July 30, 2015
NASA/Goddard Space Flight Center
A new study has concluded California accumulated a debt of about 20 inches of precipitation between 2012 and 2015 — the average amount expected to fall in the state in a single year. The deficit was driven primarily by a lack of air currents moving inland from the Pacific Ocean that are rich in water vapor.
A new NASA study has concluded California accumulated a debt of about 20 inches of precipitation between 2012 and 2015 — the average amount expected to fall in the state in a single year. The deficit was driven primarily by a lack of air currents moving inland from the Pacific Ocean that are rich in water vapor.
In an average year, 20 to 50 percent of California’s precipitation comes from relatively few, but extreme events called atmospheric rivers that move from over the Pacific Ocean to the California coast.
“When they say that an atmospheric river makes landfall, it’s almost like a hurricane, without the winds. They cause extreme precipitation,” said study lead author Andrey Savtchenko at NASA’s Goddard Space Flight Center in Greenbelt, Maryland.
Savtchenko and his colleagues examined data from 17 years of satellite observations and 36 years of combined observations and model data to understand how precipitation has varied in California since 1979. The results were published Thursday in Journal of Geophysical Research — Atmospheres, a journal of the American Geophysical Union.
The state as a whole can expect an average of about 20 inches of precipitation each year, with regional differences. But, the total amount can vary as much as 30 percent from year to year, according to the study.
In non-drought periods, wet years often alternate with dry years to balance out in the short term. However, from 2012 to 2014, California accumulated a deficit of almost 13 inches, and the 2014-2015 wet season increased the debt another seven inches, for a total 20 inches accumulated deficit during the course of three dry years.
The majority of that precipitation loss is attributed to a high-pressure system in the atmosphere over the eastern Pacific Ocean that has interfered with the formation of atmospheric rivers since 2011.
Atmospheric rivers occur all over the world. They are narrow, concentrated tendrils of water vapor that travel through the atmosphere similar to, and sometimes with, the winds of a jet stream. Like a jet stream, they typically travel from west to east. The ones destined for California originate over the tropical Pacific, where warm ocean water evaporates a lot of moisture into the air. The moisture-rich atmospheric rivers, informally known as the Pineapple Express, then break northward toward North America.
Earlier this year, a NASA research aircraft participated in the CalWater 2015 field campaign to improve understanding of when and how atmospheric rivers reach California.
Some of the water vapor rains out over the ocean, but the show really begins when an atmospheric river reaches land. Two reached California around Dec. 1 and 10, 2014, and brought more than three inches of rain, according to NASA’s Tropical Rainfall Measuring Mission (TRMM)’s multi-satellite dataset. The inland terrain, particularly mountains, force the moist air to higher altitudes where lower pressure causes it to expand and cool. The cooler air condenses the concentrated pool of water vapor into torrential rains, or snowfall as happens over the Sierra Nevada Mountains, where water is stored in the snowpack until the spring melt just before the growing season.
The current drought isn’t the first for California. Savtchenko and his colleagues recreated a climate record for 1979 to the present using the Modern-Era Retrospective Analysis for Research and Applications, or MERRA. Their efforts show that a 27.5 inch deficit of rain and snow occurred in the state between 1986 and 1994.
“Drought has happened here before. It will happen again, and some research groups have presented evidence it will happen more frequently as the planet warms,” Savtchenko said. “But, even if the climate doesn’t change, are our demands for fresh water sustainable?”
The current drought has been notably severe because, since the late 1980s, California’s population, industry and agriculture have experienced tremendous growth, with a correlating growth in their demand for water. Human consumption has depleted California’s reservoirs and groundwater reserves, as shown by data from NASA’s Gravity Recovery and Climate Experiment (GRACE) mission, leading to mandatory water rationing.
“The history of the American West is written in great decade-long droughts followed by multi-year wet periods,” said climatologist Bill Patzert at NASA’s Jet Propulsion Laboratory in Pasadena, California. He was not involved in the research. “Savtchenko and his team have shown how variable California rainfall is.”
According to Patzert, this study added nuance to how scientists may interpret the atmospheric conditions that cause atmospheric rivers and an El Niño’s capacity to bust the drought. Since March, rising sea surface temperatures in the central equatorial Pacific have indicated the formation of El Niño conditions. El Niño conditions are often associated with higher rainfall to the western United States, but it’s not guaranteed.
Savtchenko and his colleagues show that El Niño contributes only six percent to California’s precipitation variability and is one factor among other, more random effects that influence how much rainfall the state receives. While it’s more likely El Niño increases precipitation in California, it’s still possible it will have no, or even a drying, effect.
