Culture

A new study investigates a genetic culprit behind abdominal aortic aneurysm, a serious condition that puts people at risk of their aorta rupturing - a potentially deadly event.

Finding a viable genetic target for AAA could change the game, says senior author Katherine Gallagher, M.D., a vascular surgeon and an associate professor of surgery and microbiology and immunology at Michigan Medicine, the academic medical center of the University of Michigan.

That's because there are no medications to directly treat the condition and prevent an aneurysm from growing. Current options include things like addressing blood pressure to lower the stress on the arteries and veins running through the body, and making lifestyle changes like quitting smoking. Most people monitor their aneurysm to see if it grows enough to eventually require endovascular or open surgical repair.

For this study, a team of Michigan Medicine researchers investigated the role of an epigenetic enzyme called JMJD3 in the development of AAAs. They found the gene was turned on in both people and mice who had an AAA and that the gene promoted inflammation in monocyte/macrophages. When they blocked the enzyme, it prevented an aneurysm from forming.

"Targeting the JMJD3 pathway in a cell specific-manner offers the opportunity to limit AAA progression and rupture," says lead author Frank Davis, M.D., a vascular surgery resident at the Frankel Cardiovascular Center.

"We are the first to perform an extensive single-cell RNA sequencing and gene expression analysis on human AAAs and non-aneurysmal aortic control samples," Gallagher adds.

INDIANAPOLIS -- A new report from the National Academies of Sciences, Engineering, and Medicine (National Academies) details the state of dementia care and research in America and provides guidance on future research to make sure both patients and their families are having their needs met by the care they receive. Sections of the report highlight the effectiveness of the collaborative care model as well as successful implementation, citing research from Regenstrief Institute, Eskenazi Health and the Indiana University School of Medicine.

There are between 3.7 million and 5.8 million people living with dementia in the United States, and that number is likely to grow as the population ages.

The report, Meeting the Challenge of Caring for Persons Living with Dementia and Their Care Partners and Caregivers: A Way Forward, sponsored by the National Institutes of Health's National Institute on Aging, looked at the various needs of people with dementia, including help with medication use, paying bills and managing day-to-day activities. It notes several limitations of current care interventions. However, based on an independent systematic review by the Agency for Healthcare Research and Quality, found two types of interventions that are supported by low-strength evidence of benefit: collaborative care models, which integrate medical and psychosocial care; and Resources for Enhancing Alzheimer's Caregiver Health (REACH) II, an intervention aimed at supporting family caregivers.

Regenstrief Research Scientist and IU School of Medicine Professor of Medicine Christopher Callahan, M.D., was a member of the committee that compiled the report. He has worked extensively with colleagues at Regenstrief, IU and Eskenazi Health on developing and implementing collaborative care models for Alzheimer's disease. Improving care for persons living with dementia and their care partners is an important research focus for a large team of scientists in the Center for Aging Research at the Regenstrief Institute.

"This report incorporated feedback from people with dementia and their families, and they indicated that outcomes measured by past research have been too narrow and there are other areas of wellbeing that are important to them that have not been taken into consideration," said Dr. Callahan. "Collaborative care works to provide holistic care to the patients and their families, and the model can be adapted to address needs that are not currently being met."

Collaborative care models integrate medical and psychosocial care, delivered by a team of providers including physicians, nurses, psychologists, care coordinators and social workers. This model has proven to significantly improve patient and caregiver outcomes and reduce costs and has been successfully implemented at the Sandra Eskenazi Center for Brain Care Innovation.

The National Academies report highlighted the urgent need to put into practice evidence-based interventions, referencing the work of Regenstrief Research Scientist and IU School of Medicine Professor Malaz Boustani, M.D., MPH. Dr. Boustani is creating strategies for more trials that take place in real-world situations, while still being rigorous in testing important outcomes.

"Patients and families indicated that they understand that interventions will not be perfect, but they want them implemented now, in the real world, while research and refinement continues," said Dr. Callahan.

The report proposes a blueprint for future research, which includes methodological improvements and approaches that can complement randomized control trials. A major focus should be assessing real-world effectiveness and prioritizing inclusive research.

JACKSONVILLE, Fla. -- In a new paper published in Nature Communications, Mayo Clinic researchers and collaborators report the protein-coding gene SERPINA5 may worsen tau protein tangles, which are characteristic of Alzheimer's disease, and advance disease. By combining clinical expertise, brain tissue samples, pathology expertise and artificial intelligence, the team clarified and validated the relevance of the gene to Alzheimer's disease.

The researchers used tissue samples from 385 brains donated to the Mayo Clinic Brain Bank, which houses more than 9,000 brain tissue specimens for the study of neurodegenerative disorders. The samples were from people who were diagnosed with Alzheimer's disease and lacked co-existing diseases found in the brain. This ensured a spotlight on Alzheimer's disease, which enabled the team to focus on targets relevant to the disease.

These samples were used to classify the pattern of protein tangles associated with Alzheimer's. Then the team used digital pathology and RNA sequencing to identify gene expression in the samples, which effectively measures gene changes responsible for instructing proteins.

"We were able to look at an entire disease spectrum and find gene changes that may really influence the hippocampus, the brain's memory center," says Melissa Murray, Ph.D., a Mayo Clinic translational neuropathologist and lead author on the paper. "That means we may have targets that indicate why some people have relative preservation and some people have relative exacerbation of memory loss symptoms."

