Culture

College course syllabi written in a warm, friendly tone are more likely to encourage students to reach out when they are struggling or need help, a new study from Oregon State University found.

Conversely, when a syllabus is written in a more cold, detached tone, students are less likely to reach out.

The study also compared the effect of syllabus tone with the effect of a deliberate "Reach out for help" statement included in the document.

"The instructor has to ask themselves, what's the first point of contact with the class for the student? In an online class and in remote learning, the syllabus is often the first thing. An impression of the course and you the instructor is formed on the syllabus," said Regan A.R. Gurung, lead author of the study and director of the general psychology program in OSU's College of Liberal Arts.

"In the old days, before Canvas and other online teaching tools, the student wouldn't see the syllabus until I handed it out. That gave me a lot of time to create that impression," he said. Now, however, students often read syllabi to determine if they want to take a course or not.

During the pandemic, when the majority of courses have moved online and students may be struggling with more stress and pressure than they would in a normal school year, conveying that it's OK to ask for help is even more important, Gurung said.

The study, published recently in the journal Teaching of Psychology, recruited 257 student volunteers from introductory psychology courses at OSU. They were tasked with reading one of four sample syllabi: warm-toned with or without a "reach out" statement, or cold-toned with or without the "reach out" statement.

The warm-toned syllabi included phrases like "I welcome you to contact me outside of class and student hours," and used more "We will" framing instead of the cold-toned version's "You will."

Student participants rated the hypothetical instructor based on the syllabus and answered some basic questions to verify they had read the document. They then ranked how likely they would be to reach out to the professor in each of five situations: help on an assignment, when feeling low, personal issues with friends or family, medical issues and to ask about campus resources.

"Reach out" statements have become more popular in recent years as a way to destigmatize mental health needs and point students toward available mental health and academic resources. But the study found that syllabus tone, more than these statements, made students more likely to seek help.

Results showed an increase in likelihood to reach out on three of the five situations among students who read the warm-tone syllabi, while students who read the syllabi with a "reach out" statement were more likely to ask for help in only one of the five situations. Warm versus cold tone had no impact on how students perceived the instructor's overall competence.

Gurung cautioned that the study is limited by being performed in lab conditions rather than in a real classroom. Researchers capped the syllabi used for the study at two pages each, when real course syllabi may be 15 pages or more. And the syllabus was the sole component for students to judge.

"But that's exactly why I think a study like this is powerful -- that even without that human component, even something as black-and-white as a syllabus can make a difference," Gurung said. "If you're a great approachable person, good for you; you'll just be able to magnify these effects."

With this study, researchers are not suggesting that professors ditch all discipline or craft an overly touchy-feely syllabus.

It's the difference between rapport and rules, Gurung said.

"You can absolutely have rules, and you should be firm and you should be fair and you should be clear, but that is sort of separate from your interaction with the student as a person," he said. "You don't have to be extroverted or cracking jokes, but you can still show that you listen."

A recent study of how human resources professionals review online information and social media profiles of job candidates highlights the ways in which so-called "cybervetting" can introduce bias and moral judgment into the hiring process.

"The study drives home that cybervetting is ultimately assessing each job candidate's moral character," says Steve McDonald, corresponding author of the study and a professor of sociology at North Carolina State University. "It is equally clear that many of the things hiring professionals are looking at make it more likely for bias to play a role in hiring."

For this study, the researchers conducted in-depth interviews with 61 human resources professionals involved in recruitment and hiring across many industries. Study participants ranged from in-house HR staff to executive recruitment consultants to professionals at staffing agencies.

"One of the things that cropped up repeatedly was that cybervetting not only judges people's behavior, but how that behavior is presented," says Amanda Damarin, co-author of the paper and an associate professor of sociology at Georgia State University. "For example, one participant noted that his organization had no problem with employees drinking alcohol, but did not want to see any photos of alcohol in an employee's social media feed.

"There's a big disconnect here. One the one hand, HR professionals view social media as being an 'authentic' version of who people really are; but those same HR professionals are also demanding that people carefully curate how they present themselves on social media."

"It was also clear that people were rarely looking for information related to job tasks - a point some study participants brought up themselves," McDonald says. "And the things they did look for reflected their explicit or implicit biases."

For example, study participants referenced looking for things like posts about hiking and family photos of Christmas. But most people who hike are white, and most people who post Christmas photos are Christians. Study participants also expressed a preference for online profiles that signaled "active" and "energetic" lifestyles, which could lead to discrimination against older or disabled job seekers.

And it was often unclear what job candidates could do to address concerns about bias in cybervetting. For example, while many study participants noted that putting a photo online created the opportunity for bias to affect the hiring process, other study participants noted that not having a "professional" profile picture was in itself a "red flag."

"Some workers have a social media profile that sends the right signals and can take advantage of cybervetting," McDonald says. "But for everyone else, they are not only at a disadvantage, but they don't even know they are at a disadvantage - much less why they are at a disadvantage. Because they don't necessarily know what employers are looking for."

"Some of the people we interviewed were very aware that cybervetting could lead to increased bias; some even avoided cybervetting for that reason," Damarin says. "But others were enthusiastic about its use."

Researchers say one of the key takeaways from the work is that there need to be clear guidelines or best practices for the use of cybervetting, if it is going to be used at all.

"The second takeaway is that the biases and moral judgments we are hearing about from these HR professionals are almost certainly being incorporated into software programs designed to automate the review of job candidates," McDonald says. "These prejudices will simply be baked into the algorithms, making them a long-term problem for both organizations and job seekers."

