Culture

ABERDEEN PROVING GROUND, Md. -- Future technology may be able to monitor and modify the brain to produce enhanced team performance, while increasing the efficiency and accuracy of decisions.

The U.S. Army may be able to use this information to enhance future operations.

"We are working toward fused human-technology systems that work synergistically to not only impact perceptions, decisions and actions of the Soldier, but also to enhance the hybrid human system's capabilities for rapid and adaptive decision making," said Dr. Javier Garcia, an Army neuroscientist.

The U.S. Army Combat Capabilities Development Command's Army Research Laboratory, the Italian Institute of Technology, Italy, Harvard Medical School and the University of California, Irvine teamed up to study and advance research on the complexities of the human brain. Scientific Reports recently published the discoveries from their study.

Building on previous studies, the researchers used transcranial magnetic stimulation, or TMS, and within minutes of continuous stimulation, subjects were placed in a functional magnetic resonance imaging, or fMRI, scanner and asked to perform a very challenging attention tracking task.

"TMS is the type of neurostimulation that is simply an electromagnet that you put on your head and as you quickly send pulses through the electromagnetic, it induces current into whatever conductive body is next to it will, modifying neural activity -- and sometimes behavior," Garcia said. "We are stimulating the brain, except in this stimulation protocol, we use very rapid and consecutive pulses to the brain to inhibit a part of the brain."

Researchers used a stroke model to see neural changes after a specific part of the brain was inhibited and then tracked the brain's recovery. They wanted to know how long the changes would last, the brain network changes due to the stimulation, and the behavioral consequences.

"Noninvasive brain stimulation is a tool that allows neuroscientists to gain insight into disease spreading and compensatory reorganization following stroke," said Prof. Emily Grossman, UCI professor of cognitive science. "We know from patient and brain imaging work that brain injury to a focal, or localized, brain site has a spreading effect that destabilizes connected circuits far from the actual site of impact."

She said in many cases the downstream effects are significant, but also difficult to predict due to the complicated nature of brain organization -- best described as a set of large-scale networks that have various points of connection.

"In this study, we target the attention network of the brain, which consists of a specialized set of brain regions involved in controlling where and when we best encode information about the world around us," Grossman said. "Visual attention is essential for everything we do in daily life, including tasks like monitoring streams of visual information when driving, engaging in conversation and tracking our children on a busy soccer field."

When individuals experience an injury to the attention network, tracking skills become impaired and it is more difficult to maintain focus on individual items embedded in a cluttered environment, she said.

"This study suggests that recovery may depend, in part, on the compensatory reorganization of brain networks downstream and connected to the site of impact," Grossman said. "These downstream networks experienced a brief interval of dynamic reorganization after stimulation, and are known to be important for manipulating information that we are attending to and are using to make decisions about events in the visual environment."

Researchers at the lab are investing in a variety of techniques and methods to extend the state of the art in real-world neuroimaging.

"This unique collaboration brings cognitive, clinical, and army researchers together from across the globe to probe the dynamic network changes as a consequence of neurostimulation," Garcia said. "While we provided the innovative methods and analysis to this research -- others brought the clinical and cognitive aspects."

Together they plan to explore more neurostimulation protocols and bring this technology to a closed-loop, human-autonomy teaming perspective, building upon the work that proves the brain may be nudged to specific behaviorally-relevant configurations.

Kidney injury is a dreaded complication in patients hospitalized for COVID-19, with more than a third of patients ending up in need of dialysis. Patients with COVID-19-related kidney injury are also at much higher risk of death.

"We don't known exactly why patients with severe COVID-19 have a high rate of kidney injury," says Salim Hayek, M.D., a cardiologist at the Michigan Medicine (University of Michigan) Frankel Cardiovascular Center and senior author of a new observational study." It is, however, becoming clearer that a hyperactive immune system plays a major role in the morbidity of COVID-19, including kidney-related complications."

In the multi-center study published in the Journal of the American Society of Nephrology, Hayek and an international team of experts report that levels of a protein in blood produced by immune cells and known to be involved in causing kidney disease are very high in patients hospitalized for COVID-19 and strongly predictive of kidney injury.

The research team tested soluble urokinase plasminogen activator receptor (suPAR) levels of 352 study participants when they were admitted to the hospital for COVID-19 infection.

A quarter of the participants developed acute kidney injury while hospitalized, and their median suPAR levels were more than 60% higher than those of the rest of the participants. The risk of needing dialysis was increased 20-fold in patients with the highest suPAR levels. Overall, median suPAR levels for these study participants hospitalized with severe COVID-19 were almost three times higher than levels of healthy people.

"SuPAR is an immune-derived circulating factor we've seen contribute to kidney injury in thousands of patients," says Jochen Reiser, M.D., Ph.D., a professor of medicine at Rush University and expert in the biology of suPAR. "RNA viruses such as HIV and SARS-CoV-2 elicit a suPAR response of the innate immune system leading to a rise in blood suPAR levels. If there is a hyperinflammatory suPAR response, kidney cells may be damaged."

Study author Subramaniam Pennathur, M.D., a professor of nephrology at Michigan Medicine, says identifying suPAR levels at hospital admission as a strong predictor for AKI during the hospitalization has important implications for future care.

"For example, obtaining suPAR levels may allow us to risk-stratify, i.e., identify high risk patients early, and institute appropriate preventive treatment, thereby reducing AKI risk and improving COVID-19 outcomes," he says. "Second, therapies aimed at interrupting suPAR pathway may also be explored for preventative as well as a therapeutic option for COVID-19 AKI."

