Culture

Irvine, Calif., Oct. 7, 2020 - Electrical engineers, computer scientists and biomedical engineers at the University of California, Irvine have created a new lab-on-a-chip that can help study tumor heterogeneity to reduce resistance to cancer therapies.

In a paper published today in Advanced Biosystems, the researchers describe how they combined artificial intelligence, microfluidics and nanoparticle inkjet printing in a device that enables the examination and differentiation of cancers and healthy tissues at the single-cell level.

"Cancer cell and tumor heterogeneity can lead to increased therapeutic resistance and inconsistent outcomes for different patients," said lead author Kushal Joshi, a former UCI graduate student in biomedical engineering. The team's novel biochip addresses this problem by allowing precise characterization of a variety of cancer cells from a sample.

"Single-cell analysis is essential to identify and classify cancer types and study cellular heterogeneity. It's necessary to understand tumor initiation, progression and metastasis in order to design better cancer treatment drugs," said co-author Rahim Esfandyarpour, UCI assistant professor of electrical engineering & computer science as well as biomedical engineering. "Most of the techniques and technologies traditionally used to study cancer are sophisticated, bulky, expensive, and require highly trained operators and long preparation times."

He said his group overcame these challenges by combining machine learning techniques with accessible inkjet printing and microfluidics technology to develop low-cost, miniaturized biochips that are simple to prototype and capable of classifying various cell types.

In the apparatus, samples travel through microfluidic channels with carefully placed electrodes that monitor differences in the electrical properties of diseased versus healthy cells in a single pass. The UCI researchers' innovation was to devise a way to prototype key parts of the biochip in about 20 minutes with an inkjet printer, allowing for easy manufacturing in diverse settings. Most of the materials involved are reusable or, if disposable, inexpensive.

Another aspect of the invention is the incorporation of machine learning to manage the large amount of data the tiny system produces. This branch of AI accelerates the processing and analysis of large datasets, finding patterns and associations, predicting precise outcomes, and aiding in rapid and efficient decision-making.

By including machine learning in the biochip's workflow, the team has improved the accuracy of analysis and reduced the dependency on skilled analysts, which can also make the technology appealing to medical professionals in the developing world, Esfandyarpour said.

"The World Health Organization says that nearly 60 percent of deaths from breast cancer happen because of a lack of early detection programs in countries with meager resources," he said. "Our work has potential applications in single-cell studies, in tumor heterogeneity studies and, perhaps, in point-of-care cancer diagnostics - especially in developing nations where cost, constrained infrastructure and limited access to medical technologies are of the utmost importance."

A recent report published in Science Translational Medicine by MUSC Hollings Cancer Center investigator Sophie Paczesny, M.D., Ph.D., sheds light on immune cell biomarkers that may reveal which patients are most at risk for graft-versus-host disease (GVHD), a life-threatening condition that can arise after hematopoietic stem cell transplantation (HSCT) for treatment of liquid cancers such as leukemia.

"Allogeneic HSCT remains the only validated treatment to cure leukemia," explained Paczesny, chairwoman of the MUSC Department of Microbiology and Immunology. "In HSCT, donor-matched cells are infused into the bloodstream of sick patients and ultimately travel to the bone marrow. Some of these cells are immune cells, which help eliminate residual leukemic cells not killed by chemotherapy. Yet despite careful donor-recipient matching and use of immunosuppressive therapies following transplantation, some of the donor's immune cells may begin to attack the patient's tissues, which is called graft-versus-host disease."

GVHD impacts up to 50% of patients receiving HSCT and can manifest in multiple organs. About a third of those with GVHD experience localized effects within the gastrointestinal tract (GI-GVHD), which carries the highest risk for fatality.

Paczesny described the phenomenon further. "For patients with leukemia, you are providing donor cells that have a different biological, or antigen, signature as compared to the recipient. That is how these immune cells recognize the leukemia and destroy it. However, these antigens are also present in normal tissue, particularly in areas of the body with the most microbiota, like the gut. So that is where the donor immune cells attack and where symptoms are the hardest to treat."

A biomarker story

Bone marrow-derived stem cells are referred to as multipotent, meaning they can mature into many different types of cells. This includes red and white blood cells as well as other immune cell types such as dendritic cells and T-cells that are responsible for balancing immunity and tolerance.

Dendritic cells exchange messages with T-cells by displaying short protein chains on the cell surface, called antigens. T-cells, which become activated when they recognize "non-self" antigens, then play a key role in triggering the body's other defense systems against foreign invaders that can include transplanted cells from a different host.

Previous work from the Paczesny laboratory has shown that immune cell signaling pathways in GI-GVHD increased numbers of "super activated" pathogenic T-cells (Th17 cells) in the blood of these patients. The presence of these aggressive T-cells correlated with lower survival as compared to patients either lacking GVHD or those with less severe forms of GVHD in the skin. These cells were also unique in their ability to be induced by a T-cell signaling receptor called ICOS, short for "inducible T-cell co-stimulator."

"This started as a biomarker story," Paczesny said. "We were trying to understand where the activation of these T-cells was coming from. What was the antigen presenting cell? If you have markers of ICOS signaling on the T-cell side, there should be an ICOS ligand somewhere on the antigen presenting cell in that same cohort of patients."

Because ICOS ligand is located on the surface of antigen-presenting cells, such as dendritic cells, it can easily be detected using existing technologies like flow cytometry that can scan for these external markers on cells in the blood. In this way, individuals who are actively developing symptoms of GI-GVHD following HSCT could potentially be flagged.