This release has been removed upon request of the submitting institution. Please contact Ilyana Zolotareva, I.Zolotareva@skoltech.ru for more information.

An analysis of law enforcement seizures of illegal drugs in five key regions of the United States revealed a rise in methamphetamine and marijuana (cannabis) confiscations during the COVID-19 pandemic. Seizures of the two drugs were higher at their peak in August 2020 than at any time in the year prior to the pandemic. While investigators found that trends in heroin, cocaine and fentanyl seizures were not affected by the pandemic, provisional overdose death data show that the increased drug mortality seen in 2019 rose further through the first half of 2020.

The findings suggest that the pandemic and its related restrictions may have impacted the availability and demand of some, but not all, illegal drugs, and that availability may have increased in summer and fall of 2020 in the five regions included in this study.

The study, published today in Drug and Alcohol Dependence, was supported by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.

"At the beginning of the pandemic, it was unclear how social distancing, travel restrictions and economic hardship in communities would impact drug supply and demand," said Nora D. Volkow, M.D., NIDA director. "Drug seizure data like these give us additional insight into the changing drug use landscape during COVID-19 and may inform our understanding of rising rates of methamphetamine- and opioid-involved overdose deaths during the pandemic."

Measures to address the COVID-19 pandemic have limited social gatherings, closed international borders, and reduced economic activity across many sectors. While provisional data reveal drug overdose deaths have risen during the pandemic, there is little scientific evidence to illuminate the impact of these measures on drug availability and use in the United States.

Seeking answers, investigators led by Joseph J. Palamar, Ph.D., M.P.H., associate professor at the New York University Grossman School of Medicine and co-investigator on the National Drug Early Warning System (NDEWS), mined data on drug seizures by law enforcement. The data were collected through the High Intensity Drug Trafficking Areas program, a grant program aimed at reducing drug trafficking and misuse administered by the Office of National Drug Control Policy in which the Drug Enforcement Administration and the Centers for Disease Control and Prevention play an active role.

Drug seizure data from March 2019 through September 2020 was analyzed in five key U.S. regions: Washington, D.C./Baltimore, Chicago, Ohio, New Mexico, and North Florida. Investigators analyzed 29,574 seizures of five drugs: marijuana, methamphetamine, fentanyl, heroin, and cocaine.

Incidences of marijuana and methamphetamine seizures dipped at the beginning of the pandemic, with low points in April 2020. But confiscations of both substances subsequently rose, exceeding pre-COVID-19 seizure rates and reaching their peaks in August 2020. The quantities of marijuana seized, measured by weight, also climbed significantly from April through September 2020.

While decreases in seizures can indicate decreases in drug availability in communities, it is also possible that decreases may indicate reduced law enforcement during the early months of the pandemic. Study authors noted that it remains unknown if the high post-COVID-19 seizures represent greater drug availability, or whether law enforcement officials were merely 'catching up' regarding previous months of delayed seizures.

Investigators found no significant shifts in the pattern of fentanyl, cocaine, or heroin seizures since the onset of COVID-19, although they emphasize fentanyl seizures have continued to rise steadily from March 2019 through September 2020 irrespective of the pandemic.

"Our understanding of how the COVID-19 pandemic affects drug use is evolving, but we do know that social isolation, even for short periods, can cause psychological distress that may drive some people to seek out psychoactive substances," said Dr. Palamar. "It is critical for us to obtain a clearer picture of how the pandemic has influenced drug supply and demand, so that we may better mitigate potential harmful effects of changing drug use patterns."

The researchers emphasize drug seizure rates are only rough measures of drug availability and use and that additional research is needed to understand how individuals' drug use may be changing during the pandemic. These are critical public health questions, as changes in an individual's drug use--such as abruptly stopping a certain substance or switching to a different one--can increase the chance of drug-related harm, such as withdrawal or overdose. Additionally, further research is needed to assess if patterns observed in these key U.S. regions extend to other parts of the country.

Overdose deaths involving methamphetamine started rising steeply in 2009, and provisional numbers from the CDC show overdose deaths involving stimulant drugs, including methamphetamine, have increased 39% in the year ending in June 2020 compared to the year ending in June 2019. Previous research has found that methamphetamine use has increased significantly among people with an existing opioid use disorder and has disproportionately impacted certain racial and ethnic communities, especially American Indians/Alaska Natives.

In the 1995 movie "Outbreak," Dustin Hoffman's character realizes, with appropriately dramatic horror, that an infectious virus is "airborne" because it's found to be spreading through hospital vents.

The issue of whether our real-life pandemic virus, SARS-CoV-2, is "airborne" is predictably more complex. The current body of evidence suggests that COVID-19 primarily spreads through respiratory droplets - the small, liquid particles you sneeze or cough, that travel some distance, and fall to the floor. But consensus is mounting that, under the right circumstances, smaller floating particles called aerosols can carry the virus over longer distances and remain suspended in air for longer periods. Scientists are still determining SARS-CoV-2's favorite way to travel.

That the science was lacking on how COVID-19 spreads seemed apparent a year ago to Tami Bond, professor in the Department of Mechanical Engineering and Walter Scott, Jr. Presidential Chair in Energy, Environment and Health. As an engineering researcher, Bond spends time thinking about the movement and dispersion of aerosols, a blanket term for particles light and small enough to float through air ­- whether cigarette smoke, sea spray, or hair spray.