Hayek, an expert on this protein is currently researching how best to reduce suPAR levels in those people at highest risk.

"We're preparing to launch the first clinical trial targeting suPAR to prevent COVID-19 related kidney injury, and by doing so hope to alleviate the burden of kidney disease in both COVID-19 and non-COVID-19 patients with high suPAR levels," he says.

Two scientists from IP2I (CNRS/Université Claude Bernard Lyon 1), in collaboration with a researcher from the University of Southern Denmark and the University of Naples Federico II, have developed a new mathematical model inspired by high energy physics to predict the next waves of the Covid-19 pandemic. The extension of this technique to epidemiology, referred to as the epidemic Renormalisation group,[1] and widely used in particle physics and condensed matter physics, yields a mathematical model that can characterise the evolution of the pandemic across European territories. Their simulations, which were conducted on the basis of infection rates and travel within and between European countries from March to July 2020, suggest that a second wave will impact Europe between July 2020 and January 2021.[2] While it is not possible to provide specific details of this second wave, or to identify when exactly the next peak of infections will take place in France, the simulations underscore the importance of human behaviour in slowing the pandemic. According to this research, the precise moment of peak infection rates for each country can be controlled through social distancing, the control of local "clusters," and border control measures. The study was published in Scientific Reports on 23 September 2020.

Further information: the authors modelled the temporal dynamic of a second wave in numerous European countries, and created a simulation video of when a second wave is likely to peak in each country. This animation is the result of many simulations of the second wave. The researchers assumed that the countries included would adopt measures for the second wave similar to those for the first, and that group immunity is not yet reached. The simulations begin on calendar week 25. The fact that some countries have already experienced a second wave beginning on August 5 is taken into consideration.

People infected by the novel coronavirus can have symptoms that range from mild to deadly. Now, two new analyses suggest that some life-threatening cases can be traced to weak spots in patients' immune systems.

At least 3.5 percent of study patients with severe COVID-19, the disease caused by the novel coronavirus, have mutations in genes involved in antiviral defense. And at least 10 percent of patients with severe disease create "auto-antibodies" that attack the immune system, instead of fighting the virus. The results, reported in two papers in the journal Science on September 24, 2020, identify some root causes of life-threatening COVID-19, says study leader Jean-Laurent Casanova, a Howard Hughes Medical Institute Investigator at The Rockefeller University.

Seeing these harmful antibodies in so many patients - 101 out of 987 - was "a stunning observation," he says. "These two papers provide the first explanation for why COVID-19 can be so severe in some people, while most others infected by the same virus are okay."

The work has immediate implications for diagnostics and treatment, Casanova says. If someone tests positive for the virus, they should "absolutely" be tested for the auto-antibodies, too, he adds, "with medical follow-up if those tests are positive." It's possible that removing such antibodies from the blood could ease symptoms of the disease.

A global effort

Casanova's team, in collaboration with clinicians around the world, first began enrolling COVID-19 patients in their study in February. At the time, they were seeking young people with severe forms of the disease to investigate whether these patients might have underlying weaknesses in their immune systems that made them especially vulnerable to the virus.

The plan was to scan patients' genomes - in particular, a set of 13 genes involved in interferon immunity against influenza. In healthy people, interferon molecules act as the body's security system. They detect invading viruses and bacteria and sound the alarm, which brings other immune defenders to the scene.

Casanova's team has previously discovered genetic mutations that hinder interferon production and function. People with these mutations are more vulnerable to certain pathogens, including those that cause influenza. Finding similar mutations in people with COVID-19, the team thought, could help doctors identify patients at risk of developing severe forms of the disease. It could also point to new directions for treatment, he says.

In March, Casanova's team was aiming to enroll 500 patients with severe COVID-19 worldwide in their study. By August, they had more than 1,500, and they now have over 3,000. As the researchers began analyzing patient samples, they started to uncover harmful mutations, in people young and old. The team found that 23 out of 659 patients studied carried errors in genes involved in producing antiviral interferons.

Without a full complement of these antiviral defenders, COVID-19 patients wouldn't be able to fend off the virus, the researchers suspected. That thought sparked a new idea. Maybe other patients with severe COVID-19 also lacked interferons - but for a different reason. Maybe some patients' bodies were harming these molecules themselves. As in autoimmune disorders such as type 1 diabetes and rheumatoid arthritis, some patients might be making antibodies that target the body. "That was the eureka moment for us," Casanova says.

The team's analysis of 987 patients with life-threatening COVID-19 revealed just that. At least 101 of the patients had auto-antibodies against an assortment of interferon proteins. "We said, 'bingo'!" Casanova remembers. These antibodies blocked interferon action and were not present in patients with mild COVID-19 cases, the researchers discovered.

"It's an unprecedented finding," says study co-author Isabelle Meyts, a pediatrician at the University Hospitals KU Leuven, in Belgium, who earlier this year helped enroll patients in the study, gather samples, and perform experiments. By testing for the presence of these antibodies, she says, "you can almost predict who will become severely ill."

The vast majority - 94 percent - of patients with the harmful antibodies were men, the team found. Men are more likely to develop severe forms of COVID-19, and this work offers one explanation for that gender variability, Meyts says.

Casanova's lab is now looking for the genetic driver behind those auto-antibodies. They could be linked to mutations on the X chromosome, he says. Such mutations might not affect women, because they have a second X chromosome to compensate for any defects in the first. But for men, who carry only a single X, even small genetic errors can be consequential.

