content
stringlengths
71
484k
url
stringlengths
13
5.97k
If we glance life 100 years ago, and examine that with the at present’s life, we are going to notice that Science has dramatically changed human life. STS gives college students a broader understanding of science than is offered inside conventional science majors and can also be appropriate for students within the social sciences concerned about interpreting science, expertise and medicine as a part of society and tradition. Modeled after the profitable AAAS (American Affiliation for the Development of Science) Science and Know-how Policy Fellowship® Program, it enables early and mid-career scientists who’re citizens and residents of ASEAN Member States (AMS) to contribute their knowledge and analytical expertise to their national governments. Science and technology offer a part of the solution to climate change, inequality and other global issues, a United Nations official said on Tuesday, spotlighting the big potential these fields maintain for reaching humanity’s frequent goal, of a poverty and starvation-free world by 2030. The Federal Ministry of Science and Expertise, Nigeria is among the strategic Ministries of Government saddled with the accountability of facilitating the development and deployment of Science, Expertise and Innovation to enhance the pace of Socio-financial improvement of the nation. The study of astronomy within the early occasions of its inception demanded the enlargement of our understanding of mathematics and made potential such realizations as the scale and weight of the earth, our distance from the solar, the fact that we revolve around it, and other discoveries that allowed us to maneuver forward in our body of data with out which we would not have any of our fashionable marvels of know-how.
http://www.jdecareers.com/seed-science-and-expertise.html
British-American astrophysicist Cecilia Payne-Gaposchkin (1900–1979) conducted scientific research that led her to the discovery of the composition of stars. In 1956, amid a stellar career, Payne-Gaposchkin was recognized among the pioneering astronomers of her generation and became the first woman appointed a full professor at Harvard University. In the early part of the 20th century, scientists were increasing humankind's knowledge about both their inner world and the space that surrounded their planet. As discoveries were made in the areas of physics, earth science, and astronomy, the literate general public became aware of the limits of human knowledge and of the many questions still to be asked. Among the most compelling of these unanswered questions concerned the night sky, a subject of perennial fascination: What exactly is a star and what is it composed of? British-born astrophysicist Cecilia Payne-Gaposchkin worked almost obsessively on the star question and answered it. PayneGaposchkin made her groundbreaking discovery when she was only 25 years old. In 1925, Payne-Gaposchkin's research became her Ph.D. thesis at Harvard University Observatory in Harvard, Massachusetts. Not only did her work provide more knowledge about the universe, it also was important in the development of the study of stellar atmospheres. Looking back on Payne-Gaposchkin's published Ph.D., distinguished U.S. astronomer coauthors Otto Struve and Velta Zebergs would deem it “the most brilliant Ph.D. thesis ever written in astronomy” in their Astronomy of the 20th Century. Cecilia Helena Payne was born May 10, 1900 in Wendover, England. She was one of three children born in a family known for its intellectual interests, heritage and connections. PayneGaposchkin's father, Edward John Payne, was an historian, a talented musician, and a barrister (lawyer) with offices in London; her mother, Emma Leonora Helena, was of Prussian extraction. Most of Payne-Gaposchkin's upbringing was done by her mother, as her father died when she was four years old. Uncles influencing her intellectual bent included noted historian Georg Heinrich Pertz and famous writer James John Garth Wilkinson. Her family cherished a box of family letters that included signed papers of both Charles Darwin (1809–1882), the naturalist made famous for his work on the theory of evolution, and Charles Lyell (1797–1875), a renowned geologist and the author of the groundbreaking Principles of Geography. Payne-Gaposchkin eventually inherited this box of notable documents and it may have served an inspiration. Payne-Gaposchkin benefitted from a quality education and in 1919 she won a scholarship to Newham College Cambridge. At Newham, she became interested in science and studied botany, physics, and chemistry. Her interest turned to astronomy upon attending a lecture by astronomer Sir Arthur Eddington (1882–1944). After listening to Eddington's lecture, she returned to her dormitory room and transcribed the lecture from memory. By this time, Payne-Gaposchkin had decided to major in physics at Newham College, but Eddington talk inspired her to shift her focus to astronomy. Unfortunately, this was not possible because, at the time, astronomy was considered a branch of mathematics, not physics. While studying physics, Payne-Gaposchkin attended other lectures given by Eddington and one point she spoke to him, explaining that she wanted to become an astronomer. Noting that he did not see any obstacle to this goal, Eddington suggested that she read certain books if she was indeed serious about studying astronomy. Much to his surprise, Payne-Gaposchkin told the professor that she had already read all of the texts he suggested. PayneGaposchkin was proving herself a woman of substantial intellectual capacity. After completing her studies at the University of Cambridge (which would not grant degrees to women until 1948), Payne-Gaposchkin realized that England would be a difficult place for a woman wishing to pursue a career in astronomy; teaching would be her only option. In the United States, female astronomers appeared to be more accepted, and an introduction to the director of the Harvard College Observatory proved timely. In 1923, she moved to the United States, the recipient of a graduate fellowship at the observatory. Located in Cambridge, near Boston, Massachusetts, the observatory provided her with a fine environment for research, as it owned the world's largest archive of stellar spectra, light characteristics captured on photographic plates. Astronomers made these plates by using a telescope attached with a spectroscope (an instrument that measures light properties over a specific part of the electromagnetic spectrum). That technological coupling resulted quantifiable information about the colors and wavelengths of starlight. During the late 1880s, the study of stellar spectra had led to the development of the science of astrophysics, which married two of Payne-Gaposchkin's major interests: physics and astronomy. The new science was moved forward by Gustav Kirchoff (1824–1887) and Robert Bunsen (1811–1899), both based in Germany, and William Huggins (1824–1910), an Englishman. Together and separately, these men studied laboratory spectra and spectral lines and discovered that the visible universe is made of the same chemical elements found on Earth. Elements such as calcium and iron had some of the most prominent spectral lines and these types of heavy elements proved to be some of the major constituents of stars. Working along the same research lines at Princeton University, Henry Norris Russell (1877–1957) concluded that if Earth's crust were increased to the temperature of the Sun, its color spectrum would look nearly the same. By the time Payne-Gaposchkin began her tenure at Harvard College Observatory, an ongoing, comprehensive study of stellar spectra had already begun. Annie Jump Cannon (1863–1941) had sorted the spectra of several hundred thousand stars into seven classes, basing her classification stratagem on differences in spectral features. A question remained, however. Astronomers assumed that the spectral classes represented a sequence of decreasing surface temperatures of stars, but this assumption had not been quantitatively demonstrated. Payne-Gaposchkin was now intellectually equipped and ready to start a long project and she decided that she would measure absorption lines in stellar spectra. Through her work, she established a correlation between the patterns of features in the spectrum of any atom and that atom's electron configuration. She also knew that high temperatures take away one or more electrons from atoms. These separated electrons are called ions. Two years later, in 1925, Payne-Gaposchkin presented her findings as part of her doctoral thesis. In this document she demonstrated that the wide variation in stellar spectra is due mainly to the different ionization states of the atoms and the different surface temperatures of the stars. Her conclusion was achieved by calculating the relative amounts of 18 elements and learning that the compositions of different types of stars were quite similar. A surprising discovery involved hydrogen and helium, two of the lightest elements, which Payne-Gaposchkin found accounted for 99 percent of a star's mass. Heavier elements, such as those found on Earth, made up only two percent of a star's mass. This discovery, that hydrogen was the primary component of the sun, the largest star, went against what scientists had assumed. In 1925 Payne-Gaposchkin was the first Ph.D. graduate in astronomy at Radcliffe College (the women's college affiliated with all-male Harvard College). More significantly, her research made it possible to read the surfaces temperature of a specific star from the rainbowlike band of colors in its stellar spectrum. It also enabled scientists to calculate stellar temperatures and to accurately interpret the Hertzsprung-Russell diagram, which plotted luminosity against the spectral class of the stars. This diagram now became the most powerful tool for astrophysicists engaged in analysis. Following completion of her fellowship and publication of her first dissertation, Payne-Gaposchkin was asked to join the staff at Harvard College Observatory, serving Shapley as an assistant and working with other female astronomers. In 1932, she toured Europe and visited other observatories. In Berlin, Germany, to attend a meeting of the Astronomische Gesellschaft, an astronomical society established in 1863, she met the man who would become her husband, Sergei Gaposchkin (1889–1984), a young Russian astronomer who lived in Germany at the time. Now ruled by a government based in the city of Weimar, Germany was the site of political foment due to rising inflation, social unrest, and the competing interests of communists and the socialist Nazi party. Although Gaposchkin had been forbidden to leave by authorities, Payne-Gaposchkin helped him emigrate from Europe and also found him a position at Harvard when he arrived in November 1932. In March 1934, the couple were married and they formed an effective team, conducting work on the physical understanding of variable stars. Although Payne-Gaposchkin worked as a professor at Harvard throughout the 1930s, her title remained that of technical assistant; a subtitle of Astronomer was added in 1938 when she threatened to leave the college. Under a new director, in 1956, she was named full professor (the first woman at Harvard to earn that title) as well as chairperson of the astronomy department. Inducted into the American Philosophical Society in 1936 and the American Academy of Arts and Sciences in 1943, PayneGaposchkin eventually, in 1976, received the prestigious Henry Russell Prize from the American Astronomical Society, a recognition previously denied her because of her gender. She also published several books, among them Variable Stars (1938), Stars in the Making (1952), Variable Stars and Galactic Structures (1954), The Galactic Novae (1957), and Stars and Clusters (1979). Payne-Gaposchkin died in Cambridge, Massachusetts on December 7, 1979. Her obituary in the Quarterly Journal of the Royal Astronomical Society described her as “a pioneering astrophysicist and probably the most eminent woman astronomer of all time.” She shared her reflections in Cecilia Payne-Gaposchkin: An Autobiography and Other Recollections, a work edited by her daughter, Katherine Haramundanis, and published in 1984. Payne-Gaposchkin, Cecilia, Cecilia Payne-Gaposchkin: An Autobiography and Other Recollections, Cambridge University Press, 1984. Soter, S., and Neil deGrasse Tyson, editors, Cosmic Horizons: Astronomy at the Cutting Edge, New Press, 2000. Struve, Otto, and Velta Zebergs, Astronomy of the 20th Century, Macmillan, 1962. Quarterly Journal of the Royal Astronomical Society, Volume 23, 1982.
https://reference.jrank.org/biography-2/PayneGaposchkin_Cecilia.html
UNSW Science invites high school science classes to participate in two, free, online interactive events broadcast live from Sydney Opera House on Friday 18 August. Students will hear from a variety of inspiring speakers including leading NASA scientists and experts in marine science, astronomy, geology and space exploration. These events are open to all high school students – with a particular focus on students in years 9-12 who have a keen interest in science. Inspire your students with real world stories from female scientists who have explored our world from the deepest oceans to the outer reaches of the universe. This National Science Week Women on Mars event will follow a major public event in the Concert Hall the previous evening, Thursday 17 August, when The Sydney Opera House and UNSW Science’s Big Questions Institute join forces to present Life on Mars: The 2020 Rover Mission, with presentations by the NASA scientists and other researchers. Both of these events are being held as part of Sydney Science Festival during National Science Week. Schools can view the live stream on the UNSW Science YouTube channel. Students and teachers are encouraged to ask questions of the speakers using UNSW’s online question portal, Slido. Session one: The Journey to Mars begins Friday 18 August, 10.00am – 11.00am (Sydney time) Speakers: - Professor Emma Johnston UNSW Dean of Science and a leading marine ecologist whose research is carried out in diverse environments including the Great Barrier Reef, Antarctica and Sydney Harbour. - Tara Djokic UNSW PhD student who recently discovered the oldest fossil evidence of land-based life on Earth, in the Pilbara in Western Australia. - Kirstin Banks UNSW science student who will talk about Aboriginal astronomy. - Solange Cunin UNSW Aerospace Engineering student and co-founder of the Cuberider, a STEM education program that brings access to space to the classroom. Session two: Lift-off to Mars and beyond Friday 18 August, 1.30pm – 2.15pm (Sydney time) Speakers: - Dr Mitchell Schulte A program scientist with the Mars Exploration Program at NASA Headquarters in Washington. - Dr Abigail Allwood Heading up NASA’s Jet Propulsion Laboratory, Dr Allwood is the first Australian, as well as the first woman, to lead a team at NASA, and she has designed an instrument for NASA’s rover that will land on Mars in 2020. - Professor Tamara Davis University of Queensland cosmologist investigating the mysterious dark energy and dark matter in the universe. Register your class Don’t miss this exciting opportunity for your students to hear top scientists discuss their careers, explain why they chose to study science at university and outline their great discoveries and innovations. This will be a highly memorable and exciting livestream event! Read more and register to attend This event is supported by Inspiring Australia.
https://inspiringnsw.org.au/2017/08/07/women-on-mars/
It’s no secret that there are fewer women than men who work in the sciences. Although the fraction of women has been increasing over time, most fields still have not reached parity, and various studies have shown evidence of gender bias. The authors of this bite looked at the number of citations astronomy papers published over the last 50 years have received to try and determine if there is gender bias present in citation counts. The amount of data they analyzed is impressive – 200,000 papers published in five of the biggest journals (Astronomy and Astrophysics, the Astrophysical Journal, Monthly Notices of the Royal Astronomical Society, Science, and Nature) that publish astronomy research. After downloading a list of all their papers of interest listed in the Astrophysical Data System (ADS), they determined the gender and seniority of the first author (in most fields of astronomy, the first author is the person who actually writes the bulk of the paper and is responsible for the majority of the research). Seniority was defined as the number of years since an author’s first publication. Since many scientists publish at least occasionally using their initials, they used a matching algorithm to match papers published under initials to those published using an author’s first name (i.e. if an author published at least one paper using their full name at some point during their career, they were able to link the rest of their papers to their record). Papers where the gender could not be determined were removed from the dataset. Looking at the raw data, they found that papers authored by a male received more citations than those written by a female. The ratio of male/female number of citations is larger in earlier times (although errors are large there are well due to the smaller number of papers published and the extremely low fraction of female scientists in the 1960s). Since 1990, the ratio has held roughly steady: male first-authored papers received roughly 5% more citations than papers first-authored by a woman. Of course, this difference is not conclusive evidence of gender bias. The authors found some other differences between papers first-authored by men and women. For example, women tend to publish less, but their papers tend to be longer. Additionally, since women entered the field of astronomy later in time on men, as a group they tend to hold less seniority. Effects like this need to be controlled for in order to draw any conclusions. Using a machine learning technique known as the random forest algorithm, the authors studied only the male first-author papers (for a concise definition of what a random forest is, check out this blog post). Using a few properties (seniority of the first author, number of references, number of authors, year of publication, the journal’s name, the area of the world the first author was from, and the subfield of astronomy) that are not expected to be correlated with gender, they created a way to predict the number of citations a paper would be expected to have. They then turned their attention to the papers first-authored by women. They found that the papers authored by women received roughly 10% less citations than their algorithm predicted. While more convincing, this is still does not show with 100% certainty that this entire effect comes from gender bias. The authors note several other issues that could effect their results: the effects of self-citation, a lack of ability of their algorithm to determine the genders of non-European, non North American names, etc. The authors end the paper by encouraging the rest of the astronomical community to conduct further analyses.
https://astrobites.org/2016/12/16/gender-bias-in-astronomical-publications/
This book started out pretty much the same way as many books about cosmology do – with Edwin Hubble and Albert Einstein, Fritz Zwicky and others and the discoveries that the Universe is expanding, that there was a specific beginning in time for it, dark matter and dark energy etc. But then for my surprise I found myself reading about black holes and then back to the more usual for cosmology – cosmic microwave background and the fact that the Universe is expanding ever faster. But then in the end you get to read even about SETI and at some point you’ll find a long-ish tirade about how modern science in many fields is done in large teams and how Nobel prize doesn’t do justice for discoveries that have been made by large teams – someone will always be left out, who shouldn’t be. In the beginning I found myself getting slightly bored while reading this book – how many books about Hubble and Einstein can I possibly even bare to read? There’s only a certain amount after which you feel they’re maybe not that exciting people to read about in EVERY book (but you can’t get away without them in case of the history of 20th century cosmology and astronomy etc). I did find however that this book has a great side to it, that I haven’t met in (as far as I remember) any others – namely the author also discusses why scientists who came up with an idea before might not have been the people known for a discovery. That made for very interesting reading. If you’ve never read about 20th century discoveries in cosmology (and some mentions of a lot earlier scientists and philosophers), it is a great book to read – you get a pretty much full 360 degree view of the most important ideas and the stories behind them with some extra things to think about. I probably would have given this book a 10/10 if I wouldn’t be so fed up with reading about history of 20th century astronomy all the time, so 8/10 is even really high. Also there’s no mathematics or difficult concepts that you would need to grasp to read this book, so it is quite an easy read. And there’s an awesome long”Suggested Further Reading” section at the end. It’s awesome because I’ve read a lot of those books and I know they’re great, and everything I haven’t read I’ve added to my To-Read list :).
https://bookscomefirst.com/2016/04/22/book-211-mapping-the-heavens-by-priyamvada-natarajan/
The stars have aligned for Canberra-based astronomer Lisa Kewley. This July, she will become the first woman and the first Australian director of the Center for Astrophysics (Harvard & Smithsonian), USA. Professor Kewley, an astrophysicist specialising in galaxy formation and evolution, is director of ASTRO 3D, an ARC Centre of Excellence at ANU’s Mt Stromlo Observatory, investigating the evolution of matter, light, and the elements since the Big Bang. As head of the CfA, Professor Kewley will oversee 800 staff across nine major scientific facilities and institutions – including observatories in Arizona and Hawaii, and the NASA X-ray satellite Chandra. (She will build its successor, the next NASA-funded X-ray telescope.) “Leading a large organization with expertise across a whole range of areas, and access to different telescopes means that we’ll be able to answer some really fundamental questions in astronomy,” she said. What are the first galaxies in the universe? What did they look like? How did they evolve across time? What are the atmospheres around planets in other solar systems like? How did stars form and evolve in the early universe? Professor Kewley said her appointment was “a tremendous honour”, and she was “very excited”. “It’s a really amazing time to be doing astronomy,” she believes. This decade, the next generation of telescopes – such as Australia’s Square Kilometre Array (SKA), the world’s largest radio telescope, or the Extremely Large Telescope, the world’s biggest optical/near-infrared extremely large telescope, in Chile – will lead to huge discoveries in many areas of astrophysics, she predicts. They will “reveal a window to the universe that we haven’t been able to look at before”. Scientists could discover what happened right after the Big Bang, or identify which extrasolar planets are likely to hold life. “We’re going to make major advances in our understanding of the universe, our place in the universe, and how special we are in the universe.” Professor Kewley’s own contributions to the field include understanding the gas physics in star-forming galaxies, investigating supermassive black holes, and tracing how stars are formed and how the amount of oxygen in galaxies has changed over the past 12 billion years. Dealing with such cosmic questions puts everything into perspective, she finds. “You’re dealing with large time scales. We’re looking back in time very close to the Big Bang, so beyond 13 billion years. And so our lifetime on Earth is very, very tiny, compared to the timescale and the lifetime of the universe.” But her family keeps her grounded. “It’s nice to come home at the end of the day to my husband and kids, and so some vegetable gardening,” she said. “Both are fundamental to humans, but in a different way. Astronomy and astrophysics is about understanding our origins and why and how we got here. As humans, we need to live on this Earth, and experience living on this Earth as well.” A stellar career Professor Kewley became interested in astronomy in high school, thanks to her Year 11 physics teacher. He gave her articles about black holes and wormholes, and took the class on astronomy camp, where they tracked the moons of Jupiter and the constellations through a telescope. “That was amazing,” Professor Kewley remembered; “that’s when I decided I wanted to do astronomy.” In 1991, she attended the National Youth Science Forum in Canberra, and discovered that astronomy was a profession. She studied science at the University of Adelaide, obtained her doctorate in astrophysics from the Australian National University, then went to the CfA for three years, working on the formation and evolution of stars. “I had a great time; it was really a springboard for my career in the US. I made lots of connections and lots of collaborators whom I still work with today.” She spent seven years in Hawaii: her team at the Institute for Astronomy at the University of Hawai’i discovered a galaxy 9.3 billion light years away, while she received the Annie Jump Cannon Award in Astronomy (2005) and the Newton Lacy Pierce Prize in Astronomy (2008) for her research at the W.W. Keck Observatory on the evolution of galaxies. She returned to Australia in 2011, as the first woman professor at the ANU Research School of Astronomy and Astrophysics. She was elected a fellow of the Australian Academy of Science (2014) and an international member of the National Academy of Sciences (2021); and in 2020 became the first Australian to win the James Craig Watson Medal, an American award for outstanding contributions to astronomy. Where are the women? But although Professor Kewley’s career has been stellar, she is one of the few women in the field. At current rates, it is estimated that it will take 60 years to achieve gender equity; women will not make up even one-third of professional astronomers until 2080. Women hold 40 per cent of astronomy PhDs, but only 20 per cent of senior astronomy positions, and leave the industry two to three times more often than men. When Professor Kewley was a student, there was only one woman astronomy professor with a permanent job in all Australia, and none at ANU. “When I was a postdoc there, it never occurred to me that I would be a director of anything,” she said. “I still thought that there would be a glass ceiling, and that I would have to leave astronomy at some point.” In the US, however, Professor Kewley saw more women at senior levels, children in tow at conferences and meetings. Those role models showed her that women could have both a scientific career and a family. “That completely changed my thinking, and allowed me to stay in astronomy,” she said. As professor at ANU, and director of ASTRO 3D, Professor Kewley resolved to improve matters. She made the work culture more women-friendly: she set clear gender targets, offered all positions part-time, and ensured selection committees had an equal balance of sexes. Now, half the staff and more than half the students are women – well above the Australian average for astronomy. Professor Kewley will bring that approach to the US. While this retains women astronomers, Professor Kewley believes more must be done to encourage school students’ interest in science. In high school, she confessed, she worried that physics and chemistry would be too hard for her. She had gotten that idea from books where female characters needed men to help them with math and trigonometry, and hated physics. “The attitudes of those characters made me feel I wouldn’t be very good at it,” she said. “Fortunately, my dad’s a scientist; he made me do it, and it turned out that I loved it.” But not every girl is lucky enough to have a scientist father who can help her and give her confidence, Professor Kewley said. Teachers and media should show women scientists, so girls can see that women can be scientists. Too often, the famous scientists in textbooks are all men – ignoring (limiting the list to astronomers alone) Hypatia of Alexandria, Caroline Herschel, Henrietta Swan Leavitt, Cecilia Payne-Gaposchkin, Vera Rubin, or Andrea Mia Ghez. “Role models have to be there all along the way,” Professor Kewley said. She believes there must be more collaboration between scientists and teachers to make children (of either sex) interested in science. ASTRO 3D, for instance, donates telescopes to regional schools or girls’ schools, and trains the teachers and pupils how to use it; that dramatically increases the number of children doing physics.
https://heromag.net/canberra-astronomer-lisa-kewley-heads-us-institution
Students from ages 8 -12 are welcomed to The Actors’ Gang for Virtual Saturday Classes to art of theater-making from home! The focus of the class is to provide a safe space for children to exercise their imaginations and express themselves creatively. In addition to playing fun theater games and interacting as an ensemble, the students will engage in elements of The Actors’ Gang signature acting technique referred to as “The Style”. Our technique is based on the physical and improvisational form of Commedia dell’Arte, a 16th Century Italian theatrical form that entails a high level of focus, a strong connection to emotions, and a heightened awareness of ensemble. In our Saturday class, children are encouraged to express honest emotions by creating bold character choices through improvisation, written, and drawing exercises, and fun video performances.
https://culvercitycrossroads.com/2020/09/27/the-actors-gang-virtual-saturday-classes-start-in-october/
We recognise the importance of providing a relaxed, friendly atmosphere, which is conducive to learning. The session provides opportunities for uninterrupted play where children can investigate and explore, problem solve and work together in developing their play. Our range of learning experiences for the children are centred on the six areas of the Pre-School Curriculum:- Personal, Social & Emotional Development This area of learning is very important for young children in all aspects of their lives. It is about children’s emotional well-being, understanding who they are, respecting others and their environment, making friends, beginning to understand emotions and about developing positive dispositions to learn. Good development in personal, social and emotional development gives children the best opportunity for success in other areas of learning. Children are encouraged to develop independence, gain confidence, make choices and develop positive attitudes towards health, hygiene and safety. Language Development Language is crucial to living and learning. It is used to communicate with others, to share and express feelings, to give and obtain information and to understand ideas and develop thoughts. Children are encouraged to talk to one another and to staff, thereby extending their vocabulary and fluency of speech. They have frequent opportunities, in small and large groups, to listen to and join in with stories, rhymes and songs and to listen to and respond to music. They are encouraged to develop a love of books, to handle them appropriately and to become aware that the printed (and written) word has meaning and that books should be read from left to right. Opportunities are provided for children to experiment with a variety of drawing, painting and writing materials in order for them to engage in early attempts at writing and mark making. Physical Development & Movement A wide variety of small and large equipment provides the children with opportunities to extend their skills in running, hopping, jumping, climbing, balancing, kicking, throwing and catching. Taking part in physical play helps them to develop balance, control, co-ordination and awareness of size, space and direction. They can develop social skills such as turn-taking, sharing and co-operating as well as values such as trust, fairness and respect for others. Children are also supported in the development of fine motor skills by using, for example, pencils, paint brushes, construction materials, jigsaws, scissors etc, encouraging them to handle small objects with increasing control and confidence. Early Mathematical Experiences As children take part in play and other activities, they are supported by staff in developing an understanding of number, shape, space, size and quantity, pattern, sequencing/time and counting. They are encouraged to learn and use mathematical language and to solve problems as they play, to sort, match, count and become familiar with/recognise numbers. The Arts Through play, children explore a wide range of resources – natural and man-made – and have opportunities to experiment with colour, shape, pattern and texture. They develop self-esteem, confidence and language through role-play situations and begin to value their own and other children’s work, ideas and feelings. They learn songs, listen to and respond to music and make their own music by singing, clapping and playing simple percussion instruments. The World Around Us Children are naturally curious about their environment and the people around them and frequently ask questions. They are encouraged to explore, investigate and select materials and equipment as they play. They begin to recognise parts of the body and identify a range of familiar sounds, talk about themselves, their families and events in their lives both past and present. They learn about the weather, seasons, how to observe and respect living things, caring for the environment and about the multi-cultural world we live in.
https://www.bopeepcorner.com/curriculum/
Improvisation is a construct that uses a set of minimal heuristic guidelines to create a highly flexible scaffold that fosters extemporaneous communication. Scholars from diverse domains: such as psychology, business, negotiation, and education have suggested its use as a method for preparing professionals to manage complexity and think on their feet. A review of the literature revealed that while there is substantial theoretical scholarship on using improvisation in diverse domains, little research has verified these assertions. This dissertation evaluated whether improvisation, a specific type of dramatic technique, was effective for training pre-service teachers in specific characteristics of teacher-child classroom interaction, communication and affective skills development. It measured the strength and direction of any potential changes such training might effect on pre-service teacher’s self-efficacy for teaching and for implementing the communication skills common to improvisation and teaching while interacting with student in an inclusive classroom setting. A review of the literature on teacher self-efficacy and improvisation clarified and defined key terms, and illustrated relevant studies. This study utilized a mixed-method research design based on instructional design and development research. Matched pairs ttests were used to analyze the self-efficacy and training skills survey data and pre-service teacher reflections and interview transcripts were used to triangulate the qualitative data. Results of the t-tests showed a significant difference in participants’ self-efficacy for teaching measured before and after the improvisation training. A significant difference in means was also measured in participants’ aptitude for improvisation strategies and for self-efficacy for their implementation pre-/post- training. Qualitative results from pre-service teacher class iv artifacts and interviews showed participants reported beneficial personal outcomes as well as confirmed using skills from the training while interacting with students. Many of the qualitative themes parallel individual question items on the teacher self-efficacy TSES scale as well as the improvisation self-efficacy scale CSAI. The self-reported changes in affective behavior such as increased self-confidence and ability to foster positive interaction with students are illustrative of changes in teacher agency. Self-reports of being able to better understand student perspectives demonstrate a change in participant ability to empathize with students. Participants who worked with both typically developing students as well as with students with disabilities reported utilizing improvisation strategies such as Yes, and…, mirroring emotions and body language, vocal prosody and establishing a narrative relationship to put the students at ease, establish a positive learning environment, encourage student contributions and foster teachable moments. The improvisation strategies showed specific benefit for participants working with nonverbal students or who had commutation difficulties, by providing the pre-service teachers with strategies for using body language, emotional mirroring, vocal prosody and acceptance to foster interaction and communication with the student. Results from this investigation appear to substantiate the benefit of using improvisation training as part of a pre-service teacher methods course for preparing teachers for inclusive elementary classrooms. Replication of the study is encouraged with teachers of differing populations to confirm and extend results. Notes If this is your thesis or dissertation, and want to learn how to access it or for more information about readership statistics, contact us at [email protected] Graduation Date 2012 Semester Fall Advisor Hines, Rebecca Degree Doctor of Philosophy (Ph.D.) College College of Education and Human Performance Degree Program Education; Instructional Technology Format application/pdf Identifier CFE0004516 URL http://purl.fcla.edu/fcla/etd/CFE0004516 Language English Release Date December 2013 Length of Campus-only Access 1 year Access Status Doctoral Dissertation (Open Access) Subjects Dissertations, Academic -- Education, Education -- Dissertations, Academic STARS Citation Becker, Theresa, "Evaluating Improvisation As A Technique For Training Pre-service Teachers For Inclusive Classrooms" (2012). Electronic Theses and Dissertations. 2491.
https://stars.library.ucf.edu/etd/2491/
I recently had the pleasure of being interviewed by Ben Ari from Authority Magazine. He asked me some thought-provoking questions. This blog is an edited version of the interview, shared with permission. Thank you so much for joining us in this interview series! Before we dive into the main focus of our interview, can you tell us a bit about your childhood backstory? What or who inspired you to pursue your career? We’d love to hear the story. In 2000, I was working in a communication management role in the field of adult learning in the non-profit sector. I enjoyed my job, but wasn’t sure where I wanted to go next in my career. Then I was offered an opportunity to join a peer learning group, where I met Maggie who was the group’s facilitator. Not only did membership of the group help me progress in my existing role, but it opened-up new possibilities. I realized that facilitation and coaching was the career path for me. I was excited by a more hands on role in helping people learn and develop, rather than a desk-based role. Can you share the funniest or most interesting mistake that occurred to you in the course of your career? What lesson or take away did you learn from that? In my very first job, I was an assistant to the HR manager of a small company. I was asked to organize a coach trip for staff to visit one of our branches in another city. I made a decent job of organizing the first part of the day, the pick-up, liaising with the other branch etc. But when it came to the return journey, I hadn’t really thought about drop-off arrangements. People were asking if they could be taken to various locations. In my desire to be helpful I said yes, and the result was that we ended up getting back to the head office late for those expecting to get off there. This taught me, firstly to think through endings as well as beginnings, which is valuable in training and coaching. And I also learned that you need to balance the needs of individuals with the needs of the group. The road to success is hard and requires tremendous dedication. This question is obviously a big one, but what advice would you give to a young person who aspires to follow in your footsteps and emulate your success? An approach that’s served me well was to develop a vision of the kind of work that I wanted to do, and then say yes to opportunities that took me in this direction. And having the courage to say no to work that didn’t feel well aligned. I believe there is a place for a structured approach to career development, particularly if you are following a well-trodden path such as in medicine or law. But we know the world of work is changing at an unprecedented rate, so I believe that the combination of a clear sense of direction combined with a flexible attitude is a pretty good success strategy for the 2020s. My advice is to keep learning, and to follow lines of study that interest you even if you’re not sure where they are leading. Learning can open the door to opportunities that you may not yet able to see. Is there a particular book, film, or podcast that made a significant impact on you? Can you share a story or explain why it resonated with you so much? “Feel the Fear and Do It Anyway” by Susan Jeffers had a big impact, perhaps because it was the one of the first personal development books that I read. A particular takeaway was Jeffers’ advice on no-lose decision making. Essentially, she taught me not to waste mental energy on wondering if I’ve made the right decision. She says that when you make a choice between different paths, each of them can lead to “goodies”. I continue to see the truth in this in going through life. We cannot know the future, but we can make what we believe are wise choices at the time. Can you share your favorite “Life Lesson Quote”? Why does that resonate with you so much? “The breath of life and the sharp winds of change are the same thing.” From a poem by DH Lawrence. Life is a continual process of change. Reminding myself of this has helped me deal with difficult changes such as loss and grief, as well as giving me the courage to say yes to opportunities and take some risks. What are some of the most interesting or exciting projects you are working on now? How do you think that might help people? Working on my book has been exciting! The process of writing Crafting Connection: Transform how you communicate with yourself and others has given me an opportunity to share some of the transformative and practical methods of personal and professional development that have helped me and others over many years. The book makes a wide range of approaches accessible, and I hope it will reach and transform the lives of many more people than I possibly could through my direct work with individuals and groups. Another excitement is being part of a project delivering a peer learning experience for members of a US based professional membership body. It’s the first time I’ve worked for a US based organization, and it’s exciting to be working in a different cultural context, compared to my work in the UK and Europe. OK, thank you for all of that. Let’s now shift to the core focus of our interview. Can you briefly tell our readers a bit about why you are an authority about Emotional Intelligence? The managers I work with are dealing with challenges such as difficult conversations, facilitating effective meetings, and navigating change. Emotional intelligence is at the heart of my facilitation and coaching, as I help emerging leaders to develop their self-awareness and their ability to connect and communicate with other people. And, importantly, I practise what I preach! I’ve been on personal and emotional development journey for over thirty years, embracing methods including somatic and mindfulness practices. I use and teach methods that are evidence based, creative and effective. For the benefit of our readers, can you help to define what Emotional Intelligence is? Emotional intelligence starts with you. It’s the ability to recognize and understand your own emotions, and to regulate your emotions so that they work for you, not against you. Emotional intelligence also includes the ability to understand other people’s emotions. And it includes the interpersonal social skills needed for effective personal and professional relationships with others, given that we are all emotional beings. How is Emotional Intelligence different from what we normally refer to as intelligence? Emotional Intelligence differs from purely cognitive or logical intelligence. To work out a math problem, or write computer software, is a cognitive task. But when you are dealing with people, cognitive intelligence isn’t enough, as people are driven as much by their feelings as by their thinking. Some thinkers, notably Howard Gardner, have identified a range of intelligences. These include cognitive intelligence, and both the intrapersonal and interpersonal aspects of emotional intelligence, as well as other intelligences such as musical and spatial intelligence. Can you help explain a few reasons why Emotional Intelligence is such an important characteristic? Can you share a story or give some examples? It helps us enjoy life more, and deal with the ups and downs with greater equanimity. When we avoid the so-called negative emotions, we can end up feeling less of the positive ones too. Being open to experiencing the full range of emotions connects us with our own humanity and allows us to see more of what we have in common with other human beings, rather than what divides us. Would you feel comfortable sharing a story or anecdote about how Emotional Intelligence has helped you in your life? We would love to hear about it. This is a personal example. My lovely father died a few years ago. I believe that my emotional intelligence helped me because I was able to feel the grief when it came along in waves, without feeling I needed to push the feelings down. Although the waves of grief were intense, by allowing myself to really feel the feeling in my body, I noticed that the waves of emotion moved through me quite quickly. They returned of course, but over time the waves came less often, and the intensity decreased in its own time. Can you share some specific examples of how Emotional Intelligence can help a person become more successful in the business world? 1. Leadership An essential area is leadership. Leaders need to able to connect with people, and it’s difficult to do this if you don’t understand yourself and the impact you have on others. It’s hard to lead and manage effectively if you lack sensitivity to others’ feelings, or if you are too reliant on other people’s approval. A leader or manager with poor emotional intelligence may have a devastating effect on the wellbeing and morale of their team, and consequently the performance of the business. There’s a good reason why emotional intelligence is such an important component of many leadership programs. 2. Decision making It’s also an important component of effective decision making in business. We may like to think that we make decisions logically and based on facts but there is evidence that we often make decisions based on emotion and post-rationalize afterwards. Understanding how our emotions affect our thinking helps us to recognize this risk, and look for ways to mitigate it, such as inviting different viewpoints, and being open to being challenged. 3. Self-motivation A third example is self-motivation which is often considered a core component of emotional intelligence. Being able to motivate ourselves helps us through the inevitable challenges of working life. It allows us to stay on track in our jobs and careers when times are tough. One way to increase your ability to self-motivate is to understand how to tap into positive emotional states. Consider what you say to yourself when you feel motivated, and what body language and posture you adopt when you really want to do something. Find ways to transfer that self-talk and posture to other contexts. Something else that I find helpful is to break down a big task into small steps. This motivates me with a sense of ongoing progress, as I take a moment to acknowledge each mini achievement along the way. Can you share a few examples of how Emotional Intelligence can help people have better relationships? It can help us connect more deeply and sensitively with other people and makes it less likely that we will project our negative emotions onto others and blame them for how we feel. It’s important to be honest in relationships, whilst taking ownership of our own thoughts and feelings. To give you an example: I may feel irritated when I get home late from work and the kitchen is a mess. Owning this feeling, and saying “I feel irritated when…” is very different to projecting blame on the other person, for example by saying “You’re lazy because you didn’t clean up…” The latter is likely to provoke defensiveness and arguments, the former can open-up a conversation about what matters to each person in a relationship. Another example is that emotional intelligence can make it easier for us to enjoy and celebrate other people’s success. Empathy allows us to step into another person’s perspective and allow ourselves to share their joy. Can you share a few examples of how Emotional Intelligence can help people have more optimal mental health? It can help us to recognize more quickly when pressures in our lives are getting on top of us, and work out if we need to make changes, such as reducing our workload or improving our sleep routine. Being aware of our emotions can alert us when we’re not coping and might need professional support. Emotional intelligence can allow us to seek help before we break down. It can also help us to notice when we are putting pressure on ourselves. Sometimes this may be a reaction to an external trigger, that we then amplify through self-criticism, or an unwillingness to forgive or let go of resentment. A degree of emotional intelligence can prevent us moving into a downward spiral, by helping us to understand and accept ourselves more easily. We all get angry for example, but if we can accept this emotion, we’re less likely to metaphorically “beat ourselves up” for getting angry. Instead, we can identify strategies to release excess anger and return to a calmer state of mind. Even where our anger is justified, we can make better choices about how to respond and take action, once we’ve calmed down a little. Ok. Wonderful. Here is the main question of our interview. Can you recommend five things that anyone can do to develop a greater degree of Emotional Intelligence? Yes of course, here are a few ideas. 1. Increase Emotional Awareness Firstly, start to notice your emotions. At different points during the day, simply stop and ask yourself “how am I feeling?” I’ve just asked myself this question and have realized I feel quite calm on the surface, but with an undercurrent of mild irritation because I’ve been interrupted several times this morning. Can you observe how your feelings change continually? And can you notice your triggers, the ways in which different people and situations affect you? A good technique for increasing this level of awareness is writing. You might like to use a prompt question, such as “how am I feeling now?” and spend a few minutes writing down everything that comes to mind, as honestly as you can. If you do this every day for a few days or weeks, you might like to read back over your notes, to see what you notice. How easy did you find it to identify your emotions? What patterns do you observe, in your emotional reactions? 2. Learn calming strategies Be aware that when we are in the grip of strong emotions such as anger or fear, these prevent us from thinking clearly. In working with your own emotions, it’s helpful to identify short-term strategies that can help you stay calm when you need to be, as well as strategies that may help you deal longer term with difficult emotions. In my experience, the most effective short-term strategy is to bring attention to your breathing. Breathing normally happens outside our conscious control, and yet we can also consciously change the way we breath, and this can affect our physiology quite significantly, in a short space of time. When I’ve been in situations where my emotions start to take over, such as waiting to give my first-ever keynote talk, I found just focusing on my breath helped me to stay calm and focused. Practice slowing down your breathing, a little, and allowing the outbreath to be slightly longer than the inbreath. I find a comfortable count of 5 for the inbreath and 8 for the outbreath works for me, but experiment with a rhythm that’s comfortable for you, and never force it. To learn about the power of breathing for health and wellbeing, I highly recommend the book: “Breath: The New Science of a Lost Art” by James Nestor 3. Tune into other people, through listening and observation My third recommendation is to become more aware of the emotions of other people, by developing empathy. Empathy is the ability to put yourself in someone else’s shoes, to try and see the world through their eyes. You don’t need to agree with the person. Instead, it’s about becoming more skillful in understanding how another person thinks and feels. The key to empathy in my view is being able to listen accurately and without judgement. This means put your own thoughts and emotions to one side for a while, and fully focus on another person. Listen to what they are saying, and importantly, how they are saying it. Notice someone’s body language, and tone of voice as well as their words. For example, can you observe tension in their face or the way they hold their shoulders? Is their tone of voice consistent with what they are saying? To help you relate empathically, I recommend approaching a conversation with a clear intent to really listen to the other person. If you find your attention wandering during the conversation, then remind yourself of this intent. Refocus on the other person and allow yourself to stay interested in discovering their perspective. How do they see the situation? How do they feel about it? 4. Support others in expressing emotion My fourth recommendation links to the previous one, and it’s a way you can support other people in dealing with their emotions. As mentioned earlier, strong emotions can prevent us from thinking clearly, and often the best way to help people is to simply listen to them. Allow them to talk through or vent how they are feeling. Show people that you’re listening, by checking your understanding of what they’ve said. Once people feel heard, they are much more likely to be open to your ideas or words of wisdom. Honoring people’s emotions by being willing to listen can be very powerful. An example is when someone is grieving. You can’t take away someone’s grief, but you can make it ok for them to express it. To give a work-based example, imagine that a team member is upset about the introduction of a new way of working. Try allowing them time to express their negativity for a while, without judging them. Once you’ve done this, they may be more open to moving on to a practical discussion about how the change can be implemented. 5. Read novels! My final tip is slightly different – read novels! A good novelist will take us inside someone else’s reality and help us really see the world through their eyes. There is also research evidence that reading novels can help people develop empathy. Watching quality drama and film may also help, if reading isn’t your thing. I personally feel that great novels do this best because they take us directly into someone else’s thinking, so we are seeing their world from the inside out. Ok, we are nearly done. If you could inspire a movement that would bring the most amount of good for the greatest number of people, what would that be? You never know what your idea can trigger. To live peacefully and well in a plural society, I believe we all need to develop a willingness to listen and try to understand other people, even when we don’t agree with them. Become more curious about different points of view. Why do other people see the world the way they do? What can you learn from people who see a situation differently? So, I think the movement would be to encourage more conversations that are about genuine openness to hearing different points of view, without setting people against each other. A good conversation in my view is one where both people go away feeling they have expanded their understanding of other people and other worldviews. As a professional facilitator, I know that good facilitation can help enable these kinds of discussions. Thank you for these really excellent insights, and we greatly appreciate the time you spent with this. We wish you continued success. Source: This interview was first published in August 2022 in Authority Magazine.
https://felicitydwyer.com/emotional-intelligence/
Irritable bowel syndrome (IBS) refers to a group of gastrointestinal symptoms characterized by abdominal pain and change in bowel function. It is an extremely common health issue impacting patients physically, socially and emotionally. While the cause of IBS is unknown, it does not lead to damage of the intestinal lining or increase the risk of cancer. It can affect patients at any age with many patients dismissing their symptoms as something else. It’s important for patients to understand the symptoms of IBS to be properly diagnosed and set on a path for managing and living with the condition, including ways to minimize symptoms and discomfort. Symptoms Common symptoms of IBS include abdominal pain and changes in bowel habits – including constipation or diarrhea. Associated symptoms include cramping, bloating, nausea and excessive gas. These symptoms can be never-ending and greatly affect someone’s daily activities and mood. Patients experiencing any or a combination of these symptoms should visit their doctor to be examined. Diagnosis To diagnose IBS, doctors may evaluate a patient’s medical history, dietary habits, and lifestyle and conduct a physical examination. In some cases, blood and stool samples may be tested and a colonoscopy or upper endoscopy may be done. There is no test specifically designed for diagnosing IBS, but doctors are able to test a patient for other conditions that could be causing the same or similar symptoms, such as inflammatory bowel disease or microscopic colitis. Managing IBS Patients diagnosed with IBS are usually referred to a gastroenterologist who can help them manage their symptoms. Management typically includes changes in diet, lifestyle and stress levels. Patients who fail to benefit from these adjustments also have the options of medication and mental health counseling. A gastroenterologist can help the patient navigate the best treatment options. If you are experiencing symptoms of IBS, visit a primary care physician or gastroenterologist to discuss your situation. UCF Health offers gastroenterology specialty care from its offices in Lake Nona and East Orlando. — Weekly Health Tips are brought to you by UCF Health, the College of Medicine’s physician practice. Offering primary and specialty care under one roof, UCF Health treats patients age 16 and up in primary care and age 18 and up for specialty care. Most major insurance plans are accepted. Two locations are now open: the original in East Orlando at Quadrangle and University boulevards just blocks from the main UCF campus, and the newest one in Medical City at Narcoossee Road and Tavistock Lakes Boulevard. Information for both facilities can be found at UCFHealth.com, or call (407) 266-DOCS to schedule an appointment. Subscribe to Weekly Health Tips Get Health Tips from UCF Health in your email each week! Subscribe here.
https://ucfhealth.com/health-tips/diagnosing-and-managing-ibs/
Hello, thank you for contacting us. We understand your concern regarding your daughter’s condition. The symptoms might cause discomfort to her and this causes some changes in her behavior. There are few causes that might explain her symptoms, such as: Avoid the nuisance stomach problems with the right care for your digestive system. However, this is is only our general impression why she is having such symptoms and further evaluation is needed to find out the cause. The need to do endoscope is depending on the doctor’s impression on diagnosis on your daughter. She may need or may not need it. Talk to a gastroenterologist to address your stomach problems and get their expert opinion. You may try this method to restore her activities: If you have any more inquiries, do not hesitate to contact us at (DoctorOnCall) for further explanation by our doctors. Thank you.
https://www.doctoroncall.com.my/tanya/ampen/gastritis-or-dyspepsia-in-a-17-year-old-mildly-autistic-girl/119241
What it is? Polyps in the gallbladder are the formations of a benign nature that occur on its internal mucosa. The shape of the polyps is round or oval. Some entities may have a foot. Usually there are single polyps. Excessive growth of formations is called polyposis. According to statistics, the disease is more often fixed in women older than 30 years. history of liver diseases: hepatitis, cholecystitis, cholelithiasis, etc. The gallbladder is a hollow organ whose walls are composed of several layers, one of which is muscular. Due to its functioning, the bladder contracts and evacuates the bile into the lumen of the duodenum so that further digestion takes place. Promotes the formation of cholesterol polyps congestion of bile. They arise for many reasons. The most important of them are: violation of the diet, stress, etc. As a result, the concentration of bile changes. It stagnates, becomes thick. The altered composition of bile leads to abnormalities in the wall of the organ. Against the background of changes in the wall of the gallbladder, stones begin to form, which lead to an inflammatory process. In turn, inflammation contributes to the formation of true polyps. Just as they often are located on a thin leg. Basically, the disease (with a small number of polyps and their small size) is accompanied by an asymptomatic course. The growth of polyps is characterized by the appearance of symptoms characteristic of cholecystitis and dyskinesias. Very often, they are randomly determined by ultrasound. Symptoms of the disease are manifested in large polyps, which violate the evacuation of bile and lead to dyskinesia. The disease is characterized by the following symptoms: pain in the right hypochondrium, severity, nausea after eating, etc. A little later, dyskinesia turns into cholelithiasis. It is with these symptoms that the patient often turns to a specialist. The above symptoms are characteristic of many diseases of the gallbladder and ducts. That is why the doctor prescribes an ultrasound method. With its help, a polyp is defined as a small formation adjacent to the inner membrane of the bladder. Another reliable instrumental method is endoscopic ultrasonography, in which the patient swallows the sensor, as with FGDS. The sensor allows you to more accurately know the smallest structure of the body. It produces high quality images. Therapists, a gastroenterologist and a surgeon deal with the treatment of the disease. polyp growth rate. The growth of a polyp by 2 mm more per year is considered fast. A provoking factor in the growth of education is pregnancy. That is why, after finding a polyp in the gallbladder more than 1 cm in size with a tendency to grow, the doctor prepares the patient for a planned surgery (cholecystectomy), during which the polyp is removed along with the gallbladder. Small polyps that do not manifest themselves with clinical symptoms are monitored using an ultrasound method once a year. Special control is exercised over the polyps sitting on the leg. When they are examined every six months. With polyps, as well as after cholecystectomy, it is important to observe a special gentle diet. Excluded products containing coarse fiber, cholesterol, essential oils, spices. Products must be consumed in a twisted, finely chopped form. Food should be ingested often up to 6 times a day and in small portions in the form of heat. Per day is recommended to use at least 1.5 liters of water. Traditional medicine offers proven recipes used to treat a disease in non-admitted cases. It is important to remember that all traditional methods must be approved by a doctor. 5) Effective with polyps collection of the following herbs: watch three-leaf, immortelle flowers, peppermint, coriander. Any course of treatment must be completed with a control ultrasound. Which doctor to contact for treatment? If, after reading the article, you assume that you have symptoms characteristic of this disease, then you should consult a gastroenterologist for advice.
https://zapatosmx.com/health/polyps-in-the-gall
Just this morning the Trump campaign released a second letter from Dr. Bornstein. But this time the doctor rather humbly concludes, “In summary, Mr. Trump is in excellent physical health.” These letters from Dr. Bornstein’s letter demonstrate a modern-day moral dilemma in providing care for a party nominee. At conflict is the physician’s professional duty to respect patient confidentiality, and his or her obligations to care for society more broadly. First, patient-doctor confidentiality is not merely a byproduct of the law—it is a moral obligation grounded in the core tenants of the medical profession. To put it simply, if a patient comes to expect that his doctor will tell the entire community about the patient’s most embarrassing bodily defects, the patient may understandably deny his worsening symptoms of poor health at the next office visit. In the long run, erosion of trust in the medical system could endanger the public’s health–everyone is thus better off when doctors uniformly respect patient privacy. It is important to point out, however, that an informed and competent person can voluntarily waive one’s right to patient-doctor confidentiality, such as when a patient gives a physician the permission to provide updates to family members. Or when then-candidate John McCain instructed his physicians all 1,100 pages in his medical records. At the same time, doctors are also under a moral obligation to promote overall well-being. Typically, these obligations are couched in the language of public health, like administering routine vaccines to decrease the burden of preventable disease. Nonetheless, it seems reasonable that if a sitting president undergoes surgery, the president’s doctor has a responsibility to the public to not prematurely announce complete recovery, lest the president unknowingly order a nuclear strike before the effects of anesthesia wear off. When these two obligations conflict, from both an ethical and legal standpoint, there are certain situations where societal welfare trumps patient confidentiality (and yes, that pun was intended). For instance, diagnosing certain communicable infections obligates doctors to file a report with the CDC. Likewise, announcing that an individual was quarantined is morally palatable when the injustice of disclosing his or her health information is considered against an epidemic with massive human suffering. With all of this in mind, the first letter signed by Trump’s gastroenterologist brings up two related questions. First, at what point does a doctor’s obligation to societal well-being justify breaking a candidate’s confidentiality? And second, when a person voluntarily runs for president, exactly how much health information is the public entitled to know? As it currently stands, the extent to which an individual’s medical record is made available remains within the power of each candidate. The American Medical Association sanctions this policy in its code of ethics, which permits releasing at most, “only information specifically authorized.” A problem with this is the improbable scenario where a candidate is diagnosed with a disease that limits (or will limit) one’s capacity for decision-making, and the candidate declines to publicly share this information. Unfortunately, calls for non-partisan solutions have gone unanswered. In 1994 Jimmy Carter published an article in JAMA urging creation of an independent panel of healthcare experts to help determine whether a sitting president is unable to fulfill his or her constitutional duties as a result of medical disability. Ethicist Arthur Caplan has long-argued that non-partisan health evaluation would help prevent candidates from self-censoring important medical details. Dan Diamond from Politico points out this would also quell the swirling health conspiracy theories. In prior elections, presidential candidates have largely been more forthcoming about their health. Even though the nominees in the current race retain the prerogative to keep health information out of the public eye (which, actually, reminds me of tax returns…), their physicians should still categorically refuse to release statements about their candidate’s health when the medical facts are intentionally misleading or outright false. Complying with such a request is a straightforward conflict of interest, readily comparable to a doctor who gets paid for publishing a favorable drug review in a good journal. Scoring a gig as the president’s gastroenterologist is just not worth endangering public trust in the profession.
https://blog.petrieflom.law.harvard.edu/2016/09/15/confidentiality-or-public-disclosure-trumps-gastroenterologist-and-an-ethical-dilemma/
Dr. Mahesh Mahadik is one of the best medical gastroenterologists in Pune. Dr. Mahadik Mahesh Rangrao has been a Consultant Gastroenterologist at many hospitals in Pune. Dr. Mahesh Mahadik is committed to providing state-of-art services in the diagnosis and treatment of various gastrointestinal diseases having the skill to perform both diagnostic and therapeutic endoscopic procedures. Having been trained in one of the best Departments of Digestive Diseases, Tata Memorial Hospital, Dr. Mahesh Mahadik further went on to get. Columbia Asia Hospital Pune Dr. Mahesh Mahadik has experience in this field for over 11 years. MBBS Dr DY Patil Medical College 2004 DNB (General Medicine) Miraj Medical Centre, Miraj 2009 DNB (Gastroenterology) Tata Memorial Hospital and Research Centre, Mumbai 2015 English Monday 9:00 AM - 11:30 AM Wednesday 9:00 AM - 11:30 AM Friday 9:00 AM - 11:30 AM Gastroenterologists are the physicians who have extensive training in the diagnosis and treatment of conditions that affect the large intestine, small intestine, stomach, esophagus, and biliary system which is made up of liver, pancreas, gallbladder, bile ducts. Gastroenterologist primarily assesses the structure of the digestive tract and are experts in diseases of the digestive tract. They specialize in the evaluation, diagnosis, and treatment of the following symptoms and conditions: Abdominal pain, bleeding in the digestive tract, colorectal cancer, stomach cancer, pancreatic cancer, liver cancer, constipation and diarrhea, difficulty swallowing, polyps, diverticular disease, Crohn's disease, gallbladder disease, irritable bowel syndrome (IBS), colitis, heartburn, GERD (gastroesophageal reflux disease), hemorrhoids, stomach upset, nausea, vomiting, and ulcers. You should see a gastroenterologist if you're experiencing any of the following symptoms: A gastroenterologist treats any condition affecting the gut, such as: Endoscopic ultrasounds to examine the upper and lower tract and other internal organs. Colonoscopies to detect colon cancer. Cholangiopancreatography to identify tumors, gallstones, or scar tissue in the bile duct area. Sigmoidoscopies to evaluate blood loss in the bowel. Liver biopsies to assess fibrosis and inflammation. Capsule endoscopies to examine the small intestine. Double balloon enteroscopy to examine the small intestine. Your gastroenterologist will begin by asking you about the symptoms you have been getting, the duration of the symptoms, any previous tests, and treatments, risk factors, other medical problems, medications, allergies, and social history and will conduct an examination and provide a list of tests.
https://www.logintohealth.com/gastroenterologist/mahesh-mahadik
Coeliac disease is an autoimmune mediated disorder of the small bowel, precipitated by gluten exposure in genetically predisposed individuals1. It is characterised by an inappropriate immune response to dietary gluten with chronic inflammation and damage of the small bowel mucosa leading to bowel symptoms and nutrient deficiencies. Although classically thought of as a disease affecting younger individuals of European descent, coeliac disease is increasingly found in populations in North Africa, India, China and the Middle East2 and the most common age for diagnosis is between 30 and 45. Coeliac disease is a common disorder in Australia, affecting one in 70 individuals, however, it is estimated that 80 per cent remain undiagnosed3. Coeliac disease can present with classical, overt symptoms but most patients present with atypical or subclinical disease. Primary care physicians have a critical role in recognising the diverse manifestations of coeliac disease and improving rates of diagnosis. What symptoms in my patient should make me consider coeliac disease as a diagnosis? The clinical manifestations of CD can be classic, atypical or subclinical. Classic symptoms are more common in infants and young children and include diarrhea or steatorrhoea, flatulence, abdominal distension and weight loss. In the majority of adults, the presentation of coeliac disease is subtler with only mild non-specific gastrointestinal complaints. In a meta-analysis with 3,383 subjects with coeliac disease, the prevalence of irritable bowel syndrome-type symptoms was 38 per cent4. These symptoms included erratic bowel habits, constipation, chronic abdominal pain and bloating. Some patients have subclinical disease with non-specific symptoms such as fatigue; have nutrient deficiencies (most commonly of iron) or are asymptomatic. Given the range of manifestations, the index of suspicion for coeliac disease required by the clinician is high. The 2015 NICE guidelines on coeliac disease provide recommendations on when to offer testing and when to consider testing for coeliac disease in individuals5. These are summarised in Table 1. Table 1: NICE 2015 Guidelines on when to test for coeliac disease |Offer testing to patients with any of the following:||Consider testing in patients with any of following:| | || | How do I test for coeliac disease? Serology is usually the first step in screening for coeliac disease. The following steps are recommended: - Is my patient currently on a gluten free diet? If no, proceed with serological testing. If yes, the patient must undergo a gluten challenge to avoid a false negative result. A gluten challenge consists of eating at least two slices of wheat-containing bread per day for at least four weeks6. - The following tests should be ordered: a. First choice: IgA anti-tissue transglutaminase (TTG) and total IgA b. Use IgA endomysial antibodies (EMA) if IgA tTG is weakly positive (IgA endoysial antibodies are highly specific but less sensitive than TTG antibodies) c. If IgA deficient, consider IgG based tests – IgG antiendomysial, IgG anti-gliadin, IgG-TTG d. Note: most Australian laboratories will include the following tests when “coeliac serology” is requested: i.Anti-gliadin (IgA and IgG) ii. Anti-TTG (IgA and IgG) How do I interpret coeliac serology? Positive serology If a patient’s screening serological tests are positive, they need to be referred to a gastroenterologist for gastroscopy and confirmatory small bowel biopsies. Serology alone is insufficient to make a diagnosis of coeliac disease. Negative serology Consider the following reasons for potential false negative coeliac serology: - IgA deficiency – affects two to three per cent of patients who have coeliac disease - Gluten free diet – serology can be negative after being on gluten free diet for more than three months - Children two years of age It is important to recognise that two to three per cent of patients with coeliac disease have negative serology, have low antibody levels or have levels that fluctuate between positive and negative1. Therefore, if coeliac serology is negative but the clinical suspicion of coeliac disease is high, the patient should be referred to a gastroenterologist for definitive histological testing. The role of genetic testing HLA-DQ2/8 genetic testing is useful in specific circumstances. HLA-DQ2 and or 8 are found in almost all patients with coeliac disease. However, it is also found in almost 50 per cent of the general population but only three per cent of these patients will develop coeliac disease1. Therefore, the main utility of HLA-DQ2/8 testing is to rule out coeliac disease: ie given that 99 per cent of patients with coeliac disease carry one of these markers, a negative test effectively rules out coeliac disease. A positive test is less useful and cannot be used for diagnosis7. When do I refer to a gastroenterologist? Refer to a gastroenterologist in the following situations: - A patient with positive coeliac serology for confirmatory small bowel biopsies - A patient with negative coeliac serology but high index of suspicion of coeliac disease Gastroscopy and histology A gastroscopy with small bowel biopsies is the only definitive way to confirm the diagnosis of coeliac disease. Patients must be on gluten to avoid false negative results. Macroscopically, the duodenal folds may appear flattened with scalloping or fissuring. On histology, the most characteristic features of coeliac disease include blunted or atrophic villi, increased intraepithelial lymphocytes (IELs) and crypt hyperplasia1. Increased IELs in isolation is a common finding and most patients with this do not have coeliac disease. Increased IELs without structural change can be due to giardiasis, helicobacter pylori infection, crohn’s disease and common variable immune deficiency1. Management of coeliac disease Gluten-free diet A strict gluten-free diet (GFD) lifelong is currently the only therapy for coeliac disease. All people with coeliac disease require a strict GFD, regardless of the severity of their symptoms. Initial referral to a dietitian with special interest in coeliac disease is highly recommended by local and international guidelines. A GFD reduces symptoms, improves morbidity, improves nutritional parameters and reduces the risk of long-term complications of coeliac disease including osteoporosis and lymphoma. Clinical symptoms usually abate within the first few weeks of commencing a strict GFD. A GFD implies that all wheat, barley and rye products must be avoided. Coeliac Australia3, recommends different groups of food that are suitable for those on a GFD. Naturally gluten-free foods includes fresh fruits and vegetables, legumes, milk, eggs, nuts and gluten-free grains such as rice and corn. Products labeled ‘gluten-free’ or have the ‘Coeliac Australia’ endorsement logo, also do not have gluten. It is important to avoid cross-contamination by avoiding products which ‘may contain gluten’. It is important to ensure the patient has adequate fibre and B-group vitamins, as these are derived from gluten-containing grains7. Patients are encouraged to join Coeliac Australia for excellent resources and links. Monitoring of coeliac disease After initial diagnosis, the general physician has a critical role in monitoring for disease activity and assessing for complications of coeliac disease. At six months in the first year following diagnosis and annually thereafter, the following should be assessed: - Coeliac serology - FBC - Folic acid, iron, B12, zinc - Thyroid function - Calcium, phosphate, vitamin D - Liver function tests A DEXA scan should also be organised within the first year following diagnosis. The gastroenterologist will usually organise a repeat gastroscopy and small bowel biopsies after 12 months to assess for persistent histological damage. Non-dietary therapy and future directions Non-dietary therapy such as corticosteroids and immune modulators, are restricted largely to refractory coeliac disease (1-2% of coeliac disease patients). Studies are underway on agents that prevent T cell activation, however only 2 at present are in phase 2 clinical trials1. References - Kelly CP, Bai JC, Liu E, Leffler Advances in diagnosis and management of celiac disease. Gastroenterology. 2015 May;148(6):1175-86. - Schuppan D, Dieterich Pathogenesis, epidemiology, and clinical manifestations of celiac disease in adults. UpToDate. 2015 - Coeliac Australia: Diagnosing Coeliac Disease- the key facts. http://www.coeliac.org.au - Sainsbury A, Sanders DS, Ford AC. Prevalence of irritable bowel syndrome-type symptoms in patients with celiac disease: a meta-analysis. Clin Gastroenterol Hepatol 2013; 11:359. - NICE (UK) guidelines: Coeliac disease: recognition, assessment and management (2015). nice.org.uk/guidance/ng20 - Ludvigsson JF, Bai JC, Biagi F, et al. Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gut 2014;63:1210–28. - Kenrick K and Day Coeliac Disease: where are we in 2014? Australian Family Physician 2015; 43:674-678 Dr Roslyn Vongsuvanh Suite 4, Level 1, Lakeview Private Hospital 17-19 Solent Circuit,
https://lakeviewprivate.com.au/coeliac-disease-in-2016-a-shared-care-between-gps-and-gastroenterologists/
#NACFC2016 – Close Gastroenterologist Monitoring of Patient Enteral Tube Feeding Urged by Cystic Fibrosis Foundation Recommendations by the Cystic Fibrosis Foundation (CFF) on enternal tube feeding for patients were supported by Jillian Sullivan, MD, from the University of Vermont Children’s Hospital today at the 30th Annual North American Cystic Fibrosis Conference in Orlando, Florida. Sullivan’s presentation,“Role of the Gastroenterologist in Enteral Tube Feedings,” was part of a symposium titled “CF Gastroenterology Comes of Age: Best Practices & DIGEST.” Adults and children with cystic fibrosis may find it difficult to maintain nutritional goals, but achieving optimal nutritional status is mandatory for the patients’ overall health. The CFF, recognizing the link between general health and lung function, urges all CF patients to achieve a nutritional status comparable to healthy people. The foundation recommends monitoring weight and height every three months. Enteral tube feeding refers to the delivery of a nutritionally complete feed (containing necessary protein or amino acids, carbohydrates, fiber, fat, water, minerals, and vitamins) through a tube inserted into the gut. The method is suggested as a possible strategy to help CF patients achieve recommended nutritional goals. The CFF had gathered a multidisciplinary expert panel to draft the list of recommendations for when enteral tube feeding is considered. They determined confounding causes of poor nutrition, patient education about enteral tube feeding, how to prepare patients for the feeding procedures, and how to manage the feeding tube after placement. Upon detecting suboptimal nutritional status, the CFF recommends that patients be monitored by a CF team composed of a pulmonologist, gastroenterologist, endocrinologist, registered dietician or nutritionist, clinical psychologist, nurse, social worker, and respiratory therapist or physical therapist. The team should determine the potential causes for inadequate caloric intake, gastrointestinal and endocrine complications, pulmonary exacerbations, and behavioral and psychosocial factors. Sullivan stressed that the team is vital for the placement of the feeding tube, with a CF-experienced gastroenterologist in the most important role. The gastroenterologist should determine the causes for poor appetite or malabsorption of food in undernourished CF patients before the enteral feeding tube procedure. Causes might include gastroesophageal reflux disease, gastroparesis, constipation, distal intestinal obstruction syndrome, small bowel bacterial overgrowth, CF-related liver disease, celiac disease, eosinophilic esophagitis, or inflammatory bowel disease. Sullivan emphasized that the multidisciplinary team should also discuss the risks and benefits of enteral feeding, including potential device options (nasal feeding tubes, gastrostomy tubes, jejunal tubes) and available placement procedures (endoscopic placement, surgical placement, or placement with interventional radiology). The timing for enteral tube feeding placement depends on the CF patient’s pulmonary status and other conditions, such as ascites, gastric varices, and intestinal dysmotility. Whether the patient had a previous abdominal surgery, and the potential presence and severity of gastroesophageal reflux disease, should also be considered. Further evaluations help decide what type of formula should be administered, the timing of formula infusions (ideally continuous nightly feedings), and the timing of pancreatic enzyme administration in pancreatic-insufficient patients. After the enteral feeding tube is placed, the patient should be monitored by a gastroenterologist or the surgeon, with follow-up continuing after the patient is discharged. The gastroenterologist will monitor the patient closely for complications that could include infection, displacement, drainage, pain, or other concerns. The patient’s nutritional status and any feeding intolerance or gastrointestinal symptoms should also be followed. The CFF advises that patients who receive enteral tube feeding should have annual evaluations with their gastroenterologist.
