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The COVID-19 pandemic's heavy toll on older Americans highlights the need to strengthen the nation's safety net for people in need of long-term services and supports, an Oregon Health & Science University researcher and co-authors argue in a new report published by Milbank Quarterly.

The report proposes a system of universal coverage to support the long-term care of all older Americans.

"This approach would protect against financial catastrophe and end the current system that is based on the need to be financially destitute in order to access coverage via Medicaid," the authors write. "Such an approach would benefit both individuals and families and would also create a far more stable and more generous funding stream to providers."

Walt Dawson, D.Phil., assistant professor of neurology in the OHSU School of Medicine, said he believes the pandemic could be an inflection point to improve the U.S. system of long-term services and support.

Dawson, also a senior Atlantic Fellow of Equity in Brain Health with the Global Brain Health Institute, studies the public policy implications of Alzheimer's disease and other dementias - including the financial impact on families and the public programs that finance care.

The report lays out a series recommendations to repair what it characterized as a fragmented and patchwork system of long-term services and supports for older Americans living with physical and cognitive impairments.

Long-term recommendations

Universal coverage: The report calls for establishing universal coverage for all Americans' long-term care needs through Medicare. "Universal coverage is essential to achieving greater equity in access and coverage, but it is also essential to the fiscal viability of the financing mechanism (e.g., everyone pays into the system)," the authors write.

Creating an age-friendly health system: The report calls for better collaboration between public health, health care systems and long-term care to safeguard the health and safety of older adults.

Near-term recommendations

Improved reporting of COVID-19 infections: The report calls for improving a "lack of publicly available information" nationally about COVID-19 infections among people receiving long-term services and supports and the workforce caring for them.

Support for unpaid caregivers: Family caregivers could be identified through Medicare and compensated at the rate of home health aides. In addition, the report calls for improved lines of communication between acute care facilities and other forms of long-term services and support.

Equitable treatment: The Medicaid reimbursement system should provide resources to support independent long-term care and home care providers who often care for the most vulnerable and medically fragile older adults.

"Although these are not new problems, the pandemic has exacerbated and amplified their impact to a point that they are impossible to ignore," the report concludes. "The opportunity for reform is now."

KANSAS CITY, MO--Researchers at the Stowers Institute for Medical Research, in collaboration with colleagues at Stanford University and Technical University of Munich have developed advanced explainable artificial intelligence (AI) in a technical tour de force to decipher regulatory instructions encoded in DNA. In a report published online February 18, 2021, in Nature Genetics, the team found that a neural network trained on high-resolution maps of protein-DNA interactions can uncover subtle DNA sequence patterns throughout the genome and provide a deeper understanding of how these sequences are organized to regulate genes.

Neural networks are powerful AI models that can learn complex patterns from diverse types of data such as images, speech signals, or text to predict associated properties with impressive high accuracy. However, many see these models as uninterpretable since the learned predictive patterns are hard to extract from the model. This black-box nature has hindered the wide application of neural networks to biology, where interpretation of predictive patterns is paramount.

One of the big unsolved problems in biology is the genome's second code--its regulatory code. DNA bases (commonly represented by letters A, C, G, and T) encode not only the instructions for how to build proteins, but also when and where to make these proteins in an organism. The regulatory code is read by proteins called transcription factors that bind to short stretches of DNA called motifs. However, how particular combinations and arrangements of motifs specify regulatory activity is an extremely complex problem that has been hard to pin down.

Now, an interdisciplinary team of biologists and computational researchers led by Stowers Investigator Julia Zeitlinger, PhD, and Anshul Kundaje, PhD, from Stanford University, have designed a neural network--named BPNet for Base Pair Network--that can be interpreted to reveal regulatory code by predicting transcription factor binding from DNA sequences with unprecedented accuracy. The key was to perform transcription factor-DNA binding experiments and computational modeling at the highest possible resolution, down to the level of individual DNA bases. This increased resolution allowed them to develop new interpretation tools to extract the key elemental sequence patterns such as transcription factor binding motifs and the combinatorial rules by which motifs function together as a regulatory code.

"This was extremely satisfying," says Zeitlinger, "as the results fit beautifully with existing experimental results, and also revealed novel insights that surprised us."

For example, the neural network models enabled the researchers to discover a striking rule that governs binding of the well-studied transcription factor called Nanog. They found that Nanog binds cooperatively to DNA when multiples of its motif are present in a periodic fashion such that they appear on the same side of the spiraling DNA helix.

"There has been a long trail of experimental evidence that such motif periodicity sometimes exists in the regulatory code," Zeitlinger says. "However, the exact circumstances were elusive, and Nanog had not been a suspect. Discovering that Nanog has such a pattern, and seeing additional details of its interactions, was surprising because we did not specifically search for this pattern."

"This is the key advantage of using neural networks for this task," says ?iga Avsec, PhD, first author of the paper. Avsec and Kundaje created the first version of the model when Avsec visited Stanford during his doctoral studies in the lab of Julien Gagneur, PhD, at the Technical University in Munich, Germany.

"More traditional bioinformatics approaches model data using pre-defined rigid rules that are based on existing knowledge. However, biology is extremely rich and complicated," says Avsec. "By using neural networks, we can train much more flexible and nuanced models that learn complex patterns from scratch without previous knowledge, thereby allowing novel discoveries."

BPNet's network architecture is similar to that of neural networks used for facial recognition in images. For instance, the neural network first detects edges in the pixels, then learns how edges form facial elements like the eye, nose, or mouth, and finally detects how facial elements together form a face. Instead of learning from pixels, BPNet learns from the raw DNA sequence and learns to detect sequence motifs and eventually the higher-order rules by which the elements predict the base-resolution binding data.

Once the model is trained to be highly accurate, the learned patterns are extracted with interpretation tools. The output signal is traced back to the input sequences to reveal sequence motifs. The final step is to use the model as an oracle and systematically query it with specific DNA sequence designs, similar to what one would do to test hypotheses experimentally, to reveal the rules by which sequence motifs function in a combinatorial manner.

