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Philadelphia, January 11, 2021 - Children and adolescents with a family history of suicide attempts have lower executive functioning, shorter attention spans, and poorer language reasoning than those without a family history, according to a new study by researchers from the Lifespan Brain Institute (LiBI) of Children's Hospital of Philadelphia (CHOP) and the University of Pennsylvania. The study is the largest to date to examine the neurocognitive functioning of youth who have a biological relative who made a suicide attempt.

The findings, which were first published online last March, were published in the January 2021 edition of The Journal of Child Psychology and Psychiatry.

Researchers looked at 3,507 youth aged 8 to 21. Of those, 501 participants had a family history of suicide, defined as a fatal or non-fatal suicide attempt by a first-degree biological relative like a parent, full sibling, or child. Participants were divided into test groups and matched by age, sex, race, and lifetime depression. Researchers found that those with a family history of suicide attempt had significantly lower executive functioning and performed worse on tests that measured attention span and language reasoning. The differences in test scores could not be explained by overall psychiatric problems, suicidal ideation, trauma exposure, or socioeconomic status, leading scientists to believe family history of suicide attempt is the contributing factor.

"Executive functioning skills are incredibly important in youth development," said Jason Jones, PhD, lead author and research scientist at PolicyLab and the Youth Suicide Prevention, Intervention and Research Center at CHOP. "Even a small difference could cascade into a progressively larger issue over the course of a child's lifetime, affecting things like academic achievement, mental health, and risk-taking behaviors."

Suicide is currently the second leading cause of death in children and young adults aged 10 to 24. Previous research has shown suicidal tendencies to be highly hereditary.

"Lower executive functioning may result in poorer decision making and problem solving," said Rhonda Boyd, PhD, co-author and psychologist in the Department of Child and Adolescent Psychiatry and Behavioral Sciences at CHOP. "It's also been linked to impulsive and aggressive behavior, which has consistently been linked to suicidal behavior. This study shows us the importance of asking about suicide attempts among relatives when conducting clinical evaluations with pediatric patients, as it may be a risk factor for suicidal behavior."

The researchers say cognitive-behavioral therapy, such as helping youth verbalize thoughts and feelings, problem-solve, and understand consequences, may help address executive functioning and language difficulties. They also suggest incorporating other family members in early intervention, as other people in the family may be at-risk but not yet show risk signs for suicidal behavior.

MDC researchers have developed a new approach to CAR T-cell therapy. The team has shown in Nature Communications that the procedure is very effective, especially when it comes to fighting follicular lymphomas and chronic lymphocytic leukemia, the most common type of blood cancer in adults.

The body's defense system generally does not recognize cancer cells as dangerous. To correct this sometimes fatal error, researchers are investigating a clever new idea, one that involves taking a handful of immune cells from cancer patients and "upgrading" them in the laboratory so that they recognize certain surface proteins in the malignant cells. The researchers then multiply the immune cells and inject them back into the patients' blood - setting them off on a journey through the body to detect and attack all cancer cells in a targeted way.

In fact, the first treatments based on this idea have already been approved: So-called CAR T cells have been used in Europe since 2018, particularly in patients with B-cell lymphomas for whom conventional cancer therapies have not worked.

T cells are like the immune system's police force. The abbreviation CAR stands for "chimeric antigen receptor" - meaning that the cellular police force is equipped with a new, laboratory-designed special antenna that targets a surface protein on the cancer cells. Thanks to this antenna, a small number of T cells can round up a large number of cancer cells and destroy them. Ideally, the CAR T cells patrol the body for weeks, months or even years and thus prevent tumor relapse.

A kind of signpost for B cells

Until now, the antenna on the CAR T cells was primarily directed against the protein CD19, which B cells - a type of immune cells - carry on their surface. Yet this form of therapy is by no means effective in all patients. A team led by Dr. Uta Hoepken, head of the Microenvironmental Regulation in Autoimmunity and Cancer Lab at the Max Delbrueck Center for Molecular Medicine in the Helmholtz Association (MDC), has now developed a new twist on this therapy that sensitizes the T cells in the laboratory to a different identifying feature: the B-cell homing protein CXCR5.

"CXCR5 was first described at the MDC more than 20 years ago, and I have been studying this protein myself for almost as long," says Hoepken. "I am therefore very pleased that we have now succeeded in using CXCR5 to effectively combat non-Hodgkin's lymphomas, such as follicular and mantle cell lymphoma as well as chronic lymphocytic leukemias, in the laboratory." This protein is a receptor that helps mature B cells move from the bone marrow - where they are produced - to immune system organs such as the lymph nodes and spleen. "Without the receptor, the B cells would not find their way to their target site, the B-cell follicles of these lymphoid organs," Hoepken explains.

A well-suited target

"All mature B cells, including malignant ones, carry this receptor on their surface. So it seemed to us to be well suited to detect B-cell tumors - thereby enabling CAR-T cells directed against CXCR5 to attack the cancer," says Janina Pfeilschifter, a PhD student in Hoepken's team. She and Dr. Mario Bunse from the same research group are the lead authors of the paper, which appeared in the journal Nature Communications. "In our study, we have shown through experiments with human cancer cells and two mouse models that this immunotherapy is most likely safe and very effective," says Pfeilschifter.

The new approach may be particularly well suited for patients with a follicular lymphoma or chronic lymphocytic leukemia (CLL). "Both types of cancer involve not only B cells but also follicular T helper cells, which also carry CXCR5 on their surface," Bunse explains. The special antenna for the identifying feature, the CXCR5-CAR, was generated by Dr. Julia Bluhm during her time as a PhD student in the MDC's Translational Tumorimmunology Lab, which is headed by physician Dr. Armin Rehm. He and Hoepken are the corresponding authors of the study.