Looking ahead
Clinically, the team's new work could change how doctors and health officials think about vaccination distribution strategies, and even potential treatments. A clinical trial could examine, for instance, whether infected people who have the auto-antibodies benefit from treatment with one of the 17 interferons not neutralized by the auto-antibodies, or with plasmapheresis, a medical procedure that strips the antibodies from patients' blood. Either method could potentially counteract the effect of these harmful antibodies, Meyts says.

In addition to the current work, Meyts, Casanova, and hundreds of other scientists involved with an international consortium called the COVID Human Genetic Effort are working to understand a second piece of the coronavirus puzzle. Instead of hunting for factors that make patients especially vulnerable to COVID-19, they're looking for the opposite - genetic factors that might be protective. They're now recruiting people from the households of patients with severe COVID-19 - people who were exposed to the virus but did not develop the disease. "Our lab is currently running at full speed," Casanova says.

More than 10 percent of young and healthy people who develop severe COVID-19 have misguided antibodies that attack not the virus, but the immune system itself, new research shows. Another 3.5 percent, at least, carry a specific kind of genetic mutation.

In both groups, the upshot is basically the same: The patients lack type I interferon, a set of 17 proteins crucial for protecting cells and the body from viruses. Whether the proteins have been neutralized by so-called auto-antibodies, or were not produced in sufficient amounts in the first place due to a faulty gene, their missing-in-action appears to be a common theme among a subgroup of COVID-19 sufferers whose disease has thus far been a mystery.

Published in two papers in Science, the findings help explain why some people develop a disease much more severe than others in their age group--including, for example, individuals who required admission to the ICU despite being in their 20s and free of underlying conditions. They may also provide the first molecular explanation for why more men than women die from the disease.

"These findings provide compelling evidence that the disruption of type I interferon is often the cause of life-threatening COVID-19," says Jean-Laurent Casanova, head of the St. Giles Laboratory of Human Genetics of Infectious Diseases at The Rockefeller University and a Howard Hughes Medical Institute investigator. "And at least in theory, such interferon problems could be treated with existing medications and interventions."

The findings are the first results being published out of the COVID Human Genetic Effort, an ongoing international project spanning over 50 sequencing hubs and hundreds of hospitals around the world, co-led by Casanova and Helen Su at the National Institute of Allergy and Infectious Diseases. The study participants included various nationalities from Asia, Europe, Latin America, and the Middle East. "COVID-19 may now be the best understood acute infectious disease in terms of having a molecular and genetic explanation for nearly 15% of critical cases across diverse ancestries," Casanova says.

Genetics of COVID-19 outliers

The way SARS-CoV-2 affects people differently has been puzzling. The virus can cause a symptom-free infection and go away quietly, or it can kill in a few days. Casanova's research over the past two decades has shown that unusual susceptibility to certain infectious diseases can be traced to single-gene mutations that affect an individual's immune response.

Since February, his team and their collaborators have been enrolling thousands of COVID-19 patients to find out whether something in their genetic make-up drives the disparate clinical outcomes the disease produces.

In one study, the researchers genetically analyzed blood samples from more than 650 patients who had been hospitalized for life-threatening pneumonia due to SARS-CoV-2, 14 percent of whom had died. They also included samples from another group of over 530 people with asymptomatic or benign infection. They initially searched for differences between the two groups across 13 genes known to be critical for the body's defense against the influenza virus. These genes govern type I interferons.

It soon became obvious that a significant number of people with severe disease carried rare variants in these 13 genes, and more than 3 percent of them were in fact missing a functioning gene. Further experiments showed that immune cells from these patients did not produce any detectable type I interferons in response to SARS-CoV-2.

Interferons are part of the intrinsic and innate immunity, kicking in before the adaptive immune system mounts an antibody response. They are known to play an important role in immediately heightening the cells' defenses in response to several viruses. Follow up experiments led by Rockefeller's Charles M. Rice showed that this is also the case for SARS-CoV-2: Human fibroblast cells with mutations affecting the interferon type I pathway were more vulnerable to the virus, and died in higher numbers--and faster--than cells without those mutations.

A mysterious autoimmune condition

Three other infectious diseases caused by mutations affecting an immune signaling protein can also be caused by auto-antibodies against that protein. So next, the team checked for the possibility of a similar scenario.

Examining 987 patients with life-threatening COVID-19 pneumonia, they found that more than 10 percent had auto-antibodies against interferons at the onset of their infection. The majority of them, 95%, were men.

Biochemical experiments confirmed these auto-antibodies can effectively curb the activity of interferon type I. In some cases, they could be detected in blood samples taken before patients became infected; in others, they were found in the early stages of the infection, before the immune system had the time to mount a response.

These auto-antibodies seem to be rare in the general population. Out of 1,227 randomly selected healthy people, only four were found to have them.

"All of these findings strongly indicate that these auto-antibodies are actually the underlying reason some people get very sick, and not the consequence of the infection," Casanova says.

The findings point to certain medical interventions to consider for further investigation, Casanova says. For example, there are already two types of interferons available as drugs and approved for use to treat certain conditions such as chronic viral hepatitis.

The team continues to look for genetic variations that may affect other types of interferons or additional aspects of the immune response in COVID-19 outliers.