Paczesny's group showed that levels of dendritic cells (specifically a population known as plasmacytoid dendritic cells) expressing the ICOS ligand were increased in patients with GI-GVHD as compared to controls. Critically, patients with high levels of these cells had significantly lower three-year survival outcomes compared to those with low levels.

Djamilatou Adom, Ph.D., a postdoctoral fellow working with Paczesny, further explored the role of ICOS signaling in GI-GVHD using mice. First, they showed that genetic elimination of ICOS ligand production in donor-mouse bone marrow cells prior to transplanting them into recipient mice protected the recipient mice from GVHD-related death. Also, using "humanized" mice with nonfunctional immune systems, the researchers discovered that transplanting human ICOS ligand-expressing plasmacytoid dendritic cells into these mice (whose own bone marrow had been destroyed through radiation) led to GVHD with increased levels of Th17 cells within the intestines.

The involvement of plasmacytoid dendritic cells in GVHD was an interesting finding, said Paczesny. "If these cells are not stimulated, they are usually considered more tolerogenic. In other words, they are the good guys. They lessen the severity of GVHD. However, if they become T-cell activating - for instance the ICOS ligand is one of the factors that will activate them by binding ICOS - then they become more toxic and might drive the development of GVHD. This point has previously been controversial in the field; however, past studies have only looked at overall numbers of plasmacytoid dendritic cells in these patients, not the activation status of these cells."

A new drug target in GVHD

Next, Paczesny explored whether targeting cell-to-cell ICOSL-ICOS signaling might prevent GI-GVHD. Classical T-cell activation is induced by the CD28/B7 co-stimulation pathway, in concert with the recognition of foreign antigens by the T-cell receptor. The CD28/B7pathway can be disrupted by the currently approved drugs abatacept and belatacept (Figure 1). However, through mechanisms that are still not well understood, immune cells can escape the CD28/B7 pathway blockade by rerouting or reinforcing their activation through alternative costimulatory pathways like ICOS/ICOSL.

In collaboration with researchers at Alpine Immune Sciences in Seattle, Washington, Paczesny's team found that dosing mice with the drug candidate ALPN-101, a recombinant human Fc fusion molecule that binds and blocks both ICOS and CD28 on T-cells, conferred complete protection from GVHD while also preserving anti-tumor effects of the transplant. It also performed better than drugs targeting CD28 (belatacept) or ICOS pathways individually.

"This is the first time I've seen a drug work as a treatment for GVHD that also preserves anti-leukemic activity of HSCT. This is new," explained Paczesny. "What's also interesting is that the drug was effective when we provided it early, directly after transplantation, and also when we provided it as a later treatment, after disease had already built up. This is important because most of the time GVHD symptoms appear much later, and that's when we need to intervene."

Clinical trials with ALPN-101 have begun, and Paczesny hopes that her biomarker research, which was supported by more than $1.5 million in funding from the National Cancer Institute, will open doors for the treatment of GVHD and other immune-related diseases such as lupus.

"There has been a big jump in the number of transplantations recently because clinicians have improved their HSCT technique and expanded its applications. There is now also more demand for mitigation of allogeneic responses and more need because cellular therapies with third-party donors are also expanding. Therefore, GVHD will continue to be an issue. But now, we have a biomarker that, when it is elevated, will help us know when to begin a specifically targeted treatment."

The team's findings have been published in Nature: Scientific Reports: "Transition delay using biomimetic fish scale arrays", and in the Journal of Experimental Biology: "Streak formation in flow over biomimetic fish scale arrays".

Reducing drag means faster aircraft speeds and less fuel consumption - an important area of study for aerodynamicists such as Professor Bruecker, City's Royal Academy of Engineering Research Chair in Nature-Inspired Sensing and Flow Control for Sustainable Transport, and City's Sir Richard Oliver BAE Systems Chair for Aeronautical Engineering.

Through their biomimetic study, Professor Bruecker's team has discovered that the fish-scale array produces a zig-zag motion of fluid in overlapping regions of the surface of the fish, which in turn causes periodic velocity modulation and a streaky flow that can eliminate Tollmien-Schlichting wave induced transition to reduce skin friction drag by more than 25 percent.

An examination of oil flow visualisation using computational fluid dynamics (CFD) on sea bass and common carp enabled the authors to come up with a working hypothesis:

"Computation Fluid Dynamics (CFD) was used to study the flow pattern over the surface and revealed a hitherto unknown effect of the scales as a mechanism to generate a regular pattern of parallel streamwise velocity streaks in the boundary layer. To prove their existence also on the real fish skin, oil flow visualisation was done on sea bass and common carp, which indeed confirmed their presence in a regular manner along their real body, with the same arrangement relative to the scale array as observed along the biomimetic surface. These results let the authors hypothesize about a possible mechanism for transition delay, inspired by various previous fundamental transition studies, where streaky structures generated by cylindrical roughness elements or vortex generator arrays have shown a delay of transition".

Using the specially equipped laminar water tunnel at the University of Stuttgart in Germany, Professor Bruecker and Professor Rist (University of Stuttgart) have tested the hypothesis of a transition (drag) delay by experimenting with a smooth flat plate and a flat plate covered with biomimetic fish scale arrays.

Their surprising research outcome runs counter to the common belief that roughness promotes by-pass transition. Instead, the scales largely increase the stability of the base flow similar to an array of vortex generators.