"It quickly became clear there was some airborne component of transmission," Bond said. "A virus is an aerosol. Health-wise, they are different than other aerosols like pollution, but physically, they are not. They float in the air, and their movement depends on their size."

The rush for scientific understanding of the novel coronavirus has focused - understandably - on biological mechanisms: how people get infected, the response of the human body, and the fastest path to a vaccine. As an aerosol scientist, Bond went a different route, convening a team at Colorado State University that would treat the virus like any other aerosol. This team, now published in Environmental Science and Technology, set out to quantify the dynamics of how aerosols like viruses travel from one person to another, under different circumstances.

The cross-section of expertise to answer this question existed in droves at CSU, Bond found. The team she assembled includes epidemiologists, aerosol scientists, and atmospheric chemists, and together they created a new tool for defining how infectious pathogens, including SARS-CoV-2, transport in the air.

Effectively rebreathed air

Their tool is a metric they're calling Effective Rebreathed Volume, or simply, the amount of exhaled air from one person that, by the time it travels to the next person, contains the same number of particles. Treating virus-carrying particles agnostically like any other aerosol allowed the team to make objective, physics-based comparisons between different modes of transmission, accounting for how sizes of particles would affect the number of particles that traveled from one person to another.

They looked at three size categories of particles that cover a biologically relevant range: 1 micron, 10 microns, and 100 microns -- about the width of a human hair. Larger droplets expelled by sneezing would be closer to the 100-micron region. Particles closer to the size of a single virion would be in the 1-micron region. Each have very different air-travel characteristics, and depending on the size of the particles, different mitigation measures would apply, from opening a window, to increasing fresh air delivery with through an HVAC system.

They compiled a set of models to compare different scenarios. For example, the team compared the effective rebreathed volume of someone standing outdoors 6 feet away, to how long it would take someone to rebreathe the same amount of air indoors but standing farther away.

Confinement matters

The team found that distancing indoors, even 6 feet apart, isn't enough to limit potentially harmful exposures, because confinement indoors allows particle volumes to build up in the air. Such insights aren't revelatory, in that most people avoid confinement in indoor spaces and generally feel safer outdoors. What the paper shows, though, is that the effect of confinement indoors and subsequent particle transport can be quantified, and it can be compared to other risks that people find acceptable, Bond said.

Co-authors Jeff Pierce in atmospheric science and Jay Ham in soil and crop sciences helped the team understand atmospheric turbulence in ways that could be compared in indoor and outdoor environments.

Pierce said he sought to constrain how the virus-containing particles disperse as a function of distance from the emitting person. When the pandemic hit last year, the public had many questions about whether it was safe to run or bike on trails, Pierce said. The researchers found that longer-duration interactions outdoors at greater than 6-foot distances appeared safer than similar-duration indoor interactions, even if people were further apart indoors, due to particles filling the room rather than being carried away by wind.

"We started fairly early on in the pandemic, and we were all filled with questions about: 'Which situations are safer than others?' Our pooled expertise allowed us to find answers to this question, and I learned a lot about air filtration and air exchange in my home and in my CSU classroom," Pierce said.

More to learn

What remains unclear is which size particles are most likely to cause COVID-19 infection.

Viruses can be carried on droplets large and small, but there is likely a "sweet spot" between droplet size; ability to disperse and remain airborne; and desiccation time, all of which factor into infective potential, explained Angela Bosco-Lauth, paper co-author and assistant professor in biomedical sciences.

The paper includes an analysis of the relative infection risk of different indoor and outdoor scenarios and mitigation measures, depending on the numbers of particles being inhaled.

"The problem we face is that we still don't know what the infectious dose is for people," Bosco-Lauth said. "Certainly, the more virus present, the higher the risk of infection, but we don't have a good model to determine the dose for people. And quantifying infectious virus in the air is tremendously difficult."

Follow-up pursuits

The team is now pursuing follow-up questions, like comparing different mitigation measures for reducing exposures to viruses indoors. Some of these inquiries fall into the category of "stuff you already know, but with numbers," Bond said. "People are now thinking, OK, more ventilation is better, or remaining outside is better, but there is not a lot of quantification and numbers behind those recommendations," Bond said.

Bond hopes the team's work can lay a foundation for more up-front quantification of transmission dynamics in the unfortunate event of another pandemic. "This time, there was a lot of guessing at the beginning, because the science of transmission wasn't fully developed," she said. "There shouldn't be a next time."

Amyloid plaques are pathological hallmarks of Alzheimer's disease (AD) -- clumps of misfolded proteins that accumulate in the brain, disrupting and killing neurons and resulting in the progressive cognitive impairment that is characteristic of the widespread neurological disorder.

In a new study, published March 2, 2021 in the Journal of Experimental Medicine (JEM), researchers at University of California San Diego School of Medicine, Massachusetts General Hospital and elsewhere have identified a new drug that could prevent AD by modulating, rather than inhibiting, a key enzyme involved in forming amyloid plaques.

In studies using rodents and monkeys, the researchers report the drug was found to be safe and effective, paving the way for possible clinical trials in humans.

"Alzheimer's disease is an extraordinarily complex and multi-faceted condition that has, so far, defied effective treatment, let alone prevention," said senior author Steven L. Wagner, PhD, professor in the Department of Neurosciences at UC San Diego School of Medicine. "Our findings suggest a potential therapy that might prevent one of the key elements of AD."

