Culture

The "unparalleled" discovery of remarkably well-preserved ancient skeletons in Central American rock shelters has shed new light on when maize became a key part of people's diet on the continent.

Until now little was known about when humans started eating the crop, now a staple of meals around the globe that shapes agricultural landscapes and ecosystem biodiversity.

The rare human remains, found in the Maya Mountains of Belize, buried during the last 10,000 years, has allowed experts to date when maize became a major part of people's diets in the region for the first time.

Radiocarbon dating of the skeletal samples shows the transition from pre-maize hunter-gatherer diets, where people consumed wild plants and animals, to the introduction and increasing reliance on the crop. Maize made up about a third of people's diets in the area by 4,700 years ago, rising to 70 per cent 700 years later.

Maize was domesticated from teosinte, a wild grass growing in the lower reaches of the Balsas River Valley of Central Mexico, around 9,000 years ago. There is evidence maize was first cultivated in the Maya lowlands around 6,500 years ago, at about the same time that it appears along the Pacific coast of Mexico.

Dr Mark Robinson, from the University of Exeter, who co-directed field excavations, said: "The humid environment means it's extremely rare to find older human remains that are so well preserved in the tropics.

"This is the only example of a burial site in the Neotropics used repeatedly for 10,000 years, giving us an unparalleled opportunity to study dietary change over a long time period, including the introduction of maize into the region. This is the first direct evidence to show when the change in people's diets occurred and the rate at which maize increased in economic and dietary importance until it became fundamental to peoples dietary, economic, and religious lives."

Experts measured the carbon and nitrogen in the bones of 44 skeletons, which gave information about people's diet. The remains include male and female adults and children providing a wholistic sample of the population, . The oldest remains date from between 9,600 and 8,600 years ago, with continued burials occurring until 1,000 years ago.

The analysis shows the oldest remains were people who ate herbs, fruits and nuts from forest trees and shrubs, along with meat from hunting terrestrial animals.

By 4,700 years ago, diets became more diverse, with some individuals showing the first consumption of maize. The isotopic signature of two young nursing infants shows that their mothers were consuming substantial amounts of maize. The results show an increasing consumption of maize over the next millennium as the population transitioned to sedentary farming.

By 4,000 years ago, the population was reliant on maize, with the crop forming 70% of their diet. The increase in consumption of maize protein was accompanied by a reduction in the consumption of animal protein. Maize became a dietary staple at a time of broad continental population change, increases in social complexity and social hierarchy, and major subsequent environmental transformations. The study shows that as people ate more maize the associated farming led to an increase in forest clearing, burning and soil erosion across the Maya lowlands.

The spread of maize agriculture across the Americas was likely linked to the spread of distinct cultures, technologies, and languages. By the time the highly complex, monumental Maya civilisation developed 2,000 years ago, maize was central to lifeways and cosmology, with their creation story recording that the Maya are made out of maize.

EAST HANOVER, NJ - June 3, 2020 - Kessler Foundation released the results of the first national survey of college graduates with disabilities coming of age under the Americans with Disabilities Act, signed into law 30 years ago on July 26, 1990. The 2020 Kessler Foundation National Employment and Disability Survey: Recent College Graduates is the third in a groundbreaking series of surveys aimed at gaining detailed information on the ways people with disabilities achieve inclusion in the workplace.

Results of the 2020 Survey, which was commissioned by Kessler Foundation and implemented by the University of New Hampshire Institute on Disability (UNH-IOD), were presented to a national audience of stakeholders via a live Zoom webinar on June 3. The webinar, "The ADA Generation: New Perspectives on Employment and College Graduates with Disabilities," featured Jennifer Sheehy, deputy assistant secretary at the US Department of Labor's Office of Disability Employment Policy, Rodger DeRose, John O'Neill, PhD, and Elaine E. Katz, MS, CCC-SLP, from Kessler Foundation, and Kimberly Phillips, PhD, and Andrew Houtenville, PhD, from UNH-IOD.

A pre-screened national sample of 4,738 adults completed the survey, half of whom had at least one disability, and half without disabilities. All respondents were aged 20 to 35 and had graduated from college in the past five years with an associate's degree or higher. UNH-IOD contracted with Qualtrics to conduct the online Survey, which elicited details of their experiences in higher education and employment history since graduation.

Respondents supplied information on the types of schools they attended, their programs of study, engagement with student services, and career preparation activities. They also described their employment experiences during college and after graduation, barriers encountered looking for work, whether their work related to their field of study, their current working arrangements, and job satisfaction. Their responses provide an initial view of employment outcomes for the first generation to access higher education in the post ADA age.

Recent college graduates with disabilities were as likely to be employed as their peers without disabilities, according to the Survey, with 90 percent of each group holding jobs after college. "This Survey clearly suggests that higher education pays off for people with disabilities," said Dr. Phillips, project director for the Survey. For all recent graduates, preparing for careers by engaging in internships, paid employment, and career counseling services correlated positively with working after graduation. "Students with disabilities were just as likely to engage in these activities, and benefit from them, as their peers without disabilities," reported Dr. Phillips.

The findings reflect the pathways that have opened for people with disabilities since the ADA, according to Dr. O'Neill, director of the Foundation's Center for Employment and Disability Research, and provide direction for youth with disabilities and their families, and the counselors, educators, and therapists dedicated to supporting them as they pursue careers and economic independence. "We can confidently say that education makes a difference," Dr. O'Neill remarked, "and that taking advantage of academic support services during college is important, as well as participating in hands-on work experience. Students who work, volunteer, and do internships increase their chances for post-college employment."