Two new studies report specific mechanisms of impaired type I interferon (IFN) signaling in some hospitalized patients suffering from severe cases of COVID-19, suggesting that screens for these defects could help identify patients at the highest risk of life-threatening complications from SARS-CoV-2 infection. The results of the paired studies - which report that mutations in type I IFN-associated genes and high titers of neutralizing autoantibodies against type I IFNs may both be associated with severe COVID-19 respiratory symptoms - also suggest that administering specific type I IFNs to select high-risk patients could offer therapeutic benefits, especially early in the course of the disease. To test whether severe COVID-19 respiratory symptoms may be associated with the genetics of type I IFN signaling, Qian Zhang and colleagues performed whole-genome or whole-exome sequencing of 659 patients hospitalized with life-threatening COVID-19 pneumonia and 534 patients with asymptomatic or mild infection. Focusing on 13 gene loci known to govern TLR3- and IRF7-dependent type I IFN immunity to influenza virus, the researchers found rare loss-of-function gene variants in 3.5% of the patients with severe COVID-19 symptoms, but not in the asymptomatic/mild cohort. This subgroup of patients (23 in total) ranged in age from 17 to 77, with representation of both sexes and various ancestries. Based on their findings, the researchers suggest that mutations in other type I IFN-related genes may exist in other patients with life-threatening COVID-19 symptoms. In a related study, Paul Bastard and colleagues investigated whether neutralizing autoantibodies (which aberrantly recognize, bind to, and neutralize a patient's own proteins) against type I IFNs might also underlie severe COVID-19 pneumonia. In a screen of 987 patients with dire cases of COVID-19, the researchers found that 101 patients had autoantibodies against IFN-ω, IFN-a, or both. In contrast, 663 patients with asymptomatic or mild cases of COVID-19 had none of the autoantibodies, and only 4 of 1,227 healthy individuals, sampled before the pandemic, had one or more of the autoantibody types. Based on their findings, Bastard et al. conclude that "the neutralizing [autoantibodies] against type I IFNs, like inborn errors of type I IFN production, tip the balance in favor of the virus, resulting in devastating disease, with insufficient, and even perhaps deleterious, innate and adaptive immune responses."

Researchers from North Carolina State University have demonstrated the utility of artificial intelligence (AI) in identifying and categorizing neural degeneration in the model organism C. elegans. The tool uses deep learning, a form of AI, and should facilitate and expedite research into neural degeneration.

"Researchers want to study the mechanisms that drive neural degeneration, with the long-term goal of finding ways to slow or prevent the degeneration associated with age or disease," says Adriana San Miguel, corresponding author of a paper on the work and an assistant professor of chemical and biomolecular engineering at NC State. "Our work here shows that deep learning can accurately identify physical symptoms of neural degeneration; can do it more quickly than humans; and can distinguish between neural degeneration caused by different factors.

"Having tools that allow us to identify these patterns of neural degeneration will help us determine the role that different genes play in these processes," San Miguel says. "It will also help us evaluate the effect of various pharmaceutical interventions on neural degeneration in the model organism. This is one way we can identify promising candidates for therapeutic drugs to address neurological disorders."

For this study, researchers focused on C. elegans, or roundworm, which is a model organism widely used to study aging and the development of the nervous system. Specifically, the researchers focused on PVD neurons, which are nerve cells that can detect both touch and temperature. The researchers chose the PVD neuron because it is found throughout the nervous system of C. elegans and it is known to degenerate due to aging.

Roundworms are tiny and transparent - meaning that it is possible to see their nervous systems while they are still alive. Traditionally, identifying degeneration in C. elegans neurons requires researchers to look for microscopic changes in the cell, such as the appearance of bubbles that form on parts of individual neurons. Researchers can analyze the extent of neural degeneration by tracking the size, number and location of these bubbles.

"Counting these bubbles is a time-consuming and labor-intensive process," says Kevin Flores, co-author of the study and an assistant professor of mathematics at NC State. "We've demonstrated that we can collect all of the relevant data from an image in a matter of seconds, by combining the power of deep-learning with the advanced speed of so-called GPU computing. This enables a much faster quantitative assessment of neuronal degeneration than traditional techniques."

In addition to monitoring the effects of age on neural degeneration, the researchers also examined the effects of "cold shock," or prolonged exposure to low temperatures. The researchers were surprised to learn that cold shock could also induce neural degeneration.

"We also found that neural degeneration caused by cold shock had a different pattern of bubbles than the degeneration caused by aging," San Miguel says. "It is difficult or impossible to distinguish the difference with the naked eye, but the deep learning program found it consistently.

"This work tells us that deep learning tools are able to spot patterns we may be missing - and we may be just scratching the surface of their utility in advancing our understanding of neural degeneration."

Tiny crystals, ten thousand times thinner than a human hair, can cause explosive volcanic eruptions. This surprising connection has recently been discovered by a German-British research team led by Dr. Danilo Di Genova from the Bavarian Research Institute of Experimental Geochemistry & Geophysics (BGI) at the University of Bayreuth. The crystals increase the viscosity of the underground magma. As a result, a build-up of rising gases occurs. The continuously rising pressure finally discharges in massive eruptions. The scientists present the results of their nanogeoscientific research in the journal "Science Advances".

"Exactly what causes the sudden and violent eruption of apparently peaceful volcanoes has always been a mystery in geology research. Nanogeoscience research has now allowed us to find an explanation. Tiny crystal grains containing mostly iron, silicon, and aluminium are the first link in a chain of cause and effect that can end in catastrophe for people living in the vicinity of a volcano. The most powerful volcanic eruption in human history was Mount Tambora in Indonesia in 1815", says Dr. Danilo Di Genova. For the recently published study, he worked closely with scientists from the University of Bristol, the Clausthal University of Technology, and two European synchrotron radiation facilities.