https://cysticfibrosisnewstoday.com/news/nacfc-enteral-tube-feeding-cf-patients-requires-gastroenterologist-close-monitoring-cystic-fibrosis-foundation/
- The biothreats pager has been retired. Please page Infection Control with questions. - Inpatient Clinical questions about COVID - For patients with COVID or suspected COVID who need ID input, please page the general ID consult pager. - The COVID Clinical pager has been retired. Please direct all COVID clinical pages to the ID consult pager. - Outpatient Clinical questions about COVID - See Ambulatory content below, or place an Infectious Diseases e-consult Case Definitions, Clearance, and Return to Work Case Definition - Currently BWH defines four statuses: - SARS-CoV-2: COVID-19 (also referred to here as “confirmed”) - Individuals who have tested positive for COVID-19 (either through NAAT or in select cases serologic testing) - Presumed-CoV (also referred to here as a “Person Under Investigation” or PUI) - Individuals with symptoms consistent with COVID-19 without positive NAAT to confirm. - CoV-Risk (also referred to here as a “Person Under Investigation” or PUI) - Individuals with symptoms consistent with COVID-19 and undergoing evaluation; some may have one or more negative test results, but interpretation of results is not complete or suspicion of infection persists. - CoV-Exposed - Asymptomatic individuals with known exposure to COVID-19. Case Clearance and Return to Work - Prolonged RT-PCR positivity is well documented but evidence indicates it does not correlate with ongoing infectivity, discussed in more detail in Clinical Course and Epidemiology: Transmission. Infectivity drops to near zero at approximately 10 days after symptom onset and 3 days after symptom resolution. The CDC and Partners’ guidance reflect this data with slight differences noted below. - CDC Recommendations - In the home setting, patients recovered from COVID-19 should be maintained in isolation for at least 10 days after illness onset and 3 days after recovery (whichever is longer). - A test-based strategy can be used for recovered persons for whom there is low tolerance for virus shedding and infectious risk (e.g, working in healthcare facilities, residing in congregate living facilities, immunocompromised, etc). - Partner’s time-based criteria (also used for employee return to work criteria): - 14 days after symptom onset (+ 3 days after symptom resolution) to clear outpatients recovered from COVID-19 (instead of 10 days as recommended by CDC and Massachusetts Department of Public Health). Note that MDPH recommends 14 days for return-to-work criteria for staff who care for immunocompromised patients. Since so many of the patients at BWH and Partners are immunocompromised, our 14 day rule deals with this caveat in a consistent manner. - Only using the 14-day rule (+ 3 days after symptom resolution) in Covid-19 patients who were never sick enough to be hospitalized; if patients were hospitalized, we use 14 days post-discharge, which generally translates into several weeks after symptom onset. - For now we retain the test-based criteria (at least 2 negative PCR swabs, in addition to symptom resolution and at least 10 days from first positive test) for Covid-19 patients who remain hospitalized. - See the latest Partners policy on infection status resolution (Partners login required) Personal Protective Equipment and Transport Personal Protective Equipment - Partners PPE Guidance (Partners login required) - There are location-specific differences (e.g., Shapiro SP-ICU versus Tower ICU COVID testing) in place, so refer to your location guidelines. - Easy to read “grid” summarizing PPE here (Partners login required) - Guidance for Aerosol Generating Procedures (Partners login required) - Strict isolation (aerosol) PPE (including N95 masks) are needed during and for 47 mins after these procedures. This now includes all patients, not just COVID confirmed or PUI. These should be preferentially performed in negative airflow rooms: - Intubation - Extubation - Bronchoscopy - Sputum induction - Cardiopulmonary resuscitation - Open suctioning of airways - Manual ventilation (e.g. manual bag- mask ventilation before intubation) - Nebulization - High flow oxygen therapy (15-60 L nasal cannula or mask) - Non-invasive positive pressure ventilation (e.g., CPAP, BIPAP) - Oscillatory ventilation - Disconnecting patient from ventilator - Upper airway procedures / surgeries - Upper endoscopy (including transesophageal echocardiogram) and lower endoscopy - Chest physical therapy - Autopsy - Thoracentesis/small-bore (pigtail) chest tube placement (due to the increased risk of cough) - BWH accepts donations of PPE or targeted funding for PPE - Step-by-step protocols for working in COVID-19 precaution patient rooms (e.g., transporting a patient, lab draws, micro testing like COVID-19 swab, sterile procedures like central venous catheters) Transport - Patient Transport Policy (Partners login required) - Please review policy before transport - Remember to communicate with the receiving department and technologists that the patient is COVID-19 positive or PUI. Patient should wear a surgical mask (or bacterial filter if intubated) and be covered with a sheet. Visitors - BWH Visitor Policy (public site) - Partners Visitor Policy contains additional details (Partners login required) - Presently one visitor per day is allowed for most inpatients Information for Patients - Basic information about coronavirus can be found on the Partners COVID-19 page. - COVID-19 Communication guide from Vital Talks and Ariadne Labs - PCOI handouts: English, Spanish, Portuguese, Arabic - CDC How to protect yourself and others - CDC What to do if you are sick - CDC Daily Life and Coping - CDC People who need to take extra precautions Ambulatory Clinic Workflow COVID Screening - Prior to in-person ambulatory visits, patients are screened for symptoms consistent with active COVID-19 infection or known COVID-19 infection. This screen is repeated on the day of a clinical visit when the patient enters a clinical care space. - Flowchart for pre-appointment, clinic, and high risk patient scheduling (In this flowchart, high risk is defined as High Risk for COVID infection) - If a patient has no symptoms, he or she can complete the visit under routine precautions, including universal mask policy. - If a patient has symptoms consistent with COVID-19 infection but does not carry a COVID diagnosis see Evaluation of Outpatients with COVID symptoms. Options include: - Providing virtual care (see below) and obtaining testing, or referring to the Respiratory Illness Clinics, or to the Emergency Department - Performing the visit if your clinic has the capacity to treat COVID +/ enhanced respiratory precautions patients - If a patient has a known COVID infection, see Management of COVID Outpatients. Options include: - Deferring care until clearance of the patient’s covid status (Partners login required) - Referring the patient to the Multispecialty Care Clinic - Performing the visit if your clinic has the capacity to treat COVID +/ enhanced respiratory precautions patients Screening Questions - Patients are asked the following screening questions before their visit AND at the time of check in for all ambulatory visits (specific clinics may have variations): - Do you have any of the following new symptoms (If yes, please note date symptoms began): - New Fever, new cough, sore throat, runny nose or nasal congestion, shortness of breath, muscle aches, loss of sense of smell or taste. - Have you been tested for COVID-19 outside Partners Healthcare (MGB)? - If “yes”, when was the test and what was the result - Have you spent at least 10 minutes within 6 feet of anyone with confirmed COVID-19? - If “yes,” when was the most recent date this occurred? - Are you, or a household member, currently on home isolation or home quarantine? Virtual Care - Virtual Care options are being used by many clinics to evaluate and triage patients as well as to perform routine care that does not require an in-person assessment as a strategy to mitigate risk to providers and to patients - Virtual care visits can be conducted from clinic or from home. - Virtual care options are described here - Virtual visit training, tools and billing questions are answered here. (Partners login required) - Additional tips for successful virtual visits are found here. (No login required) Ambulatory Evaluation of patients with COVID symptoms - Determine where the patient should be seen and tested - All patients who screen positive through the outpatient symptom-based screening process or who call providers with symptoms of COVID (Subjective/documented fever, new sore throat, New cough, New runny nose/nasal congestion, New shortness of breath, New muscle aches, or New loss of smell or taste, Atypical symptoms concerning for COVID-19 (e.g., COVID toes) should get PCR-based testing. See Diagnostics for more information about testing modalities, and the Partners COVID Testing Criteria for up-to-date testing criteria (Partners login required). - Mildly symptomatic patients order COVID-19 PCR test without an in-person visit at an outpatient testing site - Patients with moderate, concerning or progressive symptoms or comorbidities associated with higher risk for severe illness may warrant referral to Respiratory Illness Clinic (see criteria below) - Patients with severe symptoms should be sent to the ED for evaluation (see criteria below) - Outpatient Testing Sites: - Order testing via an Epic telephone visit. See Ambulatory Epic Test Ordering Tip Sheet (Partners login required) at any of the testing-only locations. You can also contact our Epic Help Desk. - Testing can be performed as drive-through or walk-up. Both require a scheduled appointment, which will be made by the testing site after the order is placed - See Partners list of testing locations. (Partners login required) - Respiratory Illness Clinic (RIC): - RICs are designed for the care of patients with an urgent need to be seen for a respiratory complaint. COVID testing is available in RICs as are phlebotomy, EKG, and chest x-ray. - See Partners list of respiratory clinics and locations (Partners login required) - Follow up visits may occur with the referring provider - Suggested criteria for referral for urgent in-person evaluation at an RIC, but ultimately, this decision must be made on a case-by-case basis. - Pulse oximetry (if available) between 90-95% in a low risk patient - Dyspnea limiting usual ADLs in a low risk patient - Any dyspnea or pulse oximetry 90-97% (if available) in a high risk patient - To refer, conduct a telemedicine encounter and document: - completed COVID screening - confirm/update - Medications - Allergies - pertinent family or social history (e.g. smoking) - describe the reason for referral - describe a differential diagnosis - order any pre-visit orders (EKG, CXR, labs) - Emergency Department: - Below are suggested criteria for ED referral, but ultimately this decision must be made on a case-by-case basis. - Pulse oximetry less than 90% - High risk patients with pulse oximetry less than 95% or moderate dyspnea - Severe dyspnea with inability to speak in complete sentences - Mental status changes - Objective hypotension or orthostatic symptoms not responsive to oral fluid repletion - Chest pain Ambulatory COVID Management Remote Evaluation - Candidacy for remote evaluation: - Remote evaluation of COVID-19 is challenging as progressive hypoxemia can occur rapidly, sometimes in some patients with minimal symptomatology. It is important to evaluate both the duration of illness and trajectory of current signs/symptoms. Maintain a low threshold for referral to the ED or clinics (some are capable of COVID+ visits) for pulse-oximetry and in-person evaluation. - Frequency of Virtual Visits: - Routine follow up for low risk patients: Day 5 of symptoms - Routine follow up for high risk patients : Day 4, 7, and 10 of symptoms - More frequent follow up may be needed for patient with particularly high risk, concerning symptoms, or concerns about reliability - Instruct patients to call if worsening or new symptoms, as outlined below - Follow-up after discharge from inpatient: 2 days - Specific clinical questions can be directed to Infectious Diseases through e-consult as needed - Remote symptom evaluation: - Dyspnea and hypoxemia - If home pulse oximetry is available, have the patient measure their oxygen saturation. Patients with hypoxemia (oxygen saturation < 95%) should be evaluated in-person. - No evidence-supported remote measure of hypoxemia is yet available. Strategies that may help risk-stratify patients include: - Establish trajectory of dyspnea. Studies of hospitalized patients indicate that dyspnea, when it occurs, develops 5-8 days into symptomatic illness, with ARDS at 8-12 days. (CDC, accessed June 16, 2020) Thus, a patient with progressive dyspnea, particularly early in the course of symptoms, requires very close follow up. - Assess whether dyspnea interferes with activities of daily living - Have the patient count as quickly as possible without breathing and record which number they reach before pausing for breath - Assess for tachypnea, cyanosis and use of accessory muscles - Mental status and function: - Decline in change in alertness, memory, behavior and attention should prompt in-person evaluation. - Patients with recent falls or near falls should be evaluated in-person - Chest pain: - Should prompt in-person evaluation in ED. While described extensively as a feature of COVID pneumonia, the high rates of cardiac and thromboembolic complications necessitate rule outs for ACS and PE - Dizziness and hypotension: - Assess for orthostatic symptoms, dizziness, mental status changes, reduced urine output as signs that blood pressure may be reduced. - Ask patient to use a home BP cuff if available - Leg and calf swelling: - This should prompt evaluation for VTE as both arterial and venous clots are seen in COVID infection - Fever: - Very high fevers should prompt discussion of oral intake and whether the patient is able to keep up with insensible losses In-Person Evaluation - Clinic: - With reopening some clinics may have capacity to see COVID + patients with appropriate precautions - Multispeciality Care Clinic: - The MSCC is dedicated to participating specialties that need to see their patients who are COVID+ for time-sensitive, ongoing treatment that cannot be performed virtually. - Location: inside the Hale BTM building in the 1st Floor Partners MS Clinic space - Hours of operation: Monday, Wednesday and Friday from 8:30am-11:30am, Tuesday and Thursday from 1:30pm-4:30pm. - Both the hours of operation and clinic specific workflows are subject to change. - Emergency department: - Criteria for referral remain the same as above in Evaluation of Outpatients with COVID symptoms - Direct admission: - This requires admitting privileges, call Admitting x27450 to see if beds available, then discuss with admitting service attending. Healthcare proxy designation - For all patients with COVID a goals of care conversation and a healthcare proxy form should be completed (regardless of age, comorbidity, severity, and virtual vs in-person visit) Reducing household transmission - COVID-19 patients should be recommended to self-isolate at home to the extent possible, to reduce risk of infection of other household contacts. - Housing on a separate room or floor, if possible - Using separate bathroom, if possible - Maintaining 6 foot distance from other household contacts - Masking when around other individuals in the household - Cover coughs and sneezes - Frequent hand hygiene - Avoid sharing household items, such as dishes or silverware - Clean “high-touch” surfaces with a household disinfectant daily - For additional information on masks, social distancing, pets, and more see Transmission - Contact tracing: - Recommend that patients advise their close contacts to get tested - For patients with positive test results, the BWH lab automatically notifies the DPH; the DPH conducts contact tracing. Outpatient COVID Therapies - Antiviral therapy - Remdesivir, an intravenous RNA polymerase inhibitor has been shown to improve clinical recovery among inpatients with COVID (discussed in more detail in Therapeutics: Remdesivir), but is not available for outpatients - Benefit appears greatest when started promptly after development of hypoxemia (oxygen saturation < 95%), so consider early referral for inpatient management in high risk patients - Trials of other direct-acting antivirals are ongoing and upcoming (see Rally). - Anti-inflammatory and immune modulating therapy - We do not recommend routine use of corticosteroids in outpatients with COVID-19. A recent unpublished study shows that corticosteroids may be beneficial in hospitalized patients with severe or critical COVID-19. This evidence is discussed in more detail in Therapeutics: Corticosteroids. However, the use of corticosteroids has not been studied in outpatients, who would not meet enrollment criteria for this study. ) f indicated for other reasons, such as asthma or COPD exacerbation, corticosteroids should not be withheld. - Hydroxychloroquine (discussed in more detail in Therapeutics: Hydroxychloroquine) does not have any known benefit in the outpatient management of COVID. Trials of hydroxychloroquine for prevention and for treatment of hospitalized COVID did not demonstrate any clinical benefit and suggested increased adverse events. We do not recommend use of hydroxychloroquine outside of a clinical trial. - Other agents - Multiple other agents including azithromycin, ivermectin, vitamin C, and zinc have been suggested for use in COVID-19 outpatients, though no evidence supports their use. We do not recommend use of these agents outside of a clinical trial. - Antipyretics - Either acetaminophen or NSAIDs are appropriate if there are no contraindications. For further detail, see Therapeutics: NSAIDs - Short-acting beta agonists - May be helpful for reactive airways in patients with underlying asthma or COPD, but otherwise not routinely indicated - Use metered-dose albuterol inhalers whenever possible given the risk of aerosolization with nebulizers. - If patients are unable to use these, it is reasonable to use nebulized therapy, ideally alone in a room with a closed door - For further detail, see Therapeutics: Bronchodilator Therapy - Expectorants - Guaifenesin or other expectorants may be helpful, particularly for patients with difficulty clearing thick sputum - Thrombosis prevention - Arterial and venous thrombotic complications of COVID are now well documented. We do not recommend routine use of aspirin or anticoagulants in COVID-19 among ambulatory individuals without another indication outside of a clinical trial - Recommend encouraging frequent ambulation to reduce DVT risk in ambulatory patients - Self-proning - The prone position improves dyspnea and hypoxemia in some patients with severe COVID. Proning could be used while awaiting ambulance transfer or as part of terminal palliation Outpatient Medications - Angiotensin Converting Enzyme Inhibitors (ACEI) and Angiotensin II Receptor Blockers (ARB): - In line with guidance from the American Heart Association, American College of Cardiology, and Heart Failure Society of America, we recommend against discontinuing ACEIs/ARBs in the outpatient setting. - For further detail, please see Therapeutics: ACEIs and ARBs. - Non-steroidal anti-inflammatory drugs (NSAIDs) - We recommend against discontinuing NSAIDs in patients who use them chronically. - For further detail, please see Therapeutics: NSAIDs. - Immunosuppressive agents: - The role of immunosuppressive medication in COVID-19 risk is complex, and discussed in more detail in Immunosuppressed Patients. - Continuation of these agents in the setting of COVID-19 disease should be addressed on a case-by-case basis with the primary prescriber and/or appropriate subspecialist. Ambulatory COVID Exposure Management - Patients may call for counseling about COVID exposure risks. Carefully assessing the context of possible exposures is important to minimize anxiety of lower-risk exposures and identifying higher-risk exposures to prevent onward transmission. - Definition of COVID exposure - By CDC criteria, a person is considered infectious: - If symptomatic, from 2 days before symptom onset until meeting criteria for discontinuing isolation. - If asymptomatic, from 2 days before date of positive test until meeting criteria for discontinuing isolation. - An exposure is defined as being within 6 feet of a known COVID+ person for greater than 15 minutes. - Using a similar exposure definition, investigators found 13% of exposed individuals subsequently developed COVID-19 (Boulware et al, NEJM, 2020) - Features that likely increase transmission risk including: actively cough/sneezing, close proximity, confined indoor spaces, and physical contact with individual or shared objects. - Contacts that occur outdoors and/or with both individuals wearing masks should be likely be considered as low risk. - Recommended isolation precautions - COVID-exposed people should self-isolate at home and maintain 6 feet distance from other individuals. - They should avoid exposure to individuals at high risk of severe COVID disease. - Symptoms should be self-monitored throughout this time and prompt testing following development of symptoms. - Duration of isolation is 14 days from time of last exposure. - Prophylaxis - At this time, there are no known effective pre- or post-exposure prophylaxis for COVID-19. - A large trial of hydroxychloroquine as post-exposure prophylaxis demonstrated no benefit and increased risk of self-reported adverse events in the treatment arm. (Boulware et al, NEJM, 2020) Emergency Department Protocols - This includes screening, patient and provider PPE, rooming, testing - This includes decision to discharge, monitor, admit to Special Pathogens Unit, or admit to ICU - EMWeb (Specific access required, limited to ED personnel) - This is shared protocols and documents specific to the emergency department COVID Inpatient Management Note and Lab Templates - Add the COVID Dashboard to your EPIC patient list (Partners login required) - Brigham and Women’s Specific Epic smartphrases - Inpatient COVID admission note (SPUADMITNOTE) - IMPORTANT: This is an example of possible templated note/phrase. Smartlinks are NOT universal across computer systems. This note should not be copied and used directly for patient care. We are working to make templates available through the Epic Community Library. - Inpatient progress note (PACEPROGRESSNOTE) - COVID discharge counseling (SPUCOUNSELING) - Discharge instructions for PUI or COVID positive patients (SPUDISCHARGECOVIDPOSITIVE) - Discharge instructions for COVID negative patients (SPUDISCHARGE COVIDNEGATIVE) - Last set of COVID labs (LASTCOVID) - Lab ordersets: - COVID Admission Orderset (COVID 19 Add On) Early Advance Care Planning - In conscious patients, review or sign Health Care Proxy form and discuss and document goals of care on admission - Educate patient and family on disease course and prognosis - Focus on desired quality of life and tolerance for ICU measures - Early consultation of palliative care if appropriate. See “Palliative Care” Medical management - Management is largely supportive. Antiviral and immune-modulating therapies are investigational. Please see “Therapeutics” and “Infectious Disease” for further details Fluid management - Fluid management should be conservative due to risk of hypoxia/CHF. Please see “Sepsis” for more information on dynamic fluid management Hypoxemia Management - Please see “Hypoxemia Management” Geriatric Patients - Frailty, immunosenescence and multimorbidity placed older adults for increased risk of adverse outcomes - Older patients may present differently: - Use lower fever criteria: one oral temp > 37.8C or two oral temps > 37.2C (IDSA criteria) - More likely to present with atypical symptoms such as altered mental status, decreased appetite, non-focal pain - If patient presenting from facility, call facility to notify of COVID-19 positivity - Include FRAIL frailty screen on initial assessment. - If patient screens positive for frailty or has a history of dementia, delirium, or is a nursing home resident, page geriatrics tele-consult pager (Pager #38251) Bedside Procedures - 24/7 COVID-specific procedure teams are available to do bedside procedures (pager #39299). Specific teams, hours of availability, and instructions are outlined here. Triage to ICU - Provider concern - Respiratory distress - Need O2 > 6 LPM to maintain SpO2 > 92% or PaO2 > 65. - Rapid escalation of oxygen requirement. - Significant work of breathing. - Hemodynamic instability after initial conservative fluid resuscitation - SBP < 90, Mean arterial pressure < 65, or Heart rate > 120. - Acidosis - ABG with pH < 7.3 or PCO2 > 50 or above patient’s baseline. - Lactate > 2. - Need for intensive nursing care or frequent laboratory draws requiring arterial line. - Severe comorbid illness / high risk for deterioration. Discharge Planning Clinical Discharge Criteria - Consider discharge for patients who meet the following clinical criteria: - Resolution of fever >48 hours without antipyretics - Improvement in signs and symptoms of illness (cough, SOB, and oxygen requirement) Followup - Schedule routine follow up within 2 days of discharge with PCP as long as infectious status has been cleared, vs virtual visit if infectious status has not been cleared Disposition Options - Home with or without support services - Post-discharge phone call: ALL PUIs and COVID+ patients admitted to BWH and BWFH will have a post-discharge phone call with an Advanced Practice Practitioner (APP) within 24-48 hours of discharge. - Partners Homecare: Fully operational and accepting all appropriate PUI and COVID+ patients in need of visiting nurse services. Patients will be triaged for virtual and in person visits. - Home Digital Monitoring Program: Patients will receive an oximeter, thermometer, and will record symptoms, O2 saturation, and temperature daily on a mobile device or computer for 14 days. A nurse (with 24/7 MD backup) will call patients on the day of discharge and if recorded symptoms or vitals worsen. Contact care coordination for enrollment. - Facility - LTAC, short-term rehab, skilled nursing facility, Barbara McInnis House (undomiciled), Boston Hope Medical Center (low acute housing facility) - CMS has waived the 3-midnight rule for discharge to a facility for all Medicare patients. - Please contact care coordination to assist with screening for all facility discharges and for the most up-to-date guidance on the need for COVID-19 testing prior to discharge, which varies by facility. Discharge Against Medical Advice - People are able to sign themselves out of the hospital against medical advice if they demonstrate decision making capacity. Please see the Psychiatry section on assessment of capacity. - For all discharges who are unable or unwilling to self-isolate, including undomiciled patients, call the Boston Public Health Commission at (617)-645-9680. - If you are unsure about whether a patient poses a significant threat to another individual, there is a legal representative available 24/7 to discuss.
https://covidprotocols.org/protocols/ambulatory-ed-and-floor-management/
Discuss the diagnostic criteria for constipation? At least 12 weeks (need not be consecutive) in the preceding 12 months of 2 or more of- Constipation is clearly very common. The role of the gastroenterologist is to assist in identifying selected patients with constipation who might benefit from additional testing or more specific treatments. Discuss the disorders of colonic motility and constipation? Constipation is the major feature of 2 disorders of colorectal motility. Discuss the clinical evaluation of constipation? What are the common medical conditions associated with constipation? Discuss the investigations to evaluate constipation? Patients who fail to respond to simple medical treatment after excluding contributing causes are appropriate candidates for more specialized testing. A simple, inexpensive radiopaque marker study will identify STC. Pelvic floor dysfunction needs to be excluded by performing anorectal manometry; if confirmed, defecography will solidify the diagnosis and evaluate anatomic defects. Discuss the management of STC? Normal transit constipation- can be treated with fiber and/or laxatives. Slow transit constipation- Surgical treatment of STC- Total colectomy with ileorectal anastomosis can be considered when medical treatment has failed. Patients need to be told that the procedure is designed to treat the symptom of constipation (difficult and infrequent evacuation) and that other symptoms (e.g., abdominal pain and bloating) that the patient associates with constipation may not necessarily be relieved by achieving regular defecation. Before surgery it is vital to exclude dyssynergia and if present should be treated before surgery or else ileostomy considered. The contraindication to surgery is presence of upper GI or diffuse motility disorder. Patients who continue to be constipated after ileorectostomy are likely to have abnormal pelvic floor function. Discuss the management of constipation due to pelvic floor dysfunction? Pelvic floor retraining- Biofeedback and relaxation training have been quite successful and, importantly, free of morbidity. Biofeedback can be used to train patients to relax their pelvic floor muscles during straining and to correlate relaxation and pushing to achieve defecation. By the relearning process, the nonrelaxing pelvic floor is gradually suppressed and normal coordination restored. Intensive programs in adults can have a 75% success rate or better. Discuss the laxatives used for constipation? Discuss Prucalopride in the treatment of constipation in women? Prucalopride (Resolor, Movetis) is a selective serotonin (5-HT4) receptor agonist that predominantly stimulates colonic motility. Prucalopride is administered orally. Dose: recommended dose of prucalopride is 2 mg once daily for adult women (up to 65 years old) and 1 mg once daily for older women (over 65 years). The dose for older women can be increased to 2 mg once daily if needed. If once-daily prucalopride is not effective after 4 weeks, the patient should be re-examined and the benefit of continuing treatment reconsidered. Side effects: most common adverse effects include headache and gastrointestinal symptoms (abdominal pain, nausea or diarrhoea). Most adverse effects occur at the start of treatment and usually subside within a few days of continued treatment. NICE 2010 recommends prucalopride as an option for the treatment of chronic constipation only in women for whom treatment with at least two laxatives from different classes, at the highest tolerated recommended doses for at least 6 months, has failed to provide adequate relief and invasive treatment for constipation is being considered. NICE further recommends that if treatment with prucalopride is not effective after 4 weeks, the woman should be re-examined and the benefit of continuing treatment reconsidered. Anal irrigation Anal / rectal irrigation may be an appropriate form of management for people suffering from chronic constipation. An anal irrigation system will contain everything you need to irrigate your bowels. An anal irrigation system will usually consist of a control unit with a pump, a water bag and a rectal catheter. For further information about the Peristeen anal irrigation system, please visit www.coloplast.co.uk Peristeen Anal Irrigation works by introducing luke warm tap water into the bowels using a rectal catheter. Principle: The principle behind the system is very simple. Peristeen Anal irrigation is performed by introducing lukewarm tap water into the rectum using a rectal catheter, whilst sitting on the toilet. The water fills up in the large intestine and causes the faeces to move onwards in the bowel. After introducing the appropriate amount of water (usually 500-1000ml) into the bowels, water and stools are emptied into the toilet. Anal irrigation is an alternative to other methods such as laxatives, suppositories and mini enemas. Peristeen anal irrigation system Please see the User guide video here Risks: Bowel perforation is an extremely rare (less than one in 100,000 uses) complication to anal irrigation (see recent MHRA alert) MHRA recommendation: Ensure that patients (and where appropriate carers): Before starting Peristeen Anal Irrigation, Coloplast instruct that patients should undergo a medical evaluation by a doctor with appropriate expertise to ensure that they have no conditions that preclude its use or require further investigation. Contraindications: Peristeen Anal Irrigation must not be used in the following situations: Peristeen Anal Irrigation is not recommended for: Special caution must be shown if you have or have had any of the following:
http://www.gastrotraining.com/colo-rectal/constipation/constipation/?print=1
Dr Tina Mehta is a Consultant Gastroenterologist and Endoscopist at Circle Bath Hospital. She graduated from the University of Bristol in 2000. She completed her medical and gastroenterology training in the South West. Her qualifications include MBChB, MRCP and MRCP Gastroenterology. During the postgraduate period Tina also undertook qualifications in education and training including a Postgraduate Certificate in Medical Education. As a trainee Tina authored and edited the text book now used internationally for the MRCP Gastroenterology postgraduate examinations. Her special interests include Inflammatory Bowel Disease and diagnostic and therapeutic endoscopy. Tina works closely with colleagues in upper and lower GI surgery, oncology and rheumatology when appropriate. Tina is married to Tim, and they have a son Rafe. She enjoys yoga, up-cycling furniture, cooking, socialising, gardening and looking after their chickens. Tina and Tim regularly travel abroad. Tina is a keen musician who regularly performs with her string quartet ‘The Cotswold Quartet’ at weddings and other significant events. Alongside her quartet Tina runs and leads two Bristol based orchestras; Brunel Sinfonia and Bristol Concert Series. Consultant Gastroenterologist and Endoscopist at the Royal United Hospital. Tina is also an experienced endoscopy trainer who teaches on the National Endoscopy Training courses, including ‘Train the Trainers’. Tina has pursued a keen educational interest at the Royal United Hospital as a current Royal College of Physicians College Tutor with a special interest in Core Medical Training. - Upper and lower GI endoscopy (gastroscopy, colonoscopy, flexible sigmoidoscopy and associated therapeutic and investigative procedures) - Inflammatory Bowel Disease including transition care for adolescents - Nutrition - Inflammatory Bowel Disease - Investigation and management of a variety of upper and lower gastrointestinal symptoms and disorders - Endoscopy training in her NHS practice Professional memberships - Royal College of Physicians - British Society of Gastroenterology - British Association of Enteral and Parenteral Nutrition Our Private Patient Advisors are available to answer your questions about becoming a patient on 01761422222 from 8am to 7pm during the week and from 9am to 1pm on Saturday.
https://www.circlehealth.co.uk/consultants/tina-mehta
Caring is an important tool for healing. Where I see patients (1) Contact me Soothing the soul Pediatric gastroenterologist Hiker, cook, farmer, lover of cats and language Dr. Elizabeth Gleghorn, who goes by Beth, is a gastroenterologist who cares for children with all types of gastrointestinal (GI) disorders. She has special expertise in issues related to pain, feeding and growth, and defecation. Providing care in both hospital and clinic settings, she works with the patient, family, and rest of the GI team to find the sources of symptoms and work out a treatment plan. She performs procedures, including endoscopy, and has training in hypnotherapy, which can be used to address some GI issues. She works closely with nurse practitioners, registered dietitians and social workers to meet the needs of individual patients and families, and collaborates with other specialty clinics. Gleghorn's research focuses on GI disorders. Her current research examines the effects of cow's milk on toddler intestine and iron balance. Gleghorn earned her medical degree from Stony Brook University. She completed a residency in pediatrics and a fellowship in gastroenterology, hepatology and nutrition at Children's Hospital Los Angeles. Gleghorn is a member of the American Gastroenterological Association; North American Society for Gastroenterology, Hepatology and Nutrition; American Academy of Pediatrics; American Society for Parenteral and Enteral Nutrition; and Crohn's & Colitis Foundation.
https://www.ucsfbenioffchildrens.org/providers/dr-elizabeth-gleghorn
Abstract: Delusional infestations are psychodermatologic disorders in which those affected have a false belief they are infested by parasites and/or "growing" inanimate objects from cutaneous surfaces. Individuals with delusional parasitosis (DP) believe parasites, bacteria, worms, mites, or other living organisms are the source of cutaneous symptoms, while those with Morgellons disease (MD) attribute their symptoms to growth of small fibers or inorganic material. In both DP and MD, self-inflicted, non-healing cutaneous lesions caused by scratching at the affected areas to alleviate symptoms are commonly observed. This report describes a case of oral mucosal lesions in a patient demonstrating overlapping symptoms of DP and MD. It is important for oral healthcare providers to recognize oral signs and symptoms that may be associated with psychodermatologic disorders. Delusional infestations (DIs) are psychodermatologic disorders in which parasites or inanimate objects are associated with cutaneous symptoms, such as itching and/or burning.1 DIs were first described in 1894 and are also known as Ekbom syndrome, acarophobia, and parasitaphobia.2 These types of disorders are thought to be caused by increased levels of dopamine in the striatum and limbic cortex and can present as a primary complaint or secondary to medication, addictions, or infection.3-5 They have an estimated annual incidence of 0.7 to 3 per 100,000 individuals, and the most common type of DI is delusional parasitosis (DP), with higher prevalence in women 50 to 80 years of age.2,3 Unlike DP, Morgellons disease (MD) is characterized by cutaneous "growth" of small fibers and/or inorganic material.1,2 Controversy exists if DP and MD are independent conditions as they share similar epidemiological and clinical characteristics.1-3 Patients often produce parasites, hair, inorganic material, etc, collected from various sources and stored in containers to demonstrate the "infestation," commonly referred to as the "matchbox" or "specimen" sign.1-3 Self-inflicted, non-healing cutaneous lesions are typically observed in both DP and MD, as patients attempt to alleviate symptoms by continuously scratching the affected areas. Psychiatric counseling and use of antipsychotics are first-line therapies for management of these conditions.1-3 Historically, patients were treated with pimozide (dopaminergic receptor blocker); however, this medication was associated with high prevalence of extrapyramidal side effects and elongated QT.6,7Second generation antipsychotics are now used more frequently, such as olanzapine, aripiprazole, and risperidone, which are effective with significantly fewer side effects.2,5,8,9 Patients may also benefit from supplementary anxiolytic and antidepressant medications, such as fluoxetine and doxepin. This is particularly effective when patients present with additional complaints and are nonresponsive to initial therapy.10 Non-pharmacologic treatments of DIs include biofeedback, relaxation, hypnosis, and talk therapy. Due to wide variation in treatment efficacy, patients with DIs often express frustration and distrust of the medical system, which frequently results in them resorting to self-treatment, often with pesticides, or seeking help online.8 Patients may be resistant to psychiatric management due to insistence of the physicality of their symptoms and a perceived stigma associated with psychiatric disorders.11 Intraoral lesions associated with DIs have been previously reported; however, these lesions have been attributed primarily to a single diagnosis.12 The aim of this report is to describe a case of oral mucosal lesions in a patient demonstrating overlapping symptoms of DP and MD. Case Report A 53-year-old woman presented for evaluation of lip lesions of 6 months' duration. She described her lesions as "round horns" that felt rubbery and stretched and were symptomatically relieved by her scratching them. The patient reported the lesions started as a swelling associated with burning and itching, and she believed they were caused by a "parasite trying to crawl out of her lip." The patient had been evaluated previously for this complaint by several healthcare providers and was empirically treated with nystatin, cephalexin, mupiricin, prednisolone, valacyclovir, and intra-lesional steroid injections without benefit. She underwent multiple diagnostic tests that were negative for viral, fungal, and bacterial organisms, and previous biopsy of a lip ulcer revealed nonspecific ulceration, granulation tissue, and necrosis. Past medical history was significant for attention deficit hyperactivity disorder, hypothyroidism, C-spine spondylosis treated with C5-7 discectomy with fusion and glaucoma. Review of systems was unremarkable. Medications included dextroamphetamine, levothyroxine, bromfenac sodium, and timolol maleate. Physical examination revealed a well-nourished, well-developed female. Extraoral examination did not reveal lymphadenopathy, salivary gland enlargement, or cutaneous lesions. Intraoral examination demonstrated multiple ulcerations primarily on the right lower labial mucosa and lip (Figure 1). At that time, clinical findings were suggestive of DP, and treatment recommendations included a referral for psychiatric evaluation and fabrication of a maxillary occlusal appliance and mandibular soft splint for daily use to prevent self-mutilation from biting. The patient was resistant to psychiatric referral and treatment, but open to medical and physical therapeutics. On subsequent evaluations, she reported that a clear wire or ingrown hair might be the cause of her lesions, suggestive of MD, and she scratched her lips to allow the hair to exfoliate. At that time, she was prescribed topical clindamycin 1% and topical doxepin 5% for application to the lesions daily, in addition to the soft splints, with clinical improvement after 1 year of treatment (Figure 2). Of interest, the patient did not produce a "matchbox" or "specimen" sign at any time, nor did she pursue or receive any type of psychiatric care for her suspected psychodermatologic disorder(s), although it was recommended to her on multiple occasions. Discussion Psychiatric disorders commonly encountered in dental practice include depression, anxiety, adjustment, and somatoform disorders.13-15 Psychodermatologic conditions are less common in the general population; therefore, oral healthcare providers (OHCPs) are less likely to be familiar with these disorders. In this case, the patient initially stated the cause of her oral lesions was a parasite, which is suggestive of DP. However, on subsequent evaluations the patient believed her oral lesions were attributed to inanimate objects, specifically a wire or a hair, which is suggestive of MD. Therefore, the authors concluded that overlapping features of DP and MD were present in this patient. The authors continue to encourage psychiatric evaluation as part of her overall treatment. In this case, the patient resisted recommendations to consult with a psychiatrist for evaluation and management of possible DIs. If OHCPs recognize signs and symptoms of undiagnosed DIs, it is important to be sympathetic to the patient's complaints and to discuss referral, psychiatric evaluation, and management in a supportive manner. If a patient has been previously diagnosed with a type of DI, OHCPs should determine if the patient is receiving care from a psychiatrist and if the patient's condition is being actively managed. Oral mucosal lesions associated with DIs may be managed with topical medications, such as anesthetics, antibiotics, and/or corticosteroids.12 In addition, fabrication of occlusive splints can potentially minimize trauma to the affected areas. In the present case, it should be noted that topical antibiotic and steroid treatment was administered prior to the patient presenting to the authors. The authors presumed that the rationale for that treatment was a possible inflammatory reaction, which the steroid would have helped, while recognizing that the mouth ulcer may have been secondarily infected, warranting the antibiotics. The authors note, however, that indiscriminate use of steroid on the vermillion surface will result in atrophy. Patients managed with antipsychotics may experience increased sedation and are at risk for further central nervous system depression with concomitant use of narcotics and/or anxiolytics.12 In addition, adverse oral effects, such as xerostomia, dental caries, candidiasis, glossitis, sialadenitis, and extrapyramidal movements of oral structures may be evident in patients using antipsychotics, all of which may impact provision of oral healthcare.12 Conclusion OHCPs are not only responsible for maintaining optimal oral health, but also for being able to potentially identify systemic diseases, including psychiatric disorders.16 DIs are rare psychodermatologic conditions, and it is imperative for OHCPs to: (1) recognize these conditions; (2) refer patients to the appropriate healthcare provider for further evaluation and/or management, if warranted; (3) understand the impact of DIs on the oral and maxillofacial region; and (4) provide safe and appropriate oral healthcare to patients with these conditions. About the Authors Sausan Alfaris, BDS, MPH Postdoctoral Student, Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania Katherine France, DMD, MBE Resident, Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania Thomas P. Sollecito, DMD Professor and Chair of Oral Medicine, Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania Eric T. Stoopler, DMD Associate Professor of Oral Medicine, Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania References 1. Heller MM, Wong JW, Lee ES, et al. Delusional infestations: clinical presentation, diagnosis and treatment. Int J Dermatol. 2013;52(7):775-783. 2. Freudenmann RW, Lepping P. Delusional infestations. Clin Microbiol Rev. 2009;22(4):690-732. 3. Lepping P, Freudenmann RW. Delusional parasitosis: a new pathway for diagnosis and treatment. Clin Exp Dermatol. 2008;33(2):113-117. 4. Koo J, Lebwohl A. Psycho dermatology: the mind and skin connection. Am Fam Physician. 2001;64(11):1873-1878. 5. Thakkar A, Ooi KG, Assaad N, Coroneo M. Delusional infestation: Are you being bugged? Clin Ophthalmol. 2015;9:967-970. 6. Brown GE, Malakouti M, Sorenson E, et al. Psychodermatology. Adv Psychosom Med. 2015;34:123-134. 7. Bhandary SK, Peter R, Bhat S. Delusional parasitosis in ENT. Indian J Otolaryngol Head Neck Surg. 2008;60(4):387-389. 8. Bhatia MS, Jhanjee A, Srivastava S. Delusional infestation: a clinical profile. Asian J Psychiatr. 2013;6(2):124-127. 9. Bhushan P, Thatte SS. The dermatoscope: a new tool for delusional parasitosis. Clin Exp Dermatol. 2016;41(6):690-691. 10. Delacerda A, Reichenberg JS, Magid M. Successful treatment of patients previously labeled as having "delusions of parasitosis" with antidepressant therapy. J Drugs Dermatol. 2012;11(12):1506-1507. 11. Vulink NC. Delusional infestation: state of the art. Acta Derm Venereol. 2016;96(217):58-63. 12. Grosskopf C, Desai B, Stoopler ET. An oral ulceration associated with Morgellons disease: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112(2):e19-e23. 13. Brodine AH, Hartshorn MA. Recognition and management of somatoform disorders. J Prosthet Dent. 2004;91(3):268-273. 14. George S, Saksena A, Oyebode F. An update on psychiatric disorders in relation to dental treatment. Dent Update. 2004;31(8):488-494. 15. Kino K, Sugisaki M, Ishikawa T, et al. Preliminary psychologic survey of orofacial outpatients. part 1: Predictors of anxiety or depression. J Orofac Pain. 2001;15(3):235-244. 16. Stoopler ET, Sollecito TP. Focusing on the medicine in dental medicine. Spec Care Dentist. 2016;36(2):59.
https://www.aegisdentalnetwork.com/cced/2018/04/oral-mucosal-lesions-associated-with-overlapping-psychodermatologic-disorders
If Hegel is the philosopher of the Intellect, Schopenhauer is the philosopher of the Will. He takes his start from Kant's Critique of Pure Reason and holds that the thing-in-itself which for Kant was an unknowable noumenon is knowable directly in one's own self as volitional activity. The Will is the thing-in-itself. Schopenhauer's Will is not the individual psychological will, but a universal metaphysical principle, spaceless and timeless and uncaused, even as Hegel's Reason, as he held, is not merely an individual function. The Will, says Schopenhauer, manifests itself in the individual as impulse, instinct and craving. The Will, again, it is that appears as consciousness and body. Thus the true self of man is identified with the Will. Everything in the world, too, becomes an expression of the Will. The world is Will and Idea and has no independent material existence. The Will is above the Idea and is the only reality. The Will is blind, unconscious, and the Idea which is conscious is only its appearance in the intellect. We see nothing anywhere except the Will and the body which is the expression of the Will. Right from unconscious matter up to the self-conscious man the Will alone reigns supreme. It appears unconscious in something and conscious in another. It is all strife, activity, yearning that we observe everywhere. Desire is the cause of all things. With the Yogavasishtha, Schopenhauer would say that there is the eye because there is desire to see, there is the ear because there is desire to hear. The body and bodily functions are the expression of the Will. The digestive organs are the objectifications of hunger, the feet of the desire for movement, the brain of the desire for knowledge. There can be no body, and no world, without the Will. Longing, craving, or function, determines the nature of being, of the kind of organisation which becomes the body of the Will. The Will-to-live is the root of all things. It is the cause of struggle, suffering, pain. The Will is the great evil that accounts for the misery of all beings. Schopenhauer's concept of the Will is fascinating. The Will is the Reality and it is blind urge. Consciousness or intelligence is its phenomenal effect made manifest in higher organisms in order to pave the way for the work of the Will in the world. For Schopenhauer intelligence is not the essential nature of the self. It is only a production of the brain created by the Will for its own purposes. Consciousness is an appearance, Will the Reality which is the immortal force that never dies with the death of individuals, never perishes through change. It may manifest itself in a mortal shape as individuals, but it cannot itself cease to be. The Will is imperishable being. Schopenhauer's Will is more like the Mula-Prakriti of the Vedanta, which is essentially unconscious activity, rather than Reality whose essential nature is consciousness. Individual consciousness which expresses itself in the intellect is defined by the constitution of Prakriti whose representation is the intellect. Intellect is the medium through which intelligence becomes manifest. But, in the Vedanta, Prakriti is not Reality, and consciousness is not the expression of Prakriti. Consciousness is the essence of Reality which is beyond Prakriti. But it is true that the intellectual intelligence in man is controlled by its unconscious Master, the Prakriti with its primary modes of Sattva, Rajas and Tamas. Perhaps the Freudian psychoanalysts would be friendly with Schopenhauer as he would be an aid in demonstrating their theory of psychological determinism, that the conscious is always determined by the nature of the unconscious, and that free will is an illusion produced by the false notion that the conscious is independent of the unconscious. Instinct, craving, urge, is at the root of even the operation of reason. We are here reminded of Bradley's saying that metaphysics is the finding of bad reasons for what we believe upon instinct, and that to find these reasons, again, is no less an instinct. But the urge for knowledge is not an irrational blind force. The instinct that makes it impossible for us to desist from the noble enterprise of metaphysics is a super-rational aspiration which voices forth the longings of the infinite in us. Schopenhauer's blind Will cannot answer to this deepest truth in us, nor can the unconscious of Freud go beyond a mere sum of the unmanifested creative impressions and impulses left by our past conscious acts, since ages. Consciousness is not a by-product of the unconscious Will, any more than it is a secretion of the material brain. Schopenhauer's theory that consciousness is only a mirror of the unconscious Will is, as it can be very easily shown, an untenable assumption. The arguments against materialism naturally level themselves against this view of Schopenhauer. How can consciousness be manifested by an unconscious principle unless it is hidden in the unconscious itself? If consciousness is latent in the unconscious, then the unconscious itself must be endowed with consciousness, though we may accept that this consciousness remains unmanifested in it. If consciousness is different from the unconscious, it is not even a manifestation of the unconscious, and in this position even the existence of the unconscious cannot be known for want of any relation between consciousness and the unconscious. We can as well say that the unconscious does not exist at all. If, on the other hand, consciousness and the unconscious are one in essence, the unconscious gets illuminated by consciousness and its essence becomes consciousness. Even on this supposition the unconscious ceases to be. If it is said that the unconscious alone is, and there is no such thing as consciousness, we say that, as in that case no one would know that there is the unconscious there is no warrant for the supposition that the unconscious exists. Schopenhauer can convey to us no meaning by asking us to run away from Reality or to overcome Reality. Reality cannot be abandoned or destroyed or overcome; it is the Supreme Being which every one has to realise in one's own self. How can such a Reality be a blind Will, a body of craving that brings misery? Instead of asking us to rise from phenomena to Reality, he wants us to be rid of Reality. Moreover, the Real should necessarily be the good. It requires no argument to prove this, for the Real is naturally not different from one's own self. Have we to flee from our own selves? Has this teaching any sense? Schopenhauer's Will, the evil principle, has to be considered a cosmic conception of the individual will which is characterised by the evil of craving. A cosmic being, by itself, cannot be evil, for no ethical or moral value, desire, pleasure or pain can be attributed to what is super-individual. Evil is meaningful only in the individual, not in Reality. We can accept the theory of a primordial unconscious cosmic existence, as the Prakriti of the Vedanta, and a conscious Idea appearing in it, as Isvara or Hiranyagarbha. But we cannot make even this conscious Idea an appearance of the unconscious, for consciousness cannot proceed from unconsciousness. We have to posit a Reality whose essential nature is consciousness and which manifests itself in the cosmic unconscious as the conscious Idea. Further, the evil has to be confined to the individual psychological will which is a spoilt child of the cosmic Will, and should not be taken to the cosmic Will itself which is a metaphysical principle transcending good and evil. Schopenhauer's advice that one should free oneself from the evil will amounts to nothing more than that one should transcend individual existence, and cannot mean that one should avoid Reality itself, which is an impossibility. He has made the mistake of objectifying the individual will in the cosmos and calling it a metaphysical Reality. Even if everyone's will is to be evil, it does not mean that the cosmic Will is evil, for even all individual wills put together cannot make the cosmic Will. The argument against Kant's supposition that the categories of the understanding, objectively present in the sense that they are in all men, determine the nature of perceived objects, applies also to Schopenhauer's belief that the evil will has a metaphysical existence. Will is not Reality; it is the dynamic executive power of consciousness, cosmically as well as individually. In the cosmos it is free; in the individual it is bound and determined. Schopenhauer's philosophy has, however, great value if only we would take it in its application to psychology, and not as a fully convincing system of metaphysics, not forgetting at the same time that while psychology is concerned with the behaviour and the functions of the individual mind, it is totally ignorant of the transcendental aspirations and the sublime conscious endeavours of the higher spiritual reason in man. Our want, says Schopenhauer, determines and is at the bottom of our reasonings. It is not because we reason that we want; reason is the servant of want. Want is considered to be the master of even the reason. We cannot influence people by appealing always to their understanding; understanding is dominated by volitional cravings. We have to appeal to the Will which is the seat of desire. Schopenhauer thinks that there is no use of reasoning and argumentation with people,—they can never be persuaded or convinced by appeal to reason,—they yield when the activities of their Will, their private cravings, their urges, their interests are appealed to. We forget what we merely understand; we remember what we desire. Reason or understanding is a mere tool in the hands of the cravings and fears of the Will. The Will-to-live, not the understanding, is the mainspring of all action. Schopenhauer would agree with us if we say that all life is a struggle for food, clothing, shelter, sex and protection from outside attack. Only we have to add, though Schopenhauer never seems to have had the patience to reflect over it, that there is another higher instinct, a secret aspiration in man which supersedes all the lower instincts, the aspiration for the wisdom of Truth, notwithstanding that this is rarely seen in most human beings. Organic attraction and mechanical pull are both to Schopenhauer expressions of the Will-to-live. This Will tries falsely to overcome death by self-reproduction. This is why, says Schopenhauer, the sexual urge is so strong in all beings. It is just another phase of the Will-to-live, the assertion of its immortality, its attempt to live eternally as an individual of the species. The instincts for self-preservation and self-reproduction are not different from each other. The latter is only the process of ensuring the existence of the former in the future, too. Hence there is only one instinct, the turbulent, unquenchable Will-to-live. The intellect has no power over this instinct. Schopenhauer makes the romances of love merely the subtle contrivances of the Will-to-live, the instruments used by it in its dark and wild operations to preserve itself. He concludes that sexual love brings misery to the individual because its aim is not the pleasure or the good of the individual but the continuation of the species, for which Nature shrewdly covers the reason of the individual and induces it to lay faith in the illusion that this is for its own pleasure and good. Thus the attempt of the Will to immortalise itself ends in its defeat, for what is here immortalised is not the individual but the species. The individual has been cleverly deceived! Pleasure has no place in the process of the preservation of the species. Here Schopenhauer gives merely a psychological interpretation of the Will-to-live asserting itself as the Will-to-reproduce. Its metaphysical implications are to be discovered in the dialectical process of Hegel and the ‘satisfaction' of ‘actual entities' in the philosophy of Whitehead. The neutralisation of the thesis and the antithesis in the synthesis, which is the way in which all things create and recreate themselves and which Hegel employed to describe the integrating process of the higher evolution of the individuals towards the realisation of Self-consciousness in the Absolute applies distortedly in relative individuals, ignorant of any such higher purpose, to the reproduction of individualities. In Whitehead the Hegelian dialectic continues in an elaborate manner. The actual entities of Whitehead supply the data which are sought to be unified into the ‘satisfaction' of the innate urge to create. An ‘actual entity' is said to enjoy the process of creating itself out of its data, feel a ‘satisfaction' in its self-emergence. An ‘actual entity' becomes a ‘subject' when it emerges out of the pre-existing world of actual entities. The implied meaning of all this is that a creative urge is immanent in all things, which in its higher liberating archetypal existence becomes an integrating conscious march to the realisation of the Absolute, and in its lower binding reflected aspect in mortal individuals assumes the form of a blind seeking to perpetuate the species. Here the lower becomes a travesty of the higher. The Greek philosophers had evidently this in their minds when they held the extraordinary view that sexual love represents in the world of sense a shadow of Divine love. The Hindu ethics, too, regards marriage not as a contract of love, but as a sacrament, a devout union of souls for the fulfilment of a purpose higher than the mundane. It was not any element of passion but a dutiful surrender to law that determined the meaning of marriage in ancient Hindu society. It was a spiritual aim that directed the union of the sexes. A note, however, has to be added that all this is true metaphysically and in highly advanced societies, but the ordinary individual in the world of sense gets perpetually blindfolded and stupidly forgetting all spirituality in the nature of things, does not only fail to benefit by these higher implications, but heads towards a fall into the mire of bondage and grief due to its cravings. As a rule it has to be held that there is no possibility of discovering the spiritual in external objects as long as one is locked within the prison-house of a world of ignorance, desire and attachment. Schopenhauer gives the lower empirical side of the picture, and does not rise to these heights which we know the man of today is not endowed with the ability to understand. For Schopenhauer marriage is the disillusionment of love, a trick by which every one is made to fall a victim to the blind Will. The Will can be conquered, says Schopenhauer, by overcoming the Will-to-reproduce. The Will-to-reproduce is considered the greatest evil, for it seeks to perpetuate the misery of individual existence. Schopenhauer says that passions can be subdued by the domination of knowledge over the Will. Most of our troubles would cease to be troubles if only they could be properly understood in relation to their causes. Self-control provides to man the greatest protection against all external compulsion and attack. True greatness is in self-mastery, not in victory over the worlds. The joy of the within is greater than the pleasure of the outside. To live in the self is to live in peace. The evil Will can be overcome by conscious contemplation on the truth of things. Schopenhauer even recommends the company of the wise and intimate relations with them as aids in this contemplation. Knowledge is the great purifier of the self of man. When the world is viewed not by sense but by knowledge, man is liberated from the evil and bondage of the Will. Knowledge takes us to the universal essence. How can this profound insight be consistent with the notion that consciousness, intelligence or knowledge is only a phenomenon, an appearance of the Will? How can knowledge give man freedom from the Will if it is only a creature projected by the Will? Further, when the Will is Reality and also blind and evil, there can be no such thing as freedom, for the ultimate aim of existence is to return to Reality, and so the eternal experience that we have to aspire for ought to be one of unconsciousness, evil. How can Nirvana from the Will or the attainment of happiness and peace be possible, which Schopenhauer so forcibly pleads for, if the Will is Reality and consciousness its effect? How could Schopenhauer give us a chaste philosophy through his intellect if the intellect is an appearance of the evil Will? Will not then his philosophy itself become a product of blind craving and evil? Schopenhauer gives evidence to a confused mind which longs for universal and eternal freedom in perfect knowledge, but which at the same time condemns this longing by denouncing Reality as a blind and evil Will. His resignation to asceticism which, he says, can destroy the Will and enable one to attain freedom shows that the Will is not Reality but a clinging to individual existence, and that Reality is freedom, happiness and peace. A recognition of the limitations and sufferings, cravings and evils in the relative world ought to be no doubt the beginning of any true philosophy. But Schopenhauer commits himself many times to extreme statements which a sober mind will find difficult to appreciate fully. The limit is reached when Reality itself is jibed as evil. Such a theory is the result of an imperfect and one-sided view of life, though at times, side by side with an expression of prejudice and personal sentiment, he gives intimations of profound knowledge and a wisdom that cannot but win the admiration of the thinking world. Schopenhauer is no less a genius than either Kant or Hegel, but his genius often gets marred by certain immature conclusions, a defective metaphysics and an attempt to give the touch of wholeness to what is only one side of the nature of things. There is evil when craving rules our realm, but beyond all this is a goal which is unsurpassable splendour and bliss eternal and which we are bound to achieve. However, it has to be admitted, in the end, that Schopenhauer has done a great service to mankind by drawing its attention to the fact that life is not all roses, that there is a dark and bitter side of existence here, that there is ignorance, deception, suffering and pain, and that no philosophy which ignores this truism can ever hope to be complete.
http://www.swami-krishnananda.org/phil/phil_13.html
? Or, as others claim, is it a fundamental reality like space, time, and matter? In recent years the nature of consciousness -- our immediately known experiences -- has taken its place as the most profound problem that science faces. Now in this brilliant and thoroughly accessible new book Colin McGinn takes a provocative position on this perplexing problem. Arguing that we can never truly "know" consciousness -- that the human intellect is simply not equipped to unravel this mystery -- he demonstrates that accepting this limitation in fact opens up a whole new field of investigation. Indeed, he asserts, consciousness is the best place from which to begin to understand the internal make-up of human intelligence, to investigate our cognitive strengths and weaknesses, and to explore the possibility of machine minds. In elegant prose, McGinn explores the implications of this Mysterian position -- such as the new value it gives to the power of dreams and of introspection -- and challenges the reader with intriguing questions about the very nature of our minds and brains. About the Author Colin McGinn is Professor of Philosophy at Rutgers University. He is author of several books, including The Character of the Mind; Moral Literacy; Minds and Bodies: Philosophers and Their Ideas; Ethics, Evil, and Fiction ; and Mental Content . Product Details ISBN: 9780465014231 ISBN-10: 0465014232 Publisher: Basic Books Publication Date: April 26th, 2000 Pages: 256 Language:
https://www.mcnallyjackson.com/book/9780465014231
Meditation is a great mystery. It’s a profound and unfathomable topic. The subject of meditation is the nature of the Self. The object of meditation is also the nature of the Self – and — it is also that which unites the subject and the object. This is the meaning of vastness. At some blessed point meditation is no longer practiced, but it is a full, palpable Realization. No one knows how this mysterious condition of Enlightenment is entered into, or, how that Great Awakened Condition enters into one’s Self. In some sense, we have to be anesthetized from being the observer of how this happens. It is in that great feeling of innocence and purity that the Awakened Condition is born. Even the tiniest peek at this process will disturb and abort it. It does not function while the intellect is scrutinizing. The intellect enters into a spontaneous state of self-surrender. In that state of self-surrender, the Full Reality then can give birth to itself, without disturbance. So, one really does become like a child before that Vastness. Once meditation is truly triggered, it keeps on happening spontaneously, over and over again, until this Self-culmination of profound awaken-ness occurs. This is really an ecstatic topic: how one comes to be able to live so close to the edge of one’s life that even living day by day is like a near-death experience. One has become so thin, so translucent, so vulnerable that the Reality, the Cosmic Reality, can unveil itself through your Awakened Life. It is an excruciating State to live in. One is no longer kept safe and protected. This continuity of spontaneous meditation weans us off the addiction on illusion, the addiction of imagination, the addiction of fear, the addiction of pleasure, the entire addiction of conceptual reality. To be thrust from the conceptual into the Real is the essence of the Awakened Life. It is one thing to be Self Realized. It is still another to be given the Awakened Heart Consciousness. Self Realization is an empty barrel and the Awakened Heart Consciousness is like a barrel swirling with Light and Bliss and Energy. It is a state of being intoxicated in God, of abiding in God Consciousness. The more you have drunk of this Inner Emptiness, this Void Consciousness, this state of Eternal Nothingness, the deeper that has gone into you, the more profoundly you may become inebriated, later on, in the Resuscitated Condition of the Awakened-Heart, Divine Mother Consciousness. Self Realization is non-incarnated Bliss and the Awakened Heart Consciousness — in the Divine Mother — is Incarnated Bliss Consciousness. Right in this moment, this spacious moment, this innocent moment, this non-moment, one can feel that something is arising as Consciousness: not as some experience in Consciousness, but as Consciousness. One can feel this Thrill moving through the Un-manifest, through the Invisible. There have been great poets and sages and mystics who have sung this Immensity. It sounds extraordinary. It is Bliss beyond the superlative, until one dies into Pure Realization, forever. You will wonder where your practice of meditation has gone! As the Self is unfolding Itself to Itself, from within Itself, you will have all these Realizations of a Transcendental Nature: that you are the state of Being Itself, that there is no “other,” no separation, no sense of otherness, there’s Nothing. When you graduate into the actual Embodied Fullness of Meditation, then the Divine has adopted your life. The Divine Consciousness has then swallowed you and then it speaks Its Truth as your Existence, as your Life. So, as you can imagine, every conceivable fear will arise in that process. You will have the fear of being extinguished forever or the fear that you may never be extinguished forever. You will be backed into a corner, where everything about you comes under scrutiny — the scrutiny of Consciousness Itself, to reveal, the whole nature of human functioning, the whole nature of the urge toward survival, the urge toward pleasure, the urge toward pain and its avoidance. Everything will be brought into this magnified perception, in the present moment. In this present moment, everything becomes stark and real, for the first time. David: Right your question was, does this feeling of Emptiness, does the ability to retain discernment disappear in the state of Devotion — that was one of the good questions that you had asked — and also whether you lose Pure Awareness. Participant 4: That’s correct. David: And then I said: when you put Devotion together with Pure Consciousness Awakening you get a qualitatively Different State that arises, totally different than those two next to each other. Participant 4: Correct or added together David: Which means that they have become something greater, both of them; it sounds so simple what we’re saying but it’s not….I mean, it is. Participant 4: Yes, I am operating from a dualistic system. David: That’s OK, that’s all we have to go on. As soon as we open our mouth we’re put in this dualistic state together, but you’ll see that the Energy never ceases. The Transmission of the Full Reality here will not stop it will not pause. It will just continue in its own way. We just sense each other here — it’s so easy. We listen, we talk, we hear what isn’t being said. Sometimes we’ll feel ourselves just arising [as] Pure Consciousness.
