Culture

Analyses of lung fluid cells from COVID-19 patients conducted on the nation's fastest supercomputer point to gene expression patterns that may explain the runaway symptoms produced by the body's response to SARS-CoV-2.

A team led by Dan Jacobson of the Department of Energy's Oak Ridge National Laboratory used the Summit supercomputer at ORNL to analyze genes from cells in the lung fluid of nine COVID-19 patients compared with 40 control patients.

The computational analyses suggest that genes related to one of the body's systems responsible for lowering blood pressure -- the bradykinin system -- appear to be excessively "turned on" in the lung fluid cells of those with the virus. The results were published in eLife.

Based on their analyses, the team posits that bradykinin -- the compound that dilates blood vessels and makes them permeable -- is overproduced in the body of COVID-19 patients; related systems either contribute to overproduction or cannot slow the process. Excessive bradykinin leads to leaky blood vessels, allowing fluid to build up in the body's soft tissues.

Much attention has focused on what's known as the cytokine storm, a severe reaction in which the body releases an excess of cytokines, a variety of small proteins that help regulate the immune system. Jacobson's team thinks a bradykinin storm may instead be to blame for much of the viral pathogenesis. If the team's disease mechanism model is accurate and substantiated by experimental analysis, it may mean that existing medicines could be repurposed to slow the pathogenesis of COVID-19. This would require extensive clinical trials of drugs currently used to treat other bradykinin-related conditions.

"If we can block this pathogenesis in severe patients, we can keep the human response from going overboard and give their immune system time to fight off the virus so they can recover," Jacobson said.

The bradykinin storm could explain the wide variety of symptoms experienced by COVID-19 patients, such as muscle pain, fatigue, nausea, vomiting, diarrhea, headaches, and decreased cognitive function. Similar symptoms are also experienced by patients with other bradykinin-related conditions such as hereditary angioedema, a genetic condition that is characterized by episodes of severe swelling throughout the body.

"This is one of those rare times where you can really tie everything back to a eureka moment," said Jacobson, staff scientist in ORNL's Biosciences Division. "I was looking at data, and I suddenly saw some very distinct patterns happening in the pathways of the renin-angiotensin and bradykinin systems. That led us to do a deep dive of the gene families of the blood pressure regulatory system." The renin-angiotensin system, or RAS, and bradykinin pathway regulate blood pressure and fluid balance in the body.

Using the Summit and Rhea supercomputers at the Oak Ridge Leadership Computing Facility, the team compared the genes of COVID-19 patients against a control group and analyzed population-scale gene expression data -- 17,000 samples from uninfected individuals -- to see which genes were normally co-expressed, or turned on or off at the same time.

Summit is currently the nation's most powerful supercomputer, with a theoretical peak performance of 200 petaflops, or 200 quadrillion calculations per second. Jacobson and his colleagues required the power of Summit to run 2.5 billion correlation calculations that helped them understand the normal regulatory circuits and relationships for the genes of interest. With Summit, the team completed the calculations in one week rather than spending months doing them on a desktop computer.

Researchers found an increased expression of enzymes that can trigger the production of bradykinin and a decreased expression of enzymes that would break down bradykinin -- the perfect storm. The team also uncovered that an enzyme that forestalls the bradykinin cascade -- the angiotensin-converting enzyme, known as ACE -- was less expressed in COVID-19 patients. At least ten existing drugs are known to act on the specific pathways Jacobson's team studied, but large-scale clinical trials are needed to determine whether they might be effective at treating COVID-19.

"We believe that when you take the inhibition at the top of this pathway off, you end up with an out-of-control cascade that leads to an opening up of the blood vessels, causing them to leak," Jacobson said. "If that happens in the lung, that's not good. Immune cells that are normally contained in the blood vessels flood into the surrounding infected tissue, causing inflammation."

The lungs of COVID-19 patients are known to have an increased amount of hyaluronic acid, a gooey substance found in connective tissues that can trap around 1,000 times its own weight in water to form a hydrogel. The team also found that genes in the cells of COVID-19 patients increased the production of the substance and decreased its breakdown. The findings suggest that further experimental study of drug compounds known to slow the synthesis of hyaluronic acid and the mechanisms involved in the process is warranted.

"When the lungs end up with an excess of hyaluronic acid in them, it's like trying to breathe through Jell-O," Jacobson said. "It reaches a point where regardless of how much oxygen you pump in, it doesn't matter, because the alveoli in the lungs are filled with this hydrogel. With this excess of hyaluronic acid, any water leaking out of the blood vessels due to bradykinin will soak up this structure and the lungs become like a water balloon."

The team also used the Compute and Data Environment for Science, or CADES, at ORNL to determine which genes in the RAS-bradykinin pathways have vitamin D binding sites. The results of their analyses might help scientists determine through experimentation which parts of these pathways could potentially be influenced by vitamin D. Because vitamin D helps regulate the RAS and vitamin D deficiencies have already been associated with more severe illness in COVID-19 patients, Jacobson said it's another molecule worth further study.

WASHINGTON, D.C.--The signs of physical abuse among elderly people can be challenging for health care professionals to recognize, resulting in as few as one in 24 cases being reported to authorities. However, a new study in Annals of Emergency Medicine explores injury patterns and characteristics to help experts spot key differences between abuse and unintentional injury.

"The first place that many vulnerable older patients turn for care is the emergency department," said lead study author Tony Rosen, MD, MPH, FACEP, assistant professor of emergency medicine at Weill Cornell Medicine and director of the Vulnerable Elder Protection Team based at New York-Presbyterian/Weill Cornell Medical Center's emergency department. "Emergency physicians have a unique opportunity to identify the 'red flags' for elder abuse. Improving the ability to recognize, treat, and prevent these incidents can improve the lives of millions of older patients."

The study, "Identifying Injury Patterns Associated with Physical Elder Abuse: Analysis of Legally Adjudicated Cases," compares 78 physical abuse cases with visible injuries among patients aged 60 or older with 78 patients of similar age and sex who visited a New York City emergency department for an unintentional fall between 2001-2014.

