Culture

Bottom Line:

Baseline levels of circulating tumor DNA (ctDNA) predicted responses to first-line, but not second-line, immune checkpoint inhibition in patients with melanoma.

Journal in Which the Study was Published:

Clinical Cancer Research, a journal of the American Association for Cancer Research

Author:

Elin Gray, PhD, an associate professor at Edith Cowan University in Australia and senior author on the study

Background:

"Immunotherapy has become an increasingly common treatment for patients with melanoma, often as the second-line treatment after disease progression on BRAF inhibitors," explained Gray. "There is a lot of interest in identifying biomarkers that reliably indicate how patients will respond to this treatment."

Circulating tumor DNA (ctDNA) is shed from tumors and can be detected in the bloodstream. ctDNA levels have been shown to correlate with responses to targeted therapies in patients with melanoma, but the potential of ctDNA to predict responses to immunotherapy remained unclear.

How the Study was Conducted:

In this study, Gray and colleagues prospectively examined the association between baseline (pre-treatment) ctDNA levels and clinical outcomes in a discovery cohort of 125 adult patients with metastatic melanoma. Thirty-two patients were treated with immune checkpoint inhibition in the first-line setting, while 27 patients received immune checkpoint inhibition in the second-line setting. The remaining 66 patients were not treated with immune checkpoint inhibition and instead received first-line treatment with targeted therapy.

Results:

Consistent with previous studies, patients with low baseline ctDNA levels (fewer than or equal to 20 copies per milliliter) who were treated with targeted therapy had longer progression-free survival than those with high baseline ctDNA levels (greater than 20 copies per milliliter). In patients treated with first-line immune checkpoint inhibition, those with low baseline ctDNA levels had an 80 percent longer progression-free survival than those with high ctDNA levels. Baseline ctDNA levels were associated with progression-free survival after first-line immune checkpoint inhibition even after controlling for other factors, such as sex, age, tumor stage, BRAF mutation status, and brain metastases. In contrast, there was no significant association between baseline ctDNA levels and progression-free survival in patients who received immune checkpoint inhibitors in the second-line setting.

Gray and colleagues then verified these results in a separate validation cohort of 128 patients with melanoma recruited at other institutions across Australia (the Melanoma Institute Australia and the Peter MacCallum Cancer Centre). Patients in the validation cohort were treated with immune checkpoint inhibition in either the first- or second-line setting (77 and 51 patients, respectively). Similar to results seen in the discovery cohort, baseline ctDNA levels were associated with progression-free survival in patients who received first-line immune checkpoint inhibition, but not in those who received second-line immune checkpoint inhibition. In patients treated with first-line immune checkpoint inhibition, low baseline ctDNA levels were associated with a 58 percent longer progression-free survival than those with high baseline ctDNA levels. The association was independent of sex, age, tumor stage, BRAF mutation status, and brain metastases.

In addition, the authors observed that patients with high ctDNA levels who were treated with combination immune checkpoint inhibition (anti-CTLA4 and anti-PD1) had longer progression-free survival and overall survival than those treated with a single agent (anti-PD1); however, these results were not statistically significant. Gray cautioned that these results were obtained by combining the discovery and validation cohorts and therefore require independent validation. She added that these results, if validated, highlight a potential for ctDNA to identify patients who are more likely to benefit from combination immunotherapy.

Author's Comments:

"Our results indicate that it is necessary to carefully consider context when implementing biomarkers," said Gray. "ctDNA is often heralded as a good prognostic biomarker, but we found that this is not the case for patients receiving immune checkpoint inhibitors in the second-line setting.

"We need more of these kinds of studies evaluating the accuracy of ctDNA in various disease contexts, particularly now that liquid biopsy and ctDNA are being increasingly incorporated into the clinic," she added.

Future work from Gray and colleagues will aim to understand how tumor biology and the tumor site affect the release of ctDNA. In addition, they are interested in evaluating ctDNA as a biomarker of disease progression.

Study Limitations:

Limitations of the study included small sample sizes within some subgroups and potential variability in how progressive disease was measured among different patients.

The National Institutes of Health has launched an adaptive Phase 3 clinical trial to evaluate the safety and efficacy of three immune modulator drugs in hospitalized adults with COVID-19. Some COVID-19 patients experience an immune response in which the immune system unleashes excessive amounts of proteins that trigger inflammation -- called a "cytokine storm" -- that can lead to acute respiratory distress syndrome, multiple organ failure and other life-threatening complications. The clinical trial aims to determine if modulating that immune response can reduce the need for ventilators and shorten hospital stays. The trial, known as ACTIV-1 Immune Modulators (IM), will determine if the therapeutics are able to restore balance to an overactive immune system.

Part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative, the trial expects to enroll approximately 2,100 hospitalized adults with moderate to severe COVID-19 at medical facilities in the United States and Latin America. The National Center for Advancing Translational Sciences (NCATS), part of NIH, will coordinate and oversee the trial with funding support from the Biomedical Advanced Research and Development Authority (BARDA) of the U.S. Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response, in support of the Trump administration's Operation Warp Speed goals. BARDA's Clinical Studies Network will be responsible for operationalizing the trial through a task order awarded to contract research organization Technical Resources International, Inc.

"This is the fifth master protocol to be launched under the ACTIV partnership in an unprecedented timeframe, and focuses efforts on therapies that hold the greatest promise for treating COVID-19," said NIH Director Francis S. Collins, M.D., Ph.D. "Immune modulators provide another treatment modality in the ACTIV therapeutic toolkit to help manage the complex, multi-system conditions that can be caused by this very serious disease."

ACTIV-1 IM is a randomized, placebo-controlled trial that uses an adaptive master protocol. One of the hallmarks of master protocols is that they allow coordinated and efficient evaluation of multiple investigational agents as they become available. This enables maximum flexibility to swiftly weed out drugs that do not demonstrate effectiveness, identify those that do in a short time frame, and rapidly incorporate additional experimental agents into the trial.