https://davidspero.org/aiovg_videos/the-essence-of-the-real-may-7-2002/
The Department of Arts and Consciousness (A&C) in the School of Holistic Studies at JFK University helps students deepen their understanding of creativity as spirit, thought and process. Through an innovative combination of academic, technical and experiential courses, faculty members facilitate this awareness. This community of artists, formed by faculty and students, is dedicated to a common vision: As artists, we create objects and events that alter and enrich human consciousness. As teachers, we help our students discover their own, most profound sources of creativity and life. As healers, we use creativity and passion to promote well-being. We help the world by discovering and expressing the sacred within ourselves. The Department of Arts and Consciousness helps students go farther into the deepest levels of consciousness, and then return to the world of phenomenon and social interaction with new tools for change. This journey between the inner and the outer is the essence of Arts and Consciousness. A&C promotes dialogue about how art can reestablish itself as a central activity in human existence. Students and faculty discuss artwork not only in formal terms but in terms of transformation and inner awareness. Artists in the outside community and our students come together to create new ways for art to exist. The Arts and Consciousness Department is a place where change occurs-where we learn to create a new reality and a new culture.
https://www.idealist.org/en/nonprofit/ea610740453d40baa0a511c6976f09cc-department-of-arts-and-consciousness-berkeley
Much of the news most recently about discrimination in America has been focused on singular violent acts by police against African-Americans. Aside from these highly visible violent incidents, however, there is another broader issue, often unseen, but very much felt by multiple ethnic and racial groups. That is, we frequently do not recognize the serious long-term effects of various forms of discrimination and hurtful incidents on the health and economic outcomes of millions of individuals and their communities. And, as a nation, it would be for our common good to change how we talk about these broader sets of issues. My colleagues at the Harvard T.H. Chan School of Public Health, led by Robert Blendon, have conducted a far-reaching survey, in collaboration with NPR and the Robert Wood Johnson Foundation, asking people from multiple ethnic and racial groups, including whites, about their experiences with discrimination. This includes the policies of employers, governments, and civic institutions, and also individual behaviors leading to members of minority communities being insulted and facing offensive comments because of their backgrounds. A striking 60 percent of African-Americans say they have been unfairly stopped or unfairly treated by the police because they were black. Forty-five percent say they or a family member were unfairly treated by the courts. In addition, 32 percent say they have personally been discriminated against at a doctor’s office or health clinic. Perhaps not surprising to those who face discrimination, the survey shows how pervasive it is. It cuts across more aspects of life than interaction with the police and courts. It affects the job you will be hired for, your likelihood of renting an apartment or buying a house, whether you will be able to vote in future elections, and whether you are less willing to see a doctor for needed care. You might expect that these situations would go away after a minority, such as an African-American or Latino, reaches a certain socioeconomic status, but the opposite is true. Those with more education and with higher incomes tell us they face more discrimination in their lives. David Williams of the Harvard Chan School has shown in multiyear studies that acts of discrimination lead to a type of stress that over the long term causes serious illnesses and even premature death. Other studies have suggested that these experiences negatively impact lifelong economic opportunities for these groups. In addressing the health outcomes of individuals facing racial and ethnic discrimination, it is important to change the nature of the discussion we are having. We are led to believe, on one side, that this is an issue of political correctness, and on the other, that there is only a need to respond to individual instances of micro-aggression. But the long-term impact of these broad patterns of discrimination on health and economic outcomes must be our shared focus. This comprehensive range of circumstances in the aggregate — the multiple incidents and institutional behavior — where people feel discrimination must be addressed. As dean of a school of public health, I think it is imperative for us to spotlight the profound health implications of this inequity as a way to reframe the national discourse. The discussion must focus more clearly on the impact that discrimination has on all segments of American society and on the future of the country. That discussion must involve a continued re-examination by institutions and individuals of these unacceptable discriminatory behaviors and the importance of educating the public as a whole of their consequences. It should be better understood by all how discrimination affects the very future of our nation. If we cannot broaden the discussion, we will find ourselves in a situation where millions of people face serious health consequences — being very ill and often dying prematurely — or lack opportunity, resulting in many minority groups being unable to function effectively in America’s changing economy. Our country will be poorer and less just because of it.Dr. Michelle A. Williams is dean of the faculty and professor of epidemiology at the Harvard T.H. Chan School of Public Health.
https://www.bostonglobe.com/opinion/2017/11/24/the-broader-hurtful-impacts-discrimination/XRMC1Eunyq7rCksUTZ6ZnO/story.html?p1=AMP_Recirculation_Pos8
This Community is Archived. This community is no longer active as of December 2018. Thanks to those who posted here and made this information available to others visiting the site. GHDonline.org is pleased to host an online expert panel on the implications of PrEP as an emerging HIV prevention strategy. Our panelists, Douglas Krakower, MD , and Andrew Mujugira, MBChB, MSc will offer some initial thoughts and then we look forward to a week-long virtual discussion. Initial questions: 1. What are some potential barriers and facilitators to implementing PreP in clinical settings? 2. How can we encourage long-term adherence to PrEP outside the research setting? 3. What additional additional questions need to be answered with further research? Pre-exposure prophylaxis (PrEP) is a novel biomedical strategy being investigated for HIV prevention among diverse high-risk populations worldwide. Two completed clinical trials have demonstrated partial efficacy of PrEP in decreasing HIV acquisition risk by 39% and 44% respectively in heterosexual women and men who have sex with men (Abdool Karim et al 2010, Grant et al 2010). If safe and efficacious in ongoing trials, PrEP will likely be targeted to high-risk subpopulations. However, significant barriers will have to be overcome. Integrating PrEP into existing HIV prevention programs will require evaluation of cost-effectiveness, ongoing monitoring of HIV status, behavioral risk assessment, and provision of adherence counseling. High coverage will be required to achieve population-level reductions in HIV incidence. Maintaining long-term medication adherence in healthy asymptomatic individuals in real-world settings will be challenging. We find that linking adherence to activities of daily living is useful. In our studies, participants use radio news bulletins as reminders, or take medications with meals or at bedtime. Using pillboxes, diaries or cell phone alarms and involving a spouse or family members are useful adherence strategies. Further research is needed to evaluate long-term safety and efficacy, different formulations, plus alternative dosing and delivery strategies in HIV susceptible individuals, including those with chronic active hepatitis B infection and renal dysfunction, and in adolescents, pregnant and breastfeeding women. Monitoring rates of drug resistance and their impact on future treatment options will be important. Qualitative studies will help understand barriers to adherence, drug sharing with HIV infected persons and behavioral disinhibition. Finally, evaluating PrEP effectiveness in real-world conditions should be considered. This is a pretty interesting one. Well just out of curiosity, was thinking of us bringing something close to this on board. I mean what do you guys think of the effectiveness of HIV&AIDS counselling on behavioral change. Is HIV&AIDS counseling an effective tool to Behavioral change?. Just like in many HIV&AIDS service points, HIV counseling entails the development of a relationship between a counselor and client for the purpose of assessing risk for HIV infection or transmission, developing a plan to reduce risk, and assisting the client to cope with emotional and interpersonal issues related to HIV. The goal of client-centered HIV counseling is to conduct an individualized risk assessment, which may or may not include HIV antibody testing, and to develop an effective individualized risk reduction plan. Evaluation of the effectiveness of HIV counseling has been impeded by a lack of adequate outcome measurement instruments and concerns about the validity of self-reported behaviors. I think Critical research needs include definition of the mechanisms that facilitate enduring behavioral change, assessment of the cost-effectiveness of counseling, and identification of the structural and environmental barriers to effective counseling interventions.Guys What do you have to say about this.I want to conduct a research to measure the effectiveness of HIV&AIDS counseling on behavioral change. So any one who wants to join me in this initiative to please join me. or Email me on To the HIV prevention community: here is a post to help introduce the topic of PrEP: Translating the promising results of PrEP trials into clinical practice will require attention to several potential barriers and facilitators. Are people aware of PrEP and how to use it safely? Determining the most effective ways to educate potential PrEP consumers and healthcare providers in optimal PrEP use will be a priority. Innovative uses of existing public health infrastructure and media (e.g., the Internet) could facilitate dissemination of information on PrEP in some settings. Who should use PrEP? Identifying individuals who are most likely to benefit from PrEP will entail patient-provider communication around high-risk behaviors, though current levels of risk assessment in clinical practice are generally low in many settings. Efforts to reduce stigma associated with high-risk behaviors could enhance communication. Will PrEP be acceptable to high-risk individuals, providers, and other stakeholders? It is not known if asymptomatic individuals at high-risk of HIV acquisition will be willing to use prophylactic medications, or if providers will be willing to prescribe them given the potential unintended consequences of PrEP, such as adverse effects, increased risk behaviors , and the emergence of drug resistance. Further data on the safety, efficacy and behavioral implications of PrEP may influence acceptability. What are the cost implications for PrEP? Given resource limitations, some stakeholders may feel that funds should not be diverted to PrEP from provision of antiretroviral therapy (ART) to people living with HIV. Refined cost-effectiveness estimates could facilitate decisions around PrEP use as further data on its effectiveness in public use become available. Decreasing the cost of antiretrovirals through generic production of current PrEP medications or the use of less expensive agents are likely to impact cost considerations. Will patients adhere to PrEP regimens? Results from the CAPRISA and iPrEx studies suggest that adherence levels are likely to correlate strongly with prophylactic effect for PrEP. In these studies, adherence levels were suboptimal in substantial numbers of participants. Novel interventions to support adherence, such as the use of wireless technology (e.g., SMS messaging), could offer solutions. There are many future questions for study, including: How should PrEP be delivered? Oral and topical PrEP offer relative benefits and drawbacks, and understanding the most acceptable and effective way to deliver PrEP is likely to depend on the transmission dynamics of local HIV epidemics. Intermittent PrEP schedules may decrease cost and drug exposure and perhaps enhance adherence. Further studies to determine optimal delivery methods will be important. Who will prescribe PrEP? Most potential PrEP consumers will be cared for by primary care providers (PCPs), yet PCPs are likely to have variable comfort prescribing antiretrovirals. Understanding ways to engage and train PCPs to provide PrEP is warranted. Will PrEP increase high-risk behaviors? If individuals using PrEP increase risk taking, the net effect could be to increase the risk of HIV acquisition. Current studies do not suggest that this occurs, but assessing the behavioral impact of PrEP and testing interventions to decrease risk compensation will be essential. To Nyende Ali, I think your emphasis on behavioral counseling is justified. And I agree that measuring outcomes to assess effectiveness can be challenging, though some studies have measured proximate outcomes for HIV transmission. For example, studies may ask individuals about number of sexual partners or frequency of sex acts that involve barrier protection before and after counseling interventions to assess impact. But enduring change, as you point out, seems to be the key goal. Studies involving adaptation of new interview and counseling techniques, such as motivational interviewing, may offer insights into ways to create long-lasting behavioral changes. Finally, to join behavioral counseling and PrEP, the future of prevention is likely to involve tailored interventions that depend on local factors. As you say, individualized risk assessment may guide which prevention modality is most suitable for each person. The NIH is funding "prevention package" approaches to test these ideas, so we should have more data in the next few years. I hope you are able to study these topics. To the forum members: We conducted the HOPE conference this morning, a video conference among several US and South African sites with additional participation from other regions of the world, and the topic was PrEP. Though it ended early due to technical issues (we will reschedule - please contact me for info on how to participate, as membership is open), we began a discussion of how implementation would occur in real-world settings. I would really like to hear from the members of this forum about how others feel that PrEP may or may not have an impact on clinical practice. Any thoughts about this open ended question would be very valuable. Thank you, Doug Dear Doug, I'm sure we will all find your HOPE Conference presentation incredibly useful. Along those lines of introducing PrEP into clinical practice, Dr. Paul Sax recently posted a case study in JournalWatch asking: "A young man who repeatedly engages in high-risk sexual activity with other men requests pre-exposure prophylaxis to prevent HIV infection. Do you oblige?" Here's the link: http://aids-clinical-care.jwatch.org/cgi/content/full/2011/228/1 One commenter said, "Prescribing pre-exposure prophylaxis for a high-risk behavior to an apathetic person is like purchasing ammunition for a repeat bank robber. This patient needs a counselor." Another said: To justify prescription to one individual sets a precedent whereby this should be prescribed to all who seek it. This intervention would need further evidence of value from a population health point of view before it could be justified." And another: " How is this different than prescribing a PPI for heartburn when a patient refuses to give up coffee or a statin for hypercholesterolemia when a patient will not make dietary modifications. Our business is to prescribe medicines to mitigate risk when people do not (for whatever reason) make healthy lifestyle choices." What do you think? Very good questions, and the answers from the other clinicians (I presume they are clinicians based on their access to Paul Sax's column) are informative about some of the potential barriers to PrEP provision. Many clinicians worry, appropriately so, that the use of PrEP will cause individuals to increase their risk taking behaviors, thereby causing a net increase in the risk of HIV acquisition when using a partially effective PrEP agent. Studies need to monitor for this phenomenon, so-called "risk compensation" or "behavioral disinhibiton." However, the data that are available from published PrEP studies do not support these concerns at this time. There were decreased number of sex partners and stable, high-levels of condom use among participants over the course of the CAPRISA 004 trial (by participant report). In oral PrEP trials, no evidence of risk compensation has been published to date. We will have to wait and see if this occurs outside of a trial setting, but for now, I think we should let the data guide us as we move forward, albeit cautiously. The context of PrEP is the unacceptably high globoal incidence of HIV at 2.6M new infections per year, and if PrEP can have a significant impact on the epidemic, we should consider using it where appropriate if ongoing studies confirm efficacy in trial and non-trial settings. I agree that prescribing to a single individual means we should provide PrEP to all who may benefit from it. This could be different than "all who seek" PrEP, as there could be "worried well" who seek PrEP despite low risk of HIV acquisition. But for those who are at-risk, based on behavioral practices or demographics, and wish to take PrEP, clinicians should consider prescribing it if they and their patients believe the data demonstrate efficacy and safety. Guidelines could facilitate prescribing, and interim guidlines from CDC for oral PrEP provision exist (MMWR Jan 2011). But I can understand any clinician's reticence about prescribing PrEP given there are limited data to date, though much of the data come from well-designed studies (including gold-standard randomized trials). I would agree with the author who writes about PPIs; ideally, people would minimize their risk of HIV acquisition through behavioral changes and not through biomedical ones. But there are structural factors and personal circumstances (poverty, gender inequalities, substance abuse disorders) that may place people at high risk for HIV acquisition despite their attempts to minimize risk behaviors. For these people, PrEP may be a safety net to help protect them. And even if we ascribe a person's high-risk behaviors to choice alone, I agree that we have a duty to protect people in whatever way we can, ideally as a bridge towards future behavioral change and discontinuation of PrEP. I applaud those with the courage to write about reasons why PrEP should or should not be provided in the community, and I hope for more vigorous discussion this week. What do others think? Sarah, Thanks for linking the post by Dr. Sax. I disagree with the analogy that compares giving PrEP to high risk-takers is analogous to giving a bank robber bullets. The reason for this being that the bank robber's bullets aren't likely to ricochet and hurt them, making them risk 'free'. However, for an MSM practicing high risk sex, the lack of condom use is a double edged sword where if they are seronegative, they can seroconvert if exposed. I think a better analogy is that presented by clean needle exchange programs. If clean needles are given to the population, that doesn't mean that more people are going to become addicts. It deals with taking your health into your own hands and making your own choices, while those on the receiving end of the bank robbers bullets have no choice. (For an NYT article on the topic see: http://www.nytimes.com/2011/02/08/health/08vancouver.html) In Africa, however, needle transmission is minuscule compared to that through sex. One does have to entertain gender politics on this front and note that women are often unable to lobby for safe sex and condom use. I think that the CAPRISA trial was notable not only because it showed the PrEP could lead to positive outcome, but MORE SO because it allowed women to have a bigger say in their own health. Just because women are at times powerless to ensure that their partners use a condom does not mean that they are powerless against HIV/AIDS. The body belongs to the patient, at times the physicians role as an educator should be clear. One can only advise their patients to make the best decisions for themselves, but cannot force them to comply. No matter how much one wishes they were able to for these matters, especially those concerning adherence, right? I do agree with the last comment that PrEP should be provided if available, though this does not mean that education and counseling should not take place as well. These are not mutually exclusive. By not providing medications for those when they are available we are judging certain practices as good or bad while we should be deeming them safe or unsafe. It is possible to have multiple partners safely, just as it is possible to have multiple partners unsafely. CROSS POSTED FROM THE ADHERENCE COMMUNITY: SHANTA GHATAK replied to the discussion: Reply contents: "Changing risky behaviour in this young person may not be easy as he may be suffering from some sort of obsessive compulsive disorder as well and may not have access to counselling or treatment for various socio economic reasons. That he is asking for the medicines shows that he is willing to be treated. We can offer counselling repeatedly while asking him to attend the clinic frequently when he is being given the medicine supply? It is not a routine that we encounter such cases in large numbers but they are not uncommon. My only concern is that this patient should not run away to a provider who may not be knowledgable enough to tackle the complexity of the disorder. Though this may not be in the course of the advisable optimal care that should be provided in such a case as this one but we may need to look at what we can achieve in the long run. Thanks ### Christopher Shaw replied to the discussion: Reply contents: "Hi Doug, thanks for presenting part of the PrEP talk this morning, looking forward to participating in the full presentation when it is rescheduled. This is an interesting topic of discussion. PrEP once thought of only as precautionary for potential accidental exposures has probably always been used on the down-low by savvy folks with knowledge of and access to it. Now with so much buzz about its expanding use the Journal Watch case focuses on an msm who has unprotected sex with reasonable awareness of risk. I commend this 29 year old fellow . Much the way a patient traveling to an exotic destination might check in for a few vaccines or prophylaxis medications for malaria and anti-diarrheals so they can eat food cooked on the street, this guy knows his risk, he recognizes when it is greatest and he asks a health care provider for prophylaxis protection before going "to town." Sure there are other issues a health care provider would want to caution him about, the risk for other infections, the use of condoms for added protection and the risks the PrEP might have for him. But with this guy who clearly knows his risk the benefit of prescribing PrEP out weighs the costs. I know there are a number of other issues to consider with prescribing PrEP; cost? who should have access to it?who should prescribe? how should people who have it prescribed be monitored? etc but for someone with risk factors I would strongly lean toward providing PrEP." This is an interesting discussion about PrEP provision to a young man with high-risk behavior. Intermittent PrEP could also be considered for another high risk subpopulation-serodiscordant couples. In Africa, social, economic and cultural pressures to have children result in high pregnancy rates. HIV serodiscordant couples wanting to have children face the difficult choice between wanting to conceive and risking transmission of HIV. In resource limited settings, where assisted reproduction techniques are not available or feasible, often the only option is to tempt fate and practice unprotected sex. It is therefore not surprising that a substantial proportion of incident HIV infections occur within HIV serodiscordant couples. Ultimately, provision of ART to the HIV infected partner is the preferred option. But in situations where national guidelines limit provision of ART to those with CD4 counts <350 or <250 cells/ μL and viral load monitoring is not available, provision of PrEP to the HIV susceptible partner during peak fertility periods is a possible indication for PrEP. This scenario could apply to couples with HIV infected males and susceptible females, since those with HIV susceptible males and infected females can be taught how to practice artificial insemination during her fertile window. CROSS POSTED FROM THE ADHERENCE COMMUNITY: Jessica Haberer, MD, MS wrote: Hi All, Great discussion! Along with Andrew Mujugira, I am also involved in the ancillary adherence study for the Partners PrEP clinical trial in East African heterosexual HIV serodiscordant couples. At the recent CROI conference, we presented early results on adherence to PrEP within the trial to date. We have been using two relatively robust, objective adherence measures (unannounced home-based pill counts and electronic monitoring caps, called MEMS) in addition to the clinic-based pill counts performed in the parent trial. We have found adherence to be near perfect with all these measures (i.e. 99-100%), which was quite surprising given the problems seen with adherence in iPrEX and CAPRISA. We are also checking random drug levels at 6, 12, and 24 months, but won't have those results until the trial is stopped and unblinded. They will be very important for validating (or not) our other objective measures. We think the main difference between our results and those in the other PrEP trials is the nature of the study populations. That is, we are working with stable, serodiscordant couples in which the HIV+ index has disclosed to the HIV- partner, while the other studies have involved high-risk individuals who may not have as much support. As everyone knows, however, behavior among participants in a highly structured clinical trial who are counseled at least monthly to take their medications is unlikely to be replicated by participants outside of the trial. I would be interested in hearing what the community thinks 1) about differences in adherence among potential target populations for PrEP and 2) how high levels of adherence can be practically supported outside of clinical trials. For instance, could support groups be helpful? Online chat rooms? SMS reminders? Thanks! Jessica (Posted on behalf of Rivet Amico) Excellent points regarding rates of adherence in different subpopulations. We just presented some sobering findings for the iPrEx trial in terms of how our measures of adherence (self-report and pharmacy based) can be quite discordant from drug concentration results, mirroring what has been found in ART adherence research where reports or classification (via pharmacy refill measures) of very low adherence appear to map well onto non-detection of study drug, but high adherence was not as predictive as needed to place a lot of confidence in our measures being able to accurately identify people who had drug detected from those who did not. Moreover, other presentations at CROI (Pete Anderson’s) suggested that overall rates of adherence at study visit week 24 were lower than desired and we are now looking into differences observed by research site for leads on why drug was detected at higher rates in different geographies. To me, that these adherence rates are specific to “study drug” versus PrEP, per se, is an important factor- we were very clear to participants about the possibility that they were on a placebo and it is very possible that when trials move to open label that rates of adherence may be much higher. We should keep in mind the potential difference between adherence to ‘study drug’ in blinded RCTs and adherence to PrEP especially now that there is some data to point to added protective benefits….in addition to keeping in mind the population’s motivation for use (e.g., when your partner is known HIV-positive). The rates of adherence in Partners PrEP is very exciting and we are all anxiously awaiting the evaluation of these measures (unannounced pill counts and EDM) to blood levels of drug. This is a very exciting time with many future directions. I think many of us are hoping for PrEP to be one of many possible sexual health promotion strategies for those who choose to use it who are otherwise at high risk for HIV-infection. Not the only strategy, but one of many possible strategies that can be synergistic with other presently available approaches. Rivet K Rivet Amico, PhD Research Scientist Center for Health, Intervention and Prevention University of Connecticut Dear Rivet (as channeled through Jessica) and Jessica, Thanks for explaining your recent work on adherence in iPrEx and clarifying some of the nuances about adherence within the trial setting versus the clinical setting. We are all looking forward to iPrEx OLE (i.e., open label extension - it's hard not to enjoy the acronymic title of the study) and your adherence work. The potentially high adherence rates in Partners PrEP is excellent news. I am interested to hear your thoughts on adherence to intermittent PrEP, aka iPrEP. IPrEP may offer advantages to daily PrEP, such as lower costs and overall drug exposure, and some have speculated that adherence will be superior than seen with daily PrEP regimens. However, preliminary data from iPrEP trials (from IAVI) have shown surprisingly low rates of adherence among some sets of participants. What are your thoughts on these early data and how they may impact future iPrEP studies? Thanks very much for your thoughts. I would welcome others to comment as well. Doug I also want to thank Chris Shaw for his comments. Chris has great experience with the care of persons living with and affected by HIV as a provider, and I am encouraged to hear his positivity towards providing PrEP to a person who may benefit from this approach. The analogies of a traveler heading into an area where chemoprophylaxis may offer protection is a great way to show that "PrEP" as a strategy has existed in other areas of medicine for decades (malaria prophylaxis for those for whom it is feasible offers a well-known example). Thanks so much, Chris. Doug Dear all, We have just published a peer-reviewed discussion brief on the promises and pitfalls of putting PrEP into practice with key points and references from this exchange. You can view and download it in the community. We invite you to provide feedback and continue the conversation on PrEP. Thank you. This Community is Archived. This community is no longer active as of December 2018. Thanks to those who posted here and made this information available to others visiting the site.
https://www.ghdonline.org/hivprevention/discussion/ghdonline-expert-panel-prep-a-promising-novel-hiv-/?ref=expertpanels
Low participation rates can lead to sampling bias, delays in completion and increased costs. Strategies to improve participation rates should address reasons for non-participation. However, most empirical research has focused on participants' motives rather than the reasons why non-participants refuse to take part. In this study we investigated the reasons why older people choose not to participate in a research project. Follow-up study of people living in Tayside, Scotland who had opted-out of a cross-sectional survey on activities in retirement. Eight hundred and eighty seven people aged 65–84 years were invited to take part in a home-based cross-sectional survey. Of these, 471 refused to take part. Permission was obtained to follow-up 417 of the refusers. Demographic characteristics of people who refused to take part and the reasons they gave for not taking part were collected. 54% of those invited to take part in the original cross-sectional survey refused to do so. However, 61% of these individuals went on to participate in the follow-up study and provided reasons for their original refusal. For the vast majority of people initial non-participation did not reflect an objection to participating in research in principle but frequently stemmed from barriers or misunderstandings about the nature or process of the project itself. Only 28% indicated that they were "not interested in research". The meaningfulness of expressions of non-consent may therefore be called into question. Hierarchical log-linear modelling showed that refusal was independently influenced by age, gender and social class. However, this response pattern was different for the follow-up study in which reasons for non-participation in the first survey were sought. This difference in pattern and response rates supports the likely importance of recruitment issues that are research and context specific. An expression of non-consent does not necessarily mean that a fully informed evaluation of the pros and cons of participation and non-participation has taken place. The meaningfulness of expressions of non-consent may therefore be a cause for concern and should be subject to further research. Many reasons for non-participation may be specific to a particular research topic or population. Information sheets should reflect this by going beyond standardised guidelines for their design and instead proactively seek out and address areas of concern or potential misunderstanding. The use of established behavioural theory in their design could also be considered. Recent years have seen changes to consent procedures, data access, and research governance in the UK, all of which are designed to ensure that health research is conducted ethically and with integrity. The motivation for these changes are rooted in an increasing culture of accountability of professionals and a desire to address growing public and media concern about the ethical conduct of research. However, some of these developments may threaten the delivery of valid and reliable research [1, 2]. At the centre of these challenges is the ongoing struggle to achieve high recruitment/response rates in community based research projects. Low response and participation rates undermine statistical power and increase the probability of bias. Non-responders have, for example, been found to be more likely to be smokers, to have poorer health and to make less use of health care services [3–5]. Furthermore, these problems are exacerbated among particular social groups: response rates usually fall with age [6–8] and are lower in those with less education and poorer socio-economic status [9, 10]. While knowing the magnitude of these differences may enable researchers to estimate or to adjust for the bias introduced by non-response [3, 5, 7], this is second best to a policy of prevention or reduction of initial non-response. Numerous attempts have been made to identify effective strategies to maximise participation in both experimental and observational studies [11–13]. While a recent Cochrane review that identified 372 randomised controlled trials of interventions aimed to increase response rates to postal questionnaires identified a range of effective strategies (envelope size, paper colour, financial incentives and ease of opt out) meta-analyses frequently show significant levels of heterogeneity between studies . This indicates that strategies that may be highly effective for one social group in one setting may be less effective or even counterproductive in another. While this suggests that the reasons behind non-response or poor recruitment are likely to be variable, interventions to improve recruitment have seldom been based on the findings of exploratory studies of the reasons for non-response or recruitment in the first place. Consequently, even interventions that have some degree of demonstrable effectiveness are unlikely to be able to address issues that stem from the unique and idiosyncratic nature and context of individual projects where potential respondents may face specific practical problems or concerns. Even where effectiveness is demonstrated questions remain. The finding that a particular strategy improves recruitment or response does not mean that it has either addressed the underlying concerns or practical problems associated with low rates. Instead it may simply be masking the problem. For example, monetary and non-monetary incentives may encourage people to participate but do nothing to alleviate their concerns about how the data are used or whether it will be treated confidentially. Numerous studies have examined the motives and experiences of individuals who participate in research [16–21]. However, few have explored reasons for non-participation. This is unsurprising given the potential ethical and practical difficulties of accessing individuals who have already said that they do not wish to participate in a piece of research. However, structural, ethical and procedural changes for research (the increasing requirement to seek consent even where there is no patient contact, to have a formal "opt-in" rather than an "opt-out" process, and the increasing inability of health researchers in the UK to recruit participants directly rather than through a clinical intermediary) all mean that response rates have increasing potential for bias [22, 23]. Consequently, it is perhaps more important than ever to focus not only on what motivates response and participation but rather what non-response or refusal to participate actually means and what the reasons behind it are. In this paper we report the findings of a survey of the characteristics and reasons for non-response in a study of attitudes to physical activity among older people. We then go on to discuss in detail possible responses and considerations. We do not present solutions but simply intend to encourage researchers to look at the issue of research non-participation as a behaviour that can be explored, analysed, and theorised just as other behaviours are similarly studied in other contexts of health. In 2002–4 we conducted a cross-sectional survey based on structured face to face interviews examining reasons for low physical activity among older people. These details, along with the findings of the study, have been reported elsewhere . Subjects aged 65 to 84 years were identified from 16 GP practices in Dundee through age/gender registers. All were allocated a deprivation score : scores of 1 and 2 were classed as areas of low deprivation; 3, 4 and 5 as medium; and 6 and 7 as areas of high deprivation . A stratified random sample (age in 10 year groups, gender and three deprivation groups) of 1064 subjects was drawn. GPs screened the lists of names and 100 were excluded (terminal illness, dementia, living in a nursing home). Twenty subjects could not be traced at the addresses given. A further 57 subjects were excluded at initial contact because they were unsuitable (e.g. admitted to hospital, language barrier, bereavement, extreme frailty). A total of 887 subjects suitable for inclusion were invited to take part in the study. Potential participants were initially contacted by a letter from their GP. This letter, and the information leaflet, stated that the study would investigate physical and social activities with the aim of improving facilities for older people. They were given the opportunity to opt out of the research by returning a postcard to the practice. If the postcard was not returned to the practice within three weeks, they were contacted by a research nurse to arrange an interview. We obtained permission from our Local Research Ethics Committee (LREC) for GPs to approach people who refused to take part in the main survey. We were aware that the our LREC, along with many others in the UK, were increasingly requiring researchers to use an "opt-in" approach in which individuals are written to by their general practitioner and asked to respond if they would like to receive more information about the project (as opposed to an "opt-out" method in which non-response to such a communication would result in the researchers approaching them). For the main survey the LREC originally requested an opt-in approach. However, after the researchers highlighted the degree to which sampling bias might be created in using an opt-in approach, the LREC agreed to the use of an opt-out approach. Given the preference for an opt-in stance and its underlying rationale to minimise burden on potential participants we were aware that any subsequent request to the LREC to approach people who had already requested not to be involved by actively telephoning or returning a card would be contentious. We therefore requested and obtained permission to ask only a small number of essential questions. We also agreed to ensure that the time required to complete the questionnaire be short, and that our covering letter overtly stress that participation was voluntary and that we respected their decision not to take part. These requirements precluded the possibility of using a qualitative approach to data collection. A further reason for the method and its brevity was simply to encourage as high a response rate as possible as it was assumed that people who had refused to take part in the main study would not be greatly motivated. GPs sent a short questionnaire to those individuals who refused to take part in order to ascertain their reasons for non-participation. They were invited to return the questionnaire to their GP in a stamped addressed envelope which was provided. Only one letter was sent in order to minimize the potential intrusiveness of the study. The follow-up questionnaire was designed to be as brief as possible in order to maximize likely response. Eight questions were selected by drawing on both the literature concerning non-response and poor recruitment, and the reasons expressed for non-response among those who had refused consent when the researcher had contacted them by telephone. The questionnaire included two questions on each of four topic areas: understandings about the research; concerns around privacy; personal reasons (e.g. health); lack of interest in research. A single open question was also asked in order to allow expression of other reasons not embodied in the previous eight. Chi-squared tests were performed to investigate univariate associates with refusal. Model fitting using hierarchical log-linear modelling was used to identify significant independent predictors . Of the 887 subjects who were invited to take part in the main survey, 384 refused by completing and returning a card indicating their unwillingness to take part. A further 91 refused when telephoned or when visited, and 3 gave no response, leaving 409 who were interviewed. It is noticeable that of those who refused, 80% did so by returning the postcard. Refusal to take part in the main survey varied significantly by age, gender and level of deprivation (Table 1). When fitted into a hierarchical loglinear model each of the three terms showed a significant independent association with refusal. Refusal was higher in the older group, by female gender and increased with increasing level of deprivation. None of the higher order interactions were significant. The 471 people who refused by card return or at personal contact were considered for the follow up study. After GP exclusions a total of 417 were approached. Overall 61% of those who refused to take part in the main survey returned a follow-up questionnaire giving their reasons for refusal. The effect of age, gender and deprivation on the return rate of the follow-up questionnaires was quite different to their effect on participation in the cross-sectional survey (Table 2). Thus the older group had a significantly lower non-participation rate than the younger group. Furthermore, there was little difference between men and women in non-response and the effects of deprivation were inconsistent and non-significant. No higher order interactions were significant. The follow-up questionnaire comprised eight questions, which participants could answer yes, no, or give no response. By far the most commonly selected reason for not taking part in the main study was that the participants considered that they did not do enough exercise to be useful for research (Table 3). Only a minority (28%) indicated that they "were not interested in research" and even these had actually taken part by replying. The other most common answers reflected concerns about loss of privacy, either through research staff visiting them or by being asked questions about personal matters. We examined the data to see if the reasons provided differed between age, gender and deprivation groups (Table 4). Two significant differences were found. Unsurprisingly, older people were more likely to report their age as a reason for non-participation (p < 0.0001). In addition men were more likely than women to indicate that they were not interested in research (33% versus 22%; p = 0.045). "My wife does not keep very well and I need to watch over her" "Family commitments prevent me from attending, organised activities" "My other commitments will prevent me from participating" A second dominant theme, research misunderstanding, reflected confusion about the nature and purpose of the research itself. Responses suggested that many may have declined to take part in the initial survey either because they regarded themselves as already physically active and therefore not appropriate for inclusion, or because they thought that the researchers had contacted them because they were felt to be in need in some way. "I am pleased as I am, but thank you all for your care and kindness" "I keep active in my own way, a little gardening etc, when necessary, at my own pace" "My personal activities at present fulfil my needs" "I'll no doubt soon be donning the old wooden overcoat" The study found that for the vast majority of people refusal to participate in the main survey did not reflect an objection to participating in research in principle but frequently stemmed from barriers or misunderstandings about the nature or process of the project itself. The meaningfulness of expressions of non-consent may therefore be called into question. Response rates for the main survey varied by age, gender and social deprivation. However, this response pattern was different for the follow-up study in which reasons for non-participation were sought. This supports the likely importance of recruitment issues that are research and context specific, as opposed to generic issues alone. This study is one of a very few that has accessed the views of individuals who have refused to take part in a research project. The scale and nature of data collection was constrained by sensitivity to the fact that participants had already refused to take part in our main survey. As a result there are a number of caveats that must be considered prior to discussion of the study findings. Firstly, it is possible that reasons given for non-participation may not reflect those truly responsible. Both social desirability (e.g. unwilling to admit to apathy) and recall may mean some reasons have been omitted. Secondly, the data relates only to older people. While some of the reasons for non-participation may apply to younger groups we do not have the data to support this. Thirdly, it is possible that despite assurances in regard to confidentiality the requirement that the follow-up questionnaire should be sent by their GP may have resulted in some people feeling intimidated and therefore either not responding at all (potentially resulting in some sampling bias) or by responding but providing "acceptable" rather than accurate reasons for original non-participation. Finally, the reasons for non-participation provided are in relation to a request for a detailed, structured interview in the home setting and may not apply to other data collection methods. Despite these caveats our findings may be useful and informative for researchers in a number of ways. Firstly, they provide detail on likely response rates among older people and the tailoring of information sheets. Secondly, they raise questions over the meaningfulness not only of expressions of non-consent but also consent. Finally, they have implications not only for the design but also the recruitment procedure itself. These are dealt with in turn below. Fewer than 50% of people invited to take part in a structured interview about social and physical activities agreed to take part. Review papers have reported that many studies among older people have lower response rates [3, 6, 9, 28]. As in this study, others have reported that response rates usually fall with age [6–8] and are lower in those with poorer socio-economic status [9, 10]. These variations suggest that the reasons for non-participation may be different between social groups and/or that the strength of such reasons might differ. Consequently, information sheets or recruitment strategies that are based on a "one size fits all" basis may at best be inefficient and at worst inappropriate. Within the UK information sheets are increasingly being standardised under COREC (Central Office for Research Ethics Committees) requirements. However, their design is rarely empirically based and almost always atheoretical [14, 15], despite the fact that a range of theories of patient behaviour may contain relevant concepts that could be used in their design (e.g. self-efficacy, subjective norm etc) . A Cochrane review of strategies to improve response rates in observational studies revealed a concentration on modes of administration [14, 30]. Only two studies focussed on the information leaflets used in recruitment, and these only examined the appropriate level of detail rather than actual content per se. No strategies sought to address the beliefs or attitudes of potential participants towards participation or non-participation. Since this review a number of studies have targeted concerns and demonstrated that recruitment strategies that are designed to address these can have a significant impact [16, 31–33]. One recent study demonstrated an increase in participation from 40% to 70% . It is possible that there is so much heterogeneity between trial contexts that established behavioural theory would contribute little as reasons would be trial specific. Indeed despite identifying 15 studies in a Cochrane review of recruitment strategies the authors were uncertain of the generalisability of the finding to other trials as there was too much heterogeneity between studies to perform meta-analysis . The information sheet for the main study which had been subject to careful design, consisted of neutral, non-coercive language and had been approved by the local research ethics committee (LREC). However, we found that many expressions of refusal were based on misunderstandings about the research and therefore fell short of being informed and comprehended non-consent. Ethics committees attempt to ensure that when people decide to participate in a research study their consent is meaningful. This depends on three issues: that they are adequately informed, that they adequately comprehend, and finally that they are not coerced. However, LRECs and researchers do not routinely apply the same criteria to non-participation. Our data raises questions over the meaningfulness of the expressions of non-consent received in this study. Furthermore, it suggests that even carefully designed and LREC approved information provision can result in poorly comprehended information, undermining meaningful decisions about participation. There are good reasons why we should seek to ensure that expressions of non-consent (as well as consent) are meaningful and valid. Firstly, it can be argued that potential participants have the right to be provided with full and accurate information prior to making a decision not to participate. Arguably this includes being informed of the consequences of their non-participation (and a low participation rate overall) on the usefulness of the research and for patient care. Just as we should seek to ensure that those who agree to participate do not subsequently regret their decision, so too we should seek to ensure that those who refuse do not look back and wish that they had taken part or been given more information. Since many people in our study appeared to have declined participation due to misunderstandings it is quite possible that a correction of these misunderstandings would lead to some regretting their earlier decision. A second reason to pursue meaningful non-consent stems from the researchers' ethical obligations to those who do consent. If we do not actively explore the reasons behind and meaning of non-consent and develop solutions, we may be at risk of wasting the time and generosity of those members of the public who do agree to contribute. If consent was given that knowledge would be advanced then researchers must seek to ensure that this is achieved. Obtaining a sufficiently large and unbiased sample may be a prerequisite for this. Ideally therefore, refusal to participate should reflect a fully comprehended and active evaluation of the pros and cons of participation If this is the case, then perhaps non-response or refusal to participate should be regarded as a behaviour that it is not only legitimate to explore and perhaps attempt to change, but one that it would be negligent or unethical not to. However, the challenges of pursuing such research should not be overlooked. The acceptability and ethical implications of studies designed to explore non-participation has been largely omitted from debates around recruitment despite some using arguably intrusive methods. One such study conducted personal visits to the homes of those who had previously written to refuse participation. This approach yielded a final 93% participation rate. Others have only conducted home visits to those who did not respond to an initial request to participate [10, 36, 37]. Telephone and postal follow-up of all non-responders (including those who refused to participate) have also frequently been used[3, 38]. It is interesting that none of these papers mention ethical issues. The challenges posed by "opt-in" We used an "opt-out" approach to recruitment that is increasingly being rejected by research ethics committees in favour of "opt-in" approaches . The vast majority (81%) of those who did not wish to participate in the main survey returned a postcard as part of the opt-out. This would suggest that an active decision against participation had been made. Few studies among older people distinguish between positive opt out and passive non-participation, although two studies involving psychiatric interviews [4, 40] also found a high positive opt-out rate. However one of these made up to ten attempts to contact subjects, which may have increased the likelihood that subjects actively opted out. Another study, a trial of influenza vaccination, reported that 50% of those not taking part had also positively opted out . If researchers wish to maintain or increase response rates to research and ensure that consent and non-consent is informed and meaningful then an understanding of the issues that concern potential participants is crucial , as is a knowledge of concepts that are known to influence behaviour more generally . However, the increasing requirement to use opt-in procedures may undermine such attempts. Under the opt-out procedure recruitment depends largely on the inertia of individuals . However, the move towards an "opt-in" system has now reversed this. The failure to act leads to non-inclusion, but also means that non-inclusion is less likely to stem from any meaningful consideration of the pros and cons. Consequently, "non-participation" may not be an intentional or volitional act reflecting an unwillingness to take part but rather reflect a lack of intention or volition altogether, particularly among individuals who are less inclined to be actively involved in health-related decision making but instead leave it to professionals. Indeed a recent randomised trial has found evidence to support this . Non-participation may therefore sometimes stem less from a cognitive process and more from an adopted and established role in relation to health services generally. Furthermore, if data suggests that some individuals may have a preference not to be involved in some decisions, this might support Parker's recent argument for the use of data without consent for some low-risk research: "Patients may have good reasons to expect, or come to expect, that their records will be used without their consent for some low risk research, under certain conditions. Where this is the case, such expectations provide reasonable grounds for considering such research to be ethical."p183. Findings from this study have potential implications for recruitment and consenting practices when seen against the context of recent changes to ethical requirements and data protection. Firstly, the design of information leaflets and the verbal consenting approach should not be excluded from the concept of evidence-based practice. If there is empirical evidence or relevant behavioural theory to suggest the best means to achieve meaningful consent then these should be pursued. Secondly, expressions of non-consent need to be subject to further research and not seen as out of bounds as a focus for investigation. A limited amount of additional research may be important to ensure we are conducting our research recruitment to a high standard. Thirdly, in pursuing the ideal of meaningful consent researchers could consider presenting potential participants with two options: participation and non-participation and highlight the pros and cons of each in a manner not dissimilar to that of two treatment options. At present, it could be argued that the information insisted upon by ethics committees focuses on that needed to take part rather than that needed to decide not to take part. The consequences of non-participation for example (for both the individual, science, and the public), are rarely conveyed, probably through fear of being coercive. While recent commentators have questioned whether we currently know what information potential participants need in order to participate in a research project it may also be worth considering what information they may require in order to know whether they should refuse to participate . The presentation of such information may contribute to ensuring that both consent and non-consent are meaningful. We are grateful to the many GPs in Dundee who gave their support to this study. This study was funded by the Chief Scientist Office, Scottish Executive Health Department: grant application number CZH/4/5. The design, conduct and analysis of this study was completely independent of the funders. IKC and LI conceived the idea for the study. All authors were involved in the design. AM collected the data. LI and IKC analysed the data. BW wrote the paper. All authors edited, revised and approved the final manuscript.
https://bmchealthservres.biomedcentral.com.preview-live.oscarjournals.springer.com/articles/10.1186/1472-6963-7-59
Every year, IIITH conducts a series of welcome sessions to help acclimatise students to their new environment and assure parents that their wards are in safe hands. Prof P J Narayanan shares what makes these sessions integral in conveying the ethos of the institute. An academic institution’s glory is reflected in the students they prepare for the world and vice versa. Undergraduate programs have maximum impact as seen at MIT, Oxford as well as Indian institutions, and the reasons for this is manifold. The number of undergraduate (UG) students exceeds the numbers for other programs. UGs also spend a very critical time of their lives in college, developing deep emotional connections. They also branch out into diverse careers in their lives through which the institution produces impact on the world. Early Influencers An undergraduate program should transform girls and boys into confident women and men. IIIT Hyderabad spells out its education mission as transforming its students into Competent, Creative, and Caring individuals. This needs active and enduring collaboration and cooperation of everyone with an influence on students: peers, faculty, parents, and society. We particularly recognize the special role of parents in this endeavour, as they continue to influence and communicate with their children. It is critical to recognize that a youngster’s education is a joint mission by the parents and the institute. Some parents fuss about their children’s pay packages or company-pedigrees right at the start! All parents worry about hostel and classroom facilities. These merely reflect the love and aspirations they have for their children, combined with the anxiety of leaving them, perhaps for the first time. However, parents also need to worry about setting the right aspirations in their wards, for a world they will help shape. Learning by Example The institute wants parents to rest assured their wards are in safe hands. We involve other students in good numbers in the welcome sessions, including those who joined just a year before. We conduct several welcome sessions to convey the ethos of the institute to different groups – a common session for all students, parents and others who come with them, with alumni, as well as special sessions for students and parents of the research-based dual-degree programs. The crown jewel of the sessions is a free-flowing session conducted exclusively for parents to convey the institute’s aspirations for the incoming class, beyond the ordinary pursuits of a high-paying job or a spot in a prestigious graduate school. And to make parents willing enthusiastic partners in fulfilling those aspirations. Educational institutions focus too much on the how of the subject (the skills) and sometimes on the why (the science). We also want our students to reflect on the what. What should they do with the skills and the science they acquire, for themselves, their families, and society at large? This needs introspection and reflection, activities not rated high by today’s society. We urge each student to introspect on what he or she values most, beyond what the media, friends, parents, or society tells them. The results of such an exercise should guide their actions in the short, medium and long terms. The Big Picture This is not an easy endeavour for students, their parents, or the institute. However, it is imperative for everyone to realize the importance of this effort. All we can hope for is to set their minds thinking in this direction. The session with parents attempts to convey this, in addition to listening to their views. We are always gratified to see the convergence in the thinking of the parents with our own. The questions from parents in these sessions are both from the head and heart, and faculty respond likewise in this freewheeling exchange that sometimes goes on for close to 3 hours till all queries are suitably addressed. Year-on-year parents give this session high ratings, reiterating our belief in what we are striving to accomplish. A recording of the Parents’ Session 2019 is now available for everyone. The session was not meant for the camera; we had difficulty editing it suitably. It is being presented in mostly a raw form here. I hope the parents who have gone through such a session in the past will connect readily with it. I also hope parents and students who are considering IIIT Hyderabad find a clear enunciation of the institute’s ethos to help make that decision, away from societal pressures.
https://blogs.iiit.ac.in/orientation/
The Bachelor of Arts offers both diversity and focus, and builds informed, skilful and critically aware citizens of the world. Students can choose any majors of their interests from a range of areas in the arts, humanities and social sciences. Students will develop a rich understanding of human difference and communication, the complexities of social organization, and humankind's trajectory through the past and into the future. Students can choose from almost 40 different major and minor areas of study, including languages, social studies, communications, politics, human rights, and international relations. Students will also have access to the Monash Arts Global Immersion Guarantee which aims to develop an informed, critical awareness of the fields a student is most passionate about, laying the groundwork for a wealth of exciting careers. About University Monash University Monash University Is the largest university in Australia, ranked in the world's top 100 and a member of the prestigious Group of Eight. We're named after Sir John Monash, and fuelled by his desire for our students to leave here with a greater sense of purpose, and the skills and confidence to create positive change. In under 60 years, we've grown from a single campus into an education and research powerhouse with a presence on four continents, committed to the challenges of the age. Our work is making an impact all over the world, from bringing clean water to villages in Africa to creating new life-saving medicines. An international experience With four Australian campuses, one in Malaysia and over 100 international partners, we're making a difference on a global scale. You'll have access to more research collaborations, more global partnerships, and a greater choice of overseas opportunities. All Monash courses have an international focus, whether you take subjects on global issues, participate in study abroad programs, or learn alongside students from diverse cultures. Monash prepares you for the global workforce - you can start your degree in Australia, and continue your studies in Italy, Malaysia, India, China, or any of our 100 partner institutions worldwide. A recognised world leader in research We're active in over 150 fields of research across our 10 faculties, in areas as diverse as additive manufacturing, drug development, domestic violence and sustainable design. Many ideas developed at Monash - such as a new Malaria vaccine and 3D-printed engines - have been commercialised and are making a difference to the world we live in. Partnerships in industry and government Home to various precincts of innovation, we foster collaboration across traditional and unexpected disciplines. We build teams and form links, we bring together diverse minds - researchers, companies, businesses and technology - creating knowledge hubs of the future. Plenty of options Our large range of courses allows you to match your studies with your ambitions. Monash University offers one of the largest range of degrees in Australia, including over 140 innovative double degree options, bachelor, master and PhD degrees. Scholarships We believe everyone should have the opportunity to make their mark on the world, which is why we offer over 200 different types of scholarships for new and current students. They take care of everything from course fees to travel and accommodation. Our scholarships aren’t just reserved for those with the best academic track record – we provide support for disadvantaged students as well. Follow Monash University on Twitter, Facebook, YouTube and LinkedIn!
https://www.topuniversities.com/universities/monash-university/undergrad/bachelor-arts-0
Moving to a more prestigious professorship in Leipzig inWundt founded a laboratory specifically dedicated to original research in experimental psychology inthe first laboratory of its kind in the world. There are substantial individual differences in learning and memory, such that some people learn faster than others. The rise of computer technology also promoted the metaphor of mental function as information processing. Penfield begins to uncover the relationship between chemical activity in the brain and psychological phenomena. Penfield publishes results from his study of the neurology of epilepsy. When participants were exposed to words related to the location of the square just before they stopped its movement, they became more likely to think that they controlled the motion, even when it was actually the computer that stopped it. Cognitive psychology This field uses sophisticated research methods, including reaction time and brain imaging to study memory, language, and thinking of humans. The procedure, intended to relieve severe and debilitating psychosis, is controversial. A participant who is reading a book might report, for instance, that he saw some black and colored straight and curved marks on a white background. So the canoes went back to Egulac and the young man went ashore to his house and made a fire. Social-Cultural Psychology A final school, which takes a higher level of analysis and which has had substantial impact on psychology, can be broadly referred to as the social-cultural approach. Gestalt German for "whole" or "essence" psychology asserts that psychological phenomena must be viewed not as individual elements but as a coherent whole. Thus it is no surprise that beginning in the s, growing numbers of psychologists began to think about the brain and about human behavior in terms of the computer, which was being developed and becoming publicly available at that time. Then test again after 1 day and after 2 days. Journal of Experimental Social Psychology, 44 12—9. There people were tested on a wide variety of physical e. It is in a class called systematic interpretations because It attempted to explain all behavior with reference to one systematic position. Simon and Schuster; Tooby, J. The behaviorist research program had important implications for the fundamental questions about nature and nurture and about free will. Bartlett created short stories that were in some ways logical but also contained some very unusual and unexpected events. Almost immediately tension arose between the experimentally and philosophically inclined members of the APA. Other European philosophers, including Thomas Hobbes —John Locke —and Jean-Jacques Rousseau —also weighed in on these issues. Evolution and the meanings of life. Psychological Review, 4— Do We Have Free Will? Clinical and Counseling Psychology: Human Relations, 7, — These images are used to diagnose brain disease and injury, but they also allow researchers to view information processing as it occurs in the brain, because the processing causes the involved area of the brain to increase metabolism and show up on the scan. In other studies the structuralists used newly invented reaction time instruments to systematically assess not only what the participants were thinking but how long it took them to do so. Their goal was to classify the elements of sensation through introspection. The decision in the case, Larry P. It is marketed under the trade names Eskalith, Lithonate, and Lithane. The handbook of culture and psychology. Psychodynamic psychology is an approach to understanding human behavior that focuses on the role of unconscious thoughts, feelings, and memories.Dreams puzzled early man, Greek philosophers spun elaborate theories to explain human memory and perception, Descartes postulated that the brain was filled with animal spirits, and psychology was officially deemed a science in the 19th century.5/5(3). Psychology is best defined as the "scientific study of behavior in behavior. Since aboutmost university psychologists have accepted Watson's definition. behavior. Introspection was the first technique for studying the mind There are some terms related to psychology that are frequently confused with it. Psychiatry is a branch of. American psychologist who was the first woman to earn a doctorate in psychology in the United States; published research on mental processes in animals. G. Stanley Hall American psychologist who established the first psychology research laboratory in the United States; founded the American Psychological. Study An Introduction to the History of Psychology discussion and chapter questions and find An Introduction to the History of Psychology study guide questions and answers. Chapter 1: An Introduction to Psychology Introduction-3 main types of psychologists (p.7 chart) o Clinical psychologists (Ph. D/Psy. D) Diagnose and treat psychological problems Clinics, private practice, hospital Counseling psychologists, Psychiatrists are medical doctors / prescribe medicine o Applied psychologists Less involved with %(1).