Abuse-related injuries are frequently attributed to an unintentional fall, the authors note. By comparing a group of patients injured by an unintentional fall with medical and legal records of prosecuted abuse cases, the study reveals several distinct injury patterns:

Victims of abuse often have head or neck injuries without visible harm to other parts of the body. Abuse victims are more likely than patients who fall to have injuries on the face, head and neck area (67 percent versus 28 percent).

Abuse victims are less likely than patients who fall to have scrapes, fractures or injuries below the waist (8 percent versus 50 percent).

Facial injuries to the left cheek are frequent (22 percent) in abuse cases; a finding that confirms that abusers tend to be right-handed, the authors note.

Neck injuries raise suspicions of abuse because the neck is often protected by the head or the face during an unintentional fall. Among more than 800 examined injuries, researchers found neck injuries and ear injuries resulted from abuse rather than a fall (15 percent versus 0 percent for neck injuries and 6 percent versus 0 percent for ear injuries).

According to the study, 22 percent of cases identified and prosecuted had no visible injury recorded. In many of these cases, victims indicated pain in the arms, chest, abdomen, back, face and jaw, which can inform how to approach patients without visible injury when abuse is suspected.

"Identifying the victims of elder abuse is an important skill set for professionals working in emergency departments caring for older adults," said Dr. Rosen. "Recognizing injury patterns helps encourage an environment where more of these troubling cases of harm against some of the most vulnerable, at-risk older adult patients can be reported and addressed."

East Hanover, NJ. July 28, 2020. Researchers at Kessler Foundation conducted a pilot study comparing the effects of mental fatigue on brain activation patterns in people with and without multiple sclerosis (MS). Their findings indicate significant differences between the two groups in their recruitment of neural resources in response to increased task demands. The article, "Neural mechanisms underlying state mental fatigue in multiple sclerosis: A pilot study," was published in the Journal of Neurology on April 29, 2020. (Doi: 10.1007/s00415-09853-w) The authors are Michelle H. Chen, PhD, Glenn Wylie, DPhil, Rosalia Dacosta-Aguayo, PhD, John DeLuca, PhD, and Helen Genova, PhD, of Kessler Foundation, and Brian M. Sandroff, PhD, of the University of Alabama at Birmingham.

This pilot study extended the Foundation's investigation into the neural correlates of mental fatigue in MS. Mental fatigue comprises two types, state and trait, which are typically measured subjectively. The current study focused on state fatigue, which fluctuates over minutes to hours; trait fatigue is stable over longer periods, usually weeks.

The study comprised 36 participants, 19 with MS, and 17 controls. Participants underwent functional magnetic resonance imaging (fMRI) while performing the Symbol Digit Modalities Test (SDMT), a standard cognitive test modified for use with fMRI. Changes in brain activity were recorded while the SDMT was administered under two conditions: high and low cognitive loads. Neuroimaging studies were conducted at the research-dedicated Rocco Ortenzio Neuroimaging Center at Kessler Foundation.

"We found higher levels of fatigue and longer response times in the MS group," said Dr. Chen, postdoctoral fellow in the Center for Neuropsychology and Neuroscience Research at Kessler Foundation. "With increasing mental fatigue, the control group showed increased activation of the anterior brain regions and faster speed of response, to meet the demands of the high load condition, " added Dr. Chen. "The MS group did not show activation of these regions or an increase in processing speed, suggesting a less efficient response to the higher cognitive demands of the task."

Results of the pilot study were consistent with prior research into the functional reorganization of brain activity in response to mental fatigue, according to Dr. Genova, assistant director of the Center for Neuropsychology and Neuroscience Research. "In the absence of effective treatment for the disabling fatigue that affects many individuals with MS, it is essential to expand our understanding of these underlying brain mechanisms. Using fMRI allows us to determine how individuals with MS differ from their peers without MS in their cerebral responses to cognitive challenges, an important first step in the development of interventions to counter mental fatigue."

In a new study from the Wake Forest Institute for Regenerative Medicine (WFIRM) researchers have developed an optimized cellular platform for delivering Factor 8 to better treat patients with hemophilia A.

Hemophilia A is a genetic disorder caused by a deficiency in, or the absence of, coagulation Factor 8), an essential protein for blood to clot. Hemophilia A is an x-linked genetic disease, and thus almost always affects males, and it occurs in 1 in 5,000 live male births. Roughly 20,000 individuals in the United States suffer from hemophilia A, and it is estimated that more than 400,000 people worldwide have this devastating disease, according to http://www.hemophilia.org. Hemophilia A is currently treated with infusions of expensive Factor 8 products 2-3 times per week for the entire life of the patient.

While these treatments have dramatically improved the life expectancy of patients with hemophilia A, they are unavailable to nearly 75% of the world's patients, they cost well over $250,000 a year (per patient), and complications can send the price tag to more than $1 million. Moreover, as many as 30% of patients with the severe form of hemophilia A develop an immune response (inhibitors) to the infused Factor 8 protein, rendering subsequent treatments ineffective and placing the patient at risk of life-threatening bleeding events. In addition, and perhaps most important, these treatments are not curative.

The delivery of Factor 8 through gene and/or cellular platforms has, therefore, emerged as a promising approach to provide long-term correction of hemophilia A. For this study, the researchers investigated the suitability of human placental cells as delivery vehicles for Factor 8 and determined an optimal Factor 8 transgene to secrete therapeutic Factor 8 levels from these cells. Using cells that are modified to over express Factor 8 allows safeguards in production that are not possible when direct vector injection is used to treat patients.

"This is about the quality of life for these patients," said lead author Graca Almeida-Porada, MD, PhD of WFIRM. "We are trying to develop not just a treatment, but a cure."

The research group demonstrated, for the first time, that human placental cells constitutively secrete low levels of Factor 8, confirming these cells possess the machinery necessary to express and process this challenging protein, and suggesting they may be ideally suited as a cellular platform for delivering and producing Factor 8 to correct hemophilia A.

