Culture

Artificial intelligence is providing new opportunities in a range of fields, from business to industrial design to entertainment. But how about civil engineering and city planning? How might machine- and deep-learning help us create safer, more sustainable, and resilient built environments?

A team of researchers from the NSF NHERI SimCenter, a computational modeling and simulation center for the natural hazards engineering community headquartered at the University of California, Berkeley, have developed a suite of tools called BRAILS — Building Recognition using AI at Large-Scale — that can automatically identify characteristics of buildings in a city and even detect the risks that a city's structures would face in an earthquake, hurricane, or tsunami. The team is comprised of researchers from UC Berkeley, the International Computer Science Institute, Stanford, and UCLA.

Charles (Chaofeng) Wang, a postdoctoral researcher at the University of California, Berkeley, and the lead developer of BRAILS, says the project grew out of a need to quickly and reliably characterize the structures in a city.

"We want to simulate the impact of hazards on all of the buildings in a region, but we don't have a description of the building attributes," Wang said. "For example, in the San Francisco Bay area, there are millions of buildings. Using AI, we are able to get the needed information. We can train neural network models to infer building information from images and other sources of data."

BRAILS uses machine learning, deep learning, and computer vision to extract information about the built environment. It is envisioned as a tool for architects, engineers and planning professionals to more efficiently plan, design, and manage buildings and infrastructure systems.

The SimCenter recently released BRAILS version 2.0 which includes modules to predict a larger spectrum of building characteristics. These include occupancy class (commercial, single-family, or multi-family), roof type (flat, gabled, or hipped), foundation elevation, year built, number of floors, and whether a building has a "soft-story" -- a civil engineering term for structures that include ground floors with large openings (like storefronts) that may be more prone to collapse during an earthquake.

The basic BRAILS framework developed by Wang and his collaborators automatically extracts building information from satellite and ground level images drawn from Google Maps and merges these with data from several sources, such as Microsoft Footprint Data and OpenStreetMap -- a collaborative project to create a free editable map of the world. The framework also provides the option to fuse this data with tax records, city surveys, and other information, to complement the computer vision component.

"Given the importance of regional simulations and the need for large inventory data to execute these, machine learning is really the only option for making progress," noted SimCenter Principal Investigator and co-Director Sanjay Govindjee. "It is exciting to see civil engineers learning these new technologies and applying them to real world problems."

LEVERAGING CROWDSOURCING POWER

Recently, the SimCenter launched a project on the citizen science web portal, Zooniverse, to collect additional labelled data. The project, called "Building Detective for Disaster Preparedness," enables the public to identify specific architectural features of structures, like roofs, windows, and chimneys. These labels will be used to train additional feature extraction modules.

"We launched the Zooniverse project in March and within a couple of weeks we had a thousand volunteers, and 20,000 images annotated," Wang said.

Since no data source is complete or fully accurate, BRAILS performs data enhancements using logical and statistical methods to fill in gaps. It also computes the uncertainty for its estimates.

After developing and testing the accuracy of these modules individually, the team combined them to create the CityBuilder tool inside BRAILS. Inputting a given city or region into CityBuilder can automatically generate a characterization of every structure in that geographic area.

Wang and his collaborators performed a series of validation demonstrations, or as they call them, testbeds, to determine the accuracy of the AI-derived models. Each testbed generates an inventory of structures and simulates the impact of a hazard based on historical or plausible events.

The team has created testbeds for earthquakes in San Francisco; and hurricanes in Lake Charles, Louisiana, the Texas coast, and Atlantic City, New Jersey.

"Our objectives are two-fold," Wang said. "First, to mitigate the damage in the future by doing simulations and providing results to decision- and policy-makers. And second, to use this data to quickly simulate a real scenario - instantly following a new event, before the reconnaissance team is deployed. We hope near-real-time simulation results can help guide emergency response with greater accuracy."

The team outlined their framework in the February 2021 issue of Automation in Construction. They showed that their neural network could generate realistic spatial distributions of buildings in a region and described how it could be used for large-scale natural hazard risk management using five coastal cities in New Jersey.

The team presented a testbed for Hurricane Laura (2020), the strongest hurricane to make landfall in Louisiana, at the 2021 Workshop on SHared Operational REsearch Logistics In the Nearshore Environment (SHORELINE21).

COMPUTATIONAL RESOURCES

To train the BRAILS modules and run the simulations, the researchers used supercomputers at the Texas Advanced Computing Center (TACC) -- notably Frontera, the fastest academic supercomputer in the world, and Maverick 2, a GPU-based system designed for deep learning.

"For one model, the training could be finished in a few hours, but this depends on the number of images, the number of GPUs, the learning rate, etc.," Wang explained.

TACC, like the SimCenter, is a funded partner in the NSF NHERI program. TACC designed and maintains the DesignSafe-CI (Cyberinfrastructure) -- a platform for computation, data analysis, and tools used by natural hazard researchers.

"This project is a great example of how advanced computing through DesignSafe can enable new avenues of natural hazards research and new tools, with many components of NHERI working together," said Ellen Rathje, professor of civil engineering at The University of Texas at Austin and principal investigator of the DesignSafe project.

BRAILS/CityBuilder is designed to work seamlessly with the SimCenter Regional Resilience Determination (R2D) tool. R2D is a graphical user interface for the SimCenter application framework for quantifying the regional impact from natural hazards. Its outputs include the damage state and the loss ratio -- the percentage of a building's repair cost to its replacement value -- of each building across an entire city or region, and the degree of confidence in the prediction.

"The hazard event simulations -- applying wind fields or ground shaking to thousands or millions of buildings to assess the impact of a hurricane or earthquake -- requires a lot of computing resources and time," Wang said. "For one city-wide simulation, depending on the size, it typically takes hours to run on TACC."

TACC is an ideal environment for this research, Wang says. It provides most of the computation his team needs. "Working on NSF projects related to DesignSafe, I can compute almost without limitations. It's awesome."

IMPACTS

To make our communities more resilient to natural hazards, we need to know what level of damage we will have in the future, to inform residents and policymakers about whether to strengthen buildings or move people to other places.

