Culture

Could bile acids--the fat-dissolving juices churned out by the liver and gallbladder--also play a role in immunity and inflammation?

The answer appears to be yes, according to two separate Harvard Medical School studies published in Nature.

The findings of the two studies, both conducted in mice, show that bile acids promote the differentiation and activity of several types of T cells involved in regulating inflammation and linked to intestinal inflammatory conditions. They also reveal that gut microbes are critical for converting bile acids into immune-signaling molecules.

The work suggests possible therapeutic pathways for modulating intestinal inflammation, a process that underlies the development of autoimmune conditions such as inflammatory bowel disease, commonly referred to as IBD.

The first study, led by immunologist Jun Huh and published Nov. 27 in Nature, reveals bile acids exert their immune-modulating effect by interacting with immune cells in the gut. Once bile acids leave the gallbladder and complete their fat-dissolving duties, they make their way down the digestive tract where they are modified into immune-regulatory molecules by gut bacteria. The modified bile acids then activate two class of immune cells: regulatory T cells (Tregs) and effector helper T cells, specifically Th17, each responsible for modulating immune response by either curbing or promoting inflammation.

Under normal conditions, the levels of proinflammatory Th17 cells and anti-inflammatory Treg cells balance each other, maintaining a degree of protection against pathogens without causing too much tissue-damaging inflammation. These cells play a key role in the context of intestinal infection. Th17 cells ignite inflammation to quell the infection, while Tregs curb inflammation once the threat has subsided. Unrestrained, the activity of Th17 can also lead to aberrant inflammation that promotes autoimmune disease and damages the intestine.

In their experiments, the researchers used undifferentiated, or naïve, mouse T cells, and exposed them to various bile acid metabolites one at a time. The experiments showed that two separate bile acid molecules exerted different effects on T cells--one molecule promoted Treg differentiation, while another molecule inhibited Th17 cell differentiation. When the researchers administered each molecule to mice, they observed the animals' Th17 and Treg cells fell and rose, accordingly. Additionally, the researchers found that the two bile acid byproducts are also present in human stool, including stools of people with IBD--a finding that suggest the same mechanism is at play in humans.

"Our findings identify an important regulatory mechanism in gut immunity, showing that microbes in our intestines can modify bile acids and turn them into regulators of inflammation," said Huh, assistant professor of immunology in the Blavatnik Institute at HMS.

If affirmed in further studies, the results can inform the development of small-molecule therapies that target Treg and Th17 cells as a way to control inflammation and treat autoimmune diseases affecting the gut.

The second study, published Dec. 25 in Nature and led by Dennis Kasper, focused on a subset of inflammation-taming regulatory T cells, or Tregs, that arise in the colon as a result of exposure to gut microbes. In contrast, most other immune cells originate in the thymus.

Low levels of colonic regulatory T cells (colonic Tregs) have been linked to the development of autoimmune conditions such as IBD and Crohn's disease.

Kasper's experiments demonstrate that gut microbes and diet work in concert to modify bile acids, which in turn affect the levels of colonic Tregs in mice. They also show that low levels of Treg cells induced by lack of bile acids or deficiency in bile acid sensors makes animals prone to developing inflammatory colitis--a condition that mimics human IBD.

To test the hypothesis that gut bacteria convert food-derived bile acids produced in response to food into immune signaling molecules, the researchers silenced bile acid-converting genes in various gut microbes and then put both the modified and nonmodified microbes in mice specially bred to have germ-free guts. Animals whose guts were populated by microbes without bile acid-converting genes had notably lower levels of Treg cells. The researchers then fed animals either nutrient-rich meals or minimal food.

Animals with normal microbe populations in their guts that were receiving minimal food had lower levels of colonic Tregs and lower bile acid levels than mice eating rich food. Yet animals with germ-free guts receiving rich food also had low levels of Treg cells--a finding which shows that both gut microbes and food-derived bile acids are required to modulate immune cell levels.

To test whether bile acids are directly involved in immune cell regulation, the researchers then mixed various bile acid molecules with the drinking water of animals that had low Treg cell levels and minimal diets. Several weeks later, these animals had an increase in the levels of inflammation-curbing Treg cells.

In a final step, the researchers gave three groups of mice a compound that induces colitis. One group was fed a minimal diet, another group received nutrient-rich meals and a third group received minimal food and drank water supplemented with bile acid molecules. As expected, only mice fed minimal diets not supplemented by bile acid molecules developed colitis. The experiment confirmed that bile acids play a critical role in Treg regulation, intestinal inflammation and colitis risk.

"Our results demonstrate an elegant three-way interaction between gut microbes, bile acids and the immune system," said Kasper, who is professor of immunology in the Blavatnik Institute at HMS and the William Ellery Channing Professor of Medicine at HMS and Brigham and Women's Hospital. "Importantly, our work suggests it is plausible to think of harnessing certain gut bacteria as a way to modulate disease risk."

ROCHESTER, Minn. -- Gender pay equity in the field of medicine remains elusive. Gender-based pay differences have been shown to persist, even when controlling for experience, clinical productivity, academic rank and other factors. These inequities result in significantly lower lifetime earnings, job burnout and negative attitudes toward work, and adverse effects on the profession and society.

One model for eliminating pay disparities among physicians is a structured, salary-only plan that incorporates national benchmarks, and standardized pay steps and increments, such as the plan that is used at Mayo Clinic.