Using a machine learning algorithm, the authors narrowed the genes of interest from about 50,000 to five. The top candidate, SERPINA5, was found to be strongly associated with tau tangle progression in the hippocampus and cortex of the samples. The researchers plan to investigate how SERPINA5 interacts with tau protein to develop an inhibitor.

"Much of the focus of therapeutics is on abnormal proteins ? amyloid and tau ? used to biologically define Alzheimer's disease," says Dr. Murray. "But we hope to take a step back to look at a new interacting partner that may be actually accelerating tau or pushing tau accumulation past the tipping point."

Based on a growing understanding of how Alzheimer's disease may affect people at different ages, or differences observed between women and men, the study team did not limit their investigation by adjusting for age and sex.

The team was recently awarded a grant by the state of Florida to ensure the findings are broadly applicable across an ethno-racially diverse Alzheimer's disease cohort, as the need for more research to clarify the relevance of gene expression changes on hippocampal vulnerability may be critical for preserving memory loss in Alzheimer's disease. But, Dr. Murray says, by starting with the human brain and ending with it, the researchers hope their findings provide a deeper level of understanding that helps advance findings to clinical trials faster.

"While we have direct evidence of SERPINA5 in the context of Alzheimer's disease, SERPINA3 in this same family of genes has also been looked at in Alzheimer's, and SERPINA1 in ALS. So I think it's about collective awareness and paying attention to this group of proteins."

Hydrogen will be needed in large quantities as an energy carrier and raw material in the energy system of the future. To achieve this, however, hydrogen must be produced in a climate-neutral way, for example through so-called photoelectrolysis, by using sunlight to split water into hydrogen and oxygen. As photoelectrodes, semiconducting materials are needed that convert sunlight into electricity and remain stable in water. Metal oxides are among the best candidates for stable and inexpensive photoelectrodes. Some of these metal oxides also have catalytically active surfaces that accelerate the formation of hydrogen at the cathode or oxygen at the anode.

Why is rust not much better?

Research has long focused on haematite (α-Fe2O3), which is widely known as rust. Haematite is stable in water, extremely inexpensive and well suited as a photoanode with a demonstrated catalytic activity for oxygen evolution. Although research on haematite photoanodes has been going on for about 50 years, the photocurrent conversion efficiency is less than 50% of the theoretical maximum value. By comparison, the photocurrent efficiency of the semiconductor material silicon, which now dominates almost 90% of the photovoltaic market, is about 90% of the theoretical maximum value.

Scientists have puzzled over this for a long time. What exactly has been overlooked? What is the reason that only modest increases in efficiency have been achieved?

Israeli-German team solves the puzzle

In a recent study published in Nature Materials, however, a team led by Dr. Daniel Grave (Ben Gurion University), Dr. Dennis Friedrich (HZB) and Prof. Dr. Avner Rothschild (Technion) has provided an explanation as to why haematite falls so far short of the calculated maximum value. The group at Technion investigated how the wavelength of absorbed light in hematite thin films affects the photoelectrochemical properties, while the HZB team determined the wavelength dependent charge carrier properties in thin films of rust with time-resolved microwave measurements.

Fundamental physical property extracted

By combining their results, the researchers succeeded in extracting a fundamental physical property of the material that had generally been neglected when considering inorganic solar absorbers: The photogeneration yield spectrum. "Roughly speaking, this means that only part of the energy of the light absorbed by haematite generates mobile charge carriers, the rest generates rather localised excited states and is thus lost," Grave explains.

Rust will not get much better

"This new approach provides experimental insight into light-matter interaction in haematite and allows distinguishing its optical absorption spectrum into productive absorption and non-productive absorption," Rothschild explains. "We could show that the effective upper limit for the conversion efficiency of haematite photoanodes is significantly lower than that expected based on above band-gap absorption," says Grave. According to the new calculation, today's "champion" haematite photoanodes have already come quite close to the theoretically possible maximum. So it doesn't get much better than that.

Assessing new photoelectrode materials

The approach has also been successfully applied to TiO2, a model material, and BiVO4, which is currently the best-performing metal oxide photoanode material. "With this new approach, we have added a powerful tool to our arsenal that enables us to identify the realizable potential of photoelectrode materials. Implementing this to novel materials will hopefully expedite the discovery and development of the ideal photoelectrode for solar water splitting. It would also allow us to 'fail quickly', which is arguably just as important when developing new absorber materials" says Friedrich.

Eighteen minutes might be all it takes to ensure a full recovery for stroke patients in rural South Carolina.

By changing EMS workflows and incorporating telemedicine techniques, physicians at MUSC Health have partnered with Georgetown Memorial Hospital and Hampton Regional Medical Center to significantly shorten the time between a patient's stroke symptom onset and their treatment, as recently reported in the Journal of Stroke and Cerebrovascular Diseases.

Through MUSC Health's Telestroke Network, emergency medical technicians (EMTs) can video chat with stroke specialists to begin a patient's consult before they even arrive at the hospital.

"We realized that if we could start seeing these stroke patients before they came into the emergency room, we could reduce the time it took for us to treat them," said Christine Holmstedt, D.O., the medical director of MUSC Health's Comprehensive Stroke Center.

A stroke occurs when blood flow to the brain is interrupted. In an ischemic stroke, blood flow is clogged by a block in an artery leading to the brain. In a hemorrhagic stroke, there is bleeding into the brain tissue from a burst blood vessel, and in both cases, time is of the utmost importance.

