after in the treatment of other viral-related diseases.
Viral Resistance via Mutations. Point mutations and alternate splicing by the virus within the regions targeted by the siRNA can lead to the virus developing nucleotide sequences that are not specific to the siRNA. Thus, the virus might develop resistance to the therapeutic strategy. (Morris and Rossi, 2006).
The conducted interview with Dr. Kenneth Frauwirth and subsequent research revealed several unique characteristics of HIV infection. The results described the process of infection, reproduction and involved proteins that might be potential target for treatment. The first unique characteristic was binding of HIV to host. The host surface protein CD4 serves unique and important roles in host, but CCR5 and CXCR4 has less important role in the host, which indicate blockage of CCR5 and CXCR4 can reduce the infection by HIV. Another unique characteristic is reverse transcriptase, which is only found on the sub class of virus called retrovirus, which include HIV. It is currently the most used target for the HIV treatment, but still needs improvement. The process of HIV infection reveals more characteristics that can be used as target for treatment.
The major current treatment options of HIV infected patients involve the use of two major classes of drugs, reverse transcriptase inhibitors, and HIV protease inhibitors. When these treatment options are used they are initially successful at inhibiting viral replication. However, the HIV virus eventually develops resistance by altering its genes and changing the structure of the proteins targeted by these drugs so that they won’t be recognized. Consequently, we conclude that both current treatment options are not effective at totally stopping the HIV virus from replicating within the human body.
The use of RNA interference especially via siRNA to inhibit HIV replication is based on the idea of targeting viral RNA with complementary RNA that ultimately inhibits the viral gene product from being made. Using siRNA based therapy for AIDS treatment holds certain advantages that make it a promising treatment option. siRNAs are easy to construct and relatively cost efficient. They can be packaged in lentiviral vectors and delivered into the target cell. In addition, the use of siRNA unlike protease inhibitor drugs can employ strategies designed to overcome a key obstacle to the efficacy of protease and reverse transcriptase inhibitor drugs. To overcome the resistance inferred by HIV-1 viruses through their ability to mutate target sites, scientists believe siRNAs can be constructed that target conserved regions such as, promoter regions. A key disadvantage to using RNAi as a treatment is the possibility of inadvertent off targeted gene silencing in vivo.
Ultimately, even though siRNA treatment seems to be an effective tool to fighting the HIV-1 virus it is likely to be used in the future in conjunction with other treatment options to create a very powerful highly active antiretroviral treatment cocktail.
Current research shows that people with mutations on CCR5 and CXCR4 receptors allowed the HIV positive patient to live without getting AIDS. These mutations alter the receptor binding mechanism thereby prevent HIV from entering the host. Due to the inability of reverse transcriptase and protease inhibitor drugs to totally destroy the HIV virus and stop the progression of AIDS, it is possible that RNA interference pathways triggered via siRNA can be used to cleave the host RNA coding for these receptors in stem cells for primary T cell lines, thereby preventing expression of the genes for these receptors. Information obtained from ongoing and future experimental studies using RNAi will give us a much greater insight on how to utilize this rapidly developing genetic tool to effectively fight viral related diseases such as AIDS. Until we find ways to resolve some of the risks associated with RNAi use especially with siRNA, it is best to remain cautious rather than overly optimistic in our assessment of this therapeutic approach.
Bauman, Robert. Microbiology With Disease by Taxonomy. 2 nd ed. Pearson: Benjamin Cummings, 2007.
Hartwell, H., Hood, L., Goldberg, M., Reynolds, A., Silver, L., & Veres, R. (2004). Genetics: From Genes To Genomes. New York: McGraw- Hill.
Immunodeficiency Virus Type 1 Infection”. Human Gene Therapy. 17 (2006) 479-486.
Rana, M. Tariq.” Illuminating the silence: understanding the structure and function of small RNAs.” Nature Reviews. Molecular Cell Biology 8, (January 2007): 23-36.
Strachan, Tom., and Read P. Andrew.” Genetic Manipulation of Cells and animals”. Human Molecular Genetics 3. Ed. Fran Kingston and Michael Morales. Garland Publishing, 2004. 592-595.
Yeung Man Lung, “Changes in microRNA expression profiles in HIV-transfected human cells.” BioMed Central Ltd. 2005 December 28. doi: 10.1186/1742-4690-2-81.
Conserved Sequences: A DNA sequence that is very similar in different species or organisms. It has very few mutations.
DICER: A member of RNase III class of ribonucleases used in the RNA interference pathway to cleave double stranded RNA to 21 base pairs.
Gag: Lentiviral packaging element that codes for a structural protein.
Genes: Region of DNA coding information used to form either a functional RNA or an actual protein.
microRNA: Small RNA molecules encoded in genomes of plants and animals. They regulate gene expression by binding to 3’ untranslated region of the target RNA.
mRNA: The RNA produced directly from DNA transcription. It carries the transcribed information from the nucleus to the cytoplasm, to be used for translation.
Mutation: A change in DNA sequence between generations.
Nucleotides: Monomers of nucleic acids. They are made of ribose or deoxyribose, phosphate groups, nitrogenous bases.
Pol: Lentiviral packaging element that codes for proteins.
Reverse Transcriptase: Enzyme that converts RNA to DNA.
RISC: An siRNA directed endonuclease that catalyzes the cleavage of a single phosphodiester bond on the mRNA target.
RNAi: A technique where double stranded RNA slice specific RNA transcripts.
siRNA: 21 – 23 nucleotide double stranded RNA molecules that cause the cleavage and degrading of a target RNA.
Tat: A lentiviral element needed for the elongation of nascent viral transcripts.
Vector: A molecule used to propagate a nucleic acid or even a protein.
The following interview took place on May 2, 2007. A transcript of the interview follows.
D – Thank you Dr. Frauwirth for agreeing to have an interview with me today.
K – It is my pleasure to inform students on their curiosity in the field.
D – So, for the first question. Could you explain the infection mechanism of HIV?
K – As you know HIV binds to CD4+ T- lymphocytes and monocytes through CD4+ and gp120 interaction. This binding cause the confirmation change in gp120 to allow gp41 to bind to certain chemokine receptors such as CCR5 on T-cells and CXCR4 on monocytes, and this binding cause G-protein linked cascade and ultimately fusion occurs between HIV and host membrane.
D – Then is it possible to block the second interaction to prevent HIV from infecting the host?
K – It is not entirely sure, but the current studies show that complete state of latency in HIV+ patience with mutations in those receptors, so it is certainly possible approach for treatment.
D – One more question, so after the infection and integration of viral genome. What happens to the inserted viral gene?
K – The state of viral gene in host genome is called provirus stage and it is not entirely sure if it is in state of latency or has minimal activity. But after certain stress triggers the transcription factor to start transcription which is much rapid than regular gene transcription due to LTR on both side of viral gene. Then it follows the regular gene expression mechanism to form viral RNA and viral proteins using host machinery.
D – Thanks again for the interview Dr. Frauwirth. I’ve learned much from the interview.
K – You’re welcome. If you have any more questions feel free to email me.
This interview took place on August 7, 2007. A transcript of the interview follows.
(F) – Frosso Voulgaropoulou, PhD. National Institute of Allergy and Infectious Disease.
O – Thank you Dr. Frosso for agreeing to have an interview with me today.
F – No problem at all, I am quite impressed that you chose to research on such a complex topic.
O – First let me clarify my understanding of siRNA, miRNA and how it is applied to HIV infection. siRNAs are basically 21 to 23 nt long RNA sequences that bind with high level of complementarity to a target RNA strand. They prevent a gene from being expressed by directing enzymes that cleave the target strand. microRNAs on the other hand are 22-23nt long sequences coded by genes in the cell. microRNAs act by preventing translation rather then cleaving the target RNA.
F – Exactly, microRNAs are broad acting; they don’t have to be perfectly complementary to the target RNA unlike siRNAs that need to be almost perfect. Thus, microRNAs can lead to inadvertent gene silencing due to their lack of specificity. As a result, they would not be the ideal therapeutic tool in fighting HIV replication in a cell. Unlike siRNAs that actually cleave the mRNA, microRNAs form loops due to non-complementary base pairing, and these loops prevent the proteins needed for translation from being able to properly attach to the mRNA.
O – I was reading the article on RNA silencing you gave me, and it says a single mutation between the antisense strand and the RNA transcript drastically reduces the ability of siRNA to target genes.
F – Yes, otherwise it won’t cleave the RNA transcript. Remember when you took biochemistry and you learned about how proteins have primary, secondary, tertiary and, quaternary structures. The same applies to the principles behind the use of siRNA to cleave a target. The siRNA- directed enzymes that cleave the RNA transcript need to be in a specific secondary conformation in order to be able to act on their target. A single mutation in the anti sense strand affects this secondary structure. When you have non perfect complementarity between the target and the siRNA, the siRNA can behave as microRNA by forming a loop and triggering the microRNA interference pathway.
O – In a molecular genetics class I took, we talked about the idea of methylation of genes in order to make them inaccessible. Is targeted methylation possible? Can it be induced in receptors such as CD4 receptors targeted by HIV so that they won’t be expressed. (Use of RNA dependent DNA methylation)?
F – Targeted methylation is possible but it is an extremely difficult approach. Methylation is a mechanism that an organism uses to prevent gene accessibility. Applying directed methylation in HIV infected cells can lead to unforeseen inadvertent physiological effects. I am not that familiar with the use of methylation to silence genes.
O – siRNA resistant viruses can come about by single nucleotide changes.
Must the region targeted by siRNA be approximately 21 to 25 nucleotides long? If not, then why not build much shorter siRNA strands that target shorter regions on the target RNA. By doing so, the smaller the target region the less alternate mutant forms that the virus can employ within that region.
F – First let us consider what happens if the siRNA is too long. If their size were too big they could cause the body to trigger its interferon response. Thus, all the host cells containing siRNAs are recognized and destroyed and this would be catastrophic for the organism. Amazingly, it is thought that RNAi evolved in congruence with the body’s immune system so that their length would be such that they would not trigger an immune response. If the siRNAs were too small it will make it very difficult to properly anneal to the target RNA transcript. Thus, the siRNAs would only weakly bind to the target and would not produce sufficient interaction needed to activate cleavage due to random interaction.
O – All HIV viruses no matter how variant still share certain fundamental physical (structural and functional protein) characteristics. Thus, they all have conserved genes. Since these genes are probably least likely to mutate why not target siRNAs to them.
F – Your idea makes perfect sense. But the problem with these conserved regions is that they are located inside the virus (beyond the viral coats). Because these genes are encapsulated in the virus and surrounded by a highly variable viral coat, it is difficult to attach and penetrate the viral coat to get at these conserved regions due to the fact that the genes coding for the receptors on the viral surface are constantly changing. The only time that these conserved regions can be freely accessible is when the viral genes have been released inside the host cell during infection.
As a side note, when the HIV virus develops resistance to drugs their replication slows down. The state of a virus in the host cell in response to treatment is determined by its cost fitness. This is the ability of a virus to successfully replicate and be virulent. Each time the virus mutates in response to the treatment regimen, its replication rate slows down while its virulence increases. A good strategy to treating AIDS might be to target many of its different conserved genes thus, making it extremely difficult for the virus to mutate at all these target sites simultaneously. Yet, HIV still manages to evade targeted treatment.
O – Have any field tests been done on animals, humans?
F – Not yet, although a clinical trial is about to be underway!
O – Thank you so much for sharing your time to answering my questions. I am taking a virology course next semester and I hope to apply the knowledge gained from the course into better understanding how HIV replication can be more effectively controlled.
F – It has been my pleasure. Keep in touch if you have any more questions. | 2019-04-19T00:20:43 | http://www.kon.org/urc/v6/moghalu.html |
There is an opportunity for FRAG members to take part in a metal detecting survey on a field near Bainton. This is a continuation of previous detecting there – though this time the emphasis will be on those with their own metal detectors as we will only have a couple spare.
The event is being organised by Sue Deoraj with the assistance of Steve Critchley. It is planned to take place for a couple of hours on Thursday 18th April. Numbers will need to be capped at 10. | 2019-04-21T11:04:43 | https://peterborougharchaeology.org/event/metal-detecting-near-bainton/ |
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2010-06-09 Assigned to ASANTE SOLUTIONS, INC. reassignment ASANTE SOLUTIONS, INC. CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: M2 GROUP HOLDINGS, INC.
2015-07-02 Assigned to ASANTE LLC reassignment ASANTE LLC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ASANTE SOLUTIONS, INC.
Some embodiments of a medical infusion pump system include a pump device and a removable controller device. When the pump device and the removable controller device are removably attached to one another, the components may provide a portable infusion pump unit to dispense medicine to a user. In particular embodiments, the removable controller device includes a user interface to readily provide information, for example, about the operation of the pump.
This application is a continuation of U.S. patent application Ser. No. 11/522,603 filed on Sep. 18, 2006 by Mark Estes et al., which claims priority to: (1) U.S. Provisional Application Ser. No. 60/720,411 filed on Sep. 26, 2005 by Mernoe et al. and entitled “Precision Drive Mechanism,” (2) U.S. Provisional Application Ser. No. 60/720,405 filed on Sep. 26, 2005 by Mernoe et al. and entitled “Flexible Pushrod Mechanism,” and (3) U.S. Provisional Application Ser. No. 60/721,267 filed on Sep. 28, 2005 by Estes et al. and entitled “Infusion Pump with Removable Controller.” The contents of these earlier applications are fully incorporated by reference herein.
This document relates to an infusion pump system, such as a medical infusion pump system.
Pump devices are commonly used to deliver one or more fluids to a targeted individual. For example, a medical infusion pump device may be used to deliver a medicine to a patient as part of a medical treatment. The medicine that is delivered by the infusion pump device can depend on the condition of the patient and the desired treatment plan. For example, infusion pump devices have been used to deliver insulin to the vasculature of diabetes patients so as to regulate blood-glucose levels.
A number of factors may affect the design of infusion pump devices. One such factor is the size of the device. The pump device may be sized to house the various pump components, yet a large device may reduce the portability for the user. Another factor that may affect the design of an infusion pump device is the convenience to the user. For example, if the pump device is designed to be controlled via a user interface on a large wireless module that must be separately carried, the user may not be able to monitor the operation of the infusion pump during use without first locating, handling, and interfacing with the separate wireless module. A number of infusion pump components can impact the overall size and portability of an infusion pump system and the convenience to the user.
In some embodiments, a medical infusion pump system may include a pump device having a drive system to dispense a medicine from the pump device. At least a portion of the drive system may be in electrical communication with one or more electrical contacts of the pump device. The system may also include a removable controller device having a user interface. The removable controller device may be removably attachable to the pump device in a fixed relationship. The controller device may include one or more electrical contacts that engage the electrical contacts of the pump device when removably attached.
Particular embodiments of a medical infusion pump system may include a pump device having a drive system to dispense a medicine from the pump device. The system may also include a first removable controller device having a first user interface. The first removable controller device may be mechanically attachable to the pump device and may be electrically connected to the pump device when mechanically attached. The system may further include a second removable controller device having a second user interface that is different from the first user interface. The second removable controller device may be mechanically attachable to the pump device and may electrically connected to the pump device when mechanically attached. In certain aspects, the pump device may be mechanically attachable to only one of the first and second removable controller devices at a time.
Some embodiments of a medical infusion pump system may include a pump device having a drive system to dispense a medicine from the pump device. The pump device may include a first battery. The system may also include a removable controller device mechanically attachable to the pump device. The removable controller device may be electrically connected to the pump device when mechanically attached. The controller device may include a second battery. The first battery may have a greater energy density than the second battery and may provide energy to charge the second battery over a period of time. The second battery may provide energy to at least a portion of the drive system of the pump device.
In certain embodiments, a medical infusion pump system includes a pump device and a removable controller device. The pump device may include a pump housing that defines a space to receive a medicine and a drive system to dispense the medicine when received by the pump housing. The drive system may include a piston rod that is incrementally movable to apply a dispensing force. The pump device may also include one or more electrical contacts disposed on the pump housing. At least a portion of the drive system may be in electrical communication with the one or more of the electrical contacts. The removable controller device may include a controller housing that is removably attachable to the pump housing in a fixed relationship. The removable controller device may also include one or more electrical contacts disposed on the controller housing. The electrical contacts of the controller device may be engageable with the electrical contacts of the pump device when removably attached. The removable controller device may further include a user interface arranged on the controller housing. The user interface may include a display and one or more user-selectable buttons. The pump device and the controller device, when removably attached, may provide a hand-graspable portable unit.
Some embodiments described herein may include a method for operating a medical infusion pump system. The method may include transmitting electrical energy, from a first battery in a pump device to a second battery in a removable controller device. The pump device may include a drive system to dispense a medicine from the pump device, and the removable controller device may be removably attached to and electrically connected to the pump device. The method may also include intermittently transmitting electrical energy from the second battery in the removable controller device to at least a portion of the drive system of the pump device. The first battery may have a greater energy density than the second battery and may provide energy to charge the second battery over a period of time.
These and other embodiments may provide one or more of the following advantages. First, the infusion pump system may be portable so that a user can wear the pump device (e.g., adhered to the user's skin or carried in a user's pocket or portion of clothing) and receive the infused medicine throughout the day or night. Second, the pump device of the infusion pump system may include a drive system that controllably dispenses medicine in a reliable manner. Third, the pump device of the infusion pump system can be removably attached to a controller device having a user interface. As such, the user can readily monitor the operation of the pump device without the need for carrying and operating an separate wireless module. Fourth, the infusion pump system may comprise two or more removable controller devices having different user interfaces. In these circumstances, a first controller device having a first user interface can be selected for use with the pump device, or a second controller device having a second user interface can be selected for use with the pump device. Fifth, the pump device may be capable of dispensing a first medicine when connected with a first controller device and may be capable of dispensing a second medicine when connected with a second controller device. Sixth, the pump device may include a first battery that recharges a second battery in the controller device, which in turn provides power to the drive system of the pump. Thus, each time a new pump device is connected to the controller device, the second battery in the reusable controller device is recharged, thereby reducing or possibly eliminating the need for separate recharging of the controller device.
FIG. 1 is a perspective view of an infusion pump system, in accordance with some embodiments.
FIG. 2 is another perspective view of the infusion pump system of FIG. 1.
FIG. 3 is another perspective view of the infusion pump system of FIG. 1.
FIG. 4 is a perspective view of an infusion pump system, in accordance with some embodiments.
FIGS. 5A-D are examples of a user interface of a first controller device in the infusion pump system of FIG. 4.
FIGS. 6A-D are examples of a user interface of a second controller device in the infusion pump system of FIG. 4.
FIG. 7 is an exploded view of a pump device of the infusion pump system of FIG. 4.
FIG. 8 is a perspective view of a controller device of the infusion pump system of FIG. 4.
FIG. 9 is a perspective view of one controller device of the infusion pump system of FIG. 4.
FIG. 10 is a perspective view of another controller device of the infusion pump system of FIG. 4.
FIG. 11 is an exploded view of a portion of the pump device of the infusion pump system of FIG. 4.
FIGS. 12A-C are perspective views of a portion of the pump device of FIG. 9.
FIG. 13 is a perspective view of a portion of a pump device for an infusion pump system, in accordance with some embodiments.
Referring to FIGS. 1-2, some embodiments of an infusion pump system 10 include a pump device 100 that can communicate with a controller device 200. The pump device 100 includes a housing structure 110 that defines a cavity 116 in which a fluid cartridge 120 is received. In this embodiment, the pump system 10 in a medical infusion pump system that is configured to controllably dispense a medicine from the cartridge 120. As such, the fluid cartridge 120 may contain a medicine to be infused into the tissue or vasculature of a targeted individual, such as a human or animal patient. For example, the pump device 100 can be adapted to receive a medicine cartridge 120 in the form of carpule that is preloaded with insulin or another medicine for use in the treatment of Diabetes (e.g., Byetta®, Symlin®, or others). Such a cartridge 120 may be supplied, for example, by Eli Lilly and Co. of Indianapolis, Ind. Other examples of medicines contained in the fluid cartridge 120 include: pain relief drugs, hormone therapy, blood pressure treatments, anti-emetics, osteoporosis treatments, or other injectable medicines.