First successes in the petri dish

Pfeilschifter and Bunse first showed that various human cells, for example, from blood vessels, the gut and the brain, do not carry the CXCR5 receptor on their surface and are therefore not attacked in the petri dish by T cells equipped with CXCR5-CAR. "This is important to prevent unexpected organ damage from occurring during therapy," Pfeilschifter explains. In contrast, experiments with human tumor cell lines showed that malignant B cells from very different forms of B-non-Hodgkin's lymphoma all display the receptor.

Professor Joerg Westermann, from the Division of Hematology, Oncology and Tumor Immunology in the Medical Department of Charite - Universitaetsmedizin Berlin at the Campus Virchow Clinic, also provided the team with tumor cells from patients with CLL or B-non-Hodgkin's lymphomas. "There, too, we were able to detect CXCR5 on all B-lymphoma cells and follicular T helper cells," Pfeilschifter says. When she and Bunse placed the tumor cells in the petri dish together with the CXCR5-targeted CAR T cells, almost all of the malignant B and T helper cells disappeared from the tissue sample after 48 hours.

Mice with leukemia were cured

The researchers also tested the new procedure on two mouse models. "The CAR T cells are infused into the blood of cancer patients," Hoepken says. "So animal research is needed to show that the cells home to the niches where the cancer resides, multiply there and then do their job effectively."

One model consisted of animals with a severely suppressed immune system, which could therefore be treated with human CAR T cells without causing rejection reactions. "We also developed a pure mouse model for CLL specifically for the current study," Bunse reports. "We administered mouse CAR T cells against CXCR5 to these animals by infusion and were able to eliminate mature B cells and T helper cells, including malignant ones, from the B-cell follicles of the lymphoid organs."

The researchers discovered no serious side effects in the mice. "We know from experience with cancer patients that CAR T-cell therapy increases the risk of infection for a few months," Rehm says. But in practice this side effect is almost always easily managed.

A clinical trial is in the works

"No laboratory can tackle such a study on its own," Hoepken emphasizes. "It has only come about thanks to a successful collaboration between many colleagues at the MDC and Charite." For her, the study is the first step toward creating a "living drug" - similar to other cellular immunotherapies being developed at MDC. "We are already cooperating with two cancer specialists at Charite and are currently working with them to prepare a phase 1/2 clinical trial," adds Hoepken's colleague Rehm. Both hope that the first patients will begin to benefit from their new CAR-T cell therapy in the near future.

Stress on an expectant mother could affect her baby's chance of developing disease - perhaps even over the course of the child's life, UC researchers have found.

Psychosocial factors creating stress -- such as lack of social support, loneliness, marriage status or bereavement -- may be mutating their child's mitochondrial DNA and could be a precursor to a host of diseases, according to a University of Cincinnati study.

"There are a lot of conditions that start in childhood that have ties to mitochondrial dysfunction including asthma, obesity, attention deficit hyperactivity disorder and autism," says Kelly Brunst, PhD, assistant professor of environmental and public health sciences in the UC College of Medicine and lead author of the study.

"The fetal and infant period is a vulnerable time for environmental exposure due to heightened development during these periods," says Brunst. "We don't just wake up one day and have asthma or attention deficit hyperactivity disorder. The programming effects resulting from environmentally induced shifts occur over time and likely start during gestation at the molecular and cellular level. These shifts alter physiological states that likely play a role in who is going to go on and develop adverse health outcomes."

As part of the study, researchers sequenced the mitochondrial genome and identified mutations in 365 placenta samples from birth mothers in Boston and New York City from 2013-18. A multivariable regression model was used to look at maternal lifetime stress in relation to the number of gene mutations in the placenta mitochondrial genome.

Women experiencing increased psychosocial stress -- that can range from sexual assault, domestic violence or serious injury to incarceration, physical or mental illness and family hardship -- over their lifetime exhibited a higher number of placental mitochondrial mutations. The strongest associations were observed among Black women. Higher stress-related DNA mutations in the placenta were seen in Black and white women, but not in Hispanic women.

The study's findings were published in the scholarly journal Biological Psychiatry.

"The idea behind this work is about understanding how our environment, in this case maternal stress and trauma, impact mitochondrial function and ultimately neurobehavioral development," says Brunst. "The hope is to gain insight as to why certain children are vulnerable to developing a range of complex conditions previously linked to environmental exposures such as chronic stress or air pollution."

"We ask about events that might have occurred prior to their pregnancy even during the mother's own childhood as part of our study," says Brunst. "So what this is telling us is that the stress that a woman has experienced even before she is pregnant might have an impact on the fetal mitochondrial genome."

Brunst said there are some diseases for which Black women are more at risk -- obesity, diabetes and certain cancers -- so they might be more affected by stress and subsequently develop these diseases which have also been linked to stress."

"What was interesting about the study was that Hispanics exposed to stress had fewer placental mitochondrial DNA mutations," says Brunst.

She says one explanation could be what researchers call the "Hispanic paradox." It is the epidemiological phenomenon documenting better health and lower mortality relative to non-Hispanic whites despite greater risk and lower socioeconomic status for Hispanics."

"Despite exposure to more stress and trauma, sociocultural dynamics specific to Hispanics may attenuate experiences of stress which in turn has downstream effects on psychophysiological mechanisms and better outcomes," says Brunst. "This is just one possible explanation."

Conditions are ripe for transforming the U.S. mental health care system, with scientific advances, the growth of Medicaid and political consensus on the importance of improving mental health creating the possibility that goals once thought out of reach may be possible, according to a new RAND Corporation study.