A technical realisation of such patterns on aerodynamic surfaces will pave the way towards the drastic reduction in fuel consumption and future zero-emission flight.

CATONSVILLE, MD, October 7, 2020 - New research has shed light on how various political campaign activities influence voters. It found that a candidate's mass media advertising is more likely to influence independent voters, while the campaign's "ground game," targeting voters through grassroots outreach, is more effective at reaching a candidate's base.

The research study, to be published in the October issue of the INFORMS journal Marketing Science, "The Air War versus the Ground Game: An Analysis of Multi-Channel Marketing in U.S. Presidential Elections," is authored by Lingling Zhang of the University of Maryland and Doug J. Chung of Harvard University.

"We decided to study the effects of multichannel marketing in the context of the U.S. presidential elections to determine which approaches are not only more powerful in political applications, but also to see what we can learn and apply across other applications of multichannel marketing," said Chung.

Through their work, the researchers analyzed the multichannel marketing strategies of U.S. presidential campaigns from 2004 through 2012 to identify harbingers for how successful elections are won and will be won in battleground states (states that are considered largely undecided) going forward.

"With more technologies to better target individual voters, the question of how different campaign activities work in different voter segments presented itself to us as increasingly important," said Zhang. "As a result, we saw an opportunity to compare the 'air war' and the 'ground game' of campaigns to gauge effectiveness."

The air war constitutes mass media advertising, consisting mostly of television advertising, whereas the ground game represents door-to-door canvassing, phone calls to households, direct mail to homes, and neighborhood signage.

The study's authors found that since the ground game emerged as more influential among partisan voters, or those who already know who they plan to vote for, the primary objective of the ground game is to encourage voter turnout. And while the air war was determined to have less impact on turnout, it does have greater influence in persuading voters to see a candidate more or less favorably.

"While field campaigning tends to specifically focus on turnout of those whose minds are made up, television advertising, which is less targeted but more informational in nature, tends to be better received by those who are undecided and could still change their minds," said Chung. However, advertising by outside political groups, which has become more prevalent in recent elections, tends to be more negative in nature and is better received by a candidate's base.

A new species of an ancient marine reptile evolved to strike terror into the hearts of the normally safe, fast-swimming fish has been identified by a team of University of Alberta researchers, shedding light on what it took to survive in highly competitive ecosystems.

Gavialimimus almaghribensis, a new type of mosasaur, was catalogued and named by an international research team led by master's student Catie Strong, who performed the research a year ago as part of an undergrad honours thesis guided by vertebrate paleontologist Michael Caldwell, professor in the Faculty of Science, along with collaborators from the University of Cincinnati and Flinders University.

More than a dozen types of mosasaur--which can reach 17 metres in length and resemble an overgrown komodo dragon--ruled over the marine environment in what is now Morocco at the tail end of the Late Cretaceous period between 72 and 66 million years ago.

What differentiates Strong's version, however, is that it features a long, narrow snout and interlocking teeth--similar to the crocodilian gharials, a relative of crocodiles and alligators.

Strong said this discovery adds a layer of clarity to a diverse picture seemingly overcrowded with mega-predators all competing for food, space and resources.

"Its long snout reflects that this mosasaur was likely adapted to a specific form of predation, or niche partitioning, within this larger ecosystem."

Strong explained there is evidence that each species of the giant marine lizard shows adaptations for different prey items or styles of predation.

"For some species, these adaptations can be very prominent, such as the extremely long snout and the interlocking teeth in Gavialimimus, which we hypothesized as helping it to catch rapidly moving prey," she said.

She added another distinctive species would be Globidens simplex--described last year by the Caldwell lab--which has stout, globular teeth adapted for crushing hard prey like shelled animals.

"Not all of the adaptations in these dozen or so species are this dramatic, and in some cases there may have been some overlap in prey items, but overall there is evidence that there's been diversification of these species into different niches," Strong noted.

Alternatively, the main contrasting hypothesis would be a scenario of more direct competition among species. Strong said given the anatomical differences among these mosasaurs, though, the idea of niche partitioning seems more consistent with the anatomy of these various species.

"This does help give another dimension to that diversity and shows how all of these animals living at the same time in the same place were able to branch off and take their own paths through evolution to be able to coexist like that," she said.

The remains of the G. almaghribensis included a metre-long skull and some isolated bones. There was nothing to explain the cause of death of the specimen, which was uncovered in a phosphate mine in Morocco that is rich in fossils.

"Morocco is an incredibly good place to find fossils, especially in these phosphate mines," Strong said. "Those phosphates themselves reflect sediments that would have been deposited in marine environments, so there are a lot of mosasaurs there."

Irvine, CA - Oct. 7, 2020 - N-acetylglucosamine, a simple sugar found in human breast milk and sold as an over-the-counter dietary supplement in the United States, promotes myelin repair in mouse models and correlates with myelination levels in multiple sclerosis patients according to a new University of California, Irvine-led study.

Published in the Journal of Biological Chemistry, the study also demonstrates that in mice, delivering N-acetylglucosamine orally to lactating mothers drove primary myelination in their nursing offspring. N-acetylglucosamine is a simple sugar that is metabolically attached to proteins at the cell surface to control cellular function.

"We found that N-acetylglucosamine activates myelin stem cells to promote primary myelination and myelin repair," said Michael Demetriou, MD, PhD, FRCP(C), professor of neurology, microbiology and molecular genetics at UCI School of Medicine and leader of the study. "Our data raises the intriguing possibility that N-acetylglucosamine may be a simple therapy to promote myelin repair in multiple sclerosis patients". Formal human studies will be required to test this theory.