"That's what the simulation and modeling can provide, " Wang said. "All to create a more resilient built environment."

EVANSTON, Ill. --- Self-affirmation, the practice of reflecting upon one's most important values, can aid Black medical students in reaching their residency goals. But conversely, it can lead to the perception that they are less qualified for a prestigious residency than their peers.

The pandemic has underscored the racial disparities in the quality of healthcare, a field in which Black Americans are vastly underrepresented as medical physicians.

New Northwestern University research aims to address the "leaky pipeline" preventing Black medical students from completing medical school to pursuing residencies in high-need and underrepresented areas.

Sylvia Perry, assistant professor of psychology in the Weinberg College of Arts and Sciences at Northwestern, is the lead author of the study, which found that Black medical students reported higher levels of fatigue, a lower sense of belonging, and a greater likelihood of changing their medical residency plans than their white counterparts.

It is the first study to attempt experimentally to mitigate such discrepancies with a self-affirmation intervention and the first study to show that self-affirming can promote goal pursuit in a medical education context.

An unexpected finding of the study was that self-affirmation decreased a sense of competitiveness for prestigious residencies.

"This would suggest that if Black medical students are not properly supported during their training, then self-affirming may lead them to accept that extremely competitive residency is unobtainable," Perry said.

About the self-affirmation experiment:

For the longitudinal field experiment, the researchers sampled 234 Black and 182 white medical students across 50 schools in the U.S.

Students completed computerized tasks at three points during their second year of medical school. The self-affirmation intervention group ranked a list of values from most important to least important and wrote about why the most important value mattered to them. Control environment students were asked to write about why their least important value would be important to someone else.

Students were asked to report their well-being, sense of belonging, perceived residency competitiveness, and residency goals. Responses were coded during each wave of testing to see if responses changed or stayed the same.

The researchers found that Black students tended to report more fatigue and less belonging than white students.

They also found that the self-affirmation intervention did not significantly influence students' fatigue, depression, anxiety for belonging. Unexpectedly, Black students in the self-affirmation (vs. control) condition reported lower competitiveness of residency.

Analyses revealed that Black students, compared with white students, were less likely to indicate stable residency goals over time, which may be an indication of stereotype threat. However, this racial gap was eliminated with the intervention.

White students' perceived competitiveness for residency was unaffected by the intervention.

Next steps:

Perry says the researchers will look further into other predictors of well-being, belonging and residency goal stability, including whether going to medical school at a Historically Black College and University (HBCU), compared to a predominately white institution, provides supportive and protective effects that help Black medical students thrive.

BOSTON - In a major breakthrough, researchers at Massachusetts General Hospital (MGH) have discovered how amyloid beta--the neurotoxin believed to be at the root of Alzheimer's disease (AD)--forms in axons and related structures that connect neurons in the brain, where it causes the most damage. Their findings, published in Cell Reports, could serve as a guidepost for developing new therapies to prevent the onset of this devastating neurological disease.

Among his many contributions to research on AD, Rudolph Tanzi, PhD, vice chair of Neurology and co-director of the McCance Center for Brain Health at MGH, led a team in 1986 that discovered the first Alzheimer's disease gene, known as APP, which provides instructions for making amyloid protein precursor (APP). When this protein is cut (or cleaved) by enzymes--first, beta secretase, followed by gamma secretase--the byproduct is amyloid beta (sometimes shortened to Abeta). Large deposits of amyloid beta are believed to cause neurological destruction that results in AD. Amyloid beta formed in the brain's axons and nerve endings causes the worst damage in AD by impairing communication between nerve cells (or neurons) in the brain. Researchers around the world have worked intensely to find ways to block the formation of amyloid beta by preventing cleavage by beta secretase and gamma secretase. However, these approaches have been hampered by safety issues.

Despite years of research, a major mystery has remained. "We knew that Abeta is made in the axons of the brain's nerve cells, but we didn't know how," says Tanzi. He and his colleagues probed the question by studying the brains of mice, as well as with a research tool known as Alzheimer's in a dish, a three-dimensional cell culture model of the disease created in 2014 by Tanzi and a colleague, Doo Yeon Kim, PhD. Earlier, in 2013, several other MGH researchers, including neurobiologist Dora Kovacs, PhD (who is married to Tanzi), and Raja Bhattacharyya, PhD, a member of Tanzi's lab, showed that a form of APP that has undergone a process called palmitoylation (palAPP) gives rise to amyloid beta. That study indicated that, within the neuron, palAPP is transported in a fatty vesicle (or sac) known as a lipid raft. But there are many forms of lipid rafts. "So the question was, Which lipid rafts? And which ones are most relevant to the neuronal processes making up the neural networks of the brain?" says Tanzi.

The new investigation revealed that palAPP is stabilized and prepared for cleavage by beta secretase in special lipid rafts within the neuron known as mitochondria-associated endoplasmic reticulum membranes (MAMs). "We showed for the first time not only that the MAM is where palAPP is processed by beta secretase to make Abeta, but that this happens exclusively in axons and neuronal processes where Abeta does most of its damage," says Bhattacharyya, lead author of the Cell Reports paper. This role for MAMs was previously unknown, though earlier research indicated that they are increased in number and activity in the brains of people with Alzheimer's disease.

Next, the MGH team wanted to learn what happens when MAM levels and activity were intentionally altered. They showed for the first time that preventing assembly of MAMs, either with gene therapy or a drug that blocked a key protein called the sigma-1 receptor (S1R), dramatically decreased beta secretase cleavage of palAPP in axons and lowered Abeta production. Conversely, a drug that activated S1R triggered an increase in beta secretase cleavage of palAPP and increased production of amyloid beta in axons.