Stroke treatments are extremely time sensitive and need to be started as soon as possible after patients begin experiencing stroke symptoms in order to improve clinical outcomes and reduce their chances of disability or death.

Acute stroke treatments include the intravenous clot-busting agent alteplase (tPA) and/or a mechanical thrombectomy where a device is threaded through the blood vessel to break up the clot. With this quick response, physicians ensure the greatest chance at a recovery, and every minute reduction in treatment improves their patient's chances more. The average human brain contains 22 billion neurons, according to an article in Stroke, and during an acute ischemic stroke, 1.9 million are lost every minute.

The new telestroke workflow in the study involved three-way communication between the stroke specialist, the EMT, the patient and the receiving hospital nurse and emergency medicine physician. EMTs could even start the consult while still at the patient's home and ask family members for a more accurate history of the patient. Performing the consult and examination on the way to the hospital allowed emergency room doctors and nurses to be more prepared for their incoming stroke patient. Holmstedt pointed out a few patients who were rerouted to a comprehensive stroke center while on the way to the closest hospital because the stroke was too severe for the local hospitals. A few patients were even flown to MUSC from their homes if the examination revealed they needed more specialized treatment and care.

Before the telestroke program, stroke patients would be brought directly to the closest hospital, where they would begin their examination soon after their arrival. Their treatment would continue there, or they could be transferred to another hospital. With the new workflow, that examination happens en route, cutting down on critical treatment time.

"A 15-minute reduction in door-to-treatment time leads to patients with reduced complications from tPA and significant reduction in disability or death," said Holmstedt. "They are more likely to be discharged to an acute rehab rather than long-term care, and they have much better functional outcomes." These new protocols influenced that 15-minute reduction even further by bringing average treatment times down from 38 minutes to 20.

This program is especially important in rural areas where patients are spread out geographically. Other programs in the U.S. have been incorporating mobile stroke units, which are armed with vital stroke equipment like CT scanners, but these stroke units can cost upwards of $2,000,000 and are not feasible for South Carolina. By comparison, the telestroke console costs about $2,000 per ambulance and helps rural areas see stroke experts before they even get to the hospital, according to Holmstedt.

In its 2015 infancy, the telestroke program began with a partnership between Holmstedt and Georgetown EMS Director Dale Hewitt and Georgetown Hospital Stroke Coordinator Jessica Hewitt. They started with 5 ambulances in 1 county to test the concept and feasibility of the program and have since grown to 26 additional trucks in 5 different counties throughout the state.

Holmstedt is currently working with the MUSC College of Health Professions and Clemson University to assess the economic impact of the telestroke program and the potential for further expansion.

"These improved outcomes reduce disability and even death for patients seen with acute stroke," said Holmstedt. "And they don't negatively impact the EMT workflow, so we can bring more efficient treatment options to the state's rural population. And that's significant."

April 19, 2021 - At the current rate of change, it will take more than 200 years for the proportion of women in orthopaedic surgery to reach parity with the overall medical profession, according to a study in Clinical Orthopaedics and Related Research® (CORR®), a publication of The Association of Bone and Joint Surgeons®. The journal is published in the Lippincott portfolio by Wolters Kluwer.

"Substantive changes must be made across all levels of orthopaedic education and leadership to steepen the current curve," concludes the report by Atul F. Kamath, MD, of the Cleveland Clinic Foundation and colleagues. "Our findings support the need for changes in medical schools, orthopaedic residency programs, as well as at the level of professional specialty and subspecialty societies."

Orthopaedic surgery remains 'dead last in gender diversity'

The researchers queried the National Provider Identifier Registry of the Centers for Medicare and Medicaid Services, which requires clinicians to identify themselves as male or female. As of April 2020, the registry included data on 31,296 practicing orthopaedic surgeons, of whom 8 percent were women. That's far lower than the proportion of women in the medical profession overall: 36 percent in 2019.

Between 2010 and 2019, the compound annual growth rate of women orthopaedic surgeons was 2 percent (20 percent over the decade). Assuming this rate were sustained after 2019, it would take 217 years - until 2236 - to achieve gender parity with the rest of the medical profession. Time to achieve parity with the US population - currently 51 percent female - would be 326 years, or until 2354.

The researchers also analyzed trends by orthopaedic subspecialty and by region. In 2019, women accounted for 26 percent of surgeons in pediatric orthopaedics and 14 percent in foot and ankle surgery, but only 3 percent in adult reconstructive surgery and 3 percent in spinal surgery. After 2019, the gains in subspecialty representation are projected to be just 1 or 2 percent, with no growth in adult reconstructive surgery.

The Midwest had the greatest growth in proportion of women orthopaedic surgeons, 27 percent; followed by the Northeast, 20 percent. Rates in the West and South were 17 percent and 19 percent, respectively: less than the rate of national growth.

Dr. Kamath and colleagues call for changes throughout orthopaedics to hasten the rate of change. Medical schools should offer an orthopaedic surgery rotation to foster interest among women students and to help curb concerns related to work-life balance and a culture dominated by men. The authors also suggest benchmarks to increase the proportion of women trainees and faculty in orthopaedic surgery training programs, particularly in the South and West; and more women among the leadership of orthopaedic subspecialty societies.