"We demonstrated human placenta-derived mesenchymal cells possess a set of several fairly unique properties that make them ideal both for cellular therapies/regenerative medicine, and as vehicles for Factor 8 delivery," said Almeida-Porada. "In addition, because the pharmaceutical properties of Factor 8 can be markedly enhanced by changing the coding sequence to facilitate Factor 8 processing and secretion by the cells, we identified a modified Factor 8 transgene, amongst the several developed by our colleagues at Emory, that yielded optimal Factor 8 expression and secretion from placental cells."

While our initial goal is to use this treatment to correct hemophilia A prior to birth, Almeida-Porada said the approach could also be used in those pediatric and adult patients who develop Factor 8 inhibitors during their lifetime. Further preclinical studies will be needed to establish in vivo safety and efficacy of this therapy, for both prenatal and postnatal recipients, she added.

"It is our hope this approach can be moved forward as a long-lasting and curative treatment option for patients with hemophilia A," added co-author and WFIRM Director Anthony Atala, MD.

AMHERST, Mass. - Evolutionary and developmental biologist Craig Albertson and colleagues at the University of Massachusetts Amherst report that they have identified a molecular mechanism that allows an organism to change the way it looks depending on the environment it is exposed to, a process known as phenotypic plasticity.

In addition to lead investigators Albertson and Rolf Karlstrom, the team includes recently graduated doctoral students Dina Navon and Ira Male, current Ph.D. candidate Emily Tetrault and undergraduate Benjamin Aaronson. Their paper appears now in Proceedings of the National Academy of Sciences.

Albertson explains that the project stems from a desire to better understand how genes and the environment interact to direct anatomical shape. "We know that our features are determined by genes, but we also know that many physical features are shaped by the environment as well. In identical twins, for example, if one becomes a long-distance runner and the other a body builder, they are going to end up with very different physiques. The skeleton is especially sensitive to such environmental inputs."

Albertson works with a system - cichlid fishes - known throughout the scientific world as champions of phenotypic plasticity that can alter, in a single season, jawbone hardness or shape to match feeding conditions. They are also well known for their rapid evolution and diversity in jaw shapes, which has enabled cichlids to adapt to many different food sources, including algae, plankton, fish, snails and even the scales of other fishes.

Albertson has spent much of the past two decades trying to reveal the genetic differences that underlie differences in jaw shape between species. Now he and colleagues identify the well-studied chemical/molecular system known as the Hedgehog (Hh) signaling pathway as an important player. More recently he explored whether the same pathway might also contribute to differences in jaw shape that arise within species through phenotypic plasticity.

An important clue came as Albertson learned more about how this molecular pathway works. He explains, "There is a well-known mechano-sensor on most cells, including those that make the skeleton, called the primary cilium. Cells that lack this organelle are unable to sense or respond to environmental input, including mechanical load. It turns out that several key protein components of the Hedgehog pathway are physically associated with this structure, making it an obvious candidate for an environmentally sensitive signal."

In the current study, the research team first showed that plasticity in the rate of bone deposition in cichlids forced to feed using different foraging modes was associated with different Hh levels. Greater levels of the signal were detected in fish from the environment where more bone was laid down and vice versa. To really nail the question, Albertson teamed up with Karlstrom, who had previously developed sophisticated tools to study Hh signaling in zebrafish.

He explains, "Rolf has a bunch of really slick transgenic systems for manipulating that molecular signal in real time. It is sort of like a volume knob on your stereo - you can turn it up or turn it down, and then see how it influences your trait of interest." In this case, they wanted to see whether Hh levels influenced plasticity in bone deposition rates.

They found that unmanipulated zebrafish deposited different amounts of bone in different foraging environments. When Hh levels were reduced, these differences went away, but when Hh levels were increased, differences in bone deposition rates were dramatically increased.

Albertson, explains, "Bone cells in these fish are innately sensitive to different mechanical environments. But we were able to play with this system using a single molecular switch - you turn up the Hh signal and the cells become more sensitive to the environment, or you turn the molecular sensor down and the cells become almost deaf to the environment."

"That the same molecular machinery underlies both the evolutionary divergence and plasticity of the jaw is notable," Albertson explains. "It is consistent with long-held theory that suggests short-term plasticity might bias the direction of long-term evolution, which explains why evolution can be predictable in lineages that have repeatedly evolved to similar habitats." Albertson adds, "The Hh signal has also been shown to regulate plasticity in beetle horns, so there may be something special that positions it to be an environmental sensor across tissues and animals."

Such intriguing questions will be the topic for future investigations, the authors add.

"A watched pot never boils," as the saying goes, but that was not the case for UC Santa Barbara researchers watching a "pot" of liquids formed from DNA. In fact, the opposite happened.

With research partners at the Ludwig-Maximilians University (LMU), in Munich, Germany, the team's findings appear in the Proceedings of the National Academy of Sciences.

Recent advances in cellular biology have enabled scientists to learn that the molecular components of living cells (such as DNA and proteins) can bind to each other and form liquid droplets that appear similar to oil droplets in shaken salad dressing. These cellular droplets interact with other components to carry out basic processes that are critical to life, yet little is known about how the interactions function. To gain insight into these fundamental processes, the researchers used modern methods of nanotechnology to engineer a model system -- a liquid droplet formed from particles of DNA -- and then watched those droplets as they interacted with a DNA-cleaving enzyme.

Surprisingly, they found that, in certain cases, adding the enzyme caused the DNA droplets to suddenly start bubbling, like boiling water.

"The bizarre thing about the bubbling DNA is that we didn't heat the system; it's as if a pot of water started boiling even though you forgot to turn on the stove," said project co-leader Omar Saleh, a UC Santa Barbara assistant professor of materials and bioengineering. However, the bubbling behavior didn't always occur; sometimes adding the enzyme would cause the droplets to shrink away smoothly, and it was unclear why one response or the other would occur.

To get to the bottom of this mystery, the team carried out a rigorous set of precision experiments to quantify the shrinking and bubbling behaviors. They identified two types of shrinking behavior: the first caused by enzymes cutting the DNA only on the droplet surface, and the second caused by enzymes penetrating inside the droplet. "This observation was critical to unraveling the behavior, as it put into our heads the idea that the enzyme could start nibbling away at the droplets from the inside," said co-leader Tim Liedl, a professor at the LMU, where the experiments were conducted.