The Survey findings counter traditional viewpoints about the potential for young people with disabilities. "Our surveys give voice to people with disabilities, dispelling many of the myths about their participation in higher education and the workplace," asserted Katz, senior VP of Grants and Communications at Kessler Foundation. "Our 2015 survey showed that the majority of people with disabilities are striving to work, dispelling the myth that they are unwilling or unable to work. Our 2017 survey showed that the majority of employers are striving for more inclusive workplaces, dispelling the myth that opportunities are few for jobseekers with disabilities. Now, with our 2020 survey, we can lay to rest more myths about people with disabilities - that college isn't a good choice for them, that they cannot perform as well as their peers, that they won't find jobs after graduation."

The Survey findings can also guide decision making made more complicated by the COVID economy. Encouraging transition-age students with disabilities to pursue higher education is solid advice, according to Katz, especially in an environment of widespread unemployment. "From the survey, we learned that community colleges were more likely to be the point of entry for students with disabilities, who were also more likely to take courses at community colleges during high school. These are among the lessons learned from the ADA Generation that will apply to future generations striving to navigate from high school to college to work."

Visit https://kesslerfoundation.org/KFSurvey2020 for the recorded Webinar, Executive Summary and Main Findings, presentation slides, and FAQs.

A USC School of Pharmacy-led team has engineered a new, faster way to make drugs that precisely target malignant cells - while leaving healthy tissue undamaged - that could lead the way to better treatments for numerous types of cancer.

The drugs, called antibody-drug conjugates or ADCs, belong to a relatively new class in which drug molecules are attached to antibodies which zero in on and attach to the surface of cancer cells. As of May 2020, eight ADCs have been approved by the U.S. Food and Drug Administration, and more than 100 clinical trials are underway studying their effectiveness in treating blood, lung, breast, brain and other cancers.

In a study published today in Science Advances, USC scientists describe a new technology to rapidly create a homogeneous type of ADC, which attaches to a specific site on the cancer cell, with improved efficiency and potentially enhanced stability, effectiveness and safety.

ADCs consist of an antibody for seeking out a cancer cell, a drug for killing it and a chemical "linker" uniting them. However, currently used ADCs are manufactured through a process that yields varied products of limited stability and efficacy.

Homogenous ADCs therefore carry more potential for clinical effectiveness. But current technologies for making this type of ADC require multiple steps or long reaction times due to inefficient chemistries. Many homogenous ADCs can also trigger immune responses that hamper their use.

The USC team may have solved these issues. "Using our approach, homogenous ADCs could be made through a single-step reaction in less than two hours, much faster and more efficiently than conventional approaches," says the study's Principal Investigator, Yong (Tiger) Zhang, Assistant Professor of Pharmacology and Pharmaceutical Sciences at the USC School of Pharmacy.

"Our technology features a designer 'linker' component exclusively recognized by a human enzyme that can rapidly catalyze the conjugation of drug molecules to the antibodies at a defined position," he says. "In addition to its fast rate and high efficiency, our ADC technology offers a new type of linker for connecting the drugs to antibodies. This designer linker ensures stable attachment of the drug and rapid release of the drugs into target cells, making the generated ADCs safer and more efficacious."

Using this technology, the USC team generated an ADC that can effectively block the growth of breast cancer tumors in animals. These promising results provide a strong basis for translation of this ADC into clinical studies, the investigators say.

(Boston)--Researchers have discovered that a defective form of the protein aortic carboxypeptidase-like protein (ACLP) from patients with Ehlers-Danlos syndrome (EDS) is retained in cells and induces cellular stress. This finding may provide targets for pharmacologic and therapeutic interventions in treating individuals with EDS as well as wound healing disorders and fibrosis.

EDS is a prevalent genetic disease that results in weakened connective tissues. This disease results in joint hypermobility, vascular disruption, and aberrant wound healing. Mutations in the gene that encodes for ACLP have recently been identified to cause a novel variant of EDS. Furthermore, excessive amounts of ACLP cause fibrosis in multiple organs including the lung, liver, and adipose tissue.

Researchers from Boston University School of Medicine (BUSM) and College of Engineering identified mechanisms that control ACLP secretion in vascular cells and fibroblasts. Detailed characterization of a mutant form of ACLP identified in an EDS patient revealed that this protein was retained in cells. They then generated collagen fibers in vitro that contained ACLP. Compared to collagen only controls, they found that fibers with ACLP exhibited increased mechanical properties consistent with a function in maintaining connective tissue integrity.

"We discovered that an EDS-causing mutation in ACLP hinders its secretion and induces cellular stress. We also identified that ACLP contributes to collagen fiber mechanics which may explain in part how ACLP contributes to connective tissue function," explains corresponding author Matthew D. Layne, PhD, associate professor of biochemistry at BUSM.

According to the researchers, many human pathologies are the result of improper protein processing. "Our study provides new information on the mechanisms of ACLP secretion from cells. Research in these areas add to the continued understanding of protein processing and secretion and their connections to human connective tissue disease."

Layne and his collaborators were the first to show that ACLP contributes to the mechanical strength of collagen fibers that make up numerous connective tissues including ligaments, tendons, and cartilage.

These findings appear online in the Journal of Biological Chemistry.