A Mayo Clinic study set out to assess how well the institution adheres to its own compensation model and achieves pay equity. The study reviewed data for all permanent staff physicians employed at Mayo Clinic in Arizona, Florida and Minnesota who were in clinical roles as of January 2017. Each physician's pay, demographics, specialty, full-time equivalent status, benchmark pay, leadership roles and other factors were collected and analyzed.

Among 2,845 physicians, pay equity was affirmed in 96% of the cases, according to the analysis, which is published in Mayo Clinic Proceedings. All physicians whose salaries were not in the predicted range were evaluated further and found to have the appropriate compensation, most often due to unique or blended departmental appointments. Of the 80 physicians -- 2.8% of the total -- with higher compensation than predicted by the model, there was no correlation with gender, race or ethnicity. The same was true of the 35 physicians -- 1.2% -- who had lower-than-predicted compensation.

"Our analysis is unique and to our knowledge the first to demonstrate that a structured compensation model achieved equitable physician compensation by gender, race and ethnicity, while also meeting the practice, education and research goals of a large academic medical center such as Mayo Clinic," says Sharonne Hayes, M.D., a Mayo Clinic cardiologist and the study's first author. "The analysis of this long-standing salary-only model was reassuring, not only that it was equitable, but that we as an organization adhere to our own standards."

A structured compensation program has been used for physician salaries at Mayo Clinic for more than 40 years to remove financial incentives to do more than is necessary or less than desired for the patient. The step-based model is designed to ensure that salaries are market-competitive; advance efforts to recruit and retain staff; and support the mission, vision and values of the organization. There are no incentives or bonus pay, and nonsalary compensation and benefits are consistent across Mayo Clinic locations and specialties.

Of the 2,845 physicians whose compensation was analyzed, 861 were women and 722 were nonwhite. More men than women held one of the compensated leadership positions or had past leadership roles -- 31.4% of men were in that category, compared with 15.9% of women -- and more men than women were in the highest compensated specialties.

The study calls for health care organizations to systematically define the drivers and incentives of physician compensation, and assess whether these organizations unfairly exclude or disadvantage certain groups -- whether women, racial or ethnic minorities, or medical specialties -- and then develop processes that can achieve equity and values alignment.

"While solutions to persistent pay inequities are different for each organization, leadership must be committed to addressing those inequities by identifying and consistently tackling biases," says Gianrico Farrugia, M.D., president and CEO, Mayo Clinic, and a study co-author. "Furthermore, absolute gender pay equity will only be realized when women achieve parity in the most highly compensated specialties and leadership roles."

In the months after separating from military service, most veterans are less satisfied with their health than with their work or social relationships, found a study by Veterans Affairs researchers. While the veterans surveyed were mostly satisfied with their work and social well-being, a majority were dealing with chronic physical health conditions and a third reported chronic mental health conditions.

According to Dr. Dawne Vogt of the VA Boston Healthcare System and Boston University, lead author on the study, the results highlight the importance of addressing veterans' health concerns early.

"What remains to be seen is whether those veterans with health conditions--which were more commonly experienced by deployed veterans--continue to maintain high levels of well-being in other life domains over time," she says. "Given that it is well-established that health problems can erode functioning in other life domains, it may be that these individuals experience declines in their broader well-being over time."

The results appear Jan. 2, 2019, in the American Journal of Preventive Medicine.

More than 200,000 U.S. service members transition out of military service each year. Researchers have pointed to the early transition period as a critical time to address challenges veterans may face in readjusting to civilian life.

To investigate which of these challenges are most pressing to newly separated veterans, researchers from the VA National Center for PTSD and colleagues surveyed almost 10,000 veterans from a population-based roster of all separating service members.

All participants left the military in the fall of 2016. Veterans were surveyed about three months after their separation, and then six months after that.

The researchers found that the biggest concern was health. At both three and nine months after leaving the military, 53% of participants said they had chronic physical health conditions. About 33% reported chronic mental health conditions at both time points.

The most commonly reported health conditions were chronic pain, sleep problems, anxiety, and depression. Slightly more than half of participants said they had reduced satisfaction with their health between when they first left the military and a few months later. Health satisfaction did not change much between three and nine months after separation.

While physical and mental health was a concern for many veterans, most reported high vocational and social well-being. The majority of participants said they were satisfied with their work and social relationships and that they were functioning well in these areas. According to Vogt, the fact that most participants had high work and social satisfaction "highlights the resilience of the veteran population, and should provide some reassurance to those concerned about the well-being of newly separated veterans."

More than three-quarters of participants said they were in an intimate relationship in the months after they left the military. Almost two-thirds reported that they had regular contact with their friends and extended family and that they were involved in their broader communities.

Over half of participants had found work three months after military separation. While most participants reported high work satisfaction, the study group showed an overall decline in work functioning over the first year after military separation. Functioning declined even though overall employment rates increased. The researchers hypothesized that this decline in work functioning could be due to health concerns, which are known to erode broader well-being over time.

The study also found differences in well-being based on other factors. Enlisted veterans showed consistently poorer health, vocational, and social well-being than officers. Veterans who had deployed to a war zone had more health concerns than veterans who did not deploy.

There were also several differences between men and women. Male veterans were more likely to be employed than female veterans both three and nine months after leaving the military. Men were also more likely to report hearing conditions, high blood pressure, and high cholesterol. Women were more likely to endorse mental health conditions at nine months post-separation. They also reported more depression and anxiety at both timepoints.