"The beauty is that the model can predict way more sequence designs that we could test experimentally," Zeitlinger says. "Furthermore, by predicting the outcome of experimental perturbations, we can identify the experiments that are most informative to validate the model." Indeed, with the help of CRISPR gene editing techniques, the researchers confirmed experimentally that the model's predictions were highly accurate.

Since the approach is flexible and applicable to a variety of different data types and cell types, it promises to lead to a rapidly growing understanding of the regulatory code and how genetic variation impacts gene regulation. Both the Zeitlinger Lab and the Kundaje Lab are already using BPNet to reliably identify binding motifs for other cell types, relate motifs to biophysical parameters, and learn other structural features in the genome such as those associated with DNA packaging. To enable other scientists to use BPNet and adapt it for their own needs, the researchers have made the entire software framework available with documentation and tutorials.

A research team including the geobiologist Dr. Helge Missbach from the University of Cologne has detected organic molecules and gases trapped in 3.5 billion-year-old rocks. A widely accepted hypothesis says that the earliest life forms used small organic molecules as building materials and energy sources. However, the existence of such components in early habitats on Earth was as yet unproven. The current study, published in the journal 'Nature Communications', now shows that solutions from archaic hydrothermal vents contained essential components that formed a basis for the earliest life on our planet.

Specifically, the scientists examined about 3.5 billion-year-old barites from the Dresser Formation in Western Australia. The barite thus dates from a time when early life developed on Earth. 'In the field, the barites are directly associated with fossilized microbial mats, and they smell like rotten eggs when freshly scratched. Thus, we suspected that they contained organic material that might have served as nutrients for early microbial life,' said Dr. Helge Missbach of the Institute of Geology and Mineralogy and lead author of the study.

In the fluid inclusions, the team identified organic compounds such as acetic acid and methanethiol, in addition to gases such as carbon dioxide and hydrogen sulfide. These compounds may have been important substrates for metabolic processes of early microbial life. Furthermore, they are discussed as putative key agents in the origin of life on Earth. 'The immediate connection between primordial molecules emerging from the subsurface and the microbial organisms - 3.5 billion years ago - somehow surprised us. This finding contributes decisively to our understanding of the still unclear earliest evolutionary history of life on Earth,' Missbach concluded.

UPTON, NY--Scientists have demonstrated that modifying the topmost layer of atoms on the surface of electrodes can have a remarkable impact on the activity of solar water splitting. As they reported in Nature Energy on Feb. 18, bismuth vanadate electrodes with more bismuth on the surface (relative to vanadium) generate higher amounts of electrical current when they absorb energy from sunlight. This photocurrent drives the chemical reactions that split water into oxygen and hydrogen. The hydrogen can be stored for later use as a clean fuel. Producing only water when it recombines with oxygen to generate electricity in fuel cells, hydrogen could help us achieve a clean and sustainable energy future.

"The surface termination modifies the system's interfacial energetics, or how the top layer interacts with the bulk," said co-corresponding author Mingzhao Liu, a staff scientist in the Interface Science and Catalysis Group of the Center for Functional Nanomaterials (CFN), a U.S. Department of Energy (DOE) Office of Science User Facility at Brookhaven National Laboratory. "A bismuth-terminated surface exhibits a photocurrent that is 50-percent higher than a vanadium-terminated one."

"Studying the effects of surface modification with an atomic-level understanding of their origins is extremely challenging, and it requires tightly integrated experimental and theoretical investigations," said co-corresponding author Giulia Galli from the University of Chicago and DOE's Argonne National Laboratory.

"It also requires the preparation of high-quality samples with well-defined surfaces and methods to probe the surfaces independently from the bulk," added co-corresponding author Kyoung-Shin Choi from the University of Wisconsin-Madison.

Choi and Galli, experimental and theoretical leaders in the field of solar fuels, respectively, have been collaborating for several years to design and optimize photoelectrodes for producing solar fuels. Recently, they set out to design strategies to illuminate the effects of electrode surface composition, and, as CFN users, they teamed up with Liu.

"The combination of expertise from the Choi Group in photoelectrochemistry, the Galli Group in theory and computation, and the CFN in material synthesis and characterization was vital to the study's success," commented Liu.

Bismuth vanadate is a promising electrode material for solar water splitting because it strongly absorbs sunlight across a range of wavelengths and remains relatively stable in water. Over the past few years, Liu has perfected a method for precisely growing single-crystalline thin films of this material. High-energy laser pulses strike the surface of polycrystalline bismuth vanadate inside a vacuum chamber. The heat from the laser causes the atoms to evaporate and land on the surface of a base material (substrate) to form a thin film.

"To see how different surface terminations affect photoelectrochemical activity, you need to be able to prepare crystalline electrodes with the same orientation and bulk composition," explained co-author Chenyu Zhou, a graduate researcher from Stony Brook University working with Liu. "You want to compare apples to apples."

As grown, bismuth vanadate has an almost one-to-one ratio of bismuth to vanadium on the surface, with slightly more vanadium. To create a bismuth-rich surface, the scientists placed one sample in a solution of sodium hydroxide, a strong base.

"Vanadium atoms have a high tendency to be stripped from the surface by this basic solution," said first author Dongho Lee, a graduate researcher working with Choi. "We optimized the base concentration and sample immersion time to remove only the surface vanadium atoms."

To confirm that this chemical treatment changed the composition of the top surface layer, the scientists turned to low-energy ion scattering spectroscopy (LEIS) and scanning tunneling microscopy (STM) at the CFN.

In LEIS, electrically charged atoms with low energy--in this case, helium--are directed at the sample. When the helium ions hit the sample surface, they become scattered in a characteristic pattern depending on which atoms are present at the very top. According to the team's LEIS analysis, the treated surface contained almost entirely bismuth, with an 80-to-20 ratio of bismuth to vanadium.

