Writing in the May 2015 issue of Stroke, researchers who studied more than 900 participants of the Framingham Heart Study found evidence of smaller brain structure and of covert brain infarcts, a type of “silent” ischemic stroke resulting from a blockage in the blood vessels supplying the brain.
The study evaluated how far participants lived from major roadways and used satellite imagery to assess prolonged exposure to ambient fine particulate matter, particles with a diameter of 2.5 millionth of a meter, referred to as PM2.5. These particles come from a variety of sources, including power plants, factories, trucks and automobiles and the burning of wood. They can travel deeply into the lungs and have been associated in other studies with increased numbers of hospital admissions for cardiovascular events such as heart attacks and strokes.
“This is one of the first studies to look at the relationship between ambient air pollution and brain structure,” says Elissa Wilker, ScD, a researcher in the Cardiovascular Epidemiology Research Unit at Beth Israel Deaconess Medical Center. “Our findings suggest that air pollution is associated with insidious effects on structural brain aging, even in dementia- and stroke-free individuals.”
Study participants were at least 60 years old and were free of dementia and stroke. The evaluation included total cerebral brain volume, a marker of age-associated brain atrophy; hippocampal volume, which reflect changes in the area of the brain that controls memory; white matter hyperintensity volume, which can be used as a measure of pathology and aging; and covert brain infarcts.
The study found that an increase of only 2µg per cubic meter in PM2.5, a range commonly observed across metropolitan regions in New England and New York, was associated with being more likely to have covert brain infarcts and smaller cerebral brain volume, equivalent to approximately one year of brain aging.
“These results are an important step in helping us learn what is going on in the brain,” Wilker says. “The mechanisms through which air pollution may affect brain aging remain unclear, but systemic inflammation resulting from the deposit of fine particles in the lungs is likely important.”
“This study shows that for a 2 microgram per cubic meter of air (μg/m3) increase in PM2.5, a range commonly observed across major US cities, on average participants who lived in more polluted areas had the brain volume of someone a year older than participants who lived in less polluted areas. They also had a 46 percent higher risk of silent strokes on MRI,” said Sudha Seshadri, MD, a Professor of Neurology at Boston University School of Medicine and Senior Investigator, the Framingham Study.
“This is concerning since we know that silent strokes increase the risk of overt strokes and of developing dementia, walking problems and depression. We now plan to look at more the impact of air pollution over a longer period, its effect on more sensitive MRI measures, on brain shrinkage over time, and other risks including of stroke and dementia.”
In addition to Wilker, who is also affiliated with the Exposure Epidemiology and Risk Program in the Department of Environmental Health at the Harvard T.H. Chan School of Public Health (HSPH), and Seshadri, co-authors include: Sarah R. Preis, ScD, of the Boston University School of Public Health, Department of Biostatistics (BUSPH) and the Framingham Heart Study (FHS); Alexa S. Beiser, PhD, of BUSPH, FHS and the Boston University School of Medicine Department of Neurology (BUSM); Philip A. Wolf, MD, of FHS and BUSM; Rhoda Au, PhD of BUSM; Ital Kloog, PhD, of the Department of Geography and Environmental Development , Ben-Gurion University of the Negev, Beer Sheva, Israel; Wenyuan Li, MS, of the Department of Epidemiology of HSPH; Joel Schwartz, PhD, of HSPH; Petros Koutrakis, PhD of HSPH; Charles DeCarli, MD, of the Department of Neurology and Center for Neuroscience, University of California, Davis; and Murray Mittleman, MD, DrPH, of BIDMC and HSPH.
- Elissa H. Wilker, Sarah R. Preis, Alexa S. Beiser, Philip A. Wolf, Rhoda Au, Itai Kloog, Wenyuan Li, Joel Schwartz, Petros Koutrakis, Charles DeCarli, Sudha Seshadri, and Murray A. Mittleman. Long-Term Exposure to Fine Particulate Matter, Residential Proximity to Major Roads and Measures of Brain Structure. Stroke, 2015 DOI: 10.1161/STROKEAHA.114.008348
Source: Beth Israel Deaconess Medical Center. “Long-term exposure to air pollution may pose risk to brain structure, cognitive functions.” ScienceDaily. ScienceDaily, 23 April 2015. <www.sciencedaily.com/releases/2015/04/150423182357.htm>.
The study results, in the April 22 edition of NatureJournal, demonstrated that the treatment is the first to be shown effective against the new Makona outbreak strain of Ebola in animals that were infected with the virus and exhibited symptoms of the disease.