Broad changes will be needed to improve how Americans receive mental health care, such as integrating behavioral health care into general health care settings, providing supportive housing to the homeless and promoting comprehensive mental health education.

Federal mental health parity legislation is one recent promising development that aims to put coverage for mental health treatment and general health care on equal footing, but researchers say that more effort is needed to enforce the law.

Other efforts urged by the report include increasing the use of evidence-based mental health treatments, expanding scholarships and loan repayments to stimulate growth of the mental health workforce, and improving access to digital and telehealth services for mental health.

The RAND recommendations come from an extensive project that reviewed published research about the nation's mental health system and consulted with consumers, mental health advocates, researchers, clinicians, health system representatives, policymakers and payers.

"For decades, the nation's mental health system has faced challenges such as the underdevelopment of community-based supports, high levels of unmet need, and inequities in both access to care and the quality of care," said Ryan McBain, the study's lead author and a policy researcher at RAND, a nonprofit research organization. "Our report outlines the fundamental building blocks that policymakers should consider to bring about transformative change to the U.S. mental health system."

The RAND evaluation examined the mental health system broadly, encompassing the organization of people, institutions and resources that support delivery of mental health services, as well as adjacent sectors such as housing and education.

Researchers received stakeholder input from a broad-based advisory panel that met twice over the course of the project to discuss the conceptual model and policy options for achieving goals of health system transformation. The RAND team also conducted one-on-one interviews with more than 20 additional mental health policy experts.

Despite a wide need for services, just 45% of people in the U.S. with a mental illness received any mental health treatment during 2019. The shortcomings are even greater for members of racial and ethnic minority groups, who are about half as likely to receive mental health care as non-Hispanic White people.

Prisons and jails are now recognized as the largest institutional providers of housing for people with serious mental illness. There also are striking geographic variations in availability of mental health specialty care, with rural areas particularly underserved.

There has been a resurgence of innovation and bipartisan advocacy for people experiencing mental illness in recent years, with significant changes in how mental health care is financed and the emergence of a stronger evidence base for treatment and policy. Parity laws aim to improve access, and states have endorsed an expanded role of Medicaid in providing coverage for individuals with serious mental illness.

"There is reason to believe that the time is right for major changes to the nation's mental health shortcomings," McBain said. "Our recommendations are rooted in evidence and are patient-centered -- mapping directly to the patient journey traversed by those affected by mental illness."

This RAND report aims to lay out how policy changes at all levels of government -- federal, state and local -- can build on recent developments and effect broad transformational change to improve the lives of the 60 million Americans living with mental illness.

The report's 15 recommendations are structured around three overarching goals for improving the nation's mental health landscape: promoting pathways to care, improving access to mental health care and establishing an evidence-based continuum of care.

RAND researchers say that for people to get the mental health care they need, communities should be sensitized to the importance of mental health, ideally beginning in school systems where children and adolescents can be provided with consistent information about the importance of mental health.

To identify population-level mental health needs, screening and treatment models linked to primary medical care should be broadly implemented in both public and private sectors.

For those with serious mental illness, the report says that needs pertaining to social determinants of health should be addressed. This includes connections to housing for the homeless and diversion strategies for those who are incarcerated or end up in hospital emergency departments with no other recourse for medical care.

Many recommendations aim to make the process of accessing services straightforward.

The report recommends strategies to create a robust and well-educated mental health workforce, as well as bringing services closer to patients by expanding access and use of telehealth. Improving enforcement of mental health parity and providing financial incentives to better reimburse providers should prompt more health systems to make mental health services available.

Because the journey to care can be unnecessarily convoluted and bureaucratic for patients, researchers recommend that communities consider using established guidelines to define a continuum of care that is appropriate for meeting individuals' level of need. For patients with both physical and mental health conditions, or who have diverse mental health needs, coordination among providers is essential.

While there is strong evidence demonstrating what works, the report says that a national effort is necessary to push out care coordination models at a larger scale.

The report includes a web-based tool that allows users to quickly scan the research literature that provides the basis for the report's recommendations.

Human papillomavirus (HPV) can infect the mouth and throat to cause cancers of the oropharynx. A new study published early online in CANCER, a peer-reviewed journal of the American Cancer Society, has found that having more than 10 prior oral sex partners was associated with a 4.3-times greater likelihood of having HPV-related oropharyngeal cancer. The study also shows that having oral sex at a younger age and more partners in a shorter time period (oral sex intensity) were associated with higher likelihoods of having HPV-related cancer of the mouth and throat.

Previous studies have shown that performing oral sex is a strong risk factor for HPV-related oropharyngeal cancer. To examine how behavior related to oral sex may affect risk, Virginia Drake, MD, of Johns Hopkins University, and her colleagues asked 163 individuals with and 345 without HPV-related oropharyngeal cancer to complete a behavioral survey.

In addition to timing and intensity of oral sex, individuals who had older sexual partners when they were young, and those with partners who had extramarital sex were more likely to have HPV-related oropharyngeal cancer.

"Our study builds on previous research to demonstrate that it is not only the number of oral sexual partners, but also other factors not previously appreciated that contribute to the risk of exposure to HPV orally and subsequent HPV-related oropharyngeal cancer," said Dr. Drake. "As the incidence of HPV-related oropharyngeal cancer continues to rise in the United States, our study offers a contemporary evaluation of risk factors for this disease. We have uncovered additional nuances of how and why some people may develop this cancer, which may help identify those at greater risk."

The gut plays a central role in the regulation of the body's metabolism and its dysfunction is associated with a variety of diseases, such as obesity, diabetes, colitis and colorectal cancer that affect millions of people worldwide. Targeting endocrine dysfunction at an early stage by stimulating the formation of specific enteroendocrine cells from intestinal stem cells could be a promising regenerative approach for diabetes therapy. For this, however, a detailed understanding of the intestinal stem cell lineage hierarchy and the signals regulating the recruitment of the different intestinal cell types is critical.