Amyloid plaques are composed of small protein fragments called amyloid beta (Aβ) peptides. These peptides are generated by enzymes called β-secretase and γ-secretase, which sequentially cleave a protein called amyloid precursor protein on the surfaces of neurons to release Aβ fragments of varying lengths. Some of these fragments, such as Aβ42, are particularly prone to forming plaques, and their production is elevated in patients with mutations predisposing them to early-onset AD.

Several attempts have been made to treat or prevent AD using drugs that inhibit either β-secretase or γ-secretase, but many of these drugs have proved to be highly toxic or unsafe in humans, likely because β-secretase and γ-secretase are required to cleave additional proteins in the brain and other organs.

Instead, Wagner and colleagues investigated the therapeutic potential of drugs known as γ-secretase modulators or GSMs, which instead of inhibiting the γ-secretase enzyme, slightly alter its activity so that it produces fewer Aβ peptides that are prone to form plaques while continuing to duties cleaving other protein targets.

"GSMs offer the ability to mitigate mechanism-based toxicities associated with γ-secretase inhibitors," said Wagner.

In the new JEM study, researchers created a novel GSM and tested it on mice, rats and macaques. They found that repeated, low doses of the GSM eliminated Aβ42 production in mice and rats, without causing any toxic side effects. The drug was also safe and effective in macaques, reducing Aβ42 levels by up to 70 percent.

The novel GSM was then tested in a mouse model of early-onset AD, treating the animals either before or shortly after they began to form amyloid plaques. In both cases, the novel GSM decreased plaque formation and reduced plaque-associated inflammation, which is thought to contribute to the development of disease.

The findings suggest that the novel GSM could be used prophylactically to prevent AD, write the authors, either in patients with genetic mutations that increase susceptibility to AD or in cases where amyloid plaques have been detected by brain scans.

"In this study, we have pharmacologically characterized a potent GSM that, based on its preclinical attributes, appears to equal or exceed the potency of any previously tested GSMs," said co-author Rudolph Tanzi, PhD, professor neurology at Harvard Medical School and director of the Genetics and Aging Research Unit at Massachusetts General Hospital.

"Future clinical trials will determine whether this promising GSM is safe in humans and could be used to effectively treat or prevent Alzheimer's disease."

An estimated 5 million Americans are living with AD. The number of people with AD doubles every five years beyond age 65, according to the Centers for Disease Control, with the total number of Americans with the disease projected to nearly triple to 14 million by 2060. Currently, there is no known cure, only symptomatic therapies.

Our brains are non-stop consumers. A labyrinth of blood vessels, stacked end-to-end comparable in length to the distance from San Diego to Berkeley, ensures a continuous flow of oxygen and sugar to keep our brains functioning at peak levels.

But how does this intricate system ensure that more active parts of the brain receive enough nourishment versus less demanding areas? That's a century-old problem in neuroscience that scientists at the University of California San Diego have helped answer in a newly published study.

Studying the brains of mice, a team of researchers led by Xiang Ji, David Kleinfeld and their colleagues has deciphered the question of brain energy consumption and blood vessel density through newly developed maps that detail brain wiring to a resolution finer than a millionth of a meter, or one-hundredth of the thickness of a human hair.

A result of work at the crossroads of biology and physics, the new maps provide novel insights into these "microvessels" and their various functions in blood supply chains. The techniques and technologies underlying the results are described March 2 in the journal Neuron.

"We developed an experimental and computational pipeline to label, image and reconstruct the microvascular system in whole mouse brains with unprecedented completeness and precision," said Kleinfeld, a professor in the UC San Diego Department of Physics (Division of Physical Sciences) and Section of Neurobiology (Division of Biological Sciences). Kleinfeld says the effort was akin to reverse engineering nature. "This allowed Xiang to carry out sophisticated calculations that not just related brain energy use to vessel density, but also predicted a tipping point between the loss of brain capillaries and a sudden drop in brain health."

Questions surrounding how blood vessels carry nourishment to active and less active regions were posed as a general issue in physiology as far back as 1920. By the 1980s, a technology known as autoradiography, the predecessor of modern-day positron emission tomography (PET), allowed scientists to measure the distribution of sugar metabolism across the mouse brain.

To fully grasp and solve the problem, Ji, Kleinfeld and their colleagues at the Howard Hughes Medical Institute's Janelia Research Campus and UC San Diego Jacobs School of Engineering filled 99.9 percent of the vessels in the mouse brain--a count of nearly 6.5 million--with a dye-labeled gel. They then imaged the full extent of the brain with sub-micrometer precision. This resulted in fifteen trillion voxels, or individual volumetric elements, per brain, that were transformed into a digital vascular network that could be analyzed with the tools of data science.

With their new maps in hand, the researchers determined that the concentration of oxygen is roughly the same in every region of the brain. But they found that small blood vessels are the key components that compensate for varying energy requirements. For example, white matter tracts, which transfer nerve impulses across the two brain hemispheres and to the spinal cord, are regions of low energy needs. The researchers identified lower levels of blood vessels there. By contrast, brain regions that coordinate the perception of sound use three times more energy and, they discovered, were found with a much greater level of blood vessel density.

"In the era of increasing complexities being unraveled in biological systems, it is fascinating to observe the emergence of shared simple and quantitative design rules underlaying the seemingly complicated networks across mammalian brains," said Ji, a graduate student in physics.

Up next, the researchers hope to drill down into the finer aspects of their new maps to determine the detailed patterns of blood flow into and out from the entire brain. They will also pursue the largely uncharted relationship between the brain and the immune system.