In some embodiments, the controller device 200 may be removably attached to pump device 100 so that the two components are mechanically mounted to one another in a fixed relationship. Such a mechanical mounting can releasably secure an electrical connection between the removable controller device 200 and the pump device 100. For example, the controller device 200 may be in electrical communication with a portion of a drive system (not shown in FIGS. 1-2) of the pump device 100. As described in more detail below, the pump device 100 includes a drive system that causes controlled dispensation of the medicine or other fluid from the cartridge 120. In some embodiments, the drive system incrementally advances a piston rod (not shown in FIGS. 1-2) longitudinally into the cartridge 120 so that the fluid is force out of the output end 122. In this embodiment, the septum at the output end 122 can be pierced to permit fluid outflow when a cap member 115 is connected to the pump housing structure 110 (described in more detail below, for example, in connection with FIG. 5). Thus, when the pump device 100 and the controller device 200 are removably attached and thereby electrically connected, the controller device 200 communicates electronic control signals via hard-wire-connection to the drive system or other components of the pump device 100. In response to the electrical control signals from the controller device 200, the drive system of the pump device 100 causes medicine to incrementally dispense from the medicine cartridge 120.
Still referring to FIGS. 1-2, The controller device 200 can include a controller housing structure 210 that is configured to mate with a complementary portion of the pump housing structure 110 so as to form a releasable mechanical connection. For example, the controller housing structure 210 may define a cavity (refer, for example, to FIG. 6) that mates with a portion of the pump housing structure 110 for a snap fit engagement. Also, the controller housing structure 210 may include a finger 212 that engages a mating surface 117 of the pump housing structure 110 when the controller device 200 is removably attached to the pump device 100. As described in more detail below in connection with FIGS. 5-6, a magnetic attachment may be employed to releasably secure the pump device 100. For example, the magnetic attachment can serve to retain the pump housing structure 110 in the cavity defined by the controller housing structure 210. In alternative embodiments, one or more releasable connector devices (e.g., mating tongues and grooves, mounting protrusions friction fit into mating cavities, or the like) can be used to further implement the releasable securement of the controller device 200 to the pump device 100.
As described in more detail below in connection with FIGS. 5-6, the pump device 100 may include one or more electrical contacts (e.g., conductive pads, pins, and the like) that are exposed to the controller device 200 and that mate with complementary electrical contacts on the adjacent face of the controller device 200. The electrical contacts provide the electrical communication between the control circuitry of the controller device 200 and at least a portion of the drive system or other components of the pump device 100. For example, in some embodiments, the electrical contacts permit the transmission of electrical control signals to the pump device 100 and the reception of feedback signals (e.g., sensor signals) from particular components within the pump device 100.
Still referring to FIGS. 1-2, the controller device 200 includes a user interface 220 that permits a user to monitor the operation of the pump device 100. In some embodiments, the user interface includes a display 222 and one or more user-selectable buttons (e.g., two buttons 224 a and 224 b in this embodiment). The display 222 may include an active area 223 in which numerals, text, symbols, images, or combination thereof can be displayed. For example, the display 222 may be used to communicate a number of settings or menu options for the infusion pump system 10. In this embodiment, the user may press one or more of the buttons 224 a and 224 b to shuffle through a number of menus or program screens that show particular settings and data (e.g., review data that shows the medicine dispensing rate, the total amount of medicine dispensed in a given time period, the amount of medicine scheduled to be dispensed at a particular time or date, the approximate amount of medicine remaining the cartridge 120, or the like). As described in more detail below, in some embodiments, the user can adjust the settings or otherwise program the controller device 200 by pressing one or more buttons 224 a and 224 b of the user interface 220. In embodiments of the infusion pump system 10 configured to dispense insulin, the user may press one or more of the buttons 224 a and 224 b to change the dispensation rate of insulin or to request that a bolus of insulin be dispensed immediately or at a scheduled, later time.
As shown in FIG. 1, the display 222 of the user interface 220 may be configured to display quick reference information when no buttons 24 a and 224 b have been pressed.
In this example, the active area 223 of the display 222 can display the time and the date for a period of time after no button 224 a or 224 b has been actuated (e.g., five seconds, 10 seconds, 30 seconds, 1 minute, 5 minutes, or the like). Thereafter, the display 222 may enter sleep mode in which the active area 223 is blank, thereby conserving battery power. In addition or in the alternative, the active area can display particular device settings, such as the current dispensation rate or the total medicine dispensed, for a period of time after no button 224 a or 224 b has been actuated (e.g., five seconds, 10 seconds, 30 seconds, 1 minute, 5 minutes, or the like). Again, thereafter the display 222 may enter sleep mode to conserve battery power. In certain embodiments, the display 222 can dim after a first period of time in which no button 224 a or 224 b has been actuated (e.g., after 15 seconds or the like), and then the display 22 can enter sleep mode and become blank after a second period of time in which no button 224 a or 224 b has been actuated (e.g., after 30 seconds or the like). Thus, the dimming of the display device 222 can alert a user viewing the display device 222 when the active area 223 of the display device will soon become blank.
Accordingly, when the controller device 200 is connected to the pump device 100, the user is provided with the opportunity to readily monitor infusion pump operation by simply viewing the user interface 220 connected to the pump device 100. Such monitoring capabilities may provide comfort to a user who may have urgent questions about the current operation of the pump device 100 (e.g., the user may be unable to receive immediate answers if wearing an infusion pump device having no user interface attached thereto).
Also, there is no need for the user to carry and operate a separate module to monitor the operation of the infusion pump device 100, thereby simplifying the monitoring process and reducing the number of devices that must be carried by the user. If a need arises in which the user desires to monitor the operation of the pump device 100 or to adjust settings of the pump system 10 (e.g., to request a bolus amount of medicine), the user can readily operate the user interface 220 removably attached to the pump device 100, without the requirement of locating and operating a separate monitoring module.
It should be understood from the description herein that the user interface 200 is not limited to the display and buttons depicted in FIG. 1. For example, in some embodiments, the user interface 220 may include only one button or may include a greater numbers of buttons, such as three buttons, four buttons, five buttons, or more. In another example, the user interface of the controller device 200 may include touch screen so that a user may select buttons defined by the active area of the touch screen display. Alternatively, the user interface may comprise audio inputs or outputs so that a user can monitor the operation of the pump device. Previously incorporated U.S. Provisional Application Ser. No. 60/721,267 also describes a number of configurations for a removable controller device and a user interface for the device in addition to the configuration illustrated in FIGS. 1-2 herein.
Referring to FIG. 3, the infusion pump system 10 may be configured to be portable and can be wearable and concealable. For example, a user can conveniently wear the infusion pump system 10 on the user's skin (e.g., skin adhesive) underneath the user's clothing or carry the pump device 100 in the user's pocket (or other portable location) while receiving the medicine dispensed from the pump device 100. As described in more detail below, the drive system may be housed in the housing structure 110 of the pump device 100 in a compact manner so that the pump device 100 has a reduced length. For example, in the circumstances in which the medicine cartridge 120 has a length of about 6 cm to about 7 cm (about 6.4 cm in this embodiment), the overall length of the pump housing structure 110 (which contains medicine cartridge and the drive system) can be about 7 cm to about 9 cm (about 8.3 cm or less in this embodiment).
In addition, the pump housing structure 110 may have an overall height of about 1.5 cm to about 4 cm (about 2.9 cm or less in this embodiment) and an overall thickness of about 8 mm to about 20 mm (about 14.5 mm or less in this embodiment). In such circumstances, the controller device 200 can be figured to mate with the compact pump housing 110 so that, when removably attached to one another, the components define a portable infusion pump unit that stores a relatively large quantity of medicine compared to the overall size of the unit. For example, in this embodiment, the infusion pump system 10 (including the pump device 100 attached to the removable controller device 200) may have an overall length of about 7 cm to about 9 cm (about 8.5 cm or less in this embodiment), an overall height of about 1.5 cm to about 4 cm (about 3.5 cm or less in this embodiment),and an overall thickness of about 8 mm to about 20 mm (about 15 mm or less in this embodiment).
As shown in FIG. 3, this embodiment of the infusion pump system 10 is pocket-sized so that the pump device 100 and controller device 200 can be worn in the user's pocket or in another portion of the user's clothing. In such embodiments, the cap member 115 of the pump device 100 may be configured to connect with a flexible tube 119 of an infusion set. The infusion set may include the tube 119 that extends toward a skin adhesive patch and connects with an infusion cannula (not shown in FIG. 3). The skin adhesive patch can retain the infusion cannula in fluid communication with the tissue or vasculature of the patient so that the medicine dispensed through the tube 119 passes through the cannula and into the user's body. As described below in connection with FIG. 5, the cap member 115 may provide fluid communication between the output end 122 (FIG. 1) of the medicine cartridge 120 and the tube 119 of the infusion set. In these embodiments, the user can carry the portable infusion pump system 10 (e.g., in the user's pocket, connected to a belt clip, or adhered to the user's skin) while the tube 119 extends to the location in which the skin is penetrated for infusion. If the user desires to monitor the operation of the pump device 100 or to adjust the settings of the infusion pump system 10, the user can readily access the user interface 220 of the controller device 200 without the need for carrying and operating a separate module.
In other embodiments, the infusion pump system 10 may be configured to adhere to the user's skin directly at the location in which the skin is penetrated for medicine infusion. For example, a rear surface 102 of the pump device 100 (refer, for example, to FIG. 2) may include a skin adhesive patch so that the pump device 100 is physically adhered to the skin of the user at a particular location. In these embodiments, the cap member 115 may have a configuration in which medicine passes directly from the cap member 115 into an infusion cannula that is penetrated into the user's skin. Again, if the user desires to monitor the operation of the pump device 100 or to adjust the settings of the infusion pump system 10, the user can readily access the user interface 220 of the controller device 200 without the need for carrying and operating a second, separate device. For example, the user may look toward the pump device 100 to view the user interface 220 of the controller device 220 that is removably attached thereto.
Referring to FIG. 4, some embodiments of an infusion pump system 20 may include a pump device 100 that is configured to mate with any one of two or more controller devices (e.g., controller device 200 and controller device 300 in this embodiment) that are different from one another. The controller devices 200 and 300 may have different user interfaces 220 and 320, respectively, so as to provide different control options to the user. For example, some users may select the first controller device 200 for use in combination with the pump device 100 for a simplified input comprising two buttons 224 a and 224 b in the user interface 220. In another example, some users may select the second controller device 300 for use in combination with the pump device 100 for a larger size display 322 and increased button options (e.g., four buttons 324 a, 324 b, 324 c, and 324 d) in the user interface 320.
The pump device 100 can be releasably secured to any one of the controller devices 200 and 300 in the infusion pump system 20. As previously described, the pump device 100 includes a pump housing structure 110, and at least a portion of the pump housing structure 110 is configured to be received in a complementary cavity 215 or 315 (FIGS. 8-10) defined in the controller housing structure 210 or 310. When the pump device 100 is received by the controller device 200 or 300, a retainer finger 217 or 317, respectively, may engage a mating surface of the pump housing structure 110. In addition, a magnetic attachment can be used to releasably secure the pump device 100 to any of the controller housing structures 210 and 310. In such circumstances, the pump device 100 includes one or more magnetically attractable devices 118 a and 118 b (e.g., permanent magnets in this embodiment) exhibited on the front surface 104 of the pump housing structure 110 which magnetically engage complementary devices (refer, for example to FIG. 8) arranged on the controller housing structure 210 or 310. As such, when the pump device 100 is received in the cavity defined by the controller housing structure 210, the magnetically attractable devices 118 a and 118 b form a magnetic attachment to retain the pump device 100 therein. Also as described in more detail below, the pump device 100 may include one or more electrical contacts 149 arranged to engage complementary electrical contacts 249 (refer, for example to FIG. 8) arranged on the controller housing structure 210 or 310.
In some embodiments of the infusion pump system 20, the first and second controller devices 200 and 300 may be configured to control the dispensation of the same type of medicine when the pump device 100 is removably attached thereto. For example, a medicine cartridge containing insulin may be received in the pump device 100, and the user may select (e.g., based upon the user's preference, based upon an expert's recommendation, or a combination thereof) either the first controller device 200 or the second controller device 300 for attachment to the pump device 100. Because the first controller device 200 includes a user interface 220 that is different from the user interface 320 of the second controller device 300, the user may prefer the operation, appearance, or functionality of one controller device (200 or 300) over the other (300 or 200). For example, some users may select the first controller device 200 to provide a simplified input comprising two buttons 224 a and 224 b in the user interface 220 (e.g., lower complexity of input options may be preferable to child users). In another example, some users may select the second controller device 300 to provide a larger size display 322 and increased button options 324 a, 324 b, 324 c, and 324 d in the user interface 320 (e.g., increased input options may be preferably to users who frequently monitor a number of pump settings and summary screens). Alternatively, the controller devices 200 and 300 may include the same user interface option, but may have different appearances so as to provide the user with a variety of styles. For example, the controller device 200 may have a different outer shape or a different color than that of the second controller device 300, thereby permitting the user to select one of the controller devices 200 or 300 depending upon the desired appearance of the infusion pump system 20.
Still referring to FIG. 4, in some embodiments of the infusion pump system 20, the first and second controller devices 200 and 300 may be configured to control the dispensation of the different types of medicine when the pump device 100 is removably attached thereto. For example, a first medicine cartridge 230 containing a first type of medicine 231 can be received in the pump device 100. In these circumstances, the first controller device 200 may be removably attached to the pump device 100 (having the first medicine container 230 received therein) so as to control the dispensation of the first type of medicine 231. In another example, a second medicine cartridge 330 containing a second type of medicine 331 can be received in the pump device 100. Here, the second controller device 300 may be removably attached to the pump device 100 (having the second medicine container 330 received therein) so as to control the dispensation of the second type of medicine 331. Accordingly, the infusion pump system 20 can employ a single pump device 100 that is capable of dispensing any one of two or more medicines (e.g., medicines 231 and 331 in this embodiment) when connected to any one of two or more controller devices (e.g., controller devices 200 and 330, respectively, in this embodiment).
Such embodiments of the infusion pump device 20 permit a user to transition from the infusion of one type of medicine to a second type of medicine without learning to operate a new type of pump device. In one embodiment, the pump device 100 may be used in combination with the first controller device 200 so as to deliver a medicine 231 for the treatment of Type 2 Diabetes. Examples of such medicines 231 include Exenatide, which is commercially available under the name BYETTA™, or others in a class of medicines for Type 2 Diabetes called incretin mimetics. These medicines may improve control of Type 2 Diabetes by aiding the user's pancreas produce an appropriate amount of insulin. As described in more detail below in connection with FIGS. 5A-D, the second controller device 200 may include a user interface 220 configured to provide information and monitoring options for the infusion of Exenatide.
If the user's Diabetes progresses over time to become Type 1 Diabetes, the user may continue to use the same type of pump device 100 but with a different controller device 300 (e.g., a controller device for use in the infusion of insulin or other medicines to treat Type 1 Diabetes). Thus, the user is not required to obtain and learn about a new type of pump device 100. Instead, the user may conveniently attach the same type of pump device 100 (this time including a cartridge 330 with insulin 331) to a second controller device 300. As described in more detail below in connection with FIGS. 6A-D, the second controller device 300 may include a user interface 320 configured to provide information and monitoring options for the infusion of insulin. In some circumstances, the dispensation rate, dosage amount, and other parameters of insulin infusion may be different from other infused medicines (e.g., Exenatide), so the user interface 320 may provide different monitoring options or different textual information compared to the user interface 220 of the first controller device 200.
Moreover, such embodiments of the infusion pump system 20 may provide manufacturing benefits. For example, the manufacturer may not be required to manufacture a different type of pump device 100 for each of the different types of controllers. Instead, the pump device 100 can be mass produced in high quantities for use in conjunction with any one of a plurality of controller devices (e.g., controller devices 200 and 300 in this embodiment).
Optionally, the first controller device 200 may include an indicia 225 that identifies the particular type of medicine cartridge 230 or medicine 231 with which it is to be employed. The medicine cartridge 230 may include a similar indicia 235. As such, the user can verify that the appropriate type of medicine 231 is received in the pump device 100 for controlled dispensation by the controller device 200. For example, the indicia 225 may include a label, marking, etching, or the like disposed on the controller housing structure 210 that indicates a particular name, code, or other identifier corresponding to a particular medicine 231 (e.g., “EXENATIDE” or “BYETTA” or another identifier). The indicia 235 disposed on the medicine cartridge 230 may include a similar label, marking, etching, or the like disposed on an outer surface of the cartridge 230 so as to indicate a particular name, code, or other identifier corresponding to the particular medicine 231. The second controller device 300 may also include an indicia 325 that identifies the particular type of medicine cartridge 330 or medicine 331 with which it is to be employed (e.g., “INSULIN” or another identifier). The indicia 325 may match a corresponding indicia 335 arranged on the medicine cartridge 330. Thus, a person or machine will be able to interpret the indicia 235 on the first cartridge 230 and the indicia 225 on the first controller device 220 to know that the first cartridge 230 is used in conjunction with the first controller device 200. Similarly, a person or machine will be able to interpret the indicia 335 on the second cartridge 230 and the indicia 325 on the second controller device 320 to know that the second cartridge 330 is used in conjunction with the second controller device 300.
Referring to FIGS. 5A-D, in some embodiments, the user interface 220 of the first controller device 200 may be configured to provide information and monitoring options for the infusion of a first type of medicine, such as Exenatide. In this embodiment, the user interface 220 comprises a display and two buttons as previously described in connection with FIGS. 1-4. The user may press one or more buttons of the user interface 220 to toggle through a number of monitoring screens that provide information regarding the dispensation of the Exenatide medicine or regarding the operation of the pump device. For example, as shown in FIGS. 5A-D, the user interface 220 may provide information regarding the average amount of Exenatide infused per day (FIG. 5A), regarding the total amount of Exenatide infused on the current day and the average dispensation rate of the pump device on the current day (FIG. 5B), regarding the amount of Exenatide remaining in the medicine cartridge received in the pump device 100 (FIG. 5C), and regarding the amount of time since the pump device 100 started dispensing Exenatide (FIG. 5D). In some circumstances, the user may be able to press one or more buttons of the user interface 220 (e.g., press both buttons at the same time, press and hold one button for a period of time, or the like) so as to adjust particular settings of the infusion pump system. For example, the user may press and hold both buttons when a particular screen is displayed so as to adjust the dispensation rate, to adjust the time or date, or to reset the average dispensation calculation.
Referring to FIGS. 6A-D, in some embodiments, the user interface 320 of the second controller device 300 may be configured to provide information and monitoring options for the infusion of a second type of medicine, such as insulin. In this embodiment, the user interface 320 comprises a display and four buttons as previously described in connection with FIG. 4. The user may press one or more buttons of the user interface 320 to toggle through a number of monitoring screens that provide information regarding the dispensation of the insulin medicine or regarding the operation of the pump device 100. For example, as shown in FIGS. 6A-D, the user interface 320 may provide information regarding the average amount of insulin infused per day (FIG. 6A), regarding the total amount of insulin infused on the current day and the average dispensation rate of the pump device on the current day (FIG. 6B), regarding the amount of insulin remaining in the medicine cartridge received in the pump device 100 (FIG. 6C), and regarding the amount of time since the pump device 100 started dispensing insulin (FIG. 6D). In some circumstances, the user may be able to press the menu and select buttons button of the user interface 320 so as to toggle to a parameter adjustment screen, in which the “−” or “+” buttons may be used to adjust the values. For example, the user may adjust the dispensation rate, to adjust the time or date, or to reset the average dispensation calculation.