The ACTIV public-private partnership selected three agents for the study from a pool of over 130 immune modulators initially reviewed based on several factors, including their relevance to COVID-19, strong evidence for use against inflammatory reaction and cytokine storm, and availability for large-scale clinical studies. The initial agents are infliximab (REMICADE), developed by Janssen Research & Development, LLC., one of the Janssen Pharmaceutical Companies of Johnson & Johnson; abatacept (ORENCIA), developed by Bristol Myers Squibb; and Cenicriviroc (CVC), an investigational late-stage agent developed by AbbVie.

All participants in the trial will receive remdesivir, which is the current standard of care treatment of hospitalized patients with COVID-19. Convalescent plasma and dexamethasone will be allowed at the discretion of the site investigator and in accordance with national guidelines. They will be randomly assigned to receive a placebo or one of the immune modulators as an add-on treatment. The trial will study the different combination treatment regimens with respect to illness severity, recovery speed, mortality and hospital resource utilization.

Enrollment is now open, and the trial is expected to last approximately six months. Results will be available shortly after the trial is completed, or possibly sooner if analysis conducted during the trial indicates that one or more of the drugs is beneficial. To ensure that the trial is being conducted in a safe and effective manner, an independent data and safety monitoring board will oversee the trial and conduct periodic reviews of the accumulating data.

The protocol team chair is William G. Powderly, M.D., director of the Institute for Clinical and Translational Sciences and co-director of the Division of Infectious Diseases at Washington University School of Medicine in St. Louis. NCATS' Clinical and Translational Science Awards (CTSA) Program and the Trial Innovation Network will play a key role in adding U.S. study sites and enrolling patients, including those from communities disproportionately affected by COVID-19.

"The CTSA Program's nimbleness and innovation in conducting clinical trials--along with the network's extensive capacity and broad geographical reach--have positioned it to rapidly implement this important trial," said NCATS Director Christopher P. Austin, M.D. "The innovative trial design will allow efficient evaluation of three different potential COVID-19 treatments concurrently, delivering new possible treatments for patients more quickly and valuable insights into the science of clinical translation."

Animal cooperation typically involves sharing crucial resources -- and the rules of sharing get complicated, especially when males are involved.

Natural selection theory dictates that males generally compete with each other for food and mates. Thus male cooperation in the animal world is an enigma, especially among unrelated animals.

In a new paper published in Scientific Reports, biologists from the Wildlife Institute of India and the University of Minnesota demonstrated the hows and whys of cooperation among male lions. By studying one of the rarest lion populations in the world -- the Asian lions that live as a single population in the Gir Forest of India -- researchers found that cooperation among lions does not necessarily indicate that they are related.

"In a 2017 study, we detailed the behavioural nuances of why male lions cooperate: to better protect their territories and have more access to mating opportunities than males who live alone," said study lead author Stotra Chakrabarti, a postdoctoral research associate in the Department of Fisheries, Wildlife, and Conservation Biology at the University of Minnesota. "However, a lack of genetic data from the population at this stage had prevented us from determining if such cooperation extended to relatives only, or whether non-kin were included as well."

Subsequent monitoring of individual lions and collection of tissue, hair and blood samples from known individuals set the stage to find out whether the cooperating males were related or they came together by chance.

"Genetic analyses of the Gir lions were tricky because they have undergone two population bottlenecks that have rendered discerning kin versus non-kin quite challenging," said Vishnupriya Kolipakam, co-author and faculty at the Wildlife Institute of India..

By synthesizing long-term behavioural and genetic records of known mothers, offspring and siblings, researchers were able to develop a baseline panel against which male coalition partners were compared to understand the level of relatedness between them.

By observing 23 male lions belonging to 10 coalitions, Chakrabarti and co-authors could identify that males who lived in large coalitions (such as trios and quartets) were typically brothers and cousins, but more than 70 percent of pairs consisted of unrelated males.

In large coalitions, sharing is costlier because resources are divided between many lions, and often low-ranking partners are excluded from opportunities to breed. Such coalitions are only possible between related animals.

"Forgoing mating opportunities is generally a severe evolutionary cost, unless in doing so you help related individuals," said Joseph Bump, co-author and associate professor at the University of Minnesota. "As a consequence, this evidence supports a conclusion that large male lion coalitions are feasible only when all partners are brothers and/or cousins."

Large coalitions fared the best as a group, but the fitness of individual lions -- measured by the number of potential offspring sired -- was higher in pairs. Such high fitness for individual male lions in pairs allowed even unrelated individuals to team up, because pairs always fared better than single males in terms of territory and mate acquisition.

"The results of our study show that male coalitions prosper better than loners in established lion societies and this can have crucial implications for their conservation, especially when establishing new populations through reintroductions," said YV Jhala, principal investigator of the Gir lion project and the Dean of the Wildlife Institute of India.

Though large coalitions fared better as a group, they are rare in the Gir system because so few sets of sibling lions grow to maturity. An analysis of 20 years of lion demography data indicates only 12%-13% of the observed lion coalitions in Gir are made of three or four males.

"This calculation of demography and the availability of kin to support cooperation is often missing from studies on animal societies, but it is of fundamental value that enhances our understanding of how optimality in group formation is constrained in the real world," Jhala said.

The study revealed new details about the behavior of male lions. For example, in a rare observation, researchers determined one of the study's coalitions could be a father-son duo because they were related and had an age difference of about five years.

"Such an observation was only possible because we could combine field observations with genetic data, and it shows that there could be multiple pathways for coalition formation in lions," said Kolipakam.

Researchers also observed that related male partners were no more likely to support each other during fights with rivals than unrelated partners.

"This shows that kin support is not the only reason why males cooperate with each other, but kin support makes the cooperation even more beneficial," Bump said.

The study indicates that underlying mechanisms facilitating cooperation in lions can be multifaceted.

"We have quantified the ultimate reasons why unrelated males team up, but it would be worthwhile to investigate other aspects of male cooperation, including how their bonds are forged in the first place, how they find compatible partners, what breaks the ice between them when they first meet and how they decide who will lead and who will follow." Chakrabarti said.

Washington, DC - October 16, 2020 - In the absence of approved, effective treatments for COVID-19, some hospitals have been treating patients with severe COVID symptoms with blood plasma from recovering patients. The blood of recovered patients contains antibodies that act against the coronavirus. While plasma hasn't yet shown a benefit in randomized trials, some small retrospective studies suggest it may reduce illness severity and reduce hospitalization time.