Researchers at the University of California San Diego School of Medicine and Massachusetts General Hospital have identified a new drug that could prevent Alzheimer’s disease by modulating, rather than inhibiting, a key enzyme involved in forming amyloid plaques in the brain. The study, which will be published March 2 in the Journal of Experimental Medicine (JEM), demonstrates that the drug is safe and effective in rodents and monkeys, paving the way for future clinical trials in humans.

A key pathological hallmark of Alzheimer’s disease involves the formation of amyloid plaques composed of small protein fragments known as amyloid-β (Aβ) peptides. These peptides are generated by enzymes called β-secretase and γ-secretase, which sequentially cleave a protein called amyloid precursor protein on the surface of neurons to release Aβ fragments of varying lengths. Some of these fragments, such as Aβ42, are particularly prone to forming amyloid plaques, and their production is elevated in patients with mutations predisposing them to early-onset Alzheimer’s disease.

Several attempts have been made to treat or prevent Alzheimer’s disease using drugs that inhibit either β-secretase or γ-secretase. But many of these drugs have proved to be unsafe in humans, likely because β-secretase and γ-secretase are required to cleave additional proteins in the brain and other organs. A better approach could involve drugs known as γ-secretase modulators (GSMs), which, instead of inhibiting the γ-secretase enzyme, slightly alter its activity so that it produces fewer Aβ peptides that are prone to form plaques while continuing to cleave its other protein targets.

“GSMs therefore offer the ability to mitigate mechanism-based toxicities associated with γ-secretase inhibitors,” says Steven L. Wagner, PhD, a professor in the Department of Neurosciences at UC San Diego School of Medicine.

In the new study, Wagner and colleagues developed a novel GSM and tested it on mice, rats, and macaques. Repeated low doses of the drug completely eliminated Aβ42 production in mice and rats without causing any toxic side effects. The drug was also safe and effective in macaques, reducing Aβ42 levels by up to 70%.

The researchers then tested the drug in a mouse model of early-onset Alzheimer’s disease, treating the animals either before or shortly after they began to form amyloid plaques. In both cases, the novel GSM decreased plaque formation and reduced plaque-associated inflammation, which is thought to contribute to the development of disease.

This suggests that the drug could be used prophylactically to prevent Alzheimer’s disease, either in patients with genetic mutations that increase susceptibility to the disease or in cases where amyloid plaques have been detected by brain scans.

“In this study, we have pharmacologically characterized a potent GSM that, based on its preclinical attributes, appears to equal or exceed the potency of any previously tested GSMs,” adds Dr. Rudolph E. Tanzi, Professor of Neurology at Harvard and Massachusetts General Hospital. “Future clinical trials will determine whether this promising GSM is safe in humans and could be used to effectively treat or prevent Alzheimer’s disease.”

Law enforcement seizures of drugs, particularly marijuana and methamphetamine, dropped at the beginning of the COVID-19 pandemic, then increased significantly in the following months--exceeding pre-pandemic seizure rates and providing clues about the impact of the crisis on substance use, according to a new study in the journal Drug and Alcohol Dependence.

The research was conducted as part of the National Drug Early Warning System (NDEWS), which uses real-time surveillance to detect early signals of potential drug epidemics. NDEWS is led by a team of researchers at the University of Florida, New York University, and Florida Atlantic University, and is funded by the National Institute on Drug Abuse, part of the National Institutes of Health.

Early research about how the pandemic has affected patterns of substance use has yielded mixed results. Some sources suggest that overall drug use has increased, while others point to a drop in use and availability of certain drugs. During the same period, multiple studies show an increase in overdoses.

Given conflicting information about changes in drug use, availability, and overdoses after the onset of the COVID-19 pandemic, NDEWS researchers examined trends in drug seizures recorded in the National High Intensity Drug Trafficking Area Program's Performance Management Process database to gain additional insight as to how the pandemic and its associated restrictions have shifted drug use.

"Although seizure data is not the most robust indicator of the prevalence of drug use, it does serve as an indicator of drug supply and availability," said study author Joseph Palamar, PhD, MPH, an associate professor of population health at NYU Grossman School of Medicine, an affiliated researcher with the Center for Drug Use and HIV/HCV Research (CDUHR) at NYU School of Global Public Health, NDEWS co-investigator and chair of the NDEWS Scientific Advisory Group. "For example, fewer seizures, or lower volumes of drugs seized, can reflect a disruption of drug supply chains."

The researchers looked at trends in 29,574 seizures of marijuana, cocaine, methamphetamine, heroin, and fentanyl within five geographic areas: Washington/Baltimore, Chicago, Ohio, New Mexico, and North Florida. They examined the number and total weight of seizures from March 2019, a year before the pandemic began in the U.S., through September 2020, six months into the pandemic.

They detected a sharp decrease in drug seizures--particularly marijuana and methamphetamine--in March and April 2020, when stay-at-home orders were put into place across the country. After reaching a low point in April, the number of seizures then increased through the remainder of the spring and summer when social distancing measures became more relaxed, peaking in August 2020. The weight of drugs seized by law enforcement also significantly increased after April, driven by an increase in volume of marijuana seizures.

Notably, the August peaks in the number and volume of seizures for marijuana and methamphetamine were higher than a year earlier. However, it is unknown whether the peaks represent greater availability of the drugs or whether law enforcement officials were merely "catching up" after several months of delayed seizures.

The researchers did not detect significant shifts in seizures involving cocaine, heroin, or fentanyl during the early months of the COVID-19 pandemic, although seizures involving fentanyl slowly increased in a stable manner over the two years independent of the pandemic.