This itsy-bitsy robot can't climb up the waterspout yet but it can run, jump, carry heavy payloads and turn on a dime. Dubbed HAMR-JR, this microrobot developed by researchers at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Harvard Wyss Institute for Biologically Inspired Engineering, is a half-scale version of the cockroach-inspired Harvard Ambulatory Microrobot or HAMR.

About the size of a penny, HAMR-JR can perform almost all of the feats of its larger-scale predecessor, making it one of the most dexterous microrobots to date.

"Most robots at this scale are pretty simple and only demonstrate basic mobility," said Kaushik Jayaram, a former postdoctoral fellow at SEAS and Wyss and first author of the paper. "We have shown that you don't have to compromise dexterity or control for size."

Jayaram is currently an Assistant Professor at the University of Colorado, Boulder.

The research was presented virtually at the International Conference on Robotics and Automation (ICRA 2020) this week.

One of the big questions going into this research was whether or not the pop-up manufacturing process used to build previous versions of HAMR and other microbots, including the RoboBee, could be used to build robots at multiple scales -- from tiny surgical bots to large-scale industrial robots.

PC-MEMS (short for printed circuit microelectromechanical systems) is a fabrication process in which the robot's components are etched into a 2D sheet and then popped out in its 3D structure. To build HAMR-JR, the researchers simply shrunk the 2D sheet design of the robot -- along with the actuators and onboard circuitry -- to recreate a smaller robot with all the same functionalities.

"The wonderful part about this exercise is that we did not have to change anything about the previous design," said Jayaram. "We proved that this process can be applied to basically any device at a variety of sizes."

HAMR-JR comes in at 2.25 centimeters in body length and weighs about 0.3 grams -- a fraction of the weight of an actual penny. It can run about 14 body lengths per second, making it not only one of the smallest but also one of the fastest microrobots.

Scaling down does change some of the principles governing things like stride length and joint stiffness, so the researchers also developed a model that can predict locomotion metrics like running speeds, foot forces, and payload based on a target size. The model can then be used to design a system with the required specifications.

"This new robot demonstrates that we have a good grasp on the theoretical and practical aspects of scaling down complex robots using our folding-based assembly approach," said co-author Robert Wood, Charles River Professor of Engineering and Applied Sciences in SEAS and Core Faculty Member of the Wyss.

Scientists have tried to develop synthetic red blood cells that mimic the favorable properties of natural ones, such as flexibility, oxygen transport and long circulation times. But so far, most artificial red blood cells have had one or a few, but not all, key features of the natural versions. Now, researchers reporting in ACS Nano have made synthetic red blood cells that have all of the cells' natural abilities, plus a few new ones.

Red blood cells (RBCs) take up oxygen from the lungs and deliver it to the body's tissues. These disk-shaped cells contain millions of molecules of hemoglobin -- an iron-containing protein that binds oxygen. RBCs are highly flexible, which allows them to squeeze through tiny capillaries and then bounce back to their former shape. The cells also contain proteins on their surface that allow them to circulate through blood vessels for a long time without being gobbled up by immune cells. Wei Zhu, C. Jeffrey Brinker and colleagues wanted to make artificial RBCs that had similar properties to natural ones, but that could also perform new jobs such as therapeutic drug delivery, magnetic targeting and toxin detection.

The researchers made the synthetic cells by first coating donated human RBCs with a thin layer of silica. They layered positively and negatively charged polymers over the silica-RBCs, and then etched away the silica, producing flexible replicas. Finally, the team coated the surface of the replicas with natural RBC membranes. The artificial cells were similar in size, shape, charge and surface proteins to natural cells, and they could squeeze through model capillaries without losing their shape. In mice, the synthetic RBCs lasted for more than 48 hours, with no observable toxicity. The researchers loaded the artificial cells with either hemoglobin, an anticancer drug, a toxin sensor or magnetic nanoparticles to demonstrate that they could carry cargoes. The team also showed that the new RBCs could act as decoys for a bacterial toxin. Future studies will explore the potential of the artificial cells in medical applications, such as cancer therapy and toxin biosensing, the researchers say.

DURHAM, N.C. - Hundreds of published studies over the last decade have claimed it's possible to predict an individual's patterns of thoughts and feelings by scanning their brain in an MRI machine as they perform some mental tasks.

But a new analysis by some of the researchers who have done the most work in this area finds that those measurements are highly suspect when it comes to drawing conclusions about any individual person's brain.

Watching the brain through a functional MRI machine (fMRI) is still great for finding the general brain structures involved in a given task across a group of people, said Ahmad Hariri, a professor of psychology and neuroscience at Duke University who led the reanalysis.

"Scanning 50 people is going to accurately reveal what parts of the brain, on average, are more active during a mental task, like counting or remembering names," Hariri said

Functional MRI measures blood flow as a proxy for brain activity. It shows where blood is being sent in the brain, presumably because neurons in that area are more active during a mental task.

The problem is that the level of activity for any given person probably won't be the same twice, and a measure that changes every time it is collected cannot be applied to predict anyone's future mental health or behavior.

Hariri and his colleagues reexamined 56 published papers based on fMRI data to gauge their reliability across 90 experiments. Hariri said the researchers recognized that "the correlation between one scan and a second is not even fair, it's poor."