The failure of robust re-myelination following inflammatory demyelination in multiple sclerosis leads to chronic disability and neurodegeneration. Myelin insulates the long, cable-like nerve cell branches called axons, and serves to increase the speed of electrical signal conduction between neurons. Myelination in the central nervous system also plays an important role in cognitive development during childhood.

"Interestingly, since N-acetylglucosamine is a major component of human breast milk but not baby formula, it may explain some of the cognitive function and myelination benefits realized by children fed breast milk as opposed to formula." said Michael Sy, MD, PhD, assistant professor of neurology at UCI School of Medicine, co-director of the regional MS program at the VA Long Beach Healthcare System, and first author of the study.

Dr. med. Alexander Brandt, MD, who led the clinical parts of the study together with Dr. med. Friedemann Paul, MD, added, "The association of reduced N-acetylglucosamine serum levels with white matter changes in the brain of patients with multiple sclerosis suggests that N-acetyglucosamine deficiency may contribute to disease severity."

The Gerontological Society of America's highly cited, peer-reviewed journals are continuing to publish scientific articles on COVID-19. The following were published between September 24 and October 7; all are free to access:

Intersectionality and inequalities in medical risk for severe COVID-19 in the Canadian Longitudinal Study on Aging: Research article in The Gerontologist by Shen (Lamson) Lin, MA

Older people's non-physical contacts and depression during the COVID-19 lockdown: Research article in The Gerontologist by Bruno Arpino, PhD, Marta Pasqualini, PhD, Valeria Bordone, PhD, and Aïda Solé-Auró, PhD

Problems of Data Availability and Quality for COVID-19 and Older People in Low- and Middle-Income Countries: Forum article in The Gerontologist by Peter Lloyd-Sherlock, PhD, Lucas Sempe, MSc, Martin McKee, DSc, and Aravinda Guntupalli, PhD

URBANA, Ill. - Broiler chicken producers the world over are all too familiar with coccidiosis, a parasite-borne intestinal disease that stalls growth and winnows flocks. Various approaches, developed over decades, have been used to control coccidiosis, but the disease remains widespread.

Recent research from the University of Illinois supports the use of immunomodulatory and antioxidant feed additives to reduce the effects of coccidiosis.

"In the last two decades, partially to get around the parasite's resistance to pharmaceuticals, vaccination has become more prevalent. That's when I got interested, because nutrition is a key element in the effectiveness of vaccines. Diet and health go together in that way," says Ryan Dilger, associate professor in the Department of Animal Sciences at Illinois and principal investigator on the research. "So, what we're talking about here is not a vaccine. Instead, we used nutritional technologies to disrupt the normal reproductive cycle of the parasite."

When a chicken picks up the parasite, of which there are seven major Eimeria species affecting broilers, its body mounts an immune response, starting with a cascade of inflammatory proteins known as cytokines. These cause the bird to stop eating and rest, so the immune system can do its work. In normal disease progression, an anti-inflammatory mediator known as interleukin-10 (IL-10) is eventually produced to keep the inflammation from ramping up too high and causing tissue damage through oxidative stress.

However, Eimeria tricks chickens into over-producing IL-10 earlier than expected, before the immune system can produce enough cytokines to effectively attack the invader. "It's like the parasite is saying, 'Everything's fine. I'm not actually here!' It's really trying to evade the immune response," Dilger says.

To reverse that effect, doctoral student Muhammed Shameer Abdul Rasheed included a novel feed ingredient, a dried egg product with IL-10 antibody activity, in the diet of broiler chickens before inducing coccidiosis.

"We want the bird to have an acute pro-inflammatory response in order to clear the parasite, and that response is dampened when the parasite tricks the bird into overproducing IL-10 antibody. We're trying to take away the parasite's ability to manipulate the bird's own immune system against itself," Rasheed says.

The IL-10 dried egg product has been shown to be effective against mild Eimeria infection in other studies, but it hadn't been tested in severe cases and in the absence of vaccine administration.

"Our results suggested that dietary dried egg product could be beneficial in promoting gut health during severe infection for particular strains of the parasite, even though suppression of the IL-10 response may promote an exaggerated inflammatory reaction in the intestinal epithelium, which may cause subsequent tissue damage," Dilger says.

Uncontrolled inflammatory responses can lead to oxidative stress, where chemicals with unpaired electrons, known as free radicals, start to damage healthy tissue. When Rasheed saw the intestinal damage in this study, he decided to test the combined effects of the IL-10 antibody and an antioxidant known as methylsulfonylmethane or MSM. He had previously tested MSM in chickens and found it had no adverse effects on health or growth, but it had never been tried as a treatment for oxidative stress during coccidiosis.

"The IL-10 antibody works to combat the infection through an immune mechanism, which may inadvertently cause oxidative stress, so MSM was used in combination to specifically combat that tissue damage," Rasheed says. "So the hypothesis was that if these two interventions are working through different mechanisms, combining them together may actually give us a better response than either of them alone."

When the research team fed infected birds a combination of MSM and IL-10 antibody, the treatment showed promise. First, chickens that got the treatment showed greater body weight gain 7-14 days post-infection than birds that didn't consume the dietary products. Also, total antioxidant capacity, an overall indicator of how well an animal can counteract oxidative stress, remained higher in treated birds three and four weeks after infection, suggesting lasting dietary effects.