This week in mBio, an open-access journal of the American Society for Microbiology, researchers report that antibody levels in the blood of COVID-19 patients drop rapidly during the weeks after their bodies have cleared the virus and symptoms have subsided. If convalescent plasma is ultimately shown to have a clear benefit, the authors concluded, then it needs to be collected during a specific window of time after recovery. However, recovering patients can't donate blood until at least 14 days after symptoms have subsided, to give the body time to clear viral particles.

"We don't want to transfuse the virus, just transfuse the antibodies," said Andrés Finzi, Ph.D., at the University of Montreal, in Canada. "But at the same time, our work shows that the capacity of the plasma to neutralize viral particles is going down during those first weeks."

The spike protein of SARS-CoV-2 plays a crucial role in helping the virus grab and invade host cells. Antibodies produced by the body's immune system bind to a part of this protein and block the capacity of this "key" to engage with the host's cellular "lock", said Finzi, preventing the viral particle from infecting a cell host.

Previous studies suggest that antibodies against the SARS-CoV-2 spike protein peak 2 or 3 weeks after the onset of symptoms. Findings from an earlier cross-sectional study by Finzi's group, involving more than 100 patients, suggested that the ability of plasma to neutralize the virus decreased significantly between 3 and 6 weeks after symptom onset.

In the new longitudinal study, Finzi and his colleagues analyzed blood samples collected at one-month intervals from 31 individuals recovering from COVID-19. They measured levels of immunoglobulins that act against the coronavirus S protein and tested the ability of the antibodies to neutralize the virus.

The researchers observed variation on the level of individual patients but identified a consistent overall signal: The levels of Immunoglobulins G, A, and M that target the binding site decreased between 6 and 10 weeks after symptoms began. During the same time period, the ability of the antibodies to neutralize the virus similarly fell.

Finzi's group has continued to study blood samples from the patients. Understanding how the levels of antibodies change over time, he said, is critical not only for optimizing the use of convalescent plasma but also for understanding vaccine efficacy and whether or not previously infected people are at risk of re-infection.

"How long do antibodies protect you?" he asked.

Finzi's other research focuses on the immune response to human immunodeficiency virus, or HIV, which differs dramatically from SARS-CoV-2.

"Essential services" is a phrase that has become commonplace in the era of COVID-19. In a new commentary piece, scholars from Lehigh University and Ohio State University argue that LGBTQ+ college and university campus resource centers are essential to the health, well-being and academic achievement of LGBTQ+ students. These centers, they write, are uniquely positioned to meet the needs of these students during COVID-19 and, as such, must continue to receive support and funding.

"Why LGBTQ+ Campus Resource Centers are Essential" has been published by Psychology of Sexual Orientation and Gender Diversity, a publication of the American Psychological Association and is authored by Chelsea Gilbert, PhD student in Educational Studies at Ohio State University; Nicole L. Johnson, a faculty member in Counseling Psychology at Lehigh University; Claire Siepser, Master of Education student in Counseling Psychology at Lehigh University; and, Ann E. Fink, a faculty member in the Department of Biological Sciences at Lehigh University.

"LGBTQ+ populations are particularly vulnerable to certain stressors and risks at play during the COVID-19 pandemic, particularly if they also belong to other marginalized social groups," says Fink. "LGBTQ+ Campus Centers are essential resources for LGBTQ+ students and require adequate funding and institutional support."

Lesbian, Gay, Bisexual, Transgender, Queer (LGBTQ) and other marginalized genders and sexualities (+) face well-documented health disparities, according to information distributed by the Centers for Disease Control and Prevention. These disparities have been exacerbated by the pandemic. The authors specifically cite research which finds significantly higher risk for COVID-19 among the houseless and the fact that LGBTQ+ youth have higher rates of houselessness than the general population. In addition, they write that "The current administration's reversal of non-discrimination protections for LGBTQ+ individuals within healthcare settings has likely exacerbated these concerns around negative experiences...For those who do access care for COVID-19-related symptoms, a lack of LGBTQ+-competent providers may increase their vulnerability within healthcare settings..."

College students often experience marginalization and discrimination, according to a 2014 study that found that more than 25% of Lesgian, Gay and Bisexual college students either witnessed or experienced some of form of harassment which correlated with increased reports of anxiety and depression.

"College students' experiences shifted dramatically as a result of COVID-19, often to the detriment of their health and well-being. For example, many LGBTQ+ students returned to unsafe and/or unsupportive homes when they were unable to remain on-campus; the abrupt and unexpected shift into these harmful and traumatic environments has exacerbated the need for additional support services..." they write.

"These are challenging times within higher education, and tough budgetary decisions are being made daily," says Gilbert, who for five years served as the Director of the Pride Center for Sexual Orientation & Gender Diversity at Lehigh. "It is my hope that decision-makers for these budgets might read our piece and consider the ways that LGBTQ+ student services provide invaluable resources to campus communities in light of COVID-19."

According to the Campus LGBTQ Centers Directory, there are over 275 LGBTQ+ campus resource centers in the U.S. Research demonstrates that the presence of these centers is correlated with lower levels of discrimination, less distress and increased self-acceptance akong LGBTQ+ students. The core functions of these campus resource centers fall into three categories, the authors write: counseling, support and student sense of belonging; education and training; and, advocacy for LGBTQ+ students.

"It is my hope that the individuals who are in charge of making challenging decisions about what is considered essential during times of crisis will read this piece and see the true need for LGBTQ+ student services, especially in the midst of a pandemic," says Johnson.

Adds Siepser: "It is difficult to assess the depth and longevity of the psychological impact of this crisis and thus it is important to continue to support the LGBTQ+ students who are being disproportionately affected by COVID-19."

The authors call on administrators, faculty and students to undertake efforts to ensure that "institutional leaders and decision-makers understand the gravity of LGBTQ+ student needs under COVID-19 and then act to meet those needs."

"Students, faculty, and staff who may not have direct control over these decisions, can use their voices to advocate for such important decisions," says Johnson "This article includes a section dedicated to suggestions for action that we hope inspires many to do just that. Take action!"