Heiko Lickert and his research group have taken up this challenge. Lickert is director of the Institute of Diabetes and Regeneration Research at Helmholtz Zentrum München, professor of beta cell biology at Technical University of Munich (TUM) and member of the German Center for Diabetes Research (DZD). In the following, Lickert and first author Anika Böttcher talk about their latest paper on the basic mechanisms of intestinal stem cell function published in Nature Cell Biology.

Why is the gut so important for health research?

Heiko Lickert: As the body's digestive and largest endocrine system, the gut is central to the regulation of energy and glucose homeostasis. Intestinal functions are carried out by specialized cells which are constantly generated and renewed every 3-4 days from intestinal stem cells. For example, so-called enteroendocrine cells produce over 20 different types of hormones that signal to the brain and pancreas to regulate for instance appetite, food intake, gastric emptying and insulin secretion from pancreatic beta cells. Another important gut function is exerted by so-called Paneth cells that produce defensins and protect against invading pathogens. Consequently, it is not surprising that intestinal dysfunction is associated with a variety of diseases, such as chronic inflammation,colorectal cancer and diabetes, affecting millions of people worldwide.

What were the most important findings in your latest research about intestinal stem cells?

Anika Böttcher: We improved our understanding of how intestinal stem cells constantly renew and give rise to specialized cell types at unprecedented single cell resolution. Thus, we are now able to describe potential progenitor populations for each intestinal cell and we have shown that for every lineage intestinal stem cells give rise to unipotent lineage progenitors. Furthermore, we identified a specific intestinal stem cell niche signal pathway (called Wnt/planar cell polarity pathway) regulating intestinal stem cell self-renewal and lineage decisions. This is very important, as we know that intestinal stem cells can indefinitely renew and maintain the gut function and tissue barrier. Those are 6 meters of epithelium and more than 100 million of cells generated every day in humans! Moreover, these cells differentiate into every single cell type. The risk of failure in this self-renewal or lineage specification process to result in a chronic disease therefore is quite high.

Using a more technical term, we were able to delineate a detailed intestinal stem cell lineage tree and identified new niche signals. In order to obtain those breaking-through results, we integrated time-resolved lineage labelling of rare intestinal lineages using different reporter mouse lines with genome-wide and targeted single-cell gene expression analysis to dissect intestinal stem cell lineage decisions. Together with Fabian Theis' team of computational biologists at Helmholtz Munich and TUM, we profiled 60,000 intestinal cells. To analyze this data set, we leveraged newly developed machine learning techniques to automatically identify branching lineages and key contributing factors in the gene expression space. The findings are broadly applicable and are equally important for cancer, inflammation and colitis as well as obesity and diabetes.

How can this new knowledge be translated to therapeutic approaches?

Heiko Lickert: This study challenges current paradigms and we advanced our understanding of intestinal stem cell self-renewal, heterogeneity and lineage recruitment. We can use this basic knowledge to map what happens to intestinal stem cell lineage allocation and differentiation during chronic disease. Insights from this will put us in place to develop specific therapies for these diseases by targeting lineage progenitors for example to regenerate the formation of specific cells that are lost during disease progression or to identify and eradicate intestinal cancer stem cells. Specifically, at our institute, we will focus our efforts on diabetes.

How the larvae of colorful clownfish that live among coral reefs in the Philippines are dispersed varies widely, depending on the year and seasons - a Rutgers-led finding that could help scientists improve conservation of species.

Right after most coral reef fish hatch, they join a swirling sea of plankton as tiny, transparent larvae. Then currents, winds and waves disperse them, frequently to different reefs.

During seven years of surveys of coral reef-dwelling clownfish, scientists measured how the dispersal of larvae varied over the years and seasonally, including during monsoons, according to Rutgers-led research in the journal Molecular Ecology. They found that larvae dispersal varied a lot on both timescales.

Their research suggests that when scientists account for dispersal variability rather than just using data from a single year or an average over time, estimates of the persistence of fish populations will be lower.

"That means when we don't account for dispersal variability, we could be overestimating the stability of coral reef fish populations," said lead author Katrina A. Catalano, a doctoral student in the lab of senior author Malin L. Pinsky, an associate professor in the Department of Ecology, Evolution, and Natural Resources in the School of Environmental and Biological Sciences at Rutgers University-New Brunswick. "If we study dispersal variability in more species over greater timescales, we will better understand what causes the variation and can better design protected areas for the conservation of species."

Many studies measure patterns of larval dispersal, but often in only one year, and they don't account for how dispersal might differ over time.

"This is a problem for ecology and evolution because dispersal helps us understand population growth, adaptation, extinction and how species might be able to keep up with climate change by shifting habitats," Catalano said. "It's also important information for conservation and management of coral reef fish. We need to know which reef habitats are important sources of new fish for other reefs."

Scientists conducted a genetic analysis to detect larval dispersal events in a common coral reef fish, Amphiprion clarkii, also called yellowtail clownfish and Clark's anemonefish. The fish and their larvae lived along nearly 20 miles of coastline at 19 reef sites in Ormoc Bay, Leyte, Philippines, and the surveys went from 2012 to 2018 in partnership with Visayas State University in the Philippines.

"Measuring dispersal in more than one year is costly and difficult," Catalano said. "But we need to look at dispersal variation in more species to know if this variation is common, and we need to look at longer timescales like decades to understand the long-term impacts of variation. We also need to use population models."

Positive "tipping points" could spark cascading changes that accelerate action on climate change, experts say.