They also examined data from the brain-scanning Human Connectome Project -- "Our field's Bible at the moment," Hariri called it -- and looked at test/retest results for 45 individuals. For six out of seven measures of brain function, the correlation between tests taken about four months apart with the same person was weak. The seventh measure studied, language processing, was only a fair correlation, not good or excellent.

Finally they looked at data they collected through the Dunedin Multidisciplinary Health and Development Study in New Zealand, in which 20 individuals were put through task-based fMRI twice, two or three months apart. Again, they found poor correlation from one test to the next in an individual.

The bottom line is that task-based fMRI in its current form can't tell you what an individual's brain activation will look like from one test to the next, Hariri said. The new analysis, appears June 3 in Psychological Science

"This is more relevant to my work than just about anyone else's!" Hariri said, his voice rising. "This is my fault. I'm going to throw myself under the bus. This whole sub-branch of fMRI could go extinct if we can't address this critical limitation."

Hariri has been using fMRI data as part of a long-term study of 1,300 undergraduate Duke students. By combining brain scans, genetic testing and psychological assessments, Hariri is searching for biomarkers of individual differences in the way people process thoughts and emotions, such as why one person comes away from a traumatic event with PTSD or depression and another does not.

"We can't continue with the same old 'hot spot' research," Hariri said. "We could scan the same 1,300 undergrads again and we wouldn't see the same patterns for each of them."

One possible solution to the reliability problem, using existing technology, would be to collect data for a full hour or longer in the scanner, not just five minutes. Hariri also said developing new tasks from the ground up with the explicit purpose of reliably measuring individual differences in brain activity is another strategy. In the meanwhile, Hariri and his team have shifted their focus to MRI measures of brain structure, which are highly reliable.

"It's not as if we haven't known these issues of reliability, but this paper brings them together more sharply," said Russell Poldrack, the Albert Ray Lang Professor of Psychology at Stanford University, who had a 15-year-old fMRI paper among those that were reanalyzed.

"This is a good wakeup call, and it's a marker of Ahmad's integrity that he's taking this on," said Poldrack, who was not involved in the meta-analysis but said he has had suspicions about fMRI reliability for a few years now.

Connectivity mapping - seeing how areas of the brain are connected to address a task more than just what areas are active - is going to be the way forward, Poldrack predicted. Hariri agreed that identifying patterns of activity throughout the brain rather than in one or two areas may improve reliability.

In the meantime, the sociology behind a dramatic debunking of a scientific tool is going to be interesting to watch, Hariri and Poldrack both said.

"There's three things you can do," Poldrack said. "You can just up and quit, you can stick your head in the sand (and act as if nothing has changed), or you can dig in and try to solve the problems."

GRAND RAPIDS, Mich. (June 3, 2020) -- Van Andel Institute scientists have for the first time described the near-atomic level structure of a molecular pathway that plays critical roles in human development, blood pressure regulation, inflammation and cell death. The findings were published today in the journal Nature.

"The pannexin1 channel, or PANX1, is vitally important for maintaining normal, healthy function and, as such, is a major target for treating a host of diseases," said Wei Lü, Ph.D., an assistant professor in Van Andel Institute's Structural Biology Program and co-corresponding author of the study. "Our new images provide a blueprint for drug development and also answer longstanding questions about how PANX1 works."

PANX1 is a protein that is present in tissues throughout the body, where it forms channels that allow the passage of molecules such as the cellular fuel ATP, along with much smaller ions. Drugs that interfere with PANX1 have shown promise as therapies for a number of diseases, including cardiovascular diseases and cancer. Until now, little was known about how exactly these agents interact with PANX1.

The study revealed key changes in PANX1 during normal conditions versus times when the cells are undergoing apoptosis, a process that recycles damaged and dead cells. These variations cause molecules and ions to be routed through different areas of the channel and determine whether a large pore is open or closed.

Under normal conditions, the pore is blocked, and only small ions are allowed through seven narrow side tunnels in PANX1. However, during apoptosis, the pore is opened and ATP is released, which sends a signal that kicks off cellular recycling.

Importantly, the team also determined that a common medication that inhibits PANX1, carbenoxolone, works by preventing other molecules from entering the channel. Carbenoxolone is used to treat ulcers and is being investigated as a therapy for several cancers.

"These insights will be impactful beyond our understanding of PANX1 -- they also shed light on how other similar large-pore channels function," said Juan Du, Ph.D., an assistant professor in VAI's Structural Biology Program and co-corresponding author of the study.

In addition to Du and Lü, authors include lead author Zheng Ruan, Ph.D., and Ian J. Orozco, Ph.D., of VAI. The findings were made possible by VAI's state-of-the-art David Van Andel Advanced Cryo-Electron Microscopy Suite, which allows scientists to view some of life's smallest components in exquisite detail. VAI's most powerful microscope, the Titan Krios, can visualize molecules 1/10,000th the width of a human hair. The high-performance computing team at VAI also provided support for this work.

The sacred oath taken by physicians during graduation from medical school to "First do no harm," the first words of the Hippocratic Oath, provides a strong impetus for a commentary just published in The American Journal of Medicine. Researchers from Florida Atlantic University's Schmidt College of Medicine and collaborators from the University of Wisconsin School of Medicine and Public Health are urging all health care providers to always prioritize compassion with reliable evidence on efficacy and safety. They recommend a moratorium on the prescription of chloroquine or hydroxychloroquine, with or without azithromycin, to treat or prevent COVID-19, with the exceptions of obtaining the necessary evidence in randomized trials as well as compassionate use.

