Culture

Study: Drivers with shift work sleep disorder 3x more likely to be in crash

image: Praveen Edara

Image: 
University of Missouri

People who work nontraditional work hours, such as 11 p.m.-7 a.m., or the "graveyard" shift, are more likely than people with traditional daytime work schedules to develop a chronic medical condition -- shift work sleep disorder -- that disrupts their sleep. According to researchers at the University of Missouri, people who develop this condition are also three times more likely to be involved in a vehicle accident.

"This discovery has many major implications, including the need to identify engineering counter-measures to help prevent these crashes from happening," said Praveen Edara, department chair and professor of civil and environmental engineering. "Such measures can include the availability of highway rest areas, roadside and in-vehicle messaging to improve a driver's attention, and how to encourage drivers who may have a late-night work shift to take other modes of transportation, including public transit or ride-share services."

Edara, one of the authors on the study, said the analysis was based on data collected from a real-world driving study for the second Strategic Highway Research Program established by the U.S. Congress.

As the demand for 24/7 business operations has increased in recent years to meet customer needs during all hours of the day and across multiple time zones, the traditional work day -- once defined as 9 a.m.-5 p.m. -- has shifted for many people to include evening and night shifts, causing sleeping difficulties and leading to shift work sleep disorder. Edara said he was surprised to see shift work sleep disorder increase the risk of a traffic crash by nearly 300%, as compared to both sleep apnea and insomnia, which both increased the risk of a crash by approximately 30%.

Edara said previous studies have shown sleep disorders increase the risk for a traffic crash, but the majority of these studies were conducted in a controlled environment, such as a laboratory driving simulator. He believes this real-world data now validates those efforts.

"In the past, researchers have studied sleep disorders primarily in a controlled environment, using test-tracks and driving simulators," Edara said. "Our study goes a step further by using actual observed crash and near-crash data from approximately 2,000 events occurring in six U.S. states. We've known for a while now that sleep disorders increase crash risk, but here we are able to quantify that risk using real world crash data while accounting for confounding variables such as roadway and traffic characteristics."

Edara said some of the limitations of their study include not having data for fatal crashes, and no formal measurement to define drowsiness.

Putting a spotlight onto a national problem

In the United States, the National Transportation Safety Board, or NTSB, is the federal agency that investigates major traffic accidents. Each year, they issue an annual "most wanted list" of safety improvements, and their 2019-2020 list includes "screening and treating obstructive sleep apnea" among the top 10 topic areas.

Edara said he hopes that by showing how big of a risk there is for traffic crashes caused by excessive daytime sleepiness, the researchers can help draw additional attention toward finding ways to keep people safe behind the wheel, including taking the driver out of the equation with ride-sharing options and automated vehicles. He said the ideal next step in this research would be to partner with medical professionals who have expertise in this area to better understand why this is happening.

"We want to partner with public health and medical professionals whose expertise is in sleep-related research to better understand why this is happening," Edara said. "That will also allow us to explore what kind of countermeasures we can develop and test to improve the overall safety of these drivers and the other motorists around them."

Credit: 
University of Missouri-Columbia

Treating the COVID-19 'infodemic' as an epidemic

image: Examples from a taxonomy of misinformation about masks, with preemptive infodemiologist responses. Developed by the Annenberg Public Policy Center of the University of Pennsylvania.

Image: 
The New England Journal of Medicine ©2021

Writing in the New England Journal of Medicine, a trio of science communication researchers proposes to treat the Covid-19 misinformation "infodemic" with the same methods used to halt epidemics.

"We believe the intertwining spreads of the virus and of misinformation and disinformation require an approach to counteracting deceptions and misconceptions that parallels epidemiologic models by focusing on three elements: real-time surveillance, accurate diagnosis, and rapid response," the authors write in a Perspective article.

"The word 'communicable' comes from the Latin communicare, to share, to make common," said David Scales, M.D., Ph.D., of Weill Cornell Medical College and chief medical officer of the science-promoting nonprofit organization Critica. "What are the similarities between all the information shared on social media and communicable diseases? It's a helpful analogy in thinking through both of them."

Scales co-authored the article with Jack Gorman, M.D., president and chair of Critica, and Kathleen Hall Jamieson, Ph.D., director of the Annenberg Public Policy Center (APPC) of the University of Pennsylvania.

The publication comes as APPC has released national survey data finding that while some 75% of the American public views the approved Covid-19 vaccines as effective and safer than getting Covid-19, about 15% is not sure whether this is true and 10% to 12% thinks this is false.

A misinformation 'superspreader' event

Better infodemic-surveillance methods and a rapid response, the authors write, could have prevented the "superspreader" event that began on October 12, 2020, when the conservative website The Federalist misread a report by the Centers for Disease Control and Prevention (CDC) and reported that "masks and face coverings are not effective in preventing the spread of Covid-19." The following night, Fox News' Tucker Carlson mistakenly told his over 4 million viewers that 85% of the people infected by Covid-19 in July 2020 had been wearing a mask.

"The superspreading escalated," the researchers wrote, "when President Donald Trump echoed the same mischaracterization to more than 13 million viewers of a nationally televised October 15 town hall." Had The Federalist article been immediately and widely countered, the town hall moderator, NBC journalist Savannah Guthrie, might have been better equipped to counter the inaccurate claim than to say that Trump's characterization of the study was incorrect.

Detecting and halting misinformation

In their article, the authors recommend a series of steps to "halt such misinformation cascades":

Surveillance. Since "an overwhelming amount of misinformation and disinformation circulates on social media," sensitive surveillance systems need to be triggered before information goes viral. Companies such as Facebook should provide researchers with de-identified data on the spread of misinformation. "Lack of access to such data is the equivalent of a near-complete blackout of epidemiologic data from disease epicenters," the researchers said. If one were to conduct syndromic disease surveillance using Google, Scales said, "you could see if doctors are searching for Tamiflu, which would be highly correlated with a flu outbreak. You don't have to wait for CDC influenza data but can search for things that are correlated with the disease that show up sooner."

Diagnosis. "Just as scientists need to be able to distinguish one disease from another, infodemiologists need to distinguish different types of misinformation," said Jamieson, APPC's director. The Annenberg Public Policy Center has introduced a taxonomy featured in the NEJM article of categories of mis- and disinformation related to Covid-19 and vaccination. The part of the taxonomy regarding masking, for example, covers five types of misinformation: distortions of scientific findings; assertions that masks' effectiveness has not been proven; claims that masks are ineffective; suggestions that masks increase health risks; and conspiracy theories about masks. "Knowing the type of misinformation that is circulating allows us to develop strategies for buffering audiences from deceptions or misconceptions and, when necessary, to deploy a rapid-response system to rebut and displace inaccurate claims before they take hold," the authors wrote.