A tipping point is a moment when a small change triggers a large, often irreversible, response.

Professor Tim Lenton, Director of the Global Systems Institute (GSI) at the University of Exeter, has previously warned the world is "dangerously close" to several tipping points that could accelerate climate change.

But in a new paper in the journal Climate Policy, Professor Lenton and Simon Sharpe, a Deputy Director in the UK Cabinet Office COP 26 unit, identify tipping points in human societies that could rapidly cut carbon emissions.

They highlight examples of such tipping points that have contributed to the world's fastest low-carbon transitions in road transport and power generation - and say "small coalitions of countries" could trigger "upward-scaling tipping cascades" to achieve more.

"We have left it too late to tackle climate change incrementally," said Professor Lenton.

"Limiting global warming to well below 2°C now requires transformational change, and a dramatic acceleration of progress.

"For example, the power sector needs to decarbonise four times faster than its current rate, and the pace of the transition to zero-emission vehicles needs to double.

"Many people are questioning whether this is achievable. But hope lies in the way that tipping points can spark rapid change through complex systems."

The authors highlight two examples where policy interventions have already triggered pertinent tipping points at a national scale.

For each, they explain how further actions could turn these into "cascades" that change the global economy:

Light road transport: Electric vehicles (EVs) account for 2-3% of new car sales globally. In Norway, this figure is more than 50% (ten times higher than any other country), thanks to policies that make EVs the same price to buy as conventional cars. A global tipping point will come when EVs cost the same to manufacture as conventional cars. A small number of key locations could help drive this change. China, the EU, and California are together responsible for half the world's car sales - and each has targets to rapidly decarbonise their economies. Acting together, they could shift investment throughout the global industry, increasing EV production and decreasing costs, triggering a global tipping point to EVs. This in turn will make batteries better and cheaper, aiding decarbonisation in the power sector.

Power: In recent years, the UK has decarbonised its power sector faster than any other large country. Tipping points have played a role. A carbon tax together with an EU emissions scheme made gas cheaper than coal. Combined with increasing renewable energy generation, this tipped coal into unprofitability and led to the irreversible destruction of coal plants. Globally, renewables are already generating electricity cheaper than fossil fuels in many countries. A tipping point could be reached when the cost of capital of coal plants falls below that of wind and solar in all countries. Decarbonising global power generation would in turn help accelerate decarbonisation of large parts of transport, heating and cooling, and industry.

These positive tipping cascades are by no means inevitable - policies will be required to overcome the many barriers to transition.

But the beauty of tipping points is that thanks to reinforcing feedbacks, a relatively small number of initial actions could catalyse large changes at the global scale.

The paper encourages potential partners to work together to make these tipping cascades a reality.

"If either of these efforts - in power or road transport - succeed, the most important effect could be to tip perceptions of the potential for international cooperation to tackle climate change," Professor Lenton said.

Corals have evolved over millennia to live, and even thrive, in waters with few nutrients. In healthy reefs, the water is often exceptionally clear, mainly because corals have found ways to make optimal use of the few resources around them. Any change to these conditions can throw a coral's health off balance.

Now, researchers at MIT and the Woods Hole Oceanographic Institution (WHOI), in collaboration with oceanographers and marine biologists in Cuba, have identified microbes living within the slimy biofilms of some coral species that may help protect the coral against certain nutrient imbalances.

The team found these microbes can take up and "scrub out" nitrogen from a coral's surroundings. At low concentrations, nitrogen can be an essential nutrient for corals, providing energy for them to grow. But an overabundance of nitrogen, for instance from the leaching of nitrogen-rich fertilizers into the ocean, can trigger mats of algae to bloom. The algae can outcompete coral for resources, leaving the reefs stressed and bleached of color.

By taking up excess nitrogen, the newly identified microbes may prevent algal competition, thereby serving as tiny protectors of the coral they inhabit. While corals around the world are experiencing widespread stress and bleaching from global warming, it seems that some species have found ways to protect themselves from other, nitrogen-related sources of stress.

"One of the aspects of finding these organisms in association with corals is, there's a natural way that corals are able to combat anthropogenic influence, at least in terms of nitrogen availability, and that's a very good thing," says Andrew Babbin, the Doherty Assistant Professor in Ocean Utilization in MIT's Department of Earth, Atmospheric and Planetary Sciences. "This could be a very natural way that reefs can protect themselves, at least to some extent."

Babbin and his colleagues have reported their findings in the the ISME Journal.

Dead zone analogues

Babbin's group studies how marine communities in the ocean cycle nitrogen, a key element for life. Nitrogen in the ocean can take various forms, such as ammonia, nitrite, and nitrate. Babbin has been especially interested in studying how nitrogen cycles, or is taken up, in anoxic environments -- low-oxygen regions of the ocean, also known as "dead zones," where fish are rarely found and microbial life can thrive.

"Locations without enough oxygen for fish are where bacteria start doing something different, which is exciting to us," Babbin says. "For instance, they can start to consume nitrate, which has then an impact on how productive a specific part of the water can be."

Dead zones are not the only anoxic regions of the ocean where bacteria exhibit nitrogen-feasting behavior. Low-oxygen environments can be found at smaller scales, such as within biofilms, the microbe-rich slime that covers marine surfaces from shipwrecked hulls to coral reefs.

"We have biofilms inside us that allow different anaerobic processes to happen," Babbin notes. "The same is true of corals, which can generate a ton of mucus, which acts as this retardation barrier for oxygen."

Despite the fact that corals are close to the surface and within reach of oxygen, Babbin wondered whether coral slime would serve to promote "anoxic pockets," or concentrated regions of low oxygen, where nitrate-consuming bacteria might thrive.