The study authors noted that more research is warranted to determine the extent to which these seizures reflect changes in drug use. While decreases in seizures, for instance, likely indicate lower availability, it is also possible that fewer seizures may have indicated less drug law enforcement activity during the early months of the pandemic.

"Future research should harmonize data on seizures with other studies of drug use, availability, and overdoses in order to determine the most accurate picture of drug use trends during the pandemic," added Linda B. Cottler, PhD, MPH, FACE, of the University of Florida and principal investigator of NDEWS.

The backbone is the Swiss Army Knife of mammal locomotion. It can function in all sorts of ways that allows living mammals to have remarkable diversity in their movements. They can run, swim, climb and fly all due, in part, to the extensive reorganization of their vertebral column, which occurred over roughly 320 million years of evolution.

Open any anatomy textbook and you'll find the long-standing hypothesis that the evolution of the mammal backbone, which is uniquely capable of sagittal (up and down) movements, evolved from a backbone that functioned similar to that of living reptiles, which move laterally (side-to-side). This so called "lateral-to-sagittal" transition was based entirely on superficial similarities between non-mammalian synapsids, the extinct forerunners of mammals, and modern-day lizards.

In a paper published on March 2 in Current Biology, a team of researchers led by Harvard University challenge the "lateral-to-sagittal" hypothesis by measuring vertebral shape across a broad sample of living and extinct amniotes (reptiles, mammals, and their extinct relatives). Using cutting-edge techniques they map the impact of evolutionary changes in shape on the function of the vertebral column and show that non-mammalian synapsids moved their backbone in a manner that was distinctly their own and quite different from any living animal.

The team, led by first author Katrina E. Jones, former Postdoctoral Researcher, Department of Organismic and Evolutionary Biology, Harvard University, found that while the degree of sagittal bending does increase during mammal evolution, the backbones of the earliest synapsids were optimized for stiffness and the evolutionary transition to mammals did not include a stage characterized by reptile-like lateral bending. Instead they discovered that modern lizards and other reptiles have a unique backbone morphology and function that does not represent ancestral locomotion, and that the earliest ancestors of mammals did not move like a lizard, as scientists previously posited.

"The long-held idea that there was a transition in mammal evolution directly from lateral to sagittal bending is far too simple, said Senior author Stephanie Pierce, Thomas D. Cabot Associate Professor in the Department of Organismic and Evolutionary Biology and curator of vertebrate paleontology in the Museum of Comparative Zoology at Harvard University. "Lizards and mammals diverged from one another millions of years ago and they've each gone on their own evolutionary journey. We show that living lizards don't represent any sort of ancestral morphology or function that the two groups would have had in common so long ago."

Co-author Ken Angielczyk, MacArthur Curator of Paleomammalogy, Negaunee Integrative Research Center, Field Museum of Natural History, agreed, "Reptiles have been evolving just as long as mammals and because of that there's just as much time for changes and specializations to accumulate for reptiles. If you look at the vertebrae of a modern lizard or crocodile their vertebrae are actually very different from early ancestors of mammals and reptiles that lived at the same time around 300 million years ago. Both living mammals and reptiles have accumulated their own set of specializations over evolutionary time."

Jones and co-authors, including former Harvard graduate student Blake Dickson, PhD '20, began by measuring the shape of the vertebrae of a range of reptiles, mammals, salamanders, and some fossil non-mammalian synapsids. The specimens came from museum collections all over the world, with modern animal skeletons primarily from the Museum of Comparative Zoology (MCZ), and fossil synapsids from the MCZ, the Field Museum of Natural History, and various other museums in the USA, Europe, and South Africa.

"We first had to quantify the shape of the vertebrae and that's actually a little bit tricky," said Jones. "Each vertebral column is made up of multiple vertebrae and when you have different numbers of vertebrae their shapes and functions might divide up in different ways."

They selected five vertebrae at equivalent locations from each of the vertebral columns and measured their shapes across the different animals in three-dimension. The results showed quantitatively that non-mammalian synapsid vertebrae are very different from the vertebrae of modern mammals, and critically also from the vertebrae of lizards and other reptiles.

Next, the researchers examined how the vertebrae may have functioned using data from their previous work that compared vertebral shape to degree of vertebral motion in living lizards and mammals, providing a crucial link between form and function. The data enabled the researchers to map variation in vertebral function across the broad sample of animals, including the fossils, which allowed them to reconstruct the precise combination of functional traits that described each group of animals.

"Our team's approach to data analysis is exciting as it can reveal how different backbone shapes may result in different functional tradeoffs," Pierce said. Reptiles, for example, are very good at lateral bending, but are unable to move their spine up-and-down like mammals. "In addition to lateral and sagittal bending we also examined other functions of the backbone and then determined the optimal combination of tradeoffs for mammals, reptiles, and non-mammalian synapsids," said Pierce.

"We were able to show that non-mammalian synapsids have a different combination of functions in their backbone to both living reptiles and mammals," Jones said, "and in the course of that evolution they weren't just traversing from the reptile-like lateral to the mammal-like sagittal bending, they were actually on a completely distinctive path in which they were evolving from a separate condition."

"The historical expectation is that the synapsid ancestors of mammals were making the same set of tradeoffs that modern reptiles do. But it turns out that they have an entirely different set of tradeoffs," Angielczyk said. "The expectation that reptiles would retain ancestral locomotor patterns that existed over 320 million years ago is too simple."