Response. Rapid epidemiological response consists of containment and treatment by medical personnel. So-called infodemiologists, modeled after the CDC's Epidemic Intelligence Service officers, can counteract misinformation in traditional media sources and online, the researchers say. Just as few people were trained in CPR a few decades ago but many are today, Scales said many people could be trained in evidence-based ways to counter misinformation. "The goal is to have people ready and trained so they can spring into action when a communication emergency comes up," he said. Critica, a nonprofit organization seeking to center the role of science in making rational health decisions, is among numerous organizations, such as New York State's Citizen Public Health Training Program, training infodemiologists to do this work. Critica's focus is not on those who are staunchly opposed to the vaccines but those who are susceptible to misinformation and vaccine-hesitant.

About 15% of Americans unsure about vaccines

A national probability APPC survey released this week of 1,941 people finds that 74% of the U.S. public says that the authorized Covid-19 vaccines are effective and 75% says the vaccines are safer than getting Covid-19. About 15% is unsure whether these statements are true, a potentially persuadable group that is larger than those deniers who incorrectly say that the statements are false. Read the survey.

Identifying the various kinds of mistaken beliefs is critical to halting their proliferation.

"To make it possible to effectively interdict viral deception we not only need reliable means of finding it but also the wherewithal to predict when, where, and how it will spread," Jamieson noted. "Just as scientists need to be able to distinguish one disease from another, infodemiologists need to distinguish different types of misinformation."

In the NEJM article, the authors argue for a broad approach to combat misinformation.

"Our model will be more effective for people intrigued by misinformation but not yet under its thrall than for committed acolytes sequestered in echo chambers. But the model's strength, like that of epidemiology, is in recognizing that effective prevention and response requires mutually reinforcing interventions at all levels of society, including enhancing social-media algorithmic transparency, bolstering community-level norms, and establishing incentives for healthier media diets."

"The Covid-19 Infodemic - Applying the Epidemiologic Model to Counter Misinformation," was published in The New England Journal of Medicine on May 12, 2021.

Critica is a nonprofit organization whose mission is to promote the public's acceptance of scientific consensus, counteract misinformation about science and health, and increase the use of scientific evidence in public policymaking. Visit us at http://www.criticascience.org.

The Annenberg Public Policy Center was established in 1993 to educate the public and policy makers about communication's role in advancing public understanding of political, science, and health issues at the local, state, and federal levels.

Credit: 
Annenberg Public Policy Center of the University of Pennsylvania

Many do not recognise animal agriculture's link to infectious diseases

New research led by the University of Kent has found that people fail to recognise the role of factory farming in causing infectious diseases.

The study published by Appetite demonstrates that people blame wild animal trade or lack of government preparation for epidemic outbreaks as opposed to animal agriculture and global meat consumption.

Scientists forewarned about the imminence of global pandemics such as Covid-19, but humankind failed to circumvent its arrival. They had been warning for decades about the risks of intensive farming practices for public health. The scale of production and overcrowded conditions on factory farms make it easy for viruses to migrate and spread. Furthermore, the common practice of feeding antibiotics to farmed animals promotes antimicrobial resistance, threatens public health.

With the focus now on the need to prevent future pandemics and zoonotic diseases, it is critical that there is more understanding on the causes and risks posed by animal agriculture.

This study led by Dr Kristof Dhont (Kent), alongside Dr Jared Piazza (Lancaster University) and Professor Gordon Hodson (Brock University), explored public understanding and opinion to determine where people place the blame of zoonotic disease outbreaks.

Findings show that as well as failing to recognise the detrimental role of factory farming, those who are highly committed to eating meat struggle to acknowledge global meat consumption as a link to the problem. Even after reading about the risks of factory farms in the spread of disease, committed meat eaters were still less convinced of policies to change or ban factory farming than of policies aimed at better preparing for pandemics. Yet, when reading the same information about wild animal markets, they endorsed policies to reduce, regulate, or ban wild animal markets.

Dr Dhont said: 'As world populations swell, our dependence upon meat is likely to grow, making it increasingly pressing to come to grips with the detrimental role of intensive farming and take action to turn the tide. Undoubtedly, humankind needs to be better prepared to handle infectious disease outbreaks - which we are edging closer towards. However, it is vital to identify and uproot the causes of infectious diseases.

'Appetite for meat can be a stumbling block for considering the role of animal agriculture in the spread of zoonotic disease. Meat is a highly enjoyable product for many, a factor inhibiting us from taking actions towards a safer future.

'Solutions to this problem will require policy changes and personal sacrifices, akin to dealing with the looming climate emergency.'

Credit: 
University of Kent

NK cells with bispecific antibody show activity against lymphoma cells

image: Katy Rezvani, M.D., Ph.D.

Image: 
MD Anderson

HOUSTON - Cytokine-activated natural killer (NK) cells derived from donated umbilical cord blood, combined with an investigational bispecific antibody targeting CD16a and CD30 known as AFM13, displayed potent anti-tumor activity against CD30+ lymphoma cells, according to a new preclinical study from researchers at The University of Texas MD Anderson Cancer Center.

The findings were published today in Clinical Cancer Research, a journal of the American Association for Cancer Research. These results led to the launch of a Phase I clinical trial to evaluate the combination of cord blood-derived NK cells (cbNK cells) with AFM13 as an experimental cell-based immunotherapy in patients with CD30+ lymphoma.

"Developing novel NK cell therapies has been a priority for my team at MD Anderson to address unmet needs for the treatment of both hematologic cancers and solid tumors," said senior author Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation and Cellular Therapy. "This preclinical work provided proof of principle for NK cells precomplexed with AFM13, suggesting that they can effectively eliminate lymphoma cells expressing CD30 and warrant further clinical testing."

Natural killer cells are part of the innate immune system and work naturally to eliminate cancer cells in the body. However, they have limited persistence on their own, and tumors can develop mechanisms to evade NK cells, Rezvani explained. Therefore, her research team has worked to develop approaches to enhance the anti-tumor efficacy of NK cells.

Affimed's AFM13 is a proprietary bispecific antibody designed to bind to CD16a on NK cells and CD30 on lymphoma cells. Initial studies on NK cells isolated from the blood of patients with Hodgkin lymphoma found that AFM13 formed a stable complex with NK cells and could induce NK cell-mediated killing of CD30+ cells. However, the activity of these cells was modest, leading the researchers to evaluate alternative NK cell sources.

Further experiments suggested that cbNK cells, isolated from umbilical cord blood donations made to the MD Anderson Cord Blood Bank, displayed consistent and improved activity against lymphoma with AFM13 relative to other NK cell sources. The researchers were able to further stimulate the anti-tumor immune activity of cbNK cells by pre-activation with a combination of the cytokines IL-12/15/18.