In an accompanying 'Take 5' interview with Dr. Kamath, CORR® Editor-in-Chief Seth S. Leopold, MD, writes: "Literally every other medical and surgical specialty has overcome this problem to a greater degree than has orthopaedic surgery; we're dead last in gender diversity." He calls on his specialty to stop paying "lip service" to "the substantial absence of women from our specialty and the lack of progress towards remedying the disparity over time."

Dr. Kamath believes the orthopaedic community should seek help from other fields that have been more successful in increasing representation of women: "It is not impossible to achieve gender parity; we just have to actually acknowledge that it is a problem, and then do something about it."

"We applaud these authors for highlighting this critical issue," comments Julie Samora, MD. Dr. Samora is President of the Ruth Jackson Orthopaedic Society, a support and networking group for the growing number of women orthopaedic surgeons. "The projection of over 300 years to achieve gender parity with the US population is alarming."

"We are missing out on outstanding talent and doing a disservice to our patients," Dr. Samora adds. "The time is now to commit to action, to have intentional efforts to increase the representation of women in orthopedics. Improving gender diversity will not only make our programs and profession better, but will also improve the overall care of our patients."

A first-of-its-kind study led by The University of Texas at Austin has found that rock weathering and water storage appear to follow a similar pattern across undulating landscapes where hills rise and fall for miles.

The findings are important because they suggest that these patterns could improve predictions of wildfire and landslide risk and how droughts will affect the landscape, since weathering and water storage influence how water and nutrients flow throughout landscapes.

"There's a lot of momentum to do this work right now," said study co-author Daniella Rempe, an assistant professor at the UT Jackson School of Geosciences Department of Geological Sciences. "This kind of data, across large scales, is what is needed to inform next-generation models of land-surface processes."

The research was led by Michelle Pedrazas, who conducted the work while earning a master's degree at the Jackson School. It was published in the Journal of Geophysical Research: Earth Surface.

Despite the importance of what's happening inside hills, most computer models for simulating landscape behavior don't go deeper than the soil due to a lack of data that can scale to large areas, Rempe said.

This study helps fill that knowledge gap, being the first to methodically sample the interiors of a sequence of hill slopes. The research focused on investigating the "critical zone," the near surface layer that includes trees, soils, weathered rock and fractures.

"This study helps to unravel a mystery in the critical zone research community, the linkage between bedrock weathering, topography and storage of water in mountainous watersheds," said Eric Pierce, the director of the Environmental Sciences Division at Oak Ridge National Laboratory who was not involved with the study.

The research site is in Northern California and is part of a national network of Critical Zone Observatories. The scientists drilled 35 boreholes across a series of hill slopes and their valleys to collect subsurface samples and other data. They also collected a core sample at the peak of each hill slope that captured the entire height of the hill - a distance that varied from 34 to 57 feet (10.5 to 17.5 meters).

The samples revealed deeper weathering and fracturing in hilltops and thinner weathering in valleys, in addition to weathering that penetrates deeper into shorter hill slopes than taller ones.

This finding is important because it suggests that computer models could use this scaling trend to model the extent of weathering in similar undulating terrain.

Where water is stored in the weathered rocks of hill slopes is an important question, especially during the arid summers experienced in the field area. Research led by Rempe in 2018 revealed that trees tap into water stored as "rock moisture" in the fractures and pores of critical zone rocks during droughts.

This study also revealed rock moisture in the critical zone - but only within the first 20 feet of weathered rock.

Learning more about how hill slopes store their water can help researchers determine what areas are most at risk of becoming wildfire hazards. Pedrazas said that the wildfire connection was clear when they collected the field data in 2018. Wildfires blazing in other parts of California turned the sun red and filled the sky with smoke. The setting underscored the fact that knowing what's happening at the surface is closely connected to what's happening within the hills.

"We were really seeing the potential impact of our research, [the importance of] where is the water, and when are trees really going to dry up, and what risk that is for society," Pedrazas said.

The fact that the human body is made up of cells is a basic, well-understood concept. Yet amazingly, scientists are still trying to determine the various types of cells that make up our organs and contribute to our health.

A relatively recent technique called single-cell sequencing is enabling researchers to recognize and categorize cell types by characteristics such as which genes they express. But this type of research generates enormous amounts of data, with datasets of hundreds of thousands to millions of cells.

A new algorithm developed by Joshua Welch, Ph.D., of the Department of Computational Medicine and Bioinformatics, Ph.D. candidate Chao Gao and their team uses online learning, greatly speeding up this process and providing a way for researchers world-wide to analyze large data sets using the amount of memory found on a standard laptop computer. The findings are described in the journal Nature Biotechnology.

"Our technique allows anyone with a computer to perform analyses at the scale of an entire organism," says Welch. "That's really what the field is moving towards."

The team demonstrated their proof of principle using data sets from the National Institute of Health's Brain Initiative, a project aimed at understanding the human brain by mapping every cell, with investigative teams throughout the country, including Welch's lab.

Typically, explains Welch, for projects like this one, each single-cell data set that is submitted must be re-analyzed with the previous data sets in the order they arrive. Their new approach allows new datasets to the be added to existing ones, without reprocessing the older datasets. It also enables researchers to break up datasets into so-called mini-batches to reduce the amount of memory needed to process them.

"This is crucial for the sets increasingly generated with millions of cells," Welch says. "This year, there have been five to six papers with two million cells or more and the amount of memory you need just to store the raw data is significantly more than anyone has on their computer."