Referring now to FIG. 7, the pump device 100 of the infusion pump system 10 or 20 may include a drive system 105 that is controlled by the removable controller device 200 or 300. Accordingly, the drive system 105 can accurately and incrementally dispense fluid from the pump device 100 in a controlled manner. In this embodiment, the pump housing structure 110 includes a detachable shell 112 that covers at least a portion of the drive system 105 and includes a frame portion 113 to which at least a portion of the drive system 105 is mounted. The detachable shell 112 may include an inner curved surface against which a curved section of a piston rod 170 rests. The detachable shell 112 can be part of the pump housing structure 110 that engages with the controller device 200 (or 300) as previously described in connection with FIGS. 1-4. As such, the detachable shell portion 112 may include the magnetically attractable devices 118 a and 118 b that releasably secure the pump device 100 to the controller device 200 (or 300). In addition, the detachable shell 112 may provide access to the electrical contacts 149 a of the pump device 100. In this embodiment, the electrical contacts 149 a are configured to align with the contact circuit device 149 b arranged in the pump device 100. In other embodiments, the electrical contacts of the pump device 100 can be arranged directly on the contact circuit device 149 b, and the detachable shell 112 may include a slot (in the location shown as numeral 149 a) so as to permit electrical engagement with the controller device 200 (or 300).
One or both of the detachable shell 112 and the frame portion 114 can be molded from polymer material, such as Polycarbonate, Acrylonitrile Butadiene Styrene, or Acrylic. In this embodiment, the detachable shell portion 112 comprises a generally opaque, moldable material so that the drive system 105 and other components of the pump device are concealed from view. The frame portion 113 may include a cylindrical receiver 114 that defines the space 116 to receive the medicine cartridge 120 (FIG. 2). In some circumstances, at least a portion of the cylindrical receiver 114 is transparent or translucent so that the user may view the medicine cartridge 120 therein. Such a configuration provides the user with visual verification of when the medicine cartridge is empty or near empty (e.g., the plunger in the medicine cartridge has been fully advanced).
The receiver 114 may also include a connector to mate with the cap member 115. In this embodiment, the connector comprises an external thread pattern formed on the receiver 113 that mates with an internal thread pattern of the cap member 115. Accordingly, the cap member 115 can be secured to the frame portion 113 after the medicine cartridge 120 (FIG. 2) has been received therein. As shown in FIG. 7, the cap member may include a cartridge penetrator 115 a that pierces the output end 122 (FIG. 2) of the medicine cartridge 120 when the cap member 115 is mounted to the frame portion 113. The cartridge penetrator 115 a is in fluid communication with an tube connector 115 b, which is connected to a tube 119 of an infusion set device (as previously described in connection with FIG. 3). As previously described, in some embodiments, the fluid cartridge 120 may occupy a majority of the length of the pump housing structure 110 (with the drive system 105 being arranged in a compact manner) so that the pump device 100 is wearable and portable.
Still referring to FIG. 7, some embodiments of the pump device 100 include a first battery 145 that is capable of transmitting electrical energy to the controller device 200 (or 300) when the pump device 100 is attached to the controller device 200 (or 300). Such energy transmission is described in more detail below in connection with FIG. 8. The first battery 145 may be arranged in a first circuit 140 that includes the contact circuit device 149 b. The first circuit 140 may be simple and inexpensive so as to facilitate a low-cost pump device 100 that is disposable. The first circuit 140 may comprise a printed circuit board or a flexible circuit that is arranged in the frame portion 113 of the pump device 100. Optionally, the first circuit 140 may include a gateway circuit device 146 that permits the transmission of electrical energy from the first battery 145 to the controller device 200 (or 300). In some circumstances, the gateway circuit device 146 may be under the control of and directed by the control circuit in the controller device 200 (or 300). In some embodiments, the gateway circuit device 146 of the first circuit 140 may be in electrical communication (e.g., via one or more electrical wires or electrically conductive traces) with a force sensor 148 (refer to FIG. 11) arranged between the plunger connector 178 that the plunger 121. The force sensor 148 may comprise a force transducer or load cell that is capable of electrically communicating an applied force. As such, the force sensor 148 can provide feedback signals to the local pump circuit 140 (or to the control device 200 via the electrical contacts) so as to monitor the force transmitted to the plunger 121 of the medicine cartridge 120. Such information can be used, for example, to detect if an occlusion exists in the medicine flow path. Other sensors (e.g., a pressure sensor, a flow sensor, a rotation sensor, a displacement sensor, or the like) may be electrically connected to the first circuit 140 to provide feedback signals to the control device 200 via the electrical contacts. It should be understood that, in other embodiments, the first circuit 140 may be configured to operate without the gateway circuit device 146. For example, the control circuit in the removable controller device 200 may communicate via the electrical contacts directly with a portion of the drive system 105 (e.g., direct electrical communication with the motor 130), with one or more sensors disposed in the pump device 100 (e.g., with the force sensor 148), and with the first battery 145.
In this embodiment, the first battery 145 can be maintained in a storage mode and then switched to an activation mode when the pump device 100 used to dispense medicine. The storage mode can provide a long shelf life of storage life for the first battery 145. For example, when in storage mode, the first battery may retain a substantial portion of its charge for a period of more than six months, more than one year, or more than two years. As shown in FIG. 7, the first battery 145 may be equipped with a removable tab 147 that seals the first battery 145 to maintain it in the storage mode. Thus, when the pump device 100 is prepared for usage, the removable tab 147 can be pulled away from the first battery 145, which switches the first battery into the activation mode. When the first battery 145 is switched to the activation mode, the first battery 145 may dispense electrical energy for usage period in which the pump device is used. For example, in some embodiments, the first battery 145 may provide electrical energy to other components over a usage period of about one week to about one month, and about two weeks in this embodiment.
As shown in FIG. 7, some embodiments of the drive system 105 may include a rotational motor 130 that is coupled to a string member 135, which is used to adjust a ratchet mechanism 150. The operation of the drive system 105 is described in more detail below in connection with FIGS. 12A-C. The drive system 105 can provide a reliable and compact configuration for accurately dispensing the desired volume of fluid from the pump device 100. Moreover, the drive system 105 may comprise few, if any, high-cost actuator components or electronics, thereby facilitating the relatively low-cost production of a disposable and reliable pump device 100.
Referring to FIG. 8, the controller device 200 can be attached to the pump device 100 in a removable manner. In this embodiment, the housing structure 210 of the controller device 200 defines a cavity 215 in which at least a portion of the pump device 100 can be received (refer, for example, to FIG. 2). When the pump device 100 is received in the cavity 215, the finger 212 of the controller housing structure 212 may engage a mating surface 117 (FIG. 2) of the pump device 100. In addition, the controller device 200 can include magnetically attractable devices 218 a-b that align with the magnetically attractable devices 118 a-b (FIG. 7) of the pump device 100. As such, the magnetically attractable devices 118 a-b and 218 a-b releasably secure the pump device 100 in the cavity 215 of the controller device 200. In some embodiments, both the devices 118 a-b and 218 a-b may comprise permanent magnets. In other embodiments, one set of the devices 118 a-b or 218 a-b may comprise permanent magnets while the opposing set of the devices 218 a-b or 118 a-b comprise a metallic material that is attractable to the permanent magnets.
The controller device 200 can also include one or more electrical contacts 249 that provide electrical communication to a controller circuit 240. In this embodiment, the electrical contacts 249 are arranged on the controller housing structure 210 so as to align with the electrical contacts 149 a (or the electrical contact device 149 b) of the pump device 100 (refer, for example, to FIG. 7). Accordingly, when the pump device 100 is removably attached to the controller device 200, the controller device 200 becomes electrically connected to the pump device 100 to provide for the communication of electrical control signals.
Still referring to FIG. 8, the controller circuit 240 of the controller device 200 may include a second battery 245 that can receive electrical energy from the first battery 145 (FIG. 7) disposed in the pump device 100. The hard-wired transmission of the electrical energy can occur through the electrical contacts 249 of the controller device 200. In such circumstances, the first battery 145 may include a high density battery that is capable providing a relatively large amount of electrical energy for its package size. Accordingly, the first battery 145 disposed in the pump device 100 can be used to deliver electrical energy over time (e.g., “trickle charge”) to the second battery 245 when the controller device 200 is removably attached to the pump device 100. For example, the first battery 145 may comprise a zinc-air cell battery. The zinc-air cell battery 145 may have a large volumetric energy density compared to some other battery types. For example, the zinc-air cell battery 145 may have a volumetric energy density of greater than about 900 Watt-hours/Liter (Wh/L), about 1000 Wh/L to about 1700 Wh/L, and about 1200 Wh/L to about 1600 Wh/L. Also, the zinc-air cell battery may have long storage lives, especially in those embodiments in which the battery is sealed (e.g., by the removable tab 147 or the like) during storage and before activation. One exemplary a zinc-air cell battery is available from Duracell Corporation of Bethel, Conn., which provides a potential voltage of about 1.1V to about 1.6V (about 1.2V to about 1.4 V, and about 1.3 V in this embodiment), a current output of about 8 mA to about 12 mA (about 10 mA in this embodiment), and a storage capacity of greater than about 600 mA·h (about 650 mA·h in this embodiment).
The second battery 245 may include a high current output device that is capable discharging a brief current burst to power the drive system 105 of the pump device 100. Accordingly, the second battery 245 can be charged over a period of time by the first battery 145 and then intermittently deliver high-current bursts to the drive system 105 over a brief moment of time. For example, the second battery 245 may comprise a lithium polymer battery. The lithium polymer battery disposed in the controller device 200 may have an initial current output that is greater than the zinc-air cell battery disposed in the pump device 100, but zinc-air cell battery may have an energy density that is greater than the lithium polymer battery (e.g., the lithium polymer battery disposed in the controller device 200 may have a volumetric energy density of less than about 600 Wh/L). In addition, the lithium polymer battery is rechargeable, which permits the zinc-air battery disposed in the pump device 100 to provide electrical energy to the lithium polymer battery 245 for purposes of recharging. One exemplary lithium polymer battery is available from Sanyo Corporation of Japan, which provides a initial current output of about greater than 80 mA (about 90 mA to about 110 mA, and about 100 mA in this embodiment) and a maximum potential voltage of about 4.0V to and 4.4V (about 4.2 V in this embodiment). In other embodiments, it should be understood that the second battery 245 may comprise a capacitor device capable of recharging over time and intermittently discharging a current burst to activate the drive system 105.
Because the controller device 200 can be reusable with a number of pump devices 100 (e.g., attach a new pump device 100 after the previous pump device 100 is expended and disposed), the second battery 245 in the controller device can be recharged over a period of time each time a new pump device 100 is connected thereto. Such a configuration can be advantageous in those embodiments in which the pump device 100 is configured to be a disposable, one-time-use device that attaches to a reusable controller device 200. For example, in those embodiments, the “disposable” pump devices 100 recharge the second battery 245 in the “reusable” controller device 200, thereby reducing or possibly eliminating the need for separate recharging of the controller device 200 via a power cord plugged into a wall outlet.
The controller circuit 240 of the control device 200 includes a microcontroller device 246 that coordinates the electrical communication to and from the controller device 200. At least a portion of the controller circuit 240 can be embodied on a printed circuit board (or a flexible circuit substrate). The second battery 245 and the microcontroller 246 can be mounted to such a printed circuit board (or connect to such a flexible circuit substrate). Electrical connections from the electrical contacts 249 and the user interface 220 (FIG. 9) may extend along the printed circuit board to the microcontroller device 246. In this embodiment, the controller circuit 240 is disposed in a hollow space of the controller housing structure 210. For example, the controller housing structure can be formed from two molded portions that are welded or adhered to one another after the controller circuit 240 is assembled therein.
As shown in FIG. 8, some embodiments of the controller circuit 240 may include a cable connector 243 (e.g., a USB connection port or another data cable port). As such, a cable may be connected to the controller circuit 240 to upload data or program settings to the controller circuit or to download data from the controller circuit 240. For example, historical data of medicine delivery can be downloaded from the controller circuit 240 (via the cable connector 243) to a computer system of a physician or a user for purposes of analysis and program adjustments. Optionally, the data cable may also provide recharging power to the controller circuit 240.
Referring to FIG. 9, the user interface 220 of the controller device 200 can include input components, output components, or both that are electrically connected to the controller circuit 240 (FIG. 8). For example, in this embodiment, the user interface includes a display device 222 having an active area 223 that outputs information to a user and two buttons 224 a and 224 b that receive input from the user. Here, the display 222 may be used to communicate a number of settings or menu options for the infusion pump system 10. In this embodiment, the controller circuit 240 may receive the input commands from the user's button selection and thereby cause the display device 222 to output a number of menus or program screens that show particular settings and data (e.g., review data that shows the medicine dispensing rate, the total amount of medicine dispensed in a given time period, the amount of medicine scheduled to be dispensed at a particular time or date, the approximate amount of medicine remaining the cartridge 120, or the like). As previously described, the controller circuit 240 can be programmable in that the input commands from the button selections can cause the controller circuit 240 to change any one of a number of settings for the infusion pump system 100.
Referring to FIGS. 9 and 10, the first controller device 200 has a user interface 220 that is different from the user interface 320 of the second controller device 300 so as to provide different control options. In the depicted embodiments, the first controller device 200 provides a simplified input comprising two buttons 224 a and 224 b in the user interface 220, and the second controller device 300 provides a larger size display 322 and increased button options (e.g., four buttons 324 a, 324 b, 324 c, and 324 d). As previously described, both controller devices 200 and 300 can be used to control the dispensation of medicine from the pump device 100. It should be understood from the description herein that the second controller device 300 can include a controller circuit that is similar to the controller circuit 240 (FIG. 8) of the first controller device 200. Accordingly, some embodiments of the second controller device 300 may include a second battery (to provide bursts of current to power the drive system 105 of the pump device 100), electrical contacts (to align with the contacts 149 a or the contact device 149 b of the pump device 100), and a microcontroller device. In addition, it should be understood from the description herein that the second controller device 300 can include a cavity 315 that is similarly shaped to the cavity 215 (FIG. 8) of the first controller device 200. Also, the second controller device 300 may include a finger 312, magnetically attractable devices, or both similar to the finger 212 and devices 218 a-b depicted in FIG. 8.
Referring to FIG. 11, the pump device 100 includes a drive system 105 that is capable of accurately and incrementally dispensing fluid from the fluid cartridge 120 in a controlled manner. The drive system 105 may include a rotational motor 130 that is coupled to a string member 135. Briefly, the rotational motor 130 can be used to act upon the string member 135, thereby causing the string member 135 to adjust a pawl member 152 relative to a ratchet body 155 (e.g., a ratchet wheel integrally formed on the worm gear 156 in this embodiment). In some embodiments, the string member 135 is configured in a loop arrangement (e.g., looped around pin structures 136, 137, 138, and 139 in this embodiment). In these circumstances, the motion path of the string member 140 and the orientation of the string member 140 can be configured to provide an efficient mechanical advantage orientation during the desired motion of the adjustable pawl member 152. One of the pin structures 138 may be coupled to the adjustable pawl member 152 while the remaining pin structures 136, 137, and 139 are coupled to the frame portion 114 of the pump device 100. The spring device 154 can drive the pawl member from a reset position to a forward position, which incrementally rotates the ratchet wheel 155. As previously described, incremental rotation of the ratchet wheel 155 causes rotation of a drive wheel 160, which causes the incremental longitudinal advancement of a flexible piston rod 170. As the piston rod 170 is advanced into plunger chamber 126 (e.g., defined in this embodiment by the circumferential wall 124 of the fluid cartridge 120), the fluid in the cartridge 120 is forced from septum at the output end 122. Previously incorporated U.S. Provisional Application Ser. No. 60/720,411 also describes a number of configurations for the drive system in addition to the illustrative example depicted in FIG. 11 herein.
As shown in FIG. 11, some components of the drive system 105 can be retained by the frame portion 114, a cover mount 111 that is assembled to the frame portion 114, or a combination thereof. For example, the rotational motor 130, the string member 135, and the spring device 154 can be assembled into the frame portion 114 and then retained by the cover mount 111. The adjustable pawl member 152, the ratchet wheel 155, and the worm gear 156 can be assembled onto and axle 151 that is integrally formed with the frame portion 114 and then retained by the cover mount 111. A locking pawl 159 can be integrally formed with the frame portion 114 so as to align with the ratchet wheel 155 when the ratchet wheel 155 is assembled onto the axle 151. Also, the drive wheel 160 and an adjacent bearing 165 (to facilitate rotation of the drive wheel 160 relative to the frame portion 114) can be received in annular channels 163 and 167, respectively, of the frame portion 114. When the cover mount 111 is assembled to the frame portion 114, the cover mount 111 can restrict the radial or axial movement of the drive wheel 160 while permitting forward rotation of the drive wheel 160. In another example, the “unused” or retracted portion of the piston rod 170 may rest in a channel 113 defined in the top of the cover mount 111. In such a construction, the cover mount 111 and the frame portion 114 can collectively permit the desired motion of the components of the drive system 105 while reducing the likelihood of “backlash” movement or component dislodgement (which might otherwise occur, for example, when the pump device 100 is dropped to the ground).
The rotational motor 130 may comprise an electrically power actuator having a rotatable output shaft 132. In this embodiment, the rotational motor 130 can receive signals that cause the output shaft to rotate in a first rotational direction or in a second, opposite rotational direction. One example of a suitable rotational motor 130 is a coreless DC motor supplied by Jinlong Machinery of China. As previously described, the operation of the rotational motor 130 can be controlled by a controller device (e.g., removable controller device 200 or 300 as described in connection with FIGS. 1-10 or the like) via electrical signals communicated through one or more electrical contacts.
The string member 135 may be coupled to the rotational motor 130 so that actuation by the motor 130 causes the string member 135 to act upon the ratchet mechanism 150. One or more full rotations of the motor 130 can be translated into a tension force in the string member 135 that is applied to a pawl member 152, which (in this embodiment) is pivoted to a reset position by the tension force from the string member 135. As such, the string member 135 is coupled between the rotational motor 130 and the ratchet mechanism 150 so as to provide a reliable and consistent adjustment of the ratchet mechanism. In this embodiment, the string member 135 is coupled to the motor shaft 132 using a mechanical connector 133.
Still referring to FIG. 11, the ratchet mechanism 150 includes the pawl member 152 and the ratchet body 155, which in this embodiment is a ratchet wheel having a number of teeth along its circumferential surface. The pawl member 152 is adjustable between a reset position (refer, for example, to FIG. 12A) and a forward position (refer, for example, to FIG. 12B). In this embodiment, the adjustable pawl member 152 is pivotably coupled to about the axis of the axle 151 that receives the ratchet wheel 155 and the worm gear 156. A spring device 154 is also coupled to the pawl member 152 so as to urge the pawl member 152 toward the forward position. In this embodiment, the spring device 154 is in the form of a leaf spring that is fixed to the frame portion 114 at a first end portion and that is engaged with an abutment protrusion 157 (FIGS. 12A-C) of the pawl member 152 at a second end portion. Thus, when the pawl member 152 is adjusted to the reset position, the spring device 154 is flexed and stores potential energy that urges the pawl member 152 to return to the forward position and thereby drive the ratchet wheel 155 in a forward rotational direction. The locking pawl 159 coupled to the frame portion 114 prevents the ratchet wheel 155 from reverse motion. As such, the adjustable pawl member 152 can adjust from the forward position to the reset position to engage a new tooth of the ratchet wheel 155 while the ratchet wheel 155 remains in position due to the locking pawl 159.
It should be understood that the drive system 105 can employ one or more sensors to indicate when the pawl member 152 has reach the reset position or the forward position. For example, these sensors can be optical, magnetic, or contact type sensors. The sensors may be capable of transmitting signals that indicate when the location of the pin structure 138 or the pawl member 152 is detected. Such sensor signals may be transmitted to the first circuit 140, to the controller device 200 or 300, or a combination thereof.
Still referring to FIG. 11, in some embodiments the ratchet wheel 155 can be integrally formed with the worm gear 156 so that the incremental rotation of the ratchet wheel 155 is translated to the worm gear 156. Such rotation of the worm gear 156 causes a rotation of a drive wheel 160, which is rotatably mounted to the frame portion 114 of the pump device 100. The drive wheel 160 includes a central aperture having an internal thread pattern therein (not shown in FIG. 11), which mates is an external thread pattern on the flexible piston rod 170. Thus, the incremental motion provided by the ratchet mechanism 150, the string member 135, and the motor 130 causes the drive wheel 160 to incrementally rotate, which in turn translates to a linear advancement of the flexible piston rod 170.