Because of their diameter of a few nanometres, the crystals are also known as nanolites. Using spectroscopic and electron microscopy methods, the researchers have detected traces of these particles, invisible to the eye, in the ashes of active volcanoes. In the BGI's laboratory, they were then able to describe these crystals and finally to demonstrate how they influence the properties of volcanic magma. The investigations focused on magma of low silicon oxide content cooling to form basalt on the earth's surface after a volcanic eruption. Low silica magma is known for its low viscosity: It forms a thin lava that flows quickly and easily. The situation is different, however, if it contains a large number of nanolites. This makes the magma viscous - and far less permeable to gases rising from the earth's interior. Instead of continuously escaping from the volcanic cone, the gases in the depths of the volcano become trapped in the hot magma. As a result, the magma is subjected to increasing pressure until it is finally ejected explosively from the volcano.

"Constant light plumes of smoke above a volcanic cone need not necessarily be interpreted as a sign of an imminent dangerous eruption. Conversely, however, the inactivity of apparently peaceful volcanoes can be deceptive. Rock analyses, written and archaeological sources suggest, for example, that people in the vicinity of Vesuvius were surprised by an extremely violent eruption of the volcano in 79 AD. Numerous fatalities and severe damage to buildings were the result", says Di Genova. In his further research, the Bayreuth scientist hopes to use high-pressure facilites and computer simulation to model the geochemical processes that lead to such unexpected violent eruptions. The aim is to better understand these processes and thus also to reduce the risks for the population in the vicinity of volcanoes.

Elastic can stretch too far and that could be problematic in wearable sensors. A team of researchers at Yokohama National University has proposed a fix to prevent too much stretching while improving the sensing ability of electronics. This could lead to advanced prosthetics or disaster recovery robotics.

They published their results on July 29 in the Scientific Reports.

"Stretchable physical sensors are crucial for the development of advanced electrical systems, particularly wearable devices and soft robotics," said Hiroki Ota, paper author and associate professor in the Faculty of Engineering at Yokohama National University. "However, current stretchable pressure sensors composed of elastic materials can be highly deformed during the strain of the devices."

The bend of an elbow or a knee can push the sensor past its structural integrity, producing a large error on the pressure movement measurement. This stops the sensor from being able to measure pressure and strain at the same time, but as independent variables.

To help combat this, the researchers proposed a monolithic array of pressure and strain sensors that can simultaneously and independently detect the force and bend deformation of motion. They used two different materials--one soft and one hard--to protect the sensor's ability to stretch and still accurately measure movement. They placed a hard silicone, called PDMS, along electrodes over the array. At the center of each PDMS placement, they positioned soft porous silicone, which senses pressure.

"The PDMS around the pressure-sensing elements prevents the development of large deformations of the elements during the developed device tension," Ota said.

The soft porous silicone pressure sensor is contained within the hard shell of the PDMS, so it can measure the force of pressure without being overextended past reliable margins of error. The containment also allows the sensors to identify and measure both pressure and strain as independent contributors to movement.

"In addition, resistances of column and row electrodes in the matrix of the mapped array are much lower than the ones of the pressure sensors," Ota said. "This substrate and control of electrode resistances can prevent stretch deformation of the device from affecting the sensing of pressure."

The electrodes in the stretchable array can measure strain at a much lower rate than is required to detect pressure.

"We could recognize pressure and strain sensing of our device independently," Ota said.

Ota said the team plans to apply the new stretchable sensor approach to a physical keyboard that can be mounted on the surface of a body, which could bend with the strain of the body and still detect fingertip pressure, as well as a physical sensor on a soft robot. They also hope to use the sensor to better understand the motion and touch of the human hand.

"In the future, by molding this sensor into a glove shape, it can be applied to the device which electronically analyzes the finger movement and tactile sense of the hand," Ota said.

Through a one-of-a-kind experiment at the Department of Energy's Oak Ridge National Laboratory, nuclear physicists have precisely measured the weak interaction between protons and neutrons. The result quantifies the weak force theory as predicted by the Standard Model of Particle Physics.

The team's weak force observation, detailed in Physical Review Letters, was measured through a precision experiment called n3He, or n-helium-3, that ran at ORNL's Spallation Neutron Source, or SNS. Their finding yielded the smallest uncertainty of any comparable weak force measurement in the nucleus of an atom to date, which establishes an important benchmark.

The Standard Model describes the basic building blocks of matter in the universe and fundamental forces acting between them. Calculating and measuring the weak force between protons and neutrons is an extremely difficult task.

"Because the interactions we're looking for are very weak, the effects that we want to detect in precision nuclear physics experiments are very small and, therefore, extremely difficult to observe," said David Bowman, co-author and team leader for fundamental neutron physics at ORNL.

The weak force is one of four fundamental forces in nature, along with the strong nuclear force, electromagnetism and gravity, and describes interactions between subatomic particles called quarks that make up protons and neutrons. The weak force is also responsible for an atom's radioactive decay. Certain mechanisms of the weak force are among the least understood aspects of the Standard Model.

Detecting the elusive weak interactions requires high-precision experiments, led by large international teams with a state-of-the-art apparatus and a world-class cold neutron source with very high neutron flux, such as the Fundamental Neutron Physics Beamline at SNS. Neutrons produced at SNS are ideal for precision experiments that address the role the weak force plays in the reaction between neutrons and other nuclei.

Bowman, a leading scientist in this field, has been studying nuclear physics and subatomic interactions since the early 1960s.

"In the beginning, there were phenomenological nuclear models gleaned from an empirical research point of view. But, in recent years, there have been major advances in calculations of weak force interactions in the nuclear environment," he said. "New nuclear techniques have become available with different degrees of freedom, and the calculations now are at a very advanced level."