The treatment uses a sequence specific short strand of RNA, known as siRNA, designed to target and interfere with the Ebola virus, rendering it harmless. One of the advantages of this approach is the ability to quickly modify it to different viral strains.
“We quickly adapted our candidate treatment to target the Makona outbreak strain of Ebola virus,” said UTMB’s Thomas Geisbert, professor of microbiology and immunology. “We were able to protect all of our nonhuman primates against a lethal Makona Ebola infection when treatment began three days following infection. At this point, those infected showed clinical signs of disease and had detectable levels of virus in their blood.”
Although all infected animals showed evidence of advanced disease, those receiving treatment had milder symptoms and recovered fully. The untreated controls succumbed to the disease on days eight and nine, which is similar to that reported in the field after patients begin showing symptoms of Ebola.
This treatment also protected against liver and kidney dysfunction and blood disorders that occur during an Ebola infection. These results indicate that the treatment may confer protective benefits that go beyond improving survival rates and effective control of virus levels in the body.
“This study demonstrates that we can rapidly and accurately adapt our siRNA-LNP technology to target genetic sequences emerging from new Ebola virus outbreaks,” said Dr. Mark Murray, president and CEO of Tekmira Pharmaceuticals.
The Tekmira siRNA-based therapeutic is now being evaluated in Ebola-infected patients in Sierra Leone.
- Emily P. Thi, Chad E. Mire, Amy C. H. Lee, Joan B. Geisbert, Joy Z. Zhou, Krystle N. Agans, Nicholas M. Snead, Daniel J. Deer, Trisha R. Barnard, Karla A. Fenton, Ian MacLachlan, Thomas W. Geisbert. Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates. Nature, 2015; DOI: 10.1038/nature14442
Source: University of Texas Medical Branch at Galveston. “New Ebola treatment effective three days after infection.” ScienceDaily. ScienceDaily, 22 April 2015. <www.sciencedaily.com/releases/2015/04/150422135748.htm>.
Published April 20 in the Proceedings of the National Academy of Sciences, the research is believed to be the first to identify a sensitive period during early life when children’s stress response systems are particularly likely to be influenced by their caregiving environments.
“The early environment has a very strong impact on how the stress response system in the body develops,” said lead author Katie McLaughlin, a UW assistant professor of psychology.
“But even kids exposed to a very extreme negative environment who are placed into a supportive family can overcome those effects in the long term.”
The study focuses on children who spent the first years of their lives in Romanian orphanages and others who were removed from orphanages and placed in foster care. It finds that the institutionalized children had blunted stress system responses — for example, less heart rate acceleration and blood pressure increases during stressful tasks and lower production of cortisol, the primary hormone responsible for stress response.
By comparison, children who were removed from the Romanian institutions and placed with foster parents before the age of 24 months had stress system responses similar to those of children being raised by families in the community.
The results suggest that children’s early experiences can impact the development of the stress response system, and that removing them from adverse environments can mitigate such damaging effects.
“Institutionalization is an extreme form of early neglect,” McLaughlin said. “Placing kids into a supportive environment where they have sensitive, responsive parents, even if they were neglected for a period of time early in life, has a lasting, meaningful effect.”
The research is part of the Bucharest Early Intervention Project, launched in 2000 to study the effects of institutionalization on brain and behavior development among some of the thousands of Romanian children placed in orphanages during dictator Nicolae Ceausescu’s reign.
Researchers tested 138 children at about age 12 from three groups: those who had spent several years in institutions, others who were removed from institutions and placed into high-quality foster care, and children raised in families living in areas near the institutions.
The children placed into foster care were moved at between six months and 3 years of age. Those left in institutions remained there for varying amounts of time before eventually being adopted, reunited with their biological parents or placed in government foster care after policies around institutionalization changed in Romania.
During the tests, children were asked to perform potentially stressful tasks including delivering a speech before teachers, receiving social feedback from other children and playing a game that broke partway through. Researchers measured the children’s heart rate, blood pressure and several other markers including cortisol.
The children raised in institutions showed blunted responses in the sympathetic nervous system, associated with the flight or fight response, and in the HPA axis, which regulates cortisol. A dulled stress response system is linked to health problems including chronic fatigue, pain syndrome and autoimmune conditions, as well as aggression and behavioral problems.
“Together, the patterns of blunted stress reactivity among children who remained in institutional care might lead to heightened risk for multiple physical and mental health problems,” the researchers write.