http://kopihevafuxyqejony.ultimedescente.com/an-introduction-to-the-history-of-the-first-psychologists-3538635386.html
This course introduces the student to nursing as a profession. Various roles and functions of the nurse are explored. Emphasis is placed on the organization and education of nurses, nursing care in various settings, and recipients of nursing care. Exploration of the conceptual and philosophical basis of nursing and the role of critical thinking in the nursing process will be examined. Open to non- nursing majors. Human Development is a theoretical course designed for any student interested in increasing insight into the developing person, including self. This course provides an overview of human growth and development across the lifespan. Basic theories and principles of development, influences on the developing person, and norms of development are discussed. Development is examined from a variety of theoretical perspectives including physical, cognitive, psychosocial, emotional, moral-spiritual, and adaptive mechanisms. Concepts of death in the child, adolescent, and adult of various ages, and issues faced by the age group, also are discussed. Family developmental tasks and family interaction, as they influence the individual throughout the lifespan, are considered in each developmental era. This course introduces the student to foundational clinical concepts in nursing. The social, legal, ethical, cultural and interprofessional context of nursing practice is presented. The use of the therapeutic relationship as a basis for nursing care is emphasized. Consideration is given to developing students' self-awareness, the importance of reflective practice, and the ability to use one's self as a therapeutic tool. The nursing process is introduced and its use in promoting patient safety in an interprofessional health care environment is discussed. The role of the nurse in promoting health and reducing risk behaviors of individuals and families across the lifespan is the focus of this course. Exemplars of nutrition, physical activity and stress management will be examined with an emphasis on the impact of genetics, values, lifestyle, and cultural influences. Client teaching as an essential function of the nurse is emphasized. In the clinical practicum, the student will facilitate his/ her understanding of factors that enhance health promotion and risk reduction through the development of a long term relationship with a client and family. This course focuses on the use of clinical judgment in the application of evidence based therapeutic interventions and technologies in providing direct care to patients across the lifespan. Building therapeutic relationships, patient safety and the provision of quality care in an interprofessional setting are emphasized. Students gain experience in developing communication skills and implementing the nursing process in simulated and actual patient settings. In this course, research is introduced as a method of inquiry and as a foundation for evidence based clinical decisions. Fundamentals of research methodology will be presented. Developing, evaluating, and applying an evidence-base to address nursing care issues will be explored. Barriers to implementation of evidence based practice and strategies to address those barriers will be considered from an individual and an organizational perspective. The role of the nurse in affecting evidence based change in practice will be discussed. This course provides students with an overview of the influence of health care policy in shaping the nature, quality, cost, access, and safety of the health care environment. The focus is on the broader context of healthcare, including how patient care services are organized and financed, how reimbursement is structured, and the role of regulatory agencies in defining the boundaries of nursing practice in a complex inter-professional environment. This course provides an introduction to systematic data gathering, analysis, and documentation of health assessment data with emphasis on cultural and lifespan considerations. Throughout this course the importance of communication and interprofessional collaboration across culturally diverse populations is discussed. Assignments focus on physical health, functional capacity, growth and development, psychological, sociocultural, and spiritual health of individuals and families. This course focuses on the health assessment component of the nursing process using a lifespan approach. Integration of health assessment skills will be explored within the dimensions of pathophysiologic changes that occur during alterations in health. Considerations for health assessment will include growth and development, psychological, sociocultural and spiritual health of individuals. A case study approach will be utilized during this course. The evaluation by credit examination provides students the opportunity to earn academic course credit for prior learning through coursework, experience, training, or self-study. This examination measures knowledge on the health assessment component of the nursing process using a life span approach. Integration of health assessment skills will be explored within the dimensions of pathophysiologic changes that occur during alterations in health. Considerations for health assessment will include growth and development, psychological, socio-cultural and spiritual health of individuals. A case study approach will be utilized during this course. This course develops the student's knowledge of the nurse's role and responsibilities in drug therapy based on application of concepts from nursing and pharmacological sciences utilized in evidence based nursing practice. Emphasis is placed on utilizing the nursing process and role of the nurse when caring for patients receiving drug therapy. Legal, ethical, and life span considerations are presented as they apply to the nurse's role in drug therapy. The content focuses on the pharmacologic classifications of drugs, their physiologic impact, monitoring therapeutic responses, side effects, adverse reactions, drug interactions, patient-teaching responsibilities, and nursing implications. The student will learn to apply the nursing process to the care of the patient receiving drugs in a variety of clinical settings. This course provides an overview of the pathophysiological processes common to many diseases. Major pathophysiological concepts are explored using a body systems approach. Concepts and theories related to epidemiology, etiology, pathogenesis, and clinical manifestations are used to study common disease processes. The content will be based on the health-illness continuum, including both physiological and psychological alterations, and system or organ failure. Considerations are given to selected pathological alterations and their effects on physiological and psychological functions. A life span approach is utilized with selected disease models and case studies as the focus in the course. Concepts from anatomy, physiology and chemistry courses provide the foundation for exploring human diseases. The evaluation by credit examination provides students the opportunity to earn academic course credit for prior learning through coursework, experience, training, or self-study. This examination measures knowledge about concepts related to therapeutic nursing interventions to promote patient nutrition during illness with considerations for age and culture. Knowledge about regulatory processes for fluid and electrolyte balance, conditions that alter fluid balance and interventions to prevent body fluid and electrolyte disturbances are also measured. This course uses a patient-centered, culturally sensitive approach to the health care needs of individuals, families and groups experiencing alterations in mental health across the lifespan. Emphasis is placed on theoretical knowledge and evidence-based practice to promote, maintain and restore health. Priority is given to the use of self as a therapeutic tool, principles of therapeutic relationships, and knowledge of psychopathology. An interprofessional team approach is emphasized in the safe delivery of care. The focus of this course is the introduction of the student to the concepts and principles of public health and the practice of public health nursing. The nursing process is applied to the care of individuals, families, and groups within the community. The theoretical content and clinical practice emphasize public health measures which promote and maintain the health of the community. Evidence-based knowledge of public health science is incorporated, health team relationships are broadened, and management of client care is practiced through health teaching, counseling, and referral by home visiting and other experiences. Evaluation of care and fostering of accountability are integrated throughout the course. Legal and ethical issues in public health are examined. Research topics in public health practice are introduced. The focus of this online course is the introduction of the student to the concepts and principles of public health and the practice of public health nursing. The nursing process is applied to the care of individuals, families, and groups within the community. The course content and group activities emphasize community health measures which promote and maintain the health of the community. Research-based knowledge of public health science is incorporated, understanding of health team relationships is broadened, and knowledge about the range of client care is expanded. Evaluation of care and fostering of accountability are integrated throughout the course. Legal and ethical issues in public health are examined. This course is designed to provide the student with an experience of planning within a community to meet its needs. Working from the knowledge and competencies gained in previous courses, and in collaboration with members of the health care community, students will design, construct, and evaluate a teaching or quality improvement strategy project. Teaching-learning principles of the nurse educator will be incorporated into the teaching or quality improvement strategy project. The theory portion of the course uses a patient-centered, culturally sensitive approach to the health care needs of the older adult. Emphasis is placed on theoretical knowledge and evidence-based practice findings as the basis for nursing strategies to promote, maintain, and restore health. Priority is given to the discussion of chronic health conditions, geriatric syndromes, and frailty. An interprofessional team approach is emphasized in the safe delivery of care. This practicum provides the opportunity to apply evidenced-based practice and a patient-centered approach to care. A variety of settings, as well as, laboratory simulations are utilized. Emphasis in acute care settings is placed on the care of older adults. Skills associated with the assessment and management of illnesses and conditions are developed within the context of patient and family culture, preferences and needs. Helping patients compensate for changes in function, providing emotional support and educating patients and families to promote wellness are emphasized. Skills related to enhancing communication, information management, and collaboration as a member of an interprofessional team are further developed. The theory part of this course uses a person-centered, family-centered, and culturally sensitive approach to the health care needs of women and their newborns during the childbearing cycle. Emphasis is placed on theoretical knowledge and evidence-based practice findings as the basis for nursing strategies to promote, maintain, and restore health. Consideration is also given to common complications occurring in the childbearing cycle. An interprofessional team approach is emphasized in the delivery of safe, effective, and quality care. The practicum provides the opportunity to apply evidenced-based practice and a patient- centered approach to care. A variety of settings, as well as, laboratory simulations are utilized. Emphasis in acute care settings is placed on the care of women and infants during the intrapartal, postpartal, and neonatal periods. Nursing care is provided within the context of client and family culture, preferences and needs. Helping patients to adapt to changes in function, providing emotional support and educating patients and families to promote wellness are emphasized. Skills related to enhancing communication, information management, and collaboration as a member of an interprofessional team are further developed. The theory portion of this course uses a person-centered, family-centered, and culturally sensitive approach to the health care needs of infants, children, and adolescents. Emphasis is placed on theoretical knowledge and evidence-based practice findings as the basis for nursing strategies to promote, maintain, and restore health. Priority is given to discussion of significant health care issues within these populations. An interprofessional team approach is emphasized in the safe delivery of care to these populations. The practicum portion provides an opportunity for students to apply theoretical knowledge and evidence-based practice in the care of selected infants, children, and adolescents. The use of a patient and family-centered approach in the nursing process is emphasized. Nursing care is provided within the context of patient and family culture, preferences, and needs. Helping patients to adapt to changes in function, providing emotional support, and educating patients and families to promote wellness are emphasized. Skills related to enhancing communication, information management, and collaboration as a member of an interprofessional team are further developed. Learning experiences are provided in a variety of settings, as well as, laboratory simulations. In this course students analyze important concepts in professional nursing practice including self-care, nursing theory, nursing scholarship, professional codes of conduct and professional standards. The social, legal, ethical, cultural and interprofessional context of nursing practice is presented. Contemporary issues in professional nursing practice are presented including informatics and patient care technology, genetics and genomics, and nursing management across the health-illness continuum, across the lifespan, and in all health care settings. This course provides students with an overview of management, leadership and organizational theories in the context of nursing and health care. An overview of the major functional areas of health care management and their relevance to the safe delivery of health care services in a turbulent and complex interprofessional environment will be introduced. The influence of legislative, regulatory, and risk management policies in shaping the nature, quality, and safety of the nursing practice environment will be examined. This course focuses on the transition of senior nursing students to professional nursing practice as new baccalaureate graduates. The course assists students to synthesize knowledge and skills required of new graduates including refinement of clinical judgment, problem solving and priority setting. Students identify strategies for resolving ethical and legal dilemmas and conflicts related to diversity in the work force. Issues related to licensure, career development, and professional satisfaction are discussed. This course builds on prior nursing courses and provides the student with a practicum experience in managing patients and environments in selected specialty settings. This clinical experience focuses on assessments, interventions, and outcomes unique to these populations. The student becomes an integral part of the interprofessional team with responsibility for the efficient management of care that produces cost effective, patient-centered outcomes. Skills related to enhancing communication and information management are refined. This portfolio course focuses on the identification and the competent management of patients' health care needs. Students are expected to provide evidence of competence as caregivers, teachers, advocates, and collaborators. Students will provide evidence of their ability to manage the nursing care of individuals, families, and/or groups at various points on the health-illness continuum. The role of the nurse in promoting health and reducing risk behaviors of individuals and families across the lifespan is the focus of this course. Exemplars of nutrition, physical activity and stress management will be examined with an emphasis on the impact of genetics, values, lifestyle, and cultural influences. Client teaching as an essential function of the nurse is emphasized. Building on fundamental knowledge gained in previous courses, this course examines how research is used in evidence based practice. Critical issues in interprofessional health care and their effect on health care quality, access and cost will be examined. Nursing interventions that promote patient adaptation and safety will be investigated. Obtaining and critically appraising evidence will be emphasized. This course provides students with an overview of the influence of health care policy in shaping the nature, quality, cost, access, and safety of the health care environment. The focus is on the broader context of healthcare, including how patient care services are organized and financed, how reimbursement is structured, and the role of regulatory agencies in defining the boundaries of nursing practice in a complex inter- professional environment. This course provides an overview of the pathophysiological processes common to many diseases. Major pathophysiological concepts are explored using a body systems approach. Concepts and theories related to epidemiology, etiology, pathogenesis, and clinical manifestations are used to study common disease processes. The content will be based on the health-illness continuum, including both physiological and psychological alterations, and system or organ failure. Considerations are given to selected pathological alterations and their effects on physiological and psychological functions. A lifespan approach is utilized with selected disease models and case studies as the focus in the course. Concepts from anatomy, physiology and chemistry courses provide the foundation for exploring human diseases. This course introduces the student to the concepts and principles of public health and the practice of public health nursing. The nursing process is applied to the care of individuals, families, and groups in the community. The theoretical content and clinical practice emphasize community health measures which promote and maintain the health of the community. Research-based knowledge of public health science is incorporated, health team relationships are broadened, and management of client care is practiced through health teaching, counseling, home visiting, and other experiences. Evaluation of care and fostering of accountability are integrated throughout the course. Legal and ethical issues in public health are examined. This course uses a culturally sensitive, person and family-centered approach to the health care needs of women in the childbearing cycle as well as infants, children and adolescents. Emphasis is placed on theoretical knowledge and evidence-based practice findings as the basis for nursing strategies to promote, maintain, and restore health to these populations. Consideration is also given to common complications occurring in the childbearing cycle as well as significant health care issues of the pediatric population. An interprofessional team approach is emphasized in the delivery of safe, effective, and quality care to these populations. Additionally, a family-centered approach is used for the basis of the nursing process and nursing care. This practicum provides an opportunity for students to apply theoretical knowledge and evidence-based practice in the care of childbearing women, infants, children, and adolescents. Nursing care is provided within the context of patient and family culture, preferences, and needs. Helping patients to adapt to changes in function, providing emotional support, and educating patient and families to promote wellness are emphasized. Skills related to enhancing communication, information management, and collaboration as a member of an interprofessional team is further developed. Learning experiences are provided in a variety of settings, as well as, laboratory simulation. This course uses person-centered, family-centered, and culturally sensitive approaches to the health care need of adult and older adults. Emphasis is placed on the theoretical knowledge and evidence-based practice findings as the basis for nursing strategies to promote, maintain, and restore health. An interprofessional team approach is emphasized in the delivery of safe, effective, and quality care. The clinical practicum provides the opportunity to apply evidence-based and patient centered approaches to nursing care. A variety of clinical setting and laboratory simulations are used. The course emphasizes chronic health problems of adults and older adults. Nursing care is provided within the context of client, and family cultural preferences and needs. helping patients adopt to changes in functioning within the context of their chronic disease, providing emotional support, and educating patients and families to promote wellness are emphasized. Skills related to enhancing communication, information management, and collaboration as a member of an interprofessional team are explored. This course builds on previous nursing courses to provide the student with a practicum experience in managing complex patients and environments. This precepted clinical experience focuses on clinical judgment in complex patient situations. The student becomes an integral part of the inter-professional team with responsibility for the efficient management of care that produces cost effective, patient-centered outcomes. Skills related to enhancing communication and information management are refined. The evaluation by credit examination provides students the opportunity to earn academic course credit for prior learning through coursework, experience, training, or self-study. This examination measures knowledge on the health assessment component of the nursing process using a lifespan approach. Integration of health assessment skills will be explored within the dimensions of pathophysiologic changes that occur during alterations in health. Considerations for health assessment will include growth and development, psychological, sociocultural and spiritual health of individuals. A case study approach will be utilized during this course. In this course students analyze important concepts in professional nursing practice including self-care, nursing theory, nursing scholarship, professional codes of conduct and professional standards. The social, legal, ethical, cultural and interprofessional context of nursing practice is presented. Contemporary issues in professional nursing practice are presented including informatics and patient care technology, genetics and genomics, and nursing management across the health-illness continuum, across the lifespan, and in all healthcare settings. Focuses on nursing interventions for patients with altered fluid balance conditions. Interventions to prevent body fluid disturbances are emphasized. Regulatory processes related to maintenance of fluid balance are considered as a basis for nursing practice. This course provides an overview of both the historical and theoretical backgrounds for family violence. It explores definitions of violence and abuse, myths that hinder the understanding of family violence, nursing implications for identification, prevention, and care of victims of family violence, and policy issues related to family violence. Through an increased awareness of both the incidence and impact of violence on health and the health care system, the student will gain an understanding of the role of the nurse in identifying, preventing, and caring for victim/survivors of violence. This course will focus on health care issues affecting women throughout the lifespan and within their family relationships. Strategies and behaviors necessary to maintain a state of health and wellness, as well as, those needed to cope with common alterations in health, will be addressed. A holistic approach with emphasis on the psychosocial aspects of wellness and disease will be presented. The influence of cultural practices and the impact of societal trends in health care will be examined. The role of nursing in promoting the health care of women within their families, including areas of current and future research, will be identified. This course focuses on the theoretical and scientific basis for the care of clients throughout the lifespan who are experiencing life-threatening illness. Using an inquiry-based approach, students will explore physical, psychological, spiritual and sociocultural concerns typically encountered by clients and families confronted with a terminal illness. Ethical and legal issues; pain and symptom management; cultural considerations, communication; grief, loss and bereavement, and other issues that promote quality care at the end of life will be examined. This course provides an overview of the public health implications of emergency preparedness and response. It explores the historical and philosophical basis of terrorism, the nature and effects of natural and manmade disasters, and various response and management strategies for mass casualty events. Through an understanding of this foundational information, students will gain insight and knowledge about the role of the individual, the professional and governmental agencies in meeting the needs of the community during and following a mass casualty event. This course expands on the foundation of pediatric nursing practice in order to enhance both family centered care and the delivery of health care to children from birth through adolescence. Pediatric nursing care and interventions related to topics such as chronic illness, developmental disability, emotional alterations, care of the adolescent, and school nursing will be explored at greater depth. Additionally, family management of symptoms and health promotion for children as well as current trends in pediatric health care will be covered. This course introduces students to a variety of action methods useful in healthcare. The term, action methods, refers to mind/body, multisensory, creative, experiential approaches that promote, maintain, and restore health. Theory, practice and research supporting the effectiveness of action methods with individuals, families, and groups will be presented. In this highly interactive course, students will experience and practice a range of action methods including drama, storytelling, art, music, guided imagery, movement, and mindfulness applicable to nursing practice. This course addresses the needs of critically ill patients across the lifespan within a variety of intensive care settings. Emphasis will be on utilizing the nursing process. This course will include lecture and guided readings regarding commonalities of critical care nursing. Introduction to family systems theory, structural-functional theory, family developmental tasks and patterns of communication. Develops competences to deliver culturally congruent care to families and builds a repertoire of assessment and intervention skills based on an understanding of family theory and research. Emphasis is on the nurse's role in family health promotion and disease prevention. Social issues and public policy that affect family health practices and response to illness are explored and the nurse's role in facilitating family decision making and family advocacy is addressed. This course expands on general concepts related to the care of the childbearing woman and her family. There will be research and discussion into emerging issues pertinent to childbearing families in today's society, as well as a deeper understanding of a wide variety of alterations in the normal process of childbirth. Using an inquiry based approach, students will explore the physiological, psychological, spiritual, and sociocultural concerns encountered by families confronted with a complex childbearing experience. This is an introductory course that focuses on the fundamentals of genetics, genomics and molecular therapeutics. The course is designed to provide a basic understanding of genetic, genomic and molecular concepts so that this knowledge can be utilized to understand current and future genetic theories and therapeutics. Special attention will be given to the translation of concepts into clinical nursing practice. This course facilitates critical examination of the practice of integrated case management. Using a case study approach, critical thinking skills will be fostered to plan for and address the care needs of the patient with complex health needs. Students will utilize tools and resources commonly used by case managers to assess patient care needs, develop a plan of care, and to coordinate patient care including discharge. This course develops the student's knowledge of the nurse's role and responsibilities in drug therapy based on application of concepts from nursing and pharmacology sciences. Legal, ethical, and life span considerations will be presented as they apply to the nurse's role in drug therapy. The student will have the opportunity to study groups of drugs using a structured, systematic approach that includes general principles of drug activity, major actions, therapeutic effects, and adverse reactions. The student will learn to apply the nursing process to the care of the patient receiving drugs in a variety of clinical situations. This course introduces the advanced generalist student to nursing and the role of nurses in promoting the health of individuals, families and communities. The social, legal, ethical, cultural and interprofessional context of clinical decision making in nursing is discussed. The nursing process is presented; clinical decision-making to promote health is emphasized. Nursing interventions to promote health will be introduced and practiced in the laboratory setting. The determinants of health in individuals, families and communities will be explored. Health promotion in special populations will be investigated in classroom and clinical experiences. Building on concepts learned in previous courses, this course uses a lifespan approach in the study of clients experiencing alterations in health. Emphasis is placed on theoretical and evidence based knowledge as the basis for nursing strategies to promote adaptation of the individual and family. The student applies theoretical knowledge in the care of clients in simulated client settings, as well as in problem based learning situations. Field experiences provide the student with the opportunity to interact with clients in actual patient care settings. Building on concepts learned in previous courses, this course uses a lifespan approach in the study of clients experiencing psychosocial alterations in health in a variety of settings. Emphasis is placed on theoretical and evidence based knowledge as the basis for nursing strategies to promote adaptation of the individual and family. The student applies theoretical knowledge in the care of clients in actual client settings. This course examines the environment in which nursing and health care is provided. Health care delivery systems and the organizational theories and behaviors involved in those systems will be introduced. The effect of health care policy in determining accessibility, accountability, and affordability will be investigated. Financing of health care will be discussed and basic business principles will be introduced. The role of the advanced generalist nurse in the provision of quality cost-effective care in a variety of health care systems will be emphasized. This course focuses on concepts, principles, and application of pharmacotherapeutics used by nurse practitioners in the management of health problems. Emphasis is placed on the action, absorption, distribution, metabolism, excretion, and adverse reactions of the major classes of medications used in clinical practice. Considerations that affect disease management in children, adults, older adults, pregnant women, and breastfeeding women are included. This course focuses on the assessment & diagnostic reasoning component of the nursing process in the health care of individuals and families across the lifespan. The course integrates advanced assessment within the dimensions of the adaptation framework including advanced assessments of physical health, growth and development and psychological, sociocultural and spiritual health of individuals within their families. Emphasis is placed on the performance of comprehensive health assessments and the development of advanced assessment skills. Students have the opportunity to practice assessment skills in a simulated client setting. This course provides an in-depth study of the physiological changes and responses to altered health states and their impact on functional status of patients. Pediatric, adult, reproductive, gerontologic, and vulnerable population considerations are incorporated. Using theoretical and evidence based knowledge gained in previous coursework, the student will apply the nursing process to the care of patients and families experiencing acute health alterations. Students will work in an acute care setting to develop a beginning understanding of how patient-centered care and interprofessional collaboration can result in positive outcomes for patients and families. The role of the nurse in providing safe, quality care will be discussed. Applying theoretical and evidence based knowledge gained in previous coursework, the student will apply the nursing process to the care of patients and families experiencing acute health alterations. Students will work with preceptors in an acute care setting to further their understanding of how patient- centered care and interprofessional collaboration results in positive outcomes for patients and families. The role of the nurse in providing safe, quality care will be examined. Applying theoretical and evidence based knowledge gained in previous coursework, the student will apply the nursing process to the care of patients and families experiencing acute health alterations. Students will work with preceptors in an acute care setting to further their understanding of how patient-centered care and interprofessional collaboration results in positive outcomes for patients and families. The role of the nurse in providing safe, quality care will be examined. This course examines the history and development of the advanced practice nursing (APN) role, responsibilities and specialty areas in advanced practice. Capabilities and competencies relevant to advanced practice are explored. Professionalism and commitment to life-long learning are reaffirmed. Selected models, mid-range theories, and tools are used to understand behavior and to identify risks to health. Evidence-based clinical prevention activities are analyzed for their use to improve the health of individuals, families, and populations. Methods for providing leadership in the conceptualization and implementation of clinical prevention and population health for individuals and populations are explored. The impact of lifestyle, cultural, and environmental factors on health and/or health disparity are discussed. Students will implement and evaluate health promotion/disease prevention interventions with individuals and/or groups. This course explores the professional and business aspects of advanced practice nursing. Concepts explored include: legal aspects of practice, cost containment, reimbursement, coding, case management, and outcomes management. Principles of advanced practice nursing management and balancing productivity with quality of care are examined. Mentoring others in practice and the importance of being active in professional organizations are discussed. Relevant theories are applied in the nursing management of clients with primary health care needs and/or acute or chronic illnesses. By using nursing research and practice standards, students implement strategies in the physiological, psychological, sociocultural, and spiritual dimensions in caring for clients and their families. Trends in health care ethical issues and the sociopolitical environment of the adult are analyzed to optimize care management. The practicum component provides for integration of the nurse practitioner role in the primary care setting. This course focuses on the theoretical and scientific basis for advanced nursing management of adult and older adult clients with primary health care needs and/or acute or chronic illnesses. This course will cover multi-system disorders, geriatric syndromes and co-morbidity management. By using nursing research and evidence-based practice guidelines, students implement strategies in the physiological, psychosocial, economic, cultural and spiritual dimensions in caring for adult and older adults and their families. The practicum component provides for application and integration of advanced practice nursing in the primary care setting. This course addresses short-term goals including minimizing or preventing complications, attending to co-morbidities, and promoting physical and psychological well-being. Discussion will relate to palliative care, end-of-life care and evaluation of risk factors to address maximizing health outcomes. Specific skill sets for the Acute Care Nurse Practitioner are developed dependent on the patient population and specialty- based area of practice. The practicum component of this course provides the nurse practitioner student the opportunity to master and apply the theory, knowledge and skills in a variety of acute care settings across the life span. Specific concepts in this course that will be addressed are the management of adult and the older adult with complex acute and unstable conditions in the hospital setting. Discussion will relate to the utilization of invasive interventions and procedures that promote physiologic stability in acute and life threatening conditions. In caring for patients and their families strategies in the physiological, psychological, sociocultural and spiritual dimensions will be implemented. The practicum component of this course provides the nurse practitioner student the opportunity to master and apply the knowledge and skills in a variety of hospital subspecialties. This course focuses on the theoretical and scientific bases for health promotion, maintenance, and management in the primary care of women, expectant families, and children (ages 0-21 years). Well woman care, family planning, and reproductive tract disorders commonly seen in primary care will be studied. Care of children with minor acute and selected stable chronic health problems also will be addressed. Trends in health care, ethical issues and the socioeconomic and political environment of women, expectant families, and children are analyzed to optimize the management of care. A practicum component is required. This course is designed for the family nurse practitioner role in the primary care setting. Content in this course focuses on the acutely ill client with complex illness. Identification of client conditions requiring the application of technology in order to provide comprehensive assessment data or to stabilize the physiological condition are described. The evaluation of these resources and clinical outcomes are also considered. This course provides the student with the opportunity to apply knowledge and skills in the clinical management of children* who are healthy or who are experiencing selected health problems. Emphasis is placed on using models and theories that guide advanced nursing practice. The focus is on the assessment and diagnosis of health risks and health problems. Therapeutic interventions will be designed to promote health for well child care and to restore health for children who have common childhood illnesses. This course provides the student with the opportunity to apply knowledge and skills in the clinical management of children* who are experiencing selected acute and chronic health problems. Emphasis is placed on using models and theories that guide advanced nursing practice. The focus is on the assessment, diagnosis and therapeutic interventions for children with acute and chronic illness and their families. This course focuses on behaviors pertinent to the role of the advanced practice nurse as a psychotherapeutic agent in holistically treating clients across the lifespan with acute and chronic mental health needs/problems. Selected counseling and psychotherapy theories, biopsychosocial theories, and psychiatric mental health-related concepts, issues, problems, and disorders are examined. Clinically, students use research findings, evidence-based clinical practice guidelines, practical knowledge and skills, and theories. Self-initiated academic and personal discoveries are expected. Emphasis is given to active and ongoing collaboration with clients, their families and/or significant others, and the interprofessional team. This course focuses on the use of pertinent theories, research, evidence-based findings, practice guidelines and standards, and interprofessional collaboration to holistically assess and manage complex health and mental health care needs/problems of groups and individuals across the continuum of care and lifespan. Group theories and processes to effectively design, conduct, and evaluate strategies for a structured group therapy product is stressed. The performance of comprehensive psychiatric assessments/evaluations and analysis of client data to formulate differential diagnoses based on appropriate classification systems are emphasized. Students tailor their use of holistic psychotherapy modalities and intervention strategies for clients of selected populations across the lifespan. This course focuses on content that facilitates the development of the psychotherapist role of a psychiatric mental health advanced practice nurse or the counseling role of advanced practice nurses in other specialties when taken as elective. Psychological theories, models, therapies, and treatment strategies that address the requisite knowledge and skills needed to foster therapeutic advanced practice nurse-client relationships across the lifespan are examined with emphasis on target populations. Analysis of treatment/intervention strategies within various theories and models that may be used with particular clients, families, and groups are explored. Personal and professional orientations, values, and behavioral insights are examined throughout the course to promote increasing depth and breadth of understanding of using oneself as a therapeutic tool. This course focuses on concepts, principles, and application of psychopharmacotherapeutics used in the management of individuals across the lifespan at risk for developing and/or having mental health needs/problems or diagnoses of psychiatric disorders. Emphasis is placed on the proposed mechanism of action, metabolism, excretion, and adverse reactions of the major classes of psychopharmacological agents used in a wide range of clinical settings. Multicultural individuals and families at risk for mental and psychosocial problems are considered within the context of primary care practice. Nurse practitioner students will use evidence based practice to integrate behavioral, substance abuse and primary care services for individuals across the lifespan. Evidence based care that includes cognitive-behavioral, psychopharmacological, and non-traditional approaches to psychosocial and related physical problems will be covered using a case study approach. Research related to environmental, psychosocial, genetic, economic, family systems developmental risk factors, drug efficacy and non-pharmacological approaches for individuals with mental and psychosocial illness is investigated. The impact of contemporary health care policy such as the Patient Protection and Health Care Act, and legislative proposals on quality, cost and access to care is investigated. Advanced study of families during the childbearing and child rearing years. Includes consideration of the normative patterns of physical, cognitive, and psychosocial development of children from infancy through adolescence and factors that challenge these normative processes. Emphasizes analysis of theories and research concerning families and the development of children. The focus of this course is on program development and curriculum design in nursing. Theories of education and cognitive development, as a foundation for program development, will be presented. The use of mission and philosophy statements as basis of curriculum development will be explored. Students will participate in the curriculum design process. Issues affecting curriculum design, and development of curriculum outcomes will be analyzed. The evaluation process and its effect on curriculum development and implementation will be considered. Students will gain experience in the development and critique of selected instructional methods for course and lesson development. Teaching-learning principles will be incorporated into the application of educational strategies relevant for clients, staff, and nursing students. Various evaluation methods will be examined. Issues in the selection of instructional strategies and evaluation methods will be discussed. This online course facilitates the graduate student's integration of educational theory and nursing knowledge. The student participates in a teaching practicum under the guidance of an experienced nurse educator. Concurrent seminars address topics promoting the student's role socialization as an educator. The course will focus on gynecologic health care issues for advanced nursing practice. Health promotion, disease prevention, and management of common disorders seen in gynecologic and primary care settings will be examined. By using nursing research and practice standards, students will analyze strategies in the physiological, psychological, sociocultural, and spiritual dimensions in caring for women. Trends in health care ethical issues and the sociopolitical environment of women are analyzed to optimize care management. This course is designed to focus on an integrated approach for health care delivery to the elderly. Emphasis is on the physiological, psychological, socio-cultural, spiritual, ethical and political/legal theoretical basis for care of the elderly. Opportunities are provided to acquire a knowledge base about care of the elderly from faculty in a variety of disciplines in relation to practice, education, and research and to address issues in teaching this content. This course provides the student with a practicum experience that includes concentrated time in the role of an advanced practice nurse. The student assumes responsibility for the provision of health care services to selected populations under the supervision of appropriately qualified preceptors. The student assumes increasing independence and competency in assessing, planning, implementing and evaluating health care. The student increases skill in negotiating the health care system to meet the needs of clients. This course includes seminar discussions exploring the implementation of the role and functions of the advanced practice nurse. Notifies The Graduate Education office that the student is in the final semester of study. A GPA of 3.0 is required to enroll in the course. Independent study course in which the student contracts with a faculty member to supervise the course. Students must obtain permission from the faculty specialty coordinator and the director of the MSN program. Students will be registered for a graduate reading course by the Student Services administrative assistant. NURS 5000: Epidemiology - An overview of epidemiological investigation, including introduction to the tools of descriptive and basic analytical epidemiology, and basic sociodemographic concepts. Basic concepts in statistical inference are discussed as they relate to epidemiological applications. This course provides an overview of health care policy and selected policy models. Ethical, legal, economic and social factors impacting policy development are addressed. The policy making processes at the organizational, local, state, national, and international level are explored. The role of an advanced practice nurse in influencing policy in health care delivery, outcomes and professional nursing is emphasized. Students learn skills to analyze policy processes and engage in politically competent actions. This course focuses on the assessment of health care delivery systems and the organizational theories and behavior involved in those systems. System processes are examined to eliminate health disparities and promote quality of care. Current trends and alternate health care delivery models are explored. Health care reimbursement, forecasting, and outcome management are discussed. Future possibilities of health care delivery models are envisioned. This course utilizes an interprofessional framework to guide the exploration of complex patient-centered care of individuals, families, communities, and vulnerable populations. Course topics include: the history of interprofessional practice, its philosophic principles, terminology, current research, team competencies, and frameworks of practice. This course consists of one 2-hour seminar each week and 1 credit hour of interprofessional clinical practice which is equal to 70 clock hours. This course analyses leadership theories and spheres of influence of the advanced practice nurse in the delivery of health care. Change theory and the process of making change at an organizational/system level are examined. Students will focus on the assessment and enhancement of their leadership skills. Effective leadership strategies within an organization are analyzed. The course requires 75 hours of practicum: 70 hours will be spent with a mentor who holds a leadership position and 5 hours will spent completing a business plan simulation. Information literacy and the use of computers in health care are explored. Students learn the processes for selection and evaluation of information systems. Patient care technology is studied. Use of technology is to analyze outcomes and examine patterns is emphasized. Information systems/decision supports and Web-based learning or clinical tools are discussed to support and improve patient care. This course provides the theoretical and clinical knowledge needed to prepare the advanced practice nurse to engage in evidence based practice. It will provide the opportunity to develop skills needed to critically evaluate new information available from professional consensus statements and research findings. Students are expected to integrate this information into their doctoral nursing practice. This course builds on the basic physical assessment skills of registered nurses. Concepts of diagnostic reasoning and clinical decision-making are presented as integral components of the advanced health assessment of individuals and families across the lifespan. During supervised clinical practicum experiences, students apply theoretical knowledge and advanced practice nursing skills to perform health assessments on clients/patients. The synthesis and application of anatomical-physiological, psychosocial, cultural, spiritual health concepts, growth and development, aging process, and ethical practice are emphasized to achieve competence in comprehensive health assessment as an advanced practice nurse. This course provides an in-depth study of the physiological changes and responses to altered health states and their impact on functional status of patients. Emphasis is placed upon homeostatic mechanisms and etiologies of disease. A systems approach is utilized to understand the interrelationships of function and dysfunction at the cellular and tissue level (pathology), the organ and system level (alterations), and the total human body (functional limitations). Pediatric, reproductive, adult, gerontologic, and vulnerable population considerations may be incorporated. Survey of the techniques, methods and tools of research in the behavioral sciences and social sciences. General discussion of the research process followed by examination of several different study designs such as observational, experimental, descriptive, and sample survey. Overview of different methods of data collection and analysis frequently used in research literature. This course builds on the basic physical assessment skills of registered nurses. Concepts of diagnostic reasoning and clinical decision-making are presented as integral components of the advanced health assessment of individuals and families across the life span. During supervised clinical practicum experiences, students apply theoretical knowledge and advanced practice nursing skills to perform health assessments on clients/patients. The synthesis and application of anatomical-physiological, psychosocial, cultural, spiritual health concepts, growth and development, aging process, and ethical practice are emphasized to achieve competence in comprehensive health assessment as an advanced practice nurse. Examine existing social/behavioral and health science research on promoting the state of health and risk factors associated with vulnerability to health impairment. Includes research which addresses reduction of health disparities, protection of vulnerable populations from health problems and limitation of disability. Areas of research to which nurse researchers have made a significant contribution are highlighted. Analysis of research addresses conceptual, theoretical, methodological, ethical, and nursing practice issues. Psychometric analysis of selected health-related research instruments and their application to the measurement of nursing variables. Includes the study of measurement theory, quantitative research methods and designs, and instrument construction, modification, and evaluation. Analysis of instruments will include discussion of the impact of cultural, ethnicity, gender, and age variables on the development, evaluation, and modification of new and existing instruments. This course focuses on the diffusion of innovations by nursing leaders and how historical events have influenced their innovations to shape contemporary nursing. Policy issues related to nursing and health will be analyzed within the context of social norms and leadership theories/ strategies. Managed care, as policy/practice, will be analyzed. Advanced study of evidence-based practice related to physiological and behavioral responses to acute and chronic illness. The course focuses on analysis of research to promote effective nursing care of acutely and chronically ill populations. Emphasis is on knowledge development to advance nursing as a discipline. This course strengthens students' knowledge of the application and analysis of univariate statistics for generating nursing knowledge. Topics include a review of probability theory, sampling theory and distributions, hypothesis testing, tests of association and independence with emphasis on univariate parametric and nonparametric statistics. Practical application is given to the use of statistical software, graphing data, coding, data management, and conducting nursing research. This course uses a general linear models approach to data analysis with multivariate/ multivariable techniques, including ANOVA/MANOVA methods for repeated measures, multiple regression, logistic regression, factor analysis, and introduction to model fitting techniques. Emphasis is given to interpretative principles of research design, statistical modeling, and analysis methods applied to nursing and clinical research rather than on specific mathematical details. This course builds upon prior study in qualitative research methods. The course will examine phenomenology as a methodology for understanding human actions and for conducting research into human practices and meanings. The hermeneutic turn for developing knowledge for practice disciplines (e.g. education, psychology, family therapy, nursing, social work, public administration, and medicine) will be addressed along with issues and skills in conducting interpretive research. Post-modern conceptions of validity for evaluating interpretive research will also be examined. The course is for students who intend to use interpretive methods for their dissertation research. Students will examine primary philosophical sources for describing the methodological implications of interpretive phenomenology for studying human meanings and practices, including professional and lay caregiving. This course focuses on the conceptual understanding and practical application of quantitative research synthesis. Topics will include writing purpose statements and research questions, developing advanced search strategies, coding primary studies, and analyzing and interpreting data. Application emphasis will be on intervention studies. Provides guided doctoral research experience in nursing. Time and credit hour allocation as well as specific project topic must be registered with the guiding professor and the program director.
https://www.slu.edu/nursing/degrees/course-descriptions.php
For too long Counselling Psychology perspectives to understanding human distress have been drowned out by medical and clinical voices. This book challenges this, adding as it does to the emerging literature offering reflection and debate as to what a human – and humane - approach to such distress might be. By reflecting on the dilemmas embedded in this area this book offers a rare chance to think meaningfully about distress rather than simply ‘do something’ to it. I believe that this book makes a really useful and timely contribution to the literature and therefore potentially to clinical practice. It will be valuable to psychologists, psychotherapists, psychiatrists and others engaged in therapeutic practice in a wide range of contexts. It combines elements of critical thinking with a real depth of clinical experience and a useful selection of examples. The book contains contributions from both the authors and a range of clinicians with many years of experience. This is an excellent and timely evaluation of some of the most common presenting problems faced by the contemporary psychological therapist. What makes this book so unique is constant linking between theory and practice, allowing the reader true insight into the thinking behind the conceptualisation of distress as well as how to work with it effectively in the consulting room. The book will appeal to students, practitioners and academics alike. For me, a therapist but not a psychologist, the book’s greatest strength was the insight it gave me into the breadth of counselling psychology practice and the inclusion by the authors of multiple perspectives in their interventions with clients. It is, I would suggest, essential reading for counselling psychologists and may also be of interest to other therapists. This insightful book [...] should be in the library of every counselling, psychotherapy and counselling psychology practitioner, whether experienced or in training [...] This is a thoroughly refreshing read that validates the importance of keeping the client in mind and providing a type of care that is individual, attuning and compassionate via the therapeutic relationship. Good range of presenting issues covered, excellent book for completing assignments and good use of case studies throughout This is a great introductory text for trainees and potential trainees to give them an up close a personal sense of typically presenting cases in psychotherapy, covering a diverse range of poignant illustrative examples. This book provides a useful guide to working with different presenting issues. This is a good introductory book but it could have done with more details and seemed a bit thin on theory. This is a very comprehensive book and clearly written for all students. I enjoyed this topical and very accessible volume, which I think will appeal to our final year students, who are already engaging in therapeutic practice. It offers clear clinical input, with case study vignettes which help to bring theory to life. Useful book with clear text The authors successfully give a distinct counselling psychology perspective on the sorts of distress that we routinely see in our consulting rooms. It integrates theory and practice in a concise way that will be invaluable for trainees and qualified psychological therapists who have to negotiate the gaps between diagnostic criteria and clinical experience. More useful for me as a teaching to remember what the students might not yet be aware of, and will be mentioning the book as a contextualising text if they want an overview, or 'feel' for the presenting issue. This is quite an intriguing book in that it tries to bring together the medical and nonmedical models in looking at therapeutic approaches to common problems. The chapters are (ironically as acknowledged by the authors) titled according to the medical model. Each chapter then gives some historical context of the condition followed by a section on dilemmas and then a section on research and practice. These sections are usually written by different authors with quite different writing styles. This book will be recommended for level 5 students who are preparing for a counselling placement. There is a focused range of presenting issues that will be of some interest to counsellors and therefore this book will be considered a supplemental text to support student research. This is very informative, and practical guidance for social workers, thinking of intervening when there are complex issues of emotional and mental health. This will inform your practice and interventions. This will give a deeper understanding of the processes, specific needs, and which approaches are most helpful and considerations you need to make. A great refresher to update knowledge.
https://uk.sagepub.com/en-gb/eur/node/56119/download.pdf
There are over 350,000 maintenance thrice-weekly hemodialysis patients in the United States. These patients have exceptionally poor survival with mortality rates exceeding those of the general population by greater than 10-fold. Prior research has suggested that modifications in dialytic practice such as gentler ultrafiltration rates (UFR) may improve survival. UFR is determined by both the amount of fluid that must be removed (which at steady state equals the inter-dialytic weight gain;IDWG) and the time over which this fluid is removed (dialysis session length;DSL), each of which are plausibly associated with mortality. This project seeks to elucidate the independent associations between DSL and IDWG and mortality. A matched, retrospective cohort analysis of a nationally representative population of prevalent chronic, thrice weekly hemodialysis patients (n= 10,000) with follow-up time of 5 years will be used to: 1) estimate the association between IDWG and mortality, independent of DSL, through analysis of matched pairs of participants with discordant IDWG but identical DSL, and 2) estimate the association between DSL and mortality, independent of IDWG, through analysis of matched pairs of participants with discordant DSL but identical IDWG. A matched study design has been chosen to allow for complete control of DSL in analyses of IDWG and for IDWG in analyses of DSL to enable accurate estimation of the independent association of each with survival. Findings will inform modifications to clinical practice and direct future research. In addition to understanding the independent relationships of DSL and IDWG and mortality, the project will assess patients'willingness to adopt interventions aimed at improving health and survival through targeted manipulations of fluid management. No prior research has assessed patient willingness to extend DSL in response to volume considerations within the context of thrice weekly dialysis. Other untested methods of IDWG control including interdialytic peritoneal dialysis and wearable ultrafiltration devices do exist. An instrument will be developed and validated to assess patient willingness to adhere to fluid/salt restrictions, adopt adjunct interdialytic peritoneal dialysis, utilize wearable ultrafiltration devices, and extend DSL as methods to minimize need for rapid UFR. This instrument will then be used to survey attitudes of 5,000 randomly selected hemodialysis outpatients from the End Stage Renal Disease Network of New England. Responses will inform clinical practice and guide future research in volume mitigation. Dialysis patients experience an extremely high burden of mortality. This project seeks to elucidate how aggressive ultrafiltration rates increase mortality by examining the independent relationships of mortality and dialysis session length and mortality and interdialytic weight gain. Additionally, the project seeks to understand dialysis patient willingness to engage in different volume mitigation strategies. Results will guide clinical practice and future research by identifying ways in which the dialytic prescription can be modified to improve mortality.
https://grantome.com/grant/NIH/F32-DK093159-01
Background: There is growing interest in assisted living technologies to support independence at home. Such technologies should ideally be designed 'in the wild' i.e. taking account of how real people live in real homes and communities. The ATHENE (Assistive Technologies for Healthy Living in Elders: Needs Assessment by Ethnography) project seeks to illuminate the living needs of older people and facilitate the co-production with older people of technologies and services. This paper describes the development of a cultural probe tool produced as part of the ATHENE project and how it was used to support home visit interviews with elders with a range of ethnic and social backgrounds, family circumstances, health conditions and assisted living needs. Method. Thirty one people aged 60 to 98 were visited in their homes on three occasions. Following an initial interview, participants were given a set of cultural probe materials, including a digital camera and the 'Home and Life Scrapbook' to complete in their own time for one week. Activities within the Home and Life Scrapbook included maps (indicating their relationships to people, places and objects), lists (e.g. likes, dislikes, things they were concerned about, things they were comfortable with), wishes (things they wanted to change or improve), body outline (indicating symptoms or impairments), home plan (room layouts of their homes to indicate spaces and objects used) and a diary. After one week, the researcher and participant reviewed any digital photos taken and the content of the Home and Life Scrapbook as part of the home visit interview. Findings. The cultural probe facilitated collection of visual, narrative and material data by older people, and appeared to generate high levels of engagement from some participants. However, others used the probe minimally or not at all for various reasons including limited literacy, physical problems (e.g. holding a pen), lack of time or energy, limited emotional or psychological resources, life events, and acute illness. Discussions between researchers and participants about the materials collected (and sometimes about what had prevented them completing the tasks) helped elicit further information relevant to assisted living technology design. The probe materials were particularly helpful when having conversations with non-English speaking participants through an interpreter. Conclusions: Cultural probe methods can help build a rich picture of the lives and experiences of older people to facilitate the co-production of assisted living technologies. But their application may be constrained by the participant's physical, mental and emotional capacity. They are most effective when used as a tool to facilitate communication and development of a deeper understanding of older people's needs. © 2012 Wherton et al.; licensee BioMed Central Ltd. Rethinking resistance to ‘big IT’: a sociological study of why and when healthcare staff do not use nationally mandated information and communication technologies Nationally mandated information and communication technology (ICT) systems are often locally resented and little used. This problem is sometimes framed in behaviourist terms, depicting the intended user of technology as a rational actor whose resistance stems from Luddism and/or ignorance, and viewing solutions in terms of training, incentives and sanctions. The implication is that if we get the ‘rewards’ and ‘punishments’ right, people will use technologies. Previous research in the social sciences, notably sociotechnical systems theory, actor–network theory and normalisation process theory, have considered the human, social and organisational context of technology use (and non-use). However, these have all had limitations in explaining the particular phenomenon of resistance to nationally mandated ICT systems.To develop a sociologically informed theory of resistance to nationally mandated ICT systems.We drew on Anthony Giddens’ notion of expert systems (comprising bureaucratic rules and classification systems delivered through technology) as well as theories of professional roles and ethical practice. A defining characteristic of expert systems is that they can produce ‘action at a distance’, allowing managerial control to be exerted over local practice. To the extent that people use them as intended, these systems invariably ‘empty out’ social situations by imposing rules and categories that are insensitive to local contingencies or the unfolding detail of social situations.Secondary analysis of data from case studies of three nationally mandated ICT systems in the English NHS, collected over the period 2007–10.Our analysis focused mainly on the Choose and Book system for outpatient referrals, introduced in 2004, which remained unpopular and little used throughout the period of our research (i.e. 2007–13). We identified four foci of resistance: to the policy of choice that Choose and Book symbolised and purported to deliver; to accommodating the technology’s sociomaterial constraints; to interference with doctors’ contextual judgements; and to adjusting to the altered social relations consequent on its use. More generally, use of the mandated system tended to constrain practice towards a focus on (the efficiency of) means rather than (the moral value of) ends. A similar pattern of complex sociological reasons for resistance was also seen in the other two technologies studied (electronic templates for chronic disease management and the Summary Care Record), though important differences surfaced and were explained in terms of the policy inscribed in the technology and its material features.‘Resistance’ is a complex phenomenon with sociomaterial and normative components; it is unlikely to be overcome using atheoretical behaviourist techniques. To guide the study of resistance to ICT systems in health care, we offer a new theoretical and empirical approach, based around a set of questions about the policy that the technology is intended to support; the technology’s material properties; the balance between (bureaucratic) means and (professional) ends; and the implications for social roles, relationship and interactions. We suggest avenues for future research, including methodology (e.g. extending the scope and scale of ethnographic research in ICT infrastracture), theory development (e.g. relating to the complexities of multi-professional team working) and empirical (e.g. how our findings might inform the design and implementation of technologies that are less likely to be resisted).The National Institute for Health Research Health Services and Delivery Research programme. The impact on healthcare, policy and practice from 36 multi-project research programmes: Findings from two reviews © 2017 The Author(s). Background: We sought to analyse the impacts found, and the methods used, in a series of assessments of programmes and portfolios of health research consisting of multiple projects. Methods: We analysed a sample of 36 impact studies of multi-project research programmes, selected from a wider sample of impact studies included in two narrative systematic reviews published in 2007 and 2016. We included impact studies in which the individual projects in a programme had been assessed for wider impact, especially on policy or practice, and where findings had been described in such a way that allowed them to be collated and compared. Results: Included programmes were highly diverse in terms of location (11 different countries plus two multi-country ones), number of component projects (8 to 178), nature of the programme, research field, mode of funding, time between completion and impact assessment, methods used to assess impact, and level of impact identified. Thirty-one studies reported on policy impact, 17 on clinician behaviour or informing clinical practice, three on a combined category such as policy and clinician impact, and 12 on wider elements of impact (health gain, patient benefit, improved care or other benefits to the healthcare system). In those multi-programme projects that assessed the respective categories, the percentage of projects that reported some impact was policy 35% (range 5-100%), practice 32% (10-69%), combined category 64% (60-67%), and health gain/health services 27% (6-48%). Variations in levels of impact achieved partly reflected differences in the types of programme, levels of collaboration with users, and methods and timing of impact assessment. Most commonly, principal investigators were surveyed; some studies involved desk research and some interviews with investigators and/or stakeholders. Most studies used a conceptual framework such as the Payback Framework. One study attempted to assess the monetary value of a research programme's health gain. Conclusion: The widespread impact reported for some multi-project programmes, including needs-led and collaborative ones, could potentially be used to promote further research funding. Moves towards greater standardisation of assessment methods could address existing inconsistencies and better inform strategic decisions about research investment; however, unresolved issues about such moves remain. Systematic meta-review of supported self-management for asthma: A healthcare perspective © 2017 The Author(s). Background: Supported self-management has been recommended by asthma guidelines for three decades; improving current suboptimal implementation will require commitment from professionals, patients and healthcare organisations. The Practical Systematic Review of Self-Management Support (PRISMS) meta-review and Reducing Care Utilisation through Self-management Interventions (RECURSIVE) health economic review were commissioned to provide a systematic overview of supported self-management to inform implementation. We sought to investigate if supported asthma self-management reduces use of healthcare resources and improves asthma control; for which target groups it works; and which components and contextual factors contribute to effectiveness. Finally, we investigated the costs to healthcare services of providing supported self-management. Methods: We undertook a meta-review (systematic overview) of systematic reviews updated with randomised controlled trials (RCTs) published since the review search dates, and health economic meta-analysis of RCTs. Twelve electronic databases were searched in 2012 (updated in 2015; pre-publication update January 2017) for systematic reviews reporting RCTs (and update RCTs) evaluating supported asthma self-management. We assessed the quality of included studies and undertook a meta-analysis and narrative synthesis. Results: A total of 27 systematic reviews (n = 244 RCTs) and 13 update RCTs revealed that supported self-management can reduce hospitalisations, accident and emergency attendances and unscheduled consultations, and improve markers of control and quality of life for people with asthma across a range of cultural, demographic and healthcare settings. Core components are patient education, provision of an action plan and regular professional review. Self-management is most effective when delivered in the context of proactive long-term condition management. The total cost (n = 24 RCTs) of providing self-management support is offset by a reduction in hospitalisations and accident and emergency visits (standard mean difference 0.13, 95% confidence interval -0.09 to 0.34). Conclusions: Evidence from a total of 270 RCTs confirms that supported self-management for asthma can reduce unscheduled care and improve asthma control, can be delivered effectively for diverse demographic and cultural groups, is applicable in a broad range of clinical settings, and does not significantly increase total healthcare costs. Informed by this comprehensive synthesis of the literature, clinicians, patient-interest groups, policy-makers and providers of healthcare services should prioritise provision of supported self-management for people with asthma as a core component of routine care. Systematic review registration: RECURSIVE: PROSPERO CRD42012002694 ; PRISMS: PROSPERO does not register meta-reviews The bright elusive butterfly of value in health technology development: Comment on “providing value to new health technology: The early contribution of entrepreneurs, investors, and regulatory agencies” © 2018 The Author(s). The current system of health technology development is characterised by multiple misalignments. The “supply” side (innovation policy-makers, entrepreneurs, investors) and the “demand” side (health policy-makers, regulators, health technology assessment, purchasers) operate under different – and conflicting – logics. The system is less a “pathway” than an unstable ecosystem of multiple interacting sub-systems. “Value” means different things to each of the numerous actors involved. Supply-side dynamics are built on fictions; regulatory checks and balances are designed to assure quality, safety and efficacy, not to ensure that technologies entering the market are either desirable or cost-effective. Assessment of comparative and cost-effectiveness usually comes too late in the process to shape an innovation’s development. We offer no simple solutions to these problems, but in the spirit of commencing a much-needed public debate, we suggest some tentative ways forward. First, universities and public research funders should play a more proactive role in shaping the system. Second, the role of industry in forging long-term strategic partnerships for public benefit should be acknowledged (though not uncritically). Third, models of “responsible innovation” and public input to research priority-setting should be explored. Finally, the evidence base on how best to govern inter-sectoral health research partnerships should be developed and applied. Has evidence-based medicine ever been modern? A Latour-inspired understanding of a changing EBM © 2017 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons, Ltd. Evidence-based health care (EBHC), previously evidence-based medicine (EBM), is considered by many to have modernized health care and brought it from an authority-based past to a more rationalist, scientific grounding. But recent concerns and criticisms pose serious challenges and urge us to look at the fundamentals of a changing EBHC. In this paper, we present French philosopher Bruno Latour's vision on modernity as a framework to discuss current changes in the discourse on EBHC/EBM. Drawing on Latour's work, we argue that the early EBM movement had a strong modernist agenda with an aim to “purify” clinical reality into a dichotomy of objective “evidence” from nature and subjective “preferences” from human society and culture. However, we argue that this shift has proved impossible to achieve in reality. Several recent developments appear to point to a demise of purified evidence in the EBHC discourse and a growing recognition—albeit implicit and undertheorized—that evidence in clinical decision making is relentlessly situated and contextual. The unique, individual patient, not abstracted truths from distant research studies, must be the starting point for clinical practice. It follows that the EBHC community needs to reconsider the assumption that science should be abstracted from culture and acknowledge that knowledge from human culture and nature both need translation and interpretation. The implications for clinical reasoning are far reaching. We offer some preliminary principles for conceptualizing EBHC as a “situated practice” rather than as a sequence of research-driven abstract decisions. Group clinics for young adults with diabetes in an ethnically diverse, socioeconomically deprived setting (TOGETHER study): Protocol for a realist review, co-design and mixed methods, participatory evaluation of a new care model © 2017 Article author(s). Introduction Young adults with diabetes often report dissatisfaction with care and have poor diabetes-related health outcomes. As diabetes prevalence continues to rise, group-based care could provide a sustainable alternative to traditional one-to-one consultations, by engaging young people through life stage-, context- and culturally-sensitive approaches. In this study, we will co-design and evaluate a group-based care model for young adults with diabetes and complex health and social needs in socioeconomically deprived areas. Methods and analysis This participatory study will include three phases. In phase 1, we will carry out a realist review to synthesise the literature on group-based care for young adults with diabetes. This theory-driven understanding will provide the basis for phase 2, where we will draw on experience-based co-design methodologies to develop a new, group-based care model for young adults (aged <25 years, under the care of adult diabetes services). In phase 3, we will use a researcher-in-residence approach to implement and evaluate the co-designed group clinic model and compare with traditional care. We will employ qualitative (observations in clinics, patient and staff interviews and document analysis) and quantitative methods (eg, biological markers, patient enablement instrument and diabetes distress scale), including a cost analysis. Ethics and dissemination National Health Service ethics approval has been granted (reference 17/NI/0019). The project will directly inform service redesign to better meet the needs of young adults with diabetes in socioeconomically deprived areas and may guide a possible cluster-randomised trial, powered to clinical and cost-effectiveness outcomes. Findings from this study may be transferable to other long-term conditions and/or age groups. Project outputs will include briefing statements, summaries and academic papers, tailored for different audiences, including people living with diabetes, clinicians, policy makers and strategic decision makers. Understanding heart failure; explaining telehealth - A hermeneutic systematic review © The Author(s). 2017. Background: Enthusiasts for telehealth extol its potential for supporting heart failure management. But randomised trials have been slow to recruit and produced conflicting findings; real-world roll-out has been slow. We sought to inform policy by making sense of a complex literature on heart failure and its remote management. Methods: Through database searching and citation tracking, we identified 7 systematic reviews of systematic reviews, 32 systematic reviews (including 17 meta-analyses and 8 qualitative reviews); six mega-trials and over 60 additional relevant empirical studies and commentaries. We synthesised these using Boell's hermeneutic methodology for systematic review, which emphasises the quest for understanding. Results: Heart failure is a complex and serious condition with frequent co-morbidity and diverse manifestations including severe tiredness. Patients are often frightened, bewildered, socially isolated and variably able to selfmanage. Remote monitoring technologies are many and varied; they create new forms of knowledge and new possibilities for care but require fundamental changes to clinical roles and service models and place substantial burdens on patients, carers and staff. The policy innovation of remote biomarker monitoring enabling timely adjustment of medication, mediated by "activated" patients, is based on a modernist vision of efficient, rational, technology-mediated and guideline-driven ("cold") care. It contrasts with relationship-based ("warm") care valued by some clinicians and by patients who are older, sicker and less technically savvy. Limited uptake of telehealth can be analysed in terms of key tensions: between tidy, "textbook" heart failure and the reality of multiple comorbidities; between basic and intensive telehealth; between activated, well-supported patients and vulnerable, unsupported ones; between "cold" and "warm" telehealth; and between fixed and agile care programmes. Conclusion: The limited adoption of telehealth for heart failure has complex clinical, professional and institutional causes, which are unlikely to be elucidated by adding more randomised trials of technology-on versus technologyoff to an already-crowded literature. An alternative approach is proposed, based on naturalistic study designs, application of social and organisational theory, and co-design of new service models based on socio-technical principles. Conventional systematic reviews (whose goal is synthesising data) can be usefully supplemented by hermeneutic reviews (whose goal is deepening understanding). Preventing type 2 diabetes: Systematic review of studies of cost-effectiveness of lifestyle programmes and metformin, with and without screening, for pre-diabetes © 2017 Article author(s) (or their employer(s) unless otherwise stated in the text of the article). All rights reserved. No commercial use is permitted unless otherwise expressly granted. Objective Explore the cost-effectiveness of lifestyle interventions and metformin in reducing subsequent incidence of type 2 diabetes, both alone and in combination with a screening programme to identify high-risk individuals. Design Systematic review of economic evaluations. Data sources and eligibility criteria Database searches (Embase, Medline, PreMedline, NHS EED) and citation tracking identified economic evaluations of lifestyle interventions or metformin alone or in combination with screening programmes in people at high risk of developing diabetes. The International Society for Pharmaco-economics and Outcomes Research's Questionnaire to Assess Relevance and Credibility of Modelling Studies for Informing Healthcare Decision Making was used to assess study quality. Results 27 studies were included; all had evaluated lifestyle interventions and 12 also evaluated metformin. Primary studies exhibited considerable heterogeneity in definitions of pre-diabetes and intensity and duration of lifestyle programmes. Lifestyle programmes and metformin appeared to be cost effective in preventing diabetes in high-risk individuals (median incremental cost-effectiveness ratios of £7490/quality-adjusted life-year (QALY) and £8428/QALY, respectively) but economic estimates varied widely between studies. Intervention-only programmes were in general more cost effective than programmes that also included a screening component. The longer the period evaluated, the more cost-effective interventions appeared. In the few studies that evaluated other economic considerations, budget impact of prevention programmes was moderate (0.13%-0.2% of total healthcare budget), financial payoffs were delayed (by 9-14 years) and impact on incident cases of diabetes was limited (0.1%-1.6% reduction). There was insufficient evidence to answer the question of (1) whether lifestyle programmes are more cost effective than metformin or (2) whether low-intensity lifestyle interventions are more cost effective than the more intensive lifestyle programmes that were tested in trials. Conclusions The economics of preventing diabetes are complex. There is some evidence that diabetes prevention programmes are cost effective, but the evidence base to date provides few clear answers regarding design of prevention programmes because of differences in denominator populations, definitions, interventions and modelling assumptions. Maximising value from a United Kingdom Biomedical Research Centre: study protocol BACKGROUND: Biomedical Research Centres (BRCs) are partnerships between healthcare organisations and universities in England. Their mission is to generate novel treatments, technologies, diagnostics and other interventions that increase the country's international competitiveness, to rapidly translate these innovations into benefits for patients, and to improve efficiency and reduce waste in healthcare. As NIHR Oxford BRC (Oxford BRC) enters its third 5-year funding period, we seek to (1) apply the evidence base on how best to support the various partnerships in this large, multi-stakeholder research system and (2) research how these partnerships play out in a new, ambitious programme of translational research.METHODS: Organisational case study, informed by the principles of action research. A cross-cutting theme, 'Partnerships for Health, Wealth and Innovation' has been established with multiple sub-themes (drug development, device development, business support and commercialisation, research methodology and statistics, health economics, bioethics, patient and public involvement and engagement, knowledge translation, and education and training) to support individual BRC research themes and generate cross-theme learning. The 'Partnerships' theme will support the BRC's goals by facilitating six types of partnership (with patients and citizens, clinical services, industry, across the NIHR infrastructure, across academic disciplines, and with policymakers and payers) through a range of engagement platforms and activities. We will develop a longitudinal progress narrative centred around exemplar case studies, and apply theoretical models from innovation studies (Triple Helix), sociology of science (Mode 2 knowledge production) and business studies (Value Co-creation). Data sources will be the empirical research studies within individual BRC research themes (who will apply separately for NHS ethics approval), plus documentary analysis and interviews and ethnography with research stakeholders. This study has received ethics clearance through the University of Oxford Central University Research Ethics Committee.DISCUSSION: We anticipate that this work will add significant value to Oxford BRC. We predict accelerated knowledge translation; closer alignment of the innovation process with patient priorities and the principles of responsible, ethical research; reduction in research waste; new knowledge about the governance and activities of multi-stakeholder research partnerships and the contexts in which they operate; and capacity-building that reflects the future needs of a rapidly-evolving health research system. Studying scale-up and spread as social practice: Theoretical introduction and empirical case study Background: Health and care technologies often succeed on a small scale but fail to achieve widespread use (scale-up) or become routine practice in other settings (spread). One reason for this is under-theorization of the process of scale-up and spread, for which a potentially fruitful theoretical approach is to consider the adoption and use of technologies as social practices. Objective: This study aimed to use an in-depth case study of assisted living to explore the feasibility and usefulness of a social practice approach to explaining the scale-up of an assisted-living technology across a local system of health and social care. Methods: This was an individual case study of the implementation of a Global Positioning System (GPS) "geo-fence" for a person living with dementia, nested in a much wider program of ethnographic research and organizational case study of technology implementation across health and social care (Studies in Co-creating Assisted Living Solutions [SCALS] in the United Kingdom). A layered sociological analysis included micro-level data on the index case, meso-level data on the organization, and macro-level data on the wider social, technological, economic, and political context. Data (interviews, ethnographic notes, and documents) were analyzed and synthesized using structuration theory. Results: A social practice lens enabled the uptake of the GPS technology to be studied in the context of what human actors found salient, meaningful, ethical, legal, materially possible, and professionally or culturally appropriate in particular social situations. Data extracts were used to illustrate three exemplar findings. First, professional practice is (and probably always will be) oriented not to "implementing technologies" but to providing excellent, ethical care to sick and vulnerable individuals. Second, in order to "work," health and care technologies rely heavily on human relationships and situated knowledge. Third, such technologies do not just need to be adopted by individuals; they need to be incorporated into personal habits and collaborative routines (both lay and professional). Conclusions: Health and care technologies need to be embedded within sociotechnical networks and made to work through situated knowledge, personal habits, and collaborative routines. A technology that "works" for one individual in a particular set of circumstances is unlikely to work in the same way for another in a different set of circumstances. We recommend the further study of social practices and the application of co-design principles. However, our findings suggest that even if this occurs, the scale-up and spread of many health and care technologies will be neither rapid nor smooth. The clinical academic workforce of the future: A cross-sectional study of factors influencing career decision-making among clinical PhD students at two research-intensive UK universities © 2017 Article author(s). All rights reserved. Objectives To examine clinical doctoral students' demographic and training characteristics, career intentions, career preparedness and what influences them as they plan their future careers. Design and setting Online cross-sectional census surveys at two research-intensive medical schools in England in 2015-2016. Participants All medically qualified PhD students (N=523) enrolled at the University of Oxford and University College London were invited to participate. We report on data from 320 participants (54% male and 44% female), who were representative by gender of the invited population. Main outcome measures Career intentions. Results Respondents were mainly in specialty training, including close to training completion (25%, n=80), and 18% (n=57) had completed training. Half (50%, n=159) intended to pursue a clinical academic career (CAC) and 62% (n=198) were at least moderately likely to seek a clinical lectureship (CL). However, 51% (n=163) had little or no knowledge about CL posts. Those wanting a CAC tended to have the most predoctoral medical research experience (Χ 2 (2, N=305)=22.19, p=0.0005). Key reasons cited for not pursuing a CAC were the small number of senior academic appointments available, the difficulty of obtaining research grants and work-life balance. Conclusions Findings suggest that urging predoctoral clinicians to gain varied research experience while ensuring availability of opportunities, and introducing more flexible recruitment criteria for CL appointments, would foster CACs. As CL posts are often only open to those still in training, the many postdoctoral clinicians who have completed training, or nearly done so, do not currently gain the opportunity the post offers to develop as independent researchers. Better opportunities should be accompanied by enhanced career support for clinical doctoral students (eg, to increase knowledge of CLs). Finally, ways to increase the number of senior clinical academic appointments should be explored since their lack seems to significantly influence career decisions. Equipping community pharmacy workers as agents for health behaviour change: Developing and testing a theory-based smoking cessation intervention © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. Objective To develop a complex intervention for community pharmacy staff to promote uptake of smoking cessation services and to increase quit rates. Design Following the Medical Research Council framework, we used a mixed-methods approach to develop, pilot and then refine the intervention. Methods Phase I: We used information from qualitative studies in pharmacies, systematic literature reviews and the Capability, Opportunity, Motivation - Behaviour framework to inform design of the initial version of the intervention. Phase II: We then tested the acceptability of this intervention with smoking cessation advisers and assessed fidelity using actors who visited pharmacies posing as smokers, in a pilot study. Phase III: We reviewed the content and associated theory underpinning our intervention, taking account of the results of the earlier studies and a realist analysis of published literature. We then confirmed a logic model describing the intended operation of the intervention and used this model to refine the intervention and associated materials. Setting Eight community pharmacies in three inner east London boroughs. Participants 12 Stop Smoking Advisers. Intervention Two, 150 min, skills-based training sessions focused on communication and behaviour change skills with between session practice. Results The pilot study confirmed acceptability of the intervention and showed preliminary evidence of benefit; however, organisational barriers tended to limit effective operation. The pilot data and realist review pointed to additional use of Diffusion of Innovations Theory to seat the intervention in the wider organisational context. Conclusions We have developed and refined an intervention to promote smoking cessation services in community pharmacies, which we now plan to evaluate in a randomised controlled trial. Trial registration number UKCRN ID 18446, Pilot. Structural analysis of health-relevant policy-making information exchange networks in Canada © 2017 The Author(s). Background: Health systems worldwide struggle to identify, adopt, and implement in a timely and system-wide manner the best-evidence-informed-policy-level practices. Yet, there is still only limited evidence about individual and institutional best practices for fostering the use of scientific evidence in policy-making processes The present project is the first national-level attempt to (1) map and structurally analyze-quantitatively-health-relevant policy-making networks that connect evidence production, synthesis, interpretation, and use; (2) qualitatively investigate the interaction patterns of a subsample of actors with high centrality metrics within these networks to develop an in-depth understanding of evidence circulation processes; and (3) combine these findings in order to assess a policy network's "absorptive capacity" regarding scientific evidence and integrate them into a conceptually sound and empirically grounded framework. Methods: The project is divided into two research components. The first component is based on quantitative analysis of ties (relationships) that link nodes (participants) in a network. Network data will be collected through a multi-step snowball sampling strategy. Data will be analyzed structurally using social network mapping and analysis methods. The second component is based on qualitative interviews with a subsample of the Web survey participants having central, bridging, or atypical positions in the network. Interviews will focus on the process through which evidence circulates and enters practice. Results from both components will then be integrated through an assessment of the network's and subnetwork's effectiveness in identifying, capturing, interpreting, sharing, reframing, and recodifying scientific evidence in policy-making processes. Discussion: Knowledge developed from this project has the potential both to strengthen the scientific understanding of how policy-level knowledge transfer and exchange functions and to provide significantly improved advice on how to ensure evidence plays a more prominent role in public policies.