Accordingly, in some embodiments, the piston rod 170 may undergo only forward or positive displacement as a result of drive system 105. For example, the drive system 105 substantially hinders the piston rod 170 from retracting or “backing up” in response to fluid pressure in the medicine cartridge 120 or other reversal forces. In such circumstances, the flexible piston rod 170 can be retracted only upon disassembly of the pump device 100 (e.g., to disengage the gears or the ratchet mechanism). In those embodiments in which the pump device 100 is intended to be disposable, the non-intended piston rod configuration (due to the drive system 105) may facilitate a “one time use” disposable pump device, thereby reducing the likelihood of failure due to non-intended repeated use of the disposable pump device.
The flexible piston rod 170 comprises a plurality of segments 172 serially connected by hinge portions so that the flexible piston rod 170 is adjustable from a curved shape to a noncurved shape. As previously described, the plurality of segments 172 and the interconnecting hinge portions can be integrally formed in one piece from a moldable material, including one or more polymer materials such as Nylon or POM. In this embodiment, the plurality of segments 172 comprise generally cylindrical segments that each include an exterior thread pattern along at least one cylindrical surface portion. The flexible piston rod 170 can include an anti-rotation structure that hinders the piston rod 170 from rotating with drive wheel 160 (thereby allowing the rotation of the drive wheel 160 to translate into a longitudinal motion of the piston rod 170). For example, in this embodiment, the flexible piston 170 includes a longitudinal channel 173 extending through each of the segments 172. The longitudinal channel 173 can engage a complementary protrusion on the frame portion 114 proximate the drive wheel 160 so that the flexible piston rod 170 is hindered from rotating when the drive wheel 160 turns relative to the frame portion 114. Accordingly, the longitudinal channel in each segment 172 aligns to form a keyway that receives a mating key (e.g., a protrusion) on the frame portion 114. In other embodiments, the anti-rotation structure may include a plurality of longitudinal channels 173 (with each channel capable of engaging an associated protrusion that acts as a key to hinder rotation while permitting longitudinal motion), one or more flat surfaces along each segment 172 (with the flat surface slidably engaging a complementary flat surface on the frame portion 114), or the like. A plunger connector 178 may be coupled to the leading end of the flexible piston rod 170 so as to abut against or connect with the plunger 121 in the plunger chamber 126 of the fluid cartridge 120. Previously incorporated U.S. Provisional Application Ser. No. 60/720,405 also describes a number of configurations for the flexible piston rod 170 in addition to the configuration illustrated in FIG. 11 herein.
Referring now to FIGS. 12A-C, the incremental motion cycle of the drive system 105 may include rotation of the motor 130 so that the string member 135 transitions from a twisted state, to an untwisted state, and then again to a twisted state. Such a transition of the string member 135 can cause the pawl member 330 to adjust from the reset position (refer to FIG. 12A), to the forward position (refer to FIG. 12B), and back to the reset position (refer to FIG. 12C). The adjustment of the pawl member 152 from the reset position to the forward position drives the ratchet wheel 155 and worm gear 156, which incrementally rotates the drive wheel 160 and thereby advances the flexible piston rod 170 a longitudinal increment distance 179 (refer to FIG. 12B). In one example, the drive system 105 can advance the piston rod 170 a longitudinal increment distance 179 of about 16 microns or less (about 4 microns to about 12 microns, and preferably about 7 microns to about 8 microns) for each incremental motion cycle of the motor 130, string member 135, and ratchet mechanism 150 as previously described herein.
Referring to FIG. 12A, in this embodiment of the incremental motion cycle, the pawl member 352 begins at the reset position with the string member 135 in a twisted configuration at string portion 134. When the adjustable pawl member 152 is in the reset position as shown in FIG. 12A, it is capable of engaging a tooth of the ratchet wheel 155. In this embodiment, the string member 135 is arranged in a loop configuration around pin structures 136, 137, 138, and 139. One of the pin structures 138 is coupled to the adjustable pawl member 152 while the remaining pin structures 136, 137, and 139 are integrally formed with the frame portion 114 of the pump device 100 (pin structures 136, 137, and 139 are shown in dotted lines to represent their location on the frame portion 114 (not shown in FIGS. 12A-C)). Also, the pin structure 136 exemplifies how a single pin structure can have two sliding surfaces that oppose one another, thereby functioning similar to a configuration having two different pins. As shown in FIG. 12A, when the motor 130 rotates, a portion 134 the string member 135 twists upon itself, thus drawing the pin structure 138 toward the stationary pin structures 137 and 139. The orientation of the stationary pin structures 137 and 139 relative to the pin structure 138 (connected to the pawl member 152) can be configured to provide an efficient mechanical advantage for the tension force applied by the string member 140 during the desired motion of the adjustable pawl member 152.
Referring to FIG. 12B, in response to the controller device 200 or 300 transmitting one or more control signals to initiate the cycle, the rotational motor 130 may begin to rotate in a first rotational direction that unwinds the string member 140, thereby permitting the spring device 154 to drive the pawl member 152 toward the forward position (refer to FIG. 12B). When the adjustable pawl 152 is driving the ratchet wheel 155 in the forward rotational direction, the potential energy of the spring device 154 is being translated to kinetic energy for the motion of the pawl member 152 and the ratchet wheel 155. Such an adjustment of the pawl member 152 from the reset position to the forward position drives the ratchet wheel 155 and the integrally formed worm gear 156. The incremental rotation of the worm gear 156 results in an incremental rotation by the drive wheel 160, which advances the flexible piston rod 170 the longitudinal increment distance 179. Such an incremental advancement of the flexible piston rod 170 may cause a predetermined volume of fluid to be dispensed from the cartridge 120 (FIG. 11).
Referring to FIG. 12C, the rotational motor 130 continues to rotate in the first rotational direction so that after the pawl member 152 reaches the forward position, the string member 135 begins to twist in the opposite orientation. Such twisting of the string member 135 causes a tension force that overcomes the bias of the spring device 154 and adjusts the pawl member 152 toward the reset position. When the adjustable pawl member 152 reaches the reset position, as shown in FIG. 12C, the pawl member 152 is capable of engaging a new tooth of the ratchet wheel 155. The locking pawl 159 (shown in FIG. 11) prevents the ratchet wheel 155 from rotating in a reverse (non-forward) rotational direction while the adjustable pawl member 152 is shifting back to the reset position. Such an adjustment of the pawl member 152 back to the reset position causes the spring device 154 to flex (as shown in FIG. 12C), thereby storing potential energy to drive the adjustable pawl member 152 and ratchet wheel 155 in a subsequent cycle. After the pawl member 152 reaches the reset position, the rotational motor 130 stops rotating in the first rotational direction and the pawl member 152 remains at rest in the reset position (refer to FIG. 12C). In the event of a subsequent cycle, the rotational motor 130 would begin the cycle by rotating in a second rotational direction (opposite the first rotational direction) so as to unwind the string member 135 yet again. This pattern of cycles may continue until the piston rod 170 has reached the limit of its longitudinal travel.
It should be understood, that in other embodiments, the incremental motion cycle may begin with the pawl member 152 starting at the forward position (refer to FIG. 12B). In such circumstances, the rotation motor 130 would rotate in a first rotational direction to twist the string 135 until the pawl member 152 is moved to the reset position (refer to FIG. 12C), and then the rotational motor 130 would rotate in a second, opposite rotational direction to unwind the string member 135 until the pawl member 152 returns to the forward position (refer again to FIG. 12B).
The string member 135 may comprise braided filaments that are capable of enduring repeated twisting sequences of the string member 135. For example, the braided filaments may comprise one or more polymer materials, such as PET (e.g., DTex Dyneema material available from Honeywell, Inc.). Such braided filament string members are capable of enduring the torsion and frictional forces associated with undergoing thousands of cycles of twisting as described above in connection with FIGS. 12A-C. The string member 135 can be formed to have an outer diameter of about 0.02 mm to about 0.07 mm, and preferably about 0.05 mm. Also, in some embodiments, the string member 135 may comprise braided filaments that are arranged around a centrally disposed thin wire filament (e.g., comprising a polymer material or a metallic material) having a diameter of about 0.02 mm or less, which is also capable of enduring the repeated twisting sequences of the string member 135. Such a construction may permit the outer filament surfaces to frictionally engage one another during the twisting process while the filament surfaces contacting the centrally disposed thin wire are exposed to a reduced friction load.
Referring now to FIG. 13, some embodiments of drive system 405 for the pump device can include a string member and a rotational motor like the previously described embodiments, except that the string member 435 is configured to wind (or unwind or both) around a spindle device 434. Such a configuration may reduce the torsion and friction loads upon the string member material while providing a tension force to adjust the ratchet mechanism. Moreover, the spindle configuration may further reduce the space requirements for drive system 405 in the pump housing, thereby providing a reliable and compact infusion pump system that is portable and wearable by the user.
As shown in FIG. 10, the spindle device 434 can be coupled to a rotational motor 430 so that the spindle device 434 rotates with the motor shaft. A string member 435 can be attached to the spindle device 434 so that the string member 435 winds or unwinds around the spindle device 434 in response to the rotation of the motor 430. It should be understood from the description herein that the string member 435 may comprise braided filaments that are capable of enduring repeated winding sequences of the string member 435. The string member 435 is also coupled to the ratchet mechanism 450, which provides incremental motion to thereby advance the piston rod 470. The ratchet mechanism 450 includes the pawl member 452 and the ratchet body 455, which in this embodiment is a ratchet wheel having a number of teeth along its circumferential surface. The pawl member 452 is adjustable between a reset position and a forward position. For example, the rotational motor 430 may be activated to rotate the spindle device 434 and thereby wind the string member 435 (as previously described), and the string member 435 then applies a tension force that adjusts the pawl member 452 to the reset position. In the reset position, the pawl member 452 can engage one or more new teeth of the ratchet wheel 455. A spring device 454 is also coupled to the pawl member 452 so as to urge the pawl member 452 toward the forward position. This spring force causes the pawl member 452 to drive the ratchet wheel 455 an incremental amount in a forward rotational direction. Similar to the embodiments previously described in connection with FIG. 12A, a locking pawl prevents the ratchet wheel 455 from reverse motion. As such, the adjustable pawl member 452 can adjust from the forward position to the reset position to engage a new tooth of the ratchet wheel 455 while the ratchet wheel 455 remains in position due to the locking pawl 459.
Accordingly, in one incremental motion cycle, the pawl member 452 may start at the reset position with the string member 435 wound around the spindle device 434. In response to the controller device 200 or 300 (FIG. 4) transmitting one or more control signals to initiate the cycle, the rotational motor 430 may begin to rotate in a first rotational direction that unwinds the string member 435 from the spindle device 434, thereby permitting the spring device 454 to force the pawl member 452 toward the forward position. The rotational motor 430 continues to rotate in the first rotational direction so that after the pawl member 452 reaches the forward position, the string member 435 begins to wind around the spindle device 434 in the opposite orientation. Such winding of the string member 435 causes a tension force that overcomes the bias of the spring device 454 and adjusts the pawl member 452 toward the reset position. After the pawl member 452 reaches the reset position, the rotational motor 430 stops rotating in the first rotational direction and the pawl member 452 remains at rest in the reset position. In the event of a second cycle, the rotational motor 430 would begin the cycle by rotating in a second rotational direction (opposite the first rotational direction) so as to unwind the string member 440 from the spindle device 442 yet again.
In other embodiments, the incremental motion cycle may begin with the pawl member 452 starting at the forward position. In such circumstances, the rotational motor 430 would rotate in a first rotational direction to wind the string member 435 around the spindle device 434 until the pawl member 452 is moved to the reset position (as shown in FIG. 10), and then the rotational motor 430 would rotate in a second, opposite rotational direction to unwind the string member 435 from the spindle device 434 until the pawl member 452 returns to the forward position.
It should be understood that the drive system 405 can be contained in the housing structure 110 of the pump device 100 in a compact manner so that the pump device 100 is portable, wearable, concealable, or a combination thereof. Similar to previously described embodiments, the pump device 100 can be part of an infusion pump system 10 or 20 in which the pump device 100 communicates with a controller device, including but not limited to the removable controller device 200 or 300 described in connection with FIGS. 1-10. The controller device 200 or 300 can communicate control signals to the drive system 405 or other components of the pump device so as to initiate or end the incremental motion cycle of the drive system 405.
a controller to generate the displacement control signal when the second housing is attached to the first housing.
2. The system of claim 1, wherein the control module further comprises a second energy storage module to receive energy from the first energy storage module in the fluid delivery module when the first housing is attached to the second housing.
3. The system of claim 1, wherein the fluid delivery module further comprises a fluid output port through which fluid flows when displaced by operation of the actuator module.
4. The system of claim 1, wherein the actuator module comprises a push rod actuated by a motor.
5. The system of claim 1, wherein the controller generates the displacement control signal based on a time schedule.
6. The system of claim 1, wherein the fluid container comprises a pre-filled carpule.
7. The system of claim 1, wherein the fluid container comprises a plunger member slidably disposed within a barrel.
8. The system of claim 1, wherein the medicinal fluid comprises insulin.
9. The system of claim 1, wherein the control module comprises an input control for receiving a user input to initiate dispensing of a bolus of the fluid.
10. The system of claim 1, wherein the control module comprises a user interface.
11. The system of claim 1, wherein the fluid container and the first housing form a disposable, one-time-use assembly.
12. The system of claim 1, wherein the actuator module operates to displace a bolus of the fluid in response to the displacement control signal.
(d) operating the actuator module to dispense a medicinal fluid from the fluid container in response to a signal from the control module.
14. The method of claim 13, further comprising initiating step (b) before initiating step (a).
15. The method of claim 13, wherein the first energy storage module comprises a capacitive energy storage element.
16. The method of claim 13, wherein the first energy storage module comprises a battery.
17. The method of claim 16, wherein the battery is rechargeable.
18. The method of claim 13, wherein the second energy storage module comprises a capacitive energy storage element.
19. The method of claim 13, wherein the second energy storage module comprises a battery.
20. The method of claim 19, wherein the battery is rechargeable.
US1025743A (en) * 1911-09-22 1912-05-07 Eli A Guthman Shoe-buckle. | 2019-04-25T19:19:06 | https://patents.google.com/patent/US20070173762A1/en |
India and France on Friday decided to expand military cooperation in the strategically key Indo-Pacific region, besides resolving to ramp up the overall defence and security ties.
Defence Minister Nirmala Sitharaman and her French counterpart, Florence Parly, held extensive talks covering a variety of issues, including the regional security situation, joint development of defence platforms and expansion of military-to-military ties.
At their delegation-level talks, the two sides also agreed to expand counter-terror cooperation, and said a lot more could be done in the maritime sphere, particularly in the Indo-Pacific region, where China was trying to expand its footprint, official sources said.
The sources said the French side explored the possibility of a follow-on order of additional Rafale fighter jets being placed by India.
India had signed a Rs. 58,000-crore deal with France for the supply of 36 Rafale jets last year and the IAF was pitching for procuring another fleet of 36.
It is Ms Parly’s first visit to India as Defence Minister and her trip is expected to lay the ground for French President Emmanuel Macron’s upcoming trip. | 2019-04-21T08:05:29 | http://www.bcompetitive.in/india-france-to-boost-defence-ties/ |
My name is Alex Bliss, a 25 year old living in Nanyuki, Kenya. I am the youngest in a family of seven.
After graduating from Mount Kenya University as a Medical Laboratory Technologist in 2016, I proceeded to work at Nakuru Provincial General Hospital as a volunteer. While still at the hospital I developed an irresistible urge to instigate a programme that would be centered on personal empowerment. This grew out of my absorption with this kind of work as a sideline to my major career at the time. This career overlap was difficult to handle but it was obvious to me that I needed to quickly align my own personal impulses with the big dream that was beckoning. I felt I had done enough in public health and needed to go a step beyond the hospital perimeter fence to ignite the spark of purpose and hope in the lives of people on both local and global scales.
In October, the Alex Bliss Personal Empowerment Program was born. Along the way I incorporated the Kibera slum Visionary School project which supports more than 80 children with education. During that time I met with Keith J. Clark, founder of the iDigitalMedium, a non-profit organization that focuses on education and preservation of information related to the paranormal sciences. I joined the iDigitalMedium team as a humanitarian and inspirational writer as well as a correspondent in Africa, sourcing for viable African stories and extending the plight of disadvantaged African people to the global audience. | 2019-04-23T04:34:34 | https://idigitalmedium.com/the-idigitalmedium-team/alex-bliss/ |
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Right off the bat, without exhausting you with the detail, let me give you a concise foundation. The Party Wall Act (The Act) as we probably am aware it today was adequately conceived from the London Building Acts (LBA). As you will acknowledge Party Wall Surveyors Cubitt Town London has an expansive number of properties which are built in nearness to each other, and neighborly debate were backing off the development procedure. The LBA acquainted measures with make it less demanding for designers and mortgage holders to complete work along limit lines and lessen the level of question by setting out particular commitments on the two gatherings. The LBA was utilized effectively in London for a long time until at last in 1996 it was chosen to patch up the demonstration and move it out across the nation as The Party Wall Act 1996.
The Act is far reaching and becomes possibly the most important factor more than you would might suspect. In any case, you’re not the only one on the off chance that you don’t know much about it.Party Wall Surveyors Cubitt Town London Numerous developers I know either don’t think about it, or more regrettable disregard it. Experts aren’t resistant either.
You’re presumably intrigued by this article since you’re going to complete a development venture, or perhaps your neighbor is. It might be a little augmentation or space transformation, or something on a bigger scale.Party Wall Surveyors Cubitt Town London The demonstration doesn’t consider measure it just chips away at essential. The underlying angle is obviously to decide if the demonstration is relevant in any case. In the event that you are in any uncertainty it is constantly fitting to look for expert exhortation and in numerous cases the position isn’t high contrast. In unrefined terms be that as it may, a gathering divider is a structure shared by two neighbors and this would incorporate limit dividers or fences and additionally the dividers to a building.Party Wall Surveyors Cubitt Town London Maybe in such manner the title of the demonstration is a bit of deluding and more than this, it might likewise be appropriate on the off chance that you propose to develop a divider or expanding ashore where no divider or physical limit as of now exists.
In an advanced domain where most properties are in nearness to each other it is for the most part the case that the demonstration will end up relevant amid any development venture that includes burrowing establishments close to a limit line. It might likewise be relevant for space transformations or building repairs where the gathering divider isn’t being adjusted, however bolster is required from the divider for steel underpins or suspended timber floors or roofs and so on.Party Wall Surveyors Cubitt Town London Related, it might become possibly the most important factor for work that you would feel is minor, for example, slicing into a divider to embed a weatherproof detail or blazing.
As you will have found the demonstration is far extending and is as a rule pertinent when you do development work close to neighboring structures/arrive.Party Wall Surveyors Cubitt Town London My recommendation is counsel a surveyor who hosts get-together divider encounter on the off chance that you are uncertain. Most surveyors would give some free guidance via telephone and if the task is neighborhood to them, you will frequently find that they will give you a free visit to evaluate your specific venture with the expectation that, if the demonstration is relevant you will choose them to embrace the job for you. Unquestionably as far as I can tell as a contracted building surveyor I give free counsel all the time with the expectation that it will prompt a guidance. There are surveyors who will charge notwithstanding however the key, as dependably is to concur an extent of administration and any expense in advance to maintain a strategic distance from disarray. At that point you know where you stand.
Area 2: Repair and so on: of gathering divider: privileges of proprietor – This segment sets out the privileges of the proprietors of a gathering divider subject to serving the proper notice. Such rights numbered from (2) (a) – (2) (n) incorporate such fills in as; “to make great, repair, or decimate and remake, a gathering structure or gathering wall divider” and in addition “to cut into a gathering structure for any reason (which might be or incorporate the motivation behind embeddings a moist evidence course). The whole rundown is set out in the demonstration and covers most work, other than exceptionally shallow, that could be done to a divider.Party Wall Surveyors Cubitt Town London Under most conditions where any work is being completed specifically to a mutual divider, it would be normal that the demonstration will become an integral factor, in spite of the fact that there are exemptions and you should accept guidance.