The researchers have shared their findings with the VA Transition Assistance Program (TAP), which helps Veterans transition back to civilian life. The program is jointly managed by VA and the departments of Defense and Labor, in coordination with the departments of Education and Homeland Security, as well as the U.S. Office of Personnel Management and the U.S. Small Business Administration. According to Vogt, the results could help TAP and other programs that help veterans with readjustment decide how to allocate their resources. Vogt writes that the findings "suggest that maybe we don't need as much focus on promoting employment right now, and need more emphasis on treatment of mental/physical health conditions."

The researchers say their findings have implications not only for VA but for the wide spectrum of organizations nationwide--more than 40,000 in all--that provide programs, services, and support for veterans making their transition back to civilian life. Historically, much of the support for veterans leaving the military has primarily focused on providing employment and educational assistance and informing veterans of their benefits. But the findings suggest that veterans' health concerns should be prioritized, says Vogt. Interventions should also target at-risk subgroups of veterans. The researchers concluded that addressing newly separated veterans' health concerns could promote their broader well-being and longer-term readjustment.

Vogt points out the importance of addressing veterans' readjustment challenges before they worsen and have a chance to erode broader well-being. She says this may require re-evaluating support methods. "Given that most transition support is targeted to veterans with the most acute or chronic concerns," she says, "this recommendation may require rethinking how veteran programs prioritize their efforts. While it makes sense to target resources to those with greatest need, it is better to support individuals before their concerns become chronic when we can."

Work is underway to expand on this study using the same study group. The research team is analyzing how veterans' health and well-being changes in the second and third year after leaving service, as well as how veterans' initial health status impacts their subsequent well-being in other areas.

In October this year, weather researchers in Utah measured the lowest temperature ever recorded in the month of October in the US (excluding Alaska): -37.1°C. The previous low-temperature record for October was -35°C, and people wondered what had happened to climate change.

Until now, climate researchers have responded that climate is not the same thing as weather. Climate is what we expect in the long term, whereas weather is what we get in the short term - and since local weather conditions are highly variable, it can be very cold in one location for a short time despite long-term global warming. In short, the variability of local weather masks long-term trends in global climate.

A paradigm shift

Now, however, a group led by ETH professor Reto Knutti has conducted a new analysis of temperature measurements and models. The scientists concluded that the weather-is-not-climate paradigm is no longer applicable in that form. According to the researchers, the climate signal - that is, the long-term warming trend - can actually be discerned in daily weather data, such as surface air temperature and humidity, provided that global spatial patterns are taken into account.

In plain English, this means that - despite global warming - there may well be a record low temperature in October in the US. If it is simultaneously warmer than average in other regions, however, this deviation is almost completely eliminated. "Uncovering the climate change signal in daily weather conditions calls for a global perspective, not a regional one," says Sebastian Sippel, a postdoc working in Knutti's research group and lead author of a study recently published in Nature Climate Change.

Statistical learning techniques extract climate change signature

In order to detect the climate signal in daily weather records, Sippel and his colleagues used statistical learning techniques to combine simulations with climate models and data from measuring stations. Statistical learning techniques can extract a "fingerprint" of climate change from the combination of temperatures of various regions and the ratio of expected warming and variability. By systematically evaluating the model simulations, they can identify the climate fingerprint in the global measurement data on any single day since spring 2012.

A comparison of the variability of local and global daily mean temperatures shows why the global perspective is important. Whereas locally measured daily mean temperatures can fluctuate widely (even after the seasonal cycle is removed), global daily mean values show a very narrow range.

If the distribution of global daily mean values from 1951 to 1980 are then compared with those from 2009 to 2018, the two distributions (bell curves) barely overlap. The climate signal is thus prominent in the global values but obscured in the local values, since the distribution of daily mean values overlaps quite considerably in the two periods.

Application to the hydrological cycle

The findings could have broad implications for climate science. "Weather at the global level carries important information about climate," says Knutti. "This information could, for example, be used for further studies that quantify changes in the probability of extreme weather events, such as regional cold spells. These studies are based on model calculations, and our approach could then provide a global context of the climate change fingerprint in observations made during regional cold spells of this kind. This gives rise to new opportunities for the communication of regional weather events against the backdrop of global warming."

The study stems from a collaboration between ETH researchers and the Swiss Data Science Center (SDSC), which ETH Zurich operates jointly with its sister university EPFL. "The current study underlines how useful data science methods are in clarifying environmental questions, and the SDSC is of great use in this," says Knutti. Data science methods not only allow researchers to demonstrate the strength of the human "fingerprint", they also show where in the world climate change is particularly clear and recognisable at an early stage. This is very important in the hydrological cycle, where there are very large natural fluctuations from day to day and year to year. "In future, we should therefore be able to pick out human-induced patterns and trends in other more complex measurement parameters, such as precipitation, that are hard to detect using traditional statistics," says the ETH professor.

New research reveals a key insight into the development of hair bundles, the intricately complex assemblies in the inner ear responsible for hearing.

Hair bundles are precisely arranged cellular structures deep within the spiral cavity of the inner ear. Together, they convert vibrational energy into electrical signals in the brain that translate into the sensation of hearing. Once they're lost - whether by loud noise, toxins, disease or aging - they do not naturally regenerate in people and other mammals.