In animal models, pre-activated and expanded cbNK cells complexed with AFM13 resulted in improved tumor control and survival relative to controls, with minimal side effects observed.

"These findings suggest that, in animal models, ex vivo pre-activated and expanded cord blood-derived NK cells complexed with AFM13 were able to safely eliminate CD30+ lymphoma cells," Rezvani said. "We look forward to learning if this investigational therapy may provide benefits to patients with advanced lymphoma in the ongoing clinical trial."

Credit: 
University of Texas M. D. Anderson Cancer Center

COVID-19 mRNA vaccines are immunogenic in pregnant and lactating women

Boston - Pregnant women with symptomatic COVID-19 have a higher risk of intensive care unit admissions, mechanical ventilation and death compared to non-pregnant reproductive age women. Increases in preterm birth and still birth have also been observed in pregnancies complicated by the viral infection. The Centers for Disease Control and Prevention (CDC) recommended that people who are pregnant may choose to be vaccinated at their own discretion with their healthcare provider. However, pregnant and lactating women were not included in Phase 3 vaccine efficacy trials; thus, data on vaccine safety and immunogenicity in this population is limited.

In a new study from Beth Israel Deaconess Medical Center (BIDMC), specialists in the Department of Obstetrics and Gynecology and the Center for Virology and Vaccine Research evaluated the immunogenicity of COVID-19 mRNA vaccines in pregnant and lactating women who received either the Pfizer or Moderna COVID-19 vaccines. The researchers found that both vaccines triggered immune responses in pregnant and lactating women. Further analyses revealed that maternal vaccine antibodies are transferred into infant cord blood and breast milk. The team's findings appear today in the Journal of the American Medical Association.

"Our study supports the use of vaccines in pregnant and lactating individuals. The vaccine-elicited antibodies we detected in both infant cord blood and breast milk suggest that vaccinating pregnant mothers may potentially protect infants from COVID-19 infection," said lead author Ai-ris Y. Collier, MD, a Maternal-Fetal Medicine specialist at BIDMC. "Future research should focus on determining the timing of vaccination that optimizes delivery of antibodies through the placenta and breast milk to newborns."

Collier and colleagues conducted an exploratory, descriptive study of 103 women, ages 18-45, who received an mRNA COVID-19 vaccine (54 percent received Pfizer; 46 percent received Moderna). The scientists found similar levels of vaccine-induced antibody function and T cell responses in all non-pregnant, pregnant and lactating women after their second vaccine dose. Additionally, both pregnant and non-pregnant women who received the mRNA vaccines developed cross-reactive immune responses against the COVID-19 variants of concern B.1.1.7 and B.1.351.

"The COVID-19 mRNA vaccines raised robust immune responses in pregnant, lactating, and non-pregnant non-lactating women," said senior corresponding author Dan. H. Barouch, MD, PhD, Director of the Center for Virology and Vaccine Research at BIDMC. "Additionally, the vaccine-elicited antibody responses were greater than antibody responses seen after COVID-19 infections. These findings add to the emerging data that support the use of these vaccines in pregnant and lactating women."

Credit: 
Beth Israel Deaconess Medical Center

High genomic diversity is good news for California condor

image: A critically endangered California condor, Gymnogyps californianus.

Image: 
Photo courtesy of San Diego Zoo Wildlife Alliance

Despite having been driven nearly to extinction, the California condor has a high degree of genetic diversity that bodes well for its long-term survival, according to a new analysis by University of California researchers.

Nearly 40 years ago, the state's wild condor population was down to a perilous 22. That led to inbreeding that could have jeopardized the population's health and narrowed the bird's genetic diversity, which can reduce its ability to adapt to changing environmental conditions.

In comparing the complete genomes of two California condors with those of an Andean condor and a turkey vulture, UC San Francisco and UC Berkeley scientists did find genetic evidence of inbreeding over the past few centuries, but, overall, a wealth of diversity across most of the genome.

"You need genetic diversity in order to adapt, and the more genetic diversity they (California condors) have, hopefully, the more chance they have to adapt and persist," said Jacqueline Robinson, a UCSF postdoctoral fellow and first author of a paper about the analysis appearing today in the journal Current Biology. "Our study is the first to begin quantifying diversity across the entire California condor genome, which provides us a lot of baseline information and will inform future research and conservation."

The health of the bird's genome is probably due to the species' great abundance in the past. Robinson and her colleagues, including Rauri Bowie, UC Berkeley professor of integrative biology, used statistical techniques to estimate the bird's historical population and found that it was far more abundant across the United States a million years ago than even the turkey vulture, America's most common vulture today. The bird likely numbered in the tens of thousands, soaring and scavenging from New York and Florida to California and into Mexico.

"They have this legacy of high genetic diversity from their former abundance, so I think there is a chance that, with genetic information, we could manage the population going into the future to really maintain the genetic diversity that they do have now and not have any further losses," Robinson said. "You could even choose individual mates to, in a sense, reverse the inbreeding."

Co-author Cynthia Steiner, associate director in conservation genetics for the San Diego Zoo Wildlife Alliance, a nonprofit conservation organization affiliated with the San Diego Zoo, agreed that the genomic information will help refine conservation strategies to maintain genetic diversity and reduce inbreeding. Inbreeding may already be causing an increase among wild condors in a lethal form of dwarfism, chondrodystrophy, and leading to an increase among some birds in the number of tail feathers, from 12 to 14.

"We finally have a genomic resource or tool in-hand for the species that will allow understanding the genetic basis of disease and phenotypic traits, such as chondrodystrophy and the 14-tail feather syndrome, and potentially manage these deleterious traits in the breeding program," Steiner said.

Bowie, an ornithology curator in UC Berkeley's Museum of Vertebrate Zoology (MVZ), hopes to continue working with the San Diego Zoo to analyze the genomes of all 22 original individual condors in the founding population -- the ancestors of all living California condors -- to assess the species' overall genetic diversity. With captive breeding, the aim has always been to mate unrelated condors in order to prevent inbreeding. By generating genome profiles of all individuals of an endangered species, conservationists could more finely tune breeding to weed out any negative health consequences, called inbreeding depression.

"With most endangered species, when you look at their genomes, they have very little genetic diversity left. In other words, they have very little capacity to adapt to change," he said. "That is definitely not the case with the California condor. With these genome data in hand, maybe there is a way to mitigate chondrodystrophy by cross-breeding certain individuals or finding other ways to help them deal with that."

Condor's steady decline

The California condor, Gymnogyps californianus, is considered critically endangered, despite herculean efforts to rescue the species that began in 1987. This involved capturing all wild condors -- 27 at that time -- and breeding them in zoos. The program's success was celebrated in 1991 with the reintroduction of captive-bred condors into the wild. Today, more than 300 individuals roam California, Mexico, Arizona and Utah, while another 200 remain in captivity. With a wingspan larger than any other bird in the United States -- up to 3 meters, or nearly 10 feet, slightly less than that of the Andean condor (Vultur gryphus), its closest relative -- it also is one of the longest-lived birds, often surviving until the age of 60.