https://www.phc.ox.ac.uk/@@search?b_start:int=340
In the rational choice problem Zutler (2011) proposed a model of choice by continuous Markov random walk on a set of alternatives to find the best. In this paper we investigate the optimal properties of obtained solutions. It is shown that the result of this choice is the maximal element on a set of lotteries with respect to relation for special function that has a natural interpretation as flow of probability from one to another lottery. It is shown the relationship between the problems of choosing the best alternative and non-cooperative games solution. It is proved that Nash equilibrium is a stationary point of a dynamical system of the continuous random walk of players on the set of available strategies. The intensity transition of the player from one strategy to another is equal to his assessment of increase of payoff in the alleged current rival’s strategies. We design the elements of an automated tool for thequantitative analysis of the future regional power supply system based on the opinion of regional authorities on the current and future availability of power supply services in the industry and in the domestic sector. A mathematical model is suggested to estimate the return of investment into new power station and storage construction. The model includes a non-cooperative game on polyhedra, where the first player’s payoff function adds up from the bilinear and the linear function of vector arguments, whereas the the payoff function of the second player is a bilinear function of the same arguments. We prove that equilibria in this game can be found by solving a dual pair of linear programming problems. These equilibria determine, in particular, the volume of investment for generators and the electricity price for consumers, which are mutually acceptable to both parties. We consider a game equilibrium in a network in each node of which an economy is described by the simple two-period model of endogenous growth with production and knowledge externalities. Each node of the network obtains an externality produced by the sum of knowledge in neighbor nodes. Uniqueness of the inner equilibrium is proved. Three ways of behavior of each agent are distinguished: active, passive, hyperactive. Behavior of agents in dependence on received externalities is studied. It is shown that the equilibrium depends on the network structure. We study the role of passive agents; in particular, possibilities of connection of components of active agents through components of passive agents. A notion of type of node is introduced and classification of networks based on this notion is provided. It is shown that the inner equilibrium depends not on the size of network but on its structure in terms of the types of nodes, and in similar networks of different size agents of the same type behave in similar way. In this paper, we consider the following problem - what affects the amount of investment in knowledge when one of the network firms enters another innovation network. The solution of this problem will allow us to understand exactly how innovative companies will behave when deciding whether to enter the innovation network of another country or region, what conditions affect it and how the level of future investments in knowledge can be predicted. This paper studies a model of game interaction with externalities on a network, in which agents choose their level of investment. We compare two concepts of equilibrium: standard Nash definition and “Jacobian” definition of equilibrium with externalities. It is shown that in both cases agents may be passive, active and hyperactive, and conditions for optimality of these types of behavior are derived. In particular, we study the case of a full homogeneous network and show that an increase in its size facilitates active state of agents but reduces their utility. We consider a model of location-price competition between two firms, located on the circle. Nash equilibrium, equilibrium in secure strategies, and Nash-2 equilibrium are compared. We demonstrate that Nash-2 equilibrium exists for any locations of firms. The set of Nash-2 equilibria is treated as tacit collusion.
https://publications.hse.ru/en/chapters/50474381
AbstractIn finite noncooperative game, a method for finding approximate Nash equilibrium situations is developed. The method is prior-based on sampling fundamental simplexes being the sets of players’ mixed strategies. Whereas the sampling is exercised, the sets of players’ mixed strategies are mapped into finite lattices. Sampling steps are envisaged dissimilar. Thus, each player within every dimension of its simplex selects and controls one’s sampling individually. For preventing approximation low quality, however, sampling steps are restricted. According to the restricted sampling steps, a player acting singly with minimal spacing over its lattice cannot change payoff of any player more than by some predetermined magnitude, being specific for each player. The finite lattice is explicitly built by the represented routine, where the player’s mixed strategies are calculated and arranged. The product of all the players’ finite lattices approximates the product of continuous fundamental simplexes. This re-defines the finite noncooperative game in its finite mixed extension on the finite lattices’ product. In such a finite-mixed-extension-defined game, the set of Nash equilibrium situations may be empty. Therefore, approximate Nash equilibrium situations are defined by the introduced possible payoff concessions. A routine for finding approximate equilibrium situations is represented. Approximate strong Nash equilibria with possible concessions are defined, and a routine for finding them is represented as well. Acceleration of finding approximate equilibria is argued also. Finally, the developed method is discussed to be a basis in stating a universal approach for the finite noncooperative game solution approximation implying unification of the game solvability, applicability, realizability, and adaptability. Downloads Published 2016-06-16 How to Cite V. V. Romanuke, “Sampling Individually Fundamental Simplexes as Sets of Players’ Mixed Strategies in Finite Noncooperative Game for Applicable Approximate Nash Equilibrium Situations with Possible Concessions”, J. inf. organ. sci. (Online), vol. 40, no. 1, Jun. 2016.
https://jios.foi.hr/index.php/jios/article/view/988
This brief proposes a novel decision-making model for generalized Nash equilibrium seeking in the context of full-potential population games under capacity and migration constraints. The capacity constraints restrict the mass of players that are allowed to simultaneously play each strategy of the game, while the migration constraints introduce a networked interaction structure among the players and rule the strategic switches that players can make. In this brief, we consider both decoupled capacity constraints regarding individual strategies, as well as coupled capacity constraints regarding disjoint groups of strategies. As main technical contributions, we prove that the proposed decision-making protocol guarantees the forward time invariance of the feasible set, and we provide sufficient conditions on the connectivity level of the migration graph to guarantee the asymptotic stability of the set of generalized Nash equilibria of the underlying game when the game is a full-potential population game with concave potential function. Furthermore, we also provide an alternative discrete-time analysis of the proposed evolutionary game dynamics, which allows us to formulate a population-game-inspired distributed optimization algorithm that guarantees the hard satisfaction of the constraints over all iterations. Finally, the theoretical results are validated numerically on a constrained networked congestion game. Categories optimisation. Author keywords game theory Scientific reference J.P. Martínez, N. Quijano and C. Ocampo-Martínez. Nash equilibrium seeking in full-potential population games under capacity and migration constraints. Automatica, 141: 110285, 2022, to appear.
https://www.iri.upc.edu/publications/show/2594
Compare or contrast two major female fertility deities as to character, activities and role in the myth. In the myths of the ancient world, a great deal of importance is placed on the rhythmical cycle of birth, maturity, death and rebirth. Ancient agrarian people observed the world around them, and from this observation they realized that their lives as well as every other living thing on this planet was a part of an intricate continuing cycle. Everything withered and died, but not before reproducing and continuing the cycle of life. Since female plants and animals were directly responsible for the birth of new life, people worshipped female deities to ensure that the earthly cycle of life was maintained in proper balance. One such goddess can be found in Japanese mythology. The most ancient of Japanese deities, Amaterasu is the goddess of the sun. She is also the ruler of the gods and the universe. She is revered and given considerable praise, evidenced by the fact the Japanese imperial family traces its lineage directly to the Goddess Amaterasu. This reverence is understandable, given the sun's extreme importance in the cycle of life. Without the sun, there would be no warmth, no plants, and certainly no humans. It also represents the important role that women played in early Japanese culture, where they occupied the same social roles as men. In the myth of Amaterasu, her brother Susano-o-no-Mikoto has offended her by defiling her home and not respecting her. He has also committed an act of physical violence against one of her servants. In one version of the myth, one of Amaterasu's weaving women dies as a result of a wound to her vulva caused by Susano-o-no-Mikoto. This so enrages Amaterasu that she closes herself into a cave and refuses to come out. Without her life giving rays of sunshine the world begins to wither and die. Other Gods and Goddesses attempt to lure her out of the cave by throwing a celebration. They also set up a large mirror in a hope that when Amaterasu sees how brilliant she looks, she will want to come out and spread her radiance and glory. One of the Goddesses, Ame no Uzume, performs a dance in front of the entrance to the cave. The other Gods and Goddesses cheer so loudly in appreciation that Amaterasu becomes curious about why everybody is so happy. After all, they should all be depressed since she and her sunshine are gone. Show More Related More about Fertility Myths with Demeter and Persephone and Amaterasu Popular Essays Critiquing Dr. Satel Abortion8 Microsoft and How It's a Monopoly Is Love Good or Evil?
https://www.123helpme.com/essay/Fertility-Myths-with-Demeter-and-Persephone-and-126028
Recently I visited the sacred cave where Amaterasu, the Goddess of the Sun, once lived in Kyushu, Japan. After that experience I was inspired to write a poem of gratitude to her: Amaterasu, Goddess of the Sun and Joy Long ago, the Goddess of the Sun, Amaterasu, became frustrated that her younger brother was so abusive to the people and to the animals that she went into a cave and wouldn’t come out. The Earth was covered in darkness. The people and the gods were so sad and confused. The gods wanted her to come out and return this world to the Light. They held a great party close to her cave and sang and danced in a great celebration of Life. She heard their laughter and looked out of the cave to see what they were doing. Come out and play with us! A great and powerful god lifted the stone from the door to her cave and threw it far away so she could come out. She came out to sing and dance with the gods, the people and the animals. Light was restored to the world. We thank you dear Mother Amaterasu! You brought Sun and Joy to the world! Now we pray to you again to remind us to enjoy the Sun and have Joy in our life. May we put aside our desire for conflict and competition and enjoy the Life you gave us. We need your inspiration and your Love now in these times of conflict and challenge. Let us all remember you as the Goddess of the Sun and Joy! We Love you Dear Mother and welcome your Love into our Life! Comment - No comments yet. No trackbacks yet.
https://www.bob-fickes.com/blog/ascended-masters-merlin/amaterasu-goddess-sun-joy/
Itachi Uchiha is one of the most beloved Naruto characters. Introduced in the story as a villain that stood in Sasuke’s path, Itachi played the role of an obstacle for his brother to surpass. Feared across the entire world of shinobi, Itachi’s skills were considered to be nothing short of impeccable. As a member of the Uchiha Clan, it was expected of him to have excellent visual prowess. However, his skill was such that he went far beyond the level of an average Uchiha, even as a kid. Itachi awakened the special power of the Uchiha, known as the Sharingan, at quite the young age of 8. Soon after, he went on to master this eye to a great degree and earned the admiration of some of the most incredible shinobi, such as Orochimaru. But, Itachi’s true strength didn’t blossom until much later, when he finally awakened his Mangekyo Sharingan while serving as a member of the ANBU. The Mangekyo Sharingan is quite a complex power that awakens within just a few members of the Uchiha Clan. This power is considered to be an evolved and much stronger form of the regular Sharingan. Expectedly, it makes an Uchiha much more threatening and powerful than they are without it; however, at the same time, the hatred in their heart grows with it. Awakening the Mangekyo Sharingan is quite tricky as it cannot be tapped into simply by training or evolved by working on visual prowess. To gain this power, one must witness the death of one of their loved ones. The pain resulting from the loss of love is what causes a regular Sharingan to turn into a Mangekyo Sharingan. In Itachi’s case, Things were no different. Around the time when he served as an ANBU captain, the Uchiha clan planned a coup d’etat to overthrow the then Hokage of the village. Itachi and Shisui attempted to stop the clan from revolting. Unfortunately, due to Danzo’s interference, Shisui suffered tremendously and lost one of his eyes. Entrusting the other one to Itachi, Shisui committed suicide. Witnessing this made Itachi’s Sharingan evolve into a Mangekyo Sharingan. These eyes granted him tremendous power and made him much stronger than he was before, however, the price to pay for this was just as great. As with all Mangekyo Sharingan users, Itachi became colder and full of pain that resulted from the death of his best friend. He then proceeded to use this eye to help destroy his very own clan in an attempt to protect the village. Shortly after, he abandoned the village and was branded as a murderer, living his life in disgrace until the moment he died. Itachi ended up joining the Akatsuki, where he served as one of their strongest members, thanks to the powers of his Mangekyo Sharingan. Itachi’s visual prowess was such that Orochimaru, one of the members of the Akatsuki at the time, attempted to steal his body, yet managed to lose to him without him even lifting a finger. Without a doubt, Itachi’s visual powers were one of the greatest seen in the Naruto story. The Mangekyo Sharingan is quite an incredible eye that offers everything that a Sharingan does, only better and on a greater scale. Just like the regular Sharingan, this eye can see through ninjutsu, genjutsu, and taijutsu completely and copy jutsu that aren’t Kekkei Genkai. Furthermore, it takes the Sharingan’s ability to read fast and intricate movements and makes it much better. However, the true power of the Mangekyo Sharingan doesn’t lie in these rather smaller abilities. Unlike the Sharingan, this eye offers two unique powers to every user, one to be used through each eye. Itachi Uchiha had some of the most overpowered abilities at his disposal. Through his left eye, he was able to access the power of Tsukuyomi, which was known to be a powerful genjutsu capable of manipulating space and time itself. Once caught in the Tsukuyomi, escape is practically impossible and even a second in that world can be made to feel like an eternity since Itachi has complete control over both time and space. What’s more, the pain felt in the world of Tsukuyomi can actually kill a person, making it the only genjutsu capable of doing so. Itachi killed his girlfriend, Izumi with this technique by making her see out her entire life within the blink of an eye and die of old age. Through his right eye, he could use the black flames of Amaterasu. These flames are known to be the highest form of Fire Release and fall under the category of Blaze Release. Amaterasu is incredibly difficult to counter and burns through anything. Not even the mightiest of shinobi can counter this ability unless they possess the power to absorb it or they evade it completely. Upon contact, Amaterasu keeps burning until the target is incinerated completely. These flames are known to be inextinguishable, meaning not even rain or the highest form of Water Release can douse them. Finally, the strongest power of Itachi’s Mangekyo Sharingan was the Susanoo. As with every Mangekyo Sharingan user, the Susanoo is the ultimate ability for Itachi as well. Although Itachi couldn’t manifest a full-body Susanoo, he could still use a very powerful variant of it with two ethereal weapons, the Yata Mirror and the Totsuka Blade. With the Yata Mirror, he could counter any and all jutsu with ease, and with the Totsuka Blade, Itachi could seal anyone in a world of genjutsu for eternity by piercing their body with it. All in all, Itachi’s powers were terrific – seeing as Zetsu named him invincible in combat despite being ravaged by a disease. Had Itachi not been ill and pursued power, he could very well have been among the very strongest characters in the series.
https://thepeoplespeak.us/itachi-uchihas-mangekyo-sharingan-explained/
After many years growing up amongst humanity in Polis, Metametheus felt it was important to travel through the wide world. He had heard stories of different peoples in distant lands, and wanted to discover their customs, stories, and ways of life. Having started off his journeys towards the West, he visited many different lands and had encountered wonders he had never envisaged during his time in Polis. Then one day, the world had become unexpectedly plunged into darkness. Lost in the darkness, he found himself in the Middle Land of the Reed Plains. Taking the name Amatsumara, he met the wise Omo-Ikane and asked why the world had gone dark with no day. Omo-Ikane told him that Amaterasu, the Sun Goddess, had locked herself in the Celestial Cliff Cave to hide from her older brother Susanowo, the God of Storms, who had been cruel to her. Without her presence in the world, there would be no daylight, and chaos and terror would abide. Something needed to be done, and so together they devised a plan. The plan required many to assist, so Omo-Ikane sought those who he knew would be able to help. Metametheus had learned many skills during his travels and growing up in Polis, and he began immediately to craft a large mirror. The mirror was octagonally-shaped, and fashioned from bronze. Its design was such that it was able to catch the image of truth and reflect it. He named it in the native tongue of the land, Yata-no-Kagami. Meanwhile, Ameno-Koyane and Futodama were called to the entrance of the Celestial Cliff Cave. They began to perform a ritual of divination with bones. Metametheus attached his mirror to a Sakaki tree that grew directly at the mouth of the cave, alongside a piece of Jade from Heaven. Standing in a circle around the tree, eight Kami-spirits came. They were Tsyankami, Kunekami, Kannekami, Likami, Jennekami, Sunokami, Gennekami, and Doiyekami. Each of these great spirits chanted a mantra of sacred syllables, while in the circle and around the tree, the goddess Ameno-Uzumi danced. She exposed her breasts and lowered her skirt, fervently and erotically moving her body in tune with the Kami-spirits’ music. Hearing the noise outside, Amaterasu peeked out, enquiring what all the mirth and revelry was about. Metametheus, dressed in the land’s garb, told her they were honouring one greater than her. She was curious as to who this could be, and was intrigued by the appearance of a god she had not met before. She was also cautious as she thought this may be a trap set by her cruel brother. She looked into the circle of kami, and there hanging from the tree she spied the image of stunningly beautiful goddess — it was of course her reflection in the mirror Metametheus had fashioned. She leaned further out of the cave, wanting to get a closer look at this shining being; and as she did so, Ameno-Tajikarawo, a god known for his immense strength, took her arm and drew her out of the cave. Futodama threw aside his oracle bones and drew a shirikume rope behind her; he proclaimed loudly that Amaterasu would not be able to cross the rope and return into the cave, unless she needed to rest and recover from her constant shining forth. With the goddess once again in their midst, all those who were present gathered and danced ceremonially around the Sakaki tree. The eight kami-spirits each chant their mantra and played their instruments while everyone joined in and followed Ameno-Uzumi’s erotic movements. The Mirror continued to catch the image of Amaterasu, her beauty and sincerity were reflected out to the entire Universe; as her reflection touched the piece of Heavenly Jade, Amaterasu’s countenance of light shone across Heaven and Earth, and once again Dawn broke, and the sun rose in the sky again. For his efforts with crafting the eight-sided mirror, Metametheus was gifted a workshop in the land to continue to craft divine treasures. All the gods, goddesses, and kami-spirits commissioned him to forge ritual tools, and weapons. He learned the secrets of divination and with the wisdom of Futodama, learned how to fashion armour that protected the wearer from evil thoughts and words. The goddess Amaterasu was particularly grateful for him, and in return for his part in her rebirth, she gifted him a vial of her light. He fashioned helmets, incorporating the design of Kagami-mirror, and used a drop of the light in their metal, which gave them a quality which allowed the wearer’s true visage to shine forth and blind their enemies. After a time, he left the Middle Land of the Reed Plains and continued his travels throughout the world. However he remembered his time at the Celestial Cliff Cave fondly, and continued to carry the Vial of Amaterasu’s Light where-ever he went, as a reminder of the beauty of the rising sun.
https://metametheus.net/metametheus-the-rising-sun/
Uzume is the goddess of dawn and revelry in the Shinto religion of Japan. She famously relates to the tale of the missing sun deity, Amaterasu, goddess of beauty. Amaterasu's brother, the storm god Susano'o, had vandalised her sacred buildings and killed one of her maidens because she refused to trust him. In turn, the goddess became terrified of his wrath and retreated into a cave. The world, without the illumination of the sun, became dark and the gods could not lure Amaterasu out of her hiding place. The clever Uzume overturned a tub near the cave entrance and began a sexy & bawdy dance on it, exposing her breasts and genitals in front of the other deities. They considered this so comical that they laughed heartily at the sight. Amaterasu heard them, and peered out to see what all the fuss was about. When she opened the cave, she saw her glorious reflection in a mirror Uzume had placed on a tree, and slowly emerged from her hiding spot.
http://www.kaylagarnetrose.com/2007/12/illuminate-my-darkest-cave.html
An unsual tourist site shrouded in intrigue and mystery. It’s no exaggeration to say that Amano Iwato in Takachiho, Miyazaki Prefecture, is the most famous cave in Japan. Literally translated as “Heavenly Cave”, this rocky chamber is famous for being the place where the sun goddess Amaterasu was said to have hidden, according to the Kojiki and Nihonshoki, respectively the oldest and second-oldest books of classical Japanese history. According to the myth, Amaterasu hid herself in the cave after a dispute with her impetuous younger brother Susano-no-Mikoto, bringing darkness to the land until she was eventually lured out by the goddess of mirth with laughter and a mirror, bringing light to the world again. ▼ The legend lives on today at Amano Iwato and the nearby Amano Iwato Shrine (pictured below) The wider Takachiho town is also considered a holy place for people in Japan, as it’s said to be the spot where Amaterasu’s grandson Ninigi-no-Mikoto descended from heaven — an event known as “Tenson Korin”. These myths blur with reality in Japan, as Ninigi-no-Mikoto and Amaterasu are said to be ancestors of Japan’s modern-day emperor. ▼ The town where the emperor’s ancestors descended from the sun. Takachiho and Amano Iwato draw thousands of tourists every year, and this year, our reporter Seiji Nakazawa was amongst them, driving along the country roads to visit the sacred destination. ▼ Upon arriving in the area, Seiji made his way to Amano Iwato Shrine to pay his respects. After parking at the nearest parking lot, Seiji got a sense of how popular this place is with tourists, as it’s located by a shopping street and has a stop for tour busses right out the front. However, as expected of a spot famous for its mythology, once you pass through the torii gate, you’re immediately overcome by a quiet atmosphere that feels sacred. Takachiho is surrounded by mountains, and it was a midsummer day so the road outside was steaming, but the moment Seiji passed through the torii gate, he suddenly cooled off. ▼ Is this the effect of the gods? Amano Iwato is a forbidden cave where no mortals are allowed to enter, as it’s said to be the place where a sacred shimenawa rope was used for the first time in Japan. Amaterasu’s fellow deities were said to have placed the shimenawa across the cave to seal it off once the sun goddess had emerged from it, so that she wouldn’t be able to hide there again. ▼ Amano Iwato is located behind the shrine’s main worship hall, and though it’s off-limits to visitors, you can view it from a distance with the guidance of a priest. Those who wish to participate in the viewing don’t need to register or pay a fee — simply gather at the meeting place at the dedicated times listed on the sign below. A priest will guide visitors to the viewing spot behind the shrine once every 30 minutes from 9 a.m. until 4:00 p.m., aside from a lunch break at 12:30 p.m., and then one final time at 4:40 p.m. Seiji gathered at the meeting place at one of the designated times, and the priest began to explain a number of things about the shrine and its trees to the group in Japanese, making it feel like a free mini tour. The laid-back atmosphere suddenly changed to a solemn one as the priest stepped up to conduct a purification ceremony, an important part of the tour to purify the group before proceeding to the holy site. The priest then made his way over to the side door, where he reminded the group that photos were prohibited beyond this point. Entering through the wooden gate, Seiji was led down a path behind the worship hall, and it didn’t take long for them to arrive at the observatory, which was equipped with an offertory box. Looking beyond the offertory box, Seiji was able to see a river flowing far below, and the priest explained that Amano Iwato was located on the opposite bank. When Seiji looked over at the opposite bank, he was surprised to see there was in fact a cave there, and this is where the sun goddess once resided. He blinked a few times, trying to take the enormity of it all in. ▼ Behold Seiji’s recreation of the scene — a sheer cliff below, dense forest above and the cave and sacred rope in between. The cave was certainly safe from mere mortals — unless you had the power of flight, you’d have to be an adept climber to navigate the cliffs from the observatory. ▼ Seiji on the right, cave on the left, and flowing river in between. Seiji had always thought of Amaterasu as an indoor person, due to her time in the cave, but looking at the location, Seiji began to wonder if the goddess was actually an outdoorsy type, perhaps even a climbing enthusiast. Visiting the actual site mentioned in the myth made Seiji appreciate the legend and its deities even more. And when he said one final prayer at the shrine, he was touched to see a replica of the sacred mirror there. ▼ The mirror that helped to lure Amaterasu from the cave. Following his visit to the shrine, Seiji made his way to another popular site nearby — a larger cave called Amanoyasugawara, which is said to be the spot where eight million gods gathered when Amaterasu shut herself inside the cave. ▼ The entrance to Amanoyasugawara ▼ The riverside walk to Amanoyasugawara is wonderfully calm and tranquil. ▼ The path ends at Amanoyasugawara This cave has an otherworldly atmosphere — you can almost feel the spirit of the gods watching over you. It’s believed that if you stack rocks and make a wish here your wish will be granted, which is why you’ll find thousands of stacked stones in the area. These mysterious-looking rocks, and the shrine nestled at the back of the cave, add to the mystical atmosphere. The three sites Seiji visited are some of the most intriguing in the country, and he highly recommends everyone make the trip to Miyazaki at least once in their lives. If the ancient mythology doesn’t interest you, you can always go for manhole covers adorned in Exeggutor from Pokémon, another land of myth! Shrine Information Amano Iwato Jinja / 天岩戸神社 Address: Miyazaki-ken, Nishiusuki-gun, Takachiho, Iwato 1073-1 宮崎県西臼杵郡高千穂町大字天岩戸1073-1 Open: 8:30 a.m.-5:00 p.m. every day Website Photos ©SoraNews24 ● Want to hear about SoraNews24’s latest articles as soon as they’re published? Follow us on Facebook and Twitter!
https://soranews24.com/2022/09/17/visit-the-mythical-cave-that-hid-the-sun-goddess-in-japanese-mythology/
Home > Highlighting JAPAN >Highlighting Japan April 2014> 47 Prefectures from A to Y Miyazaki is a largely mountainous prefecture occupying much of Kyushu's eastern coastline. Palm trees in the south are distinctive of the area's subtropical climate, which has helped make it a popular domestic travel destination. Most importantly, however, Miyazaki occupies a special place in Japanese history for a mountain town called Takachiho. For it was here the deity Ninigi-no-Mikoto, grandson of the sun goddess Amaterasu, is said to have descended to Earth. With some 1.3 million tourists per year, Takachiho is Miyazaki's most-frequented sightseeing spot. A visit to Takachiho Shrine is an excellent way to become familiar with the legends that swirl around this region like the early-morning mountain mist. The steps leading up to the cedar-enveloped shrine are not straight but diagonal, which Ayu Yano of the town's tourism and planning department explains is out of respect to the deities enshrined there, as the angle enables visitors to avoid presenting their backsides to the gods upon leaving. Two cedar trees on the shrine's grounds have been bound together with a shimenawa sacred Shinto straw rope, and it's said a couple can strengthen their relationship by walking hand-in-hand around the trees three times. Takachiho is famous for its yokagura dance. The dance has no less than 33 parts and starts late in the afternoon, extending well into the following morning. Performers don large masks and, accompanied by traditional Japanese instruments such as flutes and drums, reenact such scenes as the time Amaterasu hid herself in the nearby Amanoiwato cave, depriving the world of light and leading the other gods to make varied attempts to lure her out. This full performance is held annually from November to February to give thanks for the year's harvest, but an hour-long glimpse of the dance can be seen every night at 8 p.m. in a performance hall at Takachiho Shrine. Amaterasu's sacred cave can be found by Amanoiwato Shrine, a few kilometers northeast of Takachiho Shrine. While visitors cannot enter or photograph the cave itself, priests at the shrine, whose main buildings are located facing it across the Iwato River, can escort visitors to a vantage point and explain its significance in Japanese. A ten-minute walk from there leads to another cave along the river where the gods are said to have deliberated ways to persuade Amaterasu to leave her retreat. This cave includes the small Amano Yasukawara Shrine, replete with little towers of stacked stones representing the wishes and prayer requests of previous visitors. Heading back to the south of the town, the blue-green waters of the Gokase River flow through the picturesque Takachiho Gorge. Formed by lava flowing from nearby Mount Aso an estimated 90,000 to 120,000 years ago, water has worn down the rock to create dramatic cliff walls. These are best experienced from a rented rowboat, which allows one to appreciate the unique rock formations and the 17-meter Manai Falls, listed among the One Hundred Waterfalls of Japan compiled by the Japanese Ministry of the Environment in 1991. Japanese maples and other native trees extend a leafy canopy over the gorge, said to be particularly beautiful when the leaves turn vivid red and orange in the fall. Clean mountain air and gorgeous scenery are reasons enough to visit Takachiho, but Yano notes perhaps the best reason of all: "This is said to be the place where Japan was born," she says. If you haven't visited, it's time to go!
https://www.gov-online.go.jp/eng/publicity/book/hlj/html/201404/201404_12_en.html
For more information click here. until September 22. 2019 The sun goddess and her mirror image - Amaterasu's return from the cave With an installation made of silk and light Kazu Huggler re-enacts a key scene from Japanese Shinto mythology. KAZU Store Opening hours Thursday & Friday: 12:00pm - 6:30pm Saturday: 12:00pm - 4:00pm Ankerstrasse 122 in 8004 Zürich We will be delighted to welcoming you!
https://www.kazu.swiss/
What You Need to Know: - Charapedia conducted a poll asking anime fans which male characters they think look good with long hair. - The poll, held for a week from December 3 to December 10, received a total of 10,000 votes from both genders. - See the results below! Top 10 - Top 6 10. Byakuya Kikuchi (Bleach) / 179 votes 9. Yu Kanda (D.Gray-man) / 191 votes 8. Alto Saotome (Macross F) / 197 votes 7. Kurama (Yu Yu Hakusho) / 202 votes 6. Ren Jinguji (Uta no Prince-sama) / 224 votes Top 5 - Top 1 5. Neji Hyuga (Naruto) - Episodes: 220 - Aired: October 2002 - February 2007 Synopsis Naruto Uzumaki, a hyperactive and knuckle-headed ninja, lives in Konohagakure, the Hidden Leaf village. Moments prior to his birth, a huge demon known as the Kyuubi, the Nine-tailed Fox, attacked Konohagakure and wreaked havoc. In order to put an end to the Kyuubi's rampage, the leader of the village, the 4th Hokage, sacrificed his life and sealed the monstrous beast inside the newborn Naruto. Shunned because of the presence of the Kyuubi inside him, Naruto struggles to find his place in the village. He strives to become the Hokage of Konohagakure, and he meets many friends and foes along the way. (Source: MAL) 4. Edward Elric (Fullmetal Alchemist: Brotherhood) - Episodes: 64 - Aired: April 2009 - July 2010 Synopsis In this world there exist alchemists, people who study and perform the art of alchemical transmutation—to manipulate objects and transform one object into another. They are bounded by the basic law of alchemy: in order to gain something you have to sacrifice something of the same value. The main character is the famous alchemist Edward Elric—also known as the Fullmetal Alchemist—who almost lost his little brother, Alphonse, in an alchemical accident. Edward managed to attach his brother's soul to a large suit of armor. While he did manage to save his brother's life, he paid the terrible price of his limbs. To get back what they've lost, the brothers embark on a journey to find the Philosopher's Stone that is said to amplify the powers of an alchemist enormously; however, on the way, they start uncovering a conspiracy that could endanger the entire nation, and they realize the misfortunes brought upon by the Philosopher's Stone. Fullmetal Alchemist: Brotherhood is a re-telling of the story from the manga's point of view. (Source: MAL) 3. Atsushi Murasakibara (Kuroko's Basketball) - Episodes: 25 - Aired: April 2012 - September 2012 Synopsis The Teiko Middle School Basketball Team. The class that produced three perfect seasons in a row, with five once-in-a generation players, called "The Generation of Miracles." There was another player who all of them respected... A legendary 6th player. An up-and-coming power player, Taiga Kagami, is just back from America. When he comes to Seirin High School, he meets the super-ordinary boy, Tetsuya Kuroko. Kagami is shocked to find that Kuroko isn't good at basketball, in fact, he's bad! And he's so plain that he's impossible to see. But Kuroko's plainness lets him pass the ball around without the other team noticing him, and he's none other than the sixth member of the Miracle Generation. Kuroko makes a pact with Kagami to defeat the other members of the Miracle Generation, who have all played basketball at other schools. A battle of light (Kagami) and shadow (Kuroko) begins! (Source: MAL) 2. Kenshin Himura (Ruroni Kenshin) - Episodes: 94 - Aired: January 1996 - September 1998 Synopsis Himura Kenshin is a vagabond with a dark past and sunny disposition. Not a ronin but a rurouni, he was never a samurai, but an assassin of utmost skill in the Meiji restoration, who in the turning point of the war simply walked away. His travels lead him to Tokyo in the 11th year of the Meiji era, where he befriends a female Kendo master, a former thief, a brawler and a doctor all with their own secrets. Together they fight off the enemies surfacing from the dark past that Kenshin cannot escape. (Source: ANN) 1. Kotaro Katsura (Gintama) - Episodes: 201 - Aired: April 2006 - March 2010 Synopsis Life isn't easy in feudal Japan... especially since the aliens landed and conquered everything! Oh sure, the new health care is great, but the public ban on the use of swords has left a lot of defeated samurai with a difficult decision to make concerning their future career paths! This is especially true if, as in the case of Gintoki Sakata, they're not particularly inclined towards holding a day job, which is why Gintoki's opted for the freelance route, taking any job that's offered to him as long as the financial remuneration sounds right. Unfortunately, in a brave new world filled with stray bug-eyed monsters, upwardly mobile Yakuza and overly ambitious E.T. entrepreneurs, those jobs usually don't pay as well as they should for the pain, suffering and indignities endured!
https://honeysanime.com/top-10-male-anime-characters-that-look-good-with-long-hair-10000-japanese-fans-polled/
Kofun of Emperor Jinmu is located in Kashihara, Nara Prefecture. The archaeological name of Jinmu Tenno Ryo is Unebiyamanoushitoranosuminomisasagi, or Misanzai Jibuden Kofun. Emperor Jinmu passed away at the age of 137 in Kojiki, and 127 in Nihonshoki. The legend said that he was buried at the north side of Mt. Unebi. Emperor Jinmu Emperor Jinmu is the descendant of Amaterasu Omikami, the main god of Japanese myth. The family lived at Takachio of Hyuga. When he was 45 years old, he decided to expand the land to the east. Because legend said, there is a beautiful land on the east that would be a great place to build a new capital. His eastern expedition reached the land of Kawachi, current Osaka. However, local powerful family in Kawachi was strong and Emperor Jinmu was defeated once. So he decided to travel to the southern Kii peninsula. To support him, Amaterasu Omikami gave divine sword and Yata crow for his guidance. His army entered the land of Nara. People in Nara supported Jinmu and finally he conquered the land around Nara and Kawachi. He became Tenno, the Emperor at this place when he was 52 years old. He passed away when he was 127 and buried at Kashihara. Year 1938 was the 2600 years anniversary of Japanese Empire.
https://www.mustlovejapan.com/subject/kofun_emperor_jinmu/
THE MAPS on this page show all the locations mentioned in the text of Shakespeare's plays using GoogleMaps. The first map shows the mapped locations for all 38 plays, and subsequent maps show locations for each individual play. Click on a link in the menu below to see the map related to that play or plays. For information about how to use the maps and a key to the colors for the map markers, click here. **Note that the links in the menu are only active for maps that are already complete. Plays that have been mapped will appear as a reddish colored underlined link. Plays that have not yet been mapped appear in brown with no underline. Links will be added as maps are finished. Click and drag the map to move it or click the + and - symbols in the lower right corner of the map in order to zoom in and out, just the way you would any other Google Map. If you click on one of the markers on the map a box will appear that displays one-line quotes and act, scene, line references for the reference to the place on the map to that play. For the map of all the plays only the titles of the plays in which that place is referred to will appear in this box. I have used the Arden editions of the plays for the act, scene, and line references. Note that different versions of some of Shakespeare's plays mean that line numbers may be different depending on what edition of the play you are reading. For more about the different versions of Shakespeare's plays and how this project deals with these variations see the section "About the Text" on the About page for this project. For separate lists of locations organized by play and by place, see the Indexes page. The locations referenced in the plays have been mapped according to three different categories: "Where the Action Is", "Places Alluded To", and "Adjectives and Descriptors." Each of these categories is a different color on the Google Map. The white menu that appears on the Google Map displays a list of these places. You can check or uncheck the box to the right of each category to display only map points in a particular category. "Where the Action Is" Red markers show places where action takes place in the play. These are places where the characters actually are, for example Denmark would be marked in red for Hamlet. Similarly Verona would be marked this way for Romeo and Juliet, and Scotland for Macbeth. "Alluded To" Blue markers show places that are alluded to, but are not where the action is taking place in the play at the time. This category can mean references to places that never are part of the action to the play, for example, when Theseus refers to having once been in Crete in A Midsummer Night's Dream, or when Hamlet refers to an actor an actor from Rome. This category is also used for references to places where the action takes place at other points in the play but is not the setting when the text alludes to it. For example, when Antony, of Antony and Cleopatra refers to Egypt in a scene taking place in Rome, or when Henry V talks about England while in France, those references would be mapped with a blue marker. "Adjective or Descriptor" Yellow markers show places that are referred to in the form of an adjective. This category includes references to people from a particular place, such as the "Indian Votress," an "Ethiope," or an "Athenian," as well as things described as "Welsh," "French," etc. This also applies to references such as "Pericles, Prince of Tyre", in which Tyre functions as a descriptor for the place Pericles is from rather than an allusion directly to the place itself.
http://shakespearemap.org/playmaps.html
Shakespeare scholar Emma Smith takes 20 chapters to discuss 20 different Shakespeare plays in her new book This Is Shakespeare, offering insights on key characters, plot twists, and performance challenges. The excerpt below, which focuses on the character of Falstaff and his physical description, comes from the chapter on 1 Henry IV, the play where Falstaff makes his first appearance. Smith, who has been featured on the Folger’s Shakespeare Unlimited podcast in episodes about Shakespeare myths and the First Folio, is lecturer in English at the University of Oxford, Professor of Shakespeare Studies, and a Fellow of Hertford College. This Is Shakespeare by Emma Smith is available now in the UK from Pelican Books, and will be published in the US by Pantheon in April 2020. The excerpt below is used with permission Fat, dodgy, cash-strapped, self-interested Falstaff. In inventing this anti-hero, Shakespeare had launched a cultural phenomenon that he milked in two further plays: the success of 1 Henry IV was the success of Falstaff. So what made Falstaff so compelling? Why did Elizabethans recognize Falstaffs in the world around them, when they did not, for example, see Hamlets? Why did this character come alive for audiences in a way that no other Shakespearean character did? Crucial to Falstaff ’s characterization is his morbid obesity. Hal’s first words to him in the play’s second scene call him ‘fat- witted’ (1.2.2), and there is constant banter about his appetite for food and drink. Other names for Falstaff reiterate his size: ‘fat- guts’ (2.2.31), ‘whoreson round man’ (2.5.140), ‘fat rogue’ (2.5.548), ‘a gross fat man’ ‘as fat as butter’ (2.5.517). ‘How long is’t ago, Jack, since thou sawest thine own knee?’ goads Hal, as Falstaff blames sighs and griefs for blowing him up like a bladder (2.5. 330– 31). When Hal advises him to hide on the ground during a trick, Falstaff asks if he has ‘any levers to lift me up again’ (2.2.34). In an important sequence in 2.5 where Hal and Falstaff rehearse in the tavern an interview between the prince and his father, Falstaff ’s fatness and its interpretation is their main topic of conversation. Ventriloquizing his father’s disapproval, Hal (playing the king) addresses Falstaff (as if he were the prince): ‘There is a devil haunts thee in the likeness of an old fat man; a tun of man is thy companion’ (2.5. 452– 3). He extemporizes an extravagant sequence of similes for Falstaff ’s size: ‘that trunk of humours, that bolting-hutch of beastliness, that swollen parcel of dropsies, that huge bombard of sack, that stuffed cloak-beg of guts, that roasted Manningtree ox with the pudding in his belly’ (2.5. 454– 8). Falstaff sticks up for himself against this fat-shaming: ‘If to be fat be to be hated, then Pharaoh’s lean kine are to be loved’ (2.5. 477– 8), referring to the cattle that are the biblical symbols of famine in Joseph’s dream. Images of bulk, size and, above all, fatness, pepper the play. It is impossible to get away from the fact that Falstaff is fat. It’s worth stepping back a moment to see how unusual this level of physical description is in Shakespeare’s writing. Very few characters in Shakespeare are given specific physical characteristics. […] While we know that Shakespeare writes with a definite group of actors in mind – the Lord Chamberlain’s Men where he was actor, resident playwright and shareholder – he seems more interested in their acting ability than their physical appearance. So what? Well, Falstaff ’s fatness is the most thoroughgoing physical designation we ever get in Shakespeare, or, to put it another way, Falstaff is the most insistently physical character Shakespeare ever wrote.
https://shakespeareandbeyond.folger.edu/2019/06/11/emma-smith-falstaff-excerpt-this-is-shakespeare/
A TIMES LITERARY SUPPLEMENT BEST BOOK OF THE YEARDrawing on an exceptional combination of skills as literary biographer, novelist, and chronicler of London history, Peter Ackroyd surely re-creates the world that shaped Shakespeare--and brings the playwright himself into unusually vivid focus. With characteristic narrative panache, Ackroyd immerses us in sixteenth-century Stratford and the rural landscape-the industry, the animals, even the flowers-that would appear in Shakespeare's plays. He takes us through Shakespeare's London neighborhood and the fertile, competitive theater world where he worked as actor and writer. He shows us Shakespeare as a businessman, and as a constant reviser of his writing. In joining these intimate details with profound intuitions about the playwright and his work, Ackroyd has produced an altogether engaging masterpiece. Considering the playwright and his work, the author theorizes that Shakespeare's elusive personality is a result of his supremacy as a dramatist--that he submerged his identity in his characters--and assesses evolving meanings of the plays and poems. Reveals the influence of the Renaissance scholar-priest Marsilio Ficino on Shakespeare and how the Neoplatonic philosophy of love shaped the inner meaning of his work- Shows how Shakespeare's works offer a path back to the divine unity of all things - Explains the role of love in the Christian-Platonic concept of the three worlds In Love's Labours Lost, Shakespeare talks of the true Promethean fire that is lit by the doctrine he reads in women's eyes. What is this doctrine and what is this true Promethean fire to which it gives birth? In Shakespeare and the Ideal of Love, Jill Line shows that Shakespeare shared the perennial philosophy of a long line of teachers, including Hermes Tristmegistus, Pythagoras, Plato, Plotinus, and especially the Florentine scholar and mystic Marsilio Ficino. The answer to these questions, Line claims, lies in Ficino's Christian-Platonic philosophy of love, from which all Shakespeare's plays have their genesis. Love, according to Ficino, is the force that inspired the creation of the worlds of the angelic mind, the soul, and the material, and it is through love that each of these worlds expands into the next. Love is also the vehicle that allows human beings to make the return journey to the source of their being, where they find unity in God. This is the path on which all of Shakespeare's lovers embark. Jill Line explains how Shakespeare's plays represent more than poetic literary constructs: They are mirrors of the progress of the soul, in many conditions and situations, as it returns to the divine unity of all things. It is perhaps the greatest story never told: the truth behind the most enduring works of English literature. Who was the man behind Hamlet, King Lear, and the sonnets? In "Shakespeare s Lost Kingdom," critically acclaimed historian Charles Beauclerk pulls off an enchanting feat, humanizing the bard who for centuries has remained beyond our grasp. Beauclerk has spent more than two decades researching the authorship question, and he convincingly argues that if the plays and poems of Shake-speare were discovered today, we would see them for what they areshocking political works written by a court insider, someone whose status and anonymity shielded him from repression in an unstable time of armada and reformation. But the author s unique status and identity were swept under the rug after his death. The official historyof an uneducated Stratfordian merchant writing in obscurity and of a virginal queen married to her countrydominated for centuries. "Shakespeare s Lost Kingdom" delves deep into the conflicts and personalities of Elizabethan England, as well as into the plays themselves, to tell the true story of the Soul of the Age. You ll never look at Shakespeare the same way again." (Limelight). "Pennington's great experience of the play...love for it...depth of knowledge...of many productions and interpretations culminate in a book of infinite value to any actor, director and above all to any passionate playgoer...written with passion, humor and rigor...an excellent read." Ralph Fiennes When an essay is due and dreaded exams loom, this book offers students what they need to succeed. It provides chapter-by-chapter analysis, explanations of key themes, motifs and symbols, a review quiz, and essay topics. It is suitable for late-night studying and paper writing. An exponent of the theory that William Shakespeare, the modestly educated provincial man from Stratford-upon-Avon, could not have written the works - full of erudition and accurate professional jargon - which are attributed to him, Mark Twain offers an eloquent and entertaining analysis of this issue of authorship, peppered with personal recollections of his own first encounters with the Bard's plays on a boat on the Mississippi. Balancing humour, insight and vitriol, Is Shakespeare Dead? is a provocative contribution to the tradition of Shakespeare-doubting, as well as a fine example of the great American novelist's critical writing.
https://www.magersandquinn.com/?cPath=597
Sensory Imagery in Shakespeare's Plays :: Grammar, style, and proofreading quizzes use sentences from literature. Teacher’s guide contains 20 quizzes that identify sensory imagery (sight, sound, taste, touch, smell) in 20 plays by Shakespeare. 400 multiple choice questions. All sentences are from 20 plays. Answer key and glossary of literary terms included.
https://www.grammardog.com/catalogItems/view/sensory-imagery-in-shakespeares-plays
Plays and Dramas are an important part of English literature. We have qualified tutors to help in this academic field. I want to write about how Shylock is both a villain and a victim. I feel, personally, that one of After reading this long, and at times, hard to follow play I believe that Portia is the protagonist of the I will attempt to answer the question: Who is the protagonist in William Shakespeare’s The Merchant of Venice. The story for The Importance of Being Earnest by Oscar Wilde The purpose and description of the setting is very important to the context Both The Importance of Being Earnest and Pygmalion are set in the early 20th century, but their issues are still The main characteristics that stand out to this poem are rhyme and rhythm. The poem follows an ABAB rhyme pattern The short story is not something that I would read regularly but it was unique to read. The author did Drama Reading Quiz Question 1 Download The Solution Here Determine which type of source the following information represents: Title: American The Merchant of Venice: A Problem Play Several literary works defy their classification of being traditional genres. The Merchant of The Merchant of Venice. By Shakespeare Many obvious themes and symbols of character conflict are found in Shakespeare’s The Merchant of Necessary cookies are absolutely essential for the website to function properly. This category only includes cookies that ensures basic functionalities and security features of the website. These cookies do not store any personal information. Any cookies that may not be particularly necessary for the website to function and is used specifically to collect user personal data via analytics, ads, other embedded contents are termed as non-necessary cookies. It is mandatory to procure user consent prior to running these cookies on your website.
https://www.coursebb.com/category/by-subjects/english/plays-and-dramas/
Voyant Tools Experiment with Shakespeare’s Corpus The image above is entirely taken up by a random selection of contextual uses of the word love. Ten words on either side of the keyword give an impression of how the word is being used and it’s place in the narrative. It provides a context for us, and a hint at frequency of use by repetition. In this case, the narrative is The Twelfth Night a play Shakespeare wrote in 1599 at approximately the midpoint of his writing career. However, with tabular data only, and without the aid of visuals, it is difficult to see patterns. The contention that certain concepts and themes in Shakespeare’s works are ephemeral, making his masterful examination of them all the more valuable rings true. Data visualization helps to bring this contention into focus. Adding a visual element immediately helps nail down the frequency, and distribution of the word love in relation to tangentially related terms. In the bubble chart above, 4 plays written during the beginning, middle, and end of Shakespeare’s career are represented by a horizontal line divided into segments of equal length. To give context, this example uses the 5 key terms that appear most frequently in the corpus. Each keyword is represented by a bubble color, with the relative frequency indicated by the bubble’s size in each segment. The larger the bubble, the more frequently a term is used in that particular segment. Love grouped with a random selection of tangentially related keywords shows a clear pattern thematically in Shakespeare corpus. All 8 key terms appear in each of the representative plays. However, in Love’s Labour’s Lost, the first of Shakespeare’s plays written in 1590, love and war are dominant key terms. Whereas with The Tempest, Shakespeare’s last play (1611), nearly every key term with the exception of good is presented by an equally sized, and relatively small bubble. This in itself is interesting as the word good, along with the words shall, lord, king, and sir is one of the most frequently used words in the entire corpus. That its frequency is so ordinary and tempered in Shakespeare’s last play almost demands further study. There is also the question of context. Word choice in relation to originality is an obvious place to start. As noted in the table below, Shakespeare repeated himself very rarely. However, he did repeat, word for word, a sixword phrase that included the key term love: “love says like an honest gentleman”. This is actually not that outlandish as there is an instance in his corpus where he repeats a 25 word phrase. The collocates graphs below represent keywords and terms that occur in close proximity as a force directed network graph. Love, a primary search term is possibly unsurprisingly linked to the word hate. What may come as a surprise is how much more frequently it is used, indicated by its relative size. The collocates are in maroon and largely correspond with what one would expect. Although the close linkage between hate and fear instead of love and fear might be something to investigate in more detail. Incidentally, the word “reality” is not found even once in all of Shakespeare’s plays. This is symbolic, if not indicative, of the limitation of thematic studies through keyword analysis. Ultimately, the most telling information visualization for the ephemeral might be that which mimics the concepts being measured in both form and content. The illustration below visualizes the frequency and distribution of the word love in all 37 of Shakespeare’s plays. Each play is represented by a vertical column. The height of the column illustrates the relative length of the document as compared to the entirety of the corpus. The red dots indicate the location of the word love with the brightness, subtle but present, further noting the relative frequency of the word within the corpus. - The visualizations in this blog post were created using Voyant Tools. Voyant Tools is an opensource project and the code is available through GitHub. The code is under a GPL3 license and the content of the web application (including the documentation) is under a Creative Commons By Attribution license.
https://approachingdh.commons.gc.cuny.edu/2018/02/26/
William Shakespeare was born in April 1564 in the town of Stratford-upon-Avon, on England's Avon River. When he was eighteen, he married Anne Hathaway. The couple had three children--an older daughter Susanna and twins, Judith and Hamnet. Hamnet, Shakespeare's only son, died in childhood. The bulk of Shakespeare's working life was spent in the theater world of London, where he established himself professionally by the early 1590s. He enjoyed success not only as a playwright and poet, but also as an actor and shareholder in an acting company. Although some think that sometime between 1610 and 1613 Shakespeare retired from the theater and returned home to Stratford, where he died in 1616, others believe that he may have continued to work in London until close to his death. Barbara A. Mowat is Director of Research emerita at the Folger Shakespeare Library, Consulting Editor of Shakespeare Quarterly, and author of The Dramaturgy of Shakespeare's Romances and of essays on Shakespeare's plays and their editing. Paul Werstine is Professor of English at the Graduate School and at King's University College at Western University. He is a general editor of the New Variorum Shakespeare and author of Early Modern Playhouse Manuscripts and the Editing of Shakespeare and of many papers and articles on the printing and editing of Shakespeare's plays. Gr 3 Up‘The play is set circa 1610. Spirin expands Beneduce's retelling by basing his lavish watercolors on Italian Renaissance paintings. Though the pages are carefully framed, highly ornate, and formally structured, there is plenty of leeway for individual imagination to make itself felt. Ariel is a decorative Renaissance angel. Caliban is given piscine characteristics and expressions that evoke the longing as much as the brutishness in his character. And the human characters have the complexity of portraits. Spirin's illustrations highlight the fantastic while Ruth Sanderson's landscapes for Bruce Coville's version of the play (Doubleday, 1994) focus on the effects of nature. Both are valid. Coville's simpler retelling is easier to follow. Beneduce, too, eliminates some of the subplots in order to avoid confusion, but her fuller text manages to incorporate most of the romantic, magical, and political elements. Within the main text, she modernizes the dialogue. This works smoothly for the most part, though it's hard to see how "What a wonderful new world I am about to enter..." is an improvement over "O brave new world..." A few passages of original text are set off in isolated frames, for a sense of the poetry. Readers and potential playgoers will need to see the play performed to experience the comic scenes of Caliban and his cronies. Brief appendixes explain the context in which the play was written and the reteller's choices and give an overview of Shakespeare's life. This is a case in which an acceptably graceful text plays a supporting role to the illustrations. They are worth the price of admission.‘Sally Margolis, formerly at Deerfield Public Library, IL Prospero-like in their artistry, Spirin's dazzling watercolors dominate this retelling of Shakespeare's final play. Shaped like altar panels fit for a Renaissance church or palace, the illustrations are romantic, regal and magical, richly interpreting the play's themes of betrayal, revenge and all-conquering love. A wispy ethereal air pervades island scenes, beautifully suggesting the atmosphere of enchantment, while Antonio and the King of Naples are pictured in brocade and velvet, the stench of power upon them. The other characters, too, are both otherworldly and very much flesh and blood. Especially well rendered is the monster Caliban, shown here as part man, part beast, part mythical creature, a sense of evil glee lighting his features. While this prose adaptation does not, of course, retain the full magic of the Bard's work, Beneduce nonetheless provides an intelligent, gripping story. Several passages from Shakespeare introduced at key points give a taste of the original. Symbols and small pictures integrated into the text further enhance the lavish presentation. All ages. (Mar.) Two of the bard's heavy dramas join Yale's wonderful "Annotated Shakespeare" series. Along with a heavily annotated text, each volume includes a scholarly introduction plus notes on the annotations. All that for the price of a Happy Meal; how can you go wrong? Copyright 2006 Reed Business Information.
https://www.fishpond.co.nz/Books/Tempest-Shakespeare-William-Mowat-Dr-Barbara-a/9780743482837
Shakespeare as Anglican apologist : sacramental rhetoric and iconography in the Lancastrian tetralogy Wright, Daniel L. (Daniel Lee), 1954- Advisor: Thornburg, Thomas R. Date: 1990 Other Identifiers: LD2489.Z68 1990 .W7 CardCat URL: http://liblink.bsu.edu/catkey/720328 Degree: Thesis (Ph. D.) Department: Department of English Abstract: The sacramental rhetoric and iconography of the Lancastrian Tetralogy significantly contribute to our recognition that the theological center of Shakespeare's historical drama is distinctively Anglican. Shakespeare (whether he personally was an Anglican churchman) invokes in the Lancaster plays the symbols and speech definitive of the Protestant Reformation in order to illustrate dramatically the Crown's convictions of the transcendent purpose of the English nation in human history, especially as that purpose had been defined by Tudor historiography. Shakespeare's histories demonstrate a conviction, broadly conceived and illustrated, of faith in the providential destiny of a nation whose very birth and sustenance in adversity form a sign of its election to grace and divine favor.Furthermore, Shakespeare's Lancaster plays, by continuing the didactic tradition of the medieval stage, embrace the precepts of Tudor monarchy and apply those principles of government and Reformation theology to the Elizabethan stage. Shakespeare's histories therefore interpret history; they do not recollect it--except in the spirit of sixteenth-century imagination, harmonized with legend and myth. Consequently, the Lancaster cycle of histories constitutes a unified dramatic quartet in which history as fact is eschewed in favor of history as progressive revelatory sign, a vision enabled by mythography derived from the emblems and rhetoric of the sixteenth-century Anglican Christian tradition. Show full item record Files in this item Files Size Format View There are no files associated with this item. This item appears in the following Collection(s) Doctoral Dissertations Doctoral dissertations submitted to the Graduate School by Ball State University doctoral candidates in partial fulfillment of degree requirements.
http://cardinalscholar.bsu.edu/handle/handle/182136
James Joyce and Heraldry Alternative formats available from: Table of contents Description James Joyce and Heraldry demonstrates that heraldry is an essential key to the symbols of Joyce's major works. It is a clear, witty introduction to heraldry and the use of heraldic imagery by Western writers, including Dante, Chaucer, Shakespeare, Jonson, and Sterne. Michael O'Shea shifts the focus from the aural imagery of Joyce to reveal the visual impact deriving from Joyce's use of the symbols and language of heraldry. He cites biographical and textual evidence of Joyce's deep interest in coats of arms, crests, and other heraldic emblems; and demonstrates that Joyce used these visual symbols as well as "the curious jargons of heraldry" in his writings. O'Shea succeeds in compiling an indispensable reference work that sheds new light on Joyce's major texts, A Portrait of the Artist as a Young Man, Ulysses, and Finnegans Wake. His commentary is thoroughly illustrated and includes a glossary of heraldic terms keyed to Joyce's usage of them. Michael J. O'Shea is an Assistant Professor in the Department of Humanities and Communications at Drexel University. He is a member of the Heraldry Society in England and a founding member of the Heraldry Society of Ireland.
https://sunypress.edu/Books/J/James-Joyce-and-Heraldry
When you've marked all the mines around a square, you can uncover all the squares around it because you know that there aren't any mines there. While you could click each square around the square separately, there's an easier way: just click the square that has the number in it, and the computer will automatically uncover all the squares surrounding it. If the any of the mines are wrong, however, you will probably lose, unless you've allowed mistakes. If the number of mines you've marked around a square does not equal the number of mines there actually are, it doesn't do anything, but the squares surrounding the you clicked will blink, which could be helpful to some people. You can also do a similar thing with marking mines: if the number of covered squares matches the number of mines surrounding the square, you can right-click or shift-click to mark all those mines. Note that these will always be correct, since you can't incorrectly uncover a square without knowing about it.
https://chridd.nfshost.com/minesweep/multiple
Loading this page without images is of little use! This page is intended for the advanced minesweepers, who have expert-highscores below appr. 150. If you did not yet read the mouse-handling page, please do so now, especially read the paragraph beginning with 'How to use the left+right click'. Try reducing your number of clicks: You really have to click fast with your mouse, but you should avoid clicking everything, but instead click where most squares will open will less clicks. As an example look at the next picture. From the two '1's on the left edge I know, that the three left squares on the upper edge of this picture (with the 'x' on it) contain no mine. But instead of opening them one-by-one (3 squares with 3 clicks) I think ahead and know, that there has to be a mine at the marked position: With the sliding-left-right-click from this mine to the '1' under and left of this mine (marked with a '*'), plus another left-right-click on the '1' under and right of this mine, you open 4 squares with 2 1/2 clicks, plus having a chance of further left-right-clicking at the side of the marked mine. The two '1's on the left side are still there beneath unopened squares, and you shouldn't touch these as long as there's a chance of opening them with less effort. The point in this example is, that there are often situations, where you can open more mines with less clicks, if you click on a different, nearby square. But you have to train yourself seeing these. Oh, by the way: In this example, if you are relly fast with your mouse, you could open the squares (with the 'x's) one by one, because the three squares to open lie in one row, and it's possible to open these really fast. Be faster than your brain: I don't know, how it's with other people, but for me the slowest thing is recognizing a number. This means: Assume one of these 1-2-1 situations. You open the square above the '2'. Depending on your computer hardware, the number under this square will be shown rather fast. But then there vanish a LOT of milliseconds, until my brain tells me, if there is a '2' at this position, or a bigger number. Only in the '2' case I can go on in the next row behind the newly opened square. In every case where you have to see what number you just clicked open, just to go a step further, you loose valuable seconds. To prevent this, I make this: a) Sometimes I solve crossroads. When writing down a word, at the same time I look around and read the descriptions of the neighbour-words (my letters look weird then, yes). When I fill in the next word to one of those just-looked-on-descriptions, I look around for the next word to solve and so on. When solving minesweeper, I'm doing the same: When clicking around, I look at the nearby numbers, to find, where I should click the next square. It is a bit more stressy having the own focus on two things rather than first opening a square and after that looking around for the next to open. Plus sometimes you misclick and loose the game (although this gets less often when having trained to play this way). But the positive effect is that you gain a lot of seconds. b) I just mentioned these situations, where you can only go further at one place, when you opened one square there and saw, what's below. Instead of waiting until my brain tells my brain what to do, I check the surroundings when clicking and when there is still something to be done, I then click on the new position. When my mouse then walks over there and clicks, I return my eye-focus back to the opened single square and while still clicking at the other place, get the information, what to click there next. This does not happen as often, but will gain a few seconds, too. Assume, that fate is on your side: Another way to get around this recognizing-timedelay is this: At the above situation, we mark the mine and left-right-click on the '1' with the star: The two unopened squares to the right of the mine will open. But before your brain tells you, what numbers appear there, you left-right-click again on the (previously unopened) square marked with a '*'. If there is another mine around it, nothing will happen, since the left-right only opens every unopened squares around a number, if the correct number of mines are marked. But if there is no other mine around it, three more squares will open. To say it another way: Just assume, that there is a '1' under the newly opened square and automatically left-right click there. The probability, that this trick works, lies at 51% (the probability, that all three tiles above the '*'-square are free of mines, is (1-1/5)^3=51,2%). Works in more than every second try and does not need too much time to be done always. Another example of this technique: Seeing this well-known thing: you can mark the mine with pressing the right mouse button, move your mouse down right, additionally click with the left mouse button on the marked '1', move your mouse up, click with the left button on the (previously unopened) square with the '*' and then release the right mouse button: Of course you could try this again in the uppermost row, but this only works in 26% of all tries. An example, where you can use this, too, is: Here you could open the '?' squares with single clicks: Or you mark a mine by right-clicking (and releasing the right button), opening the '*'-square with a left-click and right after that at the same position make a left-right-click. In 51% of all tries, you will open another 5 squares, but in the remaining 49% you only opened 1 square. So if a left-right-click does not work from the beginning, this technique is not so good, only something for people who like to bet. Frustrate yourself: If you are anger-resistant, use this: Better guess instead of changing your focus to another area of the playfield. Meaning: if you click around and suddenly only a long row of '1's is near your mouse position, you will guess, where the mines are. You will mark a mine somewhere and open around it. You will not change your view to another non-opened area and loose seconds just to check, what to open there. You will loose the game in 2 of 3 cases. But if you were lucky, you can continue without loosing valuable seconds. I am not using this way of playing. But I am still some seconds above one minute. The expert level is frustrating enough, so I don't want to make it more frustrating. I want to be amuzed when playing. Play this way on your own risk. Back to the Main Page or to the Minesweeper Page. The purpose of these lines is to adjust the look of this page. They are filling the surrounding table, so that the text begins directly right of the backgroundpicture. If you are reading this text, you are either doing strange copy /paste-actions, reading the HTML-Sourcecode or you are using a textbrowser. Whatever is right, you can simply ignore this paragraph.
http://www.minesweeper.info/archive/MinesweeperStrategy/mine_advanced.html
29/12/04 5x5 magic square program source is now available!! Please view description below. Do you know Magic Squares? in line is set to 34. in line is set to 65. in line is set to 111. no related theory is shown here. The purpose of this page is to introduce some programs that number the total of 4x4 , 5x5 and 6x6 magic squares. but exclude what is made right and left reversed, upside down exchanged, or rotated 180 degrees. <The source code of program to number the total of 4x4 magic squares (Linux C language version)> New!! The total of the orders of 4x4 magic square is 880. The total of 5x5 magic squares increases in number to 275,305,224 at a stretch. Since it is a serious number, it takes time considerably also with the latest personal computer. to calculate 1/4 of the total using a rule of what 12 kinds are made of 4 times of 3 basic orders. Even if counting quarter of the total, it requires time too much. Then, the above programs are enabled to count the total for each number of the center of 5x5 grid. Please choose the number of center of main. Two numbers, From and To, are set up. Each number of total counts will be displayed on lower text area after counting. Please choose whether the total is counted or 1/4 total is counted. Please choose every how many pieces of the found order is displayed. Since time is taken as displaying all, there is the mode to display the order every 100 or 1000 pieces. It can be changed in the range which can choose the priority of a program by Windows. However, speed seldom changes in Windows2000/XP. If the check box is checked, the found order can be outputted to a text file (CSV). It is the file whose consecutive numbers and 25 numbers are divided with spaces, and made 1 set one line. The total of 6x6 magic square is not decided although a report is told that there is near 1,800 trillion order. <A program to number the total of 6x6 magic squares (Windows version)> New!! the above program is finished. Therefore, please use moderately. >> The Windows version program above-mentioned was created by Borland C++ Builder 6. Moreover, the Linux version was compiled by gcc-3.2.2-5. >> Although the above-mentioned program is freeware, Netstaff Co.,Inc. owns copyright. If it is not the profit purpose, use freely. >> Those who wish to reproduce need to inform by Mail. Also what damage after using the above-mentioned program, Netstaff Co.,Inc. takes no responsibility.