McLaughlin said it’s difficult to say for certain why the children’s stress response systems were blunted. It’s possible that since they endured such extreme stress early in life, the tasks the researchers put them through were relatively benign in comparison and thus did not evoke a strong response.
More significantly, McLaughlin said, their stress response systems might have been initially hyperactive at earlier points in development, then adapted to high levels of stress hormones by reducing the number of receptors in the brain that stress hormones bind to.
“If we’d been able to measure their stress systems early in life, we would expect to find very high levels of stress hormones and stress reactivity,” she said.
Related research from the study found that children raised in the orphanages had thinner brain tissue in areas linked to impulse control and attention, and less gray matter overall.
The children involved in the study are now about 16 years old, and researchers next plan to investigate whether puberty has an impact on their stress responses. It could have a positive effect, McLaughlin said, since puberty might represent another sensitive period when stress response systems are particularly tuned to environmental inputs.
“It’s possible that the environment during that period could reverse the impacts of early adversity on the system,” she said.
Co-authors are Charles Nelson at Harvard Medical School, Nathan Fox at the University of Maryland and Charles Zeanah at Tulane University, who led the Bucharest early intervention study; Margaret Sheridan at Harvard Medical School; and Florin Tibu at the Institute for Child Development in Bucharest.
- Katie A. McLaughlin, Margaret A. Sheridan, Florin Tibu, Nathan A. Fox, Charles H. Zeanah, Charles A. Nelson. Causal effects of the early caregiving environment on development of stress response systems in children. Proceedings of the National Academy of Sciences, 2015; 201423363 DOI: 10.1073/pnas.1423363112
Source: University of Washington. “Early environment has a lasting impact on stress response systems, study shows.” ScienceDaily. ScienceDaily, 20 April 2015. <www.sciencedaily.com/releases/2015/04/150420154631.htm>.
Sussex scientist Dr Marianna Obrist, Lecturer at the Department of Informatics, has pinpointed how next-generation technologies can stimulate different areas of the hand to convey feelings of, for example, happiness, sadness, excitement or fear.
For example, short, sharp bursts of air to the area around the thumb, index finger and middle part of the palm generate excitement, whereas sad feelings are created by slow and moderate stimulation of the outer palm and the area around the ‘pinky’ finger.
The findings, which will be presented April 21 at the CHI 2015 conference in South Korea, provide “huge potential” for new innovations in human communication, according to Dr Obrist.
Dr Obrist said: “Imagine a couple that has just had a fight before going to work. While she is in a meeting she receives a gentle sensation transmitted through her bracelet on the right part of her hand moving into the middle of the palm. That sensation comforts her and indicates that her partner is not angry anymore.
“These sensations were generated in our experiment using the Ultrahaptics system.
“A similar technology could be used between parent and baby, or to enrich audio-visual communication in long-distance relationships.
“It also has huge potential for ‘one-to-many’ communication — for example, dancers at a club could raise their hands to receive haptic stimulation that enhances feelings of excitement and stability.”
Using the Ultrahaptics system — which enables creating sensations of touch through air to stimulate different parts of the hand — one group of participants in the study was asked to create patterns to describe the emotions evoked by five separate images: calm scenery with trees, white-water rafting, a graveyard, a car on fire, and a wall clock. The participants were able to manipulate the position, direction, frequency, intensity and duration of the stimulations.
A second group then selected the stimulations created by the first group that they felt best described the emotions evoked by the images. They chose the best two for each image, making a total of 10.
Finally, a third group experienced all 10 selected stimulations while viewing each image in turn and rated how well each stimulation described the emotion evoked by each image.
The third group gave significantly higher ratings to stimulations when they were presented together with the image they were intended for, proving that the emotional meaning had been successfully communicated between the first and third groups.
Now Dr Obrist has been awarded £1 million by the European Research Council for a five-year project to expand the research into taste and smell, as well as touch.
The SenseX project will aim to provide a multisensory framework for inventors and innovators to design richer technological experiences.
Dr Obrist said: “Relatively soon, we may be able to realise truly compelling and multi-faceted media experiences, such as 9-dimensional TV, or computer games that evoke emotions through taste.
“Longer term, we will be exploring how multi-sensory experiences can benefit people with sensory impairments, including those that are widely neglected in Human-Computer Interaction research, such as a taste disorder.”
Catherine Bearder, Liberal Democrat MEP for south-east England, said: “I am thrilled Dr Obrist has been awarded this EU funding for her incredible research into such a ground-breaking side of science.