Based on the team's genetic analysis of two California condor genomes over the past million years, condor populations gradually fluctuated downward until a precipitate decline began around the time humans settled the Americas 15,000 years ago. This coincides with the disappearance of large land animals -- megafauna -- which were likely exterminated by early inhabitants of America between 10,000 and 12,000 years ago. The carcasses of North American megafauna were undoubtedly a major source of food for these carrion-eating scavengers, and condors may have become restricted to the Pacific Coast because they could take advantage of marine mammal carcasses after land animals became less abundant.

The decline accelerated over the last few hundred years with the rising destruction of condor habitat, increased human poaching and persistent lead poisoning from ingested shotgun pellets.

Small population inbreeding

Robinson, who works in the lab of co-author Jeffrey Wall, a professor in UCSF's Institute for Human Genetics, has focused on genetic studies of small populations where inbreeding increases the incidence of normally rare recessive traits, many of them deleterious. She currently is involved with genetic studies of Mexico's vaquita, the world's smallest porpoise, which is critically endangered in its range within the Gulf of California. She co-authored a report last year that found very low diversity in the vaquita's genome, which is a result of its natural rarity and historically low abundance prior to its recent human-driven population crash, she said.

She embarked on the current study after Bowie collaborated with the San Diego Zoo and the Baylor College of Medicine to produce what he called a "Rolls Royce" version of the condor genome -- a high-quality genome that is a rarity for any wild animal and which rivals the quality of the known genomes of the commercial chicken and the laboratory mouse.

"What I mean by a Rolls Royce genome is that it has very few fragments -- basically, all the chromosomes are intact," she said. "With that, you can get a really good assessment of not only how much genetic diversity there is, but how it is distributed across the genome. And that is really helpful if you are trying to find genes that are related to disease or if you are interested in things that are important for enabling condors to do what they do -- the adaptive genes."

Robinson compared Bowie's condor genome, obtained from the blood of an Arizona condor, and the genome of the San Diego Zoo's condor with the genomes of the Andean condor and the turkey vulture (Cathartes aura), which had already been sequenced.

Surprisingly, given the California condor's history, the two genomes contained the highest levels of diversity among all three species.

"Andean condors are somewhat rare, but turkey vultures are extremely abundant, so this result was a bit unexpected, as it doesn't match current population sizes," Robinson said. "Genetic diversity is tied to species abundance, so the high genetic diversity in California condor genomes contrasts starkly with the extremely small number alive today."

Bowie attributes the condor's success at passing through its near-extinction bottleneck while retaining much of its original genetic diversity to the bird's long lifespan and slow reproductive rate, which determine its generation time.

"Even though their numbers dramatically plummeted, because of their generation time they hadn't passed through many generations, so a lot of that genetic diversity was retained," he said.

The California condor project is one piece of Bowie's current focus on genetic diversity among all living and extinct vultures. Graduate student Mackenzie Kirchner-Smith is currently analyzing vulture skulls in the MVZ and UC Museum of Paleontology collections to understand past vulture populations, while Bowie has just launched an effort to sequence the genomes of the world's living species of vulture, in part to understand how the scavenging lifestyle developed independently among three very distinct bird groups.

Robinson hopes to continue with the condor work, as well. Despite having visited condor habitat in the past, she saw her first condor only a few weeks ago when visiting Pinnacles National Park, a popular hangout for condors along the Central California Coast.

"As I was looking at them, I was literally thinking, these almost disappeared during my lifetime. That would have been such a tragedy," she said. "I would say that we shouldn't write off any species just because there may only be a few individuals left. The California condor came back from a population size of just 22 individuals."

Robinson's co-authors, in addition to Bowie, Steiner and Wall, include David Mindell of UC Berkeley's Museum of Vertebrate Zoology. The work was funded in part by the National Science Foundation (DEB-1441652).

Credit: 
University of California - Berkeley

Evolutionary biologists discover mechanism that enables lizards to breathe underwater

image: Close-up of an Anolis lizard with a rebreathing bubble on its snout.

Image: 
Lindsey Swierk

TORONTO, ON - A team of evolutionary biologists from the University of Toronto has shown that Anolis lizards, or anoles, are able to breathe underwater with the aid of a bubble clinging to their snouts.

Anoles are a diverse group of lizards found throughout the tropical Americas. Some anoles are stream specialists, and these semi-aquatic species frequently dive underwater to avoid predators, where they can remain submerged for as long as 18 minutes.

"We found that semi-aquatic anoles exhale air into a bubble that clings to their skin," says Chris Boccia, a recent Master of Science graduate from the Faculty of Arts & Science's Department of Ecology & Evolutionary Biology (EEB). Boccia is lead author of a paper describing the finding published this week in Current Biology.

"The lizards then re-inhale the air," says Boccia, "a maneuver we've termed 'rebreathing' after the scuba-diving technology."

The researchers measured the oxygen (O2) content of the air in the bubbles and found that it decreased over time, confirming that rebreathed air is involved in respiration.

Rebreathing likely evolved because the ability to stay submerged longer increases the lizard's chances of eluding predators.

The authors studied six species of semi-aquatic anoles and found that all possessed the rebreathing trait, despite most species being distantly related. While rebreathing has been studied extensively in aquatic arthropods like water beetles, it was not expected in lizards because of physiological differences between arthropods and vertebrates.

"Rebreathing had never been considered as a potential natural mechanism for underwater respiration in vertebrates," says Luke Mahler, an assistant professor in EEB and Boccia's thesis supervisor. "But our work shows that this is possible and that anoles have deployed this strategy repeatedly in species that use aquatic habitats."

Mahler and co-author Richard Glor, from the University of Kansas, first observed anoles rebreathing in Haiti in 2009 but were unable to carry out further observations or experiments. Another co-author, Lindsey Swierk, from Binghamton University, State University of New York, described the same behaviour in a Costa Rican species in 2019. These early observations suggested that rebreathing was an adaptation for diving, but this idea had not been tested until now.

Boccia became interested in aquatic anoles after encountering one in Panama. He began his rebreathing investigations in Costa Rica in 2017 and continued the research in Colombia and Mexico.

As the authors point out, the rebreathing trait may have developed because anoles' skin is hydrophobic -- it repels water -- a characteristic that likely evolved in anoles because it protects them from rain and parasites. Underwater, air bubbles cling to hydrophobic skin and the ability to exploit these bubbles for breathing developed as a result.

While further work is required to understand how the process works in detail, Boccia, Mahler and their co-authors suggest different ways in which rebreathing may function.