"Other techniques such as x-ray photoelectron spectroscopy can also tell you what atoms are on the surface, but the signals come from several layers of the surface," explained Liu. "That's why LEIS was so critical in this study--it allowed us to probe only the first layer of surface atoms."

In STM, an electrically conductive tip is scanned very close to the sample surface while the tunneling current flowing between the tip and sample is measured. By combining these measurements, scientists can map the electron density--how electrons are arranged in space--of surface atoms. Comparing the STM images before and after treatment, the team found a clear difference in the patterns of atomic arrangements corresponding to vanadium- and bismuth-rich surfaces, respectively.

"Combining STM and LEIS allowed us to identify the atomic structure and chemical elements on the topmost surface layer of this photoelectrode material," said co-author Xiao Tong, a staff scientist in the CFN Interface Science and Catalysis Group and manager of the multiprobe surface analysis system used in the experiments. "These experiments demonstrate the power of this system for exploring surface-dominated structure-property relationships in fundamental research applications."

Simulated STM images based on surface structural models derived from first-principle calculations (those based on the fundamental laws of physics) closely matched the experimental results.

"Our first-principle calculations provided a wealth of information, including the electronic properties of the surface and the exact positions of the atoms," said co-author and Galli Group postdoctoral fellow Wennie Wang. "This information was critical to interpreting the experimental results."

After proving that the chemical treatment successfully altered the first layer of atoms, the team compared the light-induced electrochemical behavior of the treated and nontreated samples.

"Our experimental and computational results both indicated that the bismuth-rich surfaces lead to more favorable surface energetics and improved photoelectrochemical properties for water splitting," said Choi. "Moreover, these surfaces pushed the photovoltage to a higher value."

Many times, particles of light (photons) do not provide enough energy for water splitting, so an external voltage is needed to help perform the chemistry. From an energy-efficiency perspective, you want to apply as little additional electricity as possible.

"When bismuth vanadate absorbs light, it generates electrons and electron vacancies called holes," said Liu. "Both of these charge carriers need to have enough energy to do the necessary chemistry for the water-splitting reaction: holes to oxidize water into oxygen gas, and electrons to reduce water into hydrogen gas. While the holes have more than enough energy, the electrons don't. What we found is that the bismuth-terminated surface lifts the electrons to higher energy, making the reaction easier."

Because holes can easily recombine with electrons instead of being transferred to water, the team did additional experiments to understand the direct effect of surface terminations on photoelectrochemical properties. They measured the photocurrent of both samples for sulfite oxidation. Sulfite, a compound of sulfur and oxygen, is a "hole scavenger," meaning it quickly accepts holes before they have a chance to recombine with electrons. In these experiments, the bismuth-terminated surfaces also increased the amount of generated photocurrent.

"It's important that electrode surfaces perform this chemistry as quickly as possible," said Liu. "Next, we'll be exploring how co-catalysts applied on top of the bismuth-rich surfaces can help expedite the delivery of holes to water."

Several treatments for cancer have been devised by science, but unfortunately none of them are completely efficient or foolproof. Novel treatments with minimum side effects are one of the main aims of the ongoing cancer research. All research so far points to several therapy modes, of which immunotherapy, which prepares the body's own immune system to fight cancer, is a promising option. Bispecific antibodies (BsAbs) are synthetically made proteins that emerged as a promising second-generation immunotherapy. They engage with immune cells and enable them to target cancer in a specific manner.

Conventional use of T cells for this therapy has caused adverse effects in some cases. Moreover, they are ineffective against cold tumors, which are invisible to T cells of the immune system. This led to a search for other immune cells that could effectively target cold tumors with minimum adverse effects. Natural killer (NK) cells have therefore gained attention as prospective immunotherapy agents.

Now, a research team from China has designed a trispecific antibody that targets cancer cells and NK cells using anti-CD16, -IL15, and -CD19 domains. They call this molecule "161519 TriKE." As Dr. Zhigang Tian, one of the members of this research team and co-corresponding author of this study, explains, "Our intention was to attract CD19-positive tumor cells (such as the cells in Burkitt's lymphoma) to CD16-positive NK cells. IL15 can be used to maintain continuous division, development, and survival of NK cells, increasing their efficiency. Simply put, this protein acts like a handcuff, bringing cancer cells to killer immune cells. Additionally, these handcuffs have a trigger that keeps the killer cells active to destroy the cancer cells more efficiently."

In their study published in Cancer Biology & Medicine, the scientists used 161519 TriKE to target CD19-positive cancer cells in cell culture and measured the expression of markers that signify a successful immune response. They observed that several such markers increased in cells treated with 161519 TriKE. To test its preclinical efficiency, researchers developed "immune-reconstituted xenograft" mouse models, which are genetically engineered mice that constitute human peripheral blood mononuclear cells (PBMCs) and human tumors and tested to see if 161519 TriKE is able to initiate an immune response. 161519 TriKE was found to improve the interaction between NK cells and CD19-positive tumor cells. The team also found that 161519 TriKE is able to initiate a strong cytotoxic action of NK cells against tumor cells in cell culture. These results were same in live animals as well. Not only could 161519 TriKE successfully reduce tumor growth, it could also increase the overall survival of tumor-bearing mice.

So, what does this mean for cancer medicine? Prof. Haoyu Sun, co-corresponding author, explains the implications of their findings, "This study effectively provides a new method to develop immunotherapies against cancer. 161519 TriKE has the ability to transform research into application and shows potential for drug development. It can also be used in combination with other NK cell-based therapies."

The fundamental knowledge about the mechanism of action of this new molecule, 161519 TriKE, has the potential to revolutionize the current immunotherapy technology and can be redesigned to target other types of cancers.

WASHINGTON--A potentially dangerous side effect of testosterone therapy for transgender men is an increase in red blood cells that can raise the risk of blood clots, heart attack or stroke, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

Gender diverse people make up an estimated 0.6% of the U.S. population and are defined as having gender identity that is not aligned with their sex recorded at birth. Transgender men often undergo testosterone therapy as part of their gender-affirming treatment. Erythrocytosis, a condition where your body makes too many red blood cells, is a common side effect of testosterone therapy that can increase the risk of blood clots, heart attack or stroke.