The new research led by scientists at Oregon Health & Science University provides important clues that may help scientists develop new techniques to regenerate hair cells and reverse hearing loss.

In the study published in the journal Current Biology, researchers discovered the development of hair bundles occurs in a kind of feedback loop in which form follows function and function drives form.

Using mice, which closely model human hearing, the researchers found stereocilia, roughly 100 of which are assembled into a hair bundle, widened simultaneously with the onset of mechanotransduction - the action of converting mechanical signals in the form of sound into electrical signals measured within the brain. The stereocilia only elongated to their mature lengths after transduction had been established.

It turns out that form and function are mutually reinforcing.

"We've been looking at these as separate pathways," said lead author Jocelyn Krey, Ph.D., staff scientist in the Oregon Hearing Research Center and the Vollum Institute at OHSU. "But in the course of this research, we observed the change in form occurs at the same time as the conversion of mechanical to electrical signals. So we're seeing these happen together, and feeding each other in a way we hadn't seen before."

The researchers discovered when they examined mice lacking transduction or used a compound to block transduction, the animals did not develop the classic staircase-shaped form of mature hair bundles.

Researchers say the study suggests that new techniques to reverse hearing loss should focus on the critical importance of early development.

"In the future, with the rapid development of gene editing tools like CRISPR, we will be able to turn on genes at will," said senior author Peter Barr-Gillespie, Ph.D., professor in the Oregon Hearing Research Center and senior scientist in the Vollum Institute. "I have no doubt we will be there in 5 or 10 years."

Researchers at Johns Hopkins Medicine have successfully used a laser-assisted imaging tool to "see" what happens in brain cells of mice learning to reach out and grab a pellet of food. Their experiments, they say, add to evidence that such motor-based learning can occur in multiple areas of the brain, even ones not typically associated with motor control.

"Scientists should be looking at the entire brain to understand specific types of learning," says Richard Huganir, Ph.D., Bloomberg Distinguished Professor and Director of the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine. "Different parts of the brain contribute to learning in different ways, and studying brain cell receptors can help us decipher how this works."

The work, say the researchers, may ultimately inform efforts to develop treatments for learning-based and neurocognitive disorders.

In a report on the work, appearing online Dec. 31 in Neuron, Huganir and his research team say they focused on AMPA-type glutamate receptors, or AMPARs, key molecules that help send messages between brain cells called neurons. AMPARs function like antennas that form along the surface of a particular spot on neurons called a synapse, where it receives molecular signals from other neurons.

To monitor and measure AMPAR levels in mouse brains, scientists previously had to dissect the organ before and after a learning experiment and compare differences. Now, scientists have ways to directly view the brain during learning, recording thousands of synapses at a time.

In the new experiments, scientists injected DNA-encoding AMPARs carrying a fluorescent tag into the brains of mice, and used an electrical pulse to get neurons to absorb the AMPAR DNA. Next, with a tool called two-photon microscopy, the scientists used a laser -- essentially an intensely focused beam of light -- to detect and measure the amount of fluorescence coming from the tagged AMPARs.

More fluorescence is an indication of increased AMPAR activity and messaging between neurons, a good sign that learning and memory building is taking place in those neurons, Huganir says.

To "see" what learning looked like in the test animals' neurons, Huganir's team trained mice to reach for and grab a food pellet placed just outside their cage using their paws. Normally, mice get pellets with their mouths.

While the mice were learning how to reach for the pellet, the scientists found an approximately 20% increase in the activity of AMPARs in an area of the brain known as the motor cortex, which is known for controlling and precisely moving muscles. On neurons, the AMPARs look like lights on a Christmas tree and glow brighter with increasing activity.

But the experiments also showed the same increase in AMPAR activity levels in the visual cortex too.

"This made sense because vision is very important for motor control," says Richard Roth, Ph.D., currently a postdoctoral fellow at Stanford University, but who performed experiments for this study as a graduate student in Huganir's laboratory.

"So, we did the same experiment again, but with the lights switched off," says Roth.

Using infrared light, which the mice couldn't see, the mice eventually learned to successfully grab the food, but there was a smaller increase (10%) in the activity of AMPARs in the visual cortex.

"We believe the mice brains are using different sets of sensory cues in the dark to learn the motor task, including touch and smell, enabling these other senses to take over," says Roth.

Next, the research team repeated the experiments using specialized light-activated modulators to shut down neurons in either the motor or visual cortex.

If the mice were trained to get the pellet with the room lights on, the mice could not complete the task if their visual cortex was shut down. "Clearly, these mice relied on learning centralized in their visual cortex to reach the pellet," says Roth.

However, mice initially trained to grab the pellet in the dark could still complete the task, even if their visual cortex was shut down.

"We've traditionally thought that motor-based learning happens solely in the motor part of the brain, but our studies and others now show that it's not as specific as we had thought. There is more of a brainwide effect in learning," says Roth.

Huganir notes that among the genes that control neuronal receptors involved in learning is SYNGAP. His and others' research has shown that when the gene is mutated, it contributes to conditions including intellectual disability, autism and schizophrenia -- all conditions marked in part by disrupted thinking and learning.

A team of astronomers at the National Centre for Radio Astrophysics (NCRA) in Pune, India have discovered a mysterious ring of hydrogen gas around a distant galaxy, using the Giant Metrewave Radio Telescope (GMRT). The ring is much bigger than the galaxy it surrounds and has a diameter of about 380,000 light-years (about 4 times that of our Milky Way).