"In the end, the birds still got sick; they still had an infection that reduced their growth for a certain amount of time. Just like with some pharmaceutical agents designed to lessen the effects of the flu in humans, it's not actually going to prevent you from getting the disease in the first place. However, our goal is to shorten the length of time you're sick," Dilger says. "That's just as meaningful for broiler chickens."

Dilger thinks the dietary interventions may be even more effective in real-world production settings. In the clean, controlled environment of a laboratory study, these broiler chickens were raised on wire flooring to separate the birds from their excrement. However, broiler chickens raised on a commercial farm would be raised on the floor, in direct contact with litter, which is partly how the Eimeria infection cycle continues. In the end, the nutritional strategies studied here may act as a kind of insurance for producers to help birds bounce back sooner.

"Producers may not have coccidiosis when they mix this in the feed, but by the time the chickens consume it, the disease may have reared up again. So if the product is already there, you have some protection," Dilger says. "Again, it's not going to prevent the birds from getting coccidiosis, but hopefully it can reduce the untoward effects and allow them to get back to a healthy state faster and continue growing, such that they can remain productive during that time. It's another important tool in the arsenal for producers."

Studies have long suggested that oxytocin -- a hormone that can also act as a neurotransmitter -- regulates prosocial behavior such as empathy, trust and bonding, which led to its popular labeling as the "love hormone." Mysteriously, oxytocin has also been shown to play a role in antisocial behaviors and emotions, including reduced cooperation, envy and anxiety. How oxytocin could exert such opposite roles had largely remained a mystery, but a new UC Davis study sheds light on how this may work.

Working with California mice, UC Davis researches showed that the "love hormone" oxytocin can sometimes have antisocial effects depending on where in the brain it is made. (Mark Chappell/UC Riverside)

While most oxytocin is produced in an area of the brain known as the hypothalamus, some oxytocin is produced in another brain area known as the bed nucleus of the stria terminalis, or BNST. The BNST is known for its role in the stress response, and it may play a key role in psychiatric disorders such as depression, addiction and anxiety.

The findings of the study, published this week in Proceedings of the National Academy of Sciences USA, show that oxytocin produced in the BNST increases stress-induced social anxiety behaviors in mice. This may provide an explanation as to why oxytocin can sometimes have antisocial effects. The lead author is Natalia Duque-Wilckens, a former doctoral researcher at UC Davis who is now at Michigan State University. The senior author is Brian Trainor, professor of psychology and director of the Behavioral Neuroendocrinology Lab at UC Davis.

"Before this study, we knew that stress increased the activity of the oxytocin-producing neurons located in the BNST, but we didn't know if they could affect behavior. Our experiments show that production of oxytocin in the BNST is necessary for social anxiety behaviors in California mice," said Duque-Wilckens.

Social stress stronger in females

The researchers were able to show this by using a tool called morpholino-oligos, which, when injected directly into the BNST, prevents oxytocin from being produced in this area. Interestingly, while oxytocin neurons in the BNST are present in both males and females, previous studies from this group showed that social stress has stronger long term effects on these neurons in females. This is interesting because social anxiety disorders are more common and more severe in women compared to men.

This study further showed that oxytocin-producing neurons in the BNST are connected to brain regions that control anxiety-related behavior. This was achieved by using a virus to express a fluorescent molecule only in oxytocin neurons.

Remarkably, "simply infusing oxytocin into the parts of the brain that BNST oxytocin neurons connect to caused ordinarily non-stressed mice to show social anxiety behaviors as if they had experienced social stress," said Trainor. Previous studies from this and other labs had shown that oxytocin acting in other areas of the brain, including areas involved in motivated behaviors, had prosocial effects. This suggests that whether the effects of oxytocin are pro- or antisocial will largely depend on which areas of the brain oxytocin is acting in, he said.

"The results are exciting because they provide a potential explanation for why oxytocin sometimes increases anxiety in humans. The vast majority of previous work has focused on the neural mechanisms that underlie the anxiety-reducing effects of oxytocin," Trainor said. "If combined with further studies of how anxiety is connected with brain circuits in humans, these results could give us a better understanding of what conditions oxytocin could be beneficial or harmful for treating anxiety."

It's also possible that in some situations, using a drug that blocks the actions of oxytocin could reduce anxiety, he said. In future studies, researchers will try to understand how these neurons activate in response to stress and why this effect is long-lasting in females, with the final aim of finding therapeutic strategies that could help patients suffering from social anxiety disorder.

Same-gender couples have higher-quality interactions with one another than heterosexual couples in Southern California, a new UC Riverside study finds.

The study also holds that couples with two men have the smallest social networks.

Researcher Megan Robbins says the recently published study is the first to compare same- and different-sex couples' social networks and daily interactions with one another.

Past research shows that same-gender couples enjoy strengths including appreciation of individual differences, positive emotions, and effective communication. But research hasn't compared the quality of their daily interactions - inside and outside the couple dynamic - to those of heterosexual couples. 

"The comparison is important because there is so much research linking the quality of romantic relationships and other social ties to health and well-being, yet it is unclear if this applies similarly or differently to people in same-gender romantic relationships because they have been historically excluded from past research.," said Robbins, who is an associate professor of psychology at UCR. Reasons for potential differences include the stigma sexual minorities face, and also their resilience.

For the study, Robbins and her team recruited same-gender and different-gender couples throughout Southern California. The couples had to be in a married or "married-like" committed relationship; living together for at least a year; and have no physical or mental health conditions that impeded their daily functioning.