He broached the idea to WHOI marine microbiologist Amy Apprill, and in 2017, the researchers set off with a science team on a cruise to Cuba, where Apprill had planned a study of corals in the protected national park, Jardines de la Reina, or Gardens of the Queen.

"This protected area is one of the last refuges for healthy Caribbean corals," Babbin says. "Our hope was to study one of these less impacted areas to get a baseline for what kind of nitrogen cycle dynamics are associated with the corals themselves, which would allow us to understand what an anthropogenic perturbation would do to that system."

Swabbing for scrubbers

In exploring the reefs, the scientists took small samples from coral species that were abundant in the area. Onboard the ship, they incubated each coral specimen in its own seawater, along with a tracer of nitrogen -- a slightly heavier version of the molecules found naturally in seawater.

They brought the samples back to Cambridge and analyzed them with a mass spectrometer to measure how the balance of nitrogen molecules changed over time. Depending on the type of molecule that was consumed or produced in the sample, the researchers could estimate the rate at which nitrogen was reduced and essentially denitrified, or increased through other metabolic processes.

In almost every coral sample, they observed rates of denitrification were higher than most other processes; something on the coral itself was likely taking up the molecule.

The researchers swabbed the surface of each coral and grew the slimy specimens on Petri dishes, which they examined for specific bacteria that are known to metabolize nitrogen. This analysis revealed multiple nitrogen-scrubbing bacteria, which lived in most coral samples.

"Our results would imply that these organisms, living in association with the corals, have a way to clean up the very local environment," Babbin says. "There are some coral species, like this brain coral Diploria, that exhibit extremely rapid nitrogen cycling and happen to be quite hardy, even through an anthropogenic change, whereas Acropora, which is in rough shape throughout the Caribbean, exhibits very little nitrogen cycling. "

Whether nitrogen-scrubbing microbes directly contribute to a coral's health is still unclear. The team's results are the first evidence of such a connection. Going forward, Babbin plans to explore other parts of the ocean, such as the tropical Pacific, to see whether similar microbes exist on other corals, and to what extent the bacteria help to preserve their hosts. His guess is that their role is similar to the microbes in our own systems.

"The more we look at the human microbiome, the more we realize the organisms that are living in association with us do drive our health," Babbin says. "The exact same thing is true of coral reefs. It's the coral microbiome that defines the health of the coral system. And what we're trying to do is reveal just what metabolisms are part of this microbial network within the coral system."

Canada is at the forefront of global efforts to end child marriage abroad. Yet this practice remains legal and persists across the country. In Canada, more than 3,600 marriage certificates were issued to children, usually girls, under the age of 18 between 2000 and 2018, according to a new study from researchers at McGill University. In recent years, an increasing number of child marriages have been common-law unions.

Child marriage, defined as formal or informal (common-law) marriage before the age of 18, is a globally-recognized indicator of gender inequality because the negative consequences for health and personal development disproportionately affect girls. While much research has focused on developing countries, in wealthier nations like Canada, child marriage practices are overlooked and understudied.

Using data from vital statistics agencies and recent censuses, the researchers found that child marriage remains in practice from coast to coast, with the highest estimates of formal marriage found in Alberta (0.03%) and Manitoba (0.04%), and the highest estimates of any type of child marriage (formal or common-law) in Saskatchewan (0.5%) and the territories (1.7%). The study, published in Population and Development Review, is the first to shed light on how common child marriages are in the country.

"Our results show that Canada has its own work to do to achieve its commitment to the United Nations Sustainable Development Goals, which call for an end to child marriage by the year 2030," says co-author Alissa Koski, Assistant Professor in Department of Epidemiology, Biostatistics and Occupational Health at McGill University.

The researchers found that Canadian-born children are slightly more likely to marry than those born outside of the country. More than 85% of all marriage certificates granted to children were issued to girls, who typically wed much older spouses. This gendered patterning is consistent with child marriage practices observed across the globe, according to the researchers.

Common-law unions more prevalent

The study shows most child marriages in recent years have been common-law. In 2006, formal marriage accounted for more than half of all child unions. By 2016, formal marriage accounted for only 5 percent and common-law unions were twenty times as prevalent.

"While the number of marriage certificates issued to children across the country has declined, it's possible that individuals are opting for more informal unions in response to growing social disapproval of child marriage," say the authors. This makes it increasingly challenging to determine to what extent child marriage has actually decreased or whether concerns about social or legal consequences have led to changes in reporting behaviors.

Informal unions can be just as harmful as formal marriages, the researchers say. In fact, informal unions often provide less social, legal and economic protection. In Quebec, for example, individuals in common-law unions are not entitled to alimony or division of property if the union ends. This raises questions about how best to address the issue. Preventing common-law unions among children will require different and innovative approaches that address the deeper motivations for this practice.

"The persistence of this practice within Canada highlights some of the inherent challenges to fully eradicating child marriage and reveals an important inconsistency between Canada's domestic laws and its global policies" says co-author Shelley Clark, James McGill Professor of Sociology at McGill University. The next steps will be to examine the mental health consequences of child marriage in Canada and to investigate motivations for the practice.

A year ago, trying to find patients who would agree to see their University of Michigan mental health provider through a video screen felt like pulling teeth.

Only 26 video visits with a few early-adopters had happened in nearly six months, compared with more than 30,000 in-person visits.

But Jennifer Severe, M.D., one of the three psychiatrists who helped launch a test of telehealth initiatives in the U-M's outpatient psychiatry clinic, wasn't about to give up.

She prepared to give a talk at the beginning of April of 2020, hoping to convince more of her colleagues to give telepsychiatry a try, now that a major insurance company was paying for it. She even had examples of how clinic staff had "rescued" the care of patients who had called at the last minute to cancel an appointment for their depression or bipolar disorder, but agreed to a video therapy session instead.