The second area which is probably going to be most relevant is Section 6: Adjacent uncovering and development. By and by the details are set out in the demonstration however can be dazing.Party Wall Surveyors Cubitt Town London Generally in any case, on the off chance that you propose to unearth inside 6 meters of an abutting party divider/structure (recollecting that a gathering divider could likewise be a garden divider or fence) the demonstration might be material, if certain criteria identifying with profundity of uncovering in connection to any gathering dividers are accomplished. On the off chance that you are uncovering inside 3 meters the demonstration is more than likely pertinent.
It is frequently trusted that the demonstration is simply planned as a cash spinner for expert advisors however this couldn’t possibly be more off-base. Truly there is an industry worked around the demonstration and experts do charge for their administrations, however there is sufficient rivalry to guarantee that expenses stay sensible.Party Wall Surveyors Cubitt Town London It is in certainty an empowering demonstration that guarantees that the places of the two gatherings are secured and all the more essentially, guarantees that neighbors can’t stop advancement or repair without adequate reason. In such manner the demonstration can regularly spare expenses where there was at one time a prospect of suit and question.
Notwithstanding this, usually for tasks to be embraced agreeably without serving notice yet this is a hazardous recommendation as appeared by the instance of Louis v Sadiq 1996. The case spun around a finish of patio house in London and demonstrates the ramifications of the follow up on standard houses and in this manner general property holders, not simply huge scale improvements. Mr Sadiq (building proprietor) completed building work without serving notice under the demonstration.Party Wall Surveyors Cubitt Town London This work accordingly made harm the neighboring property and he was compelled to make great this harm by the court under the terms of the demonstration. This is standard system and regardless of whether he had served the right notification then he would in any case have been at risk for this expense, yet more imperatively with what we are talking about, the courts granted extra harms to Mr and Mrs Louis (abutting proprietor) since it felt that Mr Sadiq’s inability to watch the demonstration nullified any advantages of barrier. | 2019-04-24T08:02:30 | http://www.rightoflightsurveyors.uk/party-wall-surveyors-cubitt-town-london/ |
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The expert staff at Clover Comfort have been in the HVAC industry for years and have just that knowlege. So if you are seeking HVAC installations or repairs give your skilled Adams Corners Heating Contractor a call today and see what they can do for you.
Are You Looking For a Adams Corners Heating Contractor Today?
If you are seeking a Adams Corners professional to assist you with your homes heating needs then look no farther then the skilled professionals at Clover Comfort your professionals HVAC Contractors. With years of experience and knowledge you can be sure that you are getting the very best solutions for your homes HVAC needs. Calling on the skilled staff at Clover Comfort for your Adams Corners HVAC needs will get you a skilled technician that has years of experience and knowledge in the HVAC industry and that can provide you with the quality services that you need.
As the technology used for heating and cooling indoors is improving by leaps and bounds, the need to call in highly trained Adams Corners heating professionals to install and repair these systems is also increasing. In the last century, when these systems were not too complicated, people could go through the manuals and install these if they had some technical expertise and the patience to follow the instructions provided in the manuals.
When upgrading or installing your Adams Corners heating and air-conditioning system, it can be tempting to look for the cheapest contractor in hopes of saving money.
Chances are, if you do, you’ll be hiring someone who is unlicensed, and this can cause a host of problems when installing your HVAC (heating, ventilation, air-conditioning) system.
Your HVAC system is arguably one of the most important components of your home. This is how you heat your home in winter and cool it in summer. It’s one of your home’s most significant expenses and has a major effect on your home comfort.
Most cities, including Adams Corners, require or encourage their HVAC contractors to be licensed. Becoming licensed ensures that a contractor meets minimum standards for technical knowledge, experience and respect for safety. Licensed contractors are also usually monitored by a government agency or industry association and unsafe companies can lose their licences if they perform shoddy work or cheat their customers.
A shoddy HVAC system can be expensive to run, dangerous to your health and reduce the resale value of your home.
A carbon monoxide monitor is a must to detect dangerous levels of the deadly gas in your home. But if you don’t have an emergency plan, then all the alarms in the world aren’t going to help you! Here’s what you need to do when your carbon monoxide monitor goes off.
If your carbon monoxide monitor keeps going off, or you aren’t sure where the leak is coming from, get out of the house and call the fire department and your gas company. Keep emergency numbers in your cell phone, or somewhere outside of the house so that they are accessible, such as your car.
As you can see a Carbon Monoxide Detector can be a valuable tool so why not give the skilled professioals at Clover Comfort a call and have them install on in your home today. | 2019-04-22T12:05:52 | https://www.clovercool.com/adams-corners-heating-repairs/ |
you’re dead if you aim only for kids. adults are kids grown up, anyway.
george bernard shaw �never wrestle with pigs. you both get dirty and the pig likes it.
c.s. lewis evil is stupid and unimaginative.
but for the pit confounders, let them go, and find as little mercy they show!
i am what think and strongly believe in could become, therefore able to change myself at any given moment, other words full control of myself.
in every triumph there�s a lot of try.
just remember, once youre over the hill you begin to pick up speed. | 2019-04-23T16:53:46 | http://www.quotespedia.info/keyword.html |
Struggling with pests at your Gipsy home or business? We can help!
Deal with Gipsy, MO exterminators who know the area and pests that live there.
If you’ve ever dealt with pests in Gipsy, MO or have a friend or family member who has dealt with them, you know how horrible it is. They can be hard to kill and can contaminate your home. We are Exterminators Now and we can deal with any pest related problem you have. Our fast and effective Gipsy Missouri exterminators will dispose of any pest causing issues at your house or business. Our exterminators in Gipsy, MO can provide pest control services for both residential and commercial locations, changing our methods and adapting to your needs and concerns to deal quickly with any pest. We handle a wide range of pests in Gipsy including but not limited to bed bugs, ants, termites, spiders, flying insects, and rodents such as rats and mice. After your first treatment, we will highly recommend quarterly or yearly inspections to guarantee the pest stay away. Contact us now and we’ll send an exterminator to inspect your Gipsy property right away, we’re available 24 hours a day.
These minuscule pests infest your bed and live to disturb your sleep - hiding in the tight crevices of your mattress. They can harm you more than you think, even thou not transmitting any important diseases there are reported cases of severe allergic reactions amongst bed bugs victims. Bed bugs are fairly hard to exterminate, with common household pesticides and remedies mostly being ineffective against them. The majority of the time their removal requires professional service. Our Gipsy exterminators, know what it takes to deal with them, using the most up-to-date methods to get rid of them for good.
Keeping your Gipsy, MO Missouri property guarded against termites should be a top priority. The estimated damage caused by termites in the United States exceeds a billion dollars a year. Termite infestations usually only show signs when the damage is already done, but you can still prevent further damage by being proactive. If you feel you are struggling with termites, give us a call for a termite inspection.
They bring disease, contaminate your house and consume your food: rodents. Rats in Gipsy, MO are known to be carriers of significant diseases that can harm you or your loved ones. We have exterminators in Gipsy, who deal with these pesky rodents effectively and humanely before they cause severe damage. | 2019-04-21T14:41:17 | http://www.exterminatorsnow.com/exterminator-services/gipsy-mo-pest-control |
Meet the shape of things to come: an exquisitely tailored ponte knit sheath dress that is a glorification of the feminine form. Your insistence on perfect details is reflected in everything from the lance-shaped V-neck to the the expertly executed seams and shaping panels. The immaculately smooth fabric says a lot about you—graceful, grand and unafraid to be in charge. | 2019-04-19T08:47:50 | https://jessicaerickson.etcetera.com/lookbook/detail/FA18EA045/ |
Salmon roulade - Smoked salmon,dusted in lemon zest and dill,wrapped around a cream cheese,mint and roasted almond filling,bound with a basil vinaigrette.
Zuppa - Sweet baby carrot and basil pesto soup, finished with a roasted garlic and parmesan crouton.
Merluzzo - Kingklip marinated in lemon yogurt and Cointreau liquor, oven baked, and topped with cream of curried mussels.
Bistecca - Rump filled with Spanish chorizo and Danish feta, flame grilled and finished off with a Porcini mushroom and rosemary veloute.
*Both main courses served with pecorino mashed potato or polenta.
Strawberry San Valentino - Fresh strawberries layered with Chantilly cream and brandy snaps, accompanied with an orange velvet coulis.
Amoroso - Lindt chocolate brownies, glazed with caramel and served with mint and vanilla ice cream. | 2019-04-23T06:08:16 | http://www.greedypiglet.co.za/OurFood/PlatedMenus/SetMenu6.aspx |
1) Everyone in the story has his or her own tracks to cross in life. What challenges do Iris, Mrs. Nesbitt, Dot, Celeste, Iris’s father, Marie and Dr. Nesbitt need overcome? Do they accomplish this or not?
1) How would you describe Dot’s options regarding her pregnancy and her father?
Download the crossword pdf and the puzzle answers.
Book chats can include the writing process and an exploration of selected artworks and how I use them as inspiration. I also conduct “Novel Art Tours” either actual or virtual. | 2019-04-22T01:30:55 | https://barbarastuber.com/book-clubs/ |
A managed forex trading account can give an investor who cannot watch the market 24 hours a day an opportunity to participate in the colossal world of forex trading. A managed forex account may also be appropriate for the investor who prefers to have his capital managed by professionals. Studies of professionally managed forex trading accounts have shown returns that are not related to the performance of the stock market. Consequently, allocating a portion of an investment portfolio to a forex managed account may be an appropriate way to increase the portfolio's total diversification. | 2019-04-23T08:09:35 | https://madpropstobakedpotatoes.com/tag/capital |
Is it tough to find time in your schedule for workout programs in La Palma?
As we all know, getting fitter takes time. Nevertheless you dont want to waste the remainder of the day by the gymnasium after a elongated days worth of work and if you feel like you dont have time to get in shape thats good. Precluding health risks now is more time efficient than dealing with heartache down the road. Diabetes, High blood pressure, cancer and other maladies grow from having higher body fat which can be avertible with workout programs. Therefore instead of paying the price of depression down the road we have a Solution, workout programs La Palma. workout programs are only an hour long and burn the greatest expanse of calories in the shortest aggregate of time. workout programs in La Palma focus on breaking down all the muscles tissues in your body thus that way you burn fat and build muscle!
Are you Over Spending Money for the workout programs in La Palma?
With all the health fad diets out there making you buying their programs and products getting minimal return for your money for the money you spent, where do you turn? at the same time you might suppose hiring a personal trainer but dont think you can afford one. How much money does it take to have a one on one personal training session? A good question is how much is your health worth afterward how much time and money do you want to spend on your strength? workout programs in La Palma offer low-priced prompt ways to get you in shape. for the cost of a fraction of a personal training session and relative cost to a gym membership you get an expert personal trainer working with you and a group of people who have related struggles as you do. Working together in a workout programs in La Palma not only makes it great, bar by the same time you feel like pushing yourself harder because when you see other people work around you and you know if they can do it, you can too.
Are your avoiding these Smyptoms from workout programs in La Palma?
Working out does compel power to be used. After a long days work and all the stress it brings the last things you want to do is cause even supplementary stress by exercising. Your body will fit to anything you give it. Consequently if you sit at work all day, then you sit in your car, then you sit at the dinner table, later you sit on the couch and go to sleep, your body requires little to no power to do that. But if you absorb workout programs in La Palma into your routine, it forces your body to create even above force therefore after the workout you feel motivated throughout the week!
Are Your test Routines Deficient Accountability for workout programs in La Palma?
Consequently many people are so busy with their lives its hard to even get into a routine. Your life is pretty much a routine right now. You wake up, go to work, run some errands, come back home, moreover do it all over again. The part part is implementing something new into your routine. A routine is the hardest to get, and so easily broken. Habits are created and formed after about a month. Good thing workout programs in La Palma will help you break your old habits, develop a routine, and hold you accountable to coming in to exercise afterward feel great after your workout. Dont wait any longer, break that habit also become a routine with workout programs in La Palma with no obligation!
Is Your workout programs in La Palma Missing out on these Results?
Isnt it wearisome no matter how hard you workout, no matter what diet you are on, you still have unwanted extra inches and weight? Your spending so much time trying to figure out what works and doesnt work in your exercise habitual that it becomes a responsibility. Plus after you dont see results, you get even more blocked! workout programs in La Palma give you the tools and education to guarantee results or your money back! View our testimonials likewise envisage how we can change your life! Per workout programs in La Palma youll recieve a proper nutrition, flexibility then strength training program, which will positively transform your body effortlessly, and effectively. | 2019-04-21T06:25:54 | http://www.oc-personaltraining.com/bootcamps/workout-programs-La-Palma-1603.html |
AFTER 120 YEARS, MIKIMOTO KNOWS A THING OR TWO ABOUT THESE TIMELESS TREASURES.
Mikimoto, founded by Kokichi Mikimoto in 1893 and known the world over as the leading maker of cultured pearl jewelry, marks its 120th anniversary this year. Among other impressive achievements during the company’s long history, Kokichi was the first to develop a technique for the cultivation of pearls that is still in use to this day. A determined innovator, he succeeded in creating the sugar daddy baby site world’s first perfectly spherical pearl, an object he regarded as nature’s most precious gift to be shared with women everywhere. The timeless elegance found in Mikimoto pearl jewelry has been celebrated and worn by icons of style in every era, from Coco Chanel and Marilyn Monroe to Elizabeth Taylor and Sarah Jessica Parker.
To commemorate more than a century-long commitment to product design, superior craftsmanship and strict quality control, Mikimoto has proudly revealed plans to release three specially designed 120 pearl strand necklaces that embody the company’s traditions. The first design is comprised of 120 Akoya cultured pearls and represents the original pearl that Kokichi cultured in 1893 off the waters of Toba, Japan — a feat that brought him one step closer to fulfilling his dream of bringing the unsurpassed beauty of the pearl to all women. This unique Akoya strand will feature an 18K white gold clasp accented with beautiful royal blue enamel lacquer, crafted by skilled artisans in Japan.
The second design, made of multi-colored Black South Sea cultured pearls, celebrates the breathtakingly rare type of pearl that Kokichi first cultured in 1914, using a new technique that helped Mikimoto expand cultivation into the waters off Australia, Indonesia, the Philippines and Tahiti. The rich, dark colors of the pearls range from slate gray, silver and pistachio to peacock green and midnight black, with overtones of green, rosé or blue.
The third strand consists of 120 multi-colored South Sea and Freshwater pearls and marks Mikimoto’s mid 20th-century expansion into the international market that helped shape the company’s enduring legacy. This necklace is comprised of Golden South Sea, White South Sea, and Pink and Peach Freshwater cultured pearls. Both of these exquisite strands will fasten with a paisley motif version of the iconic Mikimoto clasp, exaggerated in size to accentuate the necklace.
“These 120 pearl strands represent each milestone in our brand’s 120 year history” says Meyer Hoffman, COO of Mikimoto. “Each pearl symbolizes a moment in our past where we’ve taken our founder’s vision to the next level. With this anniversary, we honor the rich legacy that Kokichi left us while looking forward to the future.” These rare and breathtaking pieces will be available in early fall 2013. | 2019-04-23T04:08:55 | http://accent.busjour.com/pearls-of-wisdom/ |
Please click here to perform a fast scan for Error Publisher as well as connected issues.
Error Publisher error codes can be caused because of damaged files inside the MS Windows operating-system.
If you have Error Publisher error then we strongly suggest that you conduct an error scan.
This article provides help and advice that teaches you the right way to fix any MS windows Error Publisher errors both manually as well as automatically. Additionally, this document will allow you to fix most common error alerts connected with Error Publisher error message you may perhaps end up with.
1. What exactly is Error Publisher error message?
2. The causes of Error Publisher error?
3. A way to instantly repair Error Publisher error message.
So what is Error Publisher error code?
The Error Publisher error code is the numerical format of the error message generated. It’s the popular error layout used by Windows and other Microsoft Windows compatible software applications and driver vendors.
This code is required by the manufacturer to recognize the error code caused. This unique Error Publisher error has a numeric value in addition to a specialised brief description. Occasionally the error may have more factors in Error Publisher formatting .The further hexadecimal code are the location of the memory sections where the directions are filled during the time of the error code.
The causes of Error Publisher error?
A Error Publisher error message is often brought on by Microsoft Windows system file malfunction. Broken system entries are often a substantial threat to the performance of any machine.
There are many situations that will trigger a system file error. A partial installation steup, an incomplete file erasure, improper deletion of utilities or components. It may also be caused if the computer system has caught a a trojan or spyware attack or through a poor shutdown of the pc. The aforementioned actions may very well end up in the deletion or corruption of Windows system files. That corrupted system file will cause missing and erroneously linked documents and archives essential for the accurate operation of the program.
How you can simply address Error Publisher error code?
2) Click on the Get started button then click on All Programs, Accessories, System Tools, and next select Restore.
3) In the next screen, select “Restore my computer to a previous date” and then press Next.
4) Pick the most current system restore date within the “click a restoration date” list, then click Next.
1) Download the (Error Publisher) restoration software application.
Here is a link to an alternative Error Publisher fix utility you may use in case the above program does not work anymore. | 2019-04-26T10:01:17 | http://www.pcrpr.com/error-publisher.php |
London is one of the largest cities in the world, and therefore the city is on all tour lists of all the big artists, musicians and bands. We will present to you some of the most important events on this page, so that you can enjoy a nice concert and interesting event while in London.
We have recently moved this page to another place here in our London Guide, so if you are looking for information on what is going on London at the moment, then visit the following site giving you information about exhibitions, concerts, festivals and events in London.
You can also find some really popular concert venues in London, and here you can read more about some of the most popular venues in London. | 2019-04-26T05:58:14 | http://www.guidetolondon.net/activities/concerts-events |
Ah, Germany, the paradise of unlimited speed highways! Well, the reality is rather different: finding a stretch of road free enough to go over 190 mph is difficult. But not impossible, as this 911 GT3 POV video shows.
MY NEW CAR IS COMING!! | 2019-04-26T04:53:41 | https://en.motorwebs.net/2017/cars/309-kmh-in-a-porsche-911-gt3-on-the-autobahn-is-legal-and-you-know-you-want-it |
§ 2.2-2734. Southwest Virginia Cultural Heritage Foundation established; purpose.
The Southwest Virginia Cultural Heritage Foundation (the Foundation) is hereby established as a body politic and corporate. The purpose of the Foundation is to encourage the economic development of Southwest Virginia through the expansion of cultural and natural heritage ventures and initiatives related to tourism and other asset-based enterprises, including the Heartwood: Southwest Virginia's Artisan Center, The Crooked Road, 'Round the Mountain, and other related cultural and natural heritage organizations and venues that promote entrepreneurial and employment opportunities. | 2019-04-18T19:07:37 | https://law.lis.virginia.gov/vacode/title2.2/chapter27/section2.2-2734/ |
TO HELP PEOPLE PROSPER, WE NEED YOUR SUPPORT.
Every dollar you donate goes to work to help individuals and families in our communities thrive.
Through our many programs, events and initiatives we are making a difference - and you are part of that story.
To make a donation online through Txt-2-Give, click the link below to be directed to Broadway Church’s online giving page. Enter your information, and select the desired option from the drop down menu.
If you have any questions, or wish to make a donation in another manner, please contact us. | 2019-04-23T10:52:22 | https://victor-alvarado-tajl.squarespace.com/donate |
This entry was posted on sabato, 23 marzo 2019 a 00:23 and is filed under Spazio aperto/open space. Contrassegnato da tag: antisemitismo, festa, purim. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, oppure trackback from your own site. | 2019-04-24T20:40:02 | https://fidest.wordpress.com/2019/03/23/purim-la-festa-della-sconfitta-anche-militare-dellantisemitismo/ |
There are many things to consider when planting a tree. As a certified arborist, we have the knowledge, experience and ability to help you choose the appropriate tree for Chestnut, IL. If you are not sure then phone 800-290-0654 as we understand the issues with soil type and soil nutrients, climate, growth rate and other important considerations when choosing tree species, location and correct spacing.