The galaxy (named AGC 203001), is located about 260 million light-years away from us. There is only one other such known system with such a large neutral hydrogen ring. The origin and formation of such rings is still a matter of debate among astrophysicists.

Neutral hydrogen emits radio waves at a wavelength of about 21cm. This radiation from neutral hydrogen atoms has allowed radio astronomers to map the amount and distribution of neutral hydrogen gas in our Milky Way galaxy and in other galaxies in the Universe. Typically, large reservoirs of neutral hydrogen gas are found in galaxies which are actively forming new stars. However, despite showing no signs of active star formation the galaxy AGC 203001 was known to have large amounts of hydrogen, although its exact distribution was not known. The unusual nature of this galaxy motivated astronomers in NCRA to use the GMRT to conduct high-resolution radio observation of this galaxy to find out where in the galaxy this gas lies.

The GMRT observations revealed that the neutral hydrogen is distributed in the form of a large off-centered ring extending much beyond the optical extent of this galaxy. More puzzlingly, the astronomers found that the existing optical images of the ring showed no sign of it containing stars. In collaboration with two French astronomers, Pierre-Alain Duc and Jean-Charles Cuillandre, the NCRA team obtained a very sensitive optical image of this system using the Canada-France-Hawaii-Telescope (CFHT) in Hawaii, USA. However, even these images do not show any sign of starlight associated with the hydrogen ring.

There is no clear answer today as to what could lead to the formation of such large, starless rings of hydrogen. Conventionally, galaxy-galaxy collisions were thought to lead to the formation of such off-centered rings around galaxies. However, such rings also generally contain stars. This is contrary to what is found in this ring. Figuring out how this ring was formed remains a challenge to astronomers.

Encouraged by this discovery, the team is now conducting a large survey to map the neutral hydrogen around several more similar galaxies. If some of them also show rings like this, it should help us to better understand the formation mechanism behind such rare rings.

This work was led by Omkar Bait, a doctoral student at NCRA working under the supervision of Yogesh Wadadekar. This work forms a part of Omkar's doctoral thesis. Sushma Kurapati, who is another doctoral student at NCRA also played a role in the radio observations. Other expert scientists who contributed include, Pierre-Alain Duc (Universite de Strasbourg, Strasbourg, France), Jean-Charles Cuillandre (PSL University, Paris, France), Peter Kamphuis (Ruhr University, Bochum, Germany) and Sudhanshu Barway (Indian Institute of Astrophysics, Bengaluru, India).

Acute myeloid leukemia is the most common type of leukemia in adults. It is characterized by the pathological expansion of immature cells (myeloblasts) that invade the bone marrow and expand into the blood, affecting the production of the rest of the healthy cells. Although patients usually respond well to chemotherapy-based treatments, a large proportion of them eventually relapse or show resistance to these procedures.

The cause of relapse or resistance to treatment is sometimes due to the existence of leukemic stem cells capable of starting cancer again, and in turn, for being resistant to chemotherapy. However, identifying them is a challenge since there are no specific markers to detect and isolate them.

The Functional Cytomics Research Group at the Josep Carreras Leukaemia Research Institute has developed innovative trials that allow the identification of these cells by testing the activity of a protein, alkaline phosphatase, present in myeloblasts.

To do this, they have used advanced cytomical methodologies that allow multiple functional characteristics to be analyzed cell by cell, individually, in a very few minutes.

The researchers identified a group of patients whose leukemic cells had high levels of alkaline phosphatase activity and another group of patients with lower levels of this activity. Both groups showed a differential response to chemotherapy treatment, with the most active phosphatase group showing the worst reaction to treatment and the shortest survival. Surprisingly, no significant association was detected between the results obtained through different cytogenetic analysis techniques and molecular studies, with the determination of prognostic factors of greater or lesser risk.

"These results represent a new approach to improve the prognosis in the diagnostic evaluation of acute myeloid leukemia and to estimate the probability of relapse and persistence of the disease. This will allow us to open new lines of research aimed at applying alternative strategies in terms of treatment," said Dr. Jordi Petriz, director of the study.

Researchers from the Moscow Institute of Physics and Technology, Kotelnikov Institute of Radio Engineering and Electronics, and N.G. Chernyshevsky Saratov State University have demonstrated that the coupling elements in magnonic logic circuits are so crucial that a poorly selected waveguide can lead to signal loss. The physicists developed a parametric model for predicting the waveguide configuration that avoids signal loss, built a prototype waveguide, and tested the model in an experiment. Their paper was published in the Journal of Applied Physics.

The underlying goal of the research on magnonic logic is creating alternative circuit elements compatible with the existing electronics. This means developing completely new elements, including faster signal processors with low power consumption, that could be incorporated into present-day electronics.

In designing new devices, various components are integrated with each other. However, magnonic circuits rely on magnetic waveguides rather than wires for this. Researchers previously conjectured that waveguides could have an adverse effect on signal intensity in transmission from one component to another.

The recent study by the Russian physicists has shown the waveguides to have a greater effect than anticipated. In fact, it turns out that a poorly chosen waveguide geometry can result in complete signal loss. The reason for this is spin wave interference. Waveguides are extremely miniature components, measuring hundredths of a micrometer, and on this scale, the lateral quantization of the signal needs to be accounted for.