Severe never got to give that talk.

Instead, on March 23, all non-urgent health care across the state of Michigan shut down to prevent the spread of COVID-19. And video chats and phone calls became the only way for most patients to connect with their psychiatrists and psychologists from Michigan Medicine, U-M's academic medical center.

For nearly all of those patients, it has stayed that way for the past nine months.

Now, a new study led by Severe suggests that more than half of those patients will want to keep going with virtual mental health care even after the pandemic subsides.

According to the new findings published in JMIR Formative Research, the convenience of seeing a provider without leaving home, and avoiding potential exposure to the coronavirus especially for those with other underlying health concerns, factor heavily into this preference. So does a patient's initial experience with seeing a provider virtually.

Patient preferences

The data come from a summer 2020 phone survey of 244 patients or parents of patients who had had appointments scheduled with a U-M mental health provider in the first weeks of the pandemic-related shutdown. Nearly 83% decided to have their or their child's first pandemic-era appointment through a video chat instead.

But the study also suggests a need for special attention to the minority of patients who initially chose to continue psychiatric care through telephone calls.

Though this accounted for less than 14% of the study population, they were more likely to be over 45. By summer, they were much less likely to want to receive mental health care remotely in the future.

As health insurers and government agencies make decisions about whether and how to pay mental health providers for virtual care in the short- and long-term, the new data could help inform them, says Severe.

"We went from not getting much traction with telepsychiatry, and encountering a lot of reluctance among providers and patients, to having nearly all our care delivered virtually, and offering help to those who need it," she says. "These data suggest an opportunity to turn the experience of the pandemic into an opportunity to improve access to mental health care and improve the continuity of care. But policy and reimbursement decisions will be important."

More about the study

Nearly all the patients in the study group who had a virtual visit by summer said it went as well as they had expected, or better.

The study does not cover the period after Mary Carol Blazek, M.D., the study's senior author, led the development of a program called GET Access. It helps older adults prepare for video visits with a geriatric psychiatry specialist.

Michigan Medicine also now offers assistance for any patient with a scheduled appointment, to help them set up their online patient portal account and test the video visit technology within it.

Parents of children receiving mental health or behavioral health care from Department of Psychiatry providers especially noted that video visits were more engaging.

Phone-visit patients said it was important to have the option to talk when their internet connection was unstable or they had trouble with the video platform. One-third said they were just more comfortable talking by phone.

Impacts on access

Although the new paper does not examine clinic appointment cancellation and no-show rates, anecdotal evidence suggests that it has come down substantially from a one-in-four rate before the pandemic.

Whether it's the debilitating effect of their mental health condition, or their access to transportation, time off from work or child care, many factors can get in the way of a patient making it to an in-person appointment, Severe says. But virtual visits remove most of these barriers.

Cost poses another potential barrier for phone-based care. In the test-run months before COVID-19, insurers wouldn't typically cover phone calls, leaving the provider to absorb the cost or to ask patients to pay out of pocket to talk on the phone with their provider.

Insurers covered phone-based mental health care for much of 2020, but that appears to be ending soon. But Severe says that for certain patients with an established relationship with their mental health provider, phone and video appointments are equally effective and should receive similar reimbursement from insurers. Both modality offer opportunity for a blended care model bridging in-person session with virtual visits as deemed appropriate".

"For the first visit with a new patient, we try to avoid using phone as it limits the initiation of the provider-patient therapeutic alliance, reduce communication cues and limits the mental status exam that includes observing patient facial expressions, interactions, and movement," she says. "Depending on the complexity of the patient's situation, we may need to do a physical examination from time to time, to assess their balance and mobility, and check for medication side effects to name a few."

Going forward, Severe hopes to study more aspects of telepsychiatry in the COVID-19 era, including understanding how socioeconomic status, rural vs. urban residence, technology access and other factors play into access. She notes that the study team chose to conduct their study by phone, instead of reaching out via email or patient portal message, to ensure maximum access.

Our bodies often dispatch stem cells to mend or replace biological damage, but how these repair agents make their way through dense tissue to arrive at the scene had been a mystery. "How stem cells squeeze through tissue openings a hundred to a thousand times smaller than themselves had been a perplexing question," says Ovijit Chaudhuri, professor of mechanical engineering.

In an article published in the Jan. 8 edition of Science Advances, Chaudhuri and colleagues reveal that stem cells use their nucleus - a large, stiff organelle within the cell - as a means of propulsion.

Their discovery was surprising because scientists had thought cells would have particular difficulty forcing this big, stiff lump through tiny pores in surrounding tissue. Instead, they found that bone-marrow derived stem cells use the physical force generated by the nucleus to help bore through biological obstacles to reach fractures and help initiate healing. "Our finding presents a completely new understanding of how cells utilize the nucleus to generate mechanical force," says Hong-Pyo Lee, the study's first author, who recently graduated as a PhD student in mechanical engineering.

To arrive at this finding, the researchers extracted stem cells from bone marrow and used hydrogels to mimic the tissues that compose their biological environments. The researchers found that stem cells propel their nucleus into a needle-like protrusion that penetrates the physical barriers inside the body. The nucleus moves into the protrusion and, through a complex biochemical mechanism, inflates the protrusion like a balloon, creating an opening in the tissue wide enough for the entire stem cell to migrate through. The piston-like behavior of the nucleus, Chaudhuri says, is reminiscent of the action of a mechanical piston within the internal combustion engine of a car.

Their insight could help guide the design of biomaterial implants that would use stem cells for regenerative medicine. Chaudhuri notes that other stem cells, immune cells and cancer cells also migrate through surrounding tissue, suggesting fruitful areas for future research into whether these cells use the same propulsion system, knowledge that might be turned to therapeutic advantage.