Welch likens the online technique to the continuous data processing done by social media platforms like Facebook and Twitter, which must process continuously-generated data from users and serve up relevant posts to people's feeds. "Here, instead of people writing tweets, we have labs around the world performing experiments and releasing their data."

The finding has the potential to greatly improve efficiency for other ambitious projects like the Human Body Map and Human Cell Atlas. Says Welch, "Understanding the normal compliment of cells in the body is the first step towards understanding how they go wrong in disease."

One of the marks of a successful idea in science is how quickly it can develop and evolve. In the case of the Anthropocene, the conceptual evolution has taken place with extraordinary speed. The strikingly influential hypothesis launched by the late Nobel laureate Paul Crutzen (Obituary, 24th Feb 2021) in 2000, was that the actions of an industrialised humanity has impacted the Earth so greatly as to trigger a new geological epoch. Originally developed within the Earth System science community in charting global environmental change, the Anthropocene then began to be analysed by geologists to see whether it really could be accepted, formally, on to the Geological Time scale--ongoing work steered from the outset by a University of Leicester team (Professors Zalasiewicz, Waters, Williams) and other UK and international scholars. "It quickly spread widely across the sciences, humanities and arts, including to become a central framing concept of the IPCC, the UN Environment Programme and in international law", Waters explains. With such profound influence across so many different communities, of such different backgrounds and perspectives, though, came large questions about what the Anthropocene is, and when it started.

Originally Crutzen suggested it began as the Industrial Revolution commenced in the late 18th century, but subsequent analysis by the Anthropocene Working Group (AWG), has refined this estimate. "The greatest changes, of population, industrialization, globalization have taken place with the 'Great Acceleration' of the boom post-WWII years of the mid-20th century", Zalasiewicz explained. "In that brief spell--a little less than one average human lifetime--humanity has burned through more energy than in the previous 12 millennia and more", Williams said. This is driving the physical, chemical and biological changes to Earth that are now destabilizing the biosphere and climate, leaving records in modern-day strata, including plastics, concrete and supermarket chicken bones that justify the Anthropocene in geology.

But look at the Anthropocene from more human-based perspectives, and one can foreground human impacts on the environment that go back thousands of years. So should the beginning of the Anthropocene be pushed back to these earliest impacts, of the felling of forests, or the domestication of animals, or the spread of farmland soils, or of the linking of the New World with the Old? "All these ideas, and more, have emerged, in intense discussions that have erupted around this vivid and powerful new concept--each of which puts it in a different light", new AWG member Jens Zinke (UofL) adds. What, then, is the Anthropocene?

A new paper from the AWG, representing a wide range of academic disciplines, faces up to this conundrum, the playing out of which will determine how the Anthropocene will survive in human thinking. "Dissecting the many interpretations of the Anthropocene suggests that a range of quite distinct, but variably overlapping, concepts are in play", Waters noted. The debate has broken many barriers between academic disciplines--but also led to the risk of confusion of different meanings of the term. How should this be resolved? The authors encourage more debate across various disciplines--and suggest that eventual formalization of the Anthropocene in geology would help stabilize its interpretation and use, including to help societies to navigate the many challenges of the emerging Anthropocene world.

April 19, 2021 -- Ensuring COVID-19 vaccine access for refugee and displaced populations, and addressing health inequities, is vital for an effective pandemic response. Yet, vaccine allocation and distribution has been neither equitable nor inclusive, despite that global leaders have stressed this as a critical aspect to globally overcoming the pandemic, according to a paper published by Columbia University Mailman School of Public Health. Read "Leave No-one Behind: Ensuring Access to COVID-19 vaccines for Refugee and Displaced Populations" in the journal Nature Medicine.

As of April 1st, high and upper-middle-income countries received 86 percent of the vaccine doses delivered worldwide, while only 0.1 percent of doses have been delivered in low-income countries. Worldwide, over 80 percent of refugees and nearly all internally displaced persons are hosted by low and middle-income countries - nations at the end of the line for COVID-19 vaccine doses.

"As the world grapples with supply challenges and inequitable vaccine access on local and global scales, marginalized groups, particularly refugees, internally displaced persons and stateless persons, face a double burden of access, even within countries that are themselves marginalized on the global stage," said Monette Zard, MA, Allan Rosenfield Associate Professor of Forced Migration and Health and director of the forced migration and health program at Columbia Mailman School. "Legal status should have no place in decisions about vaccine access, and relying on regularization as a route to vaccination will unacceptably delay the protective effects for migrants and refugees, particularly in higher risk groups."

In fragile settings with weak governance, competition for scarce COVID-19 vaccines may heighten tensions and exacerbate conflict, while unequal access raises the prospect of populations moving in an effort to access vaccines that are not available in their country or region, according to the authors.

The COVAX facility allocates around 5 percent of total available vaccine doses for humanitarian use, including vaccinating refugees, yet the total 2 billion vaccine doses targeted by the end of 2021 will only cover 20 percent of participating countries' populations, at most. Poorer countries may not be able to widely vaccinate their populations until 2023.