"Our results suggest that the sigma-1 receptor might be a viable therapeutic target for reducing Abeta production, specifically in axons," says Tanzi. The study also lends support for a strategy already under investigation by Tanzi and his team, which is developing an experimental treatment that inhibits the palmitoylation of APP, the process that produces palAPP. It's also known that another class of drugs that Kovacs is studying for preventing formation of amyloid beta, called ACAT inhibitors, works directly in MAMs. In the future, these and other interventions that thwart production of this most dangerous pool of axonal amyloid beta could be used in concert with early detection (through blood or imaging tests) to stop or slow the progression of AD.

The development of antibodies to the COVID-19 virus has been the great long-term hope of ending the pandemic. However, immune system turncoats are also major culprits in severe cases of COVID-19, Yale scientists report in the journal Nature.

These autoantibodies target and react with a person's tissues or organs similar to ones that cause autoimmune diseases such as lupus or rheumatoid arthritis. In COVID-19 cases they can attack healthy tissue in brain, blood vessels, platelets, liver, and the gastrointestinal tract, researchers report. The more autoantibodies detected, the greater the disease severity experienced by patients.

And the autoantibodies paradoxically also target and interfere with many immune system proteins that are designed to fend off infections, the study found.

"It's a two-edge sword," said Aaron Ring, assistant professor of immunobiology at Yale and senior author of the paper. "Antibodies are crucial to fend off infection, but some COVID-19 patients also develop antibodies that damage their own cells and tissues."

It is clear that in many cases the presence of coronavirus drove the creation of the damaging autoantibodies, Ring said. But it is also likely that some COVID-19 patients had pre-existing autoantibodies that made them more susceptible to infection, he said. Mice with these same autoantibodies were more susceptible to infection by the COVID-19 virus and more likely to die, the authors report.

The existence of these long-lived rogue autoantibodies could also help explain why some people infected with COVID-19 can later develop lasting medical symptoms, so-called long COVID cases. "This could be the unfortunate legacy of the virus," Ring said.

"Our findings reinforce the importance of getting vaccinated," added co-corresponding author Akiko Iwasaki, the Waldemar Von Zedtwitz Professor of Immunobiology at Yale. "The fact that even mild infections are associated with autoantibody production underscores the potential for long-term health consequences of COVID-19."

For the study, Ring's lab worked with Iwasaki's lab and members of the Yale IMPACT team -- a group of scientists, scholars, and physicians developing research and clinical efforts to combat COVID-19 -- to screen blood samples from 194 patients who had contracted the virus, with varying degrees of severity, for the presence of autoantibodies. Specifically, they used a novel technology developed by Ring's lab called Rapid Extracellular Antigen Profiling (REAP) to identify autoantibody interactions with nearly 3,000 human proteins.

Ring said the findings may lead to strategies to treat or prevent the damaging effects of autoantibodies in COVID-19 patients. In addition, the new REAP technology could be used to pinpoint important antibody responses for many other disease conditions beyond COVID-19. Ring's lab has found a host of novel autoantibodies in patients with autoimmune disease and is now searching for autoantibodies in patients with cancer and neurological illnesses.

HOUSTON -- The glutaminase (GLS1) inhibitor IACS-6274, discovered and developed by The University of Texas MD Anderson Cancer Center's Therapeutics Discovery division, appears to be well-tolerated with successful target inhibition and early signs of anti-tumor activity in a biomarker-driven Phase I trial. Interim results of the study will be presented at the 2021 American Society for Clinical Oncology (ASCO) Annual Meeting on June 4.

On the trial, 17 of 20 evaluable patients achieved a best response of stable disease, with a disease control rate of 60% at 12 weeks. Six patients with biomarker-defined advanced cancers had meaningful durable disease stabilization for greater than six months, with evidence of tumor shrinkage.

Comprehensive pharmacokinetics (PK) and pharmacodynamics (PD) analyses on serial tumor and/or blood samples from trial participants established a robust PK/PD relationship across dose levels. Using a clinical assay developed in-house to measure metabolic activity in patients' blood mononuclear cells, the team also observed strong inhibition of glutamine metabolism at the recommended Phase II dose level, suggesting IACS-6274 robustly functions as intended to block GLS1 activity.

This represents the first major clinical data reported by MD Anderson's Therapeutics Discovery division, a unique group of clinicians, researchers and drug development experts working collaboratively to advance impactful new therapies. By working seamlessly with MD Anderson physicians, the team gains unique clinical insights that aid in the development of impactful medicines.

"Within Therapeutics Discovery, we have focused our efforts to develop new therapies that meet the needs of our patients," said principal investigator Timothy A. Yap, M.B.B.S., Ph.D., associate professor of Investigational Cancer Therapeutics and medical director of the Institute for Applied Cancer Science (IACS). "Our comprehensive efforts to understand and advance IACS-6274 identified select groups of underserved patients as those most likely to benefit from treatment, and we are encouraged by the early results thus far in the study."

Developing a therapy for underserved patient groups

The development of IACS-6274, previously known as IPN60090, was led by a team of scientists and drug development experts in the IACS and Translational Research to Advance Therapeutics and Innovation in Oncology (TRACTION) platforms, both engines within Therapeutics Discovery.

IACS-6274 was selected for development based on its potency, selectivity and PK profile to provide sustained GLS-1 inhibition in patients. The research team then conducted patient-driven translational studies to identify unique populations of patients likely to respond.

Based on these studies, priority indications for the trial include non-small cell lung cancers (NSCLC) with KEAP1/NFEL2L2 mutations, ovarian cancers with low expression of asparagine synthetase (ASNS) and tumors with immune checkpoint inhibitor resistance. Additional insights have revealed that cancers with STK11 and NF1 mutations may respond to GLS1 inhibitors, so the trial also has enrolled those patients.

Evaluating IACS-6274 in a Phase I clinical trial

The first-in-human dose-escalation study was conducted by MD Anderson's Phase I Clinical Trials Program in the Department of Investigational Cancer Therapeutics. The study was designed to evaluate the safety and tolerability of IACS-6274, to identify the maximum tolerated dose and to establish a recommended Phase II dose. Secondary objectives included PK, PD, anti-tumor activity and correlation of biomarkers with clinical outcomes.