The researchers worked on an optimization problem: How does one design a waveguide for magnonic circuits to ensure maximum efficiency? The team developed a theory and a mathematical model to describe wave propagation in nanosized waveguides. To this end, senior researcher Dmitry Kalyabin of MIPT's Terahertz Spintronics Lab, adapted the team's previous results developed for acoustic systems to spin waves.

His colleagues in Saratov then created a prototype device and verified Kalyabin's calculations using a method known as Brillouin spectroscopy. This technique involves making a "snapshot" of the magnetization distribution in a sample following its exposure to laser light. The distribution observed in this way can then be compared with theoretical predictions.

"We initially aimed to build a model that enables calculating the throughput characteristics of a waveguide before it was actually made. Our expectation was that optimizing the shape of the waveguide would maximize signal transmission efficiency. But our research revealed the effects of interference to be greater than anticipated, with suboptimal parameters sometimes rendering the signal completely lost," said Sergey Nikitov, the head of the Terahertz Spintronics Lab and a corresponding member of the Russian Academy of Sciences.

Although the authors of the paper used the example of a tapering narrow ferromagnetic waveguide to demonstrate how their model works, it is applicable to the entire range of currently used waveguide types.

CHAPEL HILL, NC - "My first reaction when NASA reached out to me was to ask if I could visit the International Space Station (ISS) to examine the patient myself," said Stephan Moll, MD, UNC School of Medicine blood clot expert and long-time NASA enthusiast. "NASA told me they couldn't get me up to space quickly enough, so I proceeded with the evaluation and treatment process from here in Chapel Hill."

Moll was the only non-NASA physician NASA consulted when it was discovered that an astronaut aboard the ISS had a deep vein thrombosis (DVT) - or blood clot - in the jugular vein of their neck. The astronaut's identity is being kept anonymous for privacy reasons, so identifying information such as when this event happened is being omitted from the case study. We do know that the astronaut was two months into a six-month mission on the ISS when the DVT was discovered.

This was the first time a blood clot had been found in an astronaut in space, so there was no established method of treatment for DVT in zero gravity. Moll, a member of the UNC Blood Research Center, was called upon for his vast knowledge and treatment experience of DVT on Earth.

"Normally the protocol for treating a patient with DVT would be to start them on blood thinners for at least three months to prevent the clot from getting bigger and to lessen the harm it could cause if it moved to a different part of the body such as the lungs," Moll said. "There is some risk when taking blood thinners that if an injury occurs, it could cause internal bleeding that is difficult to stop. In either case, emergency medical attention could be needed. Knowing there are no emergency rooms in space, we had to weigh our options very carefully."

Moll and a team of NASA doctors decided blood thinners would be the best course of treatment for the astronaut. They were limited in their pharmaceutical options, however. The ISS keeps only a small supply of various medicines on board, and there was a limited amount of the blood thinner Enoxaparin (Lovenox®) available. Moll advised NASA on what dosage of Enoxaparin would effectively treat the DVT while also lasting long enough, until NASA could get a new shipment of drugs - which Moll helped select - to the ISS.

The course of treatment with Enoxaparin - a drug delivered by an injection into the skin - lasted for around 40 days. On day 43 of the astronaut's treatment, a supply of Apixaban (Eliquis®) - a pill taken orally- was delivered to the ISS by a supply spacecraft.

Throughout the treatment process, which lasted more than 90 days, the astronaut performed ultrasounds on their own neck with guidance from a radiology team on Earth in order to monitor the blood clot. Moll was also able to speak to the astronaut during this period through email and phone calls.

"When the astronaut called my home phone, my wife answered and then passed the phone to me with the comment, 'Stephan, a phone call for you from space.' That was pretty amazing," said Moll. "It was incredible to get a call from an astronaut in space. They just wanted to talk to me as if they were one of my other patients. And amazingly the call connection was better than when I call my family in Germany, even though the ISS zips around Earth at 17,000 miles per hour."

Four days before the astronaut's journey home to Earth, they stopped taking Apixaban. Moll and his NASA counterparts made that decision because of how physically demanding and potentially dangerous the re-entry process can be for astronauts, and they did not want an injury to be exacerbated by the use of blood thinners. The astronaut landed safely on Earth and the blood clot required no more treatment.

This astronaut's blood clot was asymptomatic - they didn't have any symptoms that would have otherwise made them aware of the clot. The DVT was discovered when the astronaut was taking ultrasounds of their neck for a research study on how body fluid is redistributed in zero gravity. If it wasn't for the study, there's no telling what the outcome could have been. That's why Moll continues to work with NASA and says there's a need for more research of how blood and blood clots behave in space.

"Is this something that is more common in space?" posed Moll. "How do you minimize risk for DVT? Should there be more medications for it kept on the ISS? All of these questions need answering, especially with the plan that astronauts will embark on longer missions to the moon and Mars."

(Boston)--Health concerns are the most important readjustment challenge facing veterans in the first year after they leave military service.

Every year, more than 200,000 U.S. service members transition out of military service. While many go on to have productive and fulfilling lives, researchers have called for greater attention to the military-to-civilian transition experience, suggesting that some military veterans may have difficulty securing meaningful employment, meeting health-care needs, and successfully integrating within civilian society.

In order to provide a descriptive picture of veterans' health and well-being in the first year after leaving military service based on their gender, military rank and deployment history, researchers studied more than 9,500 veterans.