To create an equitable and inclusive COVID-19 vaccination strategy, Zard and co-authors believe lessons can also be drawn from experience managing conditions such as HIV and TB among mobile populations, as well as previous large-scale vaccination campaigns in humanitarian settings. They point out how the global community approaches COVID-19 vaccinations may further entrench the inequities and distrust experienced by refugees and displaced populations around the world or is a chance to build stronger, fairer health systems that are better prepared to respond to COVID-19 and future health emergencies. "Engage, listen, and mobilize trusted community and religious leaders -- involving the community, including displaced populations, in vaccine activities is vital,"noted Zard.

"Policy makers need to seize the opportunity of the pandemic to strengthen health systems more broadly and sustainably, to better respond to the challenges of COVID-19, while addressing the comprehensive health needs of refugees and host populations," observes one of the authors S. Patrick Kachur, MD, professor of population and family health at Columbia Mailman School. "As the world confronts one of the most formidable public health challenges in recent history, how we respond today will not only determine the course of this pandemic, but also who benefits from public health advances for years to come."

Tools that allow neuroscientists to record and quantify functional activity within the living brain are in great demand. Traditionally, researchers have used techniques such as functional magnetic resonance imaging, but this method cannot record neural activity with high spatial resolution or in moving subjects. In recent years, a technology called optogenetics has shown considerable success in recording neural activity from animals in real time with single neuron resolution. Optogenetic tools use light to control neurons and record signals in tissues that are genetically modified to express light-sensitive and fluorescent proteins. However, existing technologies for imaging light signals from the brain have drawbacks in their size, imaging speed, or contrast that limit their applications in experimental neuroscience.

A technology called light-sheet fluorescence imaging shows promise for imaging brain activity in 3D with high speed and contrast (overcoming multiple limitations of other imaging technologies). In this technique, a thin sheet of laser light (light-sheet) is directed through a brain tissue region of interest, and fluorescent activity reporters within the brain tissues respond by emitting fluorescence signals that microscopes can detect. Scanning a light sheet in the tissue enables high-speed, high-contrast, volumetric imaging of the brain activity.

Currently, using light-sheet fluorescence brain imaging with nontransparent organisms (like a mouse) is difficult because of the size of the necessary apparatus. To make experiments with nontransparent animals and, in the future, freely moving animals feasible, researchers will first need to miniaturize many of the components.

A key component for the miniaturization is the light-sheet generator itself, which needs to be inserted into the brain and thus must be as small as possible to avoid displacing too much brain tissue. In a new study reported in Neurophotonics, an international team of researchers from the California Institute of Technology (USA), University of Toronto (Canada), University Health Network (Canada), the Max Planck Institute of Microstructure Physics (Germany), and Advanced Micro Foundry (Singapore) developed a miniature light-sheet generator, or a photonic neural probe, that can be implanted into a living animal's brain.

The researchers used nanophotonic technology to create ultrathin silicon-based photonic neural probes that emit multiple addressable thin sheets of light with thicknesses

Describing the significance of his team's work, the study's lead author, Wesley Sacher, says, "This new implantable photonic neural probe technology for generating light sheets within the brain circumvents many of the constraints that have limited the use of light-sheet fluorescence imaging in experimental neuroscience. We predict that this technology will lead to new variants of light-sheet microscopy for deep brain imaging and behavior experiments with freely moving animals."

Such variants would be a boon to neuroscientists seeking to understand the workings of the brain.

Below please find link(s) to new coronavirus-related content published today in Annals of Internal Medicine. All coronavirus-related content published in Annals of Internal Medicine is free to the public. A complete collection is available at https://annals.org/aim/pages/coronavirus-content.

1. Liver transplant recipient reinfected with SARS-CoV-2 infection 3 months after initial diagnosis

Viral genomic sequencing used to distinguish between relapse and reinfection

Free full text: https://www.acpjournals.org/doi/10.7326/L21-0108

A liver transplant recipient was reinfected with SARS-CoV-2 111 days after his initial diagnosis. Researchers from the University of Massachusetts Medical School and The Broad Institute of MIT and Harvard used viral genomic sequencing to distinguish whether the later positive samples were due to SARS-CoV-2 relapse or reinfection. The case report is published in Annals of Internal Medicine.

A 61-year-old man with a history of liver transplant reported to the emergency department (ED) complaining of fever, nausea, vomiting, and cough. The patient tested positive for SARS-CoV-2 infection with a RT-qPCR swab taken at the time of his visit. Swabs taken 48 and 53 days after his visit were negative for the virus. On day 111, the patient returned to the ED reporting several days of increasing confusion, hallucinations, unstable gait, and frequent falls. Once again, the patient tested positive for SARS-CoV-2 infection.

According to the study authors, the patient may have been susceptible to reinfection due to a lack of antibody response after the first infection. This case shows that genomic sequencing offers the ability to discern whether subsequent infections may be reinfection. In addition, genomic sequence data can also identify variants circulating in the population that are of high risk because of infectivity, disease severity, or resistance to treatment.

Media contacts: A PDF for this article is not yet available. Please click the link to read the full text. The corresponding author, Stuart M. Levitz, MD, can be reached at Stuart.Levitz@umassmed.edu.

2. People of color have substantially higher risk for hospitalization, intensive-level care for COVID-19 than White persons

Authors say pandemic response must be adjusted to be culturally appropriate, address mistrust in health care system

Free full text: https://www.acpjournals.org/doi/10.7326/M20-8283

Even after adjustment for known COVID-19 risk factors, such as comorbidities and body mass index, persons of color continue to have a substantially higher risk for hospitalization and requiring intensive-level care than White persons. These results confirm findings from earlier in the pandemic suggesting that COVID-19 affects Hispanic, Black or African American, and Asian persons disproportionately. Further, they provide evidence of the disproportionate effect of COVID-19 on Pacific Islanders. A brief research report is published in Annals of Internal Medicine.