A strong El Niño that lasts through the rainy months, from November to March, is more likely to increase the amount of rain that reaches California, and Savtchenko noted the current El Niño is quickly strengthening.
The National Oceanic and Atmospheric Administration (NOAA), which monitors El Niño events, ranks it as the third strongest in the past 65 years for May and June. Still, it will likely take several years of higher than normal rain and snowfall to recover from the current drought.
“If this El Niño holds through winter, California’s chances to recoup some of the precipitation increase. Unfortunately, so do the chances of floods and landslides,” Savtchenko said. “Most likely the effects would be felt in late 2015-2016.”
- Andrey K. Savtchenko, George Huffman, Bruce Vollmer. Assessment of Precipitation Anomalies in California Using TRMM and MERRA Data.Journal of Geophysical Research: Atmospheres, 2015; DOI:10.1002/2015JD023573
Source: NASA/Goddard Space Flight Center. “California ‘rain debt’ equal to average full year of precipitation.” ScienceDaily. ScienceDaily, 30 July 2015. <www.sciencedaily.com/releases/2015/07/150730220033.htm>.
July 29, 2015
North Carolina State University
An analysis of data on stomach acidity and diet in birds and mammals suggests that high levels of stomach acidity developed not to help animals break down food, but to defend animals against food poisoning. The work raises interesting questions about the evolution of stomach acidity in humans, and how modern life may be affecting both our stomach acidity and the microbial communities that live in our guts.
An analysis of data on stomach acidity and diet in birds and mammals suggests that high levels of stomach acidity developed not to help animals break down food, but to defend animals against food poisoning. The work raises interesting questions about the evolution of stomach acidity in humans, and how modern life may be affecting both our stomach acidity and the microbial communities that live in our guts.
“We started this project because we wanted to better understand the relationship between stomach acidity, diet and the microbes that live in the guts of birds and mammals,” says DeAnna Beasley, a postdoctoral researcher at North Carolina State University and corresponding author of a paper on the work. “Our idea was that this could offer some context for looking at the role of the human stomach in influencing gut microbes, and what that may mean for human health.”
The research team — including scientists from Washington University and the University of Colorado, Boulder — examined all of the existing literature on stomach acidity in birds and mammals, and found data on 68 species. They then collected data on the natural feeding habits of each species. The researchers then ran an analysis to see how feeding behavior was related to stomach acidity.
The researchers found that scavengers, or species that eat food at high risk of microbial contamination, have more acidic stomachs. This acidity allows the stomach to act as a filter, effectively controlling which microbes can pass through the stomach to the gut.
“The finding confirms our hypothesis, but you have to get that confirmation before moving forward,” Beasley says. “The next step will be for scientists to examine the microbial ecosystems in the guts of these animals to see how these ecosystems have evolved. Do animals with high stomach acidity have smaller or less diverse populations of gut microbes? Or do they simply host microbes that can survive in acidic environments?”
One surprise was that, while the researchers classified humans as omnivores, human stomachs have the high acidity levels normally associated with scavengers. Meanwhile, the literature shows that medical treatments — from surgery to antacids — can significantly alter the acidity in a human stomach.
“This raises significant questions about how humans have evolved, our species’ relationship with food over time, and how modern changes in diet and medicine are affecting our stomachs, our gut microbes and — ultimately — our health,” Beasley says. “Those are questions the research community is already exploring, and the answers should be interesting.”
- DeAnna E. Beasley, Amanda M. Koltz, Joanna E. Lambert, Noah Fierer, Rob R. Dunn. The Evolution of Stomach Acidity and Its Relevance to the Human Microbiome. PLOS ONE, 2015; 10 (7): e0134116 DOI:10.1371/journal.pone.0134116
Source: North Carolina State University. “Evolutionary link between diet, stomach acidity.” ScienceDaily. ScienceDaily, 29 July 2015. <www.sciencedaily.com/releases/2015/07/150729155141.htm>.
Early evidence suggests hybrid cochlear implants may benefit millions with common form of hearing loss
Multicenter study shows that device leads to major improvements in hearing, speech recognition
July 28, 2015
NYU Langone Medical Center / New York University School of Medicine
People with a common form of hearing loss not helped by hearing aids achieved significant and sometimes profound improvements in their hearing and understanding of speech with hybrid cochlear implant devices, according to a new multicenter study.
People with a common form of hearing loss not helped by hearing aids achieved significant and sometimes profound improvements in their hearing and understanding of speech with hybrid cochlear implant devices, according to a new multicenter study led by specialists at NYU Langone Medical Center.