By comparing the droplet response to the DNA particle design, the team cracked the case: they found that bubbling and penetration-based shrinking occurred together, and happened only when the DNA particles were lightly bound together, whereas strongly bound DNA particles would keep the enzyme on the outside. As Saleh noted, "It's like trying to walk through a crowd -- if the crowd is tightly holding hands, you wouldn't be able to get through."

The bubbles, then, happen only in the lightly bound systems, when the enzyme can get through the crowded DNA particles to the interior of the droplet, and begin to eat away at the droplet from the inside. The chemical fragments created by the enzyme lead to an osmotic effect in which water is drawn in from the outside, causing a swelling phenomenon that produces the bubbles. The bubbles grow, reach the droplet surface, and then release the fragments in a burp-like gaseous outburst. "It is quite striking to watch, as the bubbles swell and pop over and over," said Liedl.

The work demonstrates a complex relationship between the basic material properties of a biomolecular liquid and its interactions with external components. The team believes that the insight gained from studying the bubbling process will lead both to better models of living processes and to enhanced abilities to engineer liquid droplets for use as synthetic bioreactors.

The research was made possible by an award to Saleh from the Alexander von Humboldt Foundation, which enabled him to visit Munich and work directly with Liedl on this project. "These types of international collaborations are extremely productive," Saleh said.

URBANA, Ill. - As climate change becomes increasingly difficult to ignore, scientists are working to diversify and improve alternatives to fossil-fuel-based energy. Renewable bioenergy crops, such as the perennial grass Miscanthus, show promise for cellulosic ethanol production and other uses, but current hybrids are limited by environmental conditions and susceptibility to pests and diseases.

Breeders have been working to develop new Miscanthus hybrids for years, but the clonal crop's sterility, complex genome, and long time to maturity make conventional breeding difficult. In a new study, University of Illinois researchers mine the crop's vast genomic potential in an effort to speed up the breeding process and maximize its most desirable traits.

"The method we're using, genomic selection, can shorten the time it takes to breed a new hybrid by at least half," says Marcus Olatoye, lead author on the study and postdoctoral researcher in the Department of Crop Sciences at Illinois. "That's the overall goal."

In conventional breeding, one typical approach is for researchers to grow individuals from a diverse set of populations and select those with the best traits for mating. But, for Miscanthus, those traits don't show up until plants are 2-3 years old. Even after plants from this first generation are mated, it takes the offspring another 2-3 years to reveal whether the desired traits were faithfully passed on.

In genomic selection, scientists take genetic samples from seeds or seedlings in a target population. This is the group of plants that would ordinarily have to be grown to maturity before experimental crosses are made. Meanwhile, the researchers compile both genetic and phenotypic data from related populations, known as reference or training sets, into a statistical model. Cross-referencing genetic data from the target population with data in the model allows the researchers to predict the phenotypic outcome of hypothetical crosses within the target population.

This allows breeders to cut to the chase, pursuing only the most promising crosses with further field testing.

"Ideally, this process could allow breeders to make selections based on predicted phenotypic values before plants are even planted," says Alex Lipka, associate professor of biometry in the Department of Crop Sciences and co-author on the study. "Specifically, we want to make selections to optimize winter hardiness, biomass, disease tolerance, and flowering time in Miscanthus, all of which limit the crop's performance in various regions of North America."

Although it's not a simple process in the best of times, genomic selection in Miscanthus is orders of magnitude more challenging than in other crops. The hybrid of interest, Miscanthus × giganteus, is the product of two separate species, Miscanthus sinensis and Miscanthus sacchariflorus, each of which have different numbers of chromosomes and contain a great deal of variation within and across natural populations.

"As far as we know, no one has tried to train genomic selection models from two separate species before. We decided to go totally nuts here," Lipka says. "Unfortunately, we found the two parent species do not do a very good job of predicting biofuel traits in Miscanthus × giganteus."

The problem was twofold. First, the statistical model simply revealed too much genetic variation among parental subpopulations to capture the impact of genes controlling biofuel traits. This meant the parental populations chosen for the reference set were too diverse to reliably predict traits in the hybrid Miscanthus × giganteus. And second, the genes controlling a particular trait - like those related to biofuel potential - seemed to be different in the two parent species.

In other words, the genomes contributing to Miscanthus × giganteus are highly complex, explaining why the statistical approach had a hard time predicting traits in offspring from the two parents.

Still, the research team kept trying. In a simulation study, Olatoye created 50 Miscanthus × giganteus families, each derived from parents randomly selected from both species. He selectively dialed genetic contributions of each parent up and down, and these contributions formed the genetic basis of simulated phenotypes. The intention of the study was to provide a better view of which individuals and populations might be most valuable for crosses in real life.

"The results suggest the best strategy for utilizing diversity in the parents is to fit genomic selection models within each parental species separately, and then add the predicted Miscanthus × giganteus trait values from the two models separately," Olatoye says.

Although the researchers have more work to do, the simulation study proved genomic selection can work for Miscanthus × giganteus. The next step is further refining which populations are used to train the statistical model and evaluating crosses in the field.

A new blood test demonstrated remarkable promise in discriminating between persons with and without Alzheimer's disease and in persons at known genetic risk may be able to detect the disease as early as 20 years before the onset of cognitive impairment, according to a large international study published today in the Journal of the American Medical Association (JAMA) and simultaneously presented at the Alzheimer's Association International Conference.

For many years, the diagnosis of Alzheimer's has been based on the characterization of amyloid plaques and tau tangles in the brain, typically after a person dies. An inexpensive and widely available blood test for the presence of plaques and tangles would have a profound impact on Alzheimer's research and care. According to the new study, measurements of phospho-tau217 (p-tau217), one of the tau proteins found in tangles, could provide a relatively sensitive and accurate indicator of both plaques and tangles--corresponding to the diagnosis of Alzheimer's--in living people.

"The p-tau217 blood test has great promise in the diagnosis, early detection, and study of Alzheimer's," said Oskar Hansson, MD, PhD, Professor of Clinical Memory Research at Lund University, Sweden, who leads the Swedish BioFINDER Study and senior author on the study who spearheaded the international collaborative effort. "While more work is needed to optimize the assay and test it in other people before it becomes available in the clinic, the blood test might become especially useful to improve the recognition, diagnosis, and care of people in the primary care setting."