Among those who applied to be in the study, 78 couples were found to be eligible, 77 of which provided enough data to be used. Twenty-four of the couples were woman-woman; 20 were man-man, and 33 were man-woman.

Participants met with the researchers on two separate Fridays, a month apart, completing surveys. They received text or email prompts several times in the days following the in-person meetings. In the text/email prompts, participants were asked whether they had an interaction with their partner, a family member, or a friend in the past 10 minutes, then asked to rate the quality of the social interaction using a five-point scale - one being unpleasant; three, neutral; five, pleasant.

In terms of social networks, the study found couples in man-man relationships had smaller social networks than woman-woman and man-woman couples. On the other end of the results spectrum, women in relationships with men were most likely to have the largest social networks.

Robbins said the finding is consistent with previous research showing men with men experience the least acceptance among family members.

"We hypothesized that one model for how the social life of people in same-gender couples might differ from those in different-gender couples was a honing model, where people in same-gender couples reduce their social networks down to only those people who are supportive. We found some support for this by learning that the men with men had the smallest social networks in our sample.," Robbins said.

The quality of interactions with families was reported to be greatest by same-gender couples. There was no difference for interaction quality with friends.

In terms of the quality of interactions with their partners, the study found same-gendered relationships had better-quality interactions than found in different-gendered relationships.

Robbins said that may be due to greater similarity between partners when they share a gender identity, and greater equality within the couple, compared to people in different-sex couples.

"When male and female partners interact, they may do so from a culturally imposed frame wherein men and women are considered 'opposites,' which creates more potential for tension in interactions," Robbins wrote in the paper, titled Social Compensation and Honing Frameworks, and published in the Journal of Social and Personal Relationships.

Fast facts:

In a recent study, NYU Abu Dhabi faculty Alberto Gandolfi proposes alternate weeks of in-classroom and remote teaching as a way to allow students to learn in the classroom while protecting them from COVID-19.

The optimal strategy results in the school opening 90 days out of 200, with the number of COVID-19 cases among the individuals related to the school increasing by nearly 66 percent, instead of the almost 250 percent increase, which is predicted should schools fully reopen.

In the broader context, the model gives the first classification of areas or countries in which schools can reopen full time, or can reopen for a fraction of the days, with distancing and frequent testing, or cannot reopen for the time being.

Abu Dhabi, UAE - October 7, 2020: In a recent study, NYU Abu Dhabi Professor of Practice in Mathematics Alberto Gandolfi has developed a mathematical model to identify the number of days students could attend school to allow them a better learning experience while mitigating infections of COVID-19.

Published in Physicsa D journal, the study shows that blended models, with almost periodic alternations of in-class and remote teaching days or weeks, would be ideal. In a prototypical example, the optimal strategy results in the school opening 90 days out of 200, with the number of COVID-19 cases among the individuals related to the school increasing by about 66 percent, instead of the almost 250 percent increase, which is predicted should schools fully reopen.

The study features five different groups; these include students susceptible to infection, students exposed to infection, students displaying symptoms, asymptomatic students, and recovered students. In addition, Gandolfi's study models other factors, including a seven hour school day as the window for transmission, and the risk of students getting infected outside of school.

Speaking on the development of this model, Gandolfi commented: "The research comes as over one billion students around the world are using remote learning models in the face of the global pandemic, and educators are in need of plans for the upcoming 2020 - 2021 academic year. Given that children come in very close contact within the classrooms, and that the incubation period lasts several days, the study shows that full re-opening of the classrooms is not a viable possibility in most areas. On the other hand, with the development of a vaccine still in its formative stages, studies have placed the potential impact of COVID-19 on children as losing 30 percent of usual progress in reading and 50 percent or more in math."

He added: "The approach aims to provide a viable solution for schools that are planning activities ahead of the 2020 - 2021 academic year. Each school, or group thereof, can adapt the study to its current situation in terms of local COVID-19 diffusion and relative importance assigned to COVID-19 containment versus in-class teaching; it can then compute an optimal opening strategy. As these are mixed solutions in most cases, other aspects of socio-economic life in the area could then be built around the schools' calendar. This way, children can benefit as much as possible from a direct, in class experience, while ensuring that the spread of infection is kept under control."

Using the prevalence of active COVID-19 cases in a region as a proxy for the chance of getting infected, the study gives a first indication, for each country, of the possibilities for school reopening: schools can fully reopen in a few countries, while in most others blended solutions can be attempted, with strict physical distancing, and frequent, generalized, even if not necessarily extremely reliable, testing.

Washington, DC - October 7, 2020 - Researchers have outlined an approach to characterize and develop an effective environmental monitoring methodology for SARS CoV-2 virus, that can be used to better understand viral persistence in built environments. The investigators from 7 institutions published their research this week in mSystems, an open-access journal of the American Society for Microbiology. Built environment refers to the human-made environment that provides the setting for human activity, ranging in scale from buildings to cities and beyond.

"As we all know, SARS CoV-2 is of worldwide concern," said principal investigator of the study Dr. Kasthuri Venkateswaran, senior research scientist at NASA's Jet Propulsion Laboratory (JPL) in Southern California.

For the studies, the researchers used inactivated noninfectious virus that is viable and can be used as a surrogate. "Our group adapted the CDC-approved reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) methodology and then tested the efficacy of RT-qPCR in detecting SARS CoV-2 from various environmental surface samples," said Dr. Ceth W. Parker, one of the 3 lead study authors, a post-doctoral fellow at JPL. The researchers tested a variety of surface materials common in built environments, including bare stainless steal, painted stainless steel, plastics and reinforced fiberglass.