The study has enrolled 22 patients with a median age of 63.5, all of whom had received at least two prior therapies. Sixteen patients (73%) are female and six (27%) are male. The trial included patients with different tumor and molecular subtypes, including many of the identified priority patient populations.

The six patients with durable stable disease included those with advanced ASNS-low ovarian cancer, melanoma resistant to anti-PD-1 therapies, NF1-mutant leiomyosarcoma and STK11-mutant NSCLC.

The most common side effects were mild transient visual disturbances. Less common grade 3 toxicities at higher dose levels included reversible nausea, vomiting and fatigue. One patient experienced dose-limiting acute renal failure and posterior reversible encephalopathy syndrome (PRES) at the highest dose level, which fully resolved.

"IACS-6274 appears to be safe and well-tolerated at our recommended Phase II dose, with early signs of anti-tumor activity in patients with certain molecular features," Yap said. "As the study progresses and we continue to learn from those participating, we will work to explore rational combination therapies that are predicted to maximize the benefits for distinct groups of patients based on key biomarkers of response."

HAMILTON, ON (May 19, 2021) - Researchers have found that the inclusion of a third drug to commonly used dual-drug inhalers can reduce asthma exacerbations and improve control over the disease in children, adolescents, and adults with moderate-to-severe asthma.

A team from McMaster University and The Research Institute of St. Joe's Hamilton announced their findings from a systematic review and meta-analysis. Data from 20 randomized controlled trials, which included a total of almost 12,000 patients, were analyzed in the study.

Dual-drug inhalers used to treat asthma typically contain an inhaled corticosteroid (ICS) to reduce inflammation, as well as a long-acting beta-adrenoceptor agonist (LABA) that acts as a bronchodilator. High-certainty evidence showed that the inclusion of a third drug to ICS-LABA combination therapy, known as a long-acting muscarinic antagonist (LAMA), reduced severe asthma exacerbations and slightly improved asthma control without an increase in adverse events. Previously, the benefits and harms of adding a LAMA to ICS-LABA therapy for asthma treatment were unclear and based off of only 1300 patients - mainly adults - leading to weak recommendations in treatment guidelines.

"Our findings provide clear, high-quality evidence on the benefits and harms of triple therapy that will inform asthma care and should prompt revision of current asthma guidelines," said Dr. Derek Chu, lead author of the study.

Dr. Chu is a clinical scholar in the Departments of Medicine and Health Research Methods, Evidence, and Impact (HEI) at McMaster University and an affiliate of The Research Institute of St. Joe's Hamilton.

“If we can reach optimal control of patients’ asthma and reduce asthma exacerbation rates through the LAMA add-on therapy, patients may be able to avoid other treatments that carry a higher risk of adverse events, such as oral corticosteroids, or therapies that are substantially more expensive, such as biologics,” said Lisa Kim, a clinical scholar in the Department of Medicine at McMaster and co-author of the study.

Inhaled LAMAs are currently available in separate inhalers or as three-in-one inhalers that also contain an ICS and LABA. According to the study, both approaches to administering the third drug work similarly.

More than 8 percent of Canadians over the age of 12 have been diagnosed with asthma, making it the most common chronic condition among children. The disease is characterized by constriction of the bronchial tubes, which impedes air flow to and from the lungs. Symptoms can include coughing or wheezing attacks, shortness of breath, chest tightness, and more. The exact causes of asthma may vary, adding to treatment complexity.

The study was published in the Journal of the American Medical Association (JAMA) in coordination with a presentation by the authors at the Advances in Asthma Therapies symposium. The symposium is part of the American Thoracic Society's annual conference - ATS 2021 - which is being held virtually this year.

CASE STUDY SUGGESTS YOUNG PEOPLE SUSCEPTIBLE TO CHRONIC FATIGUE SYNDROME AFTER COVID-19

https://www.hopkinsmedicine.org/news/newsroom/news-releases/covid-19-story-tip-case-study-suggests-young-people-may-be-susceptible-to-chronic-fatigue-following-covid-19

Media Contact: Michael E. Newman, mnewma25@jhmi.edu

With more adolescents and young adults being treated for COVID-19, clinicians are concerned that these people also will start showing post-COVID -- or "long haul" -- symptoms from their bouts with the virus. A recent Johns Hopkins Medicine review of three case studies provides some of the first evidence that one serious post-COVID problem may be myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), the complex, multisystem disorder previously known as chronic fatigue syndrome.

The findings were published April 29 in the journal Frontiers in Medicine.

"In the three patients studied -- all of whom had confirmed or highly probable COVID-19 infections early in the pandemic -- we observed ME/CFS-like symptoms within the first two weeks of illness," says Peter Rowe, M.D., director of the Chronic Fatigue Clinic at Johns Hopkins Children's Center and professor of pediatrics at the Johns Hopkins University School of Medicine. "At six months following their illness, all three still met the criteria for being diagnosed with ME/CFS."

In a recent report, the U.S. Centers for Disease Control and Prevention (CDC) noted that U.S. hospitals are seeing more adolescents and young adults admitted with COVID-19 as more contagious variants of SARS-CoV-2 -- the virus that causes the disease -- spread. The agency believes that the youthful case surge may be the result of those ages 10 to 24 being among the last prioritized to get the coronavirus vaccines, and the fact that many who are eligible have yet to receive their shots. Also, the CDC says, this group is more likely to be involved in high-risk behaviors such as playing close-contact sports and going out to bars.

The three patients evaluated in the recent study were a 19-year-old man and two women, ages 22 and 30, whose COVID-19 symptoms began between April and June 2020, and who were referred to the Chronic Fatigue Clinic between August and October of the same year. Symptoms of orthostatic intolerance -- a group of clinical conditions that includes fatigue, lightheadedness and difficulty concentrating, and are linked with greater than 90% of the people with ME/CFS -- were prominent in all three from the outset of their COVID-19 illness.

A six-month post-COVID symptom onset examination, including evaluations of movement, neurological function and continued orthostatic intolerance, was conducted on each of the patients to determine if ME/CFS could be diagnosed. All three easily met the criteria.