Despite the fact, or perhaps due in part to the fact that there are no therapeutic or preventive measures for the COVID-19 pandemic in the United States, which accounts for less than 5 percent of the world's population and about 30 percent of the cases and deaths, the widespread prescriptions of these drugs are nine times greater than in the last several years. This widespread use is leading to nationwide shortages in patients with lupus and rheumatoid arthritis, for whom hydroxychloroquine has been an approved indication for decades. These patients are unable to refill their prescriptions.

On March 28, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization for chloroquine and hydroxychloroquine for the treatment of COVID-19. By April 24, however, the FDA issued a drug safety communication warning regarding hydroxychloroquine and heart rhythm disturbances that can lead to sudden cardiac death.

"If these drugs need to be prescribed for patients with COVID-19, baseline evaluations and serial monitoring are an absolute necessity," said Richard D. Shih, M.D., first author, a professor of emergency medicine and division director and founding program director for the emergency medicine residency program in FAU's Schmidt College of Medicine.

Further, the authors point out that the reassuring safety profile of hydroxychloroquine may be more apparent than real. The data on safety derive from decades of prescriptions by health care providers, primarily for their patients with lupus and rheumatoid arthritis, both of which are of greater prevalence in younger and middle age women, whose risks of fatal heart outcomes due to hydroxychloroquine are reassuringly very low. In contrast, the risks of hydroxychloroquine for patients with COVID-19 are significantly higher because fatal cardiovascular complications due to these drugs are so much higher in older patients and those with existing heart disease or its risk factors, both of whom are predominantly men.

In basic research, hydroxychloroquine and chloroquine are structurally related and have similar mechanisms to inhibit the virus that causes COVID-19. Despite their structural similarities, in vitro, hydroxychloroquine appears to be more effective. In addition, when used for lupus and rheumatoid arthritis, hydroxychloroquine has fewer side effects, less drug interactions and is less toxic in overdose. The authors note that the currently available evidence is restricted to eight published studies, five on hydroxychloroquine alone; two on hydroxychloroquine plus azithromycin; and one on both in combination or alone. Of these only three are randomized trials that enrolled 225, 62, and 30 patients - all too small to provide reliable evidence. All three tested hydroxychloroquine alone versus standard of care in China. One showed no significant difference in viral clearance at 28 days, the second, no difference in viral clearance at seven days, and the third, some improvements in fever, cough and chest computed tomography findings.

"With respect to hypothesis testing, only large-scale randomized trials of sufficient size, dose and duration can reliably detect the most plausible small-to-moderate effects, which can have enormous clinical and public health impacts," said Charles H. Hennekens, M.D., Dr.PH, senior author, the first Sir Richard Doll professor and senior academic advisor in FAU's Schmidt College of Medicine.

Co-authors include Heather M. Johnson, M.D., FACC, a preventive cardiologist/cardiologist at the Lynn Women's Health and Wellness Institute at Boca Raton Regional Hospital/Baptist Health South Florida, and Dennis G. Maki, M.D., professor emeritus in the Department of Medicine at the University of Wisconsin School of Medicine and Public Health, where Johnson also is an adjunct associate professor.

Hennekens and Maki have been collaborators since 1969, when they served as lieutenant commanders in the U.S. Public Health Service as epidemic intelligence service officers with the U.S. Centers for Disease Control and Prevention. Hennekens, Maki and Johnson also collaborated on a recently published commentary in The American Journal of Medicine concerning the already alarming racial inequalities in mortality from COVID-19, which are only likely to increase further unless effective drug therapies or vaccines are distributed equitably.

New research from University of Alberta microbiologists has shed new light on how the respiratory syncytial virus (RSV)--one of the most common viral infections--breaks into our cells to cause infection.

In a study published in the journal Nature, associate professor of medical microbiology and immunology David Marchant and an international team of researchers discovered that RSV tricks cells into letting it in by essentially ringing a doorbell that calls its receptor to the virus waiting at the door.

"RSV kills between 150,000 and 200,000 people--mainly children and infants--every year worldwide," said Marchant, who is also the Canada Research Chair in Viral Pathogenesis and a member of the Li Ka Shing Institute of Virology and Alberta Respiratory Centre.

"This discovery identifies one of the first steps in RSV infection, and the hope is if we can block the interaction of the virus with the receptor, we may be able to stop the infection from happening."

Currently, there is no vaccine or therapeutics to treat RSV, and nothing on the horizon, Marchant said. RSV most often affects infants and young children, infecting the lungs and airways. In fact, some experts estimate that almost all children have been infected with RSV by the time they reach the age of three. It's the leading cause of infant hospitalization in the world and the second leading cause of infant mortality next to malaria.

RSV is unique because it lies on top of the surface of a cell for hours before gaining access and infecting it, unlike other viruses such as influenza, which can break into a cell within minutes by fusing with it.

In 2011, Marchant led a team that discovered that a receptor within the cell called nucleolin played a role in facilitating RSV's entry into the cell--RSV bound itself to the receptor and piggybacked in. However, it was unknown how or why nucleolin "came to the door" in the first place.

In the new study, Marchant's team found that RSV bound itself to a second receptor, called IGF1R, and a gene protein called PKC-zeta, using both to create a signal, or "doorbell," to call nucleolin to the surface of the cell, where the virus awaits. Once nucleolin arrives at the surface, RSV binds itself to it to enter and infect the cell, like an imposing and uninvited guest.