In its simplest form, the air bubble on a lizard's snout likely acts like a scuba tank, providing a submerged animal with a supply of air in addition to the air in its lungs. This is what aquatic arthropods like water beetles do to extend the time they can remain submerged.

The researchers also suggest that the rebreathing process may facilitate using air found in a lizard's nasal passages, mouth and windpipe that would otherwise not be used by the lizard in breathing.

The bubble may also help rid waste carbon dioxide (CO2) from exhaled air through a process other researchers have already observed in aquatic arthropods. Those studies concluded that because CO2 is highly soluble in water and because the level of CO2 in the bubbles is higher than in the surrounding water, exhaled CO2 dissolves into the surrounding water rather than being rebreathed.

Finally, the authors speculate that the bubble may act as a gill and absorb oxygen from the water -- again, something already observed in arthropods. Boccia and Mahler are planning further research to confirm if these rebreathing processes are occurring with anoles.

According to Mahler, "This work enriches our understanding of the creative and unexpected ways that organisms meet the challenges posed by their environments. That is valuable in its own right, but discoveries like this can also be valuable to humans as we seek solutions to our own challenging problems."

"It's too early to tell if lizard rebreathing will lead to any particular human innovations," says Boccia, "But biomimicry of rebreathing may be an interesting proposition for several fields -- including scuba-diving rebreathing technology, which motivated our naming of this phenomenon."

Credit: 
University of Toronto

Market report: Rising stock wealth does boost spending, employment

The stock market is a staple of business news, but it is unclear how meaningful stock prices are to the larger economy. Do changes in stock prices directly affect shorter-term consumption, or are they just leading indicators for subsequent economic activity? The U.S. Federal Reserve, for its part, usually seems to act as if stock-based wealth does help drive spending and employment. But is this correct?

A new study co-authored by an MIT economist brings data to the discussion and finds that increased stock market wealth has moderate but clear economic effects. After looking at the U.S. on a county-by-county basis, the study finds that after large market shifts, people spend about 3.2 cents per year out of each increased dollar of stock wealth they possess. There are also distinct employment effects in "nontradable" -- that is, place-situated -- industries.

"We found that the empirical effect is clear," says Alp Simsek, an associate professor of economics at MIT and a co-author of a new paper detailing the study's results. "Nontradable industry activities go up, including labor compensation in these nontradable industries. That provides direct evidence policymakers should care about."

The paper, "Stock Market Wealth and the Real Economy: A Local Labor Market Approach," appears in this month's issue of the American Economic Review. The authors are Gabriel Chodorow-Reich, an associate professor of economics at Harvard University; Plamen T. Nenov, an associate professor at the Norwegian Business School in Oslo; and Simsek, the Rudi Dornbusch Career Development Associate Professor in MIT's Department of Economics.

To conduct the study, the scholars examined multiple data sources, including IRS records from 1989 to 2015; stock market data from the Center for Research in Security Prices, affiliated with the University of Chicago Booth School of Business; county-level demographic and wealth information from the Federal Reserve Board's Survey of Consumer Finances; and county-level employment and payroll information from the Bureau of Labor Statistics.

The paper's county-level analysis helps disentangle whether the relationship between increased stock wealth and economic activity is to an extent causal, or whether stock-price increases are merely foretelling economic activity occurring independently.

Because not all counties have the same levels of stock wealth, tracking the differences in their levels of economic activity after the same changes in the markets helps pinpoint how much of that activity is driven by portfolio changes.

"Take Florida as an example," Simsek says. "There are counties like Palm Beach and Miami that have very high stock wealth, and others, like those in the Florida panhandle, that do not. The stock wealth effect predicts that in Miami and Palm Beach, after a stock market boom, activity should be above average. ... And that's what we find in the data."

Simsek, Chodorow-Reich, and Nenov also found this change almost entirely in nontradable industries, where location matters. The restaurant industry is nontradable, as are construction and many services; a lot of manufacturing activity, however, can be tradable.

Combining their county-level empirical analysis with a theoretical model of the U.S. economy, the scholars concluded that -- absent countervailing actions by the U.S. Federal Reserve -- a sustained 20 percent increase in stock valuations increases the nationwide labor bill by around 1.7 percent and increases nationwide hours worked by around 0.7 percent within two years.

The research also shows that it takes time for stock-market wealth to translate into spending, with changes starting to occur within a quarter of the market event but tending to peak from one to two years afterward.

"We do find a time lag," Simsek says. "Which is natural, because financial markets move fast, but the real economy is slower. Perhaps it takes time for people to realize their wealth has changed or for their consumption habits to adjust. Or, once people start spending, restaurants take a while to adjust labor hours or compensation. It's a demand-driven mechanism."

Simsek suggests the current finding has clear policy implications, especially for central bankers, since it helps reinforce the idea that lowering interest rates not only makes business borrowing more feasible but also boosts spending through stock wealth.

"One of the things the Fed can do, if they want to stimulate economic activity, is cut the rate and increase stock wealth, and that will support economic activity," Simsek says. To be sure, the U.S. Federal Reserve has seemingly acted to shore up market wealth many times in the past. The so-called "Greenspan put" or "Fed put" was the name given to U.S. Federal Reserve rate cuts halting market slides. (Alan Greenspan is a former Fed chair, and a "put" is a financial hedge designed to limit portfolio losses.)

Those moves drew some criticism from observers who felt Federal Reserve policies may have been too investor-friendly, although, as Simsek says, "It's not so obvious that it's a bad thing. If you don't do that, according to our evidence, it would be a negative economic shock, and the Fed is not [necessarily] doing it to bail out the stockholders, but is doing it to support economic activity."

To be sure, Simsek notes, there are still-larger moral debates about whether or not society has too much wealth tied up in stocks as opposed to other kinds of assets, or whether, just in terms of growth, too much wealth goes to stockholders as opposed to workers, who might spend more of their income relative to well-off investors. But whether the object of analysis is central-bank policy or structural issues about wealth, he notes, "We are providing empirical evidence for that."

Credit: 
Massachusetts Institute of Technology

TGen-led study of 70,000 individuals links dementia to smoking and cardiovascular disease

PHOENIX, Ariz. -- May 13, 2021 -- In the largest study of the associations between smoking and cardiovascular disease on cognitive function, researchers at the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, found both impair the ability to learn and memorize; and that the effects of smoking are more pronounced among females, while males are more impaired by cardiovascular disease.

The results appear today in the journal Scientific Reports.

Previous attempts to quantify cognitive function among smokers and assess sex differences produced mixed results. The TGen researchers attribute this to the limited size of previous data sets. By analyzing data representing more than 70,000 individuals worldwide -- generated through TGen's online cognitive test called MindCrowd -- the current study produced results that indicate definitive trends.