Researchers evaluated a new p-tau217 blood test in 1,402 cognitively impaired and unimpaired research participants from well-known studies in Arizona, Sweden, and Colombia. The study, which was coordinated from Lund University in Sweden, included 81 Arizona participants in Banner Sun Health Research Institute's Brain Donation program who had clinical assessments and provided blood samples in their last years of life and then had neuropathological assessments after they died; 699 participants in the Swedish BioFINDER Study who had clinical, brain imaging, cerebrospinal fluid (CSF), and blood-based biomarker assessments; and 522 Colombian autosomal dominant Alzheimer's disease (ADAD)-causing mutation carriers and non-carriers from the world's largest ADAD cohort.

In the Arizona (Banner Sun Health Research Institute) Brain Donation Cohort, the plasma p-tau217 assay discriminated between Arizona Brain donors with and without the subsequent neuropathological diagnosis of "intermediate or high likelihood Alzheimer's" (i.e., characterized by plaques, as well as tangles that have at least spread to temporal lobe memory areas or beyond) with 89% accuracy; it distinguished between those with and without a diagnosis of "high likelihood Alzheimer's" with 98% accuracy; and higher ptau217 measurements were correlated with higher brain tangle counts only in those persons who also had amyloid plaques.

In the Swedish BioFINDER Study, the assay discriminated between persons with the clinical diagnoses of Alzheimer's and other neurodegenerative diseases with 96% accuracy, similar to tau PET scans and CSF biomarkers and better than several other blood tests and MRI measurements; and it distinguished between those with and without an abnormal tau PET scan with 93% accuracy.

In the Colombia Cohort, the assay began to distinguish between mutation carriers and non-carriers 20 years before their estimated age at the onset of mild cognitive impairment.

In each of these analyses, p-tau217 (a major component of Alzheimer's disease-related tau tangles) performed better than p-tau181 (another component of tau tangles and a blood test recently found to have promise in the diagnosis of Alzheimer's) and several other studied blood tests.

Other study leaders include Jeffrey Dage, PhD, from Eli Lilly and Company, who developed the p-tau217 assay, co-first authors Sebastian Palmqvist, MD, PhD, and Shorena Janelidz, PhD, from Lund University, and Eric Reiman, MD, Banner Alzheimer's Institute, who organized the analysis of Arizona and Colombian cohort data.

In the last two years, researchers have made great progress in the development of amyloid blood tests, providing valuable information about one of the two cardinal features of Alzheimer's. While more work is needed before the test is ready for use in the clinic, a p-tau217 blood test has the potential to provide information about both plaques and tangles, corresponding to the diagnosis of Alzheimer's. It has the potential to advance the disease's research and care in other important ways.

"Blood tests like p-tau217 have the potential to revolutionize Alzheimer's research, treatment and prevention trials, and clinical care," said Eric Reiman, MD, Executive Director of Banner Alzheimer's Institute in Phoenix and a senior author on the study.

"While there's more work to do, I anticipate that their impact in both the research and clinical setting will become readily apparent within the next two years."

Alzheimer's is a debilitating and incurable disease that affects an estimated 5.8 million Americans age 65 and older. Without the discovery of successful prevention therapies, the number of U.S. cases is projected to reach nearly 14 million by 2050.

COLUMBUS, Ohio - A new study shows the surprising way that many American taxpayers adjust their standard of living when they owe money to the IRS versus when they receive tax refunds.

Researchers found that when households received tax refunds, they immediately started spending that new money. But those same households didn't cut their spending in years when they owed taxes to the IRS.

The findings contradict economic theories that suggest people spend their tax refunds only because they need the money to buy necessities, said Itzhak Ben-David, co-author of the study and professor of finance at The Ohio State University's Fisher College of Business.

If that were true, then these households would have had to cut spending in years when they owed taxes.

"What we found is that owing money to the IRS did not disrupt normal consumption in our sample of American households," Ben-David said.

The sample in this study used a personal finance website, so they were more financially sophisticated than average consumers, he noted. But even those in the study who had had the least savings and the most credit-card debt did not reduce their spending when they owed money.

"They found ways to use money from savings accounts or other reserves to keep up their spending in years when they had to pay the IRS. They didn't cancel their vacations," Ben-David said.

The study has been conditionally accepted for publication in the American Economic Review and is currently online at the SSRN preprint server.

Ben-David's co-authors were Jonathan Parker, professor of finance at the Massachusetts Institute of Technology, and two former Ohio State doctoral students: Brian Baugh, assistant professor of finance at the University of Nebraska, and Hoonsuk Park, assistant professor of banking and finance at Nanyang Technological University in Singapore.

The researchers used anonymized data from a personal finance website that included details of spending habits of 196,565 American households from July 2010 to May 2015. The researchers included only households that had both received tax refunds and paid the IRS in different years to ensure the findings weren't simply the result of separate households behaving in different ways.

All households - from the most to the least wealthy - increased their spending immediately after receiving the refund, the study showed.

People consumed about 8 percent of the refunds during the month after they received them, which rose to about 15 percent over the following three months.

"We found that the spending increases the exact day on which the refund arrives," Ben-David said. "Even though they know the refund is coming, most Americans don't start spending until they have it in their account."

Even the wealthiest people in the sample spent a good portion of their refund, despite the fact that they had the money to spend without the refund.

"When they received the refund, people in our sample consumed more or less the same fraction of it regardless of the amount. People who received a big refund spent about the same fraction as those with a smaller refund - just a bigger dollar amount," he said.

The results suggest that people treat a tax refund like they would a cash bonus from work - they spend some and save some.

When households owed money to the IRS, the researchers found that they increased transfers among their accounts in the month before making their payment. For example, some moved money from savings to checking before writing a check to the government.

What they didn't do is spend less on dining out, clothing, recreation or other items in their budget.

"Americans in our sample viewed tax payments as a necessary cost like a car repair or new appliance that can come out of their savings," Baugh said.

"It is not something they had to change their usual spending for."