Interestingly, Rowe says, all three patients had relatively mild COVID-19 respiratory symptoms and none required hospitalization, yet it appears to have translated into the more serious secondary problem of ME/CFS for them all.

"This finding is consistent with previous studies in older patients with COVID-19 who showed persistent fatigue months after infection, regardless of the severity of the initial infection," he explains. "This raises the question of how many ME/CFS cases before the COVID-19 pandemic might have been due to mild, subclinical or asymptomatic viral infections [such as Epstein-Barr virus or human herpesvirus 6], including cases in adolescents, young adults and older people."

Rowe and his colleagues feel that further research is needed to define the biological mechanism by which ME/CFS arises from COVID-19, and then use that insight to develop treatment strategies that can return patients with post-COVID ME/CFS back to their previous quality of life.

Rowe is available for interviews.

By mapping its genetic underpinnings, researchers at University of California San Diego School of Medicine have identified a predictive causal role for specific cell types in type 1 diabetes, a condition that affects more than 1.6 million Americans.

The findings are published in the May 19, 2021 online issue of Nature.

Type 1 diabetes is a complex autoimmune disease characterized by the impairment and loss of insulin-producing pancreatic beta cells and subsequent hyperglycemia (high blood sugar), which is damaging to the body and can cause other serious health problems, such as heart disease and vision loss. Type 1 is less common than type 2 diabetes, but its prevalence is growing. The U.S. Centers for Disease Control and Prevention projects 5 million Americans will have type 1 diabetes by 2050. Currently, there is no cure, only disease management.

The mechanisms of type 1 diabetes, including how autoimmunity is triggered, are poorly understood. Because it has a strong genetic component, numerous genome-wide association studies (GWAS) have been conducted in recent years in which researchers compare whole genomes of persons with the same disease or condition, searching for differences in the genetic code that may be associated with that disease or condition.

In the case of type 1 diabetes, identified at-risk variants have largely been found in the non-coding regions of the genome. In the Nature study, senior author Kyle Gaulton, PhD, an assistant professor in the Department of Pediatrics at UC San Diego School of Medicine, and colleagues integrated GWAS data with epigenomic maps of cell types in peripheral blood and the pancreas. Epigenomic mapping details how and when genes are turned on and off in cells, thus determining the production of proteins vital to specific cellular functions.

Specifically, researchers performed the largest-to-date GWAS of type 1 diabetes, analyzing 520,580 genome samples to identify 69 novel association signals. They then mapped 448,142 cis-regulatory elements (non-coding DNA sequences in or near a gene) in pancreas and peripheral blood cell types.

"By combining these two methodologies, we were able to identify cell type-specific functions of disease variants and discover a predictive causal role for pancreatic exocrine cells in type 1 diabetes, which we were able to validate experimentally," said Gaulton.

Pancreatic exocrine cells produce enzymes secreted into the small intestine, where they help digest food.

Co-author Maike Sander, MD, professor in the departments of Pediatrics and Cellular and Molecular Medicine at UC San Diego School of Medicine and director of the Pediatric Diabetes Research Center, said the findings represent a major leap in understanding the causes of type 1 diabetes. She described the work as "a landmark study."

"The implication is that exocrine cell dysfunction might be a major contributor to disease. This study provides a genetic roadmap from which we can determine which exocrine genes may have a role in disease pathogenesis."

ITHACA, N.Y. - For the first time, Cornell University researchers have developed a technique for studying the neuroscience of motor control in mice ¬- by focusing on a mouse's tongue when it licks a water spout.

The technique incorporates high-speed cameras and machine learning in a tractable experimental setup that opens the door for revealing mysteries of how the motor cortex works, understanding the neural basis of related disorders like Parkinson's disease, and informing robots.

"We now have an approach in a mouse where we can bring all the tools of modern neuroscience to bear on this really classic problem of motor control," said senior author Jesse Goldberg, associate professor of neurobiology and behavior.

The field of motor control neuroscience has made advancements almost entirely through studies of monkeys reaching for things, Goldberg said. His lab tried for years to develop a mouse model for much faster and more malleable experiments but found too many constraints in getting mice to reach with their limbs; mice lack the necessary biomechanics and nature for such movements.

Tejapratap Bollu, a former graduate student in Goldberg's lab who was working on a different project that involved mice licking a water spout, made a discovery that led to the new technique. The water spouts were fitted with contact sensors, but often, the tongue would miss the target.

Bollu "noticed with his careful eye that [the mice] were actually sticking their tongues out and looking" for the spout, rather than licking as had been assumed, Goldberg said.

The movement in mice, which occurs on time scales of close to 100 milliseconds per lick, is analogous to a monkey reaching and making adjustments with its hand and activates the motor cortex in a surprisingly similar manner, the researchers found.

Using high-speed cameras, the researchers could observe the tongue reaching for the water spout, just as a human reaches for an object. They could also move the water spout, which forced a miss and an immediate correction. At the same time, genetically engineered mice allowed the researchers to use light to turn different parts of the brain on and off while the animals were drinking.

The researchers were able to use brain activation experiments to zoom in on the anterolateral motor cortex. "The electrical signals there exhibited remarkable similarity to the types of electrical signals people observed in primate reach tasks," Goldberg said.

"Now we can do experiments that have never been done before," he said.

Cornell Neurotech has developed technologies that make it possible to record thousands of neurons in an animal at once, for example. In next steps, Goldberg plans to use these tools to characterize for the first time the origins of pathogenic brain signals in neurological disorders, such as Parkinson's disease.

Open up Scott Roy's Twitter bio and you'll see a simple but revealing sentence: "The more I learn the more I'm confused." Now the rest of the scientific world can share in his confusion. The San Francisco State University associate professor of Biology's most recent research, published earlier this month in one of the scientific world's most prestigious journals, catalogues a strange and confounding system of genes in a tiny rodent that scientists have ignored for decades.

"This is basically the weirdest sex chromosome system known to science," Roy said. "Nobody ordered this." But he's serving it anyway.