A new Alzheimer's study found that impaired blood flow in the brain is correlated with the buildup of tau tangles, a hallmark indicator of cognitive decline.

The work, published this week in the Journal of Neuroscience, suggests that treatments targeting vascular health in the brain -- as well as amyloid plaques and tau tangles -- may be more effective in preserving memory and cognitive function than single-target therapies.

"This study confirms that we should carefully consider vascular health and associated risk factors -- like high blood pressure, smoking and physical inactivity -- in the course of Alzheimer's prevention," said Judy Pa, an associate professor of neurology at the Keck School of Medicine of USC's Mark and Mary Stevens Neuroimaging and Informatics Institute (INI) and the study's senior author.

Researchers wanted to understand how restricted blood flow in the brain relates to the buildup of tau proteins characteristic of Alzheimer's disease. To do so, the team examined MRI and PET images, as well as cerebrospinal fluid, among two groups: cognitively normal individuals and those at various stages of dementia, including mild cognitive impairment and Alzheimer's disease.

Pa and her colleagues found that those with a strong overlap between vascular dysfunction and tau pathology in key Alzheimer's brain regions had the worst cognitive symptoms.

"This connection was most pronounced among those in more advanced stages of the disease, suggesting that the pathway corresponds to cognitive decline over time," Pa said.

That finding is particularly important because it suggests the pathway could be a useful biological marker for measuring Alzheimer's progression in patients. The effect was also most pronounced in amyloid-positive individuals, pointing to a relationship between cerebrovascular, tau and amyloid pathologies.

The research team included a group of experts from the INI and across the Keck School of Medicine's departments of neurology, radiology and physiology and neuroscience. Future steps include evaluating how the synergy between these pathologies relates to cognitive decline over time.

"We're now starting to fully appreciate the role of vascular dysfunction in Alzheimer's disease," said Arthur W. Toga, a coauthor of the study and director of the INI. "Controlling risk factors like smoking and high blood pressure are accessible lifestyle modifications that offer hope for those at risk."

PISCATAWAY, NJ - When governments create a minimum price for alcoholic beverages, deaths and hospitalizations related to alcohol use significantly decrease, according to results from a new report in the Journal of Studies on Alcohol and Drugs.

Called "minimum unit pricing," such policies "would result in a substantial and lasting reduction in the harms caused by alcohol in society," says lead researcher Adam Sherk, Ph.D., of the Canadian Institute for Substance Use Research at the University of Victoria in British Columbia, Canada.

"As we continue to weather the COVID-19 pandemic and hear concerns about overwhelming our health care systems, this study shows that a minimum unit price for alcohol would help to free up valuable resources by decreasing alcohol's burden on our health care systems," says Sherk.

Minimum unit pricing strategies set a "floor price" for alcohol sales. Specifically, a standard drink -- defined by pure alcohol content [in Canada and the United States, about the amount of ethanol in a 5% bottle of beer] -- cannot be sold below a predetermined value. Such policies help prevent the sale of cheap drinks with high alcohol content. They tend to have their largest effect on inexpensive spirits and the smallest effect on wine.

Similar pricing strategies have already been implemented with initial success in places such as Scotland, Wales and some provinces in Canada. In their study, Sherk and his colleagues sought to determine the potential effect of minimum unit pricing in Québec, a province that has yet to institute such a policy.

For their research, the investigators used a new, open-access model -- the International Model of Alcohol Harms and Policies (InterMAHP) -- which can be used to estimate alcohol harms in a country or state as well as the potential health impact of alcohol policies designed to limit such harms.

Using this model, Sherk and his colleagues input per capita alcohol use data from the Canadian Institute for Substance Use Research. Further, data about hospitalizations and deaths were obtained from government statistics, as was information about sales of wine, spirits and liqueurs (which are partially controlled by the government in Canada). Information about beer sales was obtained from the market research company Nielsen.

In Québec in 2014, the year analyzed, there were an estimated 2,850 deaths and 24,694 hospitalizations attributable to alcohol use, the researchers found. These included deaths from cancer, cardiovascular conditions, and injuries. The leading causes of hospitalizations from alcohol use were unintentional injuries, psychiatric conditions, cancer, digestive conditions, and communicable disease.

The researchers' modeling determined that, if the province had previously instituted a minimum unit pricing policy of CAD$1.50 per standard drink (about USD$1.12), 169 deaths would have been prevented, a reduction of 5.9 percent. Having instituted a minimum unit price of CAD$1.75 per drink (about USD$1.31) would have prevented 327 deaths, a decrease of 11.5 percent.

Further, a minimum unit pricing policy of CAD$1.50 per drink would have resulted in 2,063 fewer hospitalizations that year (an 8.4 percent decrease). A price of CAD$1.75 would have reduced hospitalizations by 4,014, or 16.3 percent.

But what impact would this pricing have on any purported health benefits of alcohol? Although their data did show that alcohol use was related to decreased hospitalizations for cardiovascular conditions and diabetes, the modeling demonstrated that minimum unit pricing would have prevented even more hospitalizations.

"This report adds to the growing body of evidence that minimum unit pricing policies are an effective way for governments to reduce alcohol-related hospital visits and save lives," says Sherk. "National and jurisdictional governments, including Québec, should consider following the lead of countries like Scotland and implementing these policies."

(To learn more about The International Model of Alcohol Harms and Policies [InterMAHP], visit http://www.intermahp.cisur.ca.)

The increased adherence of women to Coronavirus policies may be one of the reasons for the lower vulnerability and mortality that they experienced, compared to men, in the early phase of the epidemic. "Policy makers who promote a new normality made of reduced mobility, face masks and other behavioral changes," says Vincenzo Galasso, one of the authors of a new study on gender differences in the reaction to COVID-19, "should, therefore, design a gender-differentiated communication if they want to increase the compliance of men."

Two of the authors of the research, which appeared on PNAS (Proceedings of the National Academy of Sciences) are scholars of Bocconi University, Vincenzo Galasso and Paola Profeta, affiliated to Bocconi's COVID Crisis Lab.