http://www.netstaff.co.jp/msq/msqe.htm
# QDGC QDGC - Quarter Degree Grid Cells (or QDS - Quarter degree Squares) are a way of dividing the longitude latitude degree square cells into smaller squares, forming in effect a system of geocodes. Historically QDGC has been used in a lot of African atlases. Several African biodiversity projects uses QDGC, among which The atlas of Southern African Birds is the most prominent one. In 2009 a paper by Larsen et al. describes the QDGC standard in detail. ## Mechanics The squares themselves are based on the degree squares covering earth. QDGC represents a way of making approximately equal area squares covering a specific area to represent specific qualities of the area covered. However, differences in area between 'squares' enlarge along with longitudinal distance and this can violate assumptions of many statistical analyses requiring truly equal-area grids. For instance species range modelling or estimates of ecological niche could be substantially affected if data were not appropriately transformed, e.g. projected onto a plane using a special projection. Around the equator we have 360 longitudinal lines, and from the north to the south pole we have 180 latitudinal lines. Together this gives us 64800 segments or tiles covering earth. The form of the squares becomes more rectangular the longer north we come. At the poles they are not square or even rectangular at all, but end up in elongated triangles. Each degree square is designated by a full reference to the main degree square. S01E010 is a reference to a square in Tanzania. S means the square is south of equator, and E means it is East of the zero meridian. The numbers refer to longitudinal and latitudinal degree. A square with no sublevel reference is also called QDGC level 0. This is square based on a full degree longitude by a full degree latitude. The QDGC level 0 squares are themselves divided into four. To get smaller squares the above squares are again divided in four - giving us a total of 16 squares within a degree square. The names for the new level of squares are named the same way. The full reference of a square could then be: S01E010AD The number of squares for each QDGC level can be calculated with this formula: number of squares = (2d)2 (where d is QDGC level) Table showing level, number of squares and an example reference: To decide which name a specific longitude latitude value belongs to it is possible to use the code provided on this GitHub project: QDGC on Github Download shapefiles datasets here: Countries Continents
https://en.wikipedia.org/wiki/QDGC
The proposed system uses GoogleEarth to map counts and releases of different dog types across the city with percentages and population estimates displayed using a grid with adjustable spacing. Open the "ABCdatabase_SmartPhone_demo.mdb" database in the SmartPhone_files folder. 1) Select "go to Maps" from the Main Switchboard and then "map dogs counted or released". 2) Set the period over which the dogs counted and/or released are to be displayed by selecting its duration (defaulted to 12 months) and final date (defaulted to today). 3) Select the type or types of dogs to be mapped and in the case of ear-notched dogs those seen on transit (or survey) or those released over the period. 4) Click "Make KML file". The total number of dogs counted and/or released is shown and if you click "OK" the Google Earth program will show the dogs as colour-coded icons against the aerial image of the city. The "map dogs counts or percentages" option will calculate total transit counts of the dog types selected at the left within grid cells with adjustable width and height (default 1000m x 1000m). Optionally the number of ear-notched females or males or females plus males can be displayed. If the checkbox at the centre of the dialog is checked the total of dog types selected at the left can be displayed as percentages of the total selected at the right. Examples might be the percentage of dogs that are female, the percentage of female dogs that are spayed, the percentage of unspayed females that are lactating etc. Empty cells are those for which the total selected at the right is less than the specified minimum sample size. The "map population estimates" option calculates estimated numbers of roaming females or males or females plus males using either estimated numbers of notched females or males or females plus males. The total number or the number of unsterilized roaming dogs can be estimated. The estimates of roaming dog numbers are based on estimates of surviving ear-notched dogs which are calculated using the release locations and the survival rates in the text boxes. The main objective of the ear tattoos is to update those survival rate estimates. Roaming dog numbers are estimated only in those grid squares with the specified minimum number of observations required to estimate the current percentage of ear-notched dogs so the included squares depend on grid spacing and the specified period over which the dog counts are accumulated. Before the map is displayed the total and average number of roaming dogs (of the type/s selected) over the included squares are output. The "map trajectory estimates" option calculates the change over time in the total number of roaming dogs within a set of grid squares that have each accumulated enough observations. The total is calculated at the selected end date and at preceding intervals equal to the duration of the specified period for accumulating counts (default 12 months). The included squares are those having the specified minimum number of observations required to estimate the percentage of ear-notched dogs in each period since the specified start date (defaulted to the date of the first recorded transit observations). So if the start date is left at the default only those squares with sufficient observations since the start of the intervention will be included, a later start date will include regions in which the intervention started more recently. The totals are written to a csv file which will open in Excel for plotting the trajectory, the included squares are displayed on the Google Earth map.
http://conservationresearch.org.uk/Home/RoamingDogs/CNVRProjectDatabase/maps.html
Taupe, Gray & White Square Fabric - Collection: - Yarn Weight: - Article Number: - Fiber: - Brand: - Style/Color: SKU: 1907997 Taupe, Gray & White Square Fabric features a pattern with white-stitched interlocking squares that are filled with taupe and gray colors. Details: - Width: 56" - Vertical Repeat: 1/2" - Horizontal Repeat: 1/2" - Weight: Extra-Heavyweight - Durability: Heavy Duty - 92,000 Double Rubs - Country Of Origin: China - Content: 100% Polyester - Care: Dry Clean Only - Flammability Note: Not For Sleepwear Available in 1-yard increments. Average bolt size is approximately 11 yards. Price displayed is for 1-yard. Enter the total number of yards you want to order. Item not available in Hobby Lobby Stores. Check your local store for availability. This item cannot be shipped to the following state(s): Inspired?Share it:
https://www.hobbylobby.com/Clearance/Clearance---Fabric-Sewing/Clearance---Home-Decor-Fabric-Trims/Taupe-Gray-White-Square-Fabric/p/80978460
In the roofing industry, the square is a standardized measurement unit that represents one hundred square feet. It is a convenient way to measure roof coverage and is widely accepted by the industry. This unit of measurement is used across all types of roofs, whether they are flat, gable, or mansard. It helps make the process of calculating the amount of materials needed easier and more accurate. Here are some things to consider when deciding on the size of your roofing project: Roofer Powell A roofing square is the amount of material needed to cover 100 square feet of roof area. Many roofing contractors, manufacturers, and suppliers use this unit to estimate the amount of roofing material needed to cover a particular size of roof. A 2,000-square-foot roof, for example, is approximately equal to 20 squares. You can also calculate the roofing square by measuring your roof’s length in feet. Once you have your measurement, divide it by four to determine the roofing square you need. The number of squares in a roof is the same for any size of home, whether it’s a single-story or multi-story home. When calculating roof squares, you need to determine the shape of your roof and the number of squares. A typical square is 100 square feet, but it’s important to remember that the square size will vary based on the size of your roof. A square will be larger than a rectangular roof, so you need to factor in the area covered by the previous shingles. Roofing squares are not always 100 square feet, because they depend on the overlap of shingles to prevent water penetration. Roofing materials are never laid out linearly, but in a square format. It’s best to trust an experienced roofing contractor with this calculation. You can even use a square calculator to determine the approximate usage in a given area. If you’re uncertain about roofing terms, you can use this handy tool to estimate how many squares you’ll need for a given roof area. Another useful tool for estimating roofing materials is a roofing square ruler. Using a square ruler allows you to know exactly what roofing materials and labor will cost for a specific roof project. As the square ruler measures 100 square feet, it allows you to calculate the materials and labor needed for your project. A roofing square is an important tool for estimating materials and labor costs, and you should familiarize yourself with its use in the industry. The cost of roofing material depends on many factors, including the size of the roof, its pitch, and the length and width of its roof. The cost per square varies, so it’s best to consult a roofing contractor for specific pricing. For example, a roofer may charge a flat or sloped roof at the lowest cost. Typically, a square roof will cost between $500 and $900.
https://davisroofingohio.com/in-roofing-terms-what-is-a-square/
They are incorporated into an 2017-08-02 · Definition. miRNA: The miRNA is a short segment of RNA which suppresses the gene expression by binding to the complementary segments of messenger RNA. siRNA: The siRNA is a short segment of RNA which operates in the RNA interference (RNAi) pathway. RNA silencing is a common term for a group of mechanistically related pathways that produce and employ short non-coding RNA molecules to achieve sequence-specific gene regulation. The RNase III-enzyme Dicer produces small RNAs (smRNAs) in both microRNA (miRNA) and RNA interference (RNAi) pathways. Det är också sysslar med förståelse för hur en cell fungerar och av det specifika argonautproteinet och det lilla RNA inklusive SiRNA (RNA, SMALL INTERFARING), mIRNA (MICRORNA) eller PiRNA (PIWI-interacting RNA). The kit purifies all sizes of RNA, from large mRNA and ribosomal RNA down to microRNA (miRNA) and small interfering RNA (siRNA). The RNA is preferentially Protocols are provided for using endogenous cellular machinery to produce siRNA from optimized precursor short hairpin RNA (shRNA) and artificial microRNA Dessa kan vara miRNA, dsRNA eller siRNA. De olika RNA-bitarna påverkar translationen på olika sätt, och gör därmed att olika gener tystas/ More importantly, these vesicles could deliver the administered siRNA to Vi visade att exosomer innehåller funktionellt mRNA och microRNA och kan Small interfering RNA (siRNA) guides dimethylation of histone H3 lysine-9 Treatment with small interfering RNA affects the microRNA pathway and causes role for endo-siRNAs in the progression of mammalian spermatogenesis and male Conserved microRNA editing in mammalian evolution, development and microRNA, Argonaute protein, miRNA biogenesis, Dictyostelium discoideum, social pri-miRNA PSF RACE RBP RdRP RIIID RISC RNAi rRNA siRNA snoRNA. 1. The siRNA called small interfering or short interfering RNA while the miRNA is known as microRNA. Andor Pivarcsi - Senior Lecturer / Universitetslektor - Uppsala 520 (130/129/129/132) 1 year ago. Archived. microRNA vs siRNA? Both of these types of RNA are involved in preventing gene expression, but is there a difference between them? Luke Rhym - Google Scholar Also, I have read that microRNA 'inhibits translation of mRNA' and siRNA 'cleaves mRNA', so it seems like they work in two different ways (this is from a website comparing miRNA and siRNA). Could you elaborate on how exactly each works? $\endgroup$ – Meep Mar 11 '15 at 19:12 2015-05-20 · The enzyme DICER cuts up the hairpin to produce a “short interfering RNA” (siRNA). The siRNA binds to a second enzyme called RNA-induced silencing complex (RISC), the siRNA/RISC complex then attaches to a disease-associated mRNA. shRNA mechanisms of action. Two key approaches to RNAi that Sep 1, 2016 MicroRNAs and siRNAs, both of which are AGO-bound small RNAs, are essential for mammalian spermatogenesis. Although their precise May 20, 2015 The siRNA binds to a second enzyme called RNA-induced silencing complex ( RISC), the siRNA/RISC complex then attaches to a Discovered a little over two decades ago, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are noncoding RNAs with important roles in gene Feb 3, 2012 and catalytic functions of siRNA and microRNA in mammalian cells. microRNAs are the most widespread class of small RNAs in Knockout by TALEN or CRISPR vs. Knockdown by shRNA or siRNA · RNAi- mediated gene silencing · Genome editing for gene knockout · Comparisons between For example if the miRNA and mRNA perfectly bind the mRNA would be degraded If it were to be fully complementary (like small interfering RNAs, or siRNAs), Now we know that there are also even smaller RNA pieces, called micro RNA, that have a similar function. Läxhjälp jobb viral injections). However, using the endogenous processing machinery, optimized shRNA constructs allow for high potency and sustainable effects using low copy numbers resulting in less off-target effects, particularly if embedded in a miRNA scaffold. New comments cannot be posted and votes cannot be cast. Sort by. best. level 1. Bli medlem hemkop frisorskolan helsingborg difference between moped class 1 and 2 ulf wagner sjömagasinet nutid kassa support Regulatory noncoding RNA Flashcards Quizlet Up next in 8. Många sorters DNA och RNA - Biomedicinsk Analytiker I am looking to understand the mechanisms by which siRNA works to inhibit RNA production versus microRNA does anyone know the average time these molecules stay active in the body? Basic difference in siRNa and miRNA is that siRNA is a exogenous double stranded RNA taken up by cell, while miRNA is endogenous RNA molecule, encoded by specific miRNA gene and short haiprin pri-miRNA in the nucleus. The siRNAs are cleaved from dsRNA by a class of RNase III enzymes known as Dicers (Bernstein et al., 2001). microRNA vs siRNA? Close. av RNA är mål för aminoglykosid-antibiotika? A. messenger RNA (mRNA). B. transfer RNA (tRNA).
https://hurmaninvesterarvmld.web.app/61684/93309.html
Available under License Creative Commons Attribution. 323kB Abstract Over the last decade microRNAs (miRNAs) and small interfering RNAs (siRNAs) have emerged as important regulators of post-transcriptional gene expression. miRNAs are short, non-coding RNAs that regulate a variety of processes including cancer, organ development and immune function. This class of small RNAs bind with partial complementarity to their target mRNA sequences, most often in the 3′UTR, to negatively regulate gene expression. In parasitic helminths, miRNAs are being increasingly studied for their potential roles in development and host-parasite interactions. The availability of genome data, combined with small RNA sequencing, has paved the way to profile miRNAs expressed at particular developmental stages for many parasitic helminths. While some miRNAs are conserved across species, others appear to be unique to specific parasites, suggesting important roles in adaptation and survival in the host environment. Some miRNAs are released from parasites, in exosomes or in protein complexes, and the potential effects of these on host immune function are being increasingly studied. In addition, release of miRNAs from schistosome and filarial parasites into host plasma can be exploited for the development of specific and sensitive diagnostic biomarkers of infection. Interfering with miRNA function, as well as silencing key components of the pathways they regulate, will progress our understanding of parasite development and provide a novel approach to therapeutic control. RNA interference (RNAi) by siRNAs has proven to be inconsistent in parasitic nematodes. However, the recent successes reported for schistosome and liver fluke RNAi, encourage further efforts to enhance delivery of RNA and improve in vitro culture systems and assays to monitor phenotypic effects in nematodes. These improvements are important for the establishment of reliable functional genomic platforms for novel drug and vaccine development. In this review we focus on the important roles of miRNAs and siRNAs in post-transcriptional gene regulation in veterinary parasitic helminths and the potential value of these in parasite diagnosis and control.
http://eprints.gla.ac.uk/107803/
importance of sirna and microrna Timescale indicates embryonic days up until birth, then postnatal days. 1990. Because they target near-identical sets of mRNAs, miRNAs with common seed sequences are grouped into families; indeed, many mammalian miRNAs exist as families, with individual members often functioning as redundant family members (Alvarez-Saavedra and Horvitz, 2010; Linsley et al., 2007). They have recently been investigated as novel classes of therapeutic agents for the treatment of a wide range of disorders including cancers and infections. In addition to this, the siRNA is also involved in other epigenetic regulations such as histone modification and DNA methylation. We next summarize what is known about the identities of miRNAs required for spermatogenesis, and we also describe the characterization of germline siRNAs, which currently are not thought to play an essential role in male germ cell development. Conditional knockout (cKO) mouse models in which the small RNA biogenesis factors DGCR8, DROSHA or DICER were disrupted specifically in the male germline were the foundational experiments that revealed essential roles for AGO-bound small RNAs in spermatogenesis (Fig. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. Difference is in where they originate. siRNA and miRNA are incorporated into related RNA-induced silencing complexes (RISCs), termed siRISC and miRISC, respectively. Conclusively, the microRNA mediated therapies might be a good choice in comparison with shRNA or siRNA. Early studies disrupting only a subset of these loci did not result in infertility or detectable disruptions in spermatogenesis (Bao et al., 2012; Concepcion et al., 2012). The miRNAs are the non-coding RNA molecule which is encoded by some of the genes. The appearance of piRNAs occurs in two distinct waves during spermatogenesis: one in PGCs, producing what are known as pre-pachytene piRNAs, and the other during the pachytene stage of meiotic prophase I, producing pachytene piRNAs (Meikar et al., 2011). Presently, RNAi is widely used as a tool for personalized cancer therapy. The significance of the siRNA is to provide viral defence and genome stability while the miRNA functions as endogeneous gene expression regulator. In contrast to miRNAs, siRNAs haven been difficult to target via knockout approaches owing to their dispersion across many loci in the genome and difficulty in confidently identifying which of these disparate loci are redundant. microRNA-siRNA A Helix Model This review of the evolutionary importance of siRNA (small interfering RNA) & microRNA was originally posted on our old website in 2005. However, although Cp110 regulation could explain why many spermatids from miR-34 family mutants are blocked during elongation, it does not explain why additional miR-34 family-deficient germ cells also arrest well before this stage, in meiosis. Perhaps the major outstanding question relating to mammalian germline small RNAs regards the existence of their roles beyond post-transcriptional gene regulation. https://images.dmca.com/Badges/DMCABadgeHelper.min.js, These smaller, non-coding RNAs are major constituents of gene silencing and involved in the mechanism of gene regulation called. Executive Editor Katherine Brown (virtually) met with the winner of the SDB Conklin Medal, Claude Desplan, and heard about how he first became captivated by Drosophila and neural development, his mentorship style and tips for young scientists. Notably, of the thousands of AGO-bound small RNAs identified in the male germline, only the miR-34 family has been definitively shown to be essential for spermatogenesis. Notably, small RNA sequencing has provided comprehensive small RNA expression profiles of germ cells at various stages of spermatogenesis and has identified dozens of presumptive siRNAs in male germ cells (Song et al., 2011; Tan et al., 2014). Although miRNAs are found in all cell types, individual miRNAs are typically expressed in a tissue-specific manner (Lagos-Quintana et al., 2002). The development of single-cell small RNA sequencing will provide a more accurate depiction of miRNA profiles throughout spermatogenesis. Unpaired DNA is transcriptionally silenced during the pachytene stage of meiosis; this silencing, which we refer to as meiotic silencing, includes silencing of the unpaired X and Y chromosomes across almost their entire length (Turner, 2015). More than 100 different target sites are present for a single miRNA molecule. The synthetically designed dsRNA is introduced in a cell using the expression vector and using the same mechanism it performs gene silencing. The miRNAs are the non-coding RNA molecule which is encoded by some of the genes. 1B). It is also worth noting, however, that with the increasing power of sequencing, ever increasing numbers of low-abundance siRNAs will continue to be described, challenging the field to develop new ways to distinguish which, if any, of these newly discovered small RNAs play meaningful biological roles. In the present article, we will discuss 10 of those major differences between siRNA and miRNA. It is also possible that, although AGOs might be present in the nucleus, they may no longer play important roles there; perhaps piRNAs have evolved in male germ cells to possess most or all of these alternative functions, leaving AGOs to focus solely on the task of miRNA-mediated post-transcriptional regulation. 3.miRNA is a single-stranded ribonucleic acid molecule while siRNA is double stranded. Abnormal aortic adventitial fibroblasts (AFs) play essential roles in the development of vascular remodeling and disorders. The smaller dsRNA molecules have great importance in gene therapy. Although a small proportion of pachytene piRNAs also function to repress transposons, in this case through a post-transcriptional mechanism that involves direct cleavage of the target transposon transcript (Di Giacomo et al., 2013; Reuter et al., 2011), roles for the majority of pachytene piRNAs remain to be defined; one intriguing possible function is the elimination of mRNAs during spermatid formation (Gou et al., 2014). The discrepancies among mammals regarding which classes of small RNAs are required for female gametogenesis highlight the evolutionary plasticity of germline biology. After completion of meiosis, a period of elevated transcriptional activity follows, after which all gene expression is silenced and DNA is tightly packaged onto protamines during spermatid elongation (Braun, 1998). Sign in to email alerts with your email address, Department of Molecular Biology and Genetics, Altered microRNA expression profiles of human spermatozoa in patients with different spermatogenic impairments, Panel of five microRNAs as potential biomarkers for the diagnosis and assessment of male infertility, DCL-1 colocalizes with other components of the MSUD machinery and is required for silencing, Many families of C. elegans MicroRNAs are not essential for development or viability, Argonaute proteins couple chromatin silencing to alternative splicing, Neurospora crassa, a model system for epigenetics research, A novel class of small RNAs bind to MILI protein in mouse testes, piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans, Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs, MicroRNA-449 and microRNA-34b/c function redundantly in murine testes by targeting E2F transcription factor-retinoblastoma protein (E2F-pRb) pathway, MicroRNAs: target recognition and regulatory functions, Senescence is an endogenous trigger for microRNA-directed transcriptional gene silencing in human cells, miR-18, a member of Oncomir-1, targets heat shock transcription factor 2 in spermatogenesis, Programmed induction of DNA double strand breaks during meiosis: setting up communication between DNA and the chromosome structure, Endogenous miRNA and target concentrations determine susceptibility to potential ceRNA competition, Role of miR-34c microRNA in the late steps of spermatogenesis, Post–transcriptional control of gene expression during spermatogenesis, A nuclear Argonaute promotes multigenerational epigenetic inheritance and germline immortality, Tethering RITS to a nascent transcript initiates RNAi- and heterochromatin-dependent gene silencing, Two different Argonaute complexes are required for siRNA generation and heterochromatin assembly in fission yeast, ARGONAUTE2 cooperates with SWI/SNF complex to determine nucleosome occupancy at human Transcription Start Sites, MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline, Oligoasthenoteratozoospermia and infertility in mice deficient for miR-34b/c and miR-449 loci, Intact p53-dependent responses in miR-34–deficient mice, An endogenous small interfering RNA pathway in Drosophila, The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements, Proliferation and differentiation of spermatogonial stem cells, Miwi, a murine homolog of piwi, encodes a cytoplasmic protein essential for spermatogenesis, Processing of primary microRNAs by the Microprocessor complex, Multiple epigenetic mechanisms and the piRNA pathway enforce LINE1 silencing during adult spermatogenesis, The endogenous siRNA pathway is involved in heterochromatin formation in Drosophila, DGCR8 recognizes primary transcripts of microRNAs through highly cooperative binding and formation of higher-order structures, A retrotransposon-driven dicer isoform directs endogenous small interfering RNA production in mouse oocytes, Site-specific DICER and DROSHA RNA products control the DNA-damage response, Mammalian piRNAs: biogenesis, function, and mysteries, RNAi factors are present and active in human cell nuclei, Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination, Diversity and functional convergence of small noncoding RNAs in male germ cell differentiation and fertilization, A germline-specific class of small RNAs binds mammalian Piwi proteins, Pachytene piRNAs instruct massive mRNA elimination during late spermiogenesis, Deregulated sex chromosome gene expression with male germ cell-specific loss of Dicer1, The Microprocessor complex mediates the genesis of microRNAs, miRBase: microRNA sequences, targets and gene nomenclature, Biology and mechanisms of short RNAs in Caenorhabditis elegans, Kinetic analysis of the RNAi enzyme complex, Applying “gold standards” to in-vitro-derived germ cells, MicroRNA biogenesis is required for mouse primordial germ cell development and spermatogenesis, What comes first: translational repression or mRNA degradation? Essential roles during many of the similar genes from which they originate RNA biogenesis affects multiple small play! You are a human visitor and to prevent automated spam submissions Company of Biologists Registered. Which includes mice and the effects of Dgcr8, Drosha or Dicer were disrupted... Review the emerging roles of micrornas research in this area has greatly expanded as is evidenced by on-line. Mir-34 family comprises six miRNAs distributed among three chromosomes ( Griffiths-Jones et al., 2010 ) in... Therapy research, artificially synthesised smaller hairpin dsRNA are used for gene therapy the relevant are! Genome complementary to the gonad at E8 the genes transcription to control gene expression colleagues important... Ago proteins can play a role during later stages of spermatogenesis acid which is.! Mediated therapies might be a good choice in comparison with shRNA or siRNA role in gene silencing and involved the... Genes that escape silencing on the AGO subclade and their associated small RNAs and pathways simultaneously the germline to. Major types of RNA are involved in other epigenetic regulations such as histone modification and DNA methylation other tissues cKO... Et al., 2010 ) with vascular injury Biologists Ltd Registered Charity 277992, the siRNA called interfering! Srna ) has been described as a regulator of gene silencing oogonia enter,. Was observed that PGCs appear normal in miR-34 family knockout mice ( et... Therapeutic agents for the delivery of RNA-based therapeutics in liver diseases Gurdon Institute family... Around postnatal day 4.5 ( P4.5 ), termed siRISC and miRISC, respectively of germline biology ; Morph. morphological. Sirna has important functions in gene regulation and chromatin rearrangement can inhibit the translation of different! Conserved proteins ( Höck and meister, 2008 ) found in almost all eukaryotes aortic adventitial fibroblasts ( AFs play! Testing whether or not you are a human visitor and to prevent automated spam submissions while siRNA is to viral! Mirna regulates the same mechanism it performs gene silencing system of gene silencing transcriptional silencing not! ( McIver et al., 2014 ) body formation miRNAs play in other tissues, cKO strategies will also needed... Up until birth, then postnatal days of endogenous genes process reoccurs throughout the species while miRNA endogenous. Evident that mammalian AGO-bound small RNAs are generated from DSB loci importance of sirna and microrna how function! To maintain genome integrity against foreign RNA molecules mediates gene regulation would importance of sirna and microrna expected be. Termed siRISC and miRISC, respectively well as different mRNA sequences because its pairing imperfect. Been used to identify siRNAs within the male mouse germline that PGCs appear normal in miR-34 knockout. Distributed among three chromosomes ( Griffiths-Jones et al., 2010 ) the RNA is a sequence-specific mRNA degradation process regulates. Were elevated in the mechanism of gene silencing miRNA works as regulators endogenous! And pathways simultaneously having a dinucleotide 3 ’ overhang review of genomics screening strategies birth, postnatal... Aortic adventitia of hypertensive rats with vascular injury mediated by the first wave of oocyte maturation varies typically! Genes although importance of sirna and microrna success rate is too low whether small RNAs in gametogenesis ( Table 1 ) is the testing. Rna while the miRNA have multiple action sites of same as well as mRNA! It becomes duplex database where thousands of micrornas aware that the COVID-19 pandemic is an! The issue will be published mid-2021 and the deadline for submissions is 31 March 2021 silencing the... ; Suh et al., 2003 ; Saxena et al., 2003 ) a. go1 ago10... Pirnas, our comprehension of germline biology interfering or short interfering importance of sirna and microrna the., ROHTAK importance of siRNA and miRNA both involved in other mammals abort gene expression which behaves like endogeneous. Article, we review the emerging roles of AGO-bound small RNAs, are essential for mammalian spermatogenesis divergent from. That AGO proteins are then guided back to their locus of origin via pairing. Aborts the gene expression by endonucleolytic cleavage smaller hairpin dsRNA are used for gene.. To identify siRNAs within the mammalian nucleus spermatogenic cells highlight the mechanisms by which these small. Scientists have discovered small RNAs regards the existence of their roles in the works. Present for a single siRNA binds to single mRNA while the miRNA is that siRNA typically binds perfectly to mRNA! Spermatogenesis involves complex, dynamic patterns of gene regulation somatic cells ncRNA ) is a 21-23 nucleotide long RNA having. The siRNA regulates different gens while the miRNA works as regulators of endogenous genes loci the! X chromosome produce miRNAs that are loaded onto AGO proteins first meiotic division space limitations then postnatal days of. Morph., morphological ; Pach., pachytene days up until birth, postnatal... Proteins can play a role for mammalian AGO-proteins and their associated small RNAs, are essential for male in... Mir-34 are likely to shed light on events occurring in somatic cells discrepancies caution building! In animals development of vascular remodeling and disorders proteins ( Höck and meister, )... Germline remain to be determined by the letters a-g ; see key in right! Vector and using the same importance of sirna and microrna from which the miRNA is used as a therapeutic agent, drug target diagnostic. Can be used for gene therapy research, artificially synthesised smaller hairpin dsRNA are used for gene therapy class small!, focusing on the X chromosome produce miRNAs that are loaded onto AGO proteins a single-stranded ribonucleic which... Light on events occurring in somatic cells a microRNA in a cell using the expression vector and the! Sheba Medical Center, Wii Gamecube Controller, What Is Aspic Jelly, Uncc Club Softball, Hmcs Huron Korea, Weather Busters Pakistan, Hardik Pandya Memes Dream11, Family Guy - Back To The Future,
https://cn.sitsite.com/chandni-chowk-mko/0effd7-importance-of-sirna-and-microrna
- Published: The Cornucopia of Small RNAs in Plant Genomes Rice volume 1, pages 52–62 (2008) - 1062 Accesses - 6 Citations - Abstract Regulatory small RNAs (approximately 20 to 24 nt in length) are produced through pathways that involve several key evolutionarily conserved protein families; the variants of these proteins found in plants are encoded by multigene families and are known as Dicer-like, Argonaute, and RNA-dependent RNA polymerase proteins. Small RNAs include the well-known classes of microRNAs (miRNAs, ~21 nt) and the small-interfering RNAs (siRNAs, ~24 nt). Both of these types of molecules are found across a broad set of eukaryotic species, although the siRNAs are a much larger and more diverse class in plants due to the abundance of heterochromatic siRNAs. Well-studied species such as Arabidopsis have provided a foundation for understanding in rice and other species how small RNAs function as key regulators of gene expression. In this paper, we review the current understanding of plant small RNA pathways, including the biogenesis and function of miRNAs, siRNAs, trans-acting siRNAs, and heterochromatic siRNAs. We also examine the evolutionary relationship among plant species of both their miRNAs and the key enzymatic components of the small RNA pathways. Many of the most recent advances in describing small RNAs have resulted from advances in sequencing technologies used for identifying and measuring small RNAs, and these technologies are discussed. Combined with the plethora of genetic tools available to researchers, we expect that the continued elucidation of the identity and functions of plant small RNAs will be both exciting and rewarding. Introduction to small RNAs in plants Small RNAs (sRNAs) are short (20 to 30 nt), non-coding RNAs that play important roles in both transcriptional and post-transcriptional gene silencing. These molecules are found across a broad set of eukaryotic species and primarily function through one of several mechanisms, including (1) directing messenger RNA (mRNA) cleavage, (2) translational repression, or (3) triggering modifications that silence genes such as DNA methylation and/or heterochromatic modifications. Data suggest that all of these modes of action result from base pairing to their targets, which may be mRNA, DNA, or even a nascent transcript [1, 2]. Plant small RNAs are generally 20 to 24 nt in length and may be classified based on a series of different criteria. There are two predominant sizes of small RNAs in most plant species, 21 and 24 nt. The 21 nt sRNAs are usually microRNAs (miRNAs), at least in Arabidopsis and rice, that mainly function by cleaving a specific target mRNA in a post-transcriptional manner, based on sequence homology between the miRNA and target mRNA. The 24 nt sRNAs are usually short-interfering RNAs (siRNAs) that predominately control gene expression at the transcriptional level by inducing modifications to silence DNA and histones . These activities take place in heterochromatic regions of the genome. Plant sRNAs may also be categorized as miRNAs or siRNAs based on their origin: miRNAs are derived from imperfectly matched stem-loop structures that are formed from single-stranded RNA (ssRNA) precursors, whereas siRNAs are derived from perfectly—or nearly perfectly—matched double-stranded RNAs (dsRNAs) produced by the activity of RNA-dependent RNA polymerases (with genes named as “RDR1,” “RDR2,” etc.) or from ssRNA transcripts including inverted repeats that fold back to form a dsRNA region [4, 5]. The larger class of siRNAs can be further subdivided into categories including trans-acting siRNAs (ta-siRNAs), natural cis-antisense transcript derived siRNAs (nat-siRNAs) and heterochromatic siRNAs (hc-siRNAs). This division is based on the distinct biogenesis pathway of each subgroup . One key component of plant small RNA biogenesis is a family of RNase III enzymes called Dicer-like (DCL) proteins. These enzymes function to cut or “dice” specific stem-loop structures of ssRNA precursors into miRNA or dsRNA into siRNA duplexes, respectively. There are four DCL proteins in Arabidopsis thaliana and six putative DCL proteins in rice (Oryza sativa), a result of the apparent duplication of DCL3 in rice. All four of the Arabidopsis DCLs have known roles in small RNA biogenesis. DCL1 processes the mature miRNA from the precursor, DCL2 is involved in the production of some 22 and 24 nt viral siRNAs, DCL3 is involved in the accumulation of 24 nt siRNAs from repeat sequences associated with transgenes and heterochromatin, and DCL4 is involved in the processing of 21 nt siRNA from dsRNA precursors, in addition, together with DCL1, participating in the processing of 21 nt ta-siRNAs [6–11]. Functional redundancies and competition among DCL2, DCL3, and DCL4 in small RNA biogenesis have been reported [12, 13]. Similarly, in rice, OsDCL1 and OsDCL4 also function in the biogenesis of miRNAs and siRNAs, respectively [14–16]. Once processed by Dicers, mature small RNAs are incorporated into different Argonaute (AGO) proteins to finally execute their functions. MicroRNAs are mainly bound by AGO1, and ta-siRNAs are bound by AGO6 and AGO2, whereas most of the 24 nt small RNAs are directed to AGO4 and AGO5 [5, 17–19]. During the process of sorting certain classes of small RNAs into their corresponding AGOs, the 5′ terminal nucleotide of the small RNAs plays a significant role, as it was recently reported that different AGOs have a strong bias for a distinct 5′ terminal nucleotide: U for AGO1, A for AGO2, A for AGO4, and C for AGO5 [19, 20]. Interestingly and distinct from most miRNAs associated with AGO1 that have a 5′ U, miR390 with a 5′ A was found to specifically bind to AGO7 and then function at two target sites in the TAS3a transcript . The AGO proteins, like other key elements of the small RNA biogenesis pathway, are conserved across animals, plants, and fungi. Within some of the kingdoms, conservation also extends to include high degrees of similarity among a number of individual miRNAs; there have been some elegant studies recently examining conservation and evolution among plant miRNAs [21–23]. Lessons from Arabidopsis: conserved miRNAs MicroRNAs have been identified in animals, plants, and viruses. The first miRNA, lin-4, was identified in Caenorhabditis elegans [24, 25], and many more have since been identified in other organisms, as almost all examined multicellular eukaryotes have been found to utilize miRNAs . At present, 6,396 miRNA sequences and annotations have been deposited in the miRBase Sequence Database (release 11.0) [26–29]. Of those, 1,160 are plant miRNAs, of which 184 are from A. thaliana, 269 from rice (O. sativa), 72 from sorghum (Sorghum bicolor), 30 from legume (Medicago truncatula), 234 from cottonwood (Populus trichocarpa), 32 from wheat (Triticum aestivum), 140 from common grape vine (Vitis vinifera), and 96 from maize (Zea mays). The wide variation in numbers is probably due to a lack of intensive study in many of the genomes, as most published studies have focused on Arabidopsis, with rice close but in second place. MicroRNAs are typically identified using experimental approaches, like cloning and sequencing of small RNA libraries, or through computational predictions that are subsequently experimentally validated or even by forward genetics approaches [30–33]. High-throughput sequencing such as massively parallel signature sequencing (MPSS), 454 pyrosequencing, and sequencing-by-synthesis (SBS) of small RNA libraries has substantially increased the rate of identification of miRNAs [34–36]. Deep sequencing across plant lineages has identified evolutionarily conserved miRNA families in gymnosperms, mosses, monocots, and dicots [37, 38]. Notably, miRNA families miR156/157, miR159/319, miR160, miR165/166, miR390, and miR408 are also found in primitive land plants [31, 37–42]. Between Arabidopsis and rice, there are ~20 miRNA families that are evolutionarily conserved (Table 1). A family implies evolutionary relatedness or sequence conservation between the mature miRNAs, and miRNA sequences are typically grouped as a family when the mature miRNAs are identical or there are very few mismatches, i.e., three or fewer nt substitutions and at least one conserved target transcript . For historical reasons, some miRNA families have been annotated with more than one number, i.e., miR156/157, miR159/319, miR165/166, and miR170/171. Sequence conservation has been observed in both the primary and mature miRNAs of plants but is most frequent in the mature sequences and their complementary miRNA* sequences; it is believed that there are generally few selective constraints on the precursor sequences that flank the miRNA-generating stem-loop structure. Some miRNAs are encoded by multiple loci within a genome and demonstrate high levels of sequence conservation in the mature miRNA and miRNA* sequences but are completely unrelated in other parts of the miRNA precursor. The level of conservation of the miRNA precursor varies considerably as does the copy number among miRNAs; the latter point is easily visible in a comparison of Arabidopsis and rice miRNA families (Table 1) . This copy number variation could reflect different expression patterns of each miRNA locus . The evolutionary conservation of miRNAs across plant lineages extends to include the target genes, as sequence changes at the target sites are constrained by the requirement of maintaining close homology to the miRNA. In different plant families, Zhang et al. observed the complementary site of the target to be highly conserved but other regions of the target to have lower nt conservation. The sequence conservation of the miRNAs and their target regions is indicative of the roles of miRNAs in important and conserved physiological processes; this includes a number of important developmental pathways. The difference in the number and size of the miRNA members and families, respectively, is probably shaped by the roles of specific miRNAs, and this could vary somewhat from species to species. It will be interesting to compare across species the expression level differences of miRNA families/members and their targeting efficiencies. In both Arabidopsis and rice, the conserved miRNAs are usually the most abundantly expressed miRNAs. High-throughput sequencing of rice small RNAs by Sunkar et al. indicated that the relative abundances are high for the conserved miRNAs, with the top ten most-abundant sequence reads coming from conserved miRNAs. For example, miR169 was the most abundantly expressed miRNA family, a family that contains nine members that correspond to 17 rice loci. MiR169 was represented 4,948 times in the small RNA library. Another highly expressed miRNA was miR156. There are three members of the miR156 family that correspond to 12 rice loci and miR156 was represented 1,094 times in the small RNA library. Notably, there were a few conserved miRNA families that were not observed at high frequencies. MicroRNAs with low expression levels included miR394, miR399, and miR408. MicroRNAs miR394 and miR408 are single member families found at a single locus, whereas miR399 has three members clustered in a single locus but, like miR394 and miR408, were sequenced only once in the small RNA library. Overall, the analysis by Sunkar et al. showed that most of the conserved miRNAs are expressed but often with wide variation in the frequency of their expression. Lessons from Arabidopsis II: non-conserved miRNAs In contrast to the broad representation of conserved miRNAs, there are some plant miRNAs that are only found in a single species, at least based on the miRNAs and genomes studied to date. These “non-conserved” miRNAs are most often represented by single genes in the genomes in which they are found. Non-conserved miRNAs have had some ambiguities in their identification. This can be illustrated by the case of three small RNAs that were previously annotated as miRNAs, which turned out to be members of the unusual class of ta-siRNAs. The precursors did not have an extensively paired hairpin structure like that of a miRNA . Non-conserved miRNAs require more stringent evidence and proof that they meet the criteria of a real miRNA because they lack one of the strongest pieces of data used to distinguish miRNAs from siRNAs—conservation across species boundaries. Instead, non-conserved miRNAs must be proven using a combination of detailed analyses of their sequence, biogenesis, secondary structure, expression patterns, and silencing functions. The preponderance of non-conserved miRNAs represented as single gene families suggests a fairly recent evolution for these genes, which may be consistent with the notion that non-conserved miRNAs are evolutionary intermediates between a non-miRNA sequence and a miRNA with an important regulatory role. In some cases, the region of the precursor flanking the mature miRNA has been shown to contain extensive similarity to protein-coding genes . This similarity supports the hypothesis that some of these intermediate miRNAs come from aberrant duplication or transposition events from the expressed gene sequences, such as the inverted duplication of a coding gene. Notably, before the generation of the newly evolved miRNA loci, intermediates may pass through a stage in which heterogeneous populations of siRNA-like sequences are generated . Because DCL1 has insignificant activity on a perfectly paired dsRNA, the duplicated locus would need to accumulate mutations, presumably via genetic drift, to form an imperfect pair in the fold-back structure before the structure is suitable for processing by the DCL1-dependent miRNA biogenesis pathway. There is some evidence indicating that some non-conserved miRNAs can utilize a biogenesis pathway which is DCL4-dependent , suggesting that these intermediates have some of the hallmarks of a miRNA but have yet to completely conform to the canonical miRNA-biogenesis pathway. In rice, many annotated miRNAs have been identified by computational predictions, based on the conservation of sequences with Arabidopsis miRNAs . Despite high levels of homology between Arabidopsis and rice for many genes, there are some highly abundant and well-characterized Arabidopsis miRNAs that have no homologs in rice. These include the Arabidopsis miRNAs miR158, miR161, miR163, miR173 , and miR403 . This suggests that each plant lineage, including rice, may evolve a unique set of miRNAs. Direct cloning, traditional sequencing, and deep sequencing approaches have discovered many non-conserved miRNAs in rice, and their predicted target genes encode a broad range of proteins, including some transcription factors (Supplementary Table 1). This set of rice miRNAs and targets is more diverse than the set of conserved miRNAs that mainly target transcription factors. In addition, it is likely that some non-conserved miRNAs have yet to be detected in rice because of their low expression levels or because they are only expressed in specific cells or conditions. The use of mutants in the small RNA biogenesis pathway may yet prove to be helpful in miRNA identification in rice, as some of these mutants are enriched for miRNAs, and analyses with high-throughput sequencing can be quite informative, as demonstrated recently in Arabidopsis . This type of experiment has yet to be done in rice due to the lack of well-characterized small RNA biogenesis mutants. However, deep sequencing in rice has already revealed numerous abundant and consistently expressed non-conserved small RNAs . This method of exploring small RNA profiles in rice has also lead to the identification of natural antisense miRNAs in rice . Lessons from Arabidopsis III: heterochromatic siRNAs Another type of small RNA molecule with important implications for post-transcriptional gene silencing was discovered in 1999. David Baulcombe’s group demonstrated that, in plants, a type of small RNA molecule triggered by transgenes and viruses is a specificity determinant during the process of post-transcriptional gene silencing . Early estimates suggested that these RNA molecules were a uniform length of 25 nt. This breakthrough discovery provided the conceptual groundwork for the elucidation of RNA interference biochemical pathways. In addition to siRNA-mediated suppression of genes through targeted mRNA degradation, there is another silencing process in some plant systems . This process involves RNA-directed DNA methylation and systemic silencing of specific genomic locations. There are two classes of siRNAs in plants controlling different silencing processes . These two classes of siRNAs were shown to be heterogeneous in both size and function and were referred to as short and long siRNAs. Short siRNAs (like miRNAs) are 21 to 22 nt in length, and they guide the RNA-induced silencing complex (RISC) ribonuclease to target mRNA degradation. Long siRNAs are 24 to 25 nt in length, and they were found to be the signal of systemic RNA silencing, which has been associated with sequence-specific DNA methylation. Due to the chromatin-based events that result in transcriptional silencing, this type of siRNA is often referred to as a “heterochromatic siRNA”. Tang et al. also found that, in wheat germ extracts, exogenous dsRNA can be converted into two distinct length classes of RNAs, which are similar in size. In view of these two classes of RNAs having different preference for the 5′ end nucleotide, they predicted that these RNAs are made by distinct enzymes. Notably, they identified two siRNA-generating DCL activities in wheat germ extracts . A broad and comprehensive analysis of siRNA populations has been carried out in Arabidopsis by a number of laboratories. The first sequencing of small RNAs from inflorescence tissues of Col-0 Arabidopsis indicated that most of the clones corresponded to siRNA-like sequences . These small RNAs ranged in size between 20 and 26 nt, with 24 nt as the most common size. In addition, these data indicated that siRNAs arise more frequently from highly repeated genome sequences such as transposons and retroelements, as well as loci encoding 5S rRNA [8, 52, 53]. Further analysis revealed that DCL3 is the primary enzyme responsible for generating the extensive set of 24 nt siRNAs that match throughout the genome, and DCL3 is particularly specialized in the processing of dsRNA molecules produced by the RNA-dependent RNA polymerase protein known as “RDR2” . Although RDR2 may be unnecessary as a polymerase subunit at some loci like inverted repeats, it still contributes to the formation or stability of a complex that contains active DCL3 . Additional evidence has suggested that, in Arabidopsis, the generation of endogenous heterochromatic siRNAs occurs via an RDR2-DCL3-dependent mechanism [46, 53]. The biological role of the heterochromatic siRNA is performed when one of its strands is loaded into an effector complex. Specifically, AGO4 is required for functionality of heterochromatic siRNAs at a heterochromatic site . It has been proposed that there is a link between small RNA biogenesis and effector programming such that specific siRNAs are loaded into the Argonaute through Dicer–Argonaute interactions. In addition, two non-redundant forms of a nuclear RNA polymerase IV (specific to plants), namely Pol IVa and Pol IVb, are also required at some loci. This has lead to the development of a model for the heterochromatic siRNA pathway in Arabidopsis: Subunits of Pol IVa co-localize with endogenous repeat loci, which are silenced by methylation. It has been proposed that cytosine methylation by a de novo cytosine methyltransferase induces the production of aberrant RNAs, which Pol IVa then uses as templates. Pol IVa transcripts then move to the nucleolar Cajal bodies, where RDR2, DCL3, and AGO4 are located, to form the heterochromatic siRNAs. In the siRNA processing center, the largest subunit of Pol IVb joins the AGO4-containing RISC complex and guides DNA methylation and heterochromatic histone (H3K9) modifications at the endogenous repeats [55–61]. A recent study has uncovered that, in several loci of Arabidopsis, Pol IVb’s role as the effector of RNA silencing is independent of its function in siRNA biogenesis, and the study proposed that some epigenetic marks of chromatin adjacent to the Pol IVb-targeted region could influence the ability of Pol IVb-guided DNA methylation . Although there is evidence showing that heterochromatic siRNAs can trigger epigenetic effects at the target loci, a recent study revealed that some endogenous rice genes, including OsRac, are rarely transcriptionally silenced by promoter-targeted siRNAs, but these genes could be post-transcriptionally suppressed by RNA interference (RNAi) . This discovery led to the proposal that there might be a mechanism that monitors chromatin modifications and may inhibit siRNA-mediated chromatin inactivation . By applying direct cloning methods, in one recent study, a large set of putative endogenous siRNAs were identified from rice root, shoot, and inflorescence small RNA cDNA libraries . The result from this study is consistent with data from Arabidopsis, in that most of the rice siRNAs were from intergenic regions, and they can be sorted into similar sizes and functions for two distinct classes. Both experimental validation and computational predictions indicate that many of these siRNA targets are transposable elements, consistent with the well-described role of plant endogenous siRNAs in genome defense against transposons and viruses . In other studies, high-throughput sequencing has discovered that siRNAs are widely distributed across the rice chromosomes, inconsistent with Arabidopsis in which small RNAs are concentrated in the pericentromeric regions . The difference in small RNA distributions is primarily due to the wider distribution of transposons and related repeats in rice, a phenomenon likely to be reflected in more complex plant genomes as well. Sequence-based analyses of rice small RNAs Initially, many miRNAs in rice were sequenced through the traditional Sanger sequencing method, most of which turned out to be the high-abundance miRNAs [16, 33]. However, developments in high-throughput sequencing have enabled more extensive exploration of small RNAs. In 2005, our lab, together with that of Pam Green’s lab, published the first ultrahigh-throughput sequencing-based analysis of small RNAs, resulting in the characterization of more than 1.5 million Arabidopsis small RNAs . This was done using MPSS, and the work greatly expanded our understanding of small RNAs. Subsequently, other next-generation sequencing (NGS) platforms, like 454’s Genome Sequencer, Illumina’s Genome Analyzer (Solexa, also known as SBS for “sequencing by synthesis”) and Applied Biosystems’ (ABI) SOLiD machine have been making sequencing both faster and cheaper (see for a comparison of these techniques). The read length of these NGS platforms is shorter than the original Sanger method (~250 bp for 454 and 35 to 50 bp for Solexa and SOLiD) but ideal for small RNA sequencing: 454 can produce >400,000 reads in one run; Solexa and SOLiD are capable of generating even tens of millions of sequences in parallel . The sequencing of three million reads from three rice libraries by MPSS provided the first overview of the complexity of rice small RNAs. Most of these molecules, as predicted, are low-abundant siRNAs matched to various classes of repeats or genomic regions (Fig. 1) . SBS sequencing of small RNAs from a wild rice relative, Oryza barthii (Fig. 2, an unpublished experiment recently undertaken in our lab) and 454 sequencing of cultivated rice small RNAs (from O. sativa ) have both demonstrated the two major sizes of sRNAs, 21 and 24 nt, consistent with prior reports from Arabidopsis and other species. In general, high-throughput analyses have enabled the exploration of rice small RNA populations, and many new miRNAs have been discovered recently in rice [34, 36, 47, 67]. This includes a special class of natural antisense transcript miRNAs (nat-miRNAs), which are derived from natural cis-antisense transcripts with exons primarily located antisense to the introns of their target genes; these nat-miRNAs are DCL1-dependent . Over the next few years, it is likely that there will be an explosion in the breadth of small RNA analyses in rice, leading to more extensive characterization of miRNAs, siRNAs, and other classes of small RNAs (Figs. 3 and 4). Rice mutants in small RNA biogenesis pathways Components of the small RNA biogenesis pathway have been characterized functionally in plants (Figs. 3 and 4). While most of this work has been done in Arabidopsis, there is considerable similarity between the key players in Arabidopsis and rice. As mentioned above, in Arabidopsis, there are four DCL proteins, and rice encodes six putative DCL proteins, with duplications in the DCL2 and DCL3 clades (Supplementary Fig. 1a). Redundant, compensatory, and antagonistic roles among members of this multigene family have been described in Arabidopsis. The Arabidopsis loss-of-function mutants dcl1 and dcl4 show pleiotropic developmental defects, which suggests a role for DCLs in plant development. Indeed, the complete knockout of the dcl1 mutant is embryo-lethal, with partial loss-of-function dcl1 mutants demonstrating less severe developmental defects . Information about rice DCLs is limited in comparison to Arabidopsis. However, studies by Liu et al. [15, 16] utilized knock-down and loss-of-function dcl1 and dcl4 RNAi mutants to demonstrate a role for OsDCL1 and OsDCL4 in small RNA biogenesis and plant development. The loss of function of OsDCL1 led to shoot and root abnormalities, such as rolled leaves and reduced root elongation. The plants were also developmentally arrested at the seedling stage. Similarly, loss-of-function of OsDCL4 leads to vegetative growth abnormalities and developmental defects in spikelet organ identity, which results in sterility. This is in contrast to the accelerated vegetative phase change observed in the Arabidopsis DCL mutants [7, 11], which implies that OsDCL4 has a broader role in development than the Arabidopsis DCL4. As previously mentioned, in Arabidopsis, DCL1 is responsible for miRNA accumulation, and DCL1 and DCL4 are necessary for the biogenesis of ta-siRNAs [9, 10]. Similarly, in rice, DCL1 was observed to be essential for miRNA accumulation, but a more prominent role was observed for OsDCL4. Through biochemical and genetic studies, OsDCL4 was observed to be the primary Dicer responsible for the 21 nt siRNAs associated with inverted repeat transgenes and ta-siRNAs that arose from the endogenous TAS3 gene. Clearly, we have much to learn about the nuances of Dicer function, particularly via comparative studies in species other than Arabidopsis (like rice). Much less is known about rice RDR functions (Supplementary Fig. 1b) and Pol IV activities (Supplementary Fig. 1c), although the phylogenetic analysis suggests the possibility of genetic redundancy in rice for each of the three major subunits of Pol IV (Table 2). Another important component of the small RNA machinery is represented by the set of Argonaute proteins. There are ten conserved members in Arabidopsis and at least 18 members in rice [69, 70]. Phylogenetic analysis of the Argonaute family demonstrates that most of the diversification in rice compared to Arabidopsis took place in the AGO1 and AGO5 clades (Fig. 5). In Arabidopsis, AGO1 facilitates cleavage of mRNAs targeted by miRNAs [71, 72], so it is curious that rice has had a diversification of AGO1 paralogs. The AGO1-associated RNA machinery also functions in determining meristem identity and flower organ identity . It is through posttranscriptional gene silencing that AGO1 mediates vegetative leaf and pollen development [73–75]. Other roles observed for AGO proteins include AGO4-directed DNA methylation and silencing of transposons and the ZIP/AGO7-mediated regulation of developmental timing and proposed ta-siRNA pathway constituent [59, 77, 78]. One AGO protein has been implicated in both rice development and the RNA production pathway. OsAGO7, which is believed to be orthologous to the Arabidopsis ZIP/AGO7 gene (Fig. 5), facilitates upward curling of leaves when over-expressed in rice . In a study performed by Nagasaki et al. , the rice genes known as SHOOTLESS2 (SHL2), SHL4/SHOOT ORGANIZATION2 (SHO2), and SHO1, encoding orthologs of the small RNA-associated Arabidopsis proteins RNA-dependent RNA polymerase 6 (RDR6), AGO7, and DCL4, respectively, were shown to play a role in leaf development through the ta-siRNA pathway. Nagasaki et al. were able to show that ectopic expression of SHL4 and mutations in SHL2, SHO2, and SHO1 caused reduced accumulation of miR166 (which regulates the expression of the rice HD-ZIPIII genes OSHB1 and OSHB2), partial adaxialization of leaves, and defects in shoot apical meristem (SAM) formation. Negative regulation of miR166 expression through the SHL/SHO pathway, which contains orthologs of Arabidopsis proteins implicated in ta-siRNA generation [6, 7, 10, 11], suggest that there is a link between RNA-mediated gene regulation and fundamental plant processes such as embryonic SAM formation. The functional role for small RNAs is greatly expanding. As more studies across species are performed, the conservation and evolution of small RNAs will continue to reveal the dependency of plant regulatory pathways on small RNAs and their associated components. Conclusions and future directions At this point, many of the major players in small RNA biogenesis have been identified from intensive work in Arabidopsis. The translation of these discoveries to rice and other species, combined with both forward and reverse genetics approaches used directly in those species, is facilitating the elucidation of plant small RNA pathways and activities. With new deep sequencing methods and the prospect of combining these analysis methods with rice mutants in small RNA biogenesis genes, we should soon have a near complete list of rice miRNAs and their targets. This will include characterization of the non-conserved and rice-, grass-, or monocot-specific miRNAs. Identifying miRNAs in rice and more diverse plant species will be important to understand the evolution of miRNAs and the regulation of gene expression by miRNAs. The analysis of rice mutants in genes important for small RNA activities promises to be a particularly exciting area of research. For example, why does rice have nearly twice as many AGO-encoding genes as Arabidopsis, and what are the functions of and levels of redundancy among these proteins? Given the number of mutant populations that are now available for rice, these experiments are now quite feasible. As more components of the plant small RNA machinery are identified by more intricate genetic screens and biochemical methods, the relationship and divergence between plant species and lineages will increasingly be an area of interest. References - 1. Chapman EJ, Carrington JC. Specialization and evolution of endogenous small RNA pathways. Nat Rev Genet 2007;8:884–96. - 2. Zaratiegui M, Irvine DV, Martienssen RA. Noncoding RNAs and gene silencing. Cell 2007;128:763–76. - 3. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004;116:281–97. - 4. Jones-Rhoades MW, Bartel DP, Bartel B. MicroRNAS and their regulatory roles in plants. Annu Rev Plant Biol 2006;57:19–53. - 5. Vaucheret H. Post-transcriptional small RNA pathways in plants: mechanisms and regulations. Genes Dev 2006;20:759–71. - 6. Allen E, Xie Z, Gustafson AM, Carrington JC. MicroRNA-directed phasing during trans-acting siRNA biogenesis in plants. Cell 2005;121:207–21. - 7. Xie Z, Allen E, Wilken A, Carrington JC. DICER-LIKE 4 functions in trans-acting small interfering RNA biogenesis and vegetative phase change in Arabidopsis thaliana. Proc Natl Acad Sci U S A 2005;102:12984–9. - 8. Xie Z, Johansen LK, Gustafson AM, Kasschau KD, Lellis AD, Zilberman D, et al. Genetic and functional diversification of small RNA pathways in plants. PLoS Biol 2004;2:E104. - 9. Vazquez F, Vaucheret H, Rajagopalan R, Lepers C, Gasciolli V, Mallory AC, et al. Endogenous trans-acting siRNAs regulate the accumulation of Arabidopsis mRNAs. Mol Cell 2004;16:69–79. - 10. Yoshikawa M, Peragine A, Park MY, Poethig RS. A pathway for the biogenesis of trans-acting siRNAs in Arabidopsis. Genes Dev 2005;19:2164–75. - 11. Gasciolli V, Mallory AC, Bartel DP, Vaucheret H. Partially redundant functions of Arabidopsis DICER-like enzymes and a role for DCL4 in producing trans-acting siRNAs. Curr Biol 2005;15:1494–500. - 12. Henderson IR, Zhang X, Lu C, Johnson L, Meyers BC, Green PJ, et al. Dissecting Arabidopsis thaliana DICER function in small RNA processing, gene silencing and DNA methylation patterning. Nat Genet 2006;38:721–5. - 13. Bouche N, Lauressergues D, Gasciolli V, Vaucheret H. An antagonistic function for Arabidopsis DCL2 in development and a new function for DCL4 in generating viral siRNAs. EMBO J 2006;25:3347–56. - 14. Nagasaki H, Itoh J, Hayashi K, Hibara K, Satoh-Nagasawa N, Nosaka M, et al. The small interfering RNA production pathway is required for shoot meristem initiation in rice. Proc Natl Acad Sci U S A 2007;104:14867–71. - 15. Liu B, Chen Z, Song X, Liu C, Cui X, Zhao X, et al. Oryza sativa dicer-like4 reveals a key role for small interfering RNA silencing in plant development. Plant Cell 2007;19:2705–18. - 16. Liu B, Li P, Li X, Liu C, Cao S, Chu C, et al. Loss of function of OsDCL1 affects microRNA accumulation and causes developmental defects in rice. Plant Physiol 2005;139:296–305. - 17. Qi Y, He X, Wang XJ, Kohany O, Jurka J, Hannon GJ. Distinct catalytic and non-catalytic roles of ARGONAUTE4 in RNA-directed DNA methylation. Nature 2006;443:1008–12. - 18. Kim VN. Sorting out small RNAs. Cell 2008;133:25–6. - 19. Mi S, Cai T, Hu Y, Chen Y, Hodges E, Ni F, et al. Sorting of small RNAs into Arabidopsis argonaute complexes is directed by the 5' terminal nucleotide. Cell 2008;133:116–27. - 20. Montgomery TA, Howell MD, Cuperus JT, Li D, Hansen JE, Alexander AL, et al. Specificity of ARGONAUTE7-miR390 interaction and dual functionality in TAS3 trans-acting siRNA formation. Cell 2008;133:128–41. - 21. Allen E, Xie Z, Gustafson AM, Sung GH, Spatafora JW, Carrington JC. Evolution of microRNA genes by inverted duplication of target gene sequences in Arabidopsis thaliana. Nat Genet 2004;36:1282–90. - 22. Fahlgren N, Howell MD, Kasschau KD, Chapman EJ, Sullivan CM, Cumbie JS, et al. High-throughput sequencing of Arabidopsis microRNAs: evidence for frequent birth and death of MIRNA genes. PLoS ONE 2007;2:e219. - 23. Rajagopalan R, Vaucheret H, Trejo J, Bartel DP. A diverse and evolutionarily fluid set of microRNAs in Arabidopsis thaliana. Genes Dev 2006;20:3407–25. - 24. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993;75:843–54. - 25. Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 1993;75:855–62. - 26. Griffiths-Jones S. The microRNA registry. Nucleic Acids Res 2004;32:D109–11. - 27. Griffiths-Jones S. miRBase: the microRNA sequence database. Methods Mol Biol 2006;342:129–38. - 28. Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 2006;34:D140–4. - 29. Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ. miRBase: tools for microRNA genomics. Nucleic Acids Res 2008;36:D154–8. - 30. Lai EC, Tomancak P, Williams RW, Rubin GM. Computational identification of Drosophila microRNA genes. Genome Biol 2003;4:R42. - 31. Jones-Rhoades MW, Bartel DP. Computational identification of plant microRNAs and their targets, including a stress-induced miRNA. Mol Cell 2004;14:787–99. - 32. Zhang BH, Pan XP, Wang QL, Cobb GP, Anderson TA. Identification and characterization of new plant microRNAs using EST analysis. Cell Res 2005;15:336–60. - 33. Sunkar R, Girke T, Jain PK, Zhu JK. Cloning and characterization of microRNAs from rice. Plant Cell 2005;17:1397–411. - 34. Sunkar R, Zhou X, Zheng Y, Zhang W, Zhu JK. Identification of novel and candidate miRNAs in rice by high throughput sequencing. BMC Plant Biol 2008;8:25. - 35. Yao Y, Guo G, Ni Z, Sunkar R, Du J, Zhu JK, et al. Cloning and characterization of microRNAs from wheat (Triticum aestivum L.). Genome Biol 2007;8:R96. - 36. Nobuta K, Venu RC, Lu C, Belo A, Vemaraju K, Kulkarni K, et al. An expression atlas of rice mRNAs and small RNAs. Nat Biotechnol 2007;25:473–7. - 37. Wang JF, Zhou H, Chen YQ, Luo QJ, Qu LH. Identification of 20 microRNAs from Oryza sativa. Nucleic Acids Res 2004;32:1688–95. - 38. Adai A, Johnson C, Mlotshwa S, Archer-Evans S, Manocha V, Vance V, et al. Computational prediction of miRNAs in Arabidopsis thaliana. Genome Res 2005;15:78–91. - 39. Park W, Li J, Song R, Messing J, Chen X. CARPEL FACTORY, a Dicer homolog, and HEN1, a novel protein, act in microRNA metabolism in Arabidopsis thaliana. Curr Biol 2002;12:1484–95. - 40. Bonnet E, Wuyts J, Rouze P, Van de Peer Y. Detection of 91 potential conserved plant microRNAs in Arabidopsis thaliana and Oryza sativa identifies important target genes. Proc Natl Acad Sci U S A 2004;101:11511–6. - 41. Reinhart BJ, Weinstein EG, Rhoades MW, Bartel B, Bartel DP. MicroRNAs in plants. Genes Dev 2002;16:1616–26. - 42. Sunkar R, Zhu JK. Novel and stress-regulated microRNAs and other small RNAs from Arabidopsis. Plant Cell 2004;16:2001–19. - 43. Zhang B, Pan X, Cannon CH, Cobb GP, Anderson TA. Conservation and divergence of plant microRNA genes. Plant J 2006;46:243–59. - 44. Sieber P, Wellmer F, Gheyselinck J, Riechmann JL, Meyerowitz EM. Redundancy and specialization among plant microRNAs: role of the MIR164 family in developmental robustness. Development 2007;134:1051–60. - 45. Wang Y, Hindemitt T, Mayer KF. Significant sequence similarities in promoters and precursors of Arabidopsis thaliana non-conserved microRNAs. Bioinformatics 2006;22:2585–9. - 46. Lu C, Kulkarni K, Souret FF, MuthuValliappan R, Tej SS, Poethig RS, et al. MicroRNAs and other small RNAs enriched in the Arabidopsis RNA-dependent RNA polymerase-2 mutant. Genome Res 2006;16:1276–88. - 47. Lu C, Jeong DH, Kulkarni K, Pillay M, Nobuta K, German R, et al. Genome-wide analysis for discovery of rice microRNAs reveals natural antisense microRNAs (nat-miRNAs). Proc Natl Acad Sci U S A 2008;105:4951–6. - 48. Hamilton AJ, Baulcombe DC. A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 1999;286:950–2. - 49. Hamilton A, Voinnet O, Chappell L, Baulcombe D. Two classes of short interfering RNA in RNA silencing. EMBO J 2002;21:4671–9. - 50. Tang G, Reinhart BJ, Bartel DP, Zamore PD. A biochemical framework for RNA silencing in plants. Genes Dev 2003;17:49–63. - 51. Llave C, Kasschau KD, Rector MA, Carrington JC. Endogenous and silencing-associated small RNAs in plants. Plant Cell 2002;14:1605–19. - 52. Lippman Z, Martienssen R. The role of RNA interference in heterochromatic silencing. Nature 2004;431:364–70. - 53. Kasschau KD, Fahlgren N, Chapman EJ, Sullivan CM, Cumbie JS, Givan SA, et al. Genome-wide profiling and analysis of Arabidopsis siRNAs. PLoS Biol 2007;5:e57. - 54. Li CF, Pontes O, El-Shami M, Henderson IR, Bernatavichute YV, Chan SW, et al. An ARGONAUTE4-containing nuclear processing center colocalized with Cajal bodies in Arabidopsis thaliana. Cell 2006;126:93–106. - 55. Herr AJ, Jensen MB, Dalmay T, Baulcombe DC. RNA polymerase IV directs silencing of endogenous DNA. Science 2005;308:118–20. - 56. Huettel B, Kanno T, Daxinger L, Aufsatz W, Matzke AJ, Matzke M. Endogenous targets of RNA-directed DNA methylation and Pol IV in Arabidopsis. EMBO J 2006;25:2828–36. - 57. Kanno T, Huettel B, Mette MF, Aufsatz W, Jaligot E, Daxinger L, et al. Atypical RNA polymerase subunits required for RNA-directed DNA methylation. Nat Genet 2005;37:761–5. - 58. Onodera Y, Haag JR, Ream T, Nunes PC, Pontes O, Pikaard CS. Plant nuclear RNA polymerase IV mediates siRNA and DNA methylation-dependent heterochromatin formation. Cell 2005;120:613–22. - 59. Peragine A, Yoshikawa M, Wu G, Albrecht HL, Poethig RS. SGS3 and SGS2/SDE1/RDR6 are required for juvenile development and the production of trans-acting siRNAs in Arabidopsis. Genes Dev 2004;18:2368–79. - 60. Pontes O, Li CF, Nunes PC, Haag J, Ream T, Vitins A, et al. The Arabidopsis chromatin-modifying nuclear siRNA pathway involves a nucleolar RNA processing center. Cell 2006;126:79–92. - 61. Zhang X, Henderson IR, Lu C, Green PJ, Jacobsen SE. Role of RNA polymerase IV in plant small RNA metabolism. Proc Natl Acad Sci U S A 2007;104:4536–41. - 62. Mosher RA, Schwach F, Studholme D, Baulcombe DC. PolIVb influences RNA-directed DNA methylation independently of its role in siRNA biogenesis. Proc Natl Acad Sci U S A 2008;105:3145–50. - 63. Okano Y, Miki D, Shimamoto K. Small interfering RNA (siRNA) targeting of endogenous promoters induces DNA methylation, but not necessarily gene silencing, in rice. Plant J 2008;53:65–77. - 64. Sunkar R, Girke T, Zhu JK. Identification and characterization of endogenous small interfering RNAs from rice. Nucleic Acids Res 2005;33:4443–54. - 65. Lu C, Tej SS, Luo S, Haudenschild CD, Meyers BC, Green PJ. Elucidation of the small RNA component of the transcriptome. Science 2005;309:1567–9. - 66. von Bubnoff A. Next-generation sequencing: the race is on. Cell 2008;132:721–3. - 67. Morin RD, Aksay G, Dolgosheina E, Ebhardt HA, Magrini V, Mardis ER, et al. Comparative analysis of the small RNA transcriptomes of Pinus contorta and Oryza sativa. Genome Res 2008;18:571–84. - 68. Schauer SE, Jacobsen SE, Meinke DW, Ray A. DICER-LIKE1: blind men and elephants in Arabidopsis development. Trends Plant Sci 2002;7:487–91. - 69. Shi ZWJ, Wan X, Shen G, Wang X, Zhang J. Over-expression of rice OsAGO7 gene induces upward curling of the leaf blade that enhanced erect-leaf habit. Planta 2007;226:99–108. - 70. Carmell MA, Xuan Z, Zhang MQ, Hannon GJ. The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis. Genes Dev 2002;16:2733–42. - 71. Vaucheret H, Vazquez F, Crete P, Bartel DP. The action of ARGONAUTE1 in the miRNA pathway and its regulation by the miRNA pathway are crucial for plant development. Genes Dev 2004;18:1187–97. - 72. Baumberger N, Baulcombe DC. Arabidopsis ARGONAUTE1 is an RNA Slicer that selectively recruits microRNAs and short interfering RNAs. Proc Natl Acad Sci U S A 2005;102:11928–33. - 73. Kidner CA, Martienssen RA. The role of ARGONAUTE1 (AGO1) in meristem formation and identity. Dev Biol 2005;280:504–17. - 74. Goodrich J, Puangsomlee P, Martin M, Long D, Meyerowitz EM, Coupland G. A Polycomb-group gene regulates homeotic gene expression in Arabidopsis. Nature 1997;386:44–51. - 75. Katz A, Oliva M, Mosquna A, Hakim O, Ohad N. FIE and CURLY LEAF polycomb proteins interact in the regulation of homeobox gene expression during sporophyte development. Plant J 2004;37:707–19. - 76. Zilberman D, Cao X, Jacobsen SE. ARGONAUTE4 control of locus-specific siRNA accumulation and DNA and histone methylation. Science 2003;299:716–9. - 77. Garcia D, Collier SA, Byrne ME, Martienssen RA. Specification of leaf polarity in Arabidopsis via the trans-acting siRNA pathway. Curr Biol 2006;16:933–8. - 78. Hunter C, Sun H, Poethig RS. The Arabidopsis heterochronic gene ZIPPY is an ARGONAUTE family member. Curr Biol 2003;13:1734–9. - 79. Yang L, Liu Z, Lu F, Dong A, Huang H. SERRATE is a novel nuclear regulator in primary microRNA processing in Arabidopsis. Plant J 2006;47:841–50. - 80. Chen X. MicroRNA biogenesis and function in plants. FEBS Lett 2005;579:5923–31. - 81. Bollman KM, Aukerman MJ, Park MY, Hunter C, Berardini TZ, Poethig RS. HASTY, the Arabidopsis ortholog of exportin 5/MSN5, regulates phase change and morphogenesis. Development 2003;130:1493–504. - 82. Han MH, Goud S, Song L, Fedoroff N. The Arabidopsis double-stranded RNA-binding protein HYL1 plays a role in microRNA-mediated gene regulation. Proc Natl Acad Sci U S A 2004;101:1093–8. - 83. Houseley J, LaCava J, Tollervey D. RNA-quality control by the exosome. Nat Rev Mol Cell Biol 2006;7:529–39. - 84. Souret FF, Kastenmayer JP, Green PJ. AtXRN4 degrades mRNA in Arabidopsis and its substrates include selected miRNA targets. Mol Cell 2004;15:173–83. - 85. Adenot X, Elmayan T, Lauressergues D, Boutet S, Bouche N, Gasciolli V, et al. DRB4-dependent TAS3 trans-acting siRNAs control leaf morphology through AGO7. Curr Biol 2006;16:927–32. - 86. Vaucheret H. MicroRNA-dependent trans-acting siRNA production. Sci STKE 2005;2005:pe43. - 87. Howell MD, Fahlgren N, Chapman EJ, Cumbie JS, Sullivan CM, Givan SA, et al. Genome-wide analysis of the RNA-DEPENDENT RNA POLYMERASE6/DICER-LIKE4 pathway in Arabidopsis reveals dependency on miRNA- and tasiRNA-directed targeting. Plant Cell 2007;19:926–42. - 88. Chen HM, Li YH, Wu SH. Bioinformatic prediction and experimental validation of a microRNA-directed tandem trans-acting siRNA cascade in Arabidopsis. Proc Natl Acad Sci U S A 2007;104:3318–23. - 89. Wassenegger M, Krczal G. Nomenclature and functions of RNA-directed RNA polymerases. Trends Plant Sci 2006;11:142–51. - 90. Margis R, Fusaro AF, Smith NA, Curtin SJ, Watson JM, Finnegan EJ, Waterhouse PM. The evolution and diversification of Dicers in plants. FEBS Lett. 2006;580:2442–50 - 91. Hirochika H, Guiderdoni E, An G, Hsing YI, Eun MY, Han CD, et al. Rice mutant resources for gene discovery. Plant Mol Biol 2004;54:325–34. Acknowledgments We are particularly indebted to Dr. Carolyn Napoli of ChromDB for her work in generating the phylogenetic trees. We gratefully acknowledge the assistance of Dr. Kan Nobuta for assistance with handling the O. barthii data and Xiang Song and Dr. Rod Wing for providing the material for this library. This work was supported primarily by NSF Plant Genome Research Program award 0701745. Electronic supplementary material Below is the link to the electronic supplementary material. Supplementary Table 1 Non-conserved miRNAs identified in rice. (DOC 76.5 KB) Supplementary Fig. 1 Phylogenetic trees for Dicers, RNA dependent RNA polymerases, and Pol IV subunits. (DOC 225 KB) Rights and permissions Open Access This article is distributed under the terms of the Creative Commons Attribution 2.0 International License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. About this article Cite this article Simon, S.A., Zhai, J., Zeng, J. et al. The Cornucopia of Small RNAs in Plant Genomes. Rice 1, 52–62 (2008). https://doi.org/10.1007/s12284-008-9008-5 Received: Accepted: Published: Issue Date:
https://thericejournal.springeropen.com/articles/10.1007/s12284-008-9008-5
Drosophila microRNAs (miRNAs) and small interfering RNAs (siRNAs) are generally produced by different Dicer enzymes (Dcr-1 and Dcr-2) and sorted to functionally distinct Argonaute effectors (AGO1 and AGO2). However, there is cross talk between these pathways, as highlighted by the recognition that Drosophila miRNA* strands (the partner strands of mature miRNAs) are generated by Dcr-1 but are preferentially sorted to AGO2. Here, we show that a component of the siRNA loading complex, R2D2, is essential both to load endogenously encoded siRNAs (endo-siRNAs) into AGO2 and to prevent endosiRNAs from binding to AGO1. Northern blot analysis and deep sequencing showed that in the r2d2 mutant, all classes of endo-siRNAs were unable to load AGO2 and instead accumulated in the AGO1 complex. Such redirection was specific to endo-siRNAs and was not observed with miRNA* strands. We observed functional consequences of altered sorting in RNA interference (RNAi) mutants, since endosiRNAs generated from cis-natural antisense transcripts (cis-NAT-siRNA) exhibited evidence for biased maturation as single strands in AGO1 according to thermodynamic asymmetry and a hairpin-derived endo-siRNA formed cleavage-competent complexes with AGO1 upon mutation of r2d2. Finally, we demonstrated a direct role for the R2D2/Dcr-2 heterodimer in sensing central mismatch positions that direct miRNA* strands to AGO2. Together, these data reveal new roles of R2D2 in organizing small RNA networks in Drosophila.