The owner of those chromosomes is the creeping vole, a burrowing rodent native to the Pacific Northwest. Scientists have known since the '60s that the species had some odd genes: Their number of X and Y chromosomes (bundles of DNA that play a large role in determining sex) is off from what's expected in male and female mammals.

That finding caught Roy's eye when presented by a guest speaker at a San Francisco State seminar, and he realized that modern technology might be able to shed new light on the mysteries hiding in the voles' DNA. After working with collaborators to disentangle the voles' genetic history -- resulting in one of the most completely sequenced mammal genomes that exists, according to Roy -- the story only got stranger.

The team found that the X and Y chromosomes had fused somewhere in the rodents' past, and that the X chromosome in males started looking and acting like a Y chromosome. The numbers of X chromosomes in male and female voles changed too, along with smaller pieces of DNA getting swapped between them. The researchers published their results in Science on May 7.

Drastic genetic changes like these are exceptionally rare: The way genes determine sex in mammals has stayed mostly the same for about 180 million years, Roy explains. "Mammals, with few exceptions, are kind of boring," he said. "Previously we would have thought something like this is impossible."

So how did the genes of this unassuming rodent end up so jumbled? It's not an easy question to answer, especially since evolution is bound to produce some strangeness simply by chance. Roy, however, is determined to figure out the "why." He suspects that what the team found in the vole's genome is something like the aftermath of an evolutionary battle for dominance between the X and Y chromosome.

The research couldn't have happened, Roy says, without collaborations with Oregon fish and wildlife biologists who had a creeping vole sample sitting in a lab freezer. He also teamed up with a group from Oklahoma State University when the two groups started chatting about creeping vole DNA sequences that were posted on the internet -- and both realized they were working on the same question.

Another key was working at a teaching-focused institution. Roy says he has the time to develop ideas with colleagues and students at SF State, and he can do research where he doesn't quite know what he'll find. "This is a great example of non-hypothesis-based biology," Roy explained. "The hypothesis was, 'This system is interesting. I bet if you looked into it some more, there'd be other interesting things.'"

It won't be the last time Roy's lab goes out on a limb. He and his collaborators plan to look into the genomes of other species related to the voles to chart the evolutionary path that led to this strange system. He'll also continue DNA sequencing curiosities across the tree of life.

"These bizarre systems give us a handhold to start to understand why the more common systems are the way they are and why our biology works as it does," he explained. By delving into the weirdest that nature has to offer, maybe we can come to understand ourselves better, too.

Scanning technology aimed at detecting small amounts of nuclear materials was unveiled by scientists in Sweden today, with the hope of preventing acts of nuclear terrorism.

Bo Cederwall, a professor of physics at KTH Royal Institute of Technology, says the technology can be used in airports and seaports for routine inspection of passengers and goods. The research is published and featured in the journals Science Advances and Science, respectively.

A form of tomography, the system enables quick 3D imaging of the source of neutron and gamma ray emissions from weapons-grade plutonium and other special nuclear materials, Cederwall says.

The so-called Neutron-Gamma Emission Tomography (NGET) system goes beyond the capabilities of existing radiation portal monitors, by measuring the time and energy correlations between particles emitted in nuclear fission, and using machine learning algorithms to visualize where they're coming from. The system looks for coincidences of neutron and gamma ray emissions--which when mapped together in real-time allow pinpointing their origin.

"The technology has a very high sensitivity and can within a few seconds detect gram-amounts of plutonium depending on the application and the plutonium isotope composition," Cederwall says. "It takes a little longer to get a really good picture so you can see exactly where the plutonium is. However, this can be done completely automatically."

But NGET isn't only for nuclear weapons and radiation-dispersing "dirty bombs"--it can be used to detect environmental radiation too, such as leaks from nuclear facilities or even natural sources. Cederwall says the research group is looking into equipping drones with the NGET system for this purpose.

"In case of a radiological emergency, It is extremely important to be able to quickly map the radioactive contamination in the environment in order to protect the population in the best possible way," he says.

Despite expert recommendations that children continue to get regularly scheduled vaccines during the pandemic, vaccination rates have decreased in several states.

A new study by researchers from the Texas A&M University School of Public Health and several other research institutions looked at childhood immunization rates in Texas to see what effect the COVID-19 pandemic may have had on childhood immunizations in 2020. In the study, led by public health doctoral student Tasmiah Nuzhath and published in the journal Vaccine, the researchers used data from a statewide immunization registry to determine how immunization rates changed over a 10-year period for children at four age milestones: one month, five months, 16 months and 24 months. The researchers also analyzed county-level data from 2019 and 2020 to compare rural and urban locations.

To see how much effect the pandemic had on vaccination rates in Texas, the research team analyzed data from the ImmTrac2 immunization registry from May 2010 through May 2020. The data was provided by the staff at Texas Department of State Health Services (DSHS) and included immunization records for more than 300,000 Texas children from birth to 24 months. Their analysis found that the proportion of children who were current on recommended vaccines in the four age categories increased between 2010 and 2019. However, there were sharp decreases in vaccination between 2019 and 2020 in most categories, which the authors attributed to the COVID-19 pandemic.

The decline in vaccinations the researchers found was similar to those found in other states. The declines were greatest for the 5-month-old and 16-month-old groups. The age groups saw 47 percent and 58 percent declines, respectively.

Their analysis of county-level data found that 5-month-old children in rural locations had greater declines in immunization rates than those living in urban areas. They also found that there was no decrease in Hepatitis B vaccines at birth. This points to immunizations that take place in clinics or doctor's offices as opposed to hospitals being the most affected by the pandemic.

Researchers also found that uptake of most vaccines appeared to increase prior to the pandemic between May 2010 and May 2019, with the exception of measles vaccine. MMR (measles, mumps and rubella) coverage has been declining in Texas since 2015, and is currently below the 95 percent coverage level required to achieve herd immunity. The already low level of measles vaccination coverage, exacerbated by the pandemic, increases the risk of a measles outbreak in Texas and could have substantial public health consequences.