The authors observe substantial gender differences in both attitudes and behaviors through a two-wave survey (March and April 2020), with 21,649 respondents in Australia, Austria, France, Germany, Italy, New Zealand, the UK and the US, which is part of the international project REPEAT (REpresentations, PErceptions and ATtitudes on the COVID-19).

Women around the world are more inclined than men to consider COVID-19 a very serious health problem (59% against 48.7% in March and 39.6% against 33% in April), they are more inclined to agree with public policies that fight the pandemic, such as mobility restrictions and social distancing (54,1 against 47,7 in an index that goes from 1 to 100 in March and 42,6 against 37,4 in April) and are clearly more inclined to follow the rules concerning COVID-19 (88,1% against 83,2% in March and 77,6% against 71,8% in April).

The share of individuals complying with the rules drops over time, particularly in Germany, from 85.8% of women and 81.5% of men in March to 70.5% of women and 63.7% of men in April, but the large gender gap persists.

"The biggest differences between men and women relate to behaviors that serve to protect others above all, such as coughing in the elbow, unlike those that can protect both themselves and others," says Profeta.
Gender differences persist even after the study controlled a large number of sociodemographic characteristics and psychological factors.

However, such differences are smaller among married couples, who live together and share their views with each other, and among individuals most directly exposed to the pandemic. They decrease over time if men and women are exposed to the same flow of information about the pandemic.

The share of U.S. adults who support an active government role in society increased by more than 40 percent during the initial pandemic response--up from 24 percent in September 2019 to 34 percent in April 2020--according to a new national public opinion survey conducted by researchers at the Johns Hopkins Bloomberg School of Public Health and the Johns Hopkins University SNF Agora Institute.

The survey, fielded April 7 through April 13, 2020, also found that, among U.S. adults who endorsed a strong government role in society, a majority supported health, unemployment, and income-related policies aimed at bolstering the social safety net for vulnerable groups in society.

The findings, to be published online October 15 in the American Journal of Public Health, measured public support for social safety net policies during the initial outbreak of the novel coronavirus to assess how public support was associated with beliefs about the role of government.

Among the adults who supported a stronger government role, 88 percent supported two-weeks paid sick leave, 80 percent supported increased minimum federal wage, 77 percent supported employment education and training as unemployment benefits, and 73 percent supported universal health insurance.

"Critical safety net policies passed in the initial phase of the pandemic are expiring or have expired, and finding common ground on extending them has proved difficult," says the lead author, Colleen L. Barry, PhD, MPP, Fred and Julie Soper Professor and Chair of the Department of Health Policy and Management at the Bloomberg School. "An awareness on the part of policymakers of heightened support for the government aiding individuals and families who have experienced pandemic-related dislocations could make a difference."

In the initial phase of the coronavirus outbreak in the U.S., 22 million individuals filed for unemployment benefits and an estimated 9.2 million lost their employer-based health insurance. On March 18, 2020, the U.S. Congress quickly passed the Families First Coronavirus

Response Act, which is in effect through December 2020, and included paid sick days and other leave benefits related to COVID-19. The Coronavirus Aid, Relief, and Economics Security (CARES) Act offers tax credits to support worker retention and is in effect through January 1, 2021. In addition, the CARES Act had increased unemployment benefits by an extra $600 per week through July 31, 2020 to workers affected by the pandemic. Efforts by Congress to extend these expanded unemployment benefits have repeatedly stalled.

The survey, fielded using NORC's Amerispeak Panel, drew from a nationally representative sample of 1,468 U.S. adults. The respondents were asked about their support for 11 safety net policies such as paid sick leave and universal health insurance; income support and unemployment policies; tax credits for businesses; and employment education and training.

The survey found that a majority of U.S. adults strongly supported seven of the 11 social safety net policies. Among the findings:

77 percent of adults supported employer-guaranteed two-weeks paid sick leave

60 percent supported universal health insurance

58 percent supported increasing the federal minimum wage

52 percent supported extension of unemployment benefits

66 percent supported tax credits to businesses to retain and hire workers

68 percent supported employment education and training programs

71 percent supported public spending on construction projects like building roads or highways

The researchers found less support for single payer health insurance, 47 percent; government-funded paid sick leave, 39 percent; and government-funded family leave, 48 percent. There was also less support for universal basic income, at 39 percent.

"As Congress debates continued relief for Americans suffering health and economic consequences from the pandemic, our data shows there is growing support for passing the kind of policies that they have been unable to pass in the last few months," says co-author Hahrie Han, PhD, director of the SNF Agora Institute at Johns Hopkins University.

"Public Support for Social Safety-Net Policies for Covid-19 in the US, April 2020" was written by Colleen Barry, Hahrie Han, Rachel Presskreischer, Kelly Anderson, and Emma McGinty.

Tumors of the pancreas are particularly feared. They are usually discovered late and mortality is high. Until now, no targeted and personalized therapies exist. Scientists at the German Cancer Research Center (DKFZ) and the Heidelberg Institute for Stem Cell Technology and Experimental Medicine* (HI-STEM) have now succeeded for the first time in defining two differently aggressive molecular subtypes of pancreatic carcinoma. This provides new insights into the origin of the tumors. In the more aggressive group of tumors, a phenomenon known as "viral mimicry" leads to a cancer-promoting inflammatory reaction. This could possibly be the starting point for the development of a targeted, subtype-oriented therapy. The results have now been published in the journal Cancer Discovery.

Pancreatic carcinoma is particularly insidious. The disease usually progresses without symptoms over a long period of time and is only diagnosed in advanced stages - when it is difficult to treat. The mortality rate for this tumor disease is therefore particularly high. In contrast to many other cancers, scientists have not yet succeeded in identifying efficient targets for a targeted personalized therapy. Most patients with an advanced tumor disease receive a similar treatment - usually consisting of a combination chemotherapy.

About 95 percent of all cases of pancreatic cancer are so-called adenocarcinomas. "In the past, there have been attempts to work out genetic differences, but it turned out that all adenocarcinomas of the pancreas carry a similar collection of mutations," explains Andreas Trumpp, stem cell researcher at DKFZ and HI-STEM. Trumpp's team has now chosen a different approach in collaboration with the Department of Surgery at Heidelberg University Hospital. From tissue samples from patients, they first isolated pure cancer cells from the tumors' complex cell mixture, which contains large amounts of connective tissue, vessels and immune cells. The researchers then searched the genome of the purified tumor cells for differences in the methylation pattern. These are chemical labels attached tot he DANN molecule that determine whether a gene segment is active or not.