"These results suggest that smoking and cardiovascular disease impact verbal learning and memory throughout adulthood, starting as early as age 18," said Matt Huentelman, Ph.D., TGen Professor of Neurogenomics, a MindCrowd founder, and the study's senior author. "Smoking is associated with decreased learning and memory function in women, while cardiovascular is associated with decreased learning and memory function in men."

Besides Alzheimer's disease, the most significant cause of cognitive decline is known as "vascular contributions to cognitive impairment and dementia" or VCID, which arises from stroke and other vascular brain injuries that cause significant changes to memory, thinking and behavior: smoking and cardiovascular disease exacerbate VCID.

"The reasons for these sex-modification effects are not entirely understood," said Candace Lewis, Ph.D., a Postdoctoral Fellow in Dr. Huentelman's Lab, and the study's lead author. "Our findings highlight the importance of considering biological sex in studying vascular contributions to cognitive impairment and dementia."

This study's findings are important, Dr. Lewis said, since cigarette smoking is the nation's leading cause of preventable disease and death, accounting for nearly 1 in 5 deaths, and cardiovascular disease is the leading cause of disease and death worldwide, and is an important predictor of cognitive decline and VCID. Vascular diseases also are associated with increased risk of Alzheimer's, which is the nation's 6th leading cause of death.

Because the study included a wide range of adults, 18-85, it allowed researchers to assess the relationship between smoking, cardiovascular disease, and verbal memory in the broadest single study age range used to date.

The researchers noted that few studies have previously assessed the effects of cardiovascular disease in younger adults, and that understanding the relationship between cardiovascular disease and cognitive function in young adults may be necessary for understanding possible treatment and intervention opportunities.

"This study points out some unpredicted but important differences between the sexes relating to cognitive decline," said Brian Tiep, M.D., City of Hope director of pulmonary rehabilitation and smoking cessation. "The impact on mental acuity seems progressive over time -- some more rapid than others. Living habits related to diet, exercise and smoking certainly are consequential and may differ between men and women. People undergoing cancer care may be cognitively effected by the cancer and its treatment."

"This study supports the importance of maintaining cardiovascular health and quitting smoking not only in support of their cancer care but to improve brain function," Dr. Tiep added.

Credit: 
The Translational Genomics Research Institute

Research reveals negative effects of hotel app adoption on customer spending

College Park, Md. - Companies have often considered app adoption among their customers to have a positive impact on customer spending. According to new research from marketing professor P.K. Kannan at the University of Maryland's Robert H. Smith School of Business, higher app adoption among hotel chains could be linked to lower spending among lower-level loyalty customers, who are more likely to use apps to get the best deals.

Kannan worked with Xian Gu, an assistant professor of marketing at Indiana University, for the research, published as "The Dark Side of Mobile App Adoption: Examining the Impact on Customers' Multichannel Purchase," in the Journal of Marketing Research.

They studied how a customer's spending over various channels changes after downloading a major hotel chain's app. Through several studies, they found that downloading the app had a significant and negative impact on customer spending, especially among low-level loyalty customers.

"Typically, companies launch mobile apps as a way to have a direct touchpoint with the customers and encourage them to make reservations through their channels as opposed to that of a third party," says Kannan. "However, they often don't realize that customers who have downloaded their app have likely downloaded apps from other hotel chains as well."

The research involved using a regression model to compare spending of customers who adopted the app at a specific point in time with the spending of a group of control customers who had not adopted the app at that time. The study tracked the total and channel-specific spending of each customer. Overall, the research team found that not only were customers who download the app from the hotel chain in focus more likely to have downloaded apps from other hotel chains, they were also more likely to shop around for the best rates and deals. This ended up decreasing the share of wallet of the focal hotel group.

"Customers are becoming increasingly aware of the value of mobile apps in purchase decisions," Kannan says. "When customers download multiple hotel apps, they become more of a searcher, which can have a negative impact on spending."

Kannan and his colleague's research is unique in that they studied the effect of mobile app adoption on spending in a highly competitive industry.

"There haven't been any prior studies that have examined the effect of mobile app adoption on spending in highly competitive industries like the hospitality industry," says Kannan. "Because of the highly competitive nature of the industry, people become more shoppers as opposed to loyal customers due to the ease of mobile shopping."

As technology becomes more prevalent and the entry point for new customers becomes easier, hotels are having to work harder to maintain customers. Kannan hopes that this research will help hotel chains optimize their mobile apps to include service functions that will help build loyal customers.

"In hyper competitive industries, apps are part of the cost of doing business," Kannan says. "Therefore, companies should optimize the service features of their app such as mobile check-in, room service requests and keyless entry to their room. Every additional service element added will help hotels strengthen their relationships with customers and develop more loyal customers in the process. Showing customers the value of the app beyond booking is essential."

Credit: 
University of Maryland

The Achilles heel of the coronavirus

video: Frameshifting animation.

Image: 
Said Sannuga, Cellscape.co.uk / ETH Zurich, The Ban Lab

Viruses require the resources of an infected cell to replicate and then infect further cells, and transfer to other individuals. One essential step in the viral life cycle is the production of new viral proteins based on the instructions in the viral RNA genome. Following these construction plans, the cell's own protein synthesis machine, called the ribosome, produces the viral proteins.

In the absence of viral infection, the ribosome moves along the RNA in strictly defined steps, reading three letters of RNA at a time. This three-letter code defines the corresponding amino acid that is being attached to the growing protein. It almost never happens that the ribosome slips one or two RNA letters forward or backward instead of following the regular three-letter steps. When such a slip of the ribosome occurs, it is called "a frameshift," and it leads to an incorrect reading of the genetic code.

Frameshifting almost never happens in our cells. It would lead to dysfunctional cellular proteins; however, certain viruses, such as coronaviruses and HIV, depend on a frameshifting event to regulate levels of viral proteins. For example, SARS-CoV-2 - the virus that causes COVID-19 - is critically dependent on frameshifting promoted by an unusual and intricate fold in the viral RNA.

Therefore, since frameshifting is essential for the virus but it almost never happens in our organism, any compound that inhibits frameshifting by targeting this RNA fold could potentially be useful as a drug to combat infection. However, so far, there is no information on how the viral RNA interacts with the ribosome to promote frameshifting, which would be important for drug development.

Detailed image of an essential process for coronavirus replication

A team of researchers from ETH Zurich and the Universities of Bern, Lausanne (in Switzerland) and University College Cork (UCC in Ireland) has for the first time managed to reveal the interactions between the viral genome and the ribosome during frameshifting. Their results have just been published in the journal Science.

Using sophisticated biochemical experiments, the researchers managed to capture the ribosome at the frameshifting site of the SARS-CoV-2 RNA genome. They could then study this molecular complex using cryo-electron microscopy.