"Erythrocytosis is common in transgender men treated with testosterone, especially in those who smoke, have high body mass index (BMI) and use testosterone injections," said lead study author Milou Cecilia Madsen, M.D., of the VU University Medical Center Amsterdam in the Netherlands. "A reasonable first step in the care of transgender men with high red blood cells while on testosterone therapy is to advise them to quit smoking, switch injectable testosterone to gel, and if BMI is high, to lose weight."

The researchers analyzed the medical and laboratory records of 1,073 transgender men using testosterone from the Amsterdam Cohort of Gender study (ACOG). Eleven percent of transgender men using testosterone showed erythrocytosis during 20 years of follow-up. However, less than one percent of these men had very high levels of red blood cells with a high risk of complications.

Ice is a very versatile material. In snowflakes or ice cubes, the oxygen atoms are arranged hexagonally. This ice form is called ice one (ice I). "Strictly speaking, however, these are not actually perfect crystals, but disordered systems in which the water molecules are randomly oriented in different spatial directions," explains Thomas Loerting from the Institute of Physical Chemistry at the University of Innsbruck, Austria. Including ice I, 18 crystalline forms of ice were known so far, which differ in the arrangement of their atoms. The different types of ice, known as polymorphs, form depending on pressure and temperature and have very different properties. For example, their melting points differ by several hundred degrees Celsius. "It's comparable to diamond and graphite, both of which are made of pure carbon," the chemist explains.

Icy variety

When conventional ice I is cooled strongly, the hydrogen atoms can arrange themselves periodically in addition to the oxygen atoms if the experiment is conducted correctly. Below minus 200 degrees Celsius, this can lead to the formation of so-called ice XI, in which all water molecules are ordered according to a specific pattern. Such ordered ice forms differ from the disordered parental forms, especially in their electrical properties. In the current work, the Innsbruck chemists deal with the parent form ice VI, which is formed at high pressure, for example in the Earth's mantle. Like hexagonal ice, this high-pressure form of ice is not a completely ordered crystal. More than 10 years ago, researchers at the University of Innsbruck produced a hydrogen-ordered variant of this ice, which found its way into textbooks as ice XV. By changing the manufacturing process, three years ago Thomas Loerting's team succeeded for the first time in creating a second ordered form for ice VI. To do this, the scientists significantly slowed down the cooling process and increased the pressure to around 20 kbar. This enabled them to arrange the hydrogen atoms in a second way in the oxygen lattice and produce ice XIX. "We found clear evidence at that time that it is a new ordered variant, but we were not able to elucidate the crystal structure." Now his team has succeeded in doing just that using the gold standard for structure determination - neutron diffraction.

Crystal structure solved

For the clarification of the crystal structure, an essential technical hurdle had to be overcome. In an investigation using neutron diffraction, it is necessary to replace the light hydrogen in water with deuterium ("heavy hydrogen"). "Unfortunately, this also changes the time scales for ordering in the ice manufacturing process," says Loerting. "But Ph.D. student Tobias Gasser then had the crucial idea of adding a few percent of normal water to the heavy water - which turned out to speed up the ordering immensely." With the ice obtained in this way, the Innsbruck scientists were finally able to measure neutron data on the high-resolution HRPD instrument at the Rutherford Appleton Laboratory in England and painstakingly solve the crystal structure of ice XIX. This required finding the best crystal structure out of several thousand candidates from the measured data - much like searching for a needle in a haystack. A Japanese research group confirmed the Innsbruck result in another experiment under different pressure conditions. Both papers have now been published jointly in Nature Communications.

Six ice forms discovered in Innsbruck

While conventional ice and snow are abundant on Earth, no other forms are found on the surface of our planet - except in research laboratories. However, the high-pressure forms ice VI and ice VII are found as inclusions in diamonds and have therefore been added to the list of minerals by the International Mineralogical Association (IMA). Many varieties of water ice are formed in the vastness of space under special pressure and temperature conditions. They are found, for example, on celestial bodies such as Jupiter's moon Ganymede, which is covered by layers of different ice varieties.

Ice XV and ice XIX represents the first sibling pair in ice physics in which the oxygen lattice is the same, but the pattern how hydrogen atoms are ordered is different. "This also means that for the first time it will now be possible to realize the transition between two ordered ice forms in experiments," Thomas Loerting is pleased to report. Since the 1980s, researchers at the University of Innsbruck, Austria, are now responsible for the discovery of four crystalline as well as two amorphous ice forms.

The current research work was carried out within the framework of the Research Platform for Materials and Nanoscience at the University of Innsbruck and was financially supported by the Austrian Science Fund FWF.

DALLAS – Feb. 18, 2021 – Inhalation of depleted uranium from exploding munitions did not lead to Gulf War illness (GWI) in veterans deployed in the 1991 Persian Gulf War, a new study co-authored by a leading researcher of the disease at UT Southwestern suggests. The findings, published today in Scientific Reports, help eliminate a long-suspected cause of GWI that has attracted international concern for three decades.

Using high-precision multicollector mass spectrometry for the first time in such a study, Robert Haley, M.D., director of the division of epidemiology at UTSW, and Randall Parrish, Ph.D., professor of isotope geology at the University of Portsmouth in England, collaborated to examine a representative sampling of veterans’ urine maintained by UT Southwestern’s Gulf War Illness Research program. Their report found no differences in secretion of uranium isotopic ratios from those meeting the standard-case definitions of GWI and control veterans without GWI.

“Randy Parrish is a world expert in measuring uranium isotopes, and he had already been consulting in the U.K. for their Gulf War illness studies,” says Haley, a professor of internal medicine who has been investigating GWI for 27 years and holds the U.S. Armed Forces Veterans Distinguished Chair for Medical Research, Honoring Robert Haley, M.D., and America’s Gulf War Veterans.