The scientists' latest experiment focused on helium-3, which is a light and stable isotope consisting of two protons and one neutron, the only element in nature that has more protons than neutrons in the nucleus. "When a neutron and a helium-3 nucleus combine, the reaction produces an excited, unstable helium-4 isotope, decaying to one proton and one triton (consisting of two neutrons and one proton), both of which produce a tiny but detectable electrical signal as they move through the helium gas in the target cell," said Michael Gericke, corresponding author and professor for subatomic physics at the University of Manitoba.

The n-helium-3 experiment used the same neutron beamline, polarizer and diagnostics as its predecessor, NPDGamma, which used a liquid hydrogen target that produced gamma rays from neutron-proton interactions. The team found that more gamma rays go down than up with respect to neutron spin direction, which led to the successful measurement of a mirror-asymmetric component of the weak force.

Similar to NPDGamma, the n-helium-3 experiment is the culmination of a decade of research, preparation and analysis. The experiment's configuration created an extremely low background environment where neutrons can be controlled before entering a container of helium-3 gas. Gericke led the group that built the combined helium-3 target and detector system designed to pick up the very small signals and led the subsequent analysis.

In the experiment, a beam of slow-moving, or cold, neutrons at SNS entered the helium-3 target. One instrument was designed to control the nuclear spin direction of the helium-3 atoms. When the neutrons interact with the magnetic field, another apparatus flipped their spin direction either up or down, defining the spin state. When the neutrons reached the target, they interacted with the protons within the helium-3 atoms, sending out the current signals that were measured by sensitive electronics.

"We had to develop a unique target gas cell that simultaneously served as a position-sensitive detector to measure the subatomic products of the reaction," Gericke said.

"In order to accommodate different running conditions of this experiment, we invented a novel apparatus needed to reverse the spin direction of neutrons right before they reacted with the helium-3 target," said co-author and nuclear physics professor Christopher Crawford of the University of Kentucky. "This universal spin flipper was able to operate in the large neutron velocity range with high efficiency."

Weak force experiments have to contend with the dominating nature of the strong force and background noise that could distort the data. "The n-helium-3 experiment had to be sensitive to very small effects -- 100 million times smaller than the background," Crawford said. "That is akin to searching for a 1-inch needle in a 40-foot-high barn full of hay."

For about a year, the team collected and analyzed the data to determine the strength of the parity-violation, which is a specific property of the weak force between a neutron and a proton. This phenomenon is unique to the weak force and is not observed in the strong force, electromagnetism or gravity.

N-helium-3 exploited the symmetry of the experimental configuration obtained by the well-controlled neutron polarization, by measuring a combination of the neutron spin and outgoing momentum of reaction products for both neutron polarizations. "This has a certain handedness," Crawford said. "Since right and left hands look opposite in the mirror, this observation was completely insensitive to the effects of the other three forces."

The results of n-helium-3, along with NPDGamma, have changed the way nuclear physicists understand the role of the weak force in atomic nuclei. Both help answer outstanding questions in the Standard Model through the ability to make accurate calculations.

"Now what's going to happen after this, we need more measurements - like these very precise measurements we get at SNS," Bowman said. "Advancements in this field require a dialogue between the experimentalists and theorists. As results from experiments like ours become available, they benchmark theories, and that allows theorists to improve the models that predict new observables that then could be experimentally reachable."

Black, South Asian and Aboriginal populations from disadvantaged socioeconomic backgrounds in Canada are nearly four times more likely to have three or more medical conditions that have been identified as risk factors for severe illness from COVID-19.

Shen (Lamson) Lin, a doctoral candidate in gerontology and course instructor at the University of Toronto's Factor-Inwentash Faculty of Social Work and Institute for Life Course and Aging, compared 1,102 racialized immigrants and 338 Aboriginal Canadians with 23,802 Canadian-born Whites, aged 45 and older, using population-based data from the baseline Canadian Longitudinal Study on Aging (CLSA, 2012-2015). His findings were recently published in The Gerontologist (Special collection: Gerontology in a Time of Pandemic).

"We know that COVID-19 outbreak is not affecting everyone at the same levels, and the prevalence of multiple chronic conditions within an individual -- known as multimorbidity -- has also been linked to social inequalities for decades," says Lin, the sole author of the study. "I was curious to explore how one's family income, education levels and experience of racism and nativism -- and the intersection of these three social standings -- shape the health of aging populations."

Lin's study examined nine chronic conditions associated with an increased likelihood that one will experience severe illness due to COVID-19 infection, requiring hospitalization, intensive care and the use of a ventilator. These medical conditions include diabetes, asthma, cancer, previous heart attack or myocardial infarction, kidney disease, cardiovascular disease, hypertension, chronic obstructive pulmonary disease and obesity.

The odds of having three or more of these medical conditions was greater for Black and South Asian immigrants and close to double for Aboriginal populations in Canada, relative to Canadian-born Whites. Black, South Asian and Aboriginal populations from disadvantaged socioeconomic backgrounds (those without any post-secondary education and/or those who earned less than the median household income) had the highest odds of having three or more medial conditions.

The multimorbidity differences associated with these populations were enhanced for older adults (aged 66 to 85) compared to their middle-aged counterparts (aged 45-65). Among older respondents, Black immigrants were five times more likely and Aboriginal Canadians three times more likely to have three or more medical conditions.

"These observed health gaps illustrate various minority struggles that are often obscured within a discourse of multiculturalism and diversity" says Lin, "Given the lack of socio-demographic and race-based data in Canadian health systems, my study provides a timely frame of reference for public-health decision makers to reconsider measuring upstream health inequalities to mitigate the pandemic's long-term societal harms."

Additional risk factors for multimorbidity were identified. These included being male, experiencing chronic pain, having a physical impairment, living without partners, and a lifetime of smoking.