The findings of this study are in line with those focusing on other states, but the researchers note that the findings are limited by their data source. ImmTrac2 is an opt-in registry, which means that the data may not reflect the population as a whole. However, despite this limitation, the findings point to possible disruptions in vaccination services as well as disparities between rural and urban communities. These results indicate that there is a need for better targeted public health communication to address perceived risks and for improved vaccination infrastructure to help overcome barriers to vaccination in rural areas.

Nearly two thirds (61%) expressed concern about their worsening mood in Lockdown and associated restrictions1.

34% said they felt more anxious and 28% felt more depressed during Lockdown and associated restrictions1.

Coffee helped lift nearly half (44%) of adult's negative moods in Lockdown and associated restrictions1.

A new pan-European survey funded by the Institute for Scientific Information on Coffee exploring the impact of COVID-19 Lockdowns and associated restrictions (in those countries where there has been no Lockdown), has found that nearly two thirds of adults (61%) expressed concern about their worsening mood; two times higher than those concerned about physical inactivity (24%)1.

Understanding the effects of COVID-19 restrictions on physical and mental health

The new survey of 5,170 adults aged over 18, across the UK, Italy, Finland, Germany and Poland, sought to better understand people's perceptions of the effect of COVID-19 restrictions on their physical and mental health, and aspects they felt most impacted their mood. It also sought to explore the role that everyday pleasures such as coffee had, and other simple ways that people found to lift their mood during Lockdowns and associated restrictions1.

In terms of the impact on mental health, 34% admitted to having felt more anxious, and 28% having felt more depressed1. These findings mirror other recent research on the impact of Lockdown and associated restrictions on mental wellbeing, which shows a three-fold increase to the prevalence of anxiety in the general population2 and a seven-fold increase in the prevalence of depression3 globally.

Of those in the survey who identified exercise as playing an important part in their daily routines, nearly a quarter (24%) said that not exercising negatively impacted their mood, while 27% said they used exercise as a means to lift their mood1.

Supporting people to make positive and healthy choices

The research revealed ways people had found helped improve their mood, with nearly half (44%) saying that taking time to enjoy a few cups of coffee a day helped, as did getting more sleep (31%), and eating and drinking more healthily (30%)1.

The finding that coffee had a beneficial effect on people's mood reflects previous research, which demonstrates that coffee helps to improve mood when consumed throughout the day 4, as well as enhancing alertness and attention (concentration) 5.

Nearly a third (28%) of respondents said that coffee helped motivate them to exercise and that it helped enhance their physical performance1. These findings are supported by previous research, which demonstrates that caffeine in coffee helps to improve physical performance during exercise6, 7.

Assistant Professor Giuseppe Grosso, Department of Biomedical and Biotechnological Sciences School of Medicine, University of Catania, commented: "These findings highlight the considerable, and wide reaching impact of Lockdown and associated restrictions. While this is concerning, it is helpful to see that many have found small ways to break up their routines and improve their moods during Lockdown and associated restrictions, through interventions as simple as making time to exercise or enjoying a coffee break."

"With regards to coffee breaks, this beneficial effect is likely two-fold. Firstly through the holistic benefit of taking time to relax and enjoy coffee's flavour and aroma. Additionally, coffee consumption has been demonstrated to improve mood, alertness and reduce feeling of fatigue through the acute effect of caffeine and the potential role of coffee polyphenols in neurogenesis and long-term maintenance of a healthy brain (and consequent reduction in some affective and neurodegenerative disorders)."

Geographic and gender differences

The survey revealed how impacts on mood and depression were most prominent among females, in younger age groups (aged 34 and under), and in parents with dependent children under the age of 18; which may be a result of women bearing a larger share of the home/childcare burden1. Differences were also seen between countries, with Italy and Poland reporting the highest levels of impacted mood, and feelings of anxiety and depression1 which is likely to be, for Italy in particular, reflective of the scale of the COVID-19 crisis.

In fact out of all countries surveyed, when it came to the impact of Lockdown and associated restrictions on dips in mood, this was most keenly felt in Poland where three quarters (75%) of people admitted it had declined, closely followed by Italy (72%), compared to under half in Finland (45%), 50% in the UK and 63% in Germany. Yet, when it came to the role coffee had in improving spirits, around half of people in Italy (53%) and Poland (47%) agreed that drinking a few cups of coffee a day helped to lift their mood, followed by Finland (43%), the UK (37%), and Germany (36%).

The growing appreciation for coffee as part of mood-boosting routines

As many reported a benefit to mood through drinking coffee, it was also found that nearly half of coffee drinkers (42%) increased their intake in Lockdown and associated restrictions. This was particularly the case in Italy with over half (52%) increasing their daily intake, compared to Finland (33%), Germany (39%), Poland (44%) and the UK (38%)1.

Shedding light on the ways that people enjoyed coffee during Lockdown and associated restrictions, it was found that a third (32%) of coffee drinkers said they tended to drink coffee at regular intervals to break up the day at home, whereas 43% said they relied on coffee to start the day and 30% drank coffee at times where they could relax. In fact, 35% of coffee drinkers said they appreciated their coffee breaks more during Lockdown and associated restrictions1.

While the mental wellbeing impact of Lockdown and associated restrictions is far reaching, the survey results highlight that adapting and finding small ways to help lift mood can be beneficial; whether through adopting healthy eating, taking time to enjoy a coffee or making time for exercise1.

WASHINGTON, DC (May 19, 2021) - Human genetics and genomics contributed $265 billion to the U.S. economy in 2019 and has the potential to drive significant further growth given major new areas of application, according to a new report issued today by the American Society of Human Genetics (ASHG). The findings indicate that this research and industry sector has seen its annual impact on the U.S. economy grow five-fold in the last decade and outlined at least eight areas of expanding impact for human health and society. ASHG commissioned and funded the report and is grateful for generous additional contributions from Invitae and Regeneron. Neither company had any direct input into the analyses or report content.

"Twenty years after the Human Genome Project produced the first draft of the human genome sequence, we are seeing in more and more areas the very profound benefits of genetics and genomics to human health," said ASHG President Gail Jarvik, MD, PhD. "This report also reveals the significant benefit to the American economy and outlines future areas of functional application and impact for the field."