“This is an example of the EU investing in those research projects it sees as having great potential to change our lives.”
Watch a 30-second video about the research at https://youtu.be/OBOxuFmsxBY.
Source: University of Sussex. “Technology can transfer human emotions to your palm through air, say scientists.” ScienceDaily. ScienceDaily, 20 April 2015. <www.sciencedaily.com/releases/2015/04/150420101012.htm>.
eSource in Clinical Investigations Meeting – Philadelphia
Dr. Jules T. Mitchel, President of Target Health Inc. will be presenting on the topic of The Impact on the Industry of eSource Methodologies. Results from ongoing clinical programs will be presented as well as the results from recent regulatory inspections of sites using eSource methodologies to support a regulatory submission. The meeting will be held May 4-5, 2015 at the Wyndham Philadelphia Historic District, Philadelphia. Let us know if you will be attending so we can connect.
The following metric tells it all: of 45,723 eCRFs, there were 1,063 manual queries that resulted in 550 database changes, with 4 forms representing 69.7% of the changes:
|Manual Queries (% of forms)||1,063 (2.3)|
|Date of Visit||316 (29.7)|
|Concomitant Medication||219 (20.6)|
|Other Medical History||116 (10.9)|
|Sitting Vital Signs||90 (8.47)|
|Changes to the database (% of Queries)||550 (1.2)|
Trifoliate Orange Blossom and the Fibonacci sequence
Why is it that the number of petals in a flower is often one of the following numbers: 3, 5, 8, 13, 21, 34 or 55? For example, the lily has three petals, buttercups have five of them, the chicory has 21 of them, the daisy has often 34 or 55 petals, etc. Furthermore, when one observes the heads of sunflowers, one notices two series of curves, one winding in one sense and one in another; the number of spirals not being the same in each direction. Why is the number of spirals in general either 21 and 34, either 34 and 55, either 55 and 89, or 89 and 144? The same for pinecones. Finally, why is the number of diagonals of a pineapple also 8 in one direction and 13 in the other? Are these numbers the product of chance? No! They all belong to the Fibonacci sequence: 1, 2, 3, 5, 8, 13, 21, 34, 55, 89, 144, etc. (where each number is obtained from the sum of the two preceding numbers).
Note the 5 petals below photographed by our friend and colleague James Farley. Here is what he had to say: I went on a trail nearby work and spotted a beautiful flower growing from a plant with rather large green thorns. I almost totally missed it, as I was done walking the trail. What I figured out is that it is apparently not native! Took me some searching to figure out what it was! I worked hard at some compositions, trying to give enough context to give a sense of what I was experiencing there.
Trifoliate Orange Blossom – Copyright JFarley Photography 2015
ON TARGET is the newsletter of Target Health Inc., a NYC-based, full-service, contract research organization (eCRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services to the pharmaceutical and device industries, including the paperless clinical trial.
For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.
Joyce Hays, Founder and Editor in Chief of On Target
Jules Mitchel, Editor
Probiotic/Prebiotic: Know the Difference
Onions are good prebiotics; they feed the probiotic organisms in our bodies
Bananas are another good prebiotic
Probiotics are living organisms, prebiotics are not.
A prebiotic is an ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well-being and health. Probiotics are microorganisms that are believed to provide health benefits when consumed. Live probiotic cultures are available in fermented dairy products and probiotic fortified foods. However, tablets, capsules, powders and sachets containing the bacteria in freeze dried form are also available.
The term probiotic is currently used to name ingested microorganism associated with beneficial effects to humans and other animals. A recent study suggested that probiotics, by introducing good bacteria into the gut, may help maintain immune system activity, which in turn helps the body react more quickly to new infections. Antibiotics seem to reduce immune system activity as a result of killing off the normal gut 1) ___. In diet, prebiotics are typically compounds that pass through the upper part of the gastrointestinal tract and stimulate the growth and/or activity of advantageous bacteria that colonize the large 2) ___ by acting as a substrate for them. Researchers now focus on the distinction between short-chain, long-chain, and full-spectrum prebiotics. Short-chain prebiotics, e.g. oligofructose, contain 2-8 links per saccharide molecule and are typically fermented more quickly in the right side of the colon providing nourishment to the bacteria in that area. Longer-chain prebiotics, e.g. inulin, contain 9-64 links per saccharide molecule, and tend to be fermented more slowly, nourishing bacteria predominantly in the left-side colon. Full-spectrum prebiotics provide the full range of molecular link-lengths from 2-64 links per molecule, and nourish bacteria throughout the 3) ___, e.g. Oligofructose-Enriched Inulin (OEI). The majority of research done on prebiotics is based on full-spectrum prebiotics, typically using OEI as the research substance.