In the study, described online ahead of print in the journal The LaryngoscopeJuly 7, researchers at 10 medical centers and private clinics in the United States implanted hybrid cochlear implants into one ear of 50 men and women. All study volunteers had badly damaged high-frequency, inner-ear hair cells, which prevented them from understanding speech, especially in the presence of background noise. All still had sufficient low-frequency hearing, which allowed them to tell apart some sounds and forestalled any use of a regular cochlear implant.
A year after receiving the device, 45 study participants showed overall improvement in their hearing and speech recognition, and no one’s hearing and speech recognition got worse.
“Our study offers early evidence that potentially millions more people with high-frequency hearing loss, who cannot benefit from a hearing aid, could instead possibly benefit from a hybrid cochlear implant,” says lead study investigator J. Thomas Roland, MD, the Mendik Foundation Chairman of the Department of Otolaryngology-Head and Neck Surgery at NYU Langone. Roland, who also serves as co-director of NYU Langone’s cochlear implant program, has nearly 30 years of experience in research and caring for people with the devices, which were first approved for use in the United States in 1984, and he has installed many hybrid implants, which were approved for adults by the US Food and Drug Administration in 2014.
The hybrid implant differs from the traditional device in that it has a shorter electrode (less than 2 centimeters long) that does not have to be inserted as deeply into the spiral-shaped sensory structure (the cochlea) in the inner ear. When placed correctly, the technique preserves more residual, natural, low-frequency hearing and augments high-frequency hearing with electrical stimulation.
The National Institute on Deafness and Other Communication Disorders estimates that some 26 million American adults between the ages of 20 and 69 suffer from some loss of high-frequency hearing, which makes speech recognition especially difficult.
According to Roland, the loss of high-frequency hearing had left all study participants “in a difficult spot.” Many were failing at work and in social environments because of their inability to hear and understand speech.
Roland says hearing aids were not an option for them because the sound-amplifying tools cannot sufficiently raise high-frequency sounds to improve understanding of speech, especially when there is any kind of background noise.
Roland also says the study participants had “too much residual hearing to lose,” so having traditional cochlear implants — one in each ear to replace both high- and low-frequency hearing — was not an optimal option (although five study participants did eventually choose this route.)
Among the study participants, 15 with total loss of high-frequency hearing and moderate loss of low-frequency hearing saw improvements in standard tests of their ability to understand set phrases and sentences read back to them. Their scores for correctly identifying spoken words and phrases rose from a baseline average of 21 percent before implantation to 67 percent a year after implantation and activation of their device.
For 14 other study participants with severe or total loss of their residual low-frequency hearing, test scores for correctly identifying certain spoken words and phrases improved from 12 percent to 54 percent, and from 14 percent to 35 percent, respectively. Study participants’ hearing was assessed every few months.
Researchers’ report that adverse events with the device, which typically costs about $30,000 and involves an operation lasting less than an hour to install, were relatively rare and consisted primarily of mild postoperative dizziness that quickly went away, and ringing sounds in the ear that also subsided after device activation.
The above post is reprinted from materials provided by NYU Langone Medical Center / New York University School of Medicine. Note: Materials may be edited for content and length.
- J. Thomas Roland, Bruce J. Gantz, Susan B. Waltzman, Aaron J. Parkinson. United States multicenter clinical trial of the cochlear nucleus hybrid implant system. The Laryngoscope, 2015; DOI:10.1002/lary.25451
Source: NYU Langone Medical Center / New York University School of Medicine. “Early evidence suggests hybrid cochlear implants may benefit millions with common form of hearing loss: Multicenter study shows that device leads to major improvements in hearing, speech recognition.” ScienceDaily. ScienceDaily, 28 July 2015. <www.sciencedaily.com/releases/2015/07/150728120202.htm>.
July 26, 2015
University of Exeter
Sleeping not only protects memories from being forgotten, it also makes them easier to access, according to new research. A new study tracked memories for novel, made-up words learnt either prior to a night’s sleep, or an equivalent period of wakefulness. Subjects were asked to recall words immediately after exposure, and then again after the period of sleep or wakefulness.
Sleeping not only protects memories from being forgotten, it also makes them easier to access, according to new research from the University of Exeter and the Basque Centre for Cognition, Brain and Language. The findings suggest that after sleep we are more likely to recall facts which we could not remember while still awake.
In two situations where subjects forgot information over the course of 12 hours of wakefulness, a night’s sleep was shown to promote access to memory traces that had initially been too weak to be retrieved.