Researchers from Kaiser Permanente Southern California (KPSC) studied electronic health records from KPSC to compare age- and sex-adjusted relative risk (RR) of COVID-19 testing, cases, hospitalizations, and intensive-level care among Hispanic, Black or African American, Asian, and Pacific Islander populations versus White populations before and after adjusting for comorbidities and body weight status. The researchers observed disparities across race/ethnicity for all outcomes regardless of adjustment. Patients of color were slightly more likely to be tested than White patients but were substantially more likely to be hospitalized and to receive intensive-level care. Hispanic patients had the highest RRs of being tested and testing positive or being diagnosed with COVID-19 compared with White patients; however, Pacific Islander, Black or African American, and Asian patients had higher RRs for severe COVID-19 outcomes than White patients.

According to the authors, inequities in COVID-19 outcomes are a call to action for a culturally appropriate pandemic response and vaccination strategies that go beyond addressing comorbidities and account for factors like distrust in the medical system, resource constraints, language proficiency, and health literacy.

Media contacts: A PDF for this article is not yet available. Please click the link to read the full text. The corresponding author, Claudia Nau, PhD, can be reached through Maureen McInaney at Maureen.McInaney@kp.org or Kerry Sinclair at KSinclair@webershandwick.com.

LOS ALAMOS, N.M., April 19, 2021 -- A recent series of experiments at the National High Magnetic Field Laboratory (National MagLab) at Los Alamos National Laboratory leveraged some of the nation's highest-powered nondestructive magnets to reveal an exotic new phase of matter at high magnetic fields. The experiments studied the unusual Kondo insulator ytterbium dodecaboride (or YbB12) and were the first results from the new 75-tesla duplex magnet housed at the National MagLab's Pulsed Field Facility at Los Alamos.

"This magnet and the resulting experiments are the first fruits of the National Science Foundation-supported pulsed magnet surge," said Michael Rabin, director of the Pulsed Field Facility at Los Alamos. "The surge is creating new science capabilities in the 75-85 tesla range -- leading eventually to an expanded portfolio of some of the most powerful nondestructive magnetic fields in the world."

Researchers from the University of Michigan, Kyoto University and Los Alamos conducted the research, published last week in Nature Physics.

In Kondo insulators, there is an unusual quantum-mechanical mixing of mobile electrons and magnetic atoms, making these materials attractive as model systems for basic science, electronic devices, and possibly quantum computing. Unlike simple metals and insulators, YbB12 exhibits properties of both -- its electrical resistance behaves like that of an insulator, but it also clearly shows quantum oscillations at high magnetic fields that are a fundamental metallic property.

"A plethora of theories has emerged to account for such behavior," said John Singleton, a fellow at the MagLab's Los Alamos campus and co-author on the paper. "Some physicists believe this is a condensed-matter incarnation of neutral Majorana fermions, entities normally explored in particle physics."

To test these theories, the research team wanted to observe how the neutral fermions that they found in YbB12 responded to extreme conditions. The high magnetic fields in the new 75-tesla duplex magnet available at the National MagLab's Pulsed Field Facility were used to suppress the insulating properties of YbB12 and measure quantum oscillations and various properties that are affected by the presence of the neutral fermions.

"The extra 10 tesla above our standard pulsed magnets provided by the duplex magnet enabled this new state of matter -- exotic fermions gradually being drowned in a sea of normal electrons -- to be tracked across a wide range of magnetic fields for the first time," said Singleton. This confirmed that the phenomena observed were definitely associated with the neutral fermions and provided a test of the various theoretical models.

The duplex magnet is a result of a Pulsed Field Facility "magnet surge" supported by the National Science Foundation. The purpose of the surge is to create new and expanded science capabilities in the 75-85 tesla range. The duplex magnet system is available to researchers from around the world to conduct their own experiments, and an 85-tesla duplex magnet and necessary supporting technology are under development.

These new pulsed magnets are powered solely by capacitor banks without relying on the Los Alamos generator that powers the much larger 100 tesla magnet. The generator is currently offline for repairs and maintenance, so magnets from the surge fill an important gap for condensed-matter physics in high magnetic fields.

The new magnets are called duplex magnets because they are made from two concentric electromagnet coils (solenoids) that are powered independently from separate capacitor-bank modules. When the generator is back online, technology developed by the pulsed magnet surge will be combined with Los Alamos' largest magnets to further expand the MagLab's science capabilities.

CORVALLIS, Ore. - Four decades after their capture more than a half-mile below the ocean's surface, three snailfish species have received their scientific names, two of them from school children on Guam in the island's native Chamorro language.

The rare specimens of liparids were collected in the early 1980s in traps set in the Mariana Archipelago in the western Pacific Ocean, deposited with NOAA's Pacific Islands Fisheries Science Center in Hawaii and did not get examined until recently, when they were noticed during the center's move to a new location.

Oregon State alumnus Bruce Mundy, retired from the National Marine Fisheries Service, learned of the liparid specimens from Robert Moffitt, the Pacific Islands Fisheries Science Center biologist who collected them.