Some bacteria found in the gut produce vitamins. For example, they produce vitamin K, folic acid, and vitamin B12. Certain foods are known to be best for the good bacteria in your microbiome and help to keep a healthy balance in your 4) ___. Yogurt is a familiar source. In a probiotic study, done to see the effects of stress on intestinal flora, rats that were fed probiotics had little occurrence of harmful bacteria adhering to their intestines compared to rats that were fed sterile water. Other studies suggest that probiotics can help ease lactose intolerance. They also may help tame gas, diarrhea, and other digestive problems. You can pay extra for special digestive yogurt brands. On the label look for: live and active cultures. It is suggested that people use unpasteurized sauerkraut, because pasteurization (used to treat most supermarket sauerkraut) kills active, good bacteria. This sour, salty food — and the similar but spicy Korean dish, kimchi — is also loaded with immune-boosting vitamins that may help ward off infection. Miso is a popular breakfast food in 5) ___, this fermented soybean paste can get your digestive system moving. Probiotic-filled miso reportedly has more than 160 bacteria strains. It’s often used to make a salty soup that’s low in calories and high in B vitamins and protective antioxidants.
While cheese might be good for your digestion, not all probiotics can survive the journey through your stomach and intestines. Research finds that certain strains in some fermented soft cheeses, like Gouda, Port Salut, Muenster, Brie are hardy enough to make it. Cheese also may act as a carrier for probiotics, which may boost the 6) ___ system. According to legend, kefir, a fermented milk drink made with kefir “grains” (a yeast/bacterial fermentation starter), dates back to the shepherds of Eurasia’s Caucasus Mountains. These shepherds discovered that the milk they carried tended to ferment into a bubbly beverage. Thick, creamy, and tangy like yogurt, kefir has its own strains of probiotic bacteria, plus a few helpful yeast varieties.
San Francisco’s famous 7) ___ bread contains a probiotic that may help digestion. Be sure to try delicious sourdough bread, rolls, toast instead of plain white.
One of the easiest ways to get probiotics into your diet is by adding acidophilus milk, that’s been fermented with bacteria. Sometimes it’s labeled sweet acidophilus milk. Buttermilk, cultured with lactic acid bacteria is also rich in probiotics. Choose the right pickles for probiotics, naturally fermented kinds, where vinegar wasn’t used in the pickling process. A sea salt and water solution feeds the growth of good bacteria and may give sour pickles some digestive benefits. Tempeh is made from a base of fermented 8) ___. This Indonesian patty has a type of natural antibiotic that fights certain harmful bacteria. Tempeh is also high in protein. People often describe its flavor as smoky, nutty, and similar to a mushroom. You can marinate tempeh and use it in meals in place of meat.
Aside from being found in foods, probiotics come in supplements in capsule, tablet, powder, and liquid forms. Although they don’t provide the extra 9) ___that foods can offer, they’re convenient and offer a large number of the healthy bacteria. Some doctors are not well informed about probiotics, however medical schools are now including the subject of probiotics in their curriculums. While probiotic-foods have live bacteria, prebiotic foods feed the good bacteria already living in your gut. You can find prebiotics in items such as asparagus, Jerusalem artichokes, bananas, oatmeal, red wine, honey, maple syrup, and legumes. Try 10) ___ foods on their own or with probiotic foods to perhaps give the probiotics a boost.
ANSWERS: 1) bacteria; 2) bowel; 3) colon; 4) gut; 5) Japan; 6) immune; 7) sourdough; 8) soybeans; 9) nutrition; 10) prebiotic
A field of artichokes, which are prebiotics
Artichoke contains the bioactive agents apigenin, luteolin and inulin. C. scolymus also seems to have a bifidogenic effect on beneficial gut bacteria. Its effect in arresting pathogenic bacteria may be attributed to the notable presence of phenolic compounds. Both are higher in the baby anzio artichoke (Cyrnara scolymus). Artichoke leaf extract has proved helpful for patients with functional dyspepsia, and may ameliorate symptoms of irritable bowel syndrome. The inulin cannot be broken down by the human digestive system, but is metabolized by bacteria in the colon. Sources: sciencedaily.com; webmd.com; nih.gov; Wikipedia
Shakespeare, Psychology and Software
The Chandos portrait, artist and authenticity unconfirmed. National
Portrait Gallery, London. Baptized 26 April 1564 (birth date unknown)
Shakespeare was an English poet, playwright, actor, and widely regarded as the greatest writer in the English language and the world’s pre-eminent dramatist. He is often called England’s national poet and the Bard of Avon. His extant works, including some collaborations, consist of about 38 plays, 154 sonnets, two long narrative poems, and a few other verses, of which the authorship of some is uncertain. His plays have been translated into every major living language and are performed more often than those of any other playwright.