"Widespread chronic disease and racism in addition to the contemporary pandemic make living conditions more difficult for vulnerable older adults, especially those from racialized, immigrant, and impoverished communities," says Lin. "With COVID-19 spreading globally, health equity should be placed at the center of all policy responses designed to mitigate the disproportionate impact of the pandemic on underserved aging communities."

BOSTON - Emergency departments of hospitals generate significant amounts of environmentally harmful waste which could be reduced through basic changes to disposal policies and practices, while producing lower operating costs, researchers from Massachusetts General Hospital (MGH) have found. Efforts to optimize the daily waste stream through improvements such as switching from disposable to reusable items in the ED, better sorting of infectious waste, and more effective recycling of items like glass and aluminum could have meaningful impact both environmentally and financially, according to the study published in the Western Journal of Emergency Medicine.

"People working in emergency departments have no idea how much waste they routinely generate, nor that the environmental impact is totally at odds with their professional mission to improve health and save lives," says Jonathan E. Slutzman, MD, investigator in the Department of Emergency Medicine at MGH and senior author of the study. "A greater awareness of the harm that's being done, along with the opportunities that are available to turn that situation around, should be on the agenda of every hospital in America."

Healthcare facilities in the U.S. generate 6,600 metric tons of waste each day, making them the second largest contributor to landfill waste (next to the food industry). They also produce 10 percent of all greenhouse gas emission as well as other pollutants known to adversely affect human health. The MGH investigation is the first to quantify and characterize the volume of waste emanating from emergency departments. To that end, researchers conducted a 24-hour waste audit in July 2019 at MGH's Level 1 trauma center in Boston. The team collected, manually sorted into separate categories, and weighed each waste stream component. It also calculated direct pollutant emissions from ED waste disposal activities.

Among the findings was that 85 percent of all items disposed of as regulated medical waste (RMW) -- the most hazardous ED materials that must be deposited in red bags and autoclaved to render them safe prior to being sent to landfills -- did not meet the criteria for regulated medical waste. "We always want healthcare workers to err on the side of caution when it comes to waste disposal, but the fact is regulated medical waste costs up to ten times as much to dispose of as solid waste," notes Sarah Hsu, with the Warren Alpert Medical School at Brown University, and lead author of the study. "But if we could divert through better sorting some fraction of medical waste that now goes into red biohazard bags to regular solid waste, it would open up significant cost-saving opportunities for hospitals."

Another area rife with opportunity, according to the researchers, is transitioning from the use of disposable devices to more durable, reusable alternatives that would lead to waste reduction and supply savings. One example is the laryngoscope, commonly used in the ED to insert a breathing tube into the trachea, which could be reprocessed onsite and safely used multiple times rather than discarding it after a single use. Rethinking the use of plastic packaging, which was estimated by the MGH study to be responsible for over 40 percent of all emergency department solid waste, also holds the potential for significant waste reduction. MGH, for its part, asks suppliers to ship products in non-disposable bulk packaging, whenever possible, enabling reuse. Suppliers are also "debulking" items at distribution centers, enabling packaging to be reused from that point rather than being shipped all the way to the hospital.

To determine the best opportunities for waste reduction, Slutzman suggests that hospitals conduct their own audits of emergency department waste. "Gaining a full awareness of the problem and its downstream consequences on the health of the community is an important first step toward a solution," he says. "In addition to audits, hospitals should assemble all stakeholders around the table to explore alternatives to their current waste disposal practices. Our study shows that significant improvements can be made to optimize ED waste management, and as healthcare professionals we owe it to our patients and the community to take responsible action."

For the first time, researchers have discovered how antibiotic resistance genes are spreading, at a continental scale, via bacterial plasmids in the hospital superbug, Klebsiella pneumoniae.

Researchers from the Centre for Genomic Pathogen Surveillance, based jointly at the Wellcome Sanger Institute and the Big Data Institute, University of Oxford, together with their collaborators used genome sequencing technology to analyse plasmids - genetic structures in bacteria that can carry antibiotic resistance genes - as well as bacterial chromosomes from K. pneumoniae samples taken from European hospital patients.

The findings, published today (24th September) in Proceedings of the National Academy of Sciences, reveal three different pathways by which antibiotic resistance genes spread via plasmids through bacterial populations. Researchers say it is critical that plasmids are included when tracking antibiotic resistance in order to have the best chance of stopping superbugs.

Members of the Enterobacteriaceae family of bacteria can become resistant to last-line antibiotics called carbapenems, and are listed as a critical threat in the World Health Organisation's list of priority pathogens*. Within this family, Klebsiella pneumoniae is an opportunistic pathogen that causes serious diseases, including pneumonia and meningitis.

K. pneumoniae becomes resistant to carbapenems by acquiring antibiotic resistance genes, known as carbapenemase genes, which code for an enzyme that 'chews up' the antibiotic.

In K. pneumoniae, these carbapenemase genes are usually found on plasmids - smaller circular pieces of DNA that are additional to the bacterial chromosome. Plasmids can 'jump' between different strains and species of bacteria, meaning antibiotic resistance genes can quickly spread and drive the rapid rise in antibiotic resistant bacterial infections worldwide.

Therefore, researchers must include plasmids when tracking the evolution and spread of bacteria to get a true picture of how antibiotic resistance genes are spreading. However it has previously been difficult to use genome sequencing to reliably track plasmid evolution, due to the variability in size and structure of their genetic sequences.

Now with long-read sequencing technology** researchers are able to read and reconstruct complete sequences for plasmids.