“That depleted uranium is not and never was in the bodies of those who are ill at sufficient quantities to cause disease will surprise many, including sufferers who have, for 30 years, suspected depleted uranium may have contributed to their illness,” says Parrish.

Affecting about 25 percent of the approximately 700,000 U.S. and coalition military personnel deployed in the Persian Gulf War’s theater of operations, GWI is a chronic illness with symptoms that may include fatigue, fever, night sweats, memory and concentration problems, diarrhea, sexual dysfunction, and chronic body pain. The symptoms are comparable with autonomic nervous system abnormalities and dysfunction of the brain’s cholinergic system, which is associated with cognitive functions such as memory, selective attention, and emotional processing.

Since 1998, the National Academy of Medicine has released numerous Department of Veterans Affairs-supported reports on possible causes of GWI. As Gulf War veterans were exposed to hazards not experienced in previous conflicts, the extensive list of suspected culprits through the years has included the physical and psychological stresses of war, pesticide or nerve gas exposure, depleted uranium (DU) munition exposures, pyridostigmine bromide pills taken by troops to protect against nerve agents, vaccinations for in-theater infections and toxins, and exposure to downwind oil and smoke that spewed for months from hundreds of burning oil wells.

The U.S. military has used depleted uranium since the 1990s for tank armor and some munitions due to its high density that allows for it to penetrate enemy armored vehicles. DU is produced when higher-energy uranium isotopes are removed from natural uranium found in the earth’s crust to produce “enriched” uranium suitable for use in nuclear reactors. The uranium remaining is depleted of about 40 percent of its radioactivity but retains the same chemical toxicity as natural uranium.

When a DU projectile penetrates a vehicle, the intense explosion releases tiny particles of DU that can be inhaled or swallowed as well as larger DU shrapnel fragments that can become embedded in muscle and soft tissue. Subsequent adverse effects are believed to result from heavy metal toxicity and alpha particle radiation from DU concentrated in the lungs, kidneys, and bone of those affected.

During the Gulf War, about 300 tons of DU munitions were fired at targets in Kuwait and southern Iraq, resulting in some friendly-fire incidents as well as secondary aerosol exposures. The Department of Veterans Affairs currently reports that some veterans of the Gulf War, Bosnia, Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn may have been exposed to DU when they were in or around vehicles hit with friendly fire; near burning vehicles; close to fires involving DU munitions; or around damaged vehicles being salvaged.

Haley and Parrish undertook the study after realizing that the role of DU in GWI had never been adequately tested. Using methods developed by the British Royal Society, they calculated the level of DU to be found in urine over time after varying illness-causing levels of exposure. They found that the less sensitive sector-field mass spectrometry used to measure DU in urine in previous studies, while adequate for detecting DU in the few veterans with large fragments of retained shrapnel, would not detect the smaller amounts expected from far more common inhalation exposure or oral ingestion. The type of multicollector mass spectrometer operated by Parrish, which gave results at least 10 times more sensitive and robust than the measurements employed in previous GWI studies, could detect the lower levels expected.

In their study Parrish tested for the lower levels of DU in 154 urine samples, including 106 taken from veterans with GWI meeting standard-case definitions and the rest comprising two control groups representing Gulf War veterans without GWI symptoms and veterans who were not deployed. The subjects, drawn from a nationally representative sample of Gulf War-era veterans, were studied in a hospital research unit where urine was collected for 24 hours in special collection bottles prewashed with nitric acid to remove any trace of natural uranium that could interfere with the DU assay.

In all samples, the scientific partners found no DU present – not in any of those with the illness, not in the control group deployed in theater, nor in those who weren’t on the battlefield, not even in the sample from a U.S. Army officer who survived a friendly-fire incident that destroyed his Bradley Fighting Vehicle, causing him to inhale the resulting hot DU-containing gases and peppering him with shrapnel that was removed months later. Given the high sensitivity of the DU assay, the representativeness of the veterans in the study and their typical patterns of GWI, the study would have found DU at the expected levels in the GWI veterans but not in the controls, if DU was the cause of GWI. Finding none for the first time strongly rejects the link.

“These findings essentially rule out a role for DU in causing GWI,” Haley says. “They also have implications for the international debate over whether DU has since been causing illness in other war theaters where DU munitions were used, since the concern for those situations was originally raised by speculation that depleted uranium caused GWI.”

Parrish adds, “This question of the link between depleted uranium and the illness has bubbled along now for nearly 30 years, but we would argue it’s time to look elsewhere. Disproving the suspected connection between this radioactive substance and GWI allows the medical community to focus more clearly on what the likely cause(s) actually are.”

The investigators believe the most likely remaining causes for GWI are widespread low-level exposure to sarin nerve gas caused by the destruction of Iraqi chemical weapons storage facilities in January 1991, possibly compounded by the use of anti-nerve agent medications and the use of pesticides to prevent insect-borne diseases in coalition forces.

BURNABY, BC - (February 18, 2021) -- D-Wave Systems Inc., the leader in quantum computing systems, software, and services, today published a milestone study in collaboration with scientists at Google, demonstrating a computational performance advantage, increasing with both simulation size and problem hardness, to over 3 million times that of corresponding classical methods. Notably, this work was achieved on a practical application with real-world implications, simulating the topological phenomena behind the 2016 Nobel Prize in Physics. This performance advantage, exhibited in a complex quantum simulation of materials, is a meaningful step in the journey toward applications advantage in quantum computing.

The work by scientists at D-Wave and Google also demonstrates that quantum effects can be harnessed to provide a computational advantage in D-Wave processors, at problem scale that requires thousands of qubits. Recent experiments performed on multiple D-Wave processors represent by far the largest quantum simulations carried out by existing quantum computers to date.