"Based on the methylation patterns of the tumor genomes, we were able to define two completely different subtypes of adenocarcinomas, which differ in the course of carcinogenesis and in their aggressiveness," says Elisa Espinet, first author of the current publication. One of the two subtypes is much more aggressive and actually develops directly from the ductal cells lining the ductal system of the pancreas, while the less aggressive tumors develop from glandular cells. "We have thus discovered a molecular signature that allows us to distinguish between two subtypes of pancreatic carcinoma that are also clinically different," explains Espinet.

What's more, upon closer analysis of the methylation patterns, the Heidelberg researchers discovered that very specific regions in the genome carry fewer methyl groups in the more aggressive subtype. These genome regions contained sequences of so-called endogenous retroviruses, remnants of viruses that have remained in the human genome during evolution. Due to the methylation of their DNA, they are normally silenced and do not play a significant role in healthy individuals. In this subtype, however, they become active again when the methyl groups are removed and form double-stranded RNA strands.

This type of RNA molecule does not normally occur in the body and is therefore a warning signal for the immune system that viruses have entered the cell. As a result, the interferon system is activated and tries to fight the invading viruses. As a result, inflammatory messengers are also released in the vicinity of the tumor. "Feigning a viral infection in genetically modified tumor cells is called "viral mimicry", says Espinet. In the tumor, the viral mimicry promotes certain inflammatory reactions that further drive cancer growth and, in addition, probably stimulates metastasis, i.e. the formation of the dreaded daughter tumors.

The DKFZ researchers found viral mimicry only in the ductal subtype and in traces also in healthy ductal cells, but not in the healthy glandular cells of the pancreas or the pancreatic cancer cells of the less aggressive subtype. This explained why pancreatic tumors that develop directly from the cells of the pancreatic ducts, which accounted for about one third of the tumors studied, are particularly aggressive.

At the same time, the result opens up new perspectives for a more targeted and personalized therapy of pancreatic cancer. "By blocking the interferon signaling pathways at various sites, we were able to significantly slow down cancer growth in mice to which human pancreatic cancer cells had been transferred. However, the regulation of these signals is highly complex. We are now looking for ways to not only slow down the tumor cells, but actually eliminate them," says Trumpp, explaining the further progress of preclinical research.

Your advance look at two new studies publishing online on October 15, 2020 in The American Journal of Tropical Medicine and Hygiene.

EMBARGOED UNTIL 5:00 pm US Eastern Time, October 15, 2020

Researchers find hypochlorous acid could combat latrine odor and infectious microbes--and promote greater latrine use--in developing countries

As part of an effort to establish new means to encourage toilet and pit latrine use in developing countries, researchers from the University of Washington and Briotech, a manufacturer of hypochlorous acid (HOCl), found that HOCl chemically modified the malodorous, off-putting compounds identified in the air of latrines in developing countries. This study also showed the potential of HOCl to rapidly inactivate infectious particles that can cause gastrointestinal diseases. The study was published today in the American Journal of Tropical Medicine and Hygiene.

According to the authors, promoting greater use of latrines in developing countries could limit transmission of fecal bacteria and viruses readily spread via environmental contamination of water and food sources. But they cite the odor of latrines, and the associated impression of uncleanliness, as one reason people avoid using them in favor of open defecation. "Odor control," the study authors said, "clearly needs to be included as part of improving sanitation."

Laboratory experiments tested the ability of stable, pure HOCl - in solution and spray form - to modify the malodorous compounds indole, p-cresol, dimethyl disulfide, dimethyl trisulfide and butyric acid. The studies found that after five minutes of contact with HOCl in concentrations of about 100 parts per million, greater than 94% of those compounds were modified. Spray delivery of HOCl gave comparable results after 25 sprays.

In addition, smell studies involving 80 volunteers indicated that there was a significant difference in odor between the untreated and HOCl-treated compounds, suggesting that hypochlorous acid will improve latrine odor in field studies when sprayed in the latrine headspace or swabbed on surfaces.

Importantly, the study also demonstrated that aerosolized HOCl brought about meaningful reductions in the infectivity of MS2 bacteriophage particles, which the researchers used as a surrogate for human norovirus and other diarrhea-associated viruses that can be found in latrines.

The researchers hope that HOCl could be an alternative to perfumes when it comes to making latrine use more pleasant to the nose while also inactivating infectious microbes and, to that end, are conducting further studies to optimize dosing to inactivate human noroviruses. This work was supported by an NIH grant (R03AI137626).

>> Abstract (will go live at 5 p.m. EDT, October 15; please contact us if you want to see the study PDF)

New study finds artificial light at night is increasing Aedes aegypti mosquito biting behavior

Artificial light at night abnormally increases Aedes aegypti mosquito biting behavior, according to new research published today in the American Journal of Tropical Medicine and Hygiene, highlighting the concern that increasing levels of light pollution could be enhancing transmission of diseases such as dengue fever, yellow fever, chikungunya and Zika.

Ae. aegypti normally flies and bites in the daytime. Activity terminates during or at the end of dusk, and little or no flight activity or biting occurs during the night.

Researchers at the University of Notre Dame examined the effect of artificial light at night on female Ae. aegypti biting of human arms in a laboratory setting and found that nocturnal biting activity doubled when the mosquitoes were exposed to artificial light. With no light, 29% of the mosquitoes blood-fed at night, while with artificial light 59% of the mosquitoes blood-fed.

These findings, the authors say, will help epidemiologists better understand the true risk of disease transmission by Ae. aegypti mosquitoes. The findings also suggest that sleeping under bednets meant to deter nocturnal biting insects like malaria-transmitting mosquitoes may provide some protection against yellow fever, dengue, Zika and other diseases transmitted by typically day-biting Ae. aegypti mosquitoes.