The results show the backbones of non-mammalian synapsids were actually quite stiff and completely unlike those of lizards which are very compliant in the lateral direction. Further, during the evolution of mammals, new functions were added to this stiff ancestral foundation, including sagittal bending in the posterior back and twisting up front. The addition of these new functions was pivotal in building the functionally diverse mammalian backbone, allowing modern-day mammals to run really fast and rotate their spine to groom their fur.

"By rigorously analyzing the fossil record, we are able to reject the simplistic lateral-to-sagittal hypothesis for a much more complex and interesting evolution story," Pierce said. "We are now revealing the evolutionary path towards the formation of the unique mammalian backbone."

The study is part of a series of ongoing projects on the evolution of the mammal backbone, piecing together its development, morphology, function, and evolution. "We still don't have the whole story," said Jones, "but we are getting close."

The researchers are now using three-dimensional modeling of the vertebrae to understand how the ancestors of mammals moved. "We are now testing our previous studies with CAD assisted three-dimensional models," said Jones. "So far it's working quite well and appears to support what we found in this paper."

What The Study Did: This study investigates emergency department visits for violence-related injuries occurring at home and outside the home in Cardiff, Wales, before and after COVID-19 lockdown measures were instituted in March 2020.

Authors: Jonathan P. Shepherd, Ph.D., Crime and Security Research Institute at Cardiff University in Wales, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jama.2020.25511)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

In a mouse study, Australian researchers have mapped out what happens behind the scenes in fat tissue during intermittent fasting, showing that it triggers a cascade of dramatic changes, depending on the type of fat deposits and where they are located around the body.

Using state-of-the-art instruments, University of Sydney researchers discovered that fat around the stomach, which can accumulate into a 'protruding tummy' in humans, was found to go into 'preservation mode', adapting over time and becoming more resistant to weight loss.

The findings are published today in Cell Reports.

A research team led by Dr Mark Larance examined fat tissue types from different locations to understand their role during every-other-day fasting, where no food was consumed on alternate days.

The fat types where changes were found included visceral "belly" fat, which is fat tissue surrounding our organs including the stomach, and subcutaneous fat, which lies just under the skin and is associated with better metabolic health.

"While most people would think that all fat tissue is the same, in fact, the location makes a big difference," said senior author Dr Larance from the Charles Perkins Centre and School of Life and Environmental Sciences at the University of Sydney.

"Our data show both visceral and subcutaneous fat undergo dramatic changes during intermittent fasting," said Dr Larance, who is also a Cancer Institute of NSW Future Research Fellow.

Why visceral fat can be resistant to weight loss

During fasting, fat tissue provides energy to the rest of the body by releasing fatty acid molecules.

However, the researchers found visceral fat became resistant to this release of fatty acids during fasting.

There were also signs that visceral and subcutaneous fat increased their ability to store energy as fat, likely to rapidly rebuild the fat store before the next fasting period.

Dr Larance said it was possible that a history of repeated fasting periods triggered a preservation signalling pathway in visceral fat.

"This suggests the visceral fat can adapt to repeated fasting bouts and protect its energy store," he said.

"This type of adaptation may be the reason why visceral fat can be resistant to weight loss after long periods of dieting."

Dr Larance said using a mouse model was a useful analogue ahead of studies in humans.

"Mouse physiology is similar to humans, but their metabolism is much faster, allowing us to observe changes more rapidly than in human trials, and examine tissues difficult to sample in humans," he said.

Future research in mice and humans could uncover the mechanisms by which this resistance occurs and also which types of diet and other interventions may be best at tackling belly fat.

Mapping out the inner workings of fat deposits

The research team examined more than 8500 proteins located in fat deposits, creating a catalogue of changes that occurred during intermittent fasting, using a technique called proteomics.

Proteomics - the study of all proteins - a relatively new area of study that takes its name from genomics (the study of all genes), monitors how proteins react under certain conditions, which in this case is intermittent fasting.

The results provide a rich source of data that helps to paint a more complete picture of the inner workings of fat tissue.

It was via proteomics that the research team were alerted of major cellular changes caused by intermittent fasting and, after further analysis, highlighted the visceral fat's preservation mechanism in action.

The study was conducted using the instruments of the Sydney Mass Spectrometry in the Charles Perkins Centre, part of the University of Sydney's Core Research Facilities.

Dr Larance says it should be noted that findings from the intermittent study may not apply to different diet regimes such as the 5:2 diet (fasting 2 days out of 7) or calorie restriction, which is common in people wanting to lose weight.

The results lay the foundation for future studies, which will dissect the molecules responsible for why visceral fat is resistant to energy release during fasting, and help determine what diet plans would be most beneficial for metabolic health.

"This sort of research has been enabled by these new instruments that allow us to 'look beyond the streetlight' - it's hypothesis generating; we knew we would find something but we didn't know what," Dr Larance explained.

"Now that we've shown 'belly fat' in mice is resistant to this diet, the big question will be to answer why, and how do we best tackle it?"

What The Study Did: This study suggests that, during the COVID-19 pandemic, a hotel- based isolation and quarantine strategy that delivers integrated medical and behavioral health support to people experiencing homelessness can be done safely outside the hospital setting.

Authors: Jonathan D. Fuchs, M.D., M.P.H., of the San Francisco Department of Public Health, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.0490)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

The Medicare Part D program would have saved $977 million in a single year if all branded prescription drugs requested by prescribing clinicians had been substituted by a generic option, according to a new study by researchers at the Johns Hopkins Bloomberg School of Public Health. And if Medicare patients had requested generic drugs instead of brand name drugs, the Medicare Part D program would have saved an additional $673 million in one year, for a total savings of $1.7 billion.