The research, published in the journal Cortex, tracked memories for novel, made-up words learnt either prior to a night’s sleep, or an equivalent period of wakefulness. Subjects were asked to recall words immediately after exposure, and then again after the period of sleep or wakefulness.
The key distinction was between those word memories which participants could remember at both the immediate test and the 12-hour retest, and those not remembered at test, but eventually remembered at retest.
The researcher found that, compared to daytime wakefulness, sleep helped rescue unrecalled memories more than it prevented memory loss.
Nicolas Dumay of the University of Exeter explains: “Sleep almost doubles our chances of remembering previously unrecalled material. The post-sleep boost in memory accessibility may indicate that some memories are sharpened overnight. This supports the notion that, while asleep, we actively rehearse information flagged as important. More research is needed into the functional significance of this rehearsal and whether, for instance, it allows memories to be accessible in a wider range of contexts, hence making them more useful.”
The beneficial impact of sleep on memory is well established, and the act of sleeping is known to help us remember the things that we did, or heard, the previous day. The idea that memories could also be sharpened and made more vivid and accessible overnight, however, is yet to be fully explored.
Dr Dumay believes the memory boost comes from the hippocampus, an inner structure of the temporal lobe, unzipping recently encoded episodes and replaying them to regions of the brain originally involved in their capture — this would lead the subject to effectively re-experience the major events of the day.
Nicolas Dumay is an experimental psychologist at the University of Exeter and an honorary Staff Scientist at the Basque Centre for Cognition, Brain and Language (BCBL), in Spain.
‘Sleep not just protects memories against forgetting, it also makes them more accessible’ is published in the journal Cortex.
Source: University of Exeter. “Sleep makes our memories more accessible, study shows.” ScienceDaily. ScienceDaily, 26 July 2015. <www.sciencedaily.com/releases/2015/07/150726200036.htm>.
Target Health Inc. has been developing software products for pharmaceutical industry since 1997. Our approach is to provide fully integrated software to allow for real-time management of clinical trials at one website.
We just updated Target Document to allow for easier copying and moving documents on the web, and now have a patient profile incorporated into our SAE module that also generates both Form FDA 3500A and CIOMS1 and 2 forms within Target e*CRF®. New EDC projects include Autism, ADHD, Epilepsy and wound healing. An FDA approval of a program that used Target e*CTR® (eClinical Trial Record), our eSource solution fully integrated with Target e*CRF, is expected shortly.
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Field of Sunflowers at Sunset
This picture was taken by our friend and colleague James Farley, photographer extraordinaire and contributor to On Target.
©James Farley 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.
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Link between the Brain and Immune System Found
Maps of the lymphatic system: old (left) and updated to reflect UVA’s discovery. Credit: University of Virginia Health System
T-cells present in vessels separate from arteries and veins confirm that the brain does in fact have a lymphatic system linking it directly the peripheral immune system. In a stunning discovery that overturns decades of textbook teaching, researchers at the University of Virginia School of Medicine have determined that the brain is directly connected to the immune system by vessels previously thought not to exist. That such vessels could have escaped detection when the lymphatic system has been so thoroughly mapped throughout the body is surprising on its own, but the true significance of the discovery lies in the effects it could have on the study and treatment of neurological diseases ranging from autism to Alzheimer’s disease to multiple sclerosis.
When the ancient Egyptians prepared a mummy they would scoop out the brain through the 1) ___ and throw it away. While other organs were preserved and entombed, the brain was considered separately from the rest of the body, and unnecessary for life or afterlife. Eventually, of course, healers and scientists realized that the three pounds of entangled neurons beneath our crania serve some rather critical functions. Yet even now the brain is often viewed as somewhat divorced from the rest of the body; a neurobiological Oz crewing our bodies and minds from behind the scenes with unique biology and unique pathologies. Perhaps the most commonly cited division between body and brain concerns the immune system. When exposed to foreign bacteria, viruses, tumors, and transplant tissue, the body stirs up a torrent of immune activity: white blood cells devour invading pathogens and burst compromised cells; antibodies tag outsiders for destruction. Except, that is, in the 2) ___. Thought to be too vulnerable to host an onslaught of angry defensive cells, the brain was assumed to be protected from this immune cascade. However research published this month reported a previously unknown line of communication between our brains and immune systems, adding to a fast-growing body of research suggesting that the brain and body are more connected than previously thought. The new work could have important implications for understanding and treating disorders of the brain.