"Essentially, RSV has evolved to exploit a normal, healthy function within the cell," said Marchant. "It raises some interesting questions, like 'Did the virus evolve to bind to IGF1R first or did it evolve to bind to the nucleolus first?' I think we'll be exploring this more over the next few years."

Marchant said he hopes this discovery can lead to new treatments in the future, though he noted that developing a viable treatment for RSV is still years away.

"We have a number of different therapeutic candidates that we're working on in the lab to try to help move these forward into the clinic, such as blocking other receptors that are downstream from nucleolin in the process," he said. "But we don't yet know if there are side-effects to inhibiting those other signals, so we've got to look into that."

Marchant's research was supported through grants from the Women and Children's Health Research Institute, Li Ka Shing Institute of Virology, The Lung Association, the Canadian Lung Association and the Canadian Institutes of Health Research.

One-third of American families have lost income since the beginning of shutdown triggered by the coronavirus pandemic, with such losses striking families from all economic groups, according to a new nationally representative survey by the RAND Corporation.

About 30 percent of households, representing all levels of income, are having trouble paying their bills. The problem is more highly concentrated among low-income households, with even many households whose income has remained stable reporting that they are struggling to pay bills, according to the survey of more than 2,000 Americans.

About 40 percent of non-Hispanic Black households and nearly 50 percent of Hispanic households reported problems paying their bills, compared with 21 percent of non-Hispanic White households.

Among high-income households, 25 percent of those who have lost income report they are struggling to pay their bills.

"Americans from all income levels have seen their incomes drop, but how they approach paying bills in the face of adversity differs significantly by income level," said Katherine G. Carman, the study's lead author and a senior economist at RAND, a nonprofit research organization.

Unsurprisingly, low-income households have few options in paying their bills. They report borrowing from friends and family, selling possessions and simply being unable to meet expenses. Consistent with these findings, evidence from other surveys reveals rising food insecurity among low-income households.

Middle-income households report using formal credit, including putting expenses on credit cards with the hopes of paying the debt off over time, using bank loans and lines of credit, and, in some cases, taking on payday loans.

Researchers found fewer reports of payday loans among the low-income group than among the middle-income group. Although this difference was not statistically significant, researchers say it might reflect the higher rates of job loss among low-income workers, because such loans are not available to those who are unemployed.

Among the high-income group, households are likely to report turning to existing assets (such as balances in checking or savings accounts), and they report planning to pay off those expenses that they do put on credit cards at the end of the month.

Households at all income levels report turning to available cash first to cover their expenses. Other than the lowest income group, 80 to 90 percent said they would use money currently in checking and savings.

The federal stimulus payment is a lifeline for those who report having problems meeting current bills, with more than 80 percent of those people saying they planned to use the stimulus payment to meet current expenses.

Rent and mortgage relief was less commonly reported as a way to pay bills, but it was still important; 20 percent of households having problems meeting current expenses indicated using this method.

The survey was fielded between May 1 and May 6 through the RAND American Life Panel, a nationally representative internet panel, to assess the effects of the COVID-19 pandemic on individuals and households across a variety of topics.

The report, "How Are Americans Paying Their Bills During the COVID-19 Pandemic?" is available at http://www.rand.org. Shanthi Nataraj co-authored the study.

The research was conducted in RAND Education and Labor, a division of the RAND Corporation, which conducts rigorous, objective research to help decisionmakers and practitioners find solutions to education and labor market challenges.

It begins with shortness of breath. And for approximately one third of patients, acute respiratory distress syndrome, or ARDS, ends in death. For those who survive, their lives are often turned upside-down. Michigan Medicine researchers have been investigating the downstream effects of ARDS for years. As the COVID-19 pandemic rages on, their work has relevance for hundreds of thousands of new patients.

"The way COVID-19 kills patients is by depriving them from oxygen," says Theodore (Jack) Iwashyna, M.D., professor of critical care medicine. "But only a third or fewer of COVID-19 patients who develop respiratory failure die. Most survive, and we need research that helps them not just survive but really heal."

A team led by Iwashyna wanted to look more closely at how being hospitalized for ARDS affected people months after they were discharged. They interviewed dozens of patients from around the nation. "As we knew from past research, people had new disabilities ranging from general fatigue and weakness to where they couldn't remember things," says Katrina Hauschildt of the U-M department of sociology and first author on the study. "A lot of people had emotional difficulties coming to terms with just how sick they had been--a kind of PTSD from being in the ICU."

"What I didn't expect," says Iwashyna, "was the lasting chaos into which surviving respiratory failure threw some of our patients and their families. Patients described problems coming not just from medical bills--although there were plenty of those--but also from losing their jobs and losing their insurance." Given the magnitude of recession hitting at the same time as patients are trying to recover from COVID-19, Iwashyna and Hauschildt are worried this could be devastating for many families.

One 55-year old man described having to give up his small business because he could not work after getting out of the intensive care unit (ICU). "I had to sell my business. I'm on disability now...I owned a fire prevention company...We used to clean the kitchen exhaust systems in restaurants throughout the state. Degreased the restaurants, like their exhaust hoods in the kitchen and on the roof...Yeah, I sold everything."

The team found that many respiratory failure patients experience what is known as financial toxicity, defined as the financial burdens and related distress of medical care. In turn, this financial toxicity led to additional negative effects on their physical and emotional recovery.