Medicare Part D offers supplemental outpatient drug coverage plans for seniors age 65 and older and people receiving disability benefits, and accounts for approximately one-third of total prescription drug spending in the U.S.

Despite laws in all 50 states and the District of Columbia promoting generic drug dispensing, the study found that in 2017 under the Medicare Part D program, prescribing clinicians and patients together requested brand name prescription drugs over generics 30 percent of the time when a brand name drug was dispensed.

Among the 169 million filled prescriptions analyzed in the study, 8.5 million involved dispensing a brand-name prescription drug when generics were available. Of these, 17 percent (1.4 million claims) involved the prescribing provider requesting a brand-name drug over a generic version and, in another 13.5 percent (1.1 million claims) patients requesting brand name drugs versus generic options.

The study will be published online March 2 in JAMA Network Open.

"Even with laws in place, requesting a brand name drug happens way more frequently than it should," says Gerard Anderson, PhD, professor in the Department of Health Policy and Management at the Bloomberg School. "This dispensing pattern results in exponentially higher costs for both the Medicare Part D program and patients."

For the study, the researchers analyzed Medicare Part D prescription drug claims from 2017. The analysis drew from a random sample representing 20 percent of Medicare beneficiaries and 224 drugs that had at least one generic substitute and at least 1,000 claims. The researchers analyzed information from each claim, including the type of drug dispensed, Medicare Part D spending, and the patient out-of-pocket spending.

Medicare patients would also benefit by paying less for prescriptions drugs. The study found that Medicare patients would have saved $161 million in 2017 if prescribing providers had requested generic drugs over brand name options. In addition, Medicare patients would have also saved $109 million if patients had requested generic drugs over brand name options. In all, Medicare patients spent $270 million more than necessary for prescriptions drugs in the year studied.

While branded prescription drug dispensing accounts for only 5 percent of Medicare Part D drug claims when both brand and generic drugs are available, these findings underscore how costly brand name drugs are to Medicare beneficiaries and the Medicare program.

Recent research has found that skepticism about generic medications is common among clinicians and patients. Surveys have found that more than one-third of patients reported a preference for branded products to generics, and 46 percent of patients asked their provider to prescribe a brand name drug over a generic.

The study also found that in 2017 the Medicare Part D program spent a total of $4.42 billion on brand name prescription drugs where no specific drug selection was indicated by a clinician or pharmacist. The authors recommend that the Medicare program look into these open-ended prescriptions, to see if it can reduce expenditures by encouraging opting for generic over brandname drugs when available.

The findings suggest that policies targeting both the clinician and the patient could have the greatest potential to promote generic drug use and therefore cost savings. Improving clinicians' perception of generic medication, raising awareness of the availability of generic drugs, and limiting direct pharmaceutical marketing can have substantial influence over the patients' medication preferences.

"Patients should always be mindful of the extra costs for themselves and for taxpayers associated with requesting a brand-name prescription drug," says Ge Bai, PhD, CPA, associate professor at the Johns Hopkins Carey Business School and in the Bloomberg School's Department of Health Policy and Management. "Prescribing clinicians can also play an important role in educating their patients on the safety and effectiveness of generic drugs."

Tokyo, Japan - Humans are largely omnivores, and meat in various forms has always featured in the diet of most cultures. However, with the increasing population and pressure on the environment, traditional methods of meeting this fundamental food requirement are likely to fall short. Now, researchers at the University of Tokyo report innovative biofabrication of bovine muscle tissue in the laboratory that may help meet escalating future demands for dietary meat.

With global urbanization, the economics of animal husbandry are becoming unsustainable. From an environmental viewpoint, the land and water costs of modern mega-scale livestock farming are untenable, as are the greenhouse gas emissions and the overall toll on the planet. Additionally, ethical concerns against inhuman exploitation of lower species for food are increasingly being voiced.

To address future requirements, tissue engineering of cultured meat is under development at several centers worldwide. However, most biosynthetic meat products are amorphous or granular-like minced meat, lacking the grain and texture of real animal flesh. Mai Furuhashi, lead author, explains their novel process. "Using techniques developed for regenerative medicine, we succeeded in culturing millimeter-sized chunks of meat wherein alignment of the myotubes help mimic the texture and mouthfeel of steak. For this, myoblasts drawn from commercial beef were cultured in hydrogel modules that could be stacked allowing fusion into larger chunks. We determined the optimal scaffolding and electrical stimulation to promote contractility and anatomical alignment of the muscle tissue to best simulate steak meat."

Lead author, Yuya Morimoto, describes the synthesized product. "Our morphological, functional and food feature analyses showed that the cultured muscle tissue holds promise as a credible steak substitute. Breaking force measurements showed that toughness approached that of natural beef over time. Significantly, microbial contamination was undetectable; this has implications for cleanliness, consumer acceptability and shelf-life."

"Our method paves the way for further development of larger portions of realistic cultured meat that can supplement or replace animal sources," claims Shoji Takeuchi, senior and corresponding author. "However, there is a long way to go before lab-grown meat is indistinguishable from the real thing and hurdles concerning consumer acceptance and cultural sensibilities are overcome. Nevertheless, this innovation promises to be a green and ethical alternative to animal slaughter in meeting our need for dietary meat."