"We tested these surfaces by seeding inactivated noninfectious SARS CoV-2 particles and then determining how well we could actually recover them from the surfaces," said Dr. Parker. "It takes a minimum of 1,000 viral particles per 25 cm2 to effectively and reproducibly detect SARS-CoV-2 virus on the surface. We found that viral RNA can persist on surfaces for at least 8 days. We also found that inhibitory substances and debris have to be taken into account on the surfaces they are being tested on."

A Dartmouth-Gallup study finds that women are more concerned about COVID-19 than men, a difference that transcends party lines. This female perspective towards the pandemic may be overlooked due to the underrepresentation of women in the workplace that is compounded by an underrepresentation in politics, creating what the researchers refer to as a representational "double whammy" effect. The study's findings are published in Politics & Gender.

"Men are less likely to favor precautions for COVID-19 than women, basically across the board," said co-author Deborah Jordan Brooks, an associate professor of government at Dartmouth. "We find that substantial differences exist among male and female Republicans, Independents, and Democrats, and among workplace leaders and rank-and-file workers."

Brooks adds, "The positioning of many high-profile Republicans, including President Trump, regarding a minimal need for precautions regarding COVID-19 does not match up with the substantially more cautious COVID-related preferences of women. In light of President Trump's recent COVID-19 diagnosis and its spread throughout White House staff, our findings imply that the heightened focus on the coronavirus in the final weeks of the campaign has the potential to put the Republican Party at a further disadvantage with female voters."

The study was based on a nationally, representative online survey conducted by Gallup from May 18 to June 14, 2020 on questions relating to COVID-19 concerns, individual preferences and workplace structure. (Confirmatory results from more recent surveys on many of these measures have just been posted by the co-authors on the Gallup website today, Oct. 7). The researchers sought out to examine how views towards COVID-19 may vary by gender, as well as by partisanship and an individual's role in the workplace (worker vs. workplace leader).

Women vs. Men on COVID-19 Overall

The results illustrate that women have a substantially greater concern for COVID-19 than men. One of the survey questions asked whether it was better advice for people without symptoms who are otherwise healthy to stay home as much as possible to avoid contracting or spreading the coronavirus, or lead normal lives as much as possible to avoid interruptions to work and business. The findings show that 28 percent of women thought it was better to lead normal lives versus staying at home, as compared to 40 percent of men.

When asked how soon respondents would return to normal day-to-day activities if there were no government restrictions, 37 percent of men at the time of the study answered "right now," as compared to just 24 percent of women.

These findings that men perceive COVID-19 as less of a risk seem particularly notable in light of the fact that medical research indicates that men are significantly more likely to die from the coronavirus than women.

Gender Differences by Party

While Democrats tend to view COVID-19 as a greater public health risk than Republicans, and women are more likely to be Democrats than men, this study shows that the gender findings go well beyond that. The findings show that women are more concerned and cautious about COVID-19 than their male co-partisans regardless of the party in question.

For example, if there were no government restrictions on being out in public, 69 percent of Republican men would resume regular activities immediately, versus 55 percent of Republican women (the same is true for 36 percent of independent men and 28 percent of independent women, and 7 percent of Democratic men versus 4 percent of Democratic women). Similarly, 37 percent of Republican men reported being "not worried at all" about contracting the coronavirus, versus just 25 percent of Republican women, with significant differences observed for independents and Democrats, as well. (See Table at the end of this release).

Gender Differences Among Workers & Workplace Leaders

The results also show that female workers are more worried about contracting COVID-19 at work and are significantly more worried about returning to work safely due to the pandemic than male workers. Female workers also think that the COVID-19 disruption will last longer than a year and indicated that they would prefer to work remotely, if employers were to leave the decision up to them. As the co-authors state, "male workers are far more bullish about returning to work life as usual than are their female colleagues, and similarly-gender patterns exist among workplace leaders."

The workplace in the U.S. may not reflect or even consider these distinct, female preferences towards COVID-19, since women are severely underrepresented at the highest leadership positions in healthcare, education and other fields. For example, the researchers point out how "only 3 percent of healthcare CEOs and medical divisions chiefs are women" while women account for 80 percent of healthcare workers.

Implications for Party Leadership

Brooks points out that the study's findings on workplace decision-making and political preferences regarding the coronavirus might be more related than they initially appear. "Many female leaders in the Democratic Party, including Speaker of the U.S. House of Representatives Nancy Pelosi (D-CA), have been positioned front-and-center in Democratic policymaking around COVID-19. In contrast, like most high-prestige organizations today, the Republican Party has shockingly few women in its leadership pipeline. The intense focus on COVID-19 during this election - an issue with so many substantial gender differences - may be contributing to the staggeringly-wide gender gap in candidate preference that has been evident in recent poll results," explained Brooks.

PHILADELPHIA--A pay-for performance program that offers enhanced reimbursement to oncology practices for prescribing high-quality, evidence-based cancer drugs increased use of these drugs without significantly changing total spending on care, Penn Medicine researchers report in a new study published online in the Journal of Clinical Oncology. This is the first study to demonstrate how a national insurer's voluntary pay-for-performance program can successfully change prescribing patterns among oncologists to deliver higher-quality cancer care.