The findings suggest that people's behavior involving money may not follow traditional economic theories, Parker said.

If people's spending responds primarily to how much money they have available, as some prominent theories predict, consumers should spend less when they owe the IRS, which this study didn't find. Furthermore, they also shouldn't spend their refund if they already have plenty of money - but this study showed that even the wealthiest households spent a portion of their refunds.

Instead, this research supports the theory that people use very general rules of thumb to determine how they spend money. According to this "mental accounting" theory, households think of themselves as having three accounts: current income, current assets and future incomes.

These are not real accounts, but how people track their money in their minds, Park said. In this theory, people try not to touch their current assets (like retirement savings) and future income (like inheritances they expect to receive).

All their spending comes from current income. That means when their income increases - as it does from a tax refund - they treat it like a bonus from work and spend some of it and save some of it.

If they owe money, that is outside of the usual income and spending cycle, so they use other sources of funds, if available, to pay it without reducing their usual spending - just like other unexpected costs.

"This is one of the few studies that has been able to show that mental accounting does explain how people behave in real life," Ben-David said.

Taking a few minutes to get that periodic cup of joe might not be such a bad idea.

When working at home, it's good to have a break, possibly every 30 minutes, to stay healthy and minimize injury to your back, shoulders and arms, says Kermit Davis, PhD, an expert in office ergonomics at the University of Cincinnati College of Medicine.

"The body doesn't like static postures continually," says Davis, a professor in the UC Department of Environmental and Public Health Sciences. "You don't want to do all sitting or all standing all the time. You want to alter your position and change it up throughout the day."

Workers across the nation have converted their basements, spare rooms, dining room tables or bedrooms into makeshift offices in the midst of the coronavirus pandemic. But few have much guidance when it comes to making these new spaces ergonomically safe, says Davis, who runs both UC's graduate industrial hygiene and occupational ergonomics programs.

"You can go home but you aren't allowed to take the monitor, chair and most office equipment," explains Davis. "You can use your laptop from home, but it is designed to be a short-term option. It should be used for a few hours while traveling. It is not meant to be used for eight or nine hours each day."

The screen and keyboard on laptops are smaller than a standard office computer, says Davis. As a result the user oftentimes looks downward since the smaller screen is well below eye height.

Davis conducted an ergonomic assessment of employees at the University of Cincinnati sending out an email survey to 4,500 faculty and staff after the coronavirus pandemic prompted the university to join many other employers across the nation in sending workers home to continue operations. The survey had 843 people complete it. As part of the study, 41 employees sent Davis photos of workers at home workstations for ergonomic review. This subset showed some trends and offered a glimpse into what many who work from home are encountering.

The survey's findings were recently published in the scholarly journal Ergonomics in Design.

Davis says the ergonomic evaluations of the home workstations identified many issues that could be adversely affecting the workers. Many chairs were the wrong height with about 41% too low and 2% too high. Fifty-three percent of workers had armrests on their chairs, but 32% did not use them and for 18% of workers the armrests were improperly adjusted, the study found.

Davis says not using the armrests causes contact stress on forearms when rested on the hard front edge of work surfaces and strain across the upper back as the arms need support. Also, support of the back of the chair was not used by 69% and often without any lumbar support for 73% of survey participants. That meant many individuals did not have proper support of their lower back, maintaining the lumbar curvature.

The position of a computer monitor was often too low or off to the side. Three quarters of monitors were laptops, which were too low relative to the workers' eye height, the study found.

External monitors were also routinely set up too low in 52% of participants or too high in 4%. Another common issue with the monitors was the lack of the primary screens centered in front of the workers occurring in 31% of workers and resulting in twisting of the neck and/or back to view the monitor, according to the study.

Davis says not everyone can spend hundreds of dollars on a new chair or other equipment when working from home. He says there are some cheap and easy fixes that will go a long way in improving the ergonomic well-being of office workers.

Here are a few tips that might be helpful for the homebound office worker:

Place a pillow on your seat to elevate the seat height.

Place a pillow or rolled up towel behind your back to provide lumbar and back support.

Wrap armrests when they are low and not adjustable.

Move your chair closer to the desk or table to encourage having the back against the back of the seat.

If a laptop is too low, place a lap desk or large pillow under the laptop to raise the monitor when using it on the lap.

Use an external keyboard and mouse, along with raising the laptop monitor by placing a stack of books or a box under the laptop when using a laptop on a desk.

An appropriate standing workstation should have the top of the monitor at eye height and directly in front, keyboard at a height so that forearms are parallel to the ground (approximately 90° elbow angle), and a soft or rounded front edge to the working surface.

If obtaining a new chair or identifying an appropriate sitting workstation at home is not possible, rotating between a poor sitting workstation and a standing workstation would be the next best practice. There are many simple, makeshift standing workstations available in the home, including implementing the use of an ironing board, a kitchen counter, the top of a piano, a clothes basket placed upside down on a table or desk or a large box under the laptop.

Davis says he worries that workers' discomfort levels are increasing after more than five months of working remotely. "It's not just ergonomics changing but also other factors: isolation, teamwork changes and work-life balance is distorted and changes in the stress level that people have," he says.

Giving birth in the United States is a radically different experience based on race and income, illustrated most brutally by the Black and Indigenous maternal mortality crisis.

Now, a new study from the Boston University School of Public Health (BUSPH) and the National Partnership for Women & Families finds insurance type itself also plays a role in how mothers are treated, and how much agency they have in maternity decisions.

Published in the journal PLOS ONE, the first-of-its-kind study is part of Listening to Mothers in California, which examined women's experiences giving birth in California hospitals in 2016.

The study finds that, after adjusting for demographics and health conditions, a mother on Medicaid is three times less likely than a mother on private insurance to feel she had a choice about whether she had a vaginal or cesarean birth, or an episiotomy. Compared to private coverage, coverage by Medi-Cal (California's Medicaid program) was also associated with being about half as likely to have a choice of prenatal provider or to be encouraged by maternity care staff to make one's own decisions about labor and birth.

"This study is the largest to date using women's voices to examine their maternity experiences in births funded by Medicaid," says study lead author Dr. Eugene Declercq, professor of community health sciences at BUSPH and a member of the Listening to Mothers team.