The paper, entitled "Scaling advantage over path-integral Monte Carlo in quantum simulation of geometrically frustrated magnets", was published in the journal Nature Communications (DOI 10.1038/s41467-021-20901-5, February 18, 2021). D-Wave researchers programmed the D-Wave 2000Q™ system to model a two-dimensional frustrated quantum magnet using artificial spins. The behavior of the magnet was described by the Nobel-prize winning work of theoretical physicists Vadim Berezinskii, J. Michael Kosterlitz and David Thouless. They predicted a new state of matter in the 1970s characterized by nontrivial topological properties. This new research is a continuation of previous breakthrough work published by D-Wave's team in a 2018 Nature paper entitled "Observation of topological phenomena in a programmable lattice of 1,800 qubits" (Vol. 560, Issue 7719, August 22, 2018). In this latest paper, researchers from D-Wave, alongside contributors from Google, utilize D-Wave's lower noise processor to achieve superior performance and glean insights into the dynamics of the processor never observed before.

"This work is the clearest evidence yet that quantum effects provide a computational advantage in D-Wave processors," said Dr. Andrew King, principal investigator for this work at D-Wave. "Tying the magnet up into a topological knot and watching it escape has given us the first detailed look at dynamics that are normally too fast to observe. What we see is a huge benefit in absolute terms, with the scaling advantage in temperature and size that we would hope for. This simulation is a real problem that scientists have already attacked using the algorithms we compared against, marking a significant milestone and an important foundation for future development. This wouldn't have been possible today without D-Wave's lower noise processor."

"The search for quantum advantage in computations is becoming increasingly lively because there are special problems where genuine progress is being made. These problems may appear somewhat contrived even to physicists, but in this paper from a collaboration between D-Wave Systems, Google, and Simon Fraser University, it appears that there is an advantage for quantum annealing using a special purpose processor over classical simulations for the more 'practical' problem of finding the equilibrium state of a particular quantum magnet," said Prof. Dr. Gabriel Aeppli, professor of physics at ETH Zürich and EPF Lausanne, and head of the Photon Science Division of the Paul Scherrer Institute. "This comes as a surprise given the belief of many that quantum annealing has no intrinsic advantage over path integral Monte Carlo programs implemented on classical processors."

"Nascent quantum technologies mature into practical tools only when they leave classical counterparts in the dust in solving real-world problems," said Hidetoshi Nishimori, Professor, Institute of Innovative Research, Tokyo Institute of Technology. "A key step in this direction has been achieved in this paper by providing clear evidence of a scaling advantage of the quantum annealer over an impregnable classical computing competitor in simulating dynamical properties of a complex material. I send sincere applause to the team."

"Successfully demonstrating such complex phenomena is, on its own, further proof of the programmability and flexibility of D-Wave's quantum computer," said D-Wave CEO Alan Baratz. "But perhaps even more important is the fact that this was not demonstrated on a synthetic or 'trick' problem. This was achieved on a real problem in physics against an industry-standard tool for simulation--a demonstration of the practical value of the D-Wave processor. We must always be doing two things: furthering the science and increasing the performance of our systems and technologies to help customers develop applications with real-world business value. This kind of scientific breakthrough from our team is in line with that mission and speaks to the emerging value that it's possible to derive from quantum computing today."

The scientific achievements presented in Nature Communications further underpin D-Wave's ongoing work with world-class customers to develop over 250 early quantum computing applications, with a number piloting in production applications, in diverse industries such as manufacturing, logistics, pharmaceutical, life sciences, retail and financial services. In September 2020, D-Wave brought its next-generation Advantage™ quantum system to market via the Leap™ quantum cloud service. The system includes more than 5,000 qubits and 15-way qubit connectivity, as well as an expanded hybrid solver service capable of running business problems with up to one million variables. The combination of Advantage's computing power and scale with the hybrid solver service gives businesses the ability to run performant, real-world quantum applications for the first time.

DURHAM, N.H.— A new report from the University of New Hampshire’s Crimes against Children Research Center (CCRC), using data collected by the U.S. Department of Health and Human Services, showed a marked increase in the share of child maltreatment cases resulting in fatalities as well as a decline in cases of physical abuse and neglect in 2019.

The report, which highlights 2019 statistics from the National Child Abuse and Neglect Data System (NCANDS), showed that fatalities rose 4%. The statistics gathered from child protection agencies in each state indicated that the uptick in child maltreatment fatalities was broadly distributed, with 25 states reporting an increase of 10% or more. This increase in fatalities continues an already upward trend to almost 11% since 2015. According to the report, the states with the largest increases in fatalities pointed to investigations with multiple deaths as well as increases in drownings, vehicle-related deaths and unsafe sleep deaths combined with substance abuse.

By contrast, cases of child physical abuse declined 5% and neglect declined 3%. The number of sexual abuse cases known to authorities was considered flat. Sexual abuse has been declining since the early 1990s, but then ticked up by 6% in 2018.

"We're encouraged to see that the previous rise in sexual abuse cases that we saw in 2018 hasn't continued," said David Finkelhor, director of the CCRC. "The decline in cases of neglect is particularly heartening because it has remained low compared to other forms of maltreatment over the last 25 years."

The report points out that there is not a strong consensus why there has been a long term decline in child sexual and physical abuse but it notes that the downward trend began during a time of economic improvement, increased law enforcement and child protection personnel, more aggressive prosecution, increased public awareness and expanded treatment options for family and mental health problems.

Finkelhor notes that the 2019 data does not reflect any influences from the pandemic and cautions that 2020 data may be difficult to interpret because changes in family dynamics and school attendance could both affect abuse and neglect rates as well as reporting activities.

Among patients with cancer, having additional physical comorbidities was linked with a higher risk of experiencing psychological distress. The finding comes from a Psycho-Oncology analysis of 2017 data from the National Health Survey of Spain.

The analysis included 484 patients who reported a cancer diagnosis and 484 matched controls without a history of cancer. Compared with controls, patients with cancer reported more physical comorbidities, including chronic back pain, asthma, chronic bronchitis, urinary incontinence, prostate problems, and kidney problems. They also reported higher psychological distress and were more likely to have consulted a mental healthcare professional in the past year.