We can recommend the types of trees that will thrive and add value to your property. The wrong tree in Chestnut, IL could lead to future problems due to limited growing space, insects, diseases, or poor growth. Trust a certified arborist from Tree Service Guys to guide you in this important decision.
Tree Service Guys are trained and certified arborists, and skilled in tree pruning. More than simply keeping a tree tidy, proper tree pruning will guide a tree’s shape, health, and strength over its life. Tree Pruning here in Chestnut, IL varies with species, and age. Our training and years of experience have assured the knowledge to know when to prune and how to prune. We will provide tree pruning services – beginning when your trees are young – to assure tree strength; properly pruned tress will resist damage from wind and ice. We will also prune to assure beautiful shape, safety, and with fruit trees assure the best possible yield each season.
Tree Service Guys’ Tree Trimming services in Chestnut, IL assure tree health and safety. Proper tree care is an investment in the life and beauty of your trees. Well-cared-for trees are attractive and can add considerable value to your property. A trained arborist can assure you have well maintained trees, eliminate the unneeded removal of a tree, and reduce significant danger – and significant liability. Trimming trees, particularly large trees, is dangerous work. Tree trimming is best done by a trained and certified arborits equipped to work safely in trees.
Tree Service Guys offers Deep Root Fertilization where the tree fertilizer is pressure injected into the root zone of the tree. For a better understanding of this call us using this number 800-290-0654, in Chestnut, IL This is a highly effective and concentrated method to provide tree fertilization and deliver vital and essential nutrients to the soil around the tree. | 2019-04-23T20:00:23 | http://www.treeserviceguys.com/il/arborists-in-chestnut/ |
Postpartum depression (PPD) is the most common complication of childbirth. To help raise awareness of PPD, and provide relevant information to formulary decision makers, Sage Therapeutics developed a series of three supplements each focusing on a different stakeholder: Patients, Healthcare Professionals, and Payers. The series was distributed in payer journals. | 2019-04-26T00:26:11 | https://www.pm360online.com/2018-pharma-choice-multichannel-silver-winner-icon-plc-and-sage/ |
Sure, we have organic and natural choices.
Then there's Lärabar, maker of delicious natural fruit and nut food bars. Energy in its purest form.
Our Annie's is grounded in using natural and organic ingredients sourced from places and people we trust.
And when your taste turns to chips, Food Should Taste Good has a wide variety of all-natural chips made from simple ingredients. | 2019-04-20T08:18:07 | https://www.generalmills.com/en/Brands/organic-natural |
21/03/2018�� Well you can�t really just make it disappear. Try and watch some of your favorite creators things and find inspiration from them. Or you can do what I do and doodle random stuff, read books, or just move on with life until art block wears off.... The crew over at the HostBaby blog put together 8 tips to inspire and help you get through the roughs spots in lyric writing. � Avoiding Email Spams, Scams and Malware Domain Names: Choose them wisely!
26/03/2014�� One Paradoxical Way To Get Over Artist�s Block Mar 26 by pekoeblaze Before I start, I should point out that I usually schedule my art posts a few days ahead of these articles.... The question, �What is the best way to get over Art block (not having the motivation to draw)?� needs clarification: if you WANT to draw but feel your creativity is not flowing there are things you can consider doing if you are not motivated, look elsewhere.
3 steps to get over your next Artist Blocks. by Sergio Gomez, MFA . Have you experienced an artist block? I have. Actually many times. I remember in one occasion it lasted for months.
26/03/2014�� One Paradoxical Way To Get Over Artist�s Block Mar 26 by pekoeblaze Before I start, I should point out that I usually schedule my art posts a few days ahead of these articles.
12/11/2006�� Never give up! Go to art websites like www.deviantart.com and look at other artists work. Study other people's individual styles, there is sure to be one you like, even if it's from a lesser known artists, all you have to do is look.
Before we start. I just wanted to say here, that although this document contains a lot of information, I would recommend you read it all the way through rather than skimming over it. | 2019-04-22T11:58:40 | http://tofoodreviews.com/queensland/how-to-get-over-an-artist-block.php |
I wanted to share this story just as a bit of a warning to other remodelers. When I moved into my house in Mission Viejo 7 years ago, a lot of renovation work had already been done. There was some flooring that needed extending, lots of odd job type repairs, painting and a bit of drywall. That’s not much I thought. I don’t really need a main contractor for that. I wasn’t working at the time so was confident I could be around to supervise the different sub contractors. I really thought this would save me money! Well it didn’t. Thank God it worked out OK in the end and the stress of the process had the added benefit of causing me to lose 10 lbs! But I would never do it again.
First of all my budget kept expanding because I had not sat down and planned what I wanted in detail. Everything was piecemeal with decisions made as I went along. Far more work needed doing than I had anticipated. For example I removed some old fashioned wood cladding from the living room walls only to find that the drywall was not in good condition and needed redoing. The electrical wiring needed more upgrades than I thought I would need.
When it is not your area of expertise, it is hard to supervise anyone. I had no idea whether my subcontractors were doing a good job and they would change quite frequently so I was seeing different faces all the time.
I made the mistake of paying the partner of my flooring guy with a check made out to him personally. No real paperwork. All very vague. But he had a plausible story and we had been getting along great. Turns out the partners were having difficulties between themselves and the guy ran off with the check never to be seen again!
I know I am making myself sound really stupid but it is easy to get taken in. And it is hard not to get tempted by a big saving. Even if you think your reno job is small, I would get a proper estimate, get everything in writing and definitely work with a general contractor. | 2019-04-19T13:18:09 | https://www.helpuremodel.com/i-was-my-own-general-contractor/ |
It's not a coincidence that we gain the highest price on all OUR SOLD properties in Hurlstone Park, it's also not a coincidence that we have 2 offices, the second one being in Marrickville. With our database of buyers from our Hurlstone Park office, mixed with bringing buyers into the suburb from Marrickville, once again the two strategies get our vendors the best price in any Market.
If you have a property in Hurlstone Park, I have many discerning families waiting to buy with outstanding budgets. We have 100% success rate in Hurlstone Park!
Don't chance your property with any other agents Richard Perry 0418 863 969.
Dunstaffenage Street, like Duntroon and Kilbride Streets, is a nod to the Scottish landmarks and ancestors who built many classic homes from the mid 1800's in Hurlstone Park.
Tightly held within the same family for 77 years, this freestanding, double-brick home is perfectly located in a quiet tree-lined street of period homes opposite a parkland reserve. Displaying character features throughout and with tremendous scope for renovation or expansion (STCA), the home is set on a wide and deep traditional block of land (approximately 442.6 sqm).
Boasting completely private rear gardens and manicured lawn, cultivated by the former resident who served as Head Horticulturalist at Admiralty House, the rare varieties of Clivia and Bromeliad create a tranquil and tropical retreat to relax and entertain with family and friends.
Move in ready with endless opportunity to create your forever home', this comfortable abode awaits a growing family, ready to enjoy the superb Inner West lifestyle being just moments to local cafes, village shops, Cooks River parkland and cycleways. Plus, it's only a short stroll to Light Rail, Hurlstone Park train station and quality schools including Trinity Grammar School.
Make sure you inspect this private and peaceful home with glorious garden retreat. | 2019-04-23T03:53:07 | https://www.rawmarrickville.com.au/listing/6908/ |
New York - Joel Sajiun is one of the lead performers of "Men of The Strip." He sat down and chatted with me at Gramercy Theatre in New York City, prior to their show on December 17.
This male revue is hosted by Jeff Timmons from the Grammy-nominated vocal group 98 Degrees and it is choreographed and directed by Emmy nominee Glenn Douglas Packard. Garo Bechirian from "Men of The Strip" served as the emcee at this show.
Joel praised New York's Gramercy Theatre for being a "magnificent place." "My entrepreneur, Glenn Douglas Packard, is looking forward to this night and so is Jeff Timmons. It's one of the most important nights for us," he said. "Many television networks are going to be here."
Joel continued, "I am excited about everything tonight. We are going to give 100 percent. There is nothing that will be left out tonight. If there is something left out, we make sure that we cover it."
He is originally from the Dominican Republic and he is dubbed as the "Latin Lover" of "The Men of The Strip." "I am a loving person and I a talker too and they love me for that too," he said.
Regarding his plans for the future, he shared, "Some of them will be short-term plans and they will be a part of the long-term plans. We want 'Men of The Strip' to become of the biggest empires ever, along with my boys Nate Estimada, Kyle Efthemes, Chris Boudreaux and Keith Webb. This is my biggest vision that I have and we encourage each other for it."
For more information on "Men of The Strip," visit their official website. | 2019-04-19T09:30:30 | http://www.digitaljournal.com/entertainment/interview-with-joel-sajiun-latin-lover-of-men-of-the-strip/article/364400 |
Find all questions and answers on Wrestling asked by users and answered by experts. If you don’t find an answer related to your Wrestling query, post a quick question and an expert will answer your query as it comes in the queue. Mostly you get an instant answer, but there may be a delay depending on your question.
If you’re the one who knows a lot about Wrestling, people are looking for you. Check out the unanswered questions section, find the questions you can provide best answer with and help people with their queries.
Which wrestler theme song you like?
Brook Lesner Shawn Micheal John Cena Kane Edge big show there move looks somehow realistic.
Longest Ramp walk in WWE? | 2019-04-24T16:39:54 | http://www.senore.com/Wrestling-c802 |
This is a placeholder page for Ashley Edgell, which means this person is not currently on this site. We do suggest using the tools below to find Ashley Edgell.
You are visiting the placeholder page for Ashley Edgell. This page is here because someone used our placeholder utility to look for Ashley Edgell. We created this page automatically in hopes Ashley Edgell would find it. If you are not Ashley Edgell, but are an alumni of Apollo High School Owensboro, KY, register on this site for free now. | 2019-04-25T17:59:15 | http://apollohighschool.net/owensboro-ky/alumni/4756925/ashley-edgell.html |
First impression., originally uploaded by Gus Dahlberg.
Love., originally uploaded by Gus Dahlberg.
luminaries., originally uploaded by Gus Dahlberg.
wet cookies ahoy, originally uploaded by Gus Dahlberg.
Making gingerbread., originally uploaded by Gus Dahlberg.
Christmasy: time for gingerbread houses. | 2019-04-21T03:01:24 | http://dahlbergcentral.com/ |
This exceptional Brunello is made from 100% Sangiovese Grosso, hand harvested in October, soft pressed, and vinified in stainless steel tanks for 15-20 days at a controlled temperature of 25-28°, then refined in stainless steel tanks from March to May. The wine is aged for a minimum of 5 years with at least three & a half years in oak and chestnut casks and a further 6 months in the bottle. This is a powerful wine with dark fruit flavors reminiscent of black currants and blackberries, firm and uplifting tannins, and a long sweet fruit finish on the palate. Excellent when served with game meats, steaks, sausages and dishes such as pasta with meat sauces, rosemary-pepper beef rib roast, dishes with mushrooms and truffles and aged cheeses. Decanting for two hours before serving is recommended in order to appreciate all the nuances and flavors this beautiful wine has to offer. This is a long aging wine that can be cellared for 10-12 years or more. | 2019-04-19T05:18:47 | http://portfolio.tricana.com/portfolio/italia/toscana/fattoi/brunello-di-montalcino |
In her practice, Erin O’Keefe (1962, US) is informed by the disciplines of architecture and photography. Her work consists of photographs of tabletop still life arrangements that she constructs in her studio. Her images exploit the layer of distortion and misapprehension introduced by the camera as it translates three-dimensional form and space into two-dimensional image. This inevitable misalignment is the central issue in her practice. Her photographs create an image where on the one hand object and on the other hand reflection or shadow each receive the same attention and importance. | 2019-04-23T16:13:19 | https://unseenamsterdam.com/photographers/erin-okeefe |
PLEASE SCROLL DOWN FOR MORE PHOTOS. (B228) PLEASE NOTE: THIS ITEM WILL BE SENT FIRST CLASS REGISTERED. ALL STAMPS ARE FROM A NON-SMOKING ENVIRONMENT AND ARE TOTALLY SOUND UNLESS OTHERWISE STATED.
We appreciate feedback and will reply in kind to feedback le. PLEASE CHECK OUT OUR STORE FOR MORE STAMPS, COVERS, AND RELATED PHILATELIC ITEMS. WE CURRENTLY STOCK OVER 2000 ITEMS IN OUR STORE.
S MINT #J101 $5 POSTAGE DUE MINT SHEET/100" is in sale since Friday, November 20, 2015. This item is in the category "Stamps\United States\Back of Book\Other US Back of Book Stamps". The seller is "larrysellcovers" and is located in Hornell, New York. This item can be shipped worldwide. | 2019-04-18T11:20:13 | http://mintpostagestamps.com/u_s_mint_j101_5_postage_due_mint_sheet_100.php |
The following Health Care Career Exploring resources have been hand-picked to help you navigate all your Health Care sales calls. Use them to demonstrate the value of Exploring to potential community participants, and be sure to bring a copy of each one to your next sales meeting.
The Health Care brochure outlines career options, benefits to all participants and the community, and the skills and competencies that participants will acquire throughout the program.
On a sales call, provide a copy of the brochure. That way, it will reinforce your message when you are introducing Health Care Career Exploring to a community member.
The Health Care Career Exploring Fact Sheet outlines how the Exploring program works, the skills participants learn, and facts and figures important to the program.
Share a copy of the Fact Sheet on your sales calls, and reference it to draw attention to the strengths and success of Health Care Exploring for participants and the community at large.
There’s nothing more powerful than a quote or story from a previous Health Care Career Exploring participant. They prove that Health Care Exploring really makes a difference in participants’ lives.
Sharing testimonials is a great way to make a strong impression on a sales call. Pairing appropriate testimonials with information from the fact sheet or brochure makes that information more credible and convincing, and clearly shows the real-world value of Health Care Career Exploring.
Video is one of the best marketing tools you can use. From real stories to anthem themes, watch and download high-qualityHealth Care Exploring videos that will be sure to captivate any audience. | 2019-04-26T12:47:52 | https://scoutingwire.org/exploring-tools/marketing/health-care/ |
Will New Tests Help Treat Traumatic Brain Injuries?
According to the Centers for Disease Control and Prevention, traumatic brain injuries account for 30 percent of accident-related deaths each year around the country. The agency has asserted that those deaths cost the United States $75.6 million annually. While there is no cure for TBIs, researchers believe that they may be able to stop an injury from getting worse after it occurs. It is thought that there is a two- or three-day window in which cell death can be prevented after a blow to the head.
To study the effects of a blow to the head, scientists use slices of rat brain tissue. They can simulate the impact of a tackle during a football game, the impact of a car crash or the effect that an explosion may have on brain matter. The tests aim to discover how much tissue can bend before it breaks and how many cells die immediately following such a scenario.
Although many in the scientific community applaud the work, there is more research that needs to be done. For instance, some have suggested doing experiments outside of a lab’s controlled environment. For now, the best advice may be to wear a seat belt and take other precautions to prevent a TBI from occurring.
Those who have received a brain injury as the result of another party’s negligence may wish to talk to an attorney about their legal options. It may be possible to win compensation to pay for medical bills, long-term care costs and other expenses related to the injury through the filing of a personal injury lawsuit against the responsible party. It may also be possible to win compensation for lost wages if the victim was forced to miss work. | 2019-04-24T00:14:40 | https://www.maryalexanderlaw.com/new-tests-may-help-california-tbi-patients/ |
Some people, while undergoing CPAP therapy for their sleep apnea, may experience unpleasant side effects that can get in the way of the beneficial effects of using the device. These side effects might include a dry nose, cotton-mouth, sore throat or nasal congestion. Using a CPAP humidifier can greatly reduce or even eliminate these unpleasant experiences. We highly recommend CPAP heated humidifiers to improve comfort and enhance your CPAP therapy.
How Does a CPAP Humidifier Help Sleep Apnea Therapy?
When you use a heated sleep apnea humidifier with your CPAP machine, it will produce moisture in the air you breathe from your device. This warm moisture makes the dry, compressed air more comfortable, giving you a more pleasant CPAP experience and a more relaxing, comfortable and refreshing night's sleep. Without the side effects, you're far more likely to continue to use your CPAP machine and will sleep more soundly, maximizing the beneficial effects of this highly effective sleep apnea therapy.
We offer a wide selection of CPAP humidifiers designed for seamless operation with various CPAP machines. Depending on the model, features may include a dishwasher-safe water tub, climate control, integrated construction, adjustable humidification, heated or non-heated options, large capacity water container, lightweight design, rainout protection and included headgear kit. Most of the sleep apnea humidifiers can be used with a CPAP, APAP, Bi-PAP or VPAP device.
RespShop is your sleep apnea specialist. We carry the best products from the world's most respected manufacturers at competitive prices. In addition, we offer outstanding, personalized customer service and ultra-fast shipping. We're highly knowledgeable about our products, so if you have any questions, give us a call. We can help you choose the right products and accessories to perfectly fit your needs. | 2019-04-23T16:36:12 | https://www.respshop.com/cpap-humidifiers/humidifiers/ |
Added on January 21, 2019 by Benjamin Wynn.
A few shots from the Torn In Two live show in Los Angeles.
Added on December 20, 2018 by Benjamin Wynn.
I’ll be premiering the Torn In Two live A/V show on January 16th in Los Angeles.
Added on December 13, 2018 by Benjamin Wynn.
“Warmer Nights”, the third and final video for Torn In Two is out now. Directors Notes premiered the film along with details of the behind-the-scenes process, including concept drawings and fabrication photos.
Added on October 20, 2018 by Benjamin Wynn.
Torn In Two is out now on all services and deluxe double vinyl.
Added on October 3, 2018 by Benjamin Wynn.
Refuge is now available on Vimeo and YouTube.
Added on September 19, 2018 by Benjamin Wynn.
The Torn In Two video is now available on YouTube and Vimeo.
Added on July 13, 2018 by Benjamin Wynn.
The score for Impulse is out now on most services via Lakeshore Records. Links HERE.
Added on July 12, 2018 by Benjamin Wynn.
Added on March 26, 2018 by Benjamin Wynn.
Excited to say that I composed the score to "Impulse", a new show from Doug Liman premiering on YouTube Red June 6th.
Added on March 24, 2018 by Benjamin Wynn.
I provided the score for Marvel's first podcast "Wolverine: The Long Night" available now on Stitcher Premium. It's a dark, scripted story following Logan through a small town. Recorded in ambisonics. Main titles below.
Added on September 7, 2017 by Benjamin Wynn.
Tickets are now on sale for our next Echo Society show, FAMILY. A three-day festival at a legendary residence in Los Angeles, with special guests to boot. More info HERE.
Added on August 29, 2017 by Benjamin Wynn.
Added on August 23, 2017 by Benjamin Wynn.
The newest '1979' vinyl pressing is in stock and up for sale.
Added on May 26, 2017 by Benjamin Wynn.
Territories, the first release on our new record label, 79Ancestors, is available now on all digital streaming services and vinyl + VR headsets. The album’s theme is centered around depicting “imaginary landscapes” with sound.
Order the vinyl + VR headset bundle now and you’ll be ready to dive right into the Territories virtual landscapes in the coming weeks.
Features new music by Deru, SHIGETO, Telefon Tel Aviv, Rafael Anton Irisarri, A.M. Architect, VHVL, Tongueless, and Before Tigers.
Added on May 25, 2017 by Benjamin Wynn.
2 million plays on YouTube on a random upload of '1979' feels like some sort of milestone this day and age. I'm happy that 3 years on this record is still being discovered. | 2019-04-18T20:28:29 | http://www.deru.la/ |
Triple Savings and Water Fun: 20 minutes JetSki driving & 10 minutes parasailing & 20 minutes Crazy Jet Boat. You save between € 20,00 and € 30,00. Speed up to the max when jet skiing on the Atlantic Parcours and increase your adrenaline levels. And that’s not all. The parasailing flight lifts you high in the air. See the world from a new perspective and enjoy the thrill. And finally, it gets mad again. Feel how the Crazy Jet Boat accelerates so much that it pushes deep into your seat. It’s frenetic like a rocket and makes crazy pirouettes with all inmates and even dives into the water. A wicked fun! In the south of the island you will be picked up and brought back to your hotel. Experience this extraordinary day!