As early as 1921 scientists recognized that the brain is different, immunologically speaking. Outside tissue grafted into most parts of the body often results in immunologic attack; tissue grafted into the central nervous system on the other hand sparks a far less hostile response. Thanks in part to the blood-brain 3) ___ – tightly packed cells lining the brain’s vessels that let nutrients slip by, but, for the most part, keep out unwanted invaders like bacteria and viruses – the brain was long considered immunologically privileged, meaning it can tolerate the introduction of outside pathogens and tissues. The central nervous system was seen as existing separately from the peripheral immune system, left to wield its own less aggressive immune defenses. The brain’s privilege was also considered to be due to its lack of lymphatic drainage. The lymphatic system is our body’s third and perhaps least considered set of vessels, the others being arteries and veins. 4) ___ vessels return intracellular fluid to the bloodstream while lymph nodes – stationed periodically along the vessel network – serve has storehouses for immune cells.
In most parts of the body, antigens – molecules on pathogens or foreign tissue that alert our immune system to potential threats – are presented to white blood cells in our the lymph nodes causing an immune response. But it was assumed that this doesn’t occur in the brain given its lack of a lymphatic network, which is why the new findings represent a dogmatic shift in understanding how the brain interacts with the 5) ___ system. Working primarily with mice, lead author and University of Virginia neuroscience professor Dr. Jonathan Kipnis and his group identified a previously undetected network of lymphatic vessels in the meninges ? the membranes that surround the brain and 6) ___ cord – that shuttle fluid and immune cells from the cerebrospinal fluid to a group of lymph nodes in the neck, the deep cervical lymph nodes. Kipnis and colleagues had previously shown that a type of white blood cell called T-cells in the meninges are associated with significant influences on cognition and hence were curious about the role of meningeal immunity on brain function. By mounting whole mouse meninges and using neuroimaging the team noticed that T-cells were present in vessels separate from arteries and 7) ___, confirming that the brain does in fact have a lymphatic system linking it directly to the peripheral immune system. We stumbled upon these vessels completely by serendipity, Kipnis commented. The newly discovered vessels – which were also identified in human samples – could explain a variety of pathophysiological conundrums, namely how the immune system contributes to neurological and psychiatric disease. It’s early to speculate, says Kipnis, but I think that alteration in these vessels may affect disease progression in those neurological disorders with a prominent immune component, such as multiple sclerosis, autism and Alzheimer’s disease. For example MS, at least in some cases, is thought to result from autoimmune activity in response to an infection in the central 8) ___ system and cerebrospinal fluid. Perhaps antigens from the infectious culprit find their way to the cervical lymph nodes via the meningeal lymphatic vessels, inciting the immune response that causes MS symptoms. Alzheimer’s is thought to be caused by the build-up and transmission of a protein called amyloid in the brain. It could be that the amyloid isn’t being cleared properly via these lymphatic vessels, and that somehow improving their patency might help rid the brain of the pathologic protein.
Other recent work by Kipnis and colleagues found that an injury to the central nervous system results in a strong activation of 9) ___ in the deep cervical lymph nodes. Kipnis suspects that some compound may be released from the injured CNS that is transmitted to the deep cervical lymph nodes through lymphatic vessels where it activates the immune system. A similar scenario may be at work in other neurological conditions; that too much or too little drainage from the central nervous system to the immune system might contribute to brain disease. If so, Kipnis feels targeting the vessels with drugs, genetic manipulation and surgery are therapeutic approaches worth pursuing. Dr. Josep Dalmau, a neurology professor at the University of Pennsylvania not involved with the new study, agrees that the new findings could help to explain the initiation, maintenance, and perhaps worsening of autoimmune disorders that affect the brain; and also that in light of the new findings the textbooks might need some revising It has become increasingly clear that the [central nervous system] is immune different rather than immune privileged, he says. It’s been clear for decades that there is some kind of relationship between the brain and the immune system. Abnormal immune activity was reported in 10) ___ in the 1930s, and numerous mental and neurologic illnesses are known or thought to have an immune component. However because the Kipnis’ group identified a tangible, anatomical structure facilitating this relationship, suggests that the brain and body are intimately intertwined, and that the brain is not the citadel it was once thought to be. Sources: ScienceDaily.com; Scientific American by Bret Stetka, who is an Editorial Director at Medscape (a subsidiary of WebMD) and a freelance health, science and food writer. He received his MD in 2005 from the University of Virginia and has written for WIRED, Slate and Popular Mechanics about brains, genomics and sometimes both.