Thirty percent of patients with cancer reported significant psychological distress but only 10% had consulted a professional. Each additional physical comorbidity was associated with a 9% higher odds that patients with cancer would report having high psychological distress and a 21% higher odds that they would have consulted a mental healthcare professional.

"Comorbidities often influence the choice and management of cancer treatment. These results suggest that they could also be important for patients' mental health in the months following diagnosis," said the first author Dafina Petrova, PhD, of the Andalusian School of Public Health, in Spain.

Long black, espresso, or latte, whatever your coffee preference, drink too much and you could be in hot water, especially when it comes to heart health.

In a world first genetic study, researchers from the Australian Centre for Precision Health at the University of South Australia found that that long-term, heavy coffee consumption - six or more cups a day - can increase the amount of lipids (fats) in your blood to significantly heighten your risk of cardiovascular disease (CVD).

Importantly, this correlation is both positive and dose-dependent, meaning that the more coffee you drink, the greater the risk of CVD.

It's a bitter pill, especially for lovers of coffee, but according to UniSA researcher, Professor Elina Hyppönen, it's one we must swallow if we want keep our hearts healthy.

"There's certainly a lot of scientific debate about the pros and cons of coffee, but while it may seem like we're going over old ground, it's essential to fully understand how one of the world's most widely consumed drinks can impact our health," Prof Hyppönen says.

"In this study we looked at genetic and phenotypic associations between coffee intake and plasma lipid profiles - the cholesterols and fats in your blood - finding causal evidence that habitual coffee consumption contributes to an adverse lipid profile which can increase your risk of heart disease.

"High levels of blood lipids are a known risk factor for heart disease, and interestingly, as coffee beans contain a very potent cholesterol-elevating compound (cafestol), it was valuable to examine them together.

"Cafestol is mainly present in unfiltered brews, such as French press, Turkish and Greek coffees, but it's also in espressos, which is the base for most barista-made coffees, including lattes and cappuccinos.

"There is no, or very little cafestol in filtered and instant coffee, so with respect to effects on lipids, those are good coffee choices.

"The implications of this study are potentially broad-reaching. In my opinion it is especially important for people with high cholesterol or who are worried about getting heart disease to carefully choose what type of coffee they drink.

"Importantly, the coffee-lipid association is dose-dependent - the more you drink unfiltered coffee the more it raises your blood lipids, putting you at greater risk of heart disease."

Globally, an estimated 3 billion cups of coffee are consumed every day. Cardiovascular diseases are the number one cause of death globally, taking an estimated 17.9 million lives each year.

The study used data from 362,571 UK Biobank participants, aged 37-73 years, using a triangulation of phenotypic and genetic approaches to conduct comprehensive analyses.

While the jury still may be out on the health impacts of coffee, Prof Hyppönen says it is always wise to choose filtered coffee when possible and be wary of overindulging, especially when it comes to a stimulant such as coffee.

"With coffee being close to the heart for many people, it's always going to be a controversial subject," Prof Hyppönen says.

"Our research shows, excess coffee is clearly not good for cardiovascular health, which certainly has implications for those already at risk.

"Of course, unless we know otherwise, the well-worn adage usually fares well - everything in moderation - when it comes to health, this is generally good advice."

A new study looking at how COVID-19 affects people with asthma provides reassurance that having the condition doesn't increase the risk of severe illness or death from the virus.

George Institute for Global Health researchers in Australia analysed data from 57 studies with an overall sample size of 587,280. Almost 350,000 people in the pool had been infected with COVID-19 from Asia, Europe, and North and South America and found they had similar proportions of asthma to the general population.

The results, published in the peer-reviewed Journal of Asthma, show that just over seven in every 100 people who tested positive for COVID-19 also had asthma, compared to just over eight in 100 in the general population having the condition. They also showed that people with asthma had a 14 percent lower risk of acquiring COVID-19 and were significantly less likely to be hospitalized with the virus.

There was no apparent difference in the risk of death from COVID-19 in people with asthma compared to those without.

Head of The Institute's Respiratory Program, co-author Professor Christine Jenkins said that while the reasons for these findings weren't clear, there were some possible explanations - such as some inhalers perhaps limiting the virus' ability to attach to the lungs.

"Chemical receptors in the lungs that the virus binds to are less active in people with a particular type of asthma and some studies suggest that inhaled corticosteroids - commonly used to treat asthma - can reduce their activity even further," she said.

"Also, initial uncertainty about the impact of asthma on COVID-19 may have caused anxiety among patients and caregivers leading them to be more vigilant about preventing infection."

Lead author Dr Anthony Sunjaya added that while this study provides some reassurance about the risks of exposure to COVID-19 in people with asthma, doctors and researchers were still learning about the effects of the virus.

"While we showed that people with asthma do not seem to have a higher risk of infection with COVID-19 compared to those without asthma and have similar outcomes, we need further research to better understand how the virus affects those with asthma," he said.

When the COVID-19 pandemic first spread across the world concerns were raised that people with asthma might be at a higher risk of becoming infected, or of becoming sicker or even dying.

Previous findings have shown that people with chronic respiratory conditions like asthma were reported to be at greater risk during the Middle East Respiratory Syndrome (MERS) outbreak, caused by a virus with a similar structure.

"Respiratory infections like those caused by coronaviruses can exacerbate asthma symptoms and corticosteroid treatment may increase susceptibility to COVID-19 infection and its severity," Dr Sunjaya said.

However this study using the best evidence available on the risk of infection, severe illness - requiring admission to ICU and/or ventilator use - and death from COVID-19 in people with asthma finds "no significant difference" of people with asthma being at higher risk.

Funded by Asthma Australia, the review included analysis of 45 hospital-based studies, six studies in the community and six with mixed setting. 22 of the studies were carried out in North America, 19 Asia, 14 Europe, and two in South America. Four of the studies only included children, making up 211 of the participants.