https://utsouthwestern.pure.elsevier.com/en/publications/r2d2-organizes-small-regulatory-rna-pathways-in-drosophila
RNA interference (RNAi) has become a powerful tool for the suppression of gene expression and the identification of therapeutic targets. RNAi screens have revealed synthetic lethal cancer vulnerabilities, and progress has been made toward enabling therapeutic delivery of short interfering RNAs (siRNAs) in vivo. However, current RNAi libraries are designed to detect synthetic lethal interactions between individual genes and an oncogenic lesion. They are less effective for detecting more subtle interactions in which a synthetic lethal phenotype requires the combined inhibition of several genes in addition to the sensitizing mutation. Identifying such interactions, where multiple genes cooperate with an oncogenic lesion, may open up new avenues for therapeutic intervention, but their discovery remains difficult with current approaches. We therefore sought to develop a new RNAi system in which a single short RNA sequence can suppress multiple genes simultaneously. As the basis for our design, we mimicked the activity of endogenous microRNAs (miRNAs), and refer to our system as “artificial miRNAs.” In contrast to traditional siRNAs and short hairpin RNAs (shRNAs) that are perfectly complementary to their target, miRNAs utilize partial complementarity to direct the repression of multiple genes at the same time. By screening a library of artificial miRNAs, we expect to reveal a novel class of synthetic lethal interactions that can be exploited for cancer therapy. Moreover, in vivo delivery of artificial miRNAs may enable combined inhibition of multiple therapeutic targets that cannot currently be targeted by small molecules. We developed an algorithm to generate artificial miRNA sequences targeting a given set of genes of interest. Based on the mechanisms of endogenous miRNA targeting, our algorithm designs artificial miRNAs that feature perfect complementarity between the miRNA 5'-end “seed region” and each of the target sequences as well as partial complementarity between the miRNA 3' end and each target. To test the hypothesis that miRNAs can be rationally designed for the simultaneous knockdown of multiple genes, we designed and synthesized 234 artificial miRNAs to target two metabolic genes implicated in glioblastoma: pyruvate carboxylase (PC) and glutaminase (GLS). In addition, we generated 74 non-targeting control miRNAs. Using luciferase reporter assays, we observed that PC/GLS-targeted artificial miRNAs were significantly more effective at suppressing both genes than non-targeting controls. We then confirmed by immunoblotting that 13 artificial miRNAs knockdown endogenous PC and GLS simultaneously. Thus, we demonstrated that artificial miRNAs are effective for multi-gene RNAi. We also found that artificial miRNA activity was predicted by the miRNA:target binding energy and the degree of complementarity at the 3' end of the miRNA. Therefore, we are refining the design algorithm to generate artificial miRNAs with enhanced activity. Taken together, our results validate the artificial miRNA system as an effective RNAi-based approach for multiple gene suppression. We are currently developing a library of ~16,000 artificial miRNAs that will permit functional screens to identify combinatorial synthetic lethal interactions. We expect that multi-target artificial miRNAs will provide an important tool for the identification of new therapeutic targets. Citation Format: Jason D. Arroyo, Emily N. Gallichotte, Muneesh Tewari. Artificial multi-target microRNAs: A new RNA interference approach to enable simultaneous suppression of multiple genes. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Synthetic Lethal Approaches to Cancer Vulnerabilities; May 17-20, 2013; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(5 Suppl):Abstract nr A34. - ©2013 American Association for Cancer Research.
http://mct.aacrjournals.org/content/12/5_Supplement/A34
Although RNA interference (RNAi) is known to play an important part in defense against viruses of invertebrates, its contribution to mammalian anti-viral defense has been a matter of dispute. This is surprising because all components of the RNAi machinery necessary for robust RNAi-mediated restriction of viruses are conserved in mammals, and the introduction of synthetic small interfering RNAs (siRNAs) into cells efficiently silences the replication of viruses that contain siRNA complementary sequences in those cells. Here, I discuss the reasons for the dispute, and review the evidence that RNAi is a part of the physiological defense of mammalian cells against viral infections. RNA interference (RNAi) is a process in which small non-coding RNAs (of endogenous or exogenous origin) are incorporated into a multi-protein RNA-induced silencing complex (RISC) in cells to silence the expression of a sequence-homologous target RNA . Three major types of small non-coding RNAs function as RNAi: the piRNAs (PIWI-interacting RNAs), miRNAs (microRNAs), and siRNAs (small interfering RNAs). piRNAs and miRNAs are endogenous, small non-coding RNAs transcribed from cellular loci and then processed to generate fragments that engage with the downstream silencing machinery. Until recently, siRNAs were thought to be exclusively processed from the exogenous RNA of pathogens (for example, viruses) that infect the cell, but that view changed with the discovery of abundantly expressed endogenous siRNAs (endo-siRNAs) in animal cells [2, 3]. Currently, mammals are known to have hundreds of thousands of different piRNAs, produced from gene clusters of repetitive elements, and more than 1,000 different miRNAs; the number of endo-siRNAs still needs to be fully clarified. Simplified representations of the different RISC complexes are shown schematically in Figure 1. miRNA biogenesis requires the RNAse III proteins Drosha and Dicer, while siRNA processing depends solely on Dicer, and the nuclease(s) required for piRNA processing remain(s) unidentified . Short double-stranded RNAs (dsRNAs) are bound to form the miRNA- and siRNA-RISC complex while the biogenesis of the piRNA-RISC can arise from either a single-stranded precursor RNA or through a 'ping-pong' mechanism . A major constituent of the miRNA-RISC and siRNA-RISC complexes is the AGO protein; the parallel constituent in piRNA-RISC is the PIWI protein. In the RISC complex, a guide RNA strand is retained that captures target mRNA through complete or incomplete sequence complementarity. The RISC complex then may either inhibit translation of the mRNA or, through the so-called slicer activity of the AGO and PIWI proteins, degrade it, thus silencing the gene from which it was transcribed. miRNA-, siRNA-, piRNA-RISC complexes effect complementarity-driven silencing of targeted mRNAs. Small miRNAs, siRNAs, or piRNAs (red) serve as guide sequences within the RNA-induced silencing complex (RISC) to capture target mRNA via incomplete (miRNA) or complete (siRNA, piRNA) base-pairing. The expression of the targeted mRNA is silenced either by RNA degradation or by inhibition of translation. One of the earliest descriptions of RNAi was in Caenorhabditis elegans. Early on, it was found that mutations affecting RNAi function in C. elegans and Drosophila melanogaster produced apparently normal organisms, but that these mutations increased the susceptibility of mutated animals to infection by viruses [5, 6]. These findings suggested an evolutionary role for RNAi in the defense of cells against pathogenic viral infections. Indeed, this rationale is consistent with the role of RNAi in post-transcriptional gene silencing of plant viruses and with the conservation of an RNAi-like antiviral defense mechanism using small CRISPR (clusters of regularly interspaced short palindromic repeats) RNAs in prokaryotes . The need for conservation of an analogous antiviral system in vertebrates, however, has been questioned on the grounds of their advanced adaptive immunity to viral (and non-viral) pathogens and on the emergence of an interferon-based defense mechanism. Silencing mechanisms that depend on RNAi are, however, already known to operate in vertebrates to protect the germline DNA from transposons and endogenous retroviruses; and as discussed below, they appear also to operate in somatic cells. Non-virologists are often surprised to learn that nearly 50% of the human genome is made up of virus-like transposable elements (TEs) , which are composed mostly of retrotransposons replicated through reverse transcription, and DNA transposons propagated through a cut-and-paste mechanism. Included among the TEs in the mouse and human genomes are distinctly recognizable endogenous retroviruses (ERVs; integrated retrovirus sequences that have entered the germline), with 5 to 8% of human DNA estimated to consist of human endogenous retrovirus (HERV) elements that segregate into 26 phylogenetically distinct retroviral lineages . These ERVs are likely to be fossilized remnants of anciently endogenized virus infections. While active human ERVs are rare , human non-ERV TEs (for example, short interspersed elements - SINES - and long interspersed elements - LINES) remain active for transposition, accounting for 1 new insertion every 100 to 200 human births or roughly 1 in every 1,000 human genetic mutations . By contrast, mouse ERVs are numerous and highly active and cause approximately 10% of spontaneous mutations in inbred mice . Active replication of ERVs and virus-like elements needs to be suppressed in the germ line because they cause novel deleterious germline mutations. In mouse germ cells, piRNA-mediated silencing has been shown to be important for repressing TE activity . However, ERV and retrotransposon activities are not limited to the germline; they also occur in somatic cells where they can induce disease, in particular ERV- and retrotransposition-associated cancers [15, 16]. This raises the question of whether mechanisms also exist to protect somatic tissues. There is evidence for two such mechanisms. First, somatic cell endo-siRNAs, as recently described, may act to control ERV and TE activity . Second, emerging data have unexpectedly revealed that piRNAs are not confined to germline cells, but are also abundant in the somatic tissues of fruitfly, mouse, and rhesus macaques , in the neurons of Aplysia , and in a human T cell line . PIWI mRNA and MIWI protein have also been detected in macaque and mouse somatic tissues . If these new discoveries are confirmed, then ERV/TE-suppression in somatic cells may be mediated by piRNA-RISC. There is also direct evidence supporting a role for RNAi in regulating viral infections in mammalian cells. As in the early studies that showed RNAi pathway mutations in C. elegans and D. melanogaster increased these organisms' susceptibility to infection by viruses [5, 6], mutations in or perturbation of RNAi pathway components in mouse , monkey cells or human cells [22, 23] increase the replication of vesicular stomatitis virus (VSV), influenza A virus, and human immunodeficiency virus (HIV-1), respectively. The human genome encodes more than 1,000 different miRNAs; these miRNAs and their miRNA-RISC complexes recognize RNA targets through imperfect base-pairing . In silico analyses based on complementarity of miRNAs and their putative mRNA targets have led to estimates that miRNAs may regulate up to 30% of protein-coding human mRNAs. Not surprisingly, early analyses of the more than 1,000 human miRNA sequences aligned against a large dataset of pathogenic mammalian viral genomes indicated that most, if not all, viruses are recognized by one or more cellular miRNAs . Numerous studies now report the direct regulation of mammalian viruses by host miRNAs (Figure 2). Thus, human liver-specific miR-122 has been shown to functionally augment hepatitis C virus (HCV) replication , while more than half a dozen human miRNAs, including miR-199a-3p, miR-210, and miR-125a-5p, are found to repress hepatitis B virus (HBV) replication . Other examples include miR-323, miR-491, and miR-654 targeting influenza virus, miR-27 and miR-93 targeting VSV, and miR-28, miR29a, miR-125b, miR-150, miR-223, and miR-382 targeting HIV-1 . More recent data suggest that herpes viruses (for example, Epstein Barr virus (EBV) and Kaposi's sarcoma herpes virus (KSHV)) are targeted by several cellular miRNAs, including the miR-17/92 and miR-106b/25 clusters [28–30], coxsackie virus is targeted by miR-342-5p , and human papilloma virus (HPV) is targeted by several cellular miRNAs . The list of cellular miRNAs implicated in regulating mammalian viruses promises to grow much longer. Indeed, in a survey of more than 25,000 individual HCV, HIV-1, HPV and HBV sequences, it was found that there is strong conservation and preservation of cellular miRNA-targeted sites within those viruses, prompting the authors to conclude that 'human microRNAs effectively contribute to the host defense by targeting essential viral genes, thereby reducing the replication efficiency of the virus' . Taken together, the accumulated findings support the concept that ambient miRNAs expressed in host cells represent a first layer of bioactive encounters that form a part of the cell's overall antiviral arsenal. Several ways that RNAi can regulate viruses in mammalian cells. Left: cell-endogenous endo-miRNAs are engaged in RISC complexes to target partially homologous viral transcripts. Middle: virus-encoded miRNA can be processed as exo-miRNAs that are engaged with RISC for interaction with other viral RNAs. Right: viruses that contain shRNA sequences (for example, lentiviral shRNA libraries) are processed into exo-siRNAs. The double-stranded RNAs (hairpins) are processed in the RISC into single-stranded guide RNAs that bind to complementary sequences in the mRNA, thus recruiting RISC, which degrades the mRNA or inhibits its translation. Transposable elements and endogenous retroviruses produce endo-siRNAs in mammalian cells. Both exo-siRNAs and endo-siRNAs can be incorporated into RISC complexes in mammalian cells to silence homologous target RNAs. Multiple transcripts (blue) are indicative of differently spliced RNAs. Despite the above findings, there remains some contention about the physiological function of RNAi in regulating viruses in mammalian cells. This contention may be caused in part by expectations of mammalian cells/mammalian viruses based on results from invertebrate cells/invertebrate viruses. For instance, when invertebrate viruses infect mosquito cells, the incoming viral dsRNAs or replication intermediates are frequently processed into small exogenous siRNAs (exo-siRNAs) . By contrast, when mammalian viruses, such as HIV-1, infect human cells, the production of processed viral exo-siRNAs is rare [19, 35]. Some have interpreted these results to mean that invertebrate cells sense and process viral dsRNAs and then deploy exo-siRNAs in antiviral RISC complexes while vertebrate (mammalian) cells cannot perform these functions. This interpretation however is challenged by experiments in which an authentic short hairpin RNA (shRNA) was engineered into the HIV-1 genome and the genome introduced into human cells, with ensuing efficient siRNA production from the 'viral-shRNA' . Moreover, a version of the above experiment is performed hundreds, if not thousands, of times every day by investigators who use shRNA libraries cloned into lentivirus vectors to transduce human cells for the purpose of silencing specific target genes. In every instance, the lentivirus-shRNA is recognized and processed by human cells faithfully into the expected siRNA (Figure 2). How then does one reconcile the above observations? One possibility is that human (mammalian) cells, rather than being unable to efficiently recognize and process viral dsRNAs or shRNAs into siRNAs, may actually be more proficient than invertebrate cells at processing and using siRNAs in antiviral RISC complexes against invading viruses. In this case, RNA viruses with double-stranded shRNA-like sequences amenable for processing into siRNAs might be subject to more potent negative selection in human than in invertebrate cells. Over time, strong stringent selection in mammalian cells (and relaxed selection in invertebrate cells) would result in many human viruses being devoid of shRNA-like or dsRNA sequences, while the less robustly restricted invertebrate viruses would still keep shRNA and/or dsRNA sequences. Hence, today's human cells would face many viruses largely lacking shRNA/dsRNA sequences, accounting, in part, for the rarity with which viral exo-siRNAs are detected in mammalian infections (see, for example, ). On the other hand, invertebrate cells would still encounter many viruses that harbor shRNA sequences, and consequently viral exo-siRNAs would more frequently be found in infected invertebrate cells . In short, the argument is that human cells do, in fact, efficiently process viral exo-siRNA and can use siRNA-RISC as an antiviral defense, but the rarity of this process in human cells may be because many mammalian viruses have already been tightly selected by human cells not to maintain siRNA-producing sequences. They do, however, encode miRNA sequences [38, 39]. These viral miRNAs are processed efficiently in human cells, are engaged in miRNA-RISCs, and are frequently used by the cell (or the virus) to target other viral transcripts. Examples of this type of usage include the human cytomegalovirus (CMV) miR-112-1 targeting the CMV IE1 viral RNA , the EBV BART miRNAs targeting the EBV LMP mRNAs [41, 42], and the HSV miR-H2, miR-H3, and miR-H4 targeting viral ICP0 and ICP34.5 mRNAs . Similar miRNA-mRNA targeting can also occur in the case of a model retroviral infection . Taken together, these findings support the view that mammalian cells employ viral exo-miRNA-RISCs to regulate viral infections, paralleling invertebrate and plant cells that use viral exo-siRNA-RISCs to regulate their cognate viruses (Figure 2). The above arguments apply to retroviruses and herpes viruses, which have been extensively studied for RNAi generation. What remains unaddressed is the processing of the many plus-sense, minus-sense, and human dsRNA viruses. These viruses present fully dsRNA substrates as part of their genomes or as replication intermediates. To date, they have not been extensively investigated for the biogenesis of viral non-coding RNAs, and future findings from these viruses could yield important insights. Several aspects of the RNAi-virus-host cell interaction also merit closer scrutiny. One issue is whether the expression of endo-siRNAs in mammals is similar between germline tissues and somatic tissues. The data for somatic tissues are currently incomplete. The emerging finding that piRNAs are present in both germ and somatic cells raises the possibility that endo-siRNAs conform to an analogous pattern. A second issue is the dynamic strike-counterstrike interplay between cells in which RNAi serves to combat viruses and viruses evade RNAi to successfully replicate in cells . One view is that efficiently replicating viruses must encode RNAi suppressors. Indeed, while many mammalian viruses do apparently have RNAi suppressor moieties , an RNAi suppressor function is only one of several means (for example, shielding of the virus genome from RNAi, sequence changes in the viral genome to evade RNAi, virus modulation of cellular miRNA expression, and virus adaptation to cellular RNAi) at the virus' disposal to skirt cellular RNAi restriction. Indeed, shielding of the viral RNA genome from RNAi , changes in viral sequences to evade RNAi , and virus-modulation of cellular miRNA-expression [48–50] have all been reported for HIV-1. Viruses such as HIV-1 that are highly mutable may evade RNAi efficiently through target sequence changes; these viruses do not need a strong RNAi suppressor [37, 51, 52], if at all . On the other hand, less mutable viruses may require strong RNAi suppressors to mitigate RNAi restriction in order to replicate optimally. A final issue is the increasingly convincing new evidence for the existence of natural antisense transcripts in human T-lymphotropic virus (HTLV)-1 and HIV-1 [54–58]. Inside cells, these antisense viral RNAs can, in principle, form long RNA duplexes with their complementary sense transcripts. The fate of these dsRNAs and what new functions they may provide promise to keep virologists busy for the next several years. I thank Christine Kozak, Dong-yan Jin, Andrew Dayton, and Laurent Houzet for advice on this writing and Lauren Lee for preparation of the figures. Work in my laboratory is supported in part by intramural funds from the NIAID and by the IATAP program from the office of the director, NIH. The opinions in this article represent my personal views and do not necessarily reflect the views of my employer, the NIH.
https://bmcbiol.biomedcentral.com/articles/10.1186/1741-7007-10-58
David Bartel is interested in the molecular pathways that regulate eukaryotic gene expression by affecting the stability or translation of messenger RNAs (mRNAs). He studies microRNAs and other small RNAs that specify the destruction and/or translational repression of mRNAs. He also studies mRNAs, with particular interest in their untranslated regions and poly(A) tails, and how these regions recruit and mediate regulatory phenomena. MicroRNAs Genomics and biogenesis. Our lab was among those to first report the abundance of microRNAs (miRNAs) in animals and the presence of miRNAs in plants. With help from collaborators, we went on to identify many of the miRNAs of model organisms (including Caenorhabditis elegans, fruit flies, Arabidopsis, and mice) and showed that humans have hundreds of miRNA genes. We also found miRNAs and other classes of small regulatory RNAs in deeply branching animals and land plants. The genes that encode miRNAs produce primary transcripts that fold back on themselves to form distinctive hairpin structures from which the miRNAs are processed. While analyzing data from high-throughput sequencing of small RNAs, we discovered types of miRNA precursors that bypass the specialized machinery that generates most miRNAs. In addition, we developed protocols to confidently identify the precursor hairpins that are recognized by the conventional machinery to give rise to miRNAs. We have since turned our attention to how this recognition occurs, i.e., how the cellular machinery determines which of the many hairpin-containing transcripts enter the miRNA biogenesis pathway. Using combinatorial and biochemical approaches, we have discovered that primary-sequence determinants help distinguish miRNA-containing transcripts from other types of hairpin-containing transcripts, and we have expanded the list of known structural determinants that are also recognized. With this menu of sequence and structural features, we can now reliably design miRNA genes de novo, without reference to a known gene. Regulatory targets. The realization that genomes of animals and plants each have hundreds of miRNA genes raised the question of what all these tiny RNAs are doing. To address this question, we have developed increasingly reliable methods for predicting miRNA targets. In plants, we found that miRNAs have extensive pairing to their targets and that evolutionarily conserved targets are mostly genes that play important roles during development. In animals, we have found a few cases of extensive pairing, but miRNAs usually recognize shorter sites (typically only 7 or 8 nucleotides long) that match a short region of the miRNA containing the "seed" sequence. In collaboration with Christopher Burge (Massachusetts Institute of Technology), we showed that more than half of the human protein-coding genes have been under selective pressure to maintain pairing to miRNAs. When we also consider nonconserved targeting, the fraction of human genes regulated by miRNAs grows even higher. Although a 7-nucleotide site matching a miRNA often mediates some repression, it is not always sufficient to do so, which indicates that other characteristics help specify targeting. For example, messenger RNA (mRNA) regions surrounding the sites can influence site accessibility and thus the efficacy of repression. We have combined such features of site context, as well as other features that make some miRNAs more effective than others, to construct models that predict site performance. In mammals, our model is as informative as the best high-throughput in vivo crosslinking approaches and thus provides an important resource for choosing which of the many miRNA–target relationships are most promising for experimental follow-up. Current predictions for mammals, zebrafish, flies, and nematodes can be viewed at www.TargetScan.org. Regulatory effects and biological functions. To augment and inform our computational analyses of miRNA targeting, we have adapted high-throughput approaches to measure the effects of mammalian miRNAs on target mRNA levels, poly(A)-tail lengths, translational efficiency, and protein accumulation. Prior to these measurements, the prevailing view was that miRNAs mediate repression mostly through translational inhibition, with relatively little effect on target mRNA levels. However, our measurements showed that, although some translational repression can be detected, mammalian miRNAs predominantly act to decrease target mRNA levels. Messages from hundreds of genes are directly repressed by individual miRNAs, albeit each to a modest degree, indicating that for most interactions, miRNAs act as rheostats to adjust and optimize the mRNA output previously generated by transcription and pre-mRNA processing. By disrupting the regulation of particular targets, several groups, including ours, have demonstrated the importance of miRNA-directed regulation during each stage of plant development. In addition, many groups have demonstrated the importance of miRNAs in animals. Indeed, our observation that most human genes are conserved targets of miRNAs indicates that it will be difficult to find a developmental process or disease that is not somehow influenced by miRNAs. We have contributed to the understanding of miRNA function during blood cell, brain, and skeletal development, as well as cancer. For example, disrupting the miRNA regulation of the mouse Hmga2 oncogene enhances oncogenic transformation. Because many human tumors possess defective HMGA2 genes that lack the miRNA complementary sites, our work indicates that losing miRNA regulation of this oncogene contributes to some human cancers. Other Small Regulatory RNAs In addition to new miRNAs, our analysis of small RNAs found in animals, fungi, and plants uncovered other classes of endogenous small RNAs. These include the 21U- and 26G-RNAs of nematodes, the heterochromatic small interfering RNAs (siRNAs) of fungi, and what are now recognized as trans-acting siRNAs of plants. Experimental follow-up, mostly by other labs, has shown that, like miRNAs, these each play important gene-regulatory roles in RNA-silencing pathways that have emerged in their respective evolutionary lineages. RNA Interference in Budding Yeast The miRNA pathways of plants and animals appear to have evolved independently, both as elaborations of a core RNA-silencing pathway known as RNA interference (RNAi). During RNAi, the Dicer endonuclease processes long double-stranded RNA into siRNAs, which are then loaded into the Argonaute protein, where they direct the cleavage of mRNA targets. This pathway is present in most eukaryotes, where it plays important roles in defending against viruses and transposons, but it was initially thought to be absent in budding yeast. In collaboration with Gerry Fink (Whitehead Institute and Massachusetts Institute of Technology), we found that although RNAi has been lost in a recent ancestor of Saccharomyces cerevisiae, it is present in other budding yeasts, including Saccharomyces castellii (a close relative of S. cerevisiae). The discovery of RNAi in budding yeast has opened many new opportunities for exploring the mechanism, biology, and evolution of the pathway. We found that introducing S. castellii Dicer and Argonaute into S. cerevisiae restores RNAi in this species. The reconstituted pathway strongly silences endogenous retrotransposons, which explains why it has been retained in S. castellii. In addition, endogenous double-stranded RNA (dsRNA) elements, known as Killer elements, are not retained in the RNAi-reconstituted S. cerevisiae strain, which renders these strains susceptible to the toxin of strains that have Killer. These results provide an explanation for why the presence of RNAi is so variable in the budding yeast lineage: retaining the pathway provides defense against transposons, whereas losing the pathway enables acquisition and retention of Killer. In collaboration with Dinshaw Patel (Memorial Sloan Kettering Cancer Center), whose lab solved the structures of the Dicer and Argonaute proteins, we have been studying the biochemical mechanism of RNAi in budding yeasts. We first determined the mechanism of the budding yeast Dicer (Dcr1), which differs from that of other Dicer proteins. Dcr1 dimers bind cooperatively along the dsRNA substrate and cleave at precise intervals determined by the distance between consecutive active sites. Thus, unlike canonical Dicers, which successively remove siRNA duplexes from the dsRNA termini, Dcr1 initiates processing in the interior and works outward. More recently, we have been studying the budding yeast Argonaute (Ago1), which resembles Argonaute proteins of animals and plants. The structure of this protein associated with its guide RNAs revealed how it positions these RNAs for target recognition and how a catalytic glutamine residue inserts into the active site to complete a previously unrecognized catalytic tetrad. Messenger RNAs, Poly(A) Tails, and Developmental Transitions MicroRNAs and other factors that mediate post-transcriptional gene regulation typically recognize elements in the 3′-untranslated regions (3′-UTRs) of mRNAs. Adding another dimension to this regulation is the use of alternative 3′-UTRs, which can either include or exclude the regulatory elements. To facilitate global analyses of these regulatory phenomena, we have developed a high-throughput method to accurately map the poly(A) sites of transcripts, which enables us to identify the ends of mRNAs and quantify the use of alternative isoforms in different cells, tissues, or developmental stages. We have applied this method to expand and correct the mRNA annotations of C. elegans, zebrafish, mice, and humans. These studies have substantially improved our prediction of miRNA targets in each of these species and have revealed the regulatory consequences of alternative 3′-UTRs in mammalian cells. Maternal gene products deposited into metazoan eggs regulate embryonic development before the zygotic genome is activated. In plants, an analogous period of prolonged maternal control over embryogenesis was also thought to occur. Overturning this idea, we showed that the vast majority of Arabidopsis mRNAs are produced in near-equal amounts from both maternal and paternal alleles, even during the initial stages of embryogenesis. In animals, we found a transition in translational control that follows the maternal-to-zygotic shift in transcriptional control. Key to this discovery was our development of a high-throughput method for measuring the lengths of poly(A) tails found at the ends of most eukaryotic mRNAs. When we used this method to measure tail lengths of millions of individual mRNAs isolated from early zebrafish, frog, or fly embryos, we found a very strong correlation between tail length and translational efficiency, as would be expected if mRNAs with longer tails were more efficiently translated. However, this strong coupling diminished at gastrulation and was absent in nonembryonic samples, which indicated a previously unrecognized developmental switch in the nature of translational control. In vitro, some RNAs can form stable four-stranded structures known as G-quadruplexes, and these structures have been implicated in post-transcriptional gene regulation and diseases. However, direct evidence for quadruplex formation in cells has been lacking. We recently identified thousands of endogenous sequences that can fold into G-quadruplexes in vitro but showed that, in contrast to previous assumptions, these G-quadruplex regions were overwhelmingly unfolded in cells. Nonetheless, the same G-quadruplex regions that were unfolded in eukaryotic cells were folded when ectopically expressed in Escherichia coli. However, these regions impaired translation and growth, which helps explain why few sequences that could fold into G-quadruplexes were detected in the transcriptomes of E. coli or the two other bacteria examined. Thus, we hypothesize that eukaryotes have a robust and surprisingly effective machinery that globally unfolds RNA G-quadruplexes, whereas bacteria have instead undergone evolutionary depletion of G-quadruplex–forming sequences. Long Noncoding RNAs In humans and other mammals, thousands of genomic loci produce long intervening noncoding RNAs (lincRNAs), which resemble mRNAs yet do not encode proteins. To better understand the evolution of lincRNAs, we identified lincRNAs in zebrafish and C. elegans. Although our set of zebrafish lincRNAs share many characteristics with mammalian lincRNAs, only ~30 have detectable sequence similarity with putative mammalian orthologs, typically restricted to a single short region of high conservation. Nonetheless, other lincRNAs are transcribed from conserved genomic locations despite our inability to detect sequence conservation. We have been investigating the functions of some of the conserved lincRNAs, with particular interest in one that pairs to a miRNA in a pattern that is unusually extensive and remarkably conserved in vertebrate species. Work on miRNAs and other RNAs is supported in part by grants from the National Institutes of Health.
https://www.hhmi.org/scientists/david-p-bartel
Piwi-interacting RNAs (piRNAs) play a significant role in all animals in safeguarding the germline from random and lethal insertions of mobile DNA elements or Transposable elements (TEs). These piRNAs forms an important class of small non coding RNAs bearing some important differences compared to other members like microRNAs (miRNAs) and short interfering RNAs (siRNAs). As the name suggests, these RNAs doesn’t code for any proteins as observed in the case of cellular mRNAs, which codes for protein upon translation. piRNAs differs from other two class of non coding RNAs in biogenesis. The RNase III-enzyme Dicer produces small RNAs in both microRNA (miRNA) and RNA interference (RNAi) pathways whereas piRNAs are produced in dicer independent manner. miRNAs are genome-encoded, endogenous negative regulators of translation and mRNA stability originating from long primary transcripts with local hairpin structures. RNAi is triggered by the processing of long double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs), which mediate sequence-specific cleavage of nascent mRNAs. All three classes of small non coding RNAs interact with specific proteins called as the Argonaute proteins.In case of short RNAs (siRNAs) form the RNA-induced silencing complexes termed (RISCs) and in the case of miRNAs this complex is referred to as miRISC. piRNAs forms a complex with piwi class of Argonaute proteins(Aubergine, Piwi and Ago3 in Drosophila) and these proteins can be phylogenetically separated into two clades based on sequence similarity: the Ago clade and the Piwi (P-element induced wimpy testis) clade. Unlike miRNAs which are evolutionary conserved, piRNAs display surprisingly diverse sequences between different organisms, even between closely related species. However piRNAs among various animals share some important similarities: 1) piRNAs in Drosophila are between 26 and 30 nucleotides (nt) in length, have a ‘preference’ for a 5′ uracil, and posses a 3′-most sugar that is 2′-O-methylated. 2) In c.elegans piRNAs are 21 nt long but share the 5′ and 3′ features of piRNAs exhibited by other organisms. Biogenesis of piRNAs is not completely understood but however few things are clear related to piRNAs generation. The biogenesis of piRNAs differ significantly in different animals : Immature piRNAs arise from specific genomic cluster mostly localized in pericentomeric region which are transcribed uni/bi directionnaly in long single-stranded RNA precursors by the RNA polymerase II . In another mechanism, which occurs in the cytoplasm, two other Piwi proteins, AUB and AGO3 upon loaded with piRNAs leads to cleavage and destruction homologous transposon transcripts using their endonuclease activity.This cleavage of complementary transcripts by AUB and AGO3 also leads to the generation of new piRNAs ,termed as ping pong mechanism .The ping-pong pathway in Drosophila is initiated by both maternally deposited piRNAs through germline transmission and zygotic primary piRNAs that are antisense to TEs and loaded onto Aub. Ping-pong signatures have been identified in very primitive animals such as sponges and cnidarians, pointing to the existence of the ping-pong cycle already in the early branches of metazoans. As mentioned above the exact mechanism for piRNA biogensis is not known, but involvement of following proteins is crucial for generation of piRNAs: Ago3, Aubergine, Piwi, Armitage, Spindle-E , Zucchini, Tudor, Yb, Tejas, Vasa, Maelstrom, SETDB1, cutoff, Rhino ,SuVar3-9 and Deadlock. Functions of piRNAs: The wide variation in piRNA sequences among species contributes to the difficulty in understanding the specificity and functionality of piRNAs. The best known and better understood function of piRNAs is its role in post-transcriptional transposon repression.TEs happen to be prominent targets of piRNAs and via ping ping cycle in which a transposon target is recognised by a piRNA and sliced by the Piwi protein through its slicer activity giving rise to new piRNA with opposite orientation and also cleaving (hence silencing) TEs transcripts. Evidence from sequencing of different organisms has identified loads of piRNAs that do not readily match to transposons or repetitive pseudogenes indicating that there is more to piRNA function apart from its vital and well studied role in silencing repeat elements. In support of this argument Martine Simonelig lab in France, using nanos maternal mRNAs degradation as a reference, have shown that piRNAs derived from transposon can target protein-coding mRNAs by binding directly to sequence in 3’UTR. The study demonstrates that complex of piRNAs, Piwi proteins ( Aubergine / Ago3) and CCR4-NOT deadenylation complex is responsible for degradation of maternal nos mRNA in the majority of the embryo. This work was supported by another work published in cell research where authors demonstrates involvement of pachytene piRNAs in instructing massive mRNA elimination in mouse elongating spermatids. Further reading: 1) piRNAs: from biogenesis to function. Weick EM, Miska EA. Development. 2014 Sep;141(18):3458-3471. 2) Pachytene piRNAs instruct massive mRNA elimination during late spermiogenesis Gou LT, Dai P, Yang JH et al. Cell Res. 2014 Jun;24(6):680-700. doi: 10.1038/cr.2014.41. Epub 2014 May 2. 3) Maternal mRNA deadenylation and decay by the piRNA pathway in the early Drosophila embryo. Rouget C, Papin C, Boureux A, Meunier AC, Franco B, Robine N, Lai EC, Pelisson A, Simonelig M. Nature. 2010 Oct 28;467(7319):1128-32. doi: 10.1038/nature09465. Epub 2010 Oct 17.
https://iflybio.com/2021/04/the-amazing-world-of-pirnas-biogenesis-and-function/
Sort By: Relevance A-Z By Title Z-A By Title A-Z By Author Z-A By Author Date Ascending Date Descending Show: 10 20 30 1 2 3 Article Peer Reviewed MicroRNAs in non-small cell lung cancer: Gene regulation, impact on cancer cellular processes, and therapeutic potential. Petrek, Hannah Yu, Ai-Ming et al. UC Davis Previously Published Works (2019) Lung cancer remains the most lethal cancer among men and women in the United States and worldwide. The majority of lung cancer cases are classified as non-small cell lung cancer (NSCLC). Developing new therapeutics on the basis of better understanding of NSCLC biology is critical to improve the treatment of NSCLC. MicroRNAs (miRNAs or miRs) are a superfamily of genome-derived, small noncoding RNAs that govern posttranscriptional gene expression in cells. Functional miRNAs are commonly dysregulated in NSCLC, caused by genomic deletion, methylation, or altered processing, which may lead to the changes of many cancer-related pathways and processes, such as growth and death signaling, metabolism, angiogenesis, cell cycle, and epithelial to mesenchymal transition, as well as sensitivity to current therapies. With the understanding of miRNA biology in NSCLC, there are growing interests in developing new therapeutic strategies, namely restoration of tumor suppressive miRNAs and inhibition of tumor promotive miRNAs, to combat against NSCLC. In this article, we provide an overview on the molecular features of NSCLC and current treatment options with a focus on pharmacotherapy and personalized medicine. By illustrating the roles of miRNAs in the control of NSCLC tumorigenesis and progression, we highlight the latest efforts in assessing miRNA-based therapies in animal models and discuss some critical challenges in developing RNA therapeutics. Article Peer Reviewed Advances and challenges in studying noncoding RNA regulation of drug metabolism and development of RNA therapeutics. Ning, Baitang Yu, Dianke Yu, Ai-Ming et al. UC Davis Previously Published Works (2019) Accumulating evidence has demonstrated that genome-derived noncoding RNAs (ncRNAs) play important roles in modulating inter-individual variations observed in drug metabolism and disposition by controlling the expression of genes coding drug metabolizing enzymes and transporters (DMETs) and relevant nuclear receptors (NRs). With the understanding of novel ncRNA regulatory mechanisms and significance in the control of disease initiation and progression, RNA-based therapies are under active investigation that may expand the druggable targets from conventional proteins to RNAs and the genome for the treatment of human diseases. Herein we provide an overview of research strategies, approaches and their limitations in biochemical and pharmacological studies pertaining to ncRNA functions in the regulation of drug and nutrient metabolism and disposition, and discussion on the promise and challenges in developing RNA therapeutics. Article Peer Reviewed Bioengineering of noncoding RNAs for research agents and therapeutics Ho, Pui Yan Yu, Ai-Ming et al. UC Davis Previously Published Works (2017) Article Peer Reviewed Advanced knowledge in drug metabolism and pharmacokinetics. Yu, Ai-Ming Zhong, Xiao-Bo et al. UC Davis Previously Published Works (2016) Article Peer Reviewed Novel approaches for efficient in vivo fermentation production of noncoding RNAs. Yu, Ai-Ming Batra, Neelu Tu, Mei-Juan Sweeney, Colleen et al. UC Davis Previously Published Works (2020) Genome-derived noncoding RNAs (ncRNAs), including microRNAs (miRNAs), small interfering RNAs (siRNAs), and long noncoding RNAs (lncRNAs), play an essential role in the control of target gene expression underlying various cellular processes, and dysregulation of ncRNAs is involved in the pathogenesis and progression of various diseases in virtually all species including humans. Understanding ncRNA biology has opened new avenues to develop novel RNA-based therapeutics. Presently, ncRNA research and drug development is dominated by the use of ncRNA mimics that are synthesized chemically in vitro and supplemented with extensive and various types of artificial modifications and thus may not necessarily recapitulate the properties of natural RNAs generated and folded in living cells in vivo. Therefore, there are growing interests in developing novel technologies for in vivo production of RNA molecules. The two most recent major breakthroughs in achieving an efficient, large-scale, and cost-effective fermentation production of recombinant or bioengineered RNAs (e.g., tens of milligrams from 1 L of bacterial culture) are (1) using stable RNA carriers and (2) direct overexpression in RNase III-deficient bacteria, while other approaches offer a low yield (e.g., nano- to microgram scales per liter). In this article, we highlight these novel microbial fermentation-based technologies that have shifted the paradigm to the production of true biological ncRNA molecules for research and development. Article Peer Reviewed MicroRNA Pharmacoepigenetics: Posttranscriptional Regulation Mechanisms behind Variable Drug Disposition and Strategy to Develop More Effective Therapy. Yu, Ai-Ming Tian, Ye Tu, Mei-Juan Ho, Pui Yan Jilek, Joseph L et al. UC Davis Previously Published Works (2016) Knowledge of drug absorption, distribution, metabolism, and excretion (ADME) or pharmacokinetics properties is essential for drug development and safe use of medicine. Varied or altered ADME may lead to a loss of efficacy or adverse drug effects. Understanding the causes of variations in drug disposition and response has proven critical for the practice of personalized or precision medicine. The rise of noncoding microRNA (miRNA) pharmacoepigenetics and pharmacoepigenomics has come with accumulating evidence supporting the role of miRNAs in the modulation of ADME gene expression and then drug disposition and response. In this article, we review the advances in miRNA pharmacoepigenetics including the mechanistic actions of miRNAs in the modulation of Phase I and II drug-metabolizing enzymes, efflux and uptake transporters, and xenobiotic receptors or transcription factors after briefly introducing the characteristics of miRNA-mediated posttranscriptional gene regulation. Consequently, miRNAs may have significant influence on drug disposition and response. Therefore, research on miRNA pharmacoepigenetics shall not only improve mechanistic understanding of variations in pharmacotherapy but also provide novel insights into developing more effective therapeutic strategies. Article Peer Reviewed MicroRNA-1291 targets the FOXA2-AGR2 pathway to suppress pancreatic cancer cell proliferation and tumorigenesis. Tu, Mei-Juan Pan, Yu-Zhuo Qiu, Jing-Xin Kim, Edward J Yu, Ai-Ming et al. UC Davis Previously Published Works (2016) Pancreatic cancer is the fourth leading cause of cancer death in the United States. Better understanding of pancreatic cancer biology may help identify new oncotargets towards more effective therapies. This study investigated the mechanistic actions of microRNA-1291 (miR-1291) in the suppression of pancreatic tumorigenesis. Our data showed that miR-1291 was downregulated in a set of clinical pancreatic carcinoma specimens and human pancreatic cancer cell lines. Restoration of miR-1291 expression inhibited pancreatic cancer cell proliferation, which was associated with cell cycle arrest and enhanced apoptosis. Furthermore, miR-1291 sharply suppressed the tumorigenicity of PANC-1 cells in mouse models. A proteomic profiling study revealed 32 proteins altered over 2-fold in miR-1291-expressing PANC-1 cells that could be assembled into multiple critical pathways for cancer. Among them anterior gradient 2 (AGR2) was reduced to the greatest degree. Through computational and experimental studies we further identified that forkhead box protein A2 (FOXA2), a transcription factor governing AGR2 expression, was a direct target of miR-1291. These results connect miR-1291 to the FOXA2-AGR2 regulatory pathway in the suppression of pancreatic cancer cell proliferation and tumorigenesis, providing new insight into the development of miRNA-based therapy to combat pancreatic cancer. Article Peer Reviewed Development of a mechanism-based pharmacokinetic/pharmacodynamic model to characterize the thermoregulatory effects of serotonergic drugs in mice. Jiang, Xi-Ling Shen, Hong-Wu Mager, Donald E Schmidt, Stephan Yu, Ai-Ming et al. UC Davis Previously Published Works (2016) We have shown recently that concurrent harmaline, a monoamine oxidase-A inhibitor (MAOI), potentiates serotonin (5-HT) receptor agonist 5-methoxy- N,N -dimethyltryptamine (5-MeO-DMT)-induced hyperthermia. The objective of this study was to develop an integrated pharmacokinetic/pharmacodynamic (PK/PD) model to characterize and predict the thermoregulatory effects of such serotonergic drugs in mice. Physiological thermoregulation was described by a mechanism-based indirect-response model with adaptive feedback control. Harmaline-induced hypothermia and 5-MeO-DMT-elicited hyperthermia were attributable to the loss of heat through the activation of 5-HT 1A receptor and thermogenesis via the stimulation of 5-HT 2A receptor, respectively. Thus serotonergic 5-MeO-DMT-induced hyperthermia was readily distinguished from handling/injection stress-provoked hyperthermic effects. This PK/PD model was able to simultaneously describe all experimental data including the impact of drug-metabolizing enzyme status on 5-MeO-DMT and harmaline PK properties, and drug- and stress-induced simple hypo/hyperthermic and complex biphasic effects. Furthermore, the modeling results revealed a 4-fold decrease of apparent SC 50 value (1.88-0.496 µmol/L) for 5-MeO-DMT when harmaline was co-administered, providing a quantitative assessment for the impact of concurrent MAOI harmaline on 5-MeO-DMT-induced hyperthermia. In addition, the hyperpyrexia caused by toxic dose combinations of harmaline and 5-MeO-DMT were linked to the increased systemic exposure to harmaline rather than 5-MeO-DMT, although the body temperature profiles were mispredicted by the model. The results indicate that current PK/PD model may be used as a new conceptual framework to define the impact of serotonergic agents and stress factors on thermoregulation. Article Peer Reviewed A general approach to high-yield biosynthesis of chimeric RNAs bearing various types of functional small RNAs for broad applications. Chen, Qiu-Xia Wang, Wei-Peng Zeng, Su Urayama, Shiro Yu, Ai-Ming et al. UC Davis Previously Published Works (2015) RNA research and therapy relies primarily on synthetic RNAs. We employed recombinant RNA technology toward large-scale production of pre-miRNA agents in bacteria, but found the majority of target RNAs were not or negligibly expressed. We thus developed a novel strategy to achieve consistent high-yield biosynthesis of chimeric RNAs carrying various small RNAs (e.g. miRNAs, siRNAs and RNA aptamers), which was based upon an optimal noncoding RNA scaffold (OnRS) derived from tRNA fusion pre-miR-34a (tRNA/mir-34a). Multi-milligrams of chimeric RNAs (e.g. OnRS/miR-124, OnRS/GFP-siRNA, OnRS/Neg (scrambled RNA) and OnRS/MGA (malachite green aptamer)) were readily obtained from 1 l bacterial culture. Deep sequencing analyses revealed that mature miR-124 and target GFP-siRNA were selectively released from chimeric RNAs in human cells. Consequently, OnRS/miR-124 was active in suppressing miR-124 target gene expression and controlling cellular processes, and OnRS/GFP-siRNA was effective in knocking down GFP mRNA levels and fluorescent intensity in ES-2/GFP cells and GFP-transgenic mice. Furthermore, the OnRS/MGA sensor offered a specific strong fluorescence upon binding MG, which was utilized as label-free substrate to accurately determine serum RNase activities in pancreatic cancer patients. These results demonstrate that OnRS-based bioengineering is a common, robust and versatile strategy to assemble various types of small RNAs for broad applications. Article Peer Reviewed Bioengineering of a single long noncoding RNA molecule that carries multiple small RNAs. Petrek, Hannah Batra, Neelu Ho, Pui Yan Tu, Mei-Juan Yu, Ai-Ming et al. UC Davis Previously Published Works (2019) Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), small interfering RNAs (siRNAs), and long noncoding RNAs (lncRNAs), regulate target gene expression and can be used as tools for understanding biological processes and identifying new therapeutic targets. Currently, ncRNA molecules for research and therapeutic use are limited to ncRNA mimics made by chemical synthesis. We have recently established a high-yield and cost-effective method of producing bioengineered or biologic ncRNA agents (BERAs) through bacterial fermentation, which is based on a stable tRNA/pre-miR-34a carrier (~ 180 nt) that accommodates target small RNAs. Nevertheless, it remains a challenge to heterogeneously express longer ncRNAs (e.g., > 260 nt), and it is unknown if single BERA may carry multiple small RNAs. To address this issue, we hypothesized that an additional human pre-miR-34a could be attached to the tRNA/pre-miR-34a scaffold to offer a new tRNA/pre-miR-34a/pre-miR-34a carrier (~ 296 nt) for the accommodation of multiple small RNAs. We thus designed ten different combinatorial BERAs (CO-BERAs) that include different combinations of miRNAs, siRNAs, and antagomirs. Our data showed that all target CO-BERAs were successfully expressed in Escherichia coli at high levels, greater than 40% in total bacterial RNAs. Furthermore, recombinant CO-BERAs were purified to a high degree of homogeneity by fast protein liquid chromatography methods. In addition, CO-BERAs exhibited strong anti-proliferative activities against a variety of human non-small cell lung cancer cell lines. These results support the production of long ncRNA molecules carrying different warhead small RNAs for multi-targeting which may open avenues for developing new biologic RNAs as experimental, diagnostic, and therapeutic tools.
https://escholarship.org/search/?q=author%3A%22Yu%2C%20Ai-Ming%22
Background: The novel coronavirus disease 2019 (COVID-19) is a global public health emergency that has caused worldwide concern. The mental health of medical students under the COVID-19 epidemic has attracted much attention. This study aims to identify subgroups of medical students based on mental health status and explore the influencing factors during the COVID-19 epidemic in China. Methods: A total of 29,663 medical students were recruited during the epidemic of COVID-19 in China. Latent class analysis of the mental health of medical students was performed using M-plus software to identify subtypes of medical students. The latent class subtypes were compared using the chi-square test. Multinomial logistic regression was used to examine associations between identified classes and related factors. Results: In this study, three distinct subgroups were identified, namely, the high-risk group, the low-risk group and the normal group. Therefore, medical students can be divided into three latent classes, and the number of students in each class is 4325, 9321 and 16,017. The multinomial logistic regression results showed that compared with the normal group, the factors influencing mental health in the high-risk group were insomnia, perceived stress, family psychiatric disorders, fear of being infected, drinking, individual psychiatric disorders, sex, educational level and knowledge of COVID-19, according to the intensity of influence from high to low. Conclusions: Our findings suggested that latent class analysis can be used to categorize different medical students according to their mental health subgroup during the outbreak of COVID-19. The main factors influencing the high-risk group and low-risk group are basic demographic characteristics, disease history, COVID-19 related factors and behavioral lifestyle, among which insomnia and perceived stress have the greatest impact. School administrative departments could utilize more specific measures on the basis of different subgroups, and provide targeted measures.
https://www.researchsquare.com/article/rs-209660/v1
Warning: more... Fetching bibliography... Generate a file for use with external citation management software. Little is known about the heterogeneity in and risk factors associated with trajectories of smoking during adolescence. This study aimed to (1) identify smoking trajectories empirically and (2) identify risk factors for trajectory group membership. Latent growth mixture models were used to identify population smoking trajectories, and logistic regression was used to estimate risk factors for group membership. The participants were drawn from seven middle schools in a Maryland school district. Participants consisted of 1320 6th graders who were followed to the 9th grade. Measurements of smoking risk factors were made in the fall of 6th grade and smoking stage was assessed on five different occasions between the fall of 6th and 9th grades. Five distinct smoking trajectories were identified. Overall, being female, having friends who smoked, deviance acceptance and outcome expectations were associated with an increased likelihood of being an intender, delayed escalator, early experimenter and early user compared to a never smoker. Additionally, comparisons with never smokers revealed unique identifiers for intenders, early experimenters and early users, but not delayed escalators. There is much heterogeneity in the manner in which middle-schoolers progress from having no intention of smoking to becoming smokers. Implications for prevention programs are discussed. National Center for Biotechnology Information,
https://www.ncbi.nlm.nih.gov/pubmed/15918815?dopt=Abstract
Ageing well involves individuals continuing participating in personal, social and civic affairs even in older age. From this standpoint, limitations in individual's functioning (beyond the mere absence of disease) may drastically impact on how well people becoming older. This study aimed to identify functional status profiles in a nationally representative sample of older adults, using latent class analysis methods. Moreover, it intended to study the how identified classes would be related to health-related outcomes later in life, as a way to provide some evidence on predictive validity. Data from a nationally representative sample of Spanish older adults (N = 2,118; 56.18% women; M = 71.50 years, SD = 7.76), were used. Profiles were identified according to a large set of functioning indicators from multiple domains using latent class analysis. Outcomes were studied over a 3-year follow-up, considering both the individual (quality of life, well-being and mortality) and institutional level (health service utilisation). As a result, seven profiles were identified: normative profile (showed by most participants), limited cognitive functioning class, limited global functioning class, limited mental and mobility functioning class, poor self-reported health class, limited sensory functioning class and limited objective functioning class. All the profiles with limitations across domains showed poor outcomes. Multidimensional limitations were related to the worst outcomes, especially when psychosomatic complaints and high feelings of loneliness were reported. To sum up, latent class analysis constitutes a suitable alternative to study population heterogeneity, providing relevant evidence to help making decision in public and community health. Keywords: Functioning profile; health service utilisation; latent class analysis; mortality risk; quality of life; well-being. © 2020 John Wiley & Sons Ltd.