In a new study, researchers from the Centre for Genomic Pathogen Surveillance and their collaborators conducted long-read genome sequencing on 79 K. pneumoniae samples from patients, taken from a Europe-wide survey.

The team generated complete plasmid sequences from these samples, and studied them along with more than 1700 previously short-read sequenced K. pneumoniae samples from the same survey to understand how antibiotic resistance genes are spreading through the bacterial population in European hospitals.

Dr Sophia David, first author from the Centre for Genomic Pathogen Surveillance said: "To fully understand how antibiotic resistance is spreading, we need to consider the role of plasmids. In this study, which is the first to analyse the genetic sequences of plasmids at a continental scale, we discovered three primary routes by which antibiotic resistance genes are spreading via plasmids through the K. pneumoniae population."

The three pathways of transmission involve one plasmid jumping between multiple strains, multiple plasmids spreading among multiple strains, and multiple plasmids spreading within one strain of K. pneumoniae.

Professor Hajo Grundmann, co-lead author from the University of Freiburg in Germany, said: "These new insights into the three routes of spread of antibiotic resistance genes in K. pneumoniae are critical for controlling outbreaks of antibiotic resistant infections. Knowing these transmission strategies enables tailoring of interventions, either to control the dominant plasmid, control the dominant strain, or in complicated situations, control both. For example, if there was a hospital outbreak and the strain carried a high-risk plasmid, there's a chance this plasmid might jump into other bacterial strains or species, which would need to be monitored."

The team also found that plasmids encoding carbapenemase genes were most successful in spreading when acquired by a high-risk strain. This reinforces the importance of preventing transmission of high-risk strains through early detection and rigorous infection control in healthcare environments.

Professor David Aanensen, co-lead author and Director of the Centre for Genomic Pathogen Surveillance said: "When tracking certain antibiotic resistant bacteria, plasmids are one of the missing parts of the puzzle. Analysing the genetic sequences of both bacterial chromosomes and plasmids can give us a more detailed picture of how antibiotic resistance genes and mechanisms spread in a population. Genomic surveillance of bacteria should include plasmids and other mobile elements in order to tackle the rise in antibiotic resistant infections."

Leesburg, VA, September 24, 2020--According to an open-access article in ARRS' American Journal of Roentgenology (AJR), because coronavirus disease (COVID-19) may present with medium to large arterial and venous abdominal and extremity macrothrombi, radiologists should raise concern for COVID-19 when identifying thromboembolic abdominopelvic findings.

Bari Dane of NYU Langone Medical Center in New York City and colleagues at NYU Winthrop in Mineola, New York retrospectively compared 82 patients (58 men, 24 women; mean age 58.8) with COVID-19 who underwent abdominal ultrasound or CT with 82 patients (43 men, 39 women; mean age 53.5) without COVID-19 for thromboembolism and solid-organ infarction.

Nine (11%) patients with COVID-19 had thromboembolic findings (seven men, two women; mean age 67.0). Thromboembolism was described in four of the 38 CT reports (10.5%). Two others described splenic infarctions with patent vasculature (overall positivity rate, 15.8% [6/38]). Three patients had arterial thromboembolism in the aorta or major branches.

Noting one patient without COVID-19 had known portal vein thrombus on CT, "thromboembolic findings occurred more frequently in patients with than without COVID-19 (p = 0.02)," Dane et al. concluded.

Acknowledging this study's small sample size and single-institution nature, Dane pointed out that the cohort describing patients with "COVID" in the radiology report may not include all patients with COVID-19.

"Additionally," the authors of this AJR article continued, "not all patients with thromboembolism undergo confirmative imaging, and some may not experience symptoms. Consequently, the prevalence is likely larger than reported."

Scientists have for the first time documented all of the different cell types and genes expressed in the healthy human heart, in new research published in the journal Nature.

Cardiologists from the Mazankowski Alberta Heart Institute at the University of Alberta joined teams from Cambridge, Boston and Berlin to use state-of-the-art analytical techniques to sequence the ribonucleic acids (RNA) in nine types of single cells from six regions of the heart.

"Now we have a single-cell atlas of the normal human heart, including cellular composition and gene expression," said Gavin Oudit, professor in the Faculty of Medicine & Dentistry, Canada Research Chair in Heart Failure, and director of the Mazankowski's Heart Function Clinic and its Human Explanted Heart Program.

Oudit said this is the first step toward understanding heart disease and developing new targeted treatments to stop it.

"What we are working on now is to see how the cell types and gene expression are changed in patients with genetic cardiomyopathies--a significant cause of end-stage heart failure and sudden cardiac death," he said.

Next, researchers will be able to select specific mutations as treatment targets. "We want to correct those mutations, either with drugs or gene therapy, and start to reverse cardiomyopathies, ideally at an early stage," Oudit said.

The Edmonton team helped the international consortium to isolate single cells and code the gene expressions from seven male and seven female healthy donor hearts.

"This technique is truly remarkable," Oudit said. "Rather than grinding up a piece of heart tissue and losing the cellular composition, this allows us to track the gene expression of every single cell."

The U of A research was funded by the Canadian Institutes of Health Research, Alberta Innovates and the University Hospital Foundation.

Oudit said the research could not have happened without the integrated team of transplant co-ordinators, cardiologists and cardiac surgeons working together in Canada's largest research-integrated human heart transplant program at the Mazankowski Alberta Heart Institute.

"The dedication and efforts of our trainees over the past decade have been invaluable, including our current PhD trainees, Hao Zhang and Anissa Viveiros," Oudit said.

"We have a wonderful clinical program which is also a fabulous research tool, and it will ultimately influence patient care and our approaches to treating heart disease."