The veterans were surveyed on their health, work, and social relationships within three months of leaving the military and then six months later. Among the findings: former enlisted personnel reported poorer outcomes on nearly all areas of well-being compared with officers, whereas deployed veterans reported poorer health and female veterans acknowledged more mental health concerns compared with their non-deployed and male peers.

"While many veterans indicated they had a chronic physical or mental health condition and were less satisfied with their health than other important aspects of their lives, many reported that they had found a job, were satisfied with their work and were well-integrated within their broader social communities," explained corresponding author Dawne S. Vogt, PhD, research psychologist in the Women's Health Sciences Division, National Center for PTSD at the VA Boston Healthcare System and associate professor of psychiatry at Boston University School of Medicine.

According to the researchers, the fact that veterans reported the poorest well-being in the health domain points to the importance of addressing veterans' health concerns at the time they leave military service, especially regarding chronic pain, sleep, anxiety and depression. "Given that some conditions may be in place prior to separation, it may also be necessary to bolster pre-separation health screening and intervention efforts," added Vogt.

Since health problems are known to erode broader well-being over time, the finding that many veterans reported chronic health concerns may have contributed to another key study result, which was that the proportion of veterans reporting good work functioning declined over the first year after leaving military service. "These findings point to the value of targeting intervention to at-risk veteran subgroups and implementing interventions before veterans' readjustment challenges worsen or have the chance to erode their broader well-being. This recommendation may require a fundamental re-thinking of how veteran programs prioritize efforts, as most transition support currently focuses on the needs of veterans with the most acute or chronic concerns."

These finding appear online in the American Journal of Preventive Medicine.

Brain activity synchronizes with sound waves, even without audible sound, through lip-reading, according to new research published in JNeurosci.

Listening to speech activates our auditory cortex to synchronize with the rhythm of incoming sound waves. Lip-reading is a useful aid to comprehend unintelligible speech, but we still don't know how lip-reading helps the brain process sound.

Bourguignon et al. used magnetoencephalography to measure brain activity in healthy adults while they listened to a story or watched a silent video of a woman speaking. The participants' auditory cortices synchronized with sound waves produced by the woman in the video, even though they could not hear it. The synchronization resembled that in those who actually did listen to the story, indicating the brain can glean auditory information from the visual information available to them through lip-reading. The researchers suggest this ability arises from activity in the visual cortex synchronizing with lip movement. This signal is sent to other brain areas that translate the movement information into sound information, creating the sound wave synchronization.

On frigid days, water vapor in the air can transform directly into solid ice, depositing a thin layer on surfaces such as a windowpane or car windshield. Though commonplace, this process is one that has kept physicists and chemists busy figuring out the details for decades.

In a new Nature paper, an international team of scientists describe the first-ever visualization of the atomic structure of two-dimensional ice as it formed. Insights from the findings, which were driven by computer simulations that inspired experimental work, may one day inform the design of materials that make ice removal a simpler and less costly process.

"One of the things that I find very exciting is that this challenges the traditional view of how ice grows," says Joseph S. Francisco, an atmospheric chemist at the University of Pennsylvania and an author on the paper.

"Knowing the structure is very important," adds coauthor Chongqin Zhu, a postdoctoral fellow in Francisco's group who led much of the computational work for the study. "Low-dimensional water is ubiquitous in nature and plays a critical role in an incredibly broad spectrum of sciences, including materials science, chemistry, biology, and atmospheric science.

"It also has practical significance. For example, removing ice is critical when it comes to things like wind turbines, which cannot function when they are covered in ice. If we understand the interaction between water and surfaces, then we might be able to develop new materials to make this ice removal easier."

In recent years, Francisco's lab has devoted considerable attention to studying the behavior of water, and specifically ice, at the interface of solid surfaces. What they've learned about ice's growth mechanisms and structures in this context helps them understand how ice behaves in more complex scenarios, like when interacting with other chemicals and water vapor in the atmosphere.

"We're interested in the chemistry of ice at the transition with the gas phase, as that's relevant to the reactions that are happening in our atmosphere," Francisco explains.

To understand basic principles of ice growth, researchers have entered this area of study by investigating two-dimensional structures: layers of ice that are only several water molecules thick.

In previous studies of two-dimensional ice, using computational methods and simulations, Francisco, Zhu, and colleagues showed that ice grows differently depending on whether a surface repels or attracts water, and the structure of that surface.

In the current work, they sought real-world verification of their simulations, reaching out to a team at Peking University to see if they could obtain images of two-dimensional ice.

The Peking team employed super-powerful atomic force microscopy, which uses a mechanical probe to "feel" the material being studied, translating the feedback into nanoscale-resolution images. Atomic force microscopy is capable of capturing structural information with a minimum of disruption to the material itself, allowing the scientists to identify even unstable intermediate structures that arose during the process of ice formation.

Virtually all naturally occurring ice on Earth is known as hexagonal ice for its six-sided structure. This is why snowflakes all have six-fold symmetry. One plane of hexagonal ice has a similar structure to that of two-dimensional ice and can terminate in two types of edges--"zigzag" or "armchair." Usually this plane of natural ice terminates with a zigzag edges.

However, when ice is grown in two dimensions, researchers find that the pattern of growth is different. The current work, for the first time, shows that the armchair edges can be stabilized and that their growth follows a novel reaction pathway.