First we went on a jet ski ... at full speed. Then the Parasaliling, a lovely experience to float over the water. The speedboat was fun. It turns over and throws you into the water. We were not prepared for that, but it was a great experience. | 2019-04-23T06:12:37 | https://www.cancograncanaria.com/en/product/gran-canaria-water-sport-combi-pack-5/ |
Parkland is situated in an ideal location where one can live a very peaceful life, while having all the amenities of a city. The city has several social organizations and groups that arrange a wide range of cultural and recreational activities. The beaches of South Florida are a short drive away. The city is surrounded by several miles of equestrian trails, which provide great opportunities for horse riding. The city also has many golf courses.
This affluent city in Broward County, Florida was designed to protect the "parklike" character of the city. Initially, there were no stores or traffic lights in Parkland, though this began to change in the mid-1990s and early-2000s with the additions of large neighborhood developments like Heron Bay and Parkland Isles.
Parkland is a pinnacle of beauty, both in its real estate and its surroundings. The real estate for sale in the Parkland area, and the many neighborhoods that make up the city, is comprised of a wide selection of architectural styles and home prices. This guarantees that there is really something in Parkland for every type of home buyer.
Whether you want to have an elegant night out or grab something quick before a day at the beach, you'll find something to love in Parkland. The variety of restaurants, cafes, and coffee shops is just enough to find what you’re looking for while keeping a “small town” feel throughout the city.
When you’re ready for some of the world’s most renown shopping, Boca Raton is right next door.
One of the best aspects of living in Florida is the proximity and accessibility to world class golf courses. Parkland is perfectly situated for the enthusiast. Learn more about golf courses in and around Parkland here.
Since its inception Parkland has maintained the highest standards for the community and it shows.
The City of Parkland is honored for a ninth consecutive year with a 2016 Playful City USA designation.
The Government Finance Officers Association of the United States and Canada (GFOA) has announced that the City of Parkland, Florida (City) has received the GFOA’s Distinguished Budget Presentation Award for its budget.
Parkland allows for easy access to every major city and highway throughout South Florida. The city is nestled between the Broward and Palm Beach county boarders. West Boca Raton and Boca Raton sit just minutes to the north. Coconut Creek is just to the east and Coral Springs lies to the south. The west side of Parkland is protected by The Everglades.
When you have to commute to work or visit family, accessing all of the fastest highways just takes a couple of minutes. The Florida Turnpike, the Sawgrass Expressway, and Interstate 95 are all you’ll ever need. | 2019-04-23T08:02:36 | https://www.rustyhanna.com/about-parkland/ |
Does your event have a theme? Yes or No - if yes, what is it?
What are the "no play" songs you would "NOT" like to hear during your event?
Check each genre of music that is most likely to appeal to the "DANCERS" in your crowd.
How much do you want the DJ to talk?
Your event questionnaire has been submitted. Thank you! | 2019-04-20T02:37:49 | https://www.djspradentertainment.com/event-questionnaire |
Wikipedia entries on politically controversial scientific topics such as global warming can be unreliable due to information sabotage, a new study has claimed.
Researchers analysed Wikipedia edit histories for three politically controversial scientific topics (acid rain, evolution, and global warming), and four non-controversial scientific topics (the standard model in physics, heliocentrism, general relativity, and continental drift).
"Wikipedia's acid rain entry receives near-daily edits, some of which result in egregious errors and a distortion of consensus science," said Dr Gene E Likens, President Emeritus of the Cary Institute of Ecosystem Studies and a Distinguished Research Professor at the University of Connecticut.
In an effort to see how Wikipedia's acid rain entry compared to other scientific topics, Likens partnered with Dr Adam M Wilson, a geographer at the University of Buffalo.
Using nearly a decade of data, Likens and Wilson teased out daily edit rates, the mean size of edits (words added, deleted, or edited), and the mean number of page views per day.
While the edit rate of the acid rain article was less than the edit rate of the evolution and global warming articles, it was significantly higher than the non-controversial topics, researchers said.
Across the board, politically controversial scientific topics were edited more heavily and viewed more often.
"Wikipedia's global warming entry sees 2-3 edits a day, with more than 100 words altered, while the standard model in physics has around 10 words changed every few weeks," Wilson noted.
"The high rate of change observed in politically controversial scientific topics makes it difficult for experts to monitor their accuracy and contribute time-consuming corrections," he said.
"As society turns to Wikipedia for answers, students, educators, and citizens should understand its limitations when researching scientific topics that are politically charged.
"On entries subject to edit-wars, like acid rain, evolution, and global change, one can obtain - within seconds - diametrically different information on the same topic," said Likens.
Researchers note that as Wikipedia matures, there is evidence that the breadth of its scientific content is increasingly based on source material from established scientific journals.
They also note that Wikipedia employs algorithms to help identify and correct blatantly malicious edits, such as profanity.
But in their view, it remains to be seen how Wikipedia will manage the dynamic, changing content that typifies politically-charged science topics. | 2019-04-26T04:32:13 | https://www.timesnownews.com/technology-science/article/wikipedia-info-on-global-warming-unreliable-study/10335 |
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It’s now reached that time of year again where we analyse our marketing activities from the previous 12 months that have gone by and set out our plans for the forthcoming year.
If you want to continue to thrive and gain a competitive advantage in the ever-changing world of digital in 2018, then it’s essential to set out a fresh plan that makes the most of the emerging trends and technologies this year.
Since consumers are now demanding a more integrated online experience, today’s forward-thinking marketers must be the ones to combine digital media with technology in order to increase the overall contribution of their digital marketing strategy.
From the rise of mobile-first sites to voice search and personalisation, we’ve compiled some of the most prominent digital trends that we expect to see in 2018. There are some general predictions for the coming year as well as several more specific points which could help your digital business to boost its ROI in 2018.
Augmented Reality means that brands can now merge real-world imagery with digital and augmented objects in a new and innovative way. Think Pokémon Go, Snapchat, and even Facebook’s newly introduced AR picture lenses which enable users to place virtual objects into the real world.
One of the most recent collaborations was Google’s Star Wars AR stickers which were designed to celebrate the release of The Last Jedi movie. The AR program works through the camera of Pixel 2 smartphones and it allows users to place stormtroopers and other characters from the movie into their everyday lives.
AR Technology is set to transform e-commerce in the new year. The tail end of 2017 saw furniture brands such as Ikea using AR with their ‘Ikea Place’ app to demonstrate to online shoppers what new furniture would look like in their own homes before even buying it. In a similar way, John Lewis used their 360° shoppable Facebook Ads to pave the way for an interactive shopping experience through social media. This has enabled their customers to shop quickly without visiting a store and also means that they’ll be less inclined to want to return furniture items after purchasing.
As a collection of data from traditional and digital sources, big data represents a source of ongoing discovery and analysis. In other words, it’s the same old data that marketers have always used, but it has become increasingly more accessible thanks to machine learning and Artificial Intelligence.
The big data collected from social media, online purchases and mobile app downloads etc means that digital marketers can now make even better predictions about customer behaviour and ultimately that content can be fully tailored towards your specific audience. Proximity marketing enables marketers to track where their customers are via their mobile phones and send them offers and advertisements based on their location and specific interests.
In 2018, big data will become even more readily available to small and medium-sized businesses, which means more targeted strategy and less spending. Since increasing numbers of advertising platforms and marketing outreach systems are now making big data a part of their infrastructure, businesses will find it hard to stay competitive this year if they aren’t making use of the thousands of customer data points that are now available to them.
At present, over 87% of internet users use mobile devices to access the web on a regular basis. Desktop advertising is expected to decrease for the first time ever in 2018 at a rate of 6%. The rise of mobile-first advertising comes hand in hand with live video usage and viewership, which is also forecast to hit the roof in 2018.
Marketers ought to get ahead of the competition as soon as possible by planning a mobile video strategy and integrating it into their customer experience. Native content such as Snapchat and Instagram stories that can be promoted through social will become crucial.
The reason why video is so valuable is that it can be used by both brands and influencers to depict real-life stories. In fact, Mark Zuckerberg estimates that as much as 90% of Facebook’s content will be video-based by 2019. If you consider yourself to be a DIY kind of business owner then live video is a great place to start.
• Instagram’s ‘Go Live with a Friend’ is a recent update that’s forecast to boost their go-live feature even further. This is exciting news for brands working with influencers as it means that you’ll be able to take collaboration to a whole new level for your followers to watch and engage with. This will result in a spill-over of followers and also attract new followers, which means exponential growth for both parties. It would be wise to make this feature a part of your strategy and go live every other week.
• Facebook Creator App has been projected by some to revolutionize the way people do live-streaming in 2018 and even overtake YouTube as a platform for influencers. The most well-known update is the ‘Live Creative kit’ which makes it easy for anyone to create videos through their brand’s Facebook page. With features such as custom frames, custom reactions and custom intros/outros it makes the platform arguably one of the best live-streaming and monitoring platforms on the internet.
• Navigational – The most straightforward – to do with destination. The user wants to go somewhere.
• Informational – These type of requests generate direct results. They’re processed by Hound with its live API which is based on semantic understanding.
• Transactional – If someone was going to use an IPA such as Siri for a transaction then a lot of these steps could actually happen before the app was opened.
These developments in voice search are predicted to make competition in this area hyper-concentrated. In order to appear on voice search results, you’ll have to create content that answers questions. Ensure that any advertisements you have, as well as your landing page contain the search queries that your target audience could use.
Optimizing your content for voice search means including long-tail keywords and conversational phrases (eg. best pad Thai in Manchester vs. Thai Restaurant Manchester) that people would be more likely to say out loud. Content Marketing will make optimizing for voice slightly easier because it’s not as hard to work conversational keywords into a blog post as it is to force them into your website content.
Personalising your content can provide one of the most powerful tools to boost engagement, drive value and ensure that your readers keep coming back. Personalising content means that your consumers can be in control of they type of content that they see – it’s up to you to make it accessible and timely.
As personalisation becomes more popular with the growing availability of big data, content marketing is also going to become a lot more competitive in the future. Personalisation can be easy to implement first by starting small and then investing in personalisation providers and analytics to enhance your data.
Brands like Amazon, Netflix and a number of the major social media platforms have excelled at customising individual user experiences by putting their customers’ needs above all else with personalised recommendations and offers.
Whether they’re browsing online or on their mobile devices, consumers have now come to expect personalised content, showing an obvious preference to them over overt advertising messages. Personalised content could be based on your consumers’ location or their personal preferences.
In the coming years, personalisation will need to have a clear strategy with a view of building a loyal audience and extending the time spent on their platforms.
Chatbots are streamlining how we communicate with consumers – a trend that’s directly correlated with the rise in messaging platforms. AI-driven assistants can help to boost satisfaction and sales as they’re quick to use, cheap and they provide much more of a personal and direct form of communication that allows you to put the customers’ needs and wants first.
A recent survey revealed that consumers want brands to focus on digital improvement more than innovation in 2018. With this in mind, it’s time to re-examine the functioning of any chatbot type elements on your site.
The aim of a chatbot should be to capture and nurture leads, either through your website or through your social media channels. While some chatbots have a logic behind them, others have been used purely as a form-fill whilst providing consumers with extremely basic conversations.
This year, you should ensure that chatbots on your site and social channels are fully updated. This means ensuring that they ask customers more open-ended questions and that they always answer in full sentences. Even if you don’t intend on creating a full Intelligent Virtual Assistant for your brand, then developing a chatbot strategy should involve more than merely offering communication through Facebook Messenger.
Ensure that your chatbot is designed with a personality that’s approachable, fun and engaged. Interactive features should always align with the rest of your brand message. Although chatbots are great for dealing with quick customer experiences, you should bear in mind that in some instances, a phone call with a customer care professional may be required instead.
Digital marketing is constantly changing, which is why it’s vital to ensure that you regularly review and update your strategy. New technologies such as AR, voice search, mobile video and big data programmes are forecast to continue their expansion this year, which means that your business could be set to boost its ROI by incorporating them into a strategy in the near-future. | 2019-04-24T18:56:53 | https://www.weareweb.com/6-digital-marketing-trends-for-2018/ |
What are the key differences between CIBTAC and CIBTAC Endorsed certifications?
Is your Spa Ready to be GDPR Compliant?
What are the Benefits of CIBTAC Endorsed Certification? | 2019-04-25T20:40:57 | https://www.balibisa.com/blog/page/2/ |
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Born in 1927 in Worms, Germany, Kagan’s family emigrated to the USA to escape the rise of Nazism in 1938. He studied architecture at Columbia University, before joining his father – a Russian master cabinetmaker – in the family woodworking studio, learning to create furniture drawing on the traditions of Mies van der Rohe, Le Corbusier and the Bauhaus school.
After drawing commissions such as the Delegate’s Cocktail Lounges for the UN HQ at Lake Success in New York, Kagan opened his own New York store, East 65th St, in 1948. He subsequently made his name as a creator of superlative modern furniture, creating pieces for contemporary individuals and companies as auspicious as Marilyn Monroe, Gary Cooper, General Electric, Walt Disney, Monsanto and General Motors.
The latter half of the 20th century would see Kagan partner with textile designer and artist Hugo Dreyfuss to create Kagan-Dreyfuss Inc. in 1950, and shifting his operations between Manhattan and Long Island City, before formally retiring in 1988.
Highly regarded throughout this period, his star rose again with the boom in taste for midcentury furniture from the 1990s onwards. In 1998, the reintroduction of a number of classic designs at the International Contemporary Furniture Fair comprised an effective re-boot of a career and name that has remained prominent ever since. His work is held by institutions as esteemed as the Vitra Design Museum in Weil am Rhein, Die Neue Samlung, the V&A and most prominent American museums.
Wallpaper* has long admired the designer’s work. In June 2003, the designer and his wife Erica Wilson invited us into their Park Avenue home for a shoot that explored the duo’s stylistically opposed but aesthetically complementary interior tastes. The legendary designer also attended the launch party of the US Bespoke Edition late last year.
Kagan’s influence was confirmed yet again in December 2015, with the publication of a monograph, Vladimir Kagan: A Lifetime of Avant-Garde Design, by Pointed Arrow Press – bolstered by accompanying texts by such creative heavyweights as Tom Ford and the late Zaha Hadid. | 2019-04-26T06:48:14 | https://www.wallpaper.com/design/in-memory-of-vladimir-kagan-1927-2016 |
It is well-observed that if it is possible at all to speak of God, it is only because God has spoken of Himself. That is the reason why it is of utmost importance to investigate what exactly God has said of Himself. To do this, we shall leave out a very important question – how we know that God has spoken at all – and concentrate only on the ways we believe God has spoken to man, or on the ways God has revealed Himself.
God has not revealed Himself all of the sudden, but in progressive stages. God’s first revelation or manifestation is the created order of the world of nature. That is why “The heavens declare the glory of God” (Ps 19,1). This revelation is intended for all people regardless of race or religion. The very Old Testament testifies that many nations (different from Israel) knew and reverenced the true God. This was confirmed by the New Testament in which it was shown that God never abandoned the other nations (although He preferred Israel), and that He was always approachable for them, because He “left not Himself without testimony, doing good from heaven” (Acts, 14.17). If they could not know Him, than it would not be fair to blame them for not glorifying Him as God. But they could know Him at least through the rhythms of nature (e.g. regularity of rain and harvest) as the One who “gives rains and fruitful seasons, filling our hearts with food and gladness” (Ibidem).
God, however, has not revealed Himself only in the visible world. He revealed Himself through the moral conscience as well: “For when the Gentiles who have not the law, do by nature those things that are of the law, these, having not the law, are a law to themselves: who show the work of the Lord written in their hearts, their conscience bearing witness to them” (Epistle to the Romans, 2.14-15). So, parallel to the “physical” there is also “moral” revelation. Moreover, inside the “moral” revelation there are two different types: 1) tablets given to Moses on Sinai, and 2) tablets written in human hearts. It seems that God first spoke to all men through cosmos and conscience, and only then to Moses and other prophets. So, the revelation to all humanity (written in human hearts) is older than that to Moses and Israel (written in stone and permanent). This first revelation is of a lesser degree than the one which followed but what is important is it was the revelation of the same God. The same God who revealed Himself through the regularity of the courses of the stars as through the natural hierophanies, revealed Himself also to Moses.
As was already explained by Jesus Christ, the new revelation does not destroy, but perfects the previous one. Just as Christ did not destroy the Old Testament Law, but fulfilled it, so the Old Testament Law did not destroy the cosmic religion, but fulfilled it. Of course, every next revelation is more perfect than the previous one. Also, in the cosmic religion God manifests Himself through permanent patterns of the natural cycles, while in the biblical religion He manifests Himself in the uniqueness of historical events. So, cosmic religion shows itself as the first phase in the history of salvation in which God has revealed Himself through creation and providence (i.e. maintenance of created beings). In the next phase of God’s revelation He is known through the single intervention in human history. This is the biblical revelation in which each of these divine acts is but a progressive stage in the general divine plan of salvation. We know who God is through His unique acts in our history. But to recognize that the one concrete act is divine, God’s revelation (or His inspiration) to an individual human mind is needed.
Apart from revealing Himself in cosmos and conscience, God first spoke through the Prophets of Israel. Afterwards, He spoke through Jesus Christ. And finally He spoke through the Church. The idea of God at the level of cosmic religion is known through creation, whereas the idea of God in biblical religion is known through the covenant (which is the most important way of God’s acting in the Bible). The idea of covenant implies that God made a bond between Himself and His chosen people Israel. For God this commitment is unconditional, which means that whatever the sins of men might be, they could never untie this bond which God tied once forever. Men can withdraw from this bond, but God will not. This is why He is true God.
When today we say that something is “true”, we imply that something in the world corresponds to our thought. This is the original ancient Greek concept of truth. The Hebrew concept of truth (emet) is different. It implies the solidity of something from which one receives support (e.g. the pillar on which a building rests, or the support that a child receives when resting in his mother’s arms). So, in relation to God, truth-emet means that we can lean on Him with all our weight. That God is truth means that He is reliable, that we can rely on Him. Therefore, the means of access to truth is no longer reason (as in the Greek-European mind), but faith. Only by faith, i.e. believing in God, or trusting Him can we lean on Him (and not by reason, i.e. not by having the evidence of Him). That is why the symbol of the true God in the Bible is a rock (as the unshakable firmness of the Word of God). Man expresses the recognition of this reliability of the Word of God by saying amen, which is like saying: “He is reliable, and I can lean on Him, so I can believe in Him”. God’s faithfulness to what He promised to man is as firm as a rock, so that man unreservedly can believe His Word.
God revealed Himself in the most perfect way in Jesus Christ. Because this revelation is the expression of God’s fullness, there can be no further revelation of God. The Old Testament revealed God making a covenant with Israel and drawing it away from idols. The New Testament revealed God in the flesh making a covenant with the New Israel made from all the nations. The Time of the Church revealed God making a covenant with every baptised individual who enters the Church. This is God’s progressive revelation. Likewise, “The Old Covenant proclaimed the Father openly [but primarily as the all-transcendent Father] and the Son more obscurely [only hinting at the person of the Son, presumably through prophecies of the coming Redeemer]. The New [Testament] manifested the Son [directly in the person of Jesus] and suggested the deity of the Spirit [presumably by Jesus’ promise of the other Comforter and vague references to the Spirit in Acts and Paul’s letters]. Now [in The Age of the Church, the eschatological period of salvation history that began with Jesus’ ascension to the Father and giving of the Spirit at Pentecost] the Spirit itself dwells among us and provides us with a clearer demonstration of itself [i.e. reveals itself to Christians directly]. For it was not safe to proclaim the Son clearly when the Divinity of the Father was not yet acknowledged; or to burden us further (if I can put it somewhat boldly) with the Holy Spirit when the Divinity of the Son had not yet been received” (Gregory of Nazianz, Oration 31.26). Therefore, according to Gregory the Theologian (as well as Origen, Epiphanius, etc.) there is a gradual revelation of the Trinity in the history of salvation. | 2019-04-25T01:57:05 | https://serborth.org/03302011.html |
February 25, 2014 RollOnFriday reports that Charles Russell and Speechly Bircham are in merger talks.