Shakespeare was born and brought up in Stratford-upon-Avon. While his birth date is not known, it is known that he was baptized on 26 April 1564. At the age of 18, he married Anne Hathaway, with whom he had three children: Susanna, and twins Hamnet and Judith. Between 1585 and 1592, Shakespeare began a successful career in London as an actor, writer, and part-owner of a playing company called the Lord Chamberlain’s Men, later known as the King’s Men. He appears to have retired to Stratford around 1613 at age 49, where he died three years later on 23 April 1616. Few records of Shakespeare’s private life survive, and there has been considerable speculation about such matters as his physical appearance, sexuality, religious beliefs, and whether the works attributed to him were written by others. Shakespeare produced most of his known work between 1589 and 1613. His early plays were mainly comedies and histories and these works remain regarded as some of the best work produced in these genres. He then wrote mainly tragedies until about 1608, including Hamlet, Othello, King Lear, and Macbeth, considered some of the finest works in the English language. In his last phase, he wrote tragicomedies, also known as romances, and collaborated with other playwrights.
Many of his plays were published in editions of varying quality and accuracy during his lifetime. In 1623, John Heminges and Henry Condell, two friends and fellow actors of Shakespeare, published the First Folio, a collected edition of his dramatic works that included all but two of the plays now recognized as Shakespeare’s. It was prefaced with a poem by Ben Jonson, in which Shakespeare is hailed, presciently, as not of an age, but for all time. In the 20th and 21st century, his work has been repeatedly adopted and rediscovered by new movements in scholarship and performance. His plays remain highly popular today and are constantly studied, performed, and reinterpreted in diverse cultural and political contexts throughout the world. The Shakespeare authorship question is the argument that someone other than William Shakespeare of Stratford-upon-Avon wrote the works attributed to him. Anti-Stratfordians – a collective term for adherents of the various alternative-authorship theories – say that Shakespeare of Stratford was a front to shield the identity of the real author or authors, who for some reason did not want or could not accept public credit. Although the idea has attracted much public interest, all but a few Shakespeare scholars and literary historians consider it a fringe belief and for the most part acknowledge it only to rebut or disparage the claims. Shakespeare’s authorship was first questioned in the middle of the 19th century, when adulation of Shakespeare as the greatest writer of all time had become widespread. Shakespeare’s biography, particularly his humble origins and obscure life, seemed incompatible with his poetic eminence and his reputation for genius, arousing suspicion that Shakespeare might not have written the works attributed to him. The controversy has since spawned a vast body of literature, and more than 80 authorship candidates have been proposed, the most popular being Sir Francis Bacon; Edward de Vere, 17th Earl of Oxford; Christopher Marlowe, William Stanley, 6th Earl of Derby and Lewis Theobald. Supporters of alternative candidates argue William Shakespeare lacked the education, aristocratic sensibility, or familiarity with the royal court that they say is apparent in the works. Those Shakespeare scholars who have responded to such claims hold that biographical interpretations of literature are unreliable in attributing authorship, and that the convergence of documentary evidence used to support Shakespeare’s authorship – title pages, testimony by other contemporary poets and historians, and official records – is the same used for all other authorial attributions of his era. Keep in mind, that no such direct evidence exists for any other candidate, and Shakespeare’s authorship was not questioned during his lifetime or for centuries after his death. Finally, 21st Century technology appears to have found a methodology for confirming the great bard’s accomplishments of creative genius.