With hospitalization for ARDS often resulting in weeks of high intensity care, patients end up with medical bills ranging from tens of thousands to, in some cases, millions of dollars, and the proportion covered by insurance varied substantially.

One 49-year old male survivor of ARDS told the study team "I barely make it, or my bills are pending like electricity, things and other stuff." Said another 55-year old woman "I had to pay my rent, my food and medicines and all that so I was a little bit short ... They were kind of difficult to pay after the hospital ... Because I had to get more medicines and all that."

The team reported several consequences of hospitalization including emotional distress related to insurance issues and unpaid bills, reduced physical well-being due to the inability to receive follow-up care due to cost, an increased reliance on family and friends to help cover expenses and other material hardships. Said one patient: "In the next couple of months, I may end up being homeless because of the financial aspect of it."

While these cases may seem extreme, they were not rare. And many patients described having to make hard choices about whether they could afford rehabilitation--and stopping early when their coverage ran out, even though they were not yet recovered. A 51-year old man told the study team "[Physical therapy] was very short, a couple weeks maybe; then it was over, and I just laid around basically. My insurance did not cover any more, so they had to cut me."

Another patient, a 61-year-old woman, described not having the equipment when she tried to go home: "I could pick one item that I wanted," of the hospital bed, wheelchair, and walker she needed, "because the insurance would only pay for one item."

Hauschildt says the study outlines the need for doctors to be more aware of the financial toxicity faced by survivors of ARDS, including those recovering from COVID-19. "One of the biggest things any doctor involved in follow up care can do is anticipate that patients might have real financial burdens and know what resources are available so they can help," she adds.

However, she notes, what's available is really up to policy makers. For example, the study found that patients who were already on public insurance before their illness reported less of an out-of-pocket financial impact. "Communities that put a safety net in place for ARDS and COVID-19 survivors will ultimately have better healing and recovery. People who heal are able to return to work and care for others and their communities; people who don't aren't."

This work was supported by the National Institutes of Health, National Heart, Lung and Blood Institute as part of the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network. The patients who participated in these interviews gave their consent for their words to be quoted, and were all about nine months after having had moderate to severe ARDS.

Leesburg, VA, June 3, 2020--An open-access article in the American Journal of Roentgenology (AJR) details myriad practical updates that radiologists performing cross-sectional interventional procedures should institute to minimize risks for patients and imaging personnel alike during the coronavirus disease (COVID-19) pandemic.

"Cross-sectional interventional procedures are performed under CT, ultrasound, fluoroscopy, or MRI guidance and include fluid aspiration, (thoracentesis, paracentesis, and fluid collections), drainage catheter placement, percutaneous biopsy, and tumor ablation," explained lead author Ghaneh Fananapazir at the University of California Davis Medical Center.

All of these procedures require appropriate donning and doffing of personal protective equipment by every member of the IR team--physician, trainee, nurse, technologist--and some procedures may require admitting the patient for management of postprocedure complications, necessitating a hospital bed and auxiliary resources.

Thus, for procedural delays that will not adversely affect patient outcome, Fananapazir and colleagues proposed the following tiered approach for both outpatient and inpatient scenarios: urgent procedures, procedures that should be performed within 2 weeks, procedures that should be performed within 2 months, and procedures that can safely be delayed 2 or 6 months.

"Each procedure request must be triaged into a tier on a case-by-case basis," Fananapazir et al. warned, "because clinical circumstances can dictate one procedure as urgent, whereas different clinical data may render the same procedure safe to delay." When considering any procedural delay, Fananapazir's team strongly recommended consultation with the referring physician, who may have insights not available to the interventional radiologist.

Wherever possible, procedures should be performed bedside in COVID-19 units (or patient rooms, should no dedicated COVID-19 unit exist). Regarding ultrasound-guided procedures, specifically, a mobile ultrasound unit can be left in place in the ICU or the COVID-19 unit--"used for interventional procedures, guidance for vascular access, or point-of-care thoracic and nonthoracic ultrasound," wrote Fananapazir et al. Ultrasound probes should be sterilized according to manufacturer guidelines.

Fananapazir's team also cautioned against CT technologists or sonographers entering the procedure room. Ideally, all anticipated IT tray supplies should be acquired before the procedure commences, covered with a sterile plastic drape, and opened only to the extent needed.

Additionally, patient interaction during the informed consent interview can be limited by obtaining consent in the procedure room or using documented oral consent in the medical record. "Both of these modifications to the consent process are outside of standard regulated practice," the authors of this AJR article noted, "therefore, establishment of hospital-wide frameworks may be needed."

UNIVERSITY PARK, Pa. --After the U.S. Census Bureau announced that it was changing how it protects the identities of individuals for the 2020 Census, a Penn State-led research team began to evaluate how these changes may affect census data integrity.

The Census Bureau is proposing to use differential privacy, a new method that attempts to protect the identities of individuals when publishing public data. Census data is used to distribute federal funding that impacts communities and also determines congressional representation.

Alexis Santos, assistant professor of human development and family studies at Penn State, along with researchers Jeffrey Howard, assistant professor at the University of Texas at San Antonio, and Ashton Verdery, assistant professor of sociology, demography, and social data analytics at Penn State, examined mortality rates in 2010. The researchers compared both methods of privacy protection and the implication of this change to better understand health disparities in the United States. The work was published recently in Proceedings of the National Academy of Sciences.