ANSWERS: 1) nostrils; 2) brain; 3) barrier; 4) Lymphatic; 5) immune; 6) spinal; 7) veins; 8) nervous; 9) T-cells; 10) schizophrenia
Religio Medici (The Religion of a Doctor)
Frontispiece of the 1642 pirated edition of Religio Medici. Rare Books: Houghton Library at Harvard University
Religio Medici (The Religion of a Doctor) by Sir Thomas Browne MD, is a spiritual testament and an early psychological self-portrait. Published in 1643 after an unauthorized version was distributed the previous year, it became a European best-seller which brought its author, unexpected fame at home and abroad.
Sir Thomas Browne was a highly influential intellectual of his day and long after. He graduated from Pembroke College at Oxford University in 1626, after which he studied medicine at Padua and Montpellier universities, completing his studies at Leiden, where he received a medical degree in 1633. He settled in Norwich in 1637 and practiced medicine there until his death in 1682. Browne was a polymath, exceedingly well read and an expert in many disciplines. As we are still doing today, he struggled to make sense of science and religion, utilizing his great breadth of knowledge. Structured upon the Christian virtues of Faith and Hope (part 1) and Charity (part 2), Browne expresses a belief in salvation by faith alone, the existence of hell, the day of judgement, the resurrection and other tenets of Protestantism. However, as you will read below, Browne left room in his philosophical approach, for the construct of individual reason, as separate from any church.
There is no Church whose every part so squares unto my Conscience; whose Articles, Constitutions, and Customs seem so consonant unto reason, and as it were framed to my particular Devotion, as this whereof I hold my Belief, the Church of England. In brief, where the Scripture is silent, the Church is my Text; where that speaks, ’tis but my Comment: where there is a joint silence of both, I borrow not the rules of my Religion from Rome or Geneva, but the dictates of my own reason.
Throughout Religio Medici Browne uses scientific imagery to illustrate religious truths as part of his discussion on the relationship of science to religion, a topic which has lost none of its contemporary relevance. Browne’s latitudinarian Anglicanism meanders into digressions upon alchemy, astrology, hermetic philosophy, and physiognomy. Throughout his life, the Christian mystic held an interest in esotericism, stating in Religio Medici:
I was born in the planetary hour of Saturn and I think I have a piece of that leaden planet in me. I have often admired the mystical way of Pythagoras and the secret magicke of numbers. the severe schools shall never laugh me out of the philosophy of Hermes. and I hold moreover that there is a Phytognomy, or Physiognomy, not only of men, but of Plants, and Vegetables; and in every one of them, some outward figures which hang as signs or bushes of their inward forms.
A rare surviving contemporary review by Guy Patin, a distinguished member of the Parisian medical faculty, indicates the considerable impact Religio Medici had upon the intelligentsia abroad:
Throughout the seventeenth century Religio Medici spawned numerous imitative titles, including John Dryden’s great poem, Religio Laici, but none matched the frank, intimate tone of the original in which Browne shares his thoughts, as well as the idiosyncrasies of his personality with his reader.
Samuel Pepys in his diaries complained that:
the Religio was cried up to the whole world for its wit and learning.
A translation into German of the Religio was made in 1746 and an early admirer of Browne’s spiritual testament was Goethe’s one-time associate Lavater. In the early nineteenth century Religio Medici was re-discovered by the English Romantics. Charles Lamb introduced it to Samuel Taylor Coleridge who after reading it, exclaimed:
O to write a character of this man!
Thomas de Quincey in his Confessions of an English Opium Eater also praised it, stating:
I do not recollect more than one thing said adequately on the subject of music in all literature. It is a passage in Religio Medici of Sir T. Browne, and though chiefly remarkable for its sublimity, has also a philosophical value, inasmuch as it points to the true theory of musical effects.
The book strongly influenced the prominent physician William Osler in his early years. Osler, who is considered the father of modern medicine, is said to have learned it by heart. In Virginia Woolf’s opinion Religio Medici paved the way for all future confessionals, private memoirs and personal writings. In the twentieth century, the Swiss psychologist Carl Jung used the term Religio Medici several times in his writings. In the 21st Century, the tension continues between evidence based science and religious beliefs. There should be a way for both to peacefully co-exist, since one of the most important and motivating human feeling is hope. Hope is shared by science and religion, simply defined differently. At this point in history, hope is needed everywhere.
Early Antiretroviral Therapy Prevents Non-AIDS Outcomes in HIV-Infected People
According to an article published online in the New England Journal of Medicine (20 July 2015) based on new analysis of data from the Strategic Timing of AntiRetroviral Treatment (START) study, starting antiretroviral therapy early not only prevents serious AIDS-related diseases, but also prevents the onset of cancer, cardiovascular disease, and other non-AIDS-related diseases in HIV-infected people. Rates of both serious AIDS-related events and serious non-AIDS-related events were significantly reduced with early therapy.