The results provided a molecular description of the process at unprecedented detail and revealed a number of novel unanticipated features. The frameshifting event causes the usually dynamic ribosome machine to adopt a strained conformation, which helped provide one of the sharpest and most accurate images of a mammalian ribosome, visualized in the process of frameshifting while reading the information from the viral genome. The researchers then followed up on their structural findings with in vitro and in vivo experiments including exploring how this process can be targeted with chemical compounds. Nenad Ban, Professor for Molecular Biology at ETH Zurich and co-author of the study, emphasizes that "The results presented here on SARS-CoV-2 will also be useful for understanding the frameshifting mechanisms in other RNA viruses".

Possible target for antiviral drug development

The dependence of SARS-CoV-2 on this ribosomal frameshifting event could be used to develop antiviral drugs. Previous studies reported that several compounds are able to inhibit frameshifting in coronaviruses, however, this study now provides information about the effects of these compounds on levels of SARS-CoV-2 in infected cells.

In their experiments, both compounds reduced viral replication by three to four orders of magnitude and were not toxic for the treated cells. However, one of the two reduced viral replication by inhibiting ribosomal frameshifting, while the other might act through a different mechanism.

Although these compounds are currently not potent enough to be used as therapeutic drugs, this study demonstrates that inhibition of ribosomal frameshifting has a profound effect on viral replication, which paves the way for the development of better compounds. Due to the fact that all coronaviruses depend on this conserved frameshifting mechanism, a drug that targets this process may even be useful to treat infections by more distantly related coronaviruses. "Our future work will focus on understanding the cellular defense mechanisms that suppress viral frameshifting, as this could be useful for development of small compounds with similar activity," says Ban.

Credit: 
ETH Zurich

Tests of bitumen pave way to rational approaches in road building

image: Adhesion of oxidized (a) and non-oxidized (b) bitumen to acidic rock.

Image: 
Kazan Federal University

First co-author, Junior Research Associate of the Rheological and Thermochemical Research Lab Richard Djimasbe, comments, "To obtain bitumen as a half-solid product from heavy oil, you have to extract light fractions, and the rest is non-oxidized bitumen. Because of the relatively low ratio of light fractions in heavy oil, it's a simple and cheap way of bitumen production. The method allows for rational use of both heavy oil and light oil."

Lab Head Mikhail Varfolomeev adds, "One of the priorities of our World-Level Research Center in Liquid Hydrocarbons is the use of heavy oils, which constitute the majority of reserves both in Russia and in the world. One of the most important parts of this is extraction and refining of heavy petroleum reserves. The paper makes steps in that direction."

Non-traditional reserves, such as heavy oil, natural bitumen, and shale oil, have been found in Canada, Venezuela, Brazil, Russia, Chad, Madagascar and many other countries.

The research team hopes that non-oxidized bitumen can become another popular product obtained from heavy oil in Russia.

"The researchers focused on the use of a specially packed oxidizing column to increase the contact surface between the feedstock and the injected compressed air in order to reduce production costs, followed by a comparison of oxidized and unoxidized bitumen obtained by steam distillation," says co-author, Junior Research Associate Ameen A. Al-Muntaser.

Credit: 
Kazan Federal University

Screening for ovarian cancer did not reduce deaths

A large-scale randomised trial of annual screening for ovarian cancer, led by UCL researchers, did not succeed in reducing deaths from the disease, despite one of the screening methods tested detecting cancers earlier.

Results from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) have been published in a report in the medical journal The Lancet.

In the UK, 4,000 women die from ovarian cancer each year. It is not usually diagnosed until it is at a late stage and hard to treat. UKCTOCS was designed to test the hypothesis that a reliable screening method that picks up ovarian cancer earlier, when treatments are more likely to be effective, could save lives.

The latest analysis looked at data from more than 200,000 women aged 50-74 at recruitment who were followed up for an average of 16 years. The women were randomly allocated to one of three groups: no screening, annual screening using an ultrasound scan, and annual multimodal screening involving a blood test followed by an ultrasound scan as a second line test.

The researchers found that, while the approach using multimodal testing succeeded in picking up cancers at an early stage, neither screening method led to a reduction in deaths.

Earlier detection in UKCTOCS did not translate into saving lives. Researchers said this highlighted the importance of requiring evidence that any potential screening test for ovarian cancer actually reduced deaths, as well as detecting cancers earlier.

Professor Usha Menon (MRC Clinical Trials Unit at UCL), lead investigator of UKTOCS, said: "UKCTOCS is the first trial to show that screening can definitely detect ovarian cancer earlier. However, this very large, rigorous trial shows clearly that screening using either of the approaches we tested did not save lives. We therefore cannot recommend ovarian cancer screening for the general population using these methods.

"We are disappointed as this is not the outcome we and everyone involved in the trial had hoped and worked for over so many years. To save lives, we will require a better screening test that detects ovarian cancer earlier and in more women than the multimodal screening strategy we used."

Women aged between 50 and 74 were enrolled in the trial between 2001 and 2005. Screening lasted until 2011 and was either an annual blood test, monitoring changes in the level of the protein CA125, or a yearly vaginal ultrasound scan. About 100,000 women were assigned to the no screening group, and more than 50,000 women to each of the screening groups.

Blood test screening picked up 39% more cancers at an early stage (Stage I/II), while detecting 10% fewer late-stage cancers (Stage III/IV) compared to the no screening group. There was no difference in the stage of cancers detected in the ultrasound group compared to the no screening group.

The initial analysis of deaths in the trial occurred in 2015, but there was not enough data at that time to conclude whether or not screening reduced deaths. By looking at five more years of follow up data from the women involved, researchers are now able to conclude that the screening did not save lives.

Professor Mahesh Parmar, Director of the MRC Clinical Trials Unit at UCL and a senior author on the paper, said: "There have been significant improvements in the treatment of advanced disease in the last 10 years, since screening in our trial ended. Our trial showed that screening was not effective in women who do not have any symptoms of ovarian cancer; in women who do have symptoms early diagnosis, combined with this better treatment, can still make a difference to quality of life and, potentially, improve outcomes. On top of this, getting a diagnosis quickly, whatever the stage of the cancer, is profoundly important to women and their families."

Professor Ian Jacobs, from the University of New South Wales (UNSW Sydney), a co-investigator who has led the ovarian cancer screening research programme since 1985 and who was lead investigator of UKCTOCS from 2001-2014, said: "My thanks to the thousands of women, healthcare professionals and researchers who made this trial possible. The multimodal screening strategy did succeed in detection of ovarian cancer at an earlier stage, but sadly that did not save lives. This is deeply disappointing and frustrating given the hope of all involved that we would save the lives of thousands of women who are affected by ovarian cancer each year."