Speechly has been in the market for a merger partner for a while - the firm was in negotiations with Withers last year before the deal fell through before the vote.
RollOnFriday points out that the firms seem to be a good match, with partners earning around the same amount at each firm (an average of £300,000 at Charles Russell and £293,000 at Speechlys). A merger of the two would create a firm with a combined fee income of around £126m and a headcount of 164 partners, making it the largest private client firm in England. | 2019-04-20T06:48:46 | https://biglaw.org/news/7725/charles-russell-and-speechly-bircham-in-merger-talks |
Chart of the Day: Is Your Workout Working?
Filed under: Health, Image | Tagged: Calorie, Workout | Comments Off on Chart of the Day: Is Your Workout Working?
Amy Jeter Hansen wrote . . . . . . . . . | 2019-04-20T02:58:01 | https://cookwithkathy.wordpress.com/ |
This topic explains the qualification criteria for SpB, and the situations in which a person cannot qualify for SpB.
To qualify for SpB, a person must meet the criteria listed in the following table. Where more detail about a criterion is required, the second column indicates where you will find this.
failure to enter into a participation agreement.
Exception: War widows who have been receiving a social security benefit continuously since before 1 November 1986 may be eligible for payment of SpB subject to meeting all other qualification criteria.
subclass 070 - Bridging (Removal Pending).
Note: Holders of visa subclasses 309 and 820 (Partner) qualify for SpB as a result of a determination under SSAct 729(2)(f)(v), but for applications for SpB made from 1 January 2012 these visa holders will be required to serve the SpB 2 year NARWP unless they have experienced both financial hardship and a substantial change in circumstances beyond their control after arrival in Australia. Refer 3.7.1.20.
perseveres with an unprofitable venture.
Explanation: These people have control over their circumstances, and therefore should not be granted SpB. | 2019-04-21T12:03:27 | http://guides.dss.gov.au/guide-social-security-law/3/7/1/10 |
This is a ground cover type of sedum. Bright yellow foliage and blooms. Turns coper colour in the fall. | 2019-04-23T16:31:32 | https://www.gardensplus.ca/product/angelina/ |
Beautifully restored and brought back to life.
1 of 2 Germain Grand Pianos known to be in existence. Built in the early 1890's in Saginaw, Michigan by the Germain Piano Company - the Golden Era of American piano manufacturing, the beautifully figured sapele mahogany cabinet and ornately hand carved legs are works of art unto themselves.
The original action was the well respected Wessell, Nickel and Gross, available in high end instruments. The piano has been modernized with a new carbon fiber Wessell, Nickel and Gross action custom engineered to the piano resulting in a touch that would please the most discriminating player.
A must see and play for the serious pianist/investor. The meticulous details of this restoration make all the difference.
Even though we've conducted a 5 year search for other Germain Grand Pianos, we've only located 1 other; it is currently part of the Germain Instrument Collection in the Castle Museum in Saginaw. If you know of any others, we'd love to hear from you!
Serious inquiries only, please to Nancy @ Forte Piano Gallery & Restoration Center show contact info , members PTG, MPT, NAMM. Over 40 years service, commitment and integrity in the piano industry. | 2019-04-23T01:09:26 | https://www.pianomart.com/buy-a-piano/view?id=34678 |
SV Microwave has an exciting opportunity for a driven, hardworking entry-level Mechanical Engineer. This is a great opportunity for an individual with a strong desire to develop mechanical solutions for RF connectors and passive components in accordance with customer requirements.
Evaluate new product customer requirements to initiate and model advanced designs using SolidWorks.
Meet mechanical requirements and optimize electrical performance with electromagnetic simulation and analytical methods.
Regularly communicate with internal customers (Sales, Quality, Manufacturing) and external customers to clearly define current project objectives and provide weekly updates.
Develop manufacturable designs of components, assemblies, and tooling using proper CAD modeling techniques and mechanical tolerance analysis.
Perform heat transfer and predicted stress analysis using classical engineering methods and simulation tools.
Be responsible for the design review and final document approval of junior engineers, drafters, and technicians.
Participate in and oversee the assembly and testing of engineering prototype designs.
Troubleshoot root cause design and component failures and field returns using both experimental and analytical methods.
Work cooperatively with on-site manufacturing organization and other departments to meet production requirements and cost reduction goals through design for manufacturability, process and design improvements, and assembly fixture design.
Assist Quality Assurance in the development of production test methods and quality inspection parameters throughout the company.
Interface with suppliers to analyze and recommend new advances in technology.
Perform other duties as assigned and/or required.
Complete benefit package includes medical, dental, life insurance and a 401(k) company matched contribution.
Position requires candidate to be a US Citizen, a Permanent Resident or any individual who is granted status as a “protected person” under 8 U.S.C. We are unable to provide sponsorship. | 2019-04-25T02:20:56 | http://svmicrowave.com/employment/mechanical-engineer-entry-level |
Improve your business relationships and drive your sales growth with all new powerful and dynamic DOGMA CRM. The customer relationship management application comes with a powerful web back-end that can record practices, strategies and technologies. As a result it analyzes and manages customer interactions and data throughout the customer life cycle.
CRM systems also gives customer-facing staff detailed information on customers personal information, purchase history, buying preferences and concerns.
Dogma CRM comes with a full featured mobile application. It just ensures that you are lively following your business, no matter where you are.
Please enter details, our team will contact you !! | 2019-04-24T08:22:49 | http://www.softfruit.solutions/dogma-crm/ |
Codoid's API/Webservice Automation Testing Services improve test coverage, test significantly faster than human users and eliminate human error. REST APIs back most web-based or mobile applications. Testing APIs manually for every application release increases testing time and does not give confidence enough on build quality.
Thinking automation for API testing is the right idea, but it requires good framework setup, utilities, appropriate tool and skilled resources.
We, at Codoid, use SoapUI, JMeter, custom framework & utilities for API automation testing based on requirements.
Contact us to learn how we can assist you with your REST API automation testing needs. | 2019-04-22T02:53:34 | https://codoid.com/api-webservice-automation-testing-services/ |
Quiring, Courtney, et al. "Teriparatide." Davis's Drug Guide, 16th ed., F.A. Davis Company, 2019. Nursing Central, nursing.unboundmedicine.com/nursingcentral/view/Davis-Drug-Guide/51730/all/teriparatide.
Quiring C, Sanoski CA, Vallerand AH. Teriparatide. Davis's Drug Guide. 16th ed. F.A. Davis Company; 2019. https://nursing.unboundmedicine.com/nursingcentral/view/Davis-Drug-Guide/51730/all/teriparatide. Accessed April 22, 2019.
Quiring C, Sanoski CA, Vallerand AH. Teriparatide [Internet]. In: Davis's Drug Guide. F.A. Davis Company; 2019. [cited 2019 April 22]. Available from: https://nursing.unboundmedicine.com/nursingcentral/view/Davis-Drug-Guide/51730/all/teriparatide. | 2019-04-22T14:32:56 | https://nursing.unboundmedicine.com/nursingcentral/view/Davis-Drug-Guide/51730/all/teriparatide |
I think i have a nice idea of how we could revive the market.I don`t know if technically is possible or not but a good idea to make the trading scene grow is to create a wish-list.Just like the shop,where you can set an item you would like to buy,put a price and if someone has it,he could sell it to you.maybe create a site-warehouse where you can redeem the item after someone sold it through your wish-list-offer.
I also don`t know the policy of the site about the official shop,but a more variable shop would be so much better for the player experience.You know,like the usual shop where you can 'craft' your own item by preference.But again,i don`t know your policy about how you wanna manage the business.Thanks for reading!
But I think it would be really nice to be able to say on the market "buying x item for x bonus"
Idea is good, but.. For example. You need Dragon pants+luck+dd+ref. You add to your wishlist this item. But. if somebody have dragon+luck+dd+hp+zen? And what level of item do you prefer? +9?+13?+15? If somebody have +11? They will not see your "wishlist item" as i understand?
-Dragon lk dd ref hp and someone has lk dd ref hp zen you could simply contact the player.if not,you guys can set only the good opts: DD REF HP and treat zen,mana,dsr as non options,because i think no one cares about them(as far as i know dsr is only for mobs).
Or just leave it simple and if you see a player that wants Dragon Pants lk dd ref and you got lk dd ref+zen you just send him a message and job done.
Or to make it easier to find the item that you search, you can use a filter formula. For example you just put Dragon Pants +DD in your wish-list , you can still find someone who put Dragon Pants +DD +Ref +Hp +zen etc for sale.
We were talking about a wish-list,bro.adding items that other players would have and be willing sell to us.This would ease and revive the process of items trading from which both us players and the server would benefit.
I believe it is a good idea.
Also, why don't you create a shop where you can configurate your items as you want to? Maybe I want to get +15 lvl 4 wing only with +edr or critical. Or maybe I dream about ichor pants +13 And no one can offer it.
I think this is also one of the GREATEST things you can make on your projects.
Greatest would be to remove the shop at all.
Also add improving items from +12 to +13 for higher cost.
Add OPTIONS ADDING in the services list - maximum 1 option per one item with 500 bons cost.
+100 speed / +100 def / +100 dmg = each for 100 bons per month. Max 10 boosters at time allowed to keep the balance.
Start to detect referrals-makers (self-referring shouldn't be allowed) and highly increase the referral bonuses reward for real referrals. Maybe people would start to invite others at FB, VK, etc.
Start to pay more money for the advertisments at the top monitors.
Server needs great changes from the head to the bottom. | 2019-04-19T06:25:42 | http://forum.muxglobal.com/index.php?/topic/3398-market-wish-list/ |
Australia can rightly be called the hotspot destination for countless of potential immigrants who want to further expand their educational and professional skills. Each year, the Department of Home Affairs releases the medium and long term strategic skilled occupation lists which details the occupations that are currently in demand in Australia. In this way, thousands of potential immigrants in the students and/or temporary workers get an idea what skills and educational qualifications they should be after in order for settlement chances and ultimately a better future for themselves.
Keeping in mind, these current trends, a field that has high chances of leading to settlement in Australia is Psychology. A psychiatrist’s job is among one of the most sought after job roles in Australia these days. There are several fields that branch out from the psychology field including child psychology, forensic psychology and clinical psychology.
It is also worth mentioning here that the fields and job occupations in the psychology group are readily high rewarding meaning they have better compensation pay rates in Australia currently now. It is also a good news for potential migrants that there are plenty of degree and diploma programs available to be studies in psychology. It will depend solely upon the discretion of the student as to in which field they would want to further their career in and what states have in demand certain occupations in psychology. Also, keep in mind that before pursuing the degree it must be ensured that course you are doing may get an accreditation from Australian Psychology Accreditation Council (APAC).
In addition to accreditation of your course with the APAC, before being appointed as a full time psychologist you will have to register first with the Psychology Board of Australia. For this you will have to apply for the visa issued by the Department of Immigration and Border protection. Also, you will have to consult relevant authorities of the Skills Assessing Authority for the skill assessment.
As discussed earlier, psychology is a one field that not only rewards you well, but it has high prospects of you getting a settlement visa in Australia. The Australian government has officially nominated Australia Psychology Society (APS) for assessing the psychologists’ credentials. Thus it is the body that will be conducting the skills assessment of the history of skilled employment and education of candidates. Besides you are able to apply for all three major skilled migration streams.
Applying for Temporary Skilled Shortage Visa (TSS) 482 – Here’s your guide! | 2019-04-25T23:41:26 | http://visionaus.com.au/degree-psychology-can-increase-settlement-chances-australia/ |
Led Zeppelin continue their reissue campaign with a new edition of their celebrated live album How The West Was Won, originally released in 2003, featuring newly remastered audio, which was done under the supervision of Jimmy Page.HOW THE WEST WAS WON highlights the best performances from Led Zeppelin’s legendary concerts at the Los Angeles Forum and Long Beach Arena on June 25 and 27, 1972. Melded together and sequenced to replicate a single concert from beginning to end, it captures the band at the height of its formidable powers. Standouts include a 25-plus minute version of “Dazed And Confused” and a 21-minute medley based around “Whole Lotta Love.” The performances also capture the band introducing songs from its then-unreleased album Houses Of The Holy, which would be released nine months later. | 2019-04-23T20:00:48 | http://rockvprok.com/hardrock/44685-led-zeppelin-how-the-west-was-won-live-2018.html |
Illustration in thanks to everyone wishing me a happy day on my birthday this year. Made in rememberance of Monday, near Charlotte, North Carolina. Names here are those of close friends, family members and the animals at home we keep as pets. Thanks for wishing me a happy birthday, 2012! | 2019-04-26T05:54:40 | https://www.joaochao.com/blog/2012-birthday-wishes/ |
Just because you need reading glasses doesn't mean you don't have style! Our new "Crystal Lace" non-prescription reading glasses are a fun fashion complement to your look, and are a must for women who want to look as young as they feel. These frames have a classic, cat eye shape embedded with tons of flashy crystals that shine and shimmer as the light catches them. Crystal Lace readers come in a variety of unusual tortoise color combinations that truly show off the wearer's style and grace. Premium lenses in a lightweight design let you read in comfort all day long. Hard carrying case included. On sale exclusively from Aloha Eyewear, not sold in stores.
Fits Average. Lens: 2in.x 1.5in. Temple: 5.25in. Weight: 0.6oz. | 2019-04-19T05:11:39 | https://alohaeyes.com/products/crystallacerh8985r |
Every shareholder may authorize another individual or a legal entity as the proxy thereof at the meeting of the Shareholders' Assembly, under a Power of Attorney in a written form.
Where the Power of Attorney does not comprise any voting limitations or instructions, the proxy may vote upon the discretion thereof, always observing the interests of the shareholder that has issued the Power of Attorney. The proxy must keep minutes of the received voting instructions, if any, and to keep them for a period of at least one year as of the day of the holding of the meeting of the Shareholders’ Assembly in which he/she participated and voted, as well as to confirm that he/she executed such instructions if requested to do so by the Company or by the shareholder that issued the Power of Attorney.
The shareholders may obtain a hardcopy of the template of the Power of Attorney for participation and voting via a proxy at the Headquarters of Makedonski Telekom AD - Skopje, at "Kej 13 Noemvri" No. 6, 1000 Skopje, every working day from 14:00 to 15:00 hrs or at the following link.
- They were provided with specific instructions in a written form by the shareholders that authorized them as the proxies thereof in terms of every proposed item for voting based upon the items on the Agenda for the meeting of the Shareholders' Assembly.
The Company shall publish the identity of the appointed proxies that give rise to a conflict of interests on the website thereof. | 2019-04-20T16:14:31 | https://www.telekom.mk/participation-and-voting-via-a-proxy-6117.nspx |
Get ready to roam, Tampa, on two wheels. No, you won’t have to pedal. That’s because electric scooters are coming to downtown Tampa.
City officials have reopened bids for vendors for the program. A detailed report on TampaBayInno.com notes that Uber is expanding across the country in both bikes and scooters.
The initial pilot program was expected to launch in January 2019, but city officials decided to reopen bids for the dockless e-scooter program. We’re okay with the city broadening in its search.
Currently, Bolt Mobility in Miami Beach, Frank Underwood Law in Tampa, Greenberg Traurig in Tampa, Roll Labs Inc. in New York, NY, RSA Consulting Group LLC in Brandon and VeoRideMobility in Chicago have all submitted applications, according to the report on TampaBayInno.com.
The city is set to select up to three qualified vendors to provide scooter sharing services for select parts of the city of Tampa.
Don’t fret about congestion on the Riverwalk or dangerous riders on the Bayshore Boulevard. Those areas will specifically be off limits to electric scooters.
The two-wheeled electric rides will only be allowed on the sidewalk courtesy of a Florida Statute — and they can only reach speeds up to 8-10mph.
The deadline for submissions is February 11 and the year-long pilot program should launch in early spring.
Once these scooters arrive it won’t be total chaos herding them. Each of the areas in and surrounding downtown Tampa will have parking areas for the scooters.
The program would include roughly 600 total electric scooters in the city of Tampa. Their addition would complement the already popular Coast Bikes. | 2019-04-21T16:18:55 | https://thatssotampa.com/electric-scooters-are-coming-to-tampa-this-spring/ |
Performance specifications for a train handling and locomotive research evaluator are set forth in Volume I. These are based upon a study of design concept trade-offs to create a research facility capable of eliciting realistic behavior from railroad train operators. Results of these studies are presented in Volume II along with examples of research programs that could be carried out. Initial cost, operating staff and costs, buildings and utilities test subject logistics and downstream improvements are included in Volume III. The overall research needs that can be met uniquely by such a research evaluator facility are presented along with a schedule for design, procurement, delivery and installation of such a simulator.
Report/Paper Numbers: FRA/ORD-77/47.I Final Rpt. | 2019-04-23T06:08:24 | https://trid.trb.org/view/58069 |
Content marketing is all about creating and sharing information with users and readers that consider it relevant. There are only a few business owners who can actually hit a home run when it comes to content creation for a marketing campaign. The main reason behind this is the fact that most of them make the common mistakes that end up hurting their campaigns before they even start. If you are planning on content marketing, it is in your best interest to keep the following points in mind for a successful marketing campaign.
The two might sound like the same thing and may be they are, but the point here is to ensure that the content you are writing is original. This means that the content you write should not be found anywhere else, online or offline. The common mistake people make here is to create content that contains information that is easily available online meaning that the audience can easily have access to it or has already come across it. Be original and while at it, make sure the content is relevant and highly useful.
One of the biggest and most common content marketing mistakes done by both companies and the writers is to forget all about the audience or the end user’s needs. The audience is searching for useful information that can help them solve problems in their daily life and when the content does not offer this, it will have failed in its purpose. As much that the content should provide useful information about a product or a service, it should not be an advertisement. Keep in mind that people avoid advertisements because they perceive them as being sugarcoated and overrated.
The audience is interested in expanding their knowledge and gathering information they consider useful. For this reason, it is not simply enough to post great content; the content has to keep coming. The consumers will want to put their trust in you and in turn you have to prove your reliability by providing information consistently and doing follow ups through responses and updating the information you have already provided. Without this, the audience will shift attention to other sites and you will have lost important customers to your business.
It is important to pay attention to the audience and provide relevant information; however, you will not be able to reach out to a wider audience base without the use of SEO strategies.
Search engine optimization is the reason why some websites or content appear on the first search engine result page. Search engines such as Google, Yahoo, Bing, and MSN among other use keywords that users enter to rank the websites according to relevance. With that said, you need to incorporate SEO in your content marketing to enhance your visibility and get more readers and traffic.
This is one of the major mistakes that can kill any content marketing campaign. As aforementioned, the audience is looking for useful information. When your content is unfocused, readers will easily get disinterested and move to other sources which are most probably your direct competitors even if you have useful tips to solve their problems. To be on the safe side, focus on important points and present them in such a way that the audience will want to read letter after letter and get to know what you have to offer.
Content marketing can be done through articles, blogs, and newsletters among other publications. You should be able to connect and balance the contribution to all of these tools to create a successful marketing campaign. | 2019-04-25T18:55:29 | https://www.tabithanaylor.com/blog/6-common-content-marketing-mistakes-to-avoid |
Coming from Bolivia, crossing to Chile at Ollagüe. Refused to enter Chile with bicycle - therefore by bus to Chiu Chiu.
From Calama to San Pedro de Atacama, and then on a remote route to Argentina via Paso Sico - passing Toconao and Socaire.
A great route - but we had very rough weather conditions - including storm, snowfall and icy temperatures! | 2019-04-26T02:13:36 | http://pedalglobal.net/en/ct/Images/touring-cycling/toursur/2013-2014/images/chile-2---on-the-way-to-argentina |
Lack & Sons Funeral Home was established in 1916 and has been family owned and operated for three generations.
We provide services for all ethnic and religious denominations as well as cremation, scientific donations, international shipping, public-aid and pre-arrangements. The public is invited to visit the newly remodeled chapel, meet the Lack family and their staff, and receive brochures and information at any time.
Providing excellent, compassionate service is our number one goal. | 2019-04-26T02:06:43 | http://lackfuneralhome.com/ |
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