The study’s composite endpoint had two components: serious AIDS events or death from AIDS, and serious non-AIDS events or non AIDS-related death. In May 2015, theSTART trial investigators released their initial groundbreaking findings that starting antiretroviral therapy early when immune systems are healthier, without waiting for CD4+ cell counts to decline, prevented the composite of serious AIDS events (such as AIDS-related cancers), serious non-AIDS-related events and death among HIV-infected individuals. The current results, which draw on more than two months of additional data since that announcement, show that starting treatment early significantly reduces the risk of both major components of this combined outcome: serious AIDS events and serious non-AIDS events. Non-AIDS-related events tracked by the study included cardiovascular disease, end-stage renal disease, liver disease, non-AIDS defining cancer or causes of death not attributable to AIDS. Serious AIDS events were reduced by 72% and serious non-AIDS events were reduced by 39%.
Based on the new data and analysis, the study now reports the overall risk of developing serious AIDS events, serious non-AIDS events, or death, was reduced by 57% among those in the early treatment group, compared to those in the deferred group. This reduction was seen regardless of age, gender, baseline CD4+ cell counts, geographic region or country income level. Other potentially life-threatening events and unscheduled hospitalizations for reasons other than AIDS were also assessed, and results did not differ between the immediate and deferred therapy groups, demonstrating the safety of early antiretroviral therapy.
The START study, which opened widely in March 2011, was conducted by the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT). It enrolled 4,685 HIV-infected men and women ages 18 and older in 35 countries. Participants had never taken antiretroviral therapy and were enrolled with CD4+ cell counts in the normal range-above 500 cells per cubic millimeter (cells/mm3). Approximately half of the study participants were randomized to initiate antiretroviral treatment immediately (early treatment), and the other half were randomized to defer treatment until their CD4+ cell count declined to 350 cells/mm3. On average, participants in the study were followed for three years.
Although the median age of study participants was 36 – a relatively young group of participants – the most common events observed in the study were serious non-AIDS events, including many that typically affect older individuals. The two most common individual serious non-AIDS events in the immediate and deferred groups were cardiovascular disease (12 and 14 participants with events, respectively) and non-AIDS-defining cancer (9 and 18 participants with events, respectively).
To evaluate the safety of early treatment, potentially life-threatening symptomatic events not attributable to AIDS and unscheduled hospitalizations for reasons other than AIDS were assessed in both treatment groups. Rates for these events were similar in the two groups. When these events were combined with the serious AIDS and serious non-AIDS events, as an overall measure of clinical benefit for early treatment, the rate was 18% lower in the early treatment group, compared to the deferred treatment group.
The study was conducted in 215 sites across 35 countries, representing a diverse population of HIV-positive individuals. Specific outcomes differed by geographic region, though the benefits of immediate antiretroviral therapy were consistent. Most of the cancers and cardiovascular disease events occurred among participants from higher-income countries in Europe, and Australia, Israel and the United States (22 of 27 cancer diagnoses and 19 of 26 cardiovascular events, respectively). Most of the tuberculosis occurred among participants at study sites in Africa (16 of 26 events), where both TB and HIV/AIDS are endemic.
According to the study team, these findings are subject to some limitations. The patient population enrolled in START was younger than projected and experienced fewer overall events than were originally projected in the study’s design. This limited the ability to determine the effect of immediate antiretroviral therapy on specific serious non-AIDS conditions, such as the risk of cardiovascular disease. Further follow-up of this relatively young study population may help the better understand how early antiretroviral therapy impacts the cardiovascular system.
The HIV medicines used in the trial are approved medications donated by AbbVie, Inc., Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, LLC, and Merck & Co.
NIH Study Identifies Gene Variant Linked to Compulsive Drinking
Alcohol use disorder affects about 16.6 million adults in the United States.
Brain-derived neurotrophic (BDNF) plays a role in the survival of existing neurons and the growth of new neurons and synapses, the junctures through which cell-to-cell communication occurs. The human form of this gene variant, Met66BDNF, leads to a reduction in the normal function of BDNF in the brain and is associated with several psychiatric disorders, including schizophrenia and depression. According to results of a recent study in the mouse, and published online in Biological Psychiatry (11 June 2015), carrying a gene variant that affects the release of a specific brain protein may put one at greater risk of developing an alcohol use disorder. The study found that mice carrying the Met68BDNF gene variant, which reduces the release of BDNF, would consume excessive amounts of alcohol, despite negative consequences.