"We know that prescribing evidence-based cancer drugs is high-quality care and increases both the length and quality of life for patients with cancer," said co-lead author Justin E. Bekelman, MD, director of the Penn Center for Cancer Care Innovation at the Abramson Cancer Center, a professor of Radiation Oncology in the Perelman School of Medicine at the University of Pennsylvania, and senior fellow at the Leonard Davis Institute for Health Economics. "And yet, changing prescribing patterns has been and remains a big challenge. Based on what we found here, paying oncology practices to prescribe evidence-based drugs can serve as a valuable tactic to improve the quality of cancer care."

To study the program's impact on prescriptions and spending, the researchers analyzed insurance claims data of cancer patients between 2014 and 2017. They found that a payment of $350 a month per patient to oncology practices when oncologists prescribed evidence-based cancer drugs increased prescriptions of those drugs by 5.1 percentage points. The study included nearly 1,900 oncologists and more than 25,000 patients with breast, lung, or colorectal cancers across 14 states--62.2 percent of patients under the program received evidence-based drugs compared to 57.1 percent of those patients without the program.

Evidence-based cancer regimens have been shown to lead to better outcomes, including longer life and less toxicity; however, despite this, not all patients receive them.

Historically, pay-for-performance programs in health care have shown mixed results. Insurers, including private and government entities, have implemented these programs and others as a way to improve the quality of care and also decrease cost growth in health care.

In cancer care, where spending is driven in large part by the costs of cancer drugs and is expected to reach more than $170 billion in 2020, few programs to improve care or reduce spending have had success. A three-year evaluation of Medicare's Oncology Care Model program, an episode-based payment program with no specific incentive for prescribing evidence-based drugs, showed no significant impact on spending nor utilization of emergency department, hospitalizations or cancer drugs.

While not a silver bullet, the voluntary pay-for-performance program from Anthem, Inc., a national health benefits company, known as the Cancer Care Quality Program, is the first and largest to show a significant increase on evidence-based prescriptions in the cancer care setting.

In addition to finding an increase in prescriptions, the researchers found that overall spending did not significantly change under the pay-for-performance program. The amount spent on cancer drugs over a six-month period, however, increased in the pay-for-performance group, going from $48,030 to $51,369, and patient out-of-pocket expenses increased by a small but statistically significant amount, going from $2,217 to $2,470. The researchers also found substantial variability in cancer drug prescribing among oncology practices. Over the course of the study, physicians prescribed 402 unique drug regimens, even though only 60 of those regimens were evidence-based drug regimens in the program.

Both findings highlight the need for further interventions.

"The cost of cancer care is too high, just like other areas in health care," said senior author Amol S. Navathe, MD, PhD, an assistant professor of Medical Ethics and Health Policy and the Healthcare Transformation Institute, and a senior fellow at the Leonard Davis Institute for Health Economics at Penn. "This program is a much needed example of an effective program--one that improved quality of care for patients. As we look forward, we need to build on the success of this program to design programs that also decrease costs."

Researchers from HealthCore, a health outcomes subsidiary of Anthem, and AIM Specialty Health, a wholly owned subsidiary of Anthem, also served as co-authors on the paper.

"We are pleased that this analysis demonstrates that our program indeed can improve the rate of high-value, evidence-based prescribing in oncology," said David Debono, MD, Anthem national medical director for oncology. "Anthem and AIM have placed a considerable focus on the Cancer Care Quality Program since 2014 and will continue to analyze new therapies as they are approved."

Injuries to peripheral nerves -- tissues that transmit bioelectrical signals from the brain to the rest of the body -- often result in chronic pain, neurologic disorders, paralysis or disability. Now, researchers have developed a stretchable conductive hydrogel that could someday be used to repair these types of nerves when there's damage. They report their results in ACS Nano.

Injuries in which a peripheral nerve has been completely severed, such as a deep cut from an accident, are difficult to treat. A common strategy, called autologous nerve transplantation, involves removing a section of peripheral nerve from elsewhere in the body and sewing it onto the ends of the severed one. However, the surgery does not always restore function, and multiple follow-up surgeries are sometimes needed. Artificial nerve grafts, in combination with supporting cells, have also been used, but it often takes a long time for nerves to fully recover. Qun-Dong Shen, Chang-Chun Wang, Ze-Zhang Zhu and colleagues wanted to develop an effective, fast-acting treatment that could replace autologous nerve transplantation. For this purpose, they decided to explore conducting hydrogels -- water-swollen, biocompatible polymers that can transmit bioelectrical signals.

The researchers prepared a tough but stretchable conductive hydrogel containing polyaniline and polyacrylamide. The crosslinked polymer had a 3D microporous network that, once implanted, allowed nerve cells to enter and adhere, helping restore lost tissue. The team showed that the material could conduct bioelectrical signals through a damaged sciatic nerve removed from a toad. Then, they implanted the hydrogel into rats with sciatic nerve injuries. Two weeks later, the rats' nerves recovered their bioelectrical properties, and their walking improved compared with untreated rats. Because the electricity-conducting properties of the material improve with irradiation by near-infrared light, which can penetrate tissues, it could be possible to further enhance nerve conduction and recovery in this way, the researchers say.

The authors acknowledge funding from the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Program for Changjiang Scholars and Innovative Research Team in University, and Program B for Outstanding Ph.D. Candidate of Nanjing University.

The paper's abstract will be available on October 7 at 8 a.m. Eastern time here: http://pubs.acs.org/doi/abs/10.1021/acsnano.0c05197

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