The average age of the participants was roughly 52; while 52.5% were males, 11.75% were current smokers and 16.2% were former. 54% had some form of comorbidities, 21% had diabetes and approximately 8% had chronic obstructive pulmonary disease.

Thirty-six studies were peer-reviewed publications; another 17 were preprints, 3 were government reports and 1 an open dataset.

The paper's findings also show increasing age is strongly associated with an increased risk of acquiring COVID-19 among asthmatics and explained 70% of the in-between study variance in the analysis. "This is an expected finding and in line with other COVID-19 studies showing age as one of the most important predictors for vulnerability to COVID-19 and prognosis," the authors add.

This review has "rigorously adhered to the guidelines of performing systematic reviews", limitations, however are that this is the synthesis of primarily observational studies, with a short duration of follow-up, mainly self-reported asthma and variable reporting of outcomes which may introduce bias in the pooled effect.

Transit-oriented development--which concentrates high-density housing, commercial activities and public spaces around a rapid transit station--can both be a boon and a bane for communities, suggests a new UBC study.

"Transit-oriented development (TOD) can reduce traffic congestion and air pollution, encourage active mobility, and revitalize a neighbourhood," explains study author Craig E. Jones, a PhD candidate in geography and the research coordinator for the Housing Research Collaborative at UBC's faculty of applied science.

"However, it can also cause gentrification through the demolition of affordable rental housing. It can tailor the area towards condo homeowners, creating a very clear class difference between the former residents, who may not be able to afford to stay, and the new condo dwellers."

Refugees displaced

For example, the Evergreen Line--an expansion of Metro Vancouver's SkyTrain line into the suburb of Coquitlam--improved mass transit in the region but also contributed to displacement.

Jones conducted interviews with eight former residents of Whitgift Gardens, an older rental apartment complex located near the Evergreen Line that had long been a landing place for recent immigrants and refugees.

When Whitgift Gardens was redeveloped following the construction of the Evergreen Line, many residents were displaced, including the study participants.

"This is an example of perhaps the worst possible outcome of TOD in the region--where it compounds an existing housing crisis," notes Jones. "What happened to these individuals speaks to concerns raised by researchers and policy analysts that TOD interventions could result in gentrification and the displacement of low-income groups."

From 2015-2019, this neighbourhood saw a net loss of more than 600 rental units, indicating that a large number of tenants were displaced, Jones added.

"It's important to note that new transit stations are also often put in areas where there is less resistance to high-density development, such as areas with stigmatized social housing, certain suburbs, ethnic enclaves or central business districts, rather than single-family dwellings. So ironically, even though one of the goals of TOD is to equitably enhance accessibility, these high housing costs displace low-income households, resulting in a reduction of access to affordable rapid transit for those who need it the most."

Mitigating the human costs

Jones notes that what happened in Whitgift Gardens is not unique. In Burnaby, hundreds of older rental apartments were demolished for redevelopment around Metrotown SkyTrain station prior to the last municipal election.

He forecasts that Vancouver's upcoming Broadway subway, which will go through a huge concentration of older, low-rise rental buildings in Kitsilano and Granville, will create significant pressure on these buildings.

"When plans clearly state that hundreds of affordable rental units are going to be demolished, then there has to be a lot of thought put into what the potential consequences are, and what could be done to at least mitigate those costs and the harm it will do to people," said Jones.

He added that the city of Burnaby now has one of the most ambitious tenant assistance policies in Canada in response to community outcry over the demolition of older rental buildings.

"Since 2019, tenants displaced due to demolition must be offered a replacement unit with the same number of bedrooms in the new building at 20 per cent below average rents. There are ways to pursue rapid transit and growth without causing gentrification and displacement."

A considerable portion of the efforts to realize a sustainable world has gone into developing hydrogen fuel cells so that a hydrogen economy can be achieved. Fuel cells have distinctive advantages: high energy-conversion efficiencies (up to 70%) and a clean by-product, water. In the past decade, anion exchange membrane fuel cells (AEMFC), which convert chemical energy to electrical energy via the transport of negatively charged ions (anions) through a membrane, have received attention due to their low-cost and relative environment friendliness compared to other types of fuel cells. But while inexpensive, AEMFCs suffer from several major drawbacks such as low ion conductivity, low chemical stability of the membrane, and an overall lower performance rate than its counterparts. Now, in a study published in the Journal of Materials Chemistry A, scientists from Korea report a novel membrane that is both thin and strong, and takes care of these drawbacks.

To develop their membrane, the scientists used a novel method: they chemically bonded two commercially available polymers, poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) and poly(styrene-b-(ethylene-co-butylene)-b-styrene) (SEBS) without using a crosslinking agent. Professor Tae-Hyun Kim from Incheon National University, who led the study, explains, "A previous study made a similar attempt to fabricate anion exchange membranes (AEMs) by crosslinking PPO and SEBS with diamine as a crosslinking agent. While the AEMs displayed excellent mechanical stability, the use of diamine could have led to different reactions other than those between PPO and SEBS, which made it difficult to control the properties of the resultant membrane. Therefore, in our study, we crosslinked PPO and SEBS without any crosslinking agent to ensure that only PPO and SEBS react with each other." The strategy used by Prof. Kim's team also involved adding a compound called triazole to PPO to increase the membrane's ion conductivity.

Membranes fabricated using this method were up to 10 μm thin and had excellent mechanical strength, chemical stability, and conductivity at even a 95% room humidity. Together, these conferred a high overall performance to the membrane and to the corresponding fuel cell on which the scientists tested their membrane. When operated at 60°C, this fuel cell exhibited stable performance for 300 hours with a maximum power density surpassing those of existing commercial AEMs and matching cutting-edge ones.

Excited about the future prospects of this novel promising AEM, Prof. Kim says, "The polymer electrolyte membranes in our study can be applied not only to fuel cells that generate energy, but also to water electrolysis technology that produces hydrogen. Therefore, I believe this research will play a vital role in revitalizing the domestic hydrogen economy."

Perhaps that clean and green world we envision is not far away!