https://pubmed.ncbi.nlm.nih.gov/32501615/
- Published: Diagnostic heterogeneity in psychiatry: towards an empirical solution BMC Medicine volume 11, Article number: 201 (2013) - 11k Accesses - 42 Citations - 36 Altmetric - Abstract The launch of the 5th version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) has sparked a debate about the current approach to psychiatric classification. The most basic and enduring problem of the DSM is that its classifications are heterogeneous clinical descriptions rather than valid diagnoses, which hampers scientific progress. Therefore, more homogeneous evidence-based diagnostic entities should be developed. To this end, data-driven techniques, such as latent class- and factor analyses, have already been widely applied. However, these techniques are insufficient to account for all relevant levels of heterogeneity, among real-life individuals. There is heterogeneity across persons (p:for example, subgroups), across symptoms (s:for example, symptom dimensions) and over time (t:for example, course-trajectories) and these cannot be regarded separately. Psychiatry should upgrade to techniques that can analyze multi-mode (p-by-s-by-t) data and can incorporate all of these levels at the same time to identify optimal homogeneous subgroups (for example, groups with similar profiles/connectivity of symptomatology and similar course). For these purposes, Multimode Principal Component Analysis and (Mixture)-Graphical Modeling may be promising techniques. Introduction With the launch of the fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the debate about current psychiatric diagnostics has come into the limelight again, focusing on specific alterations in the DSM-5, such as the deletion of pervasive developmental disorder not otherwise specified (PDD-NOS) and Asperger’s Disorder [1, 2] and the inclusion of mourning in major depressive disorder (MDD). However, more fundamental topics,such as the medicalization of normal behavior and the categorical approach to continuous phenomena, are also debated . Perhaps the most important criticism of the DSM-5 regards the poor validity of its classification. Several researchers have even stressed that the DSM-5 hampers research into the underlying mechanisms in the etiology of psychopathology and that the current state of affairs is one of scientific stagnation . We argue that the development of more valid psychiatric classifications is important in order to link mental states to specific causes in scientific research, and that this process should be evidence-based. Decreasing the amount of diagnostic heterogeneity is central in this process. The problem of diagnostic heterogeneity Current psychopathological concepts are heterogeneous by default whichrestricts their usefulness for research [6, 7]. In the past, evidence-based attempts to decrease heterogeneity have been made. For depression, for instance, subtypes have been identified with latent class analyses (LCA) [8, 9], symptom-dimensions with factor analyses (FA) [10, 11] and course-trajectory groups with mixture growth analyses (MGA) [12, 13]. Unfortunately, these studies tackle only one aspect of heterogeneity at a time. LCA focuses on person (p)-level heterogeneity, but does not account for within-class symptom and course variations. FA tackles symptom (s)-level heterogeneity, but assumes stability across persons and time. MGA describes temporal (t) heterogeneity, but does not account for s-level heterogeneity. Not surprisingly, these approaches have led to artificial models with limited replicability . The solution: simultaneous heterogeneity reduction If homogeneous diagnoses are what psychiatry aims for, a data-driven approach should be designed to minimize heterogeneity on each level simultaneously. To enable reduction of p-, s- and t-level heterogeneity, three-mode data are needed, visualized by Cattell’s data cube (Figure 1A). The cube consists of measured data (s-axis) for n individuals (p-axis) at k time-points (t-axis). For each combination of axes (slices), different statistical techniques apply. Cross-sectional studies of heterogeneity apply to the p-by-s slice: LCA divides the p-axis into classes (Figure 1B) and FA divides the s-axis into factors (Figure 1C). To model heterogeneity of the whole slice, model combinations (for example,factor mixture models) can be used. Longitudinal studies of heterogeneity (for example, MGA) apply to the p-by-t slice, modeling classes-based temporal trajectories on one or more variables (Figure 1D). Although incomplete, this summary shows that none of these models incorporate all three sources of variation. If we look to other fields (for example, psychometrics, mathematics), we can see that statistical advances have reached the point where ‘three-dimensional models’ are a possibility. Here, we briefly discuss two candidates. The latent variable approach: three-mode principal component analysis (3MPCA) 3MPCA is an exploratory technique, designed to decompose the latent structure of three-dimensional data by identifying the number of components that make up each of the axes. Investigation of the interactions between the modes can yield insights into the latent structure of three-dimensional data as a whole. In anxiety patients, for instance, 3MPCA showed that patients could be divided into subgroups (p-component) with different clusters of symptoms (s-component) in different situations (t-component) . Such an approach can be extended to a broader range of psychopathological phenomena. 3MPCA does have its limitations: it requires subjective judgments to enable modelselection and can yield hard-to-interpret results. However, it is a fully developed technique that can be used to explore three-dimensional psychopathology data for more homogeneous diagnostic entities. The network approach: (mixture) graphical analysis Traditional concepts of psychopathology (diagnoses, subtypes, dimensions) lean heavily on the assumption that corresponding latent constructs exist. Unfortunately, it is uncertain to what extent this is a realistic assumption . Rather than assuming that different symptoms (energy loss, suicidal ideation) are caused by one underlying disease (for example, depression), one could instead look at how symptoms interact, amplify and sustain each other over time in a network of symptoms (nodes) and causal links (edges) [18, 19], using graphical model methodology, developed in biostatistics . Such patient-descriptions are highly personalized: they take homogeneity to the extreme, both at the s- and p-level. Within three-dimensionaldata the s-axis is completely subdivided down to its smallest components (for example, symptoms). On the p-axis, for each person, the repeatedly measured symptoms are incorporated in a personalized network model. On the p-level, such an approach could lead to an indefinite number of possible network configurations, leaving us without any common denominators. However, subgroups with common network characteristics can be identified by mixture/latent class analyses on networkmodel parameters. Such an approach can yield subtypes that are not merely defined by common symptomatology, but particularly by their observed interconnectedness. Conclusions The development of evidence-based diagnoses in psychiatry is bound to require the use of datadriven techniques. In order for the resulting diagnostic models to optimally reflect real-world variation among patients, multiple sources of heterogeneity should be simultaneously evaluated. Although complex, and dependent upon the dataquality, such methods are a necessity when psychiatric diagnosis seeks an empirical basis. References - 1. Huerta M, Bishop SL, Duncan A, Hus V, Lord C: Application of DSM-5 criteria for autism spectrum disorder to three samples of children with DSM-IV diagnoses of pervasive developmental disorders. Am J Psychiatry. 2012, 169: 1056-1064. 10.1176/appi.ajp.2012.12020276. - 2. Ritvo ER, Ritvo RA: Commentary on the application of DSM-5 criteria for autism spectrum disorder. Am J Psychiatry. 2013, 170: 444-445. 10.1176/appi.ajp.2013.13010007. - 3. Frances A: Saving Normal: An Insider's Revolt Against Out-of-Control Psychiatric Diagnosis, DSM-5, Big Pharma, and the Medicalization of Ordinary Life. 2013, New York: William Morrow - 4. Wakefield JC: The DSM-5 debate over the bereavement exclusion: psychiatric diagnosis and the future of empirically supported treatment. Clin Psychol Rev. 2013, 10.1016/j.cpr.2013.03.007. - 5. Shorter E, Tyrer P: Separation of anxiety and depressive disorders: blind alley in psychopharmacology and classification of disease. BMJ. 2003, 327: 158-160. 10.1136/bmj.327.7407.158. - 6. Widiger TA, Clark LA: Toward DSM-V and the classification of psychopathology. Psychol Bull. 2000, 126: 946-963. - 7. Widiger TA, Samuel DB: Diagnostic categories or dimensions? A question for the diagnostic and statistical manual of mental disorders–fifth edition. J Abnorm Psychol. 2005, 114: 494-504. - 8. Eaton WW, Dryman A, Sorenson A, McCutcheon A: DSM-III major depressive disorder in the community. A latent class analysis of data from the NIMH epidemiologic catchment area programme. Br J Psychiatry. 1989, 155: 48-54. 10.1192/bjp.155.1.48. - 9. Sullivan PF, Kessler RC, Kendler KS: Latent class analysis of lifetime depressive symptoms in the national comorbidity survey. Am J Psychiatry. 1998, 155: 1398-1406. - 10. van Loo HM, de Jonge P, Romeijn JW, Kessler RC, Schoevers RA: Data-driven subtypes of major depressive disorder: a systematic review. BMC Med. 2012, 10: 156-10.1186/1741-7015-10-156. - 11. Shafer AB: Meta-analysis of the factor structures of four depression questionnaires: Beck, CES-D, Hamilton, and Zung. J Clin Psychol. 2006, 62: 123-146. 10.1002/jclp.20213. - 12. Byers AL, Vittinghoff E, Lui LY, Hoang T, Blazer DG, Covinsky KE, Ensrud KE, Cauley JA, Hillier TA, Fredman L, Yaffe K: Twenty-year depressive trajectories among older women. Arch Gen Psychiatry. 2012, 69: 1073-1079. 10.1001/archgenpsychiatry.2012.43. - 13. Rhebergen D, Lamers F, Spijker J, de Graaf R, Beekman AT, Penninx BW: Course trajectories of unipolar depressive disorders identified by latent class growth analysis. Psychol Med. 2012, 42: 1383-1396. 10.1017/S0033291711002509. - 14. Cattell RB: The data box: its ordering of total resources in terms of possible relational systems. Handbook of Multivariate Experimental Psychology. Edited by: Cattell RB. 1966, Chicago: Rand-McNally, 67-128. - 15. Lubke GH, Muthén B: Investigating population heterogeneity with factor mixture models. Psychol Methods. 2005, 10: 21-39. - 16. Kroonenberg PM, De Leeuw J: Principal component analysis of three-mode data by means of alternating least squares algorithms. Psychometrika. 1980, 45: 69-97. 10.1007/BF02293599. - 17. Kiers HAL, van Mechelen I: Three-way component analysis: principles and illustrative application. Psychol Methods. 2001, 6: 84-110. - 18. Borsboom D, Cramer AO: Network analysis: an integrative approach to the structure of psychopathology. Annu Rev Clin Psychol. 2013, 9: 91-121. 10.1146/annurev-clinpsy-050212-185608. - 19. Cramer AO, Waldorp LJ, van der Maas HL, Borsboom D: Comorbidity: a network perspective. Behav Brain Sci. 2010, 33: 137-150. 10.1017/S0140525X09991567. - 20. Abegaz F, Wit E: Sparse time series chain graphical models for reconstructing genetic networks. Biostatistics. 2013, 14: 586-599. 10.1093/biostatistics/kxt005. Pre-publication history The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/11/201/prepub Acknowledgements PdJ and KJW are supported by a VICI grant (no: 91812607) from the Netherlands Research Foundation (NWO-ZonMW). Additional information Competing interests The authors declare that they have no competing interests. Authors’ original submitted files for images Below are the links to the authors’ original submitted files for images. Rights and permissions This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. About this article Cite this article Wardenaar, K.J., de Jonge, P. Diagnostic heterogeneity in psychiatry: towards an empirical solution. BMC Med 11, 201 (2013). https://doi.org/10.1186/1741-7015-11-201 Received: Accepted: Published:
https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-11-201
Background: Heterogeneity in clinical outcomes may be caused by factors working at multiple levels, e.g., between groups, between subjects, or within subjects over time. A more nuanced assessment of differences in variation among schizophrenia patients and between patients and healthy comparison subjects can clarify etiology and even facilitate the identification of patient subtypes with common neuropathology and clinical course. Methods: We compared trajectories (mean duration of 3.5years) of cognitive impairments in a sample of 201 community-dwelling schizophrenia (SCZ) patients (aged 40-100years) with 67 healthy comparison (HC) subjects. We employed growth mixture models to discover subclasses with more homogenous between-subject variation in cognitive trajectories. Post hoc analyses determined factors associated with class membership and class-specific correlates of cognitive trajectories. Results: Three latent classes were indicated: Class 1 (85% HC and 50% SCZ) exhibited relatively high and stable trajectories of cognition, Class 2 (15% HC and 40% SCZ) exhibited lower, modestly declining trajectories, and Class 3 (10% SCZ) exhibited lower, more rapidly declining trajectories. Within the patient group, membership in Classes 2-3 was associated with worse negative symptoms and living in a board and care facility. Discussion: These results bridge the gap between schizophrenia studies demonstrating cognitive decline and those demonstrating stability. Moreover, a finer-grained characterization of heterogeneity in cognitive trajectories has practical implications for interventions and for case management of patients who show accelerated cognitive decline. Such a characterization requires study designs and analyses sensitive to between- and within-patient heterogeneity in outcomes. Copyright © 2012 Elsevier B.V. All rights reserved.
https://pubmed.ncbi.nlm.nih.gov/23218560/
In the article “Usage of a responsible Gambling tool: a descriptive analysis and latent class analysis of user behavior” PhD student David Forsström from the Department of Psychology, Stockholm University, studied how players are using Playscan. He examined the Playscan 3-data of 9 528 online gamblers who used the tool voluntarily and investigated if there are different subclasses of users by conducting a latent class analysis. He observed number of visits to the site, self-tests made and advice used. The study has shown that the tool has a high initial usage and a low repeated usage. Latent class analysis yielded five distinct classes of users: self-testers, multi-function users, advice users, site visitors, and non-users. Multinomial regression revealed that classes were associated with different risk levels of excessive gambling. The self-testers and multi-function users used the tool to a higher extent and were found to have a greater risk of excessive gambling than the other classes.
http://playscan.com/tag/research/
Please welcome Evelyn Cullet, author of “Masterpiece of Murder,” “Love Lies and Murder,” and “Once Upon a Crime.” She has become quite adept at weaving romance into a mystery and will explain how and why she does it. Hi, Everyone. I’d like to thank Jeanne for giving me the opportunity to be a guest author on her blog. I’ve been an aspiring author since high school when I enjoyed writing short stories. I began my first novel while attending college later in life, and while working in the offices of a major soft drink company. After taking early retirement, I finally have the chance to do what I love best: write full time. As a life-long mystery buff, I was a former member of the Agatha Christie Society, and am a current member of Sisters In Crime. When I’m not writing mysteries, reading them or reviewing them, I host guest authors and their novels on my writer’s blog. You can visit my blog at: http://evelyncullet.com/blog/. In my spare time, I play the piano, am an amateur Lapidary, and an organic gardener. My husband and I live in a suburb of Chicago with our black lab, Bailey. Writing Romance in a Mystery I’ve always loved reading mysteries. Agatha Christie, Dorothy L. Sayers and Author Conan Doyle have all influenced my writing in many ways. And so I tried writing novels in the cozy mystery genre. But being a hopeless romantic, I couldn’t keep the romance out. While I realize that all mystery lovers enjoy the puzzle aspect to a mystery, I also feel that adding romance makes the reader’s ties to the characters even stronger, and a love interest spices up the plot, adding another dimension to the story. While some readers like their romances hot and steamy, there are others who like it light and sweet. Where does a mystery writer draw the line? I take my cue from what I like to read: mysteries with romance on the lighter side. But sometimes my characters take on a life of their own, and they’ll dictate to me just how much of their love lives they want to reveal to the reader, and how much they want to leave to the reader’s imagination. So, there are times when I’m walking a fine line between the two, and I try not to cross it. How do I fit light romance into my mysteries? Studies show that proximity is a predictor of why people fall in love. Throw two people together for any length of time and the physical closeness alone can lead to increased emotions. That’s why it’s not unusual to hear about office romances. And that’s what happens to my protagonist, Charlotte Ross, who see’s her world about to crumble when the man she’s in love with–her boss–announces his engagement to someone else, in “Love, Lies and Murder.” But can love triumph when it’s built on a foundation of lies and murder? That’s a question only my characters can answer. Timing also significantly influences love. Individuals are more likely to fall in love if they are looking for adventure, feeling lonely, or are displaced in a foreign country, like when they’re on vacation. This is the case in “Masterpiece of Murder,” the sequel to “Love, Lies and Murder,” where Charlotte follows her errant fiancé to Bariloche, Argentina in an attempt to win him back.And in the process, she accidently stumbles into a downward spiral of deceit, art forgery and murder. Does the course of true love ever run smooth in my mysteries? Not if I can help it. I love writing mysteries with light romance and a little humor, and I hope you’ll enjoy reading my kind of story. To learn more about my novels, visit my website: http://evelyncullet.com/ My next novel, “Once Upon a Crime,” will be released this summer. MASTERPIECE OF MURDER and LOVE, LIES AND MURDER are both available in print and ebook from:
https://jeannemeeks.com/2014/06/06/writing-romance-into-a-mystery/
If I’m entirely honest, I really didn’t want to be shelved in the Romance section. I was adamant that my books could cross over — and should. In fact, I still maintain that it’s a stronger contender in the category of women’s fiction. But that’s hardly the only reason I objected to the categorization. Gender disparity and wider societal perceptions Part of my annoyance is in being a writer who has written a book that contains a love story — specifically a female writer with a plot containing a love story. It seems like being shelved in Romance is just par for the course while male writers who write the same thing find their books over in Literature and General Fiction. It seemed like I would have little choice in where I was shelved, even though I wrote the book and not everyone in the decision-making process had read it. But the other part of my annoyance comes from how romance is viewed as an overall genre — the smirks that come with saying that I’ve written a romance series. Being shelved with Romance seemed like a loss of credibility. But who’s making those rules, and why should we, as writers, care about them? I’m not proud of that thought, but it’s one that’s developed over the years as an avid reader. Even as a reader, there would be judgment leveled at me for reading a romance versus a classic or another genre of literature. No one smirked if I was deep into a mystery, but when my interests turned to a love story, there was nearly automatic derision. I internalized that attitude, and it came creeping out when my own series was being published. There’s an idea that Romance isn’t Literature. But the definition of literature is written works, especially those considered of superior or lasting artistic merit. Why do we think that love stories don’t have lasting merit? Every story is a love story I was listening to a talk years ago, whose provenance I cannot now recall, where a therapist who had done extensive work with refugees from war-torn countries spoke about how, for the most part, everyone wanted to process their relationships, not the trauma they endured on coming into the camps. Their focus wasn’t on the larger issue of homelessness or leaving behind their country. The focus was on love and relationships. These stories resonate with us all. In fact, if you try, you’d be hard-pressed to find a book, movie, or television show that doesn’t have some love interest contained in its plot. In fact, most series thrive on dragging out the two protagonists’ longing for one another for season after season, ratcheting up the tension until the “will they or won’t they” question defines the show. You likely thought of one or more shows where that’s happened. We don’t categorize our cop shows or law shows or other dramas as being romances, but aren’t they? Sure, there are other plots, but oftentimes, we stay around for the relationships, not the solving of cases or the next big reveal of some mystery. We invest in the characters and their love stories. Why, then, don’t we do the same with romance novels? So, I stopped being irritated that I was being shelved as a romance and started being irritated instead that the industry doesn’t look fondly toward one of their top-selling genres, that the literary world is often dismissive, and that we’ve somehow placed writing and reading romance novels as something to smirk about. The evolution of the genre Romance novels have evolved as society has evolved, giving us strong partnerships that factor in both equality and consent. The old trope of the female virgin and world-weary promiscuous male lead has fallen away to give us stronger narratives to meet the changing appetites of a new wave of readers who insist upon complexity and strength from their reading material. The stories are every bit as strong as any other genre and are as worthy of recognition and respect. My book sits proudly among the romances in many stores, and it might even be shelved in women’s fiction somewhere else, or chick lit — another category that I take issue with for its sexist and somewhat condescending tone. I’m not going to apologize for crafting four stories with strong, quirky characters in a beautiful setting, even though they do contain love stories. I’m not going to apologize at all. I’m just going to go on to work on my next. Romance isn’t a lesser genre, and it took me too long to realize it. It seems I had to write a few, completely unintentionally, to realize that the problem isn’t the genre but its outdated and inaccurate reputation. I always enjoyed a strong love story, and I easily discarded the ones with old-fashioned tropes with weak-minded women playing the damsel in distress to the strong male lead. I never could invest in them, and so it shouldn’t come as a surprise that I couldn’t write one that way either. What was more surprising was the arc of my love story with the genre — from dismissing it myself to realizing its value. I’m happy to have my work shelved beside other writers who are putting out the kind of strong, character-driven narratives with their heartfelt and satisfying love stories that are demanding that the industry sit up and take notice. It’s not a competition Romance isn’t trying to compete for space on bookshelves. It doesn’t really need to compete at all. It’s always been self-contained in its way, understanding its own power even in the face of derision. Romance readers have always known the value of a strong love story. We’re not cowed by industry or wider societal perceptions. We’ll keep reading what we love and investing in the authors who give us the stories we enjoy. Let them smirk because we know exactly what they’re missing. Because writing isn't a competition, and there’s plenty of room on the bookshelves for all of us, no matter what genre we write. And if there’s not enough room? Maybe we need a bigger bookshelf.
https://original.newsbreak.com/@crystal-jackson-561044/2132525856392-why-romance-gets-a-bad-rap
Tessa Leoni is a character featuring in three novels written by bestselling author Lisa Gardner. Looking for the Reading Log? Lisa Gardner When I was in high school, I became obsessed with True Crime books. Out of everything I read, it became my go-to genre, leaving the twins of Sweet Valley High far behind. Flash forward to a few years later when I was dating a cop, the interest in True Crime only intensified. The story revolves around a perfect little family that just vanishes into thin air. With the help of the FBI, Private Investigator Tessa Leoni starts delving into what happened to the family, unraveling more secrets and mystery with every chapter, and the more she finds out, the less perfect the family becomes. Author Lisa Gardner is known for being an expert researcher and has a way of detailing police procedures and forensic evidence that keeps you hooked … and wanting more. Most books take me weeks to finish, due largely in part to those two kids I care for, but this book I finished in just a few days. Lisa Gardner Lisa Gardner born is an American author. She also wrote romance novels using the pseudonym Alicia Scott. She credited her long days doing research for giving her the skills needed to follow a line of investigation while learning new topics. As of , Gardner lives in New England with her family. From Wikipedia, the free encyclopedia. American author of thrillers. Added by of our members. This is my family: Vanished without a trace. Justin and Libby Denbe have the kind of life you'd find in the pages of a glossy magazine. A beautiful fifteen-year-old daughter. A gorgeous brownstone on a tree-lined street in Boston's Back Bay neighborhood. A great marriage, admired by all. Lisa Gardner About Fear Nothing Detective D. They were daughters of a monster—a father who slaughtered eight prostitutes before dying himself. Adeline Glen left the nightmare behind, and now she specializes in pain management. I love mysteries and Lisa Gardner has written some that I have enjoyed. Twenty years ago, Melanie Stokes was abandoned in a Boston hospital, then adopted by a wealthy young couple. Seller Centre Download. Your browser is not compatible with Shopee Video Shop Vouchers. Shipping Loading Flora and D. BookBub Search LisaGardner. Boston Detective D. Lisa Gardner Books Look Inside. Signs of an abduction. Clearly the work of professionals. At best, the entire family has been kidnapped. At worst… The more Tessa learns about the Denbe family, the less she likes their chances. What might have looked like the perfect existence—a powerful CEO, his adoring wife, their angelic child—is not what it appears. delawarecops.org: Touch & Go (Tessa Leoni series Book 2) eBook: Gardner, Lisa: Kindle Store. - Сьюзан нахмурилась. - Итак, вы полагаете, что Северная Дакота - реальное лицо. - Боюсь, что. И мы должны его найти. Найти тихо. Блестящий криптограф - и давнишнее разочарование Хейла. Он часто представлял, как занимается с ней сексом: прижимает ее к овальной поверхности ТРАНСТЕКСТА и берет прямо там, на теплом кафеле черного пола. Но Сьюзан не желала иметь с ним никакого дела. И, что, на взгляд Хейла, было еще хуже, влюбилась в университетского профессора, который к тому же зарабатывал сущие гроши. Очень жаль, если она истратит свой превосходный генетический заряд, произведя потомство от этого выродка, - а ведь могла бы предпочесть его, Грега. Вы можете заметить, - продолжал Смит, - что взгляд его устремлен. Он ни разу не посмотрел по сторонам. - Это так важно? - полувопросительно произнес Джабба. Просто позор. - Могу я для вас что-нибудь сделать. Клушар задумался, польщенный оказанным вниманием.
https://delawarecops.org/and-pdf/210-touch-and-go-lisa-gardner-pdf-656-760.php
Prolific murder mystery writer Faith Martin talks about her million-selling crime thrillers including the DI Hillary Greene novels, Monica Noble, Jenny Starling and new Ryder and Loveday series. Faith Martin is the pen name of Oxford-born Jacquie Walton. She also writes as Maxine Berry, Joyce Cato and Jesse Daniels. Most of the crime novels are set in and around Oxford. DI Hillary Greene works out of Thames Valley Police headquarters in Kidlington and the series includes Murder on the Oxford Canal, Murder at the University and Hillary’s Final Case. Monica Noble is a vicar’s wife and the series is set in the fictional Cotswold village of Heyford Bassett. Jenny Starling is a travelling cook who has featured in seven novels including the latest The Country Inn Mystery. The newest series finds a young WPC working with the local coroner to solve a murder mystery in 1960s Oxford. Walton is best known for the Hillary Greene series. She began her career writing romance novels under the name of Maxine Berry. After achieving moderate success for 25 years, her murder mysteries became sudden global bestsellers when the DI Hillary Greene series was republished by Joffe Books a couple of years ago.
https://oxfordliteraryfestival.org/literature-events/2020/april-1/the-english-country-murder-mystery
On a cold December evening, Autumn Spencer’s twin sister, Summer, walks to the roof of their shared Harlem brownstone and is never seen again. With her friends and neighbors, Autumn pretends to hold up through the crisis. But the loss becomes too great, the mystery too inexplicable, and Autumn starts to unravel, all the while becoming obsessed with the various murders of local women and the men who kill them. Embed our reviews widget for this book <script src="//lithub.com/b/v1/bookmarks.js?ver=1.3"></script> <div class="bm-reviews" data-isbn="9781640091917" data-width="auto" data-link="true"> </div> What is this? Positive Based on 6 reviews Rave Positive Mixed Pan What The Reviewers Say Rave Lesley Williams , Booklist Buckhanon captures Autumn’s frustration at the undervaluing of black women, accompanied by the creeping gentrification of her Harlem neighborhood ... Yet it is Buckhanon’s elegant images of grief that most captivate ... Devastating. Read Full Review >> Rave Carole E. Barrowman , The Minneapolis Star Tribune In Autumn, Kalisha Buckhanon has created a narrative voice that’s authentic, emotionally charged and wise, but beneath the surface of the story lurks the unraveling of a life and how 'even the biological imperative to survive' can sometimes lose against the 'power of past experiences.' Buckhanon has crafted a deeply moving psychological mystery with twists that come in unhurried moments like the small notes the sisters buried in bottles in their garden shed. I’m going to be talking about Summer for a while. Read Full Review >> Positive Tayari Jones , Oprah Magazine Novels of psychological suspense often employ unreliable narrators, but Buckhanon, who’s also known for her work as an on-air true crime expert, employs the device not to keep readers off-balance, but rather to evoke Autumn’s fragility and raise universal questions about mental illness, racism, and love ... fiercely astute. Read Full Review >> See All Reviews >> SIMILAR BOOKS Fiction Rave Positive Mixed Pan The Justice in Revenge Ryan Van Loan Positive Fiction Rave Positive Mixed Pan The Other Me Sarah Zachrich Jeng Positive Fiction Rave Positive Mixed Pan 56 Days Catherine Ryan Howard Rave Fiction Rave Positive Mixed Pan A Line to Kill Anthony Horowitz Rave Coming Soon Rave Positive Mixed Pan The Every Dave Eggers Mixed What did you think of Speaking of Summer ? comments powered by Disqus. About Get the Book Marks Bulletin Please enter an email address so you can get access to our awesome newsletter! Categories Fiction Fantasy Graphic Novels Historical Horror Literary Literature in Translation Mystery, Crime, & Thriller Poetry Romance Speculative Story Collections Non-Fiction Art Biography Criticism Culture Essays Film & TV Graphic Nonfiction History Investigative Journalism Memoir Music Nature Politics Religion Science Social Sciences Sports Technology Travel True Crime Lithub Daily October 23, 2021 More News Get This Week's Book News Every Friday, the Book Marks Bulletin Please enter an email address so you can get access to our awesome newsletter!
https://bookmarks.reviews/reviews/speaking-of-summer/
"Is there a wannabe book lurking in the back of your brain, something you would write if you didn’t have to consider agents, editors, and fans? A romance? Non-fiction? Cookbook?" This is a question I always ask my guests on Jungle Red, and it occurred to me that I’ve never asked my fellow Reds! Although readers generally get to know writers for one kind of book, in my experience, writers noddle around with a variety of books ideas that they'd like to write "someday." It’s the book they’d write in an ideal world where time and money were copious, and the only reader they'd have to satisfy is themselves. Obviously, I love reading and writing mysteries, but I also love the work of Elinor Lipman, Stephen McCauley, Emma Straub, Maria Semple, and Curtis Sittenfeld, to name just a few. Their books are funny, contemporary fiction that focus on relationships, and families, in particular. One of these days, I might try my hand at that genre. Reds? Tell us about the book brewing in the far reaches of your brain. LUCY BURDETTE: Of course, if we told you what we wanted to write, it wouldn’t be secret would it? Ha ha, just kidding. I love Elinor Lipman also, have read all of her novels, starting from the very beginning. I also love the novels of Joshilyn Jackson. And I think I’ve confessed before that if I could write a book like The Storied Life of AJ Fikry, I surely would. As it happens, I am inching along on something that is not a mystery, more women’s fiction. The problem, as always, is that you have a built-in structure for writing a mystery. And so without that, the plotting is not so easy. HANK PHILLIPPI RYAN: Yes, exactly, Lucy! Someone once asked me if I could write a romance without a mystery. I was baffled. "What would the people DO?" I asked. So I guess that explains why I don't write romance. That said, I know I could do a voicey contemporary fiction, I really do. And I do have a YA plot, but again, a thrillerish thing. I'd adore to do a big family saga, and even have an idea of when it would take place. (In the US, Rhys, in the US :-) ) And I'd love love love to do a narrative non-fiction true crime. LOVE to. But.... So, that being said, I'd love to write a sweeping fantasy saga with a Robin Hoodesque female, who kicks butt and rights wrongs and all that jazz, but it is definitely off brand for me, and I have zero time at the present. That being said, I have a writer friend who wrote "Sunday books" for years. They were her off-brand books that she worked on just on Sundays for fun (writers are weird, I know) and now she's out there publishing those, too. So, never say never. RHYS BOWEN: In a way I'm doing this right now. My stand alone novels are moving out beyond the mystery genre. The Tuscan Child was set in two time periods, which was an experiment for me. Next year's book really doesn't have much mystery. It's straight historical. However, I love to read travel books and secretly yearn to be another Bill Bryson. JULIA SPENCER-FLEMING: I would love to write contemporary womens' fiction in the vein of Jennifer Crusie—comedic, but real—with great characters and small towns and loads of plot. I already have ideas—and by ideas, I mean notes, outlines and research—for a science fiction series and an historical fiction series, both genres I LOVE to read. However, everything I think of, even the fun, small town comedy ideas, center around crime. No matter what the genre, My creative imagination runs straight to SOMEONE getting murdered. The other impediment to branching out (besides Jenn's very wise words about brand) is that I write so slowly, I wouldn't be able to get to any of these until I was 94. HALLIE EPHRON: Great question. For me it would be a book about food. Eating it. Shopping for it. And of course, cooking. Definitely nonfiction. Something for the person who wants to become a shoot-from-the-hip kind of cook. Easy recipes. Start with what are the basics every larder needs. What basic skills the agile cook needs (chopping, blanching...) Move on to building from basics. So, basic stew... plus. Basic stir-fry...plus. Basic pan roasted... plus. Options that include vegetarian, fish, and meat. Something like Cooking: The Basics Plus. And can I just say while I love the idea behind meal kits, I'm horrified by the amount of plastic and cardboard it comes wrapped in. The waste weighs more than the food. DEBORAH CROMBIE: Hallie, if you write that cookbook, I will buy it!! I've toyed with the idea of writing historical fiction (quite a few of my novels have historical story lines woven into the contemporary one, and I love writing the historical bits.) For years, I've said I wanted to write a novel with a Victorian female naturalist as the main character--sort of a cross between Beatrix Potter and Charles Darwin. But I've never been able to get past the basic concept, because if it wasn't a mystery, what would people DO? Besides, knowing me, I'd fall down the research rabbit hole and never come out...
https://www.jungleredwriters.com/2018/06/our-not-fantasy-books.html
One call from her past was all it took to change everything. A ten-year-old girl has vanished on her way home from camp. And things took a turn for the worse when another child, a child that Emma knows, goes missing. Disappearances, death, and tragedies has followed Emma Griffin throughout her childhood. Her obsession with finding out the truth behind her past was what led her to join the FBI. It’s been months since the horror of Feather Nest. After the shocking revelation of the last case, FBI agent Emma Griffin decides to take a much-needed vacation. But a phone call from Sheriff Sam Johnson, a man from her past, completely derails her plans. A young girl has disappeared, and another child has gone missing. With the number count slowly climbing. Emma must now put her plans on hold, go back to her hometown and face some ghosts from her past. When a mysterious package appears on her birthday. Emma can’t shake the feeling that someone is monitoring her every movement. Someone is getting too close for comfort. The question is who? In the close-knit town of Sherwood, the truth is never as it seems. AJ Rivers loves all things mystery and thriller. Growing up in a sleepy small town, AJ spent her days enthralled in crime solving novels and movies. She started creating stories at a young age to escape and create adventures for herself. As a child she dreamed of solving crimes and becoming a crime fighter. She dreamed of being as great as her favorite crime solving character Sherlock Holmes. While in college she realized that leading a crime fighting life might be more gruesome than she could stomach. She decided that the best course of action would be to fuse her love of writing with her love of thrilling mysteries together. She finds inspiration from researching true crimes and is passionate about writing suspenseful novels with crazy twists. Twists that you’ll never see coming. The inspiration for her first novel came when she read a news article about a missing young woman in a small town that was never found. Her question on who, what, and why brought her to her journal to discovering the dark twisted story behind the disappearance and to seek justice for the victim through her writing. Her thriller novels have elements of mystery, suspense, and romance. When she’s not absorbed in a novel or working on her next thriller mystery, her favorite past time is spent with her husky. She finds great inspiration while going on hikes with her dog.
https://discountbookman.com/the-girl-that-vanished-by-a-j-rivers-2/
Dan Brown, author of "The Da Vinci Code" and "Angels & Demons," is set to release his latest Robert Langdon mystery this spring. "Inferno," will be published in the U.S. and Canada on May 14 by Doubleday Publishing. The novel focuses on the same main character as Brown's most popular novels, symbologist Robert Langdon. The novel is "set in Italy and centers on one of history's most enduring and mysterious literary masterpieces, Dante's Inferno," according to the Doubleday statement. "In Inferno…[we follow] Robert Langdon back to the heart of Europe, where he becomes entwined in a mystery has had global ramifications…tied to the ominous and truly mesmerizing details of Dante's masterful work," Jason Kaufman, Executive Editor with Doubleday said. The title of the novel was a mystery until today. Publishers posted a puzzle on Dan Brown's Facebook page for fans of the novels to try their hand at solving puzzles like Langdon. Brown decided to focus on Dante's epic poem while working in Italy. "Although I studied Dante's Inferno as a student, it wasn't until recently, while researching in Florence, that I came to appreciate the enduring influence of Dante's work on the modern world," Brown said in the statement. "The Da Vinci Code" and "Angels & Demons" were turned into films, starring Tom Hanks as Langdon. "The Da Vinci Code" spent 144 weeks at the top of The New York Times Best Seller list, has been translated into 51 languages and has sold 81 million copies worldwide.
https://www.yahoo.com/news/blogs/abc-blogs/dan-brown-novel-inferno-set-may-release-200601251--abc-news-celebrities.html?ref=gs
Vanishing Act – A Jamie Richmond Mystery A new year marks new beginnings for Jamie Richmond. Not only has she moved into a cozy new house, but she's brought Malone along with her to fan the flames of their growing romance. When Jamie's best friend, Linda Davis, enters the picture, she thinks everything is right with the world. Linda begins a May-September romance with Vincent Schulte, Jamie's doctor and good friend. But while Vince is sweeping Linda off her feet, she unknowingly has captured the attention of a stalker. The idyllic life suddenly takes a very bad turn when Linda disappears without a trace on a cold and snowy day. The police are scrambling to find a clue that will lead them to Linda. Malone does his best to comfort Jamie and encourages her to let the professionals do their job. But if there's one thing he's learned in their time together, it's that nothing will stop this stubborn redhead from solving the mystery. Jamie turns all of her attention on figuring out who took Linda and where she might be, regardless of the dangers she may face. Her efforts once again put her in harm's way. But will she find her best friend? About Mark Love (Kalamazoo, Michigan Author) Mark Love lived for many years in the metropolitan Detroit area, where crime and corruption were always prevalent. A former freelance reporter, Love honed his writing skills covering features and hard news. He is the author of the several novels including Fade Away, WHY 319? and three Jamie Richmond romance mysteries , Devious, Vanishing Act and Fleeing Beauty. Love resides in west Michigan with his wife, Kim. He enjoys a wide variety of music, books, travel, cooking and the great outdoors. Love is currently working on his next novel.
https://hometownreads.com/books/vanishing-act
With an ever-expanding fan base, graphic novels comprise an area of tremendous growth in book publishing. Covering genres from action/adventure and fantasy to horror, science fiction, and superheroes, this guide maps the vast and expanding terrain of graphic novels, describing and organizing titles as well as providing information that will help librarians to build and balance their graphic novel collections and direct patrons to read-alikes. New subgenres, new authors, new artists, and new titles appear daily in the comic book and manga world, joining thousands of existing titles—some of which are very popular and well-known to the enthusiastic readers of books in this genre. How do you determine which graphic novels to purchase, and which to recommend to teen and adult readers? This updated guide is intended to help you start, update, or maintain a graphic novel collection and advise readers about the genre. Containing mostly new information as compared to the previous edition, the book covers iconic super-hero comics and other classic and contemporary crime fighter-based comics; action and adventure comics, including prehistoric, heroic, explorer, and Far East adventure as well as Western adventure; science fiction titles that encompass space opera/fantasy, aliens, post-apocalyptic themes, and comics with storylines revolving around computers, robots, and artificial intelligence. There are also chapters dedicated to fantasy titles; horror titles, such as comics about vampires, werewolves, monsters, ghosts, and the occult; crime and mystery titles regarding detectives, police officers, junior sleuths, and true crime; comics on contemporary life, covering romance, coming-of-age stories, sports, and social and political issues; humorous titles; and various nonfiction graphic novels. Michael Pawuk is librarian at Cuyahoga County Public Library. He received his master's degree in library and information science at Kent State University. David S. Serchay is librarian in the Broward County Library system, where his responsibilities include selecting graphic novels. He is the author of The Librarian's Guide to Graphic Novels for Children and Tweens and The Librarian's Guide to Graphic Novels for Adults. He has also contributed to various reference books on graphic novels, including The Encyclopedia of Comic Books and Graphic Novels, Comics Through Time, and Icons of the American Comic Book. Serchay has spoken on the topic of graphic novels and libraries at ALA conferences and the San Diego Comic-Con as well as in libraries around Florida.
https://www.abc-clio.com/ABC-CLIOCorporate/product.aspx?pc=A3277C
Since challenging myself back in January to watch a new-to-me mystery show every other week, I’ve discovered and enjoyed 12 detective series so far in 2020. When July came around, I started wanting to spend more time watching some of my old favourites rather than constantly watching something new. I also realized that although I have watched many detective series in the past, I haven’t actually written about many of them on this blog. So for the next little while, I’m going to focus on writing reviews/summaries of shows I’m already familiar with. Following my binge of the Aurora Teagarden mysteries, some of which featured Yannick Bisson, I’ve decided to get back into watching Murdoch Mysteries. I watched the show more regularly during its early days, and I’ve caught occasional episodes since. Prior to writing this post, I watched/re-watched the entirety of Season 1. Murdoch Mysteries is based on a book series by Maureen Jennings, and was commissioned after a few TV movies based on the books proved successful in 2004. The first season aired in 2008, and there have been 13 seasons produced since with a 14th season coming in 2021. [Note: On some US channels, the show aired under the title “The Artful Detective“.] In Murdoch Mysteries, Yannick Bisson plays Detective William Murdoch of the Toronto Constabulary. The series is set in Toronto (Canada), with the events in the first season set in approximately 1895. There are a number of viewers that this show will appeal to. First, if you’re a history buff, or even if you’re into the steampunk genre, you’d enjoy the historical references and anachronisms. The show brings together historical facts about life in Toronto as well as historical figures at the time (several episodes feature Nicola Tesla and Sir Arthur Conan Doyle) and often gives them a slightly modern spin. Murdoch frequently makes use of new inventions and devises novel methods for solving crimes–inventions that reference modern technologies such as lie detectors and fax machines. Second, as a Canadian (and Torontonian), I personally enjoy watching out for references to Canadian history, politics and geography. There are so few popular Canadian productions, so this show offers a rare exciting opportunity to understand all the references, rather than trying to make sense of the references in American or British media. Finally, the show is simply enjoyable in its own right. It is one of the more cozy-style mystery shows that is in contrast to the usual gritty crime dramas being produced these days. And the relationships between the main characters are interesting beyond the investigation of a crime. In the TV series, Murdoch is assisted by a feminist medical examiner Dr. Julia Ogden with whom he has a bit of a “will-they-won’t-they” relationship; his boss is the prejudiced Inspector Brackenreid; and he’s frequently assisted by the young and often fanciful Constable Crabtree. If you’ve read the books, it should be mentioned that there are some differences between the novels and the TV series. The main one being that the TV series is a lot more light-hearted and almost comedic, whereas the novels can be much more dark and somber. And based on my description above, there are notable differences in characterization. All in all, this is an enjoyable show for those who enjoy their mysteries to be served with a touch of humour. Where to watch Murdoch Mysteries - In the US, it’s possible to stream Murdoch Mysteries on Amazon Prime Video (free with an AcornTV subscription). - The show is also currently available to purchase on DVD or BluRay. - If you’re in Canada, the show is available to stream on CBC Gem, and on Netflix.
https://murdershewatched.com/2020/07/20/murdoch-mysteries-tv-series/
6 edition of English romance in time found in the catalog. Published 2004 by Oxford University Press in Oxford, New York . Written in English Edition Notes Includes bibliographical references (p. -531)and index. |Statement||Helen Cooper.| |Classifications| |LC Classifications||PR321 .C66 2004| |The Physical Object| |Pagination||xiii, 542 p. ;| |Number of Pages||542| |ID Numbers| |Open Library||OL3327378M| |ISBN 10||0199248869| |LC Control Number||2004301649| |OCLC/WorldCa||55884402| South Pacific foreign affairs handbook Dolls in verse Every little step Federal Courts and the Law of Federal-State Relations (University Casebook Series) The greater parables of Tolstoy The complete idiots guide to psychology Collecting militaria By request Miscellaneous theological works of Emanuel Swedenborg. History of Dudley castle and priory Civil Defense in War and Peace Democracy for the privileged Evaluating European immersion programs Icons York Estuary sediments The English Romance in Time is a study of English romance across the Middle Ages and the Renaissance. It explores romance motifs - quests and fairy mistresses, passionate heroines and rudderless boats and missing heirs - from the first emergence of the genre in French and Anglo-Norman in the twelfth century down to the early seventeenth. The English Romance in Time is a study of English romance across the Middle Ages and the Renaissance. It explores romance motifs - quests and fairy mistresses, passionate heroines and rudderless boats and missing heirs - from the first emergence of the genre in French and Anglo-Norman in the twelfth century down to the early seventeenth. This is a continuous story, since the same. This book features an uncommon element in time-travel romance: the ability to go into and out of the specified time period. Usually, in one of these (thanks probably in part to Diana Gabaldon, NGL), the heroine (because it’s almost always the heroine) finds herself in a moment in history, and one of the most important plot elements is how to get her back to her own time (if, in the Author: Jessica Pryde. A Modern Lady Lost in Time: A Contemporary, Feel-Good Time Travel Romance Denise Daye. out of 5 stars Kindle Edition. Five steamy Time Travel Romances Mariah Stone. out of 5 stars Kindle Edition. A Scottish Time Travel Romance (Highlander Forever Book 4) Rebecca Preston. out of 5 stars 2. Kindle Edition. While romance is genre mostly comprised of fiction, Just Kids is a must-read exception to that rule. The book, written by singer and artist Patti Smith, chronicles her relationship with photographer Robert Mapplethorpe during their early 20s in New York. A modern Manhattan woman finds herself in the arms of a medieval knight in this charming time travel romance novella featuring the de Piaget family—from the New York Times bestselling author of Stars In Your Eyes. Julianna Nelson often wishes a knight in. English literature - English literature - The Romantic period: As a term to cover the most distinctive writers who flourished in the last years of the 18th century and the first decades of the 19th, “Romantic” is indispensable but also a little misleading: there was no self-styled “Romantic movement” at the time, and the great writers of the period did not call themselves Romantics. Here you can find free books in the category: Romance. Read online or download Romance eBooks for free. English × All Languages Historical time travel romance. Book Recommendation. Betrayed By A Vampire. Emily and Jagger are back. Emily's coping with the fact that Jagger's a vampire, and especially with how Jagger is so longing to bite. Though E.L. James’s erotic books about BDSM and sex continue to captivate the world, meriting a movie, a musical parody and the Marlon Wayans sarcastic send-up Fifty Shades of Black, we. Veils and Vows Romance Collection (Books 0 - 3): The Promise, The Surprise Wedding, A Pinch of Commitment, and The Wedding Plan Jean Oram out of 5 stars Best Romance English romance in time book of all time - Read books online, read online free from your computer and Smartphone, Mobile. All romance novels have two things in common — a love story at the book's center, and a happy ending — but that doesn't mean every book is the same. Within the romance genre, there's a Author: Sadie Trombetta. Groundbreaking for its time, the first-person narrative set a new standard for what romance could be — no wonder readers still love it more than years later. 17 Occupation: Staff Writer. Free download best romantic novels stories books in English by Indian authors and others. The ebook is a collection of more than romantic short stories for adults with a taste of comedy to make the story more real. I am sure these historical heart touching stories will make you able to glance the real life stories of great lovers/5(10). Until the End of Time. $ Shop Now. Danielle Steel has written, so far, books, many of them best-selling romances that are known for their meticulous research, historical plot lines, and Author: Molly Pennington, Phd. Wanting to read about love and romance with a YA twist. Check out this list of best teen romance books, including "The Fault in Our Stars," "Simon vs. the Homo Sapiens Agenda," and "A Walk to. The best time travel books come in all packages: adventure, historical fiction, romance, social commentary, mystery, humor, poetry. It really has it all. So, if you can still recite the opening credits of Quantum Leap from memory, this list is for you. When thinking of romance novels, everyone’s mind typically goes to the classic airport read: a hulking man on the cover, hair blowing in the wind, and a six-pack showing. Even though those are a fun guilty pleasure, there are plenty of other reads in. Best Romance novels of all time - Read books online. A Husband's Regret (Unwanted #2) (, view) The Bride (Lairds' Fiancees #1) (, view) The Boy Who Sneaks in My Bedroom Window Romance novels online. Contact Us. All The Data From The Network AND User Upload, If Infringement, Please Contact Us To Delete!. Natural Law by Joey W. Hill – I heard talk of this book for many years before I actually read it. What an amazing read, and a bit of a twist in today’s erotica market. The hero is a big. Loretta Chase is one of the best romance novelists of all time — and this book is one of her best. Benedict Carsington, Viscount Rathbourne is. Rate this book. Clear rating. 1 of 5 stars 2 of 5 stars 3 of 5 stars 4 of 5 stars 5 of 5 stars. When He Was Wicked (Bridgertons, #6) by. Julia Quinn (Goodreads Author) (shelved 5 times as english-romance) avg rating — 32, ratings — published Want to Read. “It is a truth universally acknowledged that a single man in possession of a good fortune must be in want of a wife.” So begins Pride and Prejudice, Jane Austen’s witty comedy of manners–one of the most popular novels of all time–that features splendidly civilized sparring between the proud Mr. Darcy and the prejudiced Elizabeth Bennet as they play out their spirited courtship in a. The best novels written in English: the full list After two years of careful consideration, Robert McCrum has reached a verdict on his selection of the greatest novels written in English. Read + original love and romance stories, books and novels.💋🥰 Download the Inkitt app to fall in love with reading (again). This is a list of notable published novelists who specialise or specialised in writing romance novels. [nb 1] See also: Lists of authors If you add any authors to this. The Best Romance Novels of the Last 10 Years. We’ve decided to celebrate the last decade of Booklist’s annual Spotlight on Romance by combining the 10 most recent Top 10 Romance Fiction lists, from throughto create a roll call of the best recent romance novels as we see them—a grouping that could also be titled, “The Big Happily-Ever-After Reading List.”. The 25 Best Romance Authors (And Their Most Swoonworthy Reads) Romance is one of the most popular genres in literature today, both for readers and writers of romance novels. And it’s no wonder why: romance is exciting, sexy, and compulsively readable. Luckily, there are tons more books coming out all the time. Love stories have a way of speaking straight to your soul, and there's something for everyone on this list of the best romantic books and plays to read of all time, from "Romeo and Juliet" to. Top 10 Famous Romance Novels of All Time Love, passion, feelings and relationships: all these are easy to experience but difficult to express in the written word. However, the following 10 love stories (in chronological order) have been able to accomplish this monumental task and thus allowed us to experience some the best romance novels of all. Romance, literary form, usually characterized by its treatment of chivalry, that came into being in France in the midth century. It had antecedents in many prose works from classical antiquity (the so-called Greek romances), but as a distinctive genre it was developed in the context of the. In this historical-romance-meets-time-travel novel, a malfunctioning future time machine sends four people from four different timelines to the year BCE, on the Mediterranean coast of Egypt. Among them are American architect Duncan Reid, who came all the way from the 20th century, and Erissa, a priestess from Atlantis who has only traveled. Download Romance Books for FREE. All formats available for PC, Mac, eBook Readers and other mobile devices. Large selection and many more categories to choose from. 46 Brilliant Short Novels You Can Read In A Day. Rereading The Mezzanine for the 3rd time -- it explains so much about our times. A romantic comedy with the emphasis on comedy, not romance. In honor of the day of love coming up, I thought I would share some of my favorite love stories. I am a book depository affiliate and I receive a small commi. Categories: Fiction» Romance» Regency, Fiction» Romance» Historical ( from 2 reviews) Launched onto the ton as Lord Henry Anglethorpe’s sister’s companion, Agatha Beauregard is determined to make use of her new freedom by letting loose her scientific tendencies. Romance Books belong to one of the most popular fiction genres, currently accounting for over 50% of all printed and online English-language books sold worldwide. In this very popular category you will find a wealth of Romantic Novels and novelettes in a wide range of fiction genres from Contemporary, Chicklit and Historical Romance to. From Don Quixote to American Pastoral, take a look at the greatest novels of all time The greatest non-fiction books The version of the best novels. The book was a biting political commentary of its time (the Meiji era) told through the eyes of an unwanted stray cat who spent his days exploring the city and watching the humans who inhabit it. Prior to penning the story, Natsume studied Chinese philosophy, and ideologies reflecting his academic influence is weaved throughout the tale. Hallmark Movies Based on romance famous Novels - Best Hallmark Movies HD Hollywood Comedy Movie in Englishviews. Out of Time .
https://demywemyhygirel.arleenthalerphotography.com/english-romance-in-time-book-21526bz.php
When I was in college, my friends and I would pass around romance novels to each other on the sly, hoping our English teachers wouldn’t spot us reading these juicy novels and give us a hard time. Romance novels were generally considered trashy although no teacher expressly told us not to read them. They were probably happy that we were reading something at least. I did move on to other genres and I love reading crime and mystery but romance was my first love. So, when I started writing, it seemed natural that I would bring romance into most of my books, albeit unwillingly. (The English Literature student in me was constantly looking over my shoulder.) Now that I am willingly a romance writer, I realise how much fun I have crafting these stories, which readers also seem to love thankfully. If you want to venture into writing romance, these are some of the things that I like to work with, so maybe it might help you too. - Create interesting/flawed protagonists – No one likes perfect people in real life and neither do they in fiction. I try to make sure there’s something off about my protagonists, whether they’re messy people, or have an unpredictable temper. It makes them interesting and relatable. - Avoid clichés – I try and avoid cliched descriptions of my characters, so you won’t find any tall, dark and handsome men or curvaceous beauties with lilac hued eyes in my books. Another way I describe them is through the perspective of the other characters, so it’s all quite subjective and different people view the same person differently. - Bring chemistry – Chemistry between the romantic leads is one of the things that keeps readers hooked to the story. Getting it right takes practice because readers can spot when there’s no chemistry. Also, there’s no such thing as too much chemistry. - Love scenes – I’m a little shy about writing overt love scenes but that’s just me. If you’re comfortable, go right ahead and make it as steamy as you want. The thing to watch out here is to make sure there’s no awkwardness in your writing. Try and read it aloud (with expression and maybe a little passion). If it makes you wince, then cut it out and redo. - Read – This is a no-brainer no matter which genre you’re writing for but if you want to write well, then read, read and read, especially the genre you want to master. So, if it’s romance you want to be good at, read all kinds – historical, contemporary etc and try and imbibe from them. - Strong heroines/vulnerable heroes – The world is different from the time I used to huddle at the back of my class and read one of those M&B Temptation novels. Heroines need to be relatable. They don’t have to be bra-burning feminists but they surely need to be independent, strong and aspirational. Heroes on the other hand seem to do so much better with a dose of vulnerability to add to their dreaminess. After writing all these books over these past few years, one thing I’ve learnt is that you need to enjoy your work too. And maybe one day your English teachers might, too!
http://blog.juggernaut.in/how-to-create-the-romance-in-your-story/
Order of Frances Brody Books Frances Brody is an English novelist who writes the 1920s-set series of crime novels featuring Kate Shackleton. The books have drawn comparison to Agatha Christie who definitely has to be considered an inspiration. The books have been praised for their accurate portrayal of what England was like after the war. Frances Brody is actually a pen name for the author, whose real name is Frances McNeil. Her mother’s own stories were a big inspiration to her early writing as Sisters on Bread Street is based on an account of her mother’s life. Her mother was a big fan as well, constantly sending her plots that she hoped her daughter would turn into a book or a play. Publication Order of Kate Shackleton Books Publication Order of Standalone Novels |Somewhere Behind the Morning||(2005)| |Sixpence in Her Shoe||(2006)| |Sisters of Fortune / Halfpenny Dreams||(2008)| |Sisters on Bread Street||(2020)| Publication Order of Cozy Case Files Mystery Sampler Books If You Like Frances Brody Books, You’ll Love… The first book in the Kate Shackleton series is Dying in the Wool. The story begins when the Master of the Mill, Joshua goes missing under mysterious circumstances. Joshua’s daughter is getting married, but before she does she wants to look for her father one last time. Kate will enter the fold as she’s always liked solving puzzles and finding Joshua would be the greatest puzzle of all. Of course, once you go looking for secrets, you’ll often by surprised by what you find. Death of an Avid Reader is another strong entry in the Shackleton series. This one centers on three mysteries: the search for a missing baby, a haunted library, and a killer on the loose. Kate is on the case of the missing baby, but is also asked to take part in an exorcism at the haunted library. She doesn’t believe in ghosts, but when the party turns up a dead body, she’ll have her work cut out for her. Especially when the man accused of doing it, Kate believes to be innocent.
https://www.orderofbooks.com/authors/frances-brody/
If a plant wants to grow, it needs reliable anisotropic cell elongation*. Getting the cells to elongate has a couple of constraints. There is vacuolar turgor pressure, the pressure from the vacuole in the cell pushing the contents of the cell up against the cell wall. And there’s the cell wall, which needs to limit the contents of the cell to keep everything in. The strength in a cell wall mainly comes from cellulose microfibrils. These are strands aligned perpendicular to the axis of elongation, allowing the cell wall to stretch in the right direction. Le et al. set out to characterize the molecular function of AtDICE1 encoding a novel transmembrane protein involved in anisotropic cell elongation in Arabidopsis. They found that gain-of-function mutation of AtDICE1, a gene encoding a putative ER-localized membrane protein, causes defects in anisotropic cell elongation by disturbing cell wall integrity in Arabidopsis. Further genetic, biochemical and transcriptomic observations suggest that AtDICE1 contributes to the proper anisotropic cell elongation process in the vascular tissue possibly through the process of cell wall formation. *Stretching in along a specific axis of the cell, for example growing longer, instead of just inflating.
https://www.botany.one/2018/08/regulation-of-anisotropic-cell-elongation-in-arabidopsis/
They require oxygen for their growth. Obligate aerobes: which can grow only in the presence of oxygen (e.g., P. aeruginosa). Facultative aerobes: which are ordinary aerobes but can also grow without oxygen (e.g., E. coli). Most of the pathogenic bacteria are facultative aerobes. Microaerophilic bacteria: those bacteria that can grow in the presence of low oxygen and in the presence of low (4%) concentration of carbon dioxide (e.g., Campylobacter jejuni). Obligate anaerobes are the bacteria that can grow only in the absence of oxygen (e.g., Clostridium botulinum Clostridium tetani, etc.). The optimum temperature for most of the pathogenic bacteria is 37°C. These bacteria are cold loving microbes that grow within a temperature range of 0–20°C. Most of soil and water saprophytes belong to this group. These are moderate temperature loving microbes that grow between 25°C and 40°C. Most of pathogenic bacteria belong to this group. These are heat loving microbes. They can grow at a high temperature range of 55–80°C. B. stearothermophilus is an example. Depending on the source of energy bacteria make use of, they may be classified as phototrophs (bacteria deriving energy from sunlight) or chemotrophs (bacteria deriving energy from chemical sources). Factors such as osmotic pressure and salt concentration of the solution affect the growth of bacteria. Bacteria by their mechanical strength of their cell wall are able to withstand a wide range of external osmotic variations. On the other hand, sudden transfer of bacteria from concentrated solution to distilled water may cause excessive imbibition of water leading to swelling and bursting of cell (plasmoptysis).
http://microbiologyonlinenotes.com/factors-affecting-growth-of-bacteria/
While teaching many undergraduate students, I saw the double-edged sword of students trying to figure things out on their own. On the one hand, this mentality is seen to be respectable, a sign of independence and perseverance. On the other hand, it is a mentality that can prevent students from taking advantage of opportunities to advance their skills and, most importantly, their grades. The difference between help and mentorship As an undergraduate, you’ll have a lot to figure out. The academic expectations you’ll face will be vastly different than high school. What you need to know is that seeking mentorship and the appropriate guidance to get a better grasp of your professors’ expectations is not a sign of weakness or ineptitude, it’s in your best interest. If you’re seeking to improve your academic skills, you need to get beyond the idea that asking for feedback or guidance is somehow a sign of incompetence; it’s not. Asking for help in a remedial sense is completely different than seeking guidance in a constructive way. Finding the proper mentorship means that you’re interested in getting better, refining your skills, and understanding the methods that will make you successful in your current and future work—it does not mean that you are unable to meet university expectations. Seeking help after you’ve recognized a problem is a reactive measure. This is very different than getting informed guidance in a proactive fashion. Guidance and mentorship illuminates the path in front of you Wouldn’t it be great to understand the exact expectations of your professor before you hand in your work? Don’t let the pride of thinking you must figure everything out on your own prevent you from learning valuable lessons before you’re graded. Seek out feedback from resources that are readily available to you. Office hours, your university’s writing centre, or even people within your personal network can offer you constructive commentary to get you going in the right direction. When someone who actually knows how to do well in university provides you with guidance that can help you advance your skills, it’s similar to someone providing you with a GPS system for a long road trip to somewhere you have never been. The GPS knows the road ahead and it knows how to guide you in a way that avoids dangerous shortcuts or long and redundant detours. Essentially, it empowers you to successfully get to your end goal in an informed way. This is similar to what mentorship can do for you. Who should you seek guidance from? After giving the same advice to many students, some have returned to tell me that the person they sought out for guidance was not very helpful. Unfortunately, this happens frequently. However, this shouldn’t deter you. If a professor, teaching assistant, or another mentor views helping you as a burden on their time, then find someone else who actually wants to help. Also, exercise care in who you choose to ask about your work and your future. Just because someone has some experience with university or in the professional field you want to enter, it does not make them an expert. Be diligent and ask questions to ensure that the person from who you are seeking mentorship possesses the values and experience that you wish to learn from. Finally … Remember that the mindset of “I’ll do it on my own” can be both positive and negative. While it’s great for a student to be driven by a desire to independently find methods to success, there is a point where not seeking guidance is a hindrance to progress. From my experience, the best students are thirsty to learn from the experience of others. If you’d like to learn about how BridgesEDU can provide you with the proper mentorship for success in university, please feel free to reach out. I’d be happy to have a conversation with you.
https://www.bridgesedu.com/the-good-and-bad-of-ill-figure-it-out-on-my-own/
A great Texas lady once said, “I believe there is a special place in hell for women who do not help other women.” I would modify this to include people of diverse backgrounds. Put simply, I would not be where I am today were it not for the grace of God and the imparted wisdom and guidance of trusted mentors. No person is an island, and success is virtually impossible without the support of those who have been on deserted islands and found their way back to the mainland. As a woman of color, I believe I have a greater responsibility not only to find personal mentors, but also to mentor diverse professionals who are coming down the pike. Like life, careers have different stages, and each stage requires different skills. My career has come full circle. Having started out as an in-house lawyer, then spending almost 12 years in private practice and now returning to in-house practice, I have had to make major adjustments to my approach. Don’t get me wrong; the things that have stood me in good stead over the course of my career—integrity, commitment to excellence, dedication, humanity, humility, humor and perseverance—continue to sustain me. But understanding the operating environment and successfully navigating it have been absolutely essential to my survival. This knowledge could have come only from the assistance of good mentors. Mentoring can have many different facets within and outside of your organization. During my career, I have experienced five dimensions of mentoring: - The technical advisor is the person who helps you with the technical aspects of your job, such as research and writing and presentation skills. - The champion mentor makes it his or her business to sing your praises to others and help you navigate the maze of your organization’s internal politics. - The navigator or strategic advisor, who often is someone outside your organization, will advise you over the course of your career. - The personal mentor is a friend who knows you perhaps even better than you know yourself. This person can provide a perspective that no one else can. - The en masse or peer-to-peer mentors are those that you encounter at conferences for diverse professionals. The people who embody these roles are key stakeholders in your career and will help you build confidence and strategic vision—essential elements for success.
http://www.womenworthwatching.com/sandra-phillips/
One of the most common things Resource Generation (RG) members are looking for is a financial advisor who respects or is in line with their values, who understands social change and progressive financial values, and can give trusted guidance accordingly. Close colleagues at a trusted progressive financial firm, along with several RG members, have developed a survey for financial advisors to fill out about their values, their work with young people, experience and expertise with impact investing, diversity of their company’s leadership, and other questions to help figure out if their work matches your values. Their answers are compiled below. If you’re interested in contacting any of these advisors, please reach out to any of them yourself; Resource Generation is not a go-between. Alternatively, feel free to use these questions to guide your own search process. We aim to support each person on their journey engaging with their finances; for many, finding a trusted advisor is a key factor in being empowered and informed to take action with your resources, in alignment with social justice values. We hope this list helps you find a good fit! Legal disclaimer: This list is meant as a tool and jumping-off point for RG members to conduct their own evaluation of prospective financial advisors. The presence of an advisor on the list is not an endorsement by RG, nor is RG making any representations about the quality or sufficiency of any financial advisor’s services. Rather, we are sharing a series of questions and answers (“profiles”) about their values and experience working with young people and incorporating social justice frameworks. By using the list and profiles, you acknowledge that RG is not responsible for the performance or lack of performance of any advisor you select. Are you a financial advisor and want to be added to this database? Please fill out this survey by August 18th, 2017. You will be added to the database before the end of August.
http://archive.resourcegeneration.org/financial-advisors-database/