"It documents the limitations on their ability to share in decisions about their own care, and is a call for clinicians and policymakers to make changes that ensure equitable rights for all mothers, regardless of insurance status," he says.

"Every indictor of disrespect and limit on choice that we examined was worse for women with Medi-Cal versus private insurance," says Carol Sakala, director of maternal health at the National Partnership for Women & Families and the survey's principal investigator. "This suggests women with Medi-Cal systemically receive substandard quality of care. Our results sound alarm bells about missed opportunities for mitigating the maternal health crisis within the Medi-Cal program.

For their analysis, the researchers used survey data from 1,087 women with commercial private insurance and 1,231 women enrolled in Medi-Cal. The sample was demographically representative of all live births in California that year.

The researchers then analyzed the relationships between the different insurance types and the women's experiences around maternal agency, including decision-making about interventions such as vaginal birth after cesarean and episiotomy, feeling pressured to have interventions, and their sense of fair treatment. The researchers then adjusted for the women's demographics, including income, as well as attitudes toward birth, type of prenatal care provider, type of birth attendant, and pregnancy complications, to identify how much of the difference in experiences was associated with insurance type.

Of course, the authors note, demographics and conditions are rarely equal for mothers on private and public insurance: In this sample, over half of non-Latina Black women and over two-thirds of Latina women were on Medi-Cal, compared to just over a quarter of non-Latina white women and just under a quarter of non-Latina Asian and Pacific Islander women; the majority of women born outside of the U.S. were on Medi-Cal; and 85% of women who spoke Spanish at home were on Medi-Cal. Before accounting for these and other demographic differences, many of the gaps between privately- and publicly-insured mothers' experiences were twice as large.

However, the researchers also found that insurance type may also influence other forms of discrimination: After adjusting for demographics and other factors, women with Medi-Cal were twice as likely to report that they were treated unfairly because of their race/ethnicity (particularly Asian and Pacific Islander women), and four times as likely because of the language they spoke.

With Medicaid covering 42% of childbearing women in the United States, the authors write, the program has huge potential to improve maternal health, and better treatment for Medicaid enrollees would have a profound effect on overall equity in maternal health.

"It is critical that maternity care providers--and really any gatekeepers to care--are made aware of these inequities," says study co-author Dr. Candice Belanoff, clinical associate professor of community health sciences at BUSPH, "and that they take steps to ensure equitable treatment and access regardless of insurer."

San Francisco (July 28, 2020) -- As part of Juul Labs' ongoing engagement with the public health community, the company today announced findings from a new study at the AcademyHealth 2020 Annual Research Meeting linking the JUUL System's market entry to decreased cigarette sales in Canada. The conference, which took place virtually, focuses on the intersection of health, health care, and policy.

The study, conducted and presented by Dr. Shivaani Prakash, Juul Labs' Director of Health Economics and Policy Research, found that the JUUL System's market entry in Canada likely decreased combustible cigarette sales, especially in urban markets. Using city-level data on cigarette and JUUL System sales in Canada and variation in timing of the JUUL System's market entry in a study, researchers ran econometric difference-in-difference models. They found that within the first 12 months of market entry, market entry and availability of the JUUL System likely led to a 1.5% decrease on average in store-level cigarette sales volume, within one large retailer chain. Overall, this could translate to over 400 million fewer cigarettes sold in Canada within the first year of the JUUL System's market entry.

They also found that the decline in cigarette sales magnified as the JUUL System's market share increased in stores, suggesting that local tobacco market competition plays a strong role in uptake and purchase of vaping products. For every 1% increase in the JUUL System's market share at the store-level, there was an associated 0.5% reduction in cigarette sales.

“This work provides strong evidence that the availability of vaping products could reduce cigarette sales, and suggests that providing alternative nicotine products to adult smokers could drive down combustible cigarette consumption,” said Rasmus Wissmann, Vice President of Data at Juul Labs. “Further research is needed to determine the long-term impact of vapor products on cigarette sales, and the net population health impact of such products.”

Identifying the impact of vaping products in global markets can help policymakers understand the role of alternative nicotine products in the commercial tobacco product market, and better evaluate the impact of such products.

As part of the Premarket Tobacco Product Application (PMTA) process in the United States, Juul Labs has built a comprehensive research program focused on examining the public health impact of the JUUL System. This includes research on the JUUL System's impact on the individual user, their ability to convert adult smokers from combustible cigarettes, and the net-population impact on public health.

Juul Labs will continue to share results from its science and research program with the public health communities as it works to support the scientific basis for the category, as well as future regulatory filings.

Pharmavite LLC, the makers of Nature Made vitamins, minerals and supplements, announced the publication of a research article in the journal PLoS ONE, which examines inadequate nutrient intake and its relationship to poor bone health, specifically risk of osteoporosis. The research was a cross sectional analysis of the U.S population [from National Health and Nutrition Examination Survey (NHANES) data], with a specific focus on those below the poverty line with food insecurities.

Poverty can be a barrier to routinely acquiring adequate nutrient intakes, specifically for calcium and vitamin D, to ensure bone health with the ultimate goal of preventing of osteoporosis. Age, gender and dietary intake are major factors that contribute to osteoporosis prevalence. This study examined the relationship between markers of poverty with calcium and vitamin D intake and osteoporosis in Americans, 50 years and older.

"This study continues to demonstrate how prevalent nutrient deficiency is among the U.S. population, and even more so, among lower income individuals and those with food insecurities. Yet, we know that nutrient adequacy is imperative in supporting overall health and wellness, including immune health, at a time when that is heavy on everyone's mind," said Susan Hazels Mitmesser, PhD, Vice President of Science & Technology at Pharmavite.

In the U.S., 25% of older Americans live below the poverty line. Within this population, 68% have inadequate calcium intakes, and 46% have inadequate vitamin D intakes. Gender, ethnic, and socio-economic differences impact overall risk for inadequate calcium and vitamin D intakes and subsequent osteoporosis risk, as seen in some of the study key findings:

American women over the age of 50 consistently have inadequate calcium intake regardless of their economic status.