The research team discovered that when differential privacy method was used on Census data, it produced dramatic changes in population counts for racial and ethnic minorities compared to the traditional methods.

"We focused on mortality rate estimates because they are an essential population-level metric for which data are collected and disseminated at the national level and because mortality rates are a critical indicator of population health," said Santos.

The research team then explored the changes in mortality rates resulting from the two disclosure avoidance systems by metropolitan classifications.

"We discovered that by using differential privacy, there were both instances of under- and over-counting of the population. In rural areas, there was undercounting of racial and ethnic minorities, while in urban areas there was an overcounting of these populations," Santos said.

The researchers found that some discrepancies between the two methods of data analysis exceeded a 10% difference.

"This is very concerning because it could impact how much funding programs receive for a specific geographic area," said Santos. "These discrepancies could result in understated health risks in some areas, and while overstating in others where there isn't a great need."

According to Santos, the findings highlight the consequences of implementing differential privacy and demonstrate the challenges in using the data products derived from this method.

"The Census Bureau has been very receptive to our research, and demonstrated concern about the accuracy of the data," Santos said. "We plan to move forward with additional research to determine how differential privacy may affect population growth estimates and populations changes from census year to census year. We still have time to fine tune the differential privacy algorithm, and our research will help pinpoint areas of improvement."

Santos, who is also a cofunded faculty member of the Social Science Research Institute, and the research team were supported by the Population Research Institute and the Administrative Data Accelerator at Penn State. The work also is supported by the Center for Community Based and Applied Health Research at the University of Texas at San Antonio.

Key Findings:

This is the first example of repairing a recessive gene mutation

Repairing a single mutation in the Tmc1 gene restored partial hearing in mice

The technique required the use of two viral vectors to deliver the base editing machinery

Cells with both vectors recovered 100 percent function

This technique opens the door to treating other genetic forms of hearing loss and other genetic diseases

Using a new genetic engineering technique, known as base editing, researchers from Boston Children's Hospital and the Broad Institute of MIT and Harvard, have restored hearing in mice with a known recessive genetic mutation.

With this technique, researchers repaired one single error in the Tmc1 gene known to cause a hereditary form of deafness. The one-time repair involved switching one incorrect DNA base in the gene with the correct version. While a similar approach has been used previously for other forms of hearing loss, this is the first time base editing has been used for a genetic sensory disorder.

Details about the approach are published in a new paper in Science Translational Medicine.

"This research is very important for the pediatric community here at Boston Children's Hospital and elsewhere because about 4,000 babies are born each year with genetic hearing loss," says co-senior author Jeffrey Holt, PhD, director of otolaryngology research at the F.M. Kirby Neurobiology Center at Boston Children's Hospital. "And, we feel this is a big step beyond the field of hearing restoration and for the broader field focused on treatment of genetic disorders.

Base editor acts as a spell-check

Earlier research in 2015 from the Holt lab and colleague showed that replacing a full DNA sequence for Tmc1 into the sensory cells in the ear restores hearing in deaf mice.

"In that case, we used a single engineering adeno-associated virus (AAV) to deliver a functioning copy of the Tmc1 gene into the ear," he says.

This research goes a step further. Instead of replacing a gene, the team repaired a single mutation in the Tmc1 gene converting it back to the correct sequence. "It's like your spell-checker," he says. "If you type the wrong letter, spell checker fixes it for you." When the team fixed the defect in the sensory cells in the ear, the edited cells recovered 100 percent of their function.

But the base editor was too large for a single AAV. The newly designed base editor that engineers the genetic repair required more space. It did not fit into a single AAV. Instead, they split up the base editor sequence into two AAVs.

"Once the cell was infected with these two parts, it was able to reassemble into a single full length sequence and then perform the base editing task we needed," says co-first author Olga Shubina-Oleini, PhD, of the Holt lab.

It is important to note the approach worked when both AAVs made their way into the cell. But that was the case in about one-quarter of the cells which was enough to provide some hearing to the mice.

"We got it to work but we need to boost the efficiency to make it broadly useful," says Holt. If only one AAV got into the cell, it did not work. "But the message is that when we got both into the cells, we went from zero function to 100 percent. That tells me all we need to do is get it into more cells and we will recover more hearing function."

Building on previous success

At least 100 different genes are involved in hearing in the inner ear. Mutations in any one of those can lead to hearing loss.

"We have been developing different strategies targeting several of these different forms of hearing loss," says Holt. "It really takes a precision medicine approach where we are trying to tailor our strategy specific, not just each gene that is involved, but in some cases the individual genetic mutation in the gene as is the case with this study."

The Holt lab has a long history of success unraveling these genetic causes of hearing loss and developing gene therapy treatments for genetic forms of hearing loss. In 2011, the team first discovered that the Tmc1 protein is required for hearing and balance. After its 2015 success, the Holt team used CRISPR-Cas9 gene editing in 2019 to prevent hearing loss in Beethoven mice, a model of a dominant Tmc1 mutation.

Just one of many mutations related to hearing and balance

Over 70 different mutations have been identified in the Tmc1 gene in humans. "We hope this new technique will allow us to pick them off one at a time to restore hearing and balance related to the inner ear," says Holt.

Along with hearing loss, balance disorders represent a large unmet medical need, though it is present mainly in aging adults. The inner ear houses the cochlea (the auditory organ) and five organs of balance - the vestibular organs. Disruptions in function in any of those five could lead to balance problems.