>> Abstract (will go live at 5 p.m. EDT, October 15; please contact us if you want to see the study PDF)

Australia was not spared as a 30-year global rise in chronic illness and related risk factors such as obesity, high blood sugar, and outdoor air pollution created a perfect storm to fuel coronavirus (COVID-19) deaths, new research shows.

The latest Global Burden of Disease Study findings also reveal that people globally are living more years in poor health, despite treatment advancements in many countries. While Australia has done relatively well with COVID-19 despite Victoria's second wave, experts are concerned about worrying levels of cardiovascular disease and stagnating life expectancy.

Published today in The Lancet, the latest results outline how well countries were prepared for COVID-19 in terms of underlying population health, and the scale of the challenge to protect the population against further pandemic threats.

The 30-year global study, which involves several University of Melbourne experts, analysed 286 causes of death, 369 diseases and injuries, and 87 risk factors in 204 countries and territories.

It found urgent action was needed to address the global syndemic--the aggregation of two or more concurrent or sequential epidemics, including chronic diseases, social inequalities, and COVID-19--to ensure more robust health systems and healthier people, making countries more resilient to future pandemic threats.

Several risk factors and non-communicable diseases highlighted, including obesity, smoking, diabetes, and cardiovascular disease, are associated with increased risk of serious illness and death from COVID-19.

Although global healthy life expectancy--the number of years a person can expect to have good health--increased steadily (by over 6.5 years) from 1990 to 2019, it has not risen as much as overall life expectancy in almost all of the 204 countries assessed, indicating that people are living more years in poor health.

The study also reveals that the rise in exposure to key risk factors, including high blood pressure, high blood sugar, high body-mass index (BMI), and elevated cholesterol, combined with rising deaths from cardiovascular disease in some countries or regions (e.g. the USA and the Caribbean), suggests that parts of the world might be approaching a turning point in life expectancy gains.

Healthy life expectancy in Australia has increased steadily over 30 years to 70.0 years in 2019 (a 4.1 year increase from 1990), but it has not risen as much as overall life expectancy (82.9 years in 2019; a 5.9-year increase from 1990), indicating that people are living longer in poor health.

Australian data also revealed:

* Ischaemic heart disease was the leading cause of health loss in Australia in 2019, followed by lower back pain, falls, major musculoskeletal disorders, and chronic obstructive pulmonary disease (COPD)

* The top-five risk factors for death in 2019 were high systolic blood pressure (contributing to an estimated 25,500 deaths), dietary risks (21,600 deaths), tobacco use (20,100), high BMI (18,700), and high blood sugar (17,700)

* Over the past 30 years, overall rates of death among 15-49-year-olds declined by 31 per cent. But rates of death due to drug use disorders rose substantially in this age group (by 55.2 per cent), as did rates of death due to endocrine, metabolic, blood, and immune disorders (by 75.2 per cent).

Senior author and University of Melbourne Laureate Professor Alan Lopez said while Australia had been comparatively "remarkably successful" in controlling COVID19 cases and especially deaths, despite Victoria's second wave, it had been much less so in controlling obesity and risks associated with poor diet. As a result, the long-term Australian decline in cardiovascular disease had ceased.

"Australian life expectancy has not increased in the past five years," Professor Lopez said.

"While the immediate global public health priority is understandably the rapid control of the COVID-19 pandemic, these findings about the state of the world's health are a wake-up call that large, avoidable causes of health loss such as smoking, alcohol, obesity and poor blood pressure and cholesterol control continue to claim millions of lives prematurely each year."

"Of even greater concern is that the impact of this risk factor 'cocktail' of smoking, poor diet and inadequate control of blood pressure and other metabolic factors is increasing in many countries, including Australia, as evidenced by the stagnation in life expectancy over the past five years."

Study authors from a range of countries and institutions stressed that government actions to prevent disease through incentivisation of healthier behaviours and facilitation of better access to healthcare are not being realised globally.

Professor Christopher Murray, Director of the Institute for Health Metrics and Evaluation at the University of Washington, USA, led the research.

"Most of these risk factors are preventable and treatable, and tackling them will bring huge social and economic benefits," Professor Murray said.

"We are failing to change unhealthy behaviours, particularly those related to diet quality, caloric intake, and physical activity, in part due to inadequate policy attention and funding for public health and behavioural research."

UNIVERSITY PARK, Pa. -- People may be skeptical about medical and health articles they encounter on crowdsourced websites, such as Wikipedia and Wikihealth, according to researchers. While that may be good news for health officials who are worried that these sites allow non-experts to easily add and edit health information, the researchers added that having medical professionals curate content on those sites may not reduce the skepticism.

"There are major concerns about health misinformation that's floating around, especially now with COVID-19," said S. Shyam Sundar, James P. Jimirro Professor of Media Effects, co-director of the Media Effects Research Laboratory and affiliate of Penn State's Institute for Computational and Data Science (ICDS). "Now that anybody and everybody can generate health-related posts, it is natural to be concerned that information on these crowdsourced websites might influence people. Our study suggests that health practitioners need not get too worked up about these sites. Laypersons, like the participants in our study, do not trust the crowd, nor do they think that the information they provide is comprehensive."

In prior research, scientists have found that people tend to trust online content that appears popular with the crowd, such as posts that earn likes and retweets, a phenomenon that is also referred to as the bandwagon effect, said Yan Huang, assistant professor of integrated strategic communication, University of Houston, lead-author of the study, who worked with Sundar. However, Huang said that the findings suggest that, as far as trust goes, people draw a line between content that has been endorsed by the crowd and content that has been edited by the crowd.

"The effect of crowdsourcing may be different from the bandwagon effect because in this case, the crowd is not just liking or recommending existing content; the crowd is actually generating it," said Huang. "And it seems that participants in our experiment were able to make that psychological distinction between the bandwagon effect -- when people are just endorsing the content -- versus people who are creating the content. Overall, participants didn't trust the content that's been collaboratively created by other people."

The researchers, who report their findings in Health Communication, added that their experiment also revealed another side of the story: When participants noticed interactive features on the site that allowed them to edit the content, they trusted crowdsourced health articles more.

"When they realize that they could serve as the editor or author of the content, they are imbued with a sense of control on the site. The more aware they are of this interactivity, the more they trust the content," said Huang.