Mundy and fellow OSU alum David Stein of the OSU College of Agricultural Sciences describe the new species, Paraliparis echongpachot, P. kadadakaleguak and P. marianae, in a paper published today in Ichthyological Research.

"David Stein came to Hawaii to assist with the description of another snailfish species from the depths of the Mariana Trench and visited PIFSC to examine the snailfish specimens," Mundy said. "That's when he found that three distinct, undescribed species were among them."

The specimens have been deposited in the Oregon State University Ichthyology Collection, curated by Brian Sidlauskas and Peter Konstantinidis in the Department of Fisheries, Wildlife, and Conservation Sciences. OSU was selected as the archive for the specimens because the Pacific Islands Fisheries Science Center does not maintain permanent biological collections.

Captured in traps as a byproduct of assessments of deepwater shrimp populations, the species are the first of the snailfish family to be described from the Mariana Islands bathyal zone - between 200 and 2,000 meters deep.

There are more than 400 species of snailfishes known from about 30 genera; they have tadpole-like bodies without scales and range from 2 inches to 30 inches in length.

Needing cool or cold water, snailfish are most abundant and diverse in temperate and polar areas; in the tropics and subtropics, suitable water temperatures occur only at bathyal depths or deeper.

"NOAA research vessels made ichthyological collections throughout the Mariana Islands in the 1980s," Mundy said. "A surprising number of snailfishes, unexamined until recently, were captured. Both collection and preservation have been hard on these soft-bodied, fragile fishes, but the condition of some of them remained good enough that description was possible. Among those are the three in this paper."

Students in Guam from elementary through high school age were invited to compete for the right to suggest names for the new species, and two of the student suggestions were chosen by Stein and Mundy. They named the third species, Paraliparis marianae, after the archipelago in which it was found.

Alyssa Roces from Okkodo High School suggested the name Paraliparis kadadakaleguak in recognition of the fish's short ribs; in Chamorro, kadada' kaleguak means short rib bone.

Aydan Charfauros of Tamuning Elementary came up with Paraliparis echongpachot, choosing echong pachot as the species name because that term means crooked mouth in Chamorro; the mouth is a key defining characteristic of this fish.

"Names for new species have traditionally been formed from Greek or Latin words, from the names of people who collected the specimens or from the names of other scientists to honor them," Mundy said. "This has resulted in Euro-American names for species worldwide, a practice that is regarded by some to be colonialist or imperialist. In recent years there has been a movement to form new names from the languages of indigenous people in the areas where new species are found, to reconnect taxonomy to them."

Stein, a globally recognized authority on snailfishes who has described more than 100 liparid species, says a goal when trying to invent a name is for it to be "euphonious."

"You want a name that sounds good, and I particularly enjoy kadadakaleguak," he said. "I just love it."

Stein notes that a gap of four decades between discovery and naming is not unusual.

"Several species have been named that were hundreds of years old," he said. "That's one of the reasons museums exist, and it's very important and largely unappreciated."

"New studies use old material all of the time, and not only for the identification of new species," Sidlauskas added. "People want DNA samples, stomach contents, parasites of fishes, measurements, photographs and skeletons. We're like a regional branch of a worldwide library of biodiversity, of scientific specimens. We send and receive specimens all the time."

Hand, Foot & Mouth Disease (HFMD) is a generally mild, contagious viral infection common in young children. In Singapore, HFMD is endemic and is most commonly caused by intestinal viruses known as coxsackieviruses and enteroviruses.

While most HFMD patients experience common symptoms such as sore throat, fever, ulcers inside the mouth and blisters and lesions on the palms and soles, infection with Enterovirus-A71 (EV-A71) may lead to serious neurological complications that can be potentially fatal or lead to long-term neurological deficits (cognitive and motor deficits). These complicated HFMD cases are mainly seen in young children.

Researchers from NUS Yong Loo Lin School of Medicine's Infectious Diseases Translational Research Programme have identified two new proteins that play a critical role in the ability of EV-A71 to invade the central nervous system. One of these proteins is a druggable target, which means that there are drugs available that target this protein and which could potentially be used to limit the neurological complications associated with this illness.

Since there are currently no antiviral treatments available for HFMD, only symptomatic relief is available to patients. This new discovery could allow for the development of more effective treatment of the disease, particularly for such severe cases. A number of compounds that have been developed to target this discovered protein have mainly been studied in the context of cancer. However, this finding is likely to change the course of the advancement of some of these compounds.

"This exciting finding will bring us one step closer to preventing EV-A71-infected HFMD patients from experiencing potential neurological complications. As this virus is considered to be endemic in Singapore, with cyclical epidemics every two to three years, our discovery is likely to have a significant impact on the country's public health," said Associate Professor Sylvie Alonso, Principal Investigator of the study and Co-Director of the Infectious Diseases TRP at NUS Medicine.

"The new data reported contributes to better understanding of the molecular mechanisms of EV-71 neuroinvasion that may lead to neurological complications of HFMD caused by EV-A71. This is a step towards identifying possible targets for interventions to reduce/prevent EV-A71 complications," shared Dr Chan Si Min, the Head and Senior Consultant of the Division of Paediatric Infectious Diseases at National University Hospital.

The Infectious Diseases TRP aims to provide a holistic, patient-centric approach to infectious diseases that are relevant to Singapore and the region. The Programme focuses on programmatic research areas including pathogen evolution and transmission, host-microbe interactions and vaccine and therapeutics development.