Shakespeare is such a towering literary figure that any new insight into the man, or his work, tends to generate a jolt of excitement in academic and non-academic communities of Shakespeare aficionados. Applying psychological theory and text-analyzing software, researchers at the University of Texas at Austin have discovered a unique psychological profile that characterizes Shakespeare’s established works, and this profile strongly identifies Shakespeare as an author of the long-contested play Double Falsehood. The findings are published in Psychological Science, a journal of the Association for Psychological Science. Research in psychology has shown that some of the core features of who a person is at their deepest level can be revealed based on how they use language. With our new study, we show that you can actually take a lot of this information and put it all together at once to understand an author like Shakespeare rather deeply, says researcher Ryan Boyd of the University of Texas at Austin. The study, conducted in collaboration with James Pennebaker, also at UT-Austin, goes beyond examining authorship from the standpoint of word counts and linguistic regularities, providing a deeper exploration of an author’s psychological profile. This research shows that it is indeed possible to start modeling peoples’ mental worlds in much more complete ways. We don’t need a time machine and a survey form to figure out what type of person Shakespeare was — we can determine that very accurately just based on how he wrote using methods that are objective and easy to do, Boyd explains.
Double Falsehood was published in 1728 by Lewis Theobald, who claimed to have based the play on three original Shakespeare manuscripts. The manuscripts have since been lost, presumably destroyed by a library fire, and authorship of the play has been hotly contested ever since. Some scholars believe that Shakespeare was the true author of Double Falsehood, while others believe that the play was actually an original work by Theobald himself that he tried to pass off as an adaptation. Boyd and Pennebaker realized that using psychological theory to inform analysis of the playwrights’ respective works may shed light on the authorship question. They examined 33 plays by Shakespeare, 12 by Theobald, and 9 by John Fletcher, a colleague (and sometime collaborator) of Shakespeare. The texts were stripped of extraneous information (such as publication information) and were processed using software that evaluated the works for specific features determined prospectively by the researchers. For example, the researchers’ software examined the playwrights’ use of function words (e.g., pronouns, articles, prepositions) and words belonging to various content categories (e.g., emotions, family, sensory perception, religion). They had the software identify themes present in each of the works to generate an overarching thematic signature for each author. They also examined the works to determine how categorical the writing was. Categorical writing tends to be heavy on nouns, articles, and prepositions, and it indicates an analytic or formal way of thinking. Research has shown that people who rate high on categorical thinking tend to be emotionally distant, applying problem-solving approaches to everyday situations. People who rate low on categorical thinking, on the other hand, tend to live in the moment and are more focused on social matters.
By aggregating dozens of psychological features of each playwright, Boyd and Pennebaker were able to create a psychological signature for each individual. They were then able to look at the psychological signature of Double Falsehood to determine who the author was most likely to be. Looking at the plays as whole units, the results were clear: Every measure but one identified Shakespeare as the likely author of Double Falsehood. Theobald was identified as the best match only when it came to his use of content words, and even then only by one of the three statistical approaches the researchers used. When Boyd and Pennebaker broke the play down into acts and analyzed the texts across acts, they found a more nuanced picture. For the first three acts, the analyses continued to identify Shakespeare as the likely author; for the fourth and fifth acts, the measures varied between Shakespeare and Fletcher. Again, Theobald’s influence on the text appeared to be very minor. Honestly, I was surprised to see such a strong signal for Shakespeare showing through in the results, says Boyd. Going into the research without any real background knowledge, I had just kind of assumed that it was going to be a pretty cut and dry case of a fake Shakespeare play, which would have been really interesting in and of itself. By using measures that tapped into the author’s psychological profile, Boyd and Pennebaker were able to see that the author of Double Falsehood was likely sociable and fairly well educated — findings that don’t jibe with accounts of Theobald as well educated but also rigid and abrasive. Together, these findings clearly show that exploring the psychological dimensions of a literary work can offer even deeper insight in the process of textual analysis.
I’ve always held huge admiration for scholars who grapple with literature — there is a great deal of detective work that goes into figuring out who the authors really are ?deep down,’ their motivations, their lives, and how these factors are embedded within their work, says Boyd. We demonstrate with our current work that an incredible amount of this information can be extracted automatically from language.
Source: Association for Psychological Science: R. L. Boyd, J. W. Pennebaker. Did Shakespeare Write Double Falsehood? Identifying Individuals by Creating Psychological Signatures with Text Analysis. Psychological Science, 2015; Wikipedia
Genetic Link Discovered for Rare Intestinal Cancer
About 30,000 Americans have small intestinal carcinoid tumors. Like most cancers, early treatment greatly increases survival rates and quality of life. Small intestinal carcinoid tumors are rare and most grow very slowly. Most of them occur in the small intestine, rectum, and appendix. Sometimes more than one tumor will form. Small intestinal carcinoid tumors form from a certain type of neuroendocrine cell (a type of cell that is like a nerve cell and a hormone -making cell). These cells are scattered throughout the chest and abdomen but most are found in the GI tract. Neuroendocrine cells make hormones that help control digestive juices and the muscles used in moving food through the stomach and intestines. A small intestinal carcinoid tumor may also make hormones and release them into the body.