According to Sundar, the findings suggest that while people trust themselves as a source of credible content, they may be reluctant to extend that trust to other people.

"When you are the source, you think that the information is credible because you can add content, but if other people can also supply content, that seems to take away the credibility," said Sundar.

Because crowdsourced content could be manipulated to include non-scientific advice or results, many health experts may think that credentialing their crowdsourced posts may add credibility to their articles. However, the researchers found that when content was curated, or even created by an expert, such as a doctor, participants did not find the information any more credible to the reader. To signal that the source was a professional, the researchers added a doctor symbol and the name and title of a doctor on the experimental website.

"Adding that professional source layer did increase the perception that there was a gatekeeper behind the content, in other words, people did think that the crowdsourced site had more gatekeeping when there were indications of a professional source, but it did not affect credibility judgments," said Sundar.

The researchers added that because the findings show a lack of trust in health content on crowdsourced sites, webmasters of these sites may want to make sure that interactive features are added and that they are prominent in the design. Interactive features tend to boost users' positive perceptions of the source and content, which could lead to better credibility on crowdsourced sites, they said.

The researchers created eight different versions of a website called "Healthpedia" to test the various conditions of the experiment. The site mimicked the interface of common crowdsourcing websites, such as Wikipedia and WikiHow, for testing the effects of crowdsourcing. While some versions identified a doctor as content editor, others offered editing functions and showed that the content was collaboratively created by over 45 individuals.

The study was conducted with a sample of 192 participants recruited from Amazon Mechanical Turk. They were exposed to articles that featured either the negative effects of sunscreen products or the potential risks of pasteurized milk. The researchers said that the content was intentionally made controversial to better test the credibility of the crowd as a source. According to the researchers, because the health articles were somewhat outlandish, future work may test whether the perception holds for fairly routine health content.

Sexually transmitted infections (STIs) are at record levels in the United States, with the Centers for Disease Control and Prevention reporting recent “steep and sustained” increases. STIs are particularly common among young adults (aged 18-24 years), yet most sexually active college students have never been tested. This presents an urgent challenge, as well as a unique opportunity, for universities to increase STI testing among their students.

New research led by George Mason University’s College of Health and Human Services found that the vast majority of sexually active students (88%) said they were "likely" or "extremely likely" to use STI self-testing services if they could take a test kit home and test themselves in the privacy of their own home/residence, while 59% said they would use STI self-testing services if they could test themselves in a private room at Student Health Services.

Dr. Lisa Lindley led the study published in the Journal of American College Health this week. This is the first study to explore college students’ comfort with and intention to use self-collection STI testing services on campus, and to identify students’ questions and concerns about the “self-testing” process before offering the service.

The researchers conducted an online survey of more than 400 students at a large mid-Atlantic university to assess their HIV/STI testing behaviors, comfort with self-collection procedures, and intention to use self-collection services for STI testing if offered on campus.

“We already know that in settings where self-collection options have been made available, there have been significant increases in testing and the detection of STIs,” explains Lindley. “This presents an opportunity to increase the detection of asymptomatic infections among sexually active students who traditionally don’t get tested, link these students to care, and prevent further transmission, as well as harmful health outcomes of untreated infections.”

Students who were older (25+ years), lived off campus, and identified as “lesbian, gay, bisexual, or an identity other than heterosexual” were significantly more likely to have ever been tested for HIV and other STIs than students who were younger (18–24 years), lived on campus, and identified as heterosexual.

“We hope to be able to offer STI self-testing options on campus in the near future and encourage other universities to consider the same, as we found that most students, regardless of age, sexual experience, and previous testing experience, were interested in self-testing,” explains Lindley. “These findings are especially timely during the COVID-19 pandemic, as access to HIV/STI testing in traditional settings has become more challenging and the CDC is recommending at-home HIV tests.”

Collection of specimens for some of the most common STIs (chlamydia and gonorrhea) as well as those for HIV can easily be collected by most people. Tests for others—such as syphilis, genital herpes, and human papilloma virus (HPV)—will continue to be conducted by clinicians due to the procedures required for sample collection.

The study offers important takeaways not just regarding the use of self-testing services among asymptomatic students, but also for increasing STI testing in clinical settings more broadly. It suggests that college students may be more likely to pursue STI testing if their contact with clinical staff could be reduced. Lindley recommends using online registration and sexual risk assessments, where appropriate, to collect necessary information and reduce interactions students find particularly embarrassing.

Supersized alcopops are single-serving flavored beverages with very high alcohol content. Consumption of these drinks is linked to dangerous consequences such as blacking out, vomiting, being injured or worse, and they are popular among underage drinkers, which is where prior research has typically focused.

However, supersized alcopops can be dangerous for everyone - regardless of age. New research led by George Mason University's College of Health and Human Services was the first to examine individual factors linked to recent consumption of supersized alcopops among adults on probation. The study was published today in Alcoholism: Clinical and Experimental Research.

Dr. Matthew Rossheim led the study that found that among adults on probation, those who were gang-affiliated or recently experienced homelessness were far more likely to have recently consumed supersized alcopops in the past 30 days.

Among those who experienced homelessness, 30% consumed supersized alcopops, compared to 11% of those who did not experience homelessness. Further, 57% of those who were gang-affiliated reported consuming a supersized alcopop within the past 30 days compared to 11% of those who were not gang-affiliated.

Adults on probation who had consumed supersized alcopops in the past 30 days had higher scores for hostility and risk-taking, and lower scores for self-esteem on the Criminal Justice Client Evaluation of Self and Treatment Intake (CJ-CEST) than non-consumers.

The researchers surveyed 253 adults (70% male) on probation in two large metropolitan areas: Baltimore City, MD and Dallas, TX who reported heavy drinking or any illicit drug use in the past 90 days.

"The marketing and retail availability of these products may be creating and perpetuating health disparities, by targeting historically disenfranchised communities," explains Rossheim. "Better regulation of supersized alcopop marketing is urgently needed to reduce dangerous alcohol consumption--particularly among high-risk groups, including people who are homeless, gang members, and display more hostility and risk-taking traits."