The report finds that human genetics and genomics research in 2019 yielded a substantial $4.75 return on every federal dollar invested in it. This determination reflects, in part, an estimated $3.3 billion in 2019 federal funding specifically for human genetics and genomics research, largely at the National Institutes of Health (NIH), in comparison to the $15.5 billion that the field generated and supported in federal tax revenues that year.

"While the report uses a conservative $3.3 billion figure, we were surprised to learn in this analysis that nearly half of all NIH funding has a genetic/genomic component, if not as the focus, then as a tool to support other biomedical research," said Lynn B. Jorde, PhD, Chair of ASHG's Government and Public Advocacy Committee. "It demonstrates how foundational genetics is for biomedical research today."

The impact on job creation is equally robust. Human genetics and genomics research enabled and supported a total of 850,000 jobs in 2019, including direct and indirect employment. This number included 152,000 industry jobs across core private-sector genetics/genomics companies (more than 89,000 jobs) and in extended industries such as major pharmaceutical and medical testing/diagnostics companies where human genetics plays an increasingly important role (nearly 63,000 jobs).

According to Jarvik, all medical science produces great returns to individuals and to society, and human genetics and genomics research is an enormous contributor in both respects. "This field is perhaps one of the best examples of the value of scientific research to our entire economy and of the case for continuing to build on that investment," she said.

To illustrate the scope of current uses of genetics or genomics, the report highlights eight major categories for emerging or future medical application: minable big data, identification of genetic predisposition to diseases and disorders, diagnosis of diseases, rational drug development that relies on genetic information to target molecules in drug design, pharmacogenomics (or personalized medicine), gene editing and gene therapy, human-microbe genetic interactions, and human-environment metagenome interactions. In addition, it describes non-medical applications as diverse as forensic science, anthropology and evolutionary biology, ancestry testing, and paternity testing.

"The report relied on 2019 data, but 2020 showed us the enormous value of genomic sequencing for viruses alone, with the creation of mRNA-based COVID-19 vaccines in an unprecedented timeframe," said Simon Tripp, a Principal and Senior Director at TEConomy Partners, and co-author of the report. "In another example, we can see that genomics-based precision medicine is not only growing in applications for cancer treatment, it is also advancing applications in the treatment of heart disease, rheumatoid arthritis, Alzheimer disease, multiple sclerosis, and many other conditions." Tripp also notes that the field of genetics and genomics is absolutely essential in developing diagnostics and treatments for thousands of rare diseases, which collectively affect more than 25 million people in the U.S. and 250 million worldwide.

Methodology:

To assess the field's total economic impact, the report's authors considered direct, indirect, and induced effects. Direct effects included human genetics and genomics research expenditures, services and corporate operations in the U.S. Indirect effects were defined as purchase of secondary inputs and services from U.S. suppliers and manufacturers. Induced effects were comprised of disposable income spending in the U.S. economy by those employed in human genetics and genomics research and related industries. All estimates in the report represent the most conservative numbers identified in the process of the authors' analysis. The estimation of economic impact is based on an input-output (I-O) model. For modeling and estimating expenditure impacts, TEConomy used a 2019 IMPLAN I-O economic impact model of the U.S. IMPLAN is the nation's most widely used economic impact modeling data and analysis platform.

Chronic exposure to second-hand smoke results in lower body weight and cognitive impairments that more profoundly affects males, according to new research in mice led by Oregon Health & Science University.

The study published today in the journal Environmental Health Perspectives.

"The hope is that we can better understand these effects for policymakers and the next generation of smokers," said lead author Jacob Raber, Ph.D., professor of behavioral neuroscience in the OHSU School of Medicine. "Many people still smoke, and these findings suggest that that the long-term health effects can be quite serious for people who are chronically exposed to second-hand smoke."

The research examined daily exposure of 62 mice over a period of 10 months. Researchers used a specially designed "smoking robot" that went through a pack of cigarettes a day in ventilated laboratory space at OHSU. The longest previous study of this kind lasted three months.

"Nobody has done this, ever. This study is unique," Raber said. "It really gives you the ability to look at long-term effects."

"This study more accurately replicates the human experience by daily exposing mice to cigarette smoke," added senior author Glen Kisby, Ph.D., professor of pharmacology at Western University of Health Sciences in Lebanon, Oregon.

Second-hand smoke is already considered a risk factor for dementia in people, but the new study put the theory to the test.

Researchers first divided mice into two groups - one wild-type and one expressing the human tau protein, important in Alzheimer's-like dementia. Starting in April of 2018, they exposed mice to cigarette smoke for 168 minutes a day, then conducted behavioral and cognitive testing. They also examined lung and brain tissue.

Key findings:

Smoke harms 'healthy' mice. Researchers theorized that second-hand smoke would be especially harmful for mice with the human tau protein. However, "we actually found the opposite," Raber said. In many of the behavioral and cognitive tests - including swimming speeds and migrating through a maze - wild-type mice were more affected than human tau mice after both groups were exposed to second-hand smoke.

Smoke especially harms males. Researchers discerned a clear sex-related difference in cognition, with clearly discernable changes in the hippocampus region of the brain among males compared to females.

Loss in body weight. Researchers found lower body weights in wild-type mice following second-hand smoke compared with human tau mice. Further, they also noticed that males were disproportionately impacted by a loss in body weight compared to females.

Brain changes: Researchers discovered more profound changes in metabolic pathways, which are linked chemical reactions, in the brains of wild-type males than females. Researchers also found more profound effects in the brains of wild-type than the human tau mice.

Although smoking rates have declined in recent generations in some countries, smoking - and exposure to second-hand smoke - remains widespread in much of the world. The World Health Organization estimates 1.5 to 1.9 billion people worldwide will be smokers in 2025.

"Long-term exposure to second-hand smoke triggers detrimental changes," Raber said. "Based on our study, it seems that males might be more susceptible than females. People should take that into consideration."