In a study reported earlier this year, NIH-supported scientists found that adolescent binge drinking was linked to lower levels of brain-derived neurotrophic factor, and these changes persisted into adulthood.
For the study, the authors tested the role of BDNF in alcohol addiction by creating a knock-in mouse carrying Met68BDNF. In this variant, the amino acid valine (Val) is replaced by methionine (Met) in a specific position within the protein sequence of BDNF, resulting in reduced activity-dependent BDNF release. Results showed that these knock-in mice drank more alcohol, even when the alcohol was treated with bitter-tasting quinine. This suggests Met68BDNF carriers compulsively drink alcohol despite aversive consequences. According to the authors, the effect of the genetic mutation seemed to be specific to alcohol consumption since the mice did not differ in their consumption of other fluids, or exhibit differences in levels of anxiety or compulsive behaviors. Significantly, the authors were able to reverse compulsive alcohol drinking in the mice using gene delivery and pharmacology. Increasing levels of BDNF in the ventromedial portion of the prefrontal cortex, a brain region involved in compulsive drug and alcohol seeking, returned the mice to moderate levels of alcohol intake. In addition, by administering a pharmaceutical compound developed to mimic the action of BDNF, it was possible to put a stop to compulsive drinking behaviors. This compound (LM22A-4) may have potential as a therapeutic for humans as it appears to reduce compulsive alcohol drinking without a generalized effect on motivation. According to the authors, knowing whether patients carry a gene that results in decreased BDNF function could help in tailoring alcohol prevention and treatment strategies in the future.
New Treatment for Basal Cell Carcinoma
Skin cancer is the most common cancer and basal cell carcinoma accounts for approximately 80% of non-melanoma skin cancers. Basal cell carcinoma starts in the top layer of the skin (called the epidermis) and usually develops in areas that have been regularly exposed to the sun and other forms of ultraviolet radiation. According to the National Cancer Institute, the number of new cases of non-melanoma skin cancer appears to be increasing every year. Locally advanced basal cell skin cancer refers to basal cancers that have not spread to other parts of the body, but cannot be curatively treated with local treatments, specifically surgery and radiation.
The FDA has approved Odomzo (sonidegib) to treat patients with locally advanced basal cell carcinoma that has recurred following surgery or radiation therapy, or who are not candidates for surgery or radiation therapy. Odomzo is a pill taken once a day. It works by inhibiting a molecular pathway, called the Hedgehog pathway, which is active in basal cell cancers. By suppressing this pathway, Odomzo may stop or reduce the growth of cancerous lesions. According to Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, Thanks to a better understanding of the Hedgehog pathway, the FDA has now approved two drugs for the treatment of basal cell carcinoma just in the last three years. In 2012, Erivedge (vismodegib) was the first drug approved to treat locally advanced and metastatic basal cell carcinoma.
Odomzo carries a Boxed Warning alerting healthcare professionals that Odomzo may cause death or severe birth defects in a developing fetus when administered to a pregnant woman. Pregnancy status should be verified prior to the start of Odomzo treatment, and both male and female patients should be warned about these risks and advised to use effective contraception.
The efficacy of Odomzo was established in a multi-center, double-blind clinical trial, in which 66 patients with locally advanced basal cell carcinoma were randomly assigned to receive Odomzo 200 mg daily and 128 patients were assigned to receive Odomzo 800 mg daily. The study’s primary endpoint was objective response rate, which is the percentage of patients who experienced partial shrinkage or complete disappearance of their tumor(s). Results showed that 58% of patients treated with Odomzo 200 mg had their tumors shrink or disappear. This effect lasted at least 1.9 to 18.6 months, and approximately half of the responding patients’ tumor shrinkage lasted six months or longer. Response rates were similar in patients who received Odomzo 800 mg daily, however side effects were more common at this dose. At a dose of 200 mg daily, the most common side effects of Odomzo were muscle spasms, alopecia (hair loss), dysgeusia (distortion in the sense of taste), fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, myalgia (muscle pain), abdominal pain, headache, pain, vomiting and pruritus (itching). Odomzo also has the potential to cause serious musculoskeletal-related side effects, including increased serum creatine kinase levels [with rare reports of muscle tissue breakdown (rhabdomyolysis)], muscle spasms, and myalgia.
Odomzo is marketed by East Hanover, New Jersey-based Novartis Pharmaceuticals Corporation.