Professor Jacobs noted: "Population screening for ovarian cancer can only be supported if a test is shown to reduce deaths in a future randomised controlled trial. I remain hopeful that a new effective screening test will be found eventually, but it will take many years to conduct a large trial of the test. Realistically, this means we have to reluctantly accept that population screening for ovarian cancer is more than a decade away."

A huge wealth of samples and data from the trial has been donated by the participants for future research. This resource, referred to as the UKCTOCS Longitudinal Women's Cohort (UKLWC), is now being used by researchers worldwide, helping to improve understanding of ovarian cancer as well as other cancers and other diseases such as cardiovascular disease.

Researchers say that the study has also generated insights into how best to design, conduct and analyse a large-scale randomised clinical trial particularly in individuals who have no signs of disease. These insights will be helpful to future trials in all areas of health. It has also contributed to advances in risk assessment, prevention and diagnosis of ovarian cancer.

The UKCTOCS trial was funded by the NIHR Health Technology Assessment (HTA) Programme and the charities Cancer Research UK and The Eve Appeal.

Michelle Mitchell, Cancer Research UK's Chief Executive, said: "Trials don't always find the result we had hoped for, but we need long-term studies like this to know whether new tests save lives. Cancer Research UK will continue to fund vital research into aggressive forms of ovarian cancer so we can reduce the impact of this disease.

"Screening is for people without symptoms, so it's still important that if you notice unusual or persistent changes to talk to your doctor. Symptoms of ovarian cancer can be quite vague and similar to symptoms caused by less serious conditions, which can make spotting the disease tricky. Whether it's needing to go to the toilet more often, pain, bloating, or something else, raise it with your GP - in most cases it won't be cancer but it's best to get it checked out."

Professor Nick Lemoine, Medical Director, NIHR Clinical Research Network, said: "These important findings from a large-scale trial, involving 200,000 participants, show that annual screening did not succeed in reducing deaths from ovarian cancer.

"However, it's important to note that negative results can be as important as positive. The study has provided important new evidence and insights into how to conduct and analyse future large-scale randomised clinical trials into ovarian cancer, in the hope that this will prevent and diagnose this disease more effectively in the future.

"We thank every single person who took part."

Athena Lamnisos, CEO, The Eve Appeal, said: "The threshold for introducing a national cancer screening programme is a mortality benefit. Of course this is key - saving lives. It's disappointing that this research programme did not show a reduction in mortality from ovarian cancer and so can't be recommended as a national screening programme. However, the impact it had on earlier diagnosis is impressive and important.

"Ovarian cancer is so often diagnosed at stage 3 or 4 and shifting diagnosis one stage earlier makes a huge difference to both treatment options and quality of life. Earlier diagnosis will often reduce the amount and intensity of treatment, and this makes all the difference to women and their families who are living with cancer. It may have also given them more precious time with their loved ones."

Credit: 
University College London

COVID-19 pandemic impacted graduate nursing students at work, home, and school

AURORA, Colo. (May 13, 2021) - Researchers at the University of Colorado College of Nursing found that many of its graduate students suffered from increased stress after the onset of the COVID-19 pandemic. More than 90% of students worked during the pandemic on average nearly 34 hours per week. Juggling school, a varied work-load and changes to their schedules all significantly influenced stress levels.

Graduate nursing students are registered nurses pursuing a Master's degree in Nursing (MS), Doctor of Nursing Practice (DNP), or Doctor of Philosophy (PhD). A total of 222 graduate nursing students completed the survey. The vast majority of students were employed before the pandemic and a significant decrease in employment occurred during the pandemic (97.3% to 90.1%, p?.001). Overall stress increased (p?.001). The increased total stress was associated with students participating in clinical rotations (q?=?0.024) and having a change in work hours (q?=?0.022).

Study findings, published recently in the Journal of Professional Nursing, also reveal that graduate school plans changed due to the pandemic for 18.2% of students.

"The past year brought challenges so unique that it's critical to understand how our students - who juggle clinical work and studies - are faring," says Priscilla Nodine, PhD, CNM, associate professor at the University of Colorado College of Nursing and study author. "Nursing schools need to address graduate student concerns during the pandemic, including having clear communication platforms and offering support services," says Nodine.

"These study results are crucial in understanding how to take care of our future workforce who are already on the front lines," says Nodine. "More federal funding for nurses going back to school to become advanced practice nurses is needed to ease their financial burden and help increase the primary care workforce."

Credit: 
University of Colorado Anschutz Medical Campus

Epigenetic changes drive the fate of a B cell

BOSTON - B cells are the immune cells responsible for creating antibodies, and most B cells, known as B2 cells, produce antibodies in response to a pathogen or a vaccine, providing defense and immunity against infections. But a small subset of long-lived B cells, known as B1 cells, are quite different from their short-lived cousins, the B2 cells. Instead of producing antibodies in response to invaders, they spontaneously make antibodies that perform vital housekeeping functions, such as removing waste like oxidized LDL cholesterol from the blood.

Like all the cells in the body, B1 and B2 cells have the same DNA, and therefore the same starting set of instructions. It is through epigenetic modifications, which open and close different areas of the genome to the machinery that reads the genetic instructions, that the same genome can be used to create unique instructions for each cell type. Understanding how the different epigenetic landscapes - the changes in instructions - allows for these differences in such similar cells is both an important fundamental question in immunology and can help scientists better understand diseases linked to B cells' dysregulation.

Shiv Pillai, MD, PhD, a core member of the Ragon Institute of MGH, MIT and Harvard, studied the DNA modifications present in both cell types during different stages of development to identify an epigenetic signature that may determine whether a cell becomes a B1 or a B2 cell. This work was published recently in the journal Nature Communications.

"Through our analysis, we found the fate of a B cell is determined by epigenetic modifications driven by a protein called DNMT3A," says Vinay Mahajan, MD, PhD, an instructor in Pathology at the Ragon Institute and the paper's first author. "Genetic studies in humans link the genomic regions with these markers to a variety of immune-mediated disorders."

The team studied CpG methylation, a type of epigenetic modification that opens up specific areas of DNA and marks regulatory elements that can turn genes on or off. They discovered a set of regulatory elements with unique features in these B1 and B2 cells. In most cases, CpG methylation is permanent and, once added, is even passed on when the cell replicates. But in B cells, the protein DNMT3A had to continually work to maintain these epigenetic modifications. If DNMT3A was removed from B1 cells, the epigenetic modifications were lost, and chronic lymphomic leukemia (CLL), a cancer caused by the uncontrolled replication of B1 cells, would arise.

"These unique B1 cells are vitally important to our ability to stay healthy," says Pillai. "The antibodies they create help prevent clots and heart attacks. At the same time, understanding what genetic factors regulate them can help us better understand what happens when their regulation goes awry and leads to CLL and other diseases."

Credit: 
Massachusetts General Hospital