"This is a totally different mechanism from what was known," Zhu says.

Although the zigzag growth patterns were previously believed to only have six-membered rings of water molecules, both Zhu's calculations and the atomic force microscopy revealed an intermediate stage where five-membered rings were present.

This result, the researchers say, may help explain the experimental observations reported in their 2017 PNAS paper, which found that ice could grow in two different ways on a surface, depending on the properties of that surface.

In addition to lending insight into future design of materials conducive to ice removal, the techniques used in the work are also applicable to probe the growth of a large family of two-dimensional materials beyond two-dimensional ices, thus opening a new avenue of visualizing the structure and dynamics of low-dimensional matter.

For chemist Jeffrey Saven, a professor in Penn Arts & Sciences who was not directly involved in the current work, the collaboration between the theorists in Francisco's group and their colleagues in China called to mind a parable he learned from a mentor during his training.

"An experimentalist is talking with theorists about data collected in the lab. The mediocre theorist says, 'I can't really explain your data.' The good theorist says, 'I have a theory that fits your data.' The great theorist says, 'That's interesting, but here is the experiment you should be doing and why.'"

To build on this successful partnership, Zhu, Francisco, and their colleagues are embarking on theoretical and experimental work to begin to fill in the gaps related to how two-dimensional ice builds into three dimensions.

"The two-dimensional work is fundamental to laying the background," says Francisco. "And having the calculations verified by experiments is so good, because that allows us to go back to the calculations and take the next bold step toward three dimensions."

"Looking for features of three-dimensional ice will be the next step," Zhu says, "and should be very important in looking for applications of this work."

What The Study Did: Researchers in this review article discuss occupational reproductive hazards for female surgeons in the operating room, including radiation exposure, surgical smoke, working conditions and physical demands, sharps injuries, anesthetic gases and the use of toxic agents.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Matilda Anderson, M.B.B.S., M.P.H., of the Western Health Surgical Department, in Victoria, Australia, and Rose H. Goldman, M.D., M.P.H., of Harvard Medical School in Boston, are the authors.

(doi:10.1001/jamasurg.2019.5420)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

AURORA, Colo. (Jan. 2, 2020) - A small minority of Americans surveyed consider the religious affiliation of the hospitals that treat them, but a majority said they didn't want religious doctrine dictating their healthcare choices, according to a study by researchers at the University of Colorado Anschutz Medical Campus.

The study, published last week today in the journal JAMA Network Open, surveyed 1,446 adults and found that just 6.4% considered the religious affiliation of the hospitals they choose. Yet 71.4%, said that care should not be curtailed by religious dogma. This was especially true among women who are often denied certain reproductive healthcare at Catholic hospitals including birth control, tubal ligations and in vitro fertilization. Emerging health concerns related to transgender health and medical aid in dying have also highlighted conflicts in care for others.

"People may expect restrictions on abortions but they are surprised to find common services like birth control are also restricted," said the study's lead author Maryam Guiahi, MD, associate professor of obstetrics and gynecology at the University of Colorado School of Medicine. "They don't realize that they may not be getting care based on science but rather the care they get is based on religious dogma and doctrine."

Guiahi said religion-based hospitals, especially Catholic ones, are expanding rapidly across the country, particularly in the Midwest. Many have merged to create expansive healthcare systems that may not advertise their religious underpinnings.

A previous website analysis by Guiahi showed that less than a third of Catholic hospitals provided any description of the kinds of care restricted at their facilities.

In 2016, 18.5% of all hospitals were religiously-affiliated. Of those, 9.4% were Catholic non-profit hospitals, 5.1% were Catholic-affiliated, and 4% were affiliated with other religions. Between 2001 and 2016, the number of Catholic acute care hospitals grew by 22%. In 2016, ten of the top 25 healthcare systems were Catholic - nearly half of them located in the Midwest. In some places, they were the only hospitals available.

Providers at such facilities are expected to abide by the Ethical and Religious Directives for Catholic Health Care Services which limit reproductive and end-of-life care, the study said.

The researchers wanted to learn how much Americans actually care about the religious nature of the hospitals they choose and whether they believed such places had the right to override their medical desires based on religious dogma.

Prior surveys indicated that financial factors, travel distance and hospital size were the most important factors when choosing a hospital. But none had specifically asked about religious affiliation.

The researchers surveyed a cross-section of 1,446 adults - 51.5% men, 62.% white and the most common religion was Protestant. The majority didn't consider the religious affiliation of a hospital and didn't think it should impact their care. Only 193 respondents (13.4% of those surveyed) preferred a religious hospital.

The study revealed that 74.9% of women and 68.1% of men agreed with the statement that their healthcare should have priority over the doctrines of a religious hospital.

Guiahi noted a `discordance' between how most patients choose health facilities and their belief about how they should receive care.

"That suggests a general lack of understanding specific to the notion of `institutional conscience' and may cause conflicts in the delivery of care," she said.

The Trump Administration established the Conscience and Religious Freedom Division of the U.S. Dept. of Health and Human Services. The division broadens and enforces the right of religious health care institutions to deny care based on `institutional conscience.'

Guiahi said restricting care based on religious beliefs can be dangerous, especially for women.

"Given the growth in ownership by religious entities in the U.S. and increasing attention to conscientious objections," she said, "our findings point to a need for advocacy and legislation that effectively balance protections for religious institutions with protections for patients."