Inadequate intake of calcium and vitamin D affects poverty-stricken men more than women with respect to osteoporosis risk.

Non-Hispanic Black men with a low income have two times greater risk for developing osteoporosis.

"Improving the consumption of nutrient-rich and fortified foods among individuals that live in poverty can help to decrease their chances of developing osteoporosis. Additionally, dietary supplements can play a critical role in helping any underserved population meet their nutrition needs --including making supplements readily available through programs like SNAP, for example," adds Mitmesser. "Our research demonstrates that participants with SNAP benefits and more access to food, have fewer nutrient inadequacies which helps them meet their nutrition needs."

It has been estimated in the U.S. population age 50 and older, about 10.2 million suffer from osteoporosis, and 80% of these affected cases are females. In addition, there are potentially 43.4 million people, or 44% of the population with osteopenia, which is a bone condition that often leads to osteoporosis. More than two million osteoporosis-related fractures occur annually, leading to more than 19 billion dollars in health care costs in the US.

An international team of volcanologists working on remote islands in the Galápagos Archipelago has found that volcanoes which reliably produce small basaltic lava eruptions hide chemically diverse magmas in their underground plumbing systems - including some with the potential to generate explosive activity.

Many volcanoes produce similar types of eruption over millions of years. For example, volcanoes in Iceland, Hawai'i and the Galápagos Islands consistently erupt lava flows - comprised of molten basaltic rock - which form long rivers of fire down their flanks. Although these lava flows are potentially damaging to houses close to the volcano, they generally move at a walking pace and do not pose the same risk to life as larger explosive eruptions, like those at Vesuvius or Mt. St. Helens. This long-term consistency in a volcano's eruptive behaviour informs hazard planning by local authorities.

The research team, led by Dr Michael Stock from Trinity College Dublin and comprising scientists from the US, UK and Ecuador, studied two Galápagos volcanoes, which have only erupted compositionally uniform basaltic lava flows at the Earth's surface for their entire lifetimes. By deciphering the compositions of microscopic crystals in the lavas, the team was able to reconstruct the chemical and physical characteristics of magmas stored underground beneath the volcanoes.

The results of the study show that - in contrast with the monotonous basaltic lavas erupted at the Earth's surface - magmas beneath the volcanoes are extremely diverse and include compositions similar to those erupted at Mt. St. Helens.

The team believes that volcanoes consistently erupt compositionally uniform basaltic lavas when the amount of magma flushing through the ground beneath the edifice is high enough to "overprint" any chemical diversity. This can occur when volcanoes are located close to a "hot spot" - a plume of hot magma rising towards the surface from deep within the Earth.

However, the chemically diverse magmas which the team discovered could become mobile and ascend towards the surface under certain circumstances. In this case, volcanoes that have reliably produced basaltic lava eruptions for millennia might undergo unexpected changes to more explosive activity in the future.

Dr Stock, from Trinity's School of Natural Sciences, and lead author on the paper, said:

"This was really unexpected. We started the study wanting to know why these volcanoes were so boring and what process caused the erupted lava compositions to remain constant over long timescales. Instead we found that they aren't boring at all - they just hide these secret magmas under the ground."

"Although there's no sign that these Galápagos volcanoes will undergo a transition in eruption style any time soon, our results show why other volcanoes might have changed their eruptive behaviour in the past. The study will also help us to better understand the risks posed by volcanoes in other parts of the world - just because they've always erupted a particular way in the past doesn't mean you can rely on them to continue doing the same thing indefinitely into the future."

Dr Benjamin Bernard, a volcanologist involved in monitoring Galápagos volcanoes at Instituto Geofísico and co-author on the paper, added:

"This discovery is a game-changer because it allows us to reconcile apparently divergent observations, such as the presence of explosive deposits at several Galápagos volcanoes. It also allows us to better understand the behaviour of these volcanoes, which is essential for volcano monitoring and hazard assessment."

A rover expected to explore below the surface of Mars in 2022 has the potential to provide more insights

The findings published in Scientific Reports, Springer Nature suggests the presence of traces of water on Mars, raising the question of the possibility of a life-supporting environment

Abu Dhabi, UAE - July 28, 2020: Although no life has been detected on the Martian surface, a new study from astrophysicist and research scientist at the Center for Space Science at NYU Abu Dhabi, Dimitra Atri finds that conditions below the surface could potentially support it. The subsurface - which is less harsh and has traces of water - has never been explored. According to Atri, the steady bombardment of penetrating Galactic Cosmic Rays (GCRs) might provide the energy needed to catalyze organic activity there.

Atri's findings are reported in the study Investigating the biological potential of galactic cosmic ray-induced radiation-driven chemical disequilibrium in the Martian subsurface environment in the journal Scientific Reports, Springer Nature.

There is growing evidence suggesting the presence of an aqueous environment on ancient Mars, raising the question of the possibility of a life-supporting environment. The erosion of the Martian atmosphere resulted in drastic changes in its climate, surface water disappeared, shrinking habitable spaces on the planet, with only a limited amount of water remaining near the surface in form of brines and water-ice deposits. Life, if it ever existed, would have had to adapt to harsh modern conditions, which include low temperatures and surface pressure, and high radiation dose.

The subsurface of Mars has traces of water in the form of water-ice and brines, and undergoes radiation-driven redox chemistry. Using a combination of numerical models, space mission data, and studies of deep-cave ecosystems on Earth for his research, Atri proposes mechanisms through which life, if it ever existed on Mars, could survive and be detected with the upcoming ExoMars mission (2022) by the European Space Agency and Roscosmos. He hypothesizes that galactic cosmic radiation, which can penetrate several meters below the surface, will induce chemical reactions that can be used for metabolic energy by extant life, and host organisms using mechanisms seen in similar chemical and radiation environments on Earth.

"It is exciting to contemplate that life could survive in such a harsh environment, as few as two meters below the surface of Mars," said Atri. "When the Rosalind Franklin rover on board the ExoMars mission (ESA and Roscosmos), equipped with a subsurface drill, is launched in 2022, it will be well-suited to detect extant microbial life and hopefully provide some important insights."