According to an article published online in Gastroenterology (9 April 2015), heredity accounts for up to 35% of small intestinal carcinoid tumors. Because the disease has long been considered randomly occurring rather than inherited, people with a family history were not typically screened. To answer the question, the study examined families with a history of the disease. The study, conducted at the NIH Clinical Center, the study screened 181 people from 33 families, each with at least two cases of small intestinal carcinoid. Genetic linkage analysis revealed a target DNA region shared by all affected members of a particularly large family. Genome sequencing narrowed that finding to a gene defect passed from one generation to the next, suggesting that the gene is an inherited risk factor for the disease. Disease was also discovered in 23 people who had not yet developed symptoms, and tumors were successfully removed in 21 of those people.
Molecule Hijacks Enzyme to Boost Alcohol Metabolism
After alcohol is consumed, it is first metabolized into acetaldehyde, a toxic chemical that can cause DNA damage and cancer. In the liver, aldehyde dehydrogenase 2 (ALDH2) is the main enzyme responsible for breaking down acetaldehyde into acetate, a nontoxic metabolite. It also removes other toxic aldehydes that can accumulate in the body. An estimated 560 million people in East Asia, and many people of East Asian descent, carry a genetic mutation that produces an inactive form of ALDH2. When individuals with the ALDH2 mutation drink alcohol, acetaldehyde accumulates in the body, resulting in facial flushing, nausea, and rapid heartbeat. People with the ALDH2 mutation are also at increased risk for cancers of the mouth, esophagus, and other areas of the upper aerodigestive tract.
According to an article published online in the Proceedings of the National Academy of Sciences (10 March 2015), an experimental compound empowers an enzyme to help process acetaldehyde, and this finding may lead to new treatments to help people with impaired ability to metabolize acetaldehyde and other toxic substances. These small molecules called aldehyde dehydrogenase activators, or Aldas, have been found to increase the activity of the ALDH2 enzyme in previous studies.
In the current study, the authors tested a new compound, Alda-89, which they found could provide another aldehyde dehydrogenase enzyme – ALDH3A1 — with accelerated acetaldehyde-metabolizing powers that it ordinarily does not possess. The authors targeted the ALDH3A1 enzyme because it metabolizes acetaldehyde poorly and is highly expressed in the upper airway, stomach and gut, all tissues that are prone to cancer development in people who drink alcohol in excess. According to the authors, by recruiting ALDH3A1 to metabolize acetaldehyde, it may be possible to accelerate the elimination of acetaldehyde from tissues that are more vulnerable to its carcinogenic effects. Results from the study showed that Alda-89 increased acetaldehyde metabolism both in normal mice and in mice carrying the ALDH2 mutation found in the East Asian population. The authors also showed that, in test tube analyses, acetaldehyde removal was faster when they combined Alda-89 with Alda-1, a compound previously shown to activate ALDH2, compared with activating each ALDH alone. Studies also showed that mice treated with the combination of Alda-89 and Alda-1 exhibit accelerated recovery from alcohol intoxication.
FDA Approves First Generic Copaxone to Treat Multiple Sclerosis
NOTE THAT SANDOZ, WHICH GOT THIS APPROVAL, IS A DIVISION OF NOVARTIS
MS is a chronic, inflammatory, autoimmune disease of the central nervous system that disrupts communication between the brain and other parts of the body. It is among the most common causes of neurological disability in young adults and occurs more frequently in women than men. For most people with MS, episodes of worsening function (relapses) are initially followed by recovery periods (remissions). Over time, recovery periods may be incomplete, leading to progressive decline in function and increased disability. MS patients often experience muscle weakness and difficulty with coordination and balance. Most people experience their first symptoms of MS between the ages of 20 and 40.
The FDA has approved the first generic version of Copaxone (glatiramer acetate injection), used to treat patients with relapsing forms of multiple sclerosis (MS). For the approval, FDA scientists established a thorough scientific approach for demonstrating active ingredient sameness that takes into consideration the complexity of glatiramer acetate. This approach was documented in the 43 page Citizen Petition Denial Letter From CDER to Teva Pharmaceuticals which is worthwhile reading.
In the clinical trials for Copaxone, the most common adverse reactions reported by those taking Copaxone were skin problems at the injection site (redness, pain, swelling and itching), flushing (vasodilation), rash, shortness of breath and chest pain.