"This is a beautiful example of how the principles of mechanical engineering can help us understand cellular behavior that affects health," he says.

An invisible flow of groundwater seeps into the ocean along coastlines all over the world. Scientists have tended to disregard its contributions to ocean chemistry, focusing on the far greater volumes of water and dissolved material entering the sea from rivers and streams, but a new study finds groundwater discharge plays a more significant role than had been thought.

The new findings, published January 8 in Nature Communications, have implications for global models of biogeochemical cycles and for the interpretation of isotope records of Earth's climate history.

"It's really hard to characterize groundwater discharge, so it has been a source of uncertainty in the modeling of global cycles," said first author Kimberley Mayfield, who led the study as a graduate student at UC Santa Cruz. "It took a large effort by researchers around the world who came together to make this happen."

The researchers focused on five key elements--lithium, magnesium, calcium, strontium, and barium--measuring concentrations and isotope ratios in coastal groundwater at 20 sites around the world, and using previously published data from additional sites.

"Those elements are important because they come from the weathering of rocks, and weathering of silicate rocks accounts for a huge uptake of carbon dioxide from the atmosphere over long time scales," Mayfield explained.

Coauthor Adina Paytan, a research professor in UCSC's Institute of Marine Sciences, said groundwater is an important source of inputs to the oceans, but has been easy to ignore because it is unseen and hard to measure.

"This is the first global assessment of groundwater discharge for most of these elements," Paytan said. "This information is useful for our understanding of how weathering of rock is related to climate, not only in the present but also in the past."

The study estimated that the amount of these elements entering the sea from groundwater is at least 5%, and up to 16%, of the contributions from rivers based on the latest global groundwater flux estimates. The results also showed that the isotopic composition of groundwater discharge can be different from that of rivers.

"The composition of groundwater discharge is very dependent on coastal geology, whereas river water is more influenced by the interiors of continents," Mayfield said. "It's important to recognize that groundwater makes a difference globally, and now that we have this large data set, people can keep improving it with more sampling and develop better models of global groundwater discharge."

A research team at the University of Basel has discovered immune cells resident in the lungs that persist long after a bout of flu. Experiments with mice have shown that these helper cells improve the immune response to reinfection by a different strain of the flu virus. The discovery could yield approaches to developing longer-lasting vaccinations against quickly-mutating viruses.

At the start of the coronavirus pandemic, some already began to raise the question of how long immunity lasts after weathering SARS-CoV-2. The same question has now arisen regarding the COVID-19 vaccination. A key role is played by immunological memory - a complex interplay of immune cells, antibodies and signaling substances that allows the body to fight off known pathogens very efficiently.

Researchers led by Professor Carolyn King from the University of Basel's Department of Biomedicine have now identified a diverse group of immune cells in the lungs that are key to the defense against reinfection by flu viruses. The same could be true of reinfection by other pathogens that cause respiratory diseases.

In experiments with mice, the researchers characterized a group of memory T cells in lung tissue that remain for a long time after a bout of flu. The team reports on these "T resident helper cells" in the peer-reviewed journal Science Immunology.

Reservoir inside tissue

"Relatively little is known about memory T cells that remain in tissue," explained Nivedya Swarnalekha, co-first author of the study. Previous studies have focused on memory cells in blood and lymphatic tissue. "But it makes sense that the body keeps a reservoir of these cells in the tissues affected by the infection, where the same or similar pathogens could invade again."

In their study, the researchers describe two types of T helper cells in the lungs. One type releases signaling substances in case of reinfection to equip other immune cells with deadlier "weapons" in the fight against the pathogen. The other type, previously characterized primarily in lymphatic tissue and thought to be absent in lung tissue, assists antibody-producing immune cells (B cells) and localizes closely with them in the lung.

The researchers were able to show that the presence of these cells in the direct proximity of the antibody-producing B cells led to a more efficient immune response against a different flu virus.

Starting point for long-term vaccine protection

"These T helper cells could be an interesting starting point for longer-lasting flu vaccinations," says David Schreiner, the other co-first author of the study, adding that it might be possible, for example, to supplement vaccines with agents that promote the formation of these T helper cells which migrate into the tissue. To that end, further research and development are needed.

CORVALLIS, Ore. - Efficiently mass-producing hydrogen from water is closer to becoming a reality thanks to Oregon State University College of Engineering researchers and collaborators at Cornell University and the Argonne National Laboratory.

The scientists used advanced experimental tools to forge a clearer understanding of an electrochemical catalytic process that's cleaner and more sustainable than deriving hydrogen from natural gas.

Findings were published today in Science Advances.

Hydrogen is found in a wide range of compounds on Earth, most commonly combining with oxygen to make water, and it has many scientific, industrial and energy-related roles. It also occurs in the form of hydrocarbons, compounds consisting of hydrogen and carbon such as methane, the primary component of natural gas.

"The production of hydrogen is important for many aspects of our life, such as fuel cells for cars and the manufacture of many useful chemicals such as ammonia," said Oregon State's Zhenxing Feng, a chemical engineering professor who led the study. "It's also used in the refining of metals, for producing man-made materials such as plastics and for a range of other purposes."

According to the Department of Energy, the United States produces most of its hydrogen from a methane source such as natural gas via a technique known as steam-methane reforming. The process involves subjecting methane to pressurized steam in the presence of a catalyst, creating a reaction that produces hydrogen and carbon monoxide, as well as a small amount of carbon dioxide.

The next step is referred to as the water-gas shift reaction in which the carbon monoxide and steam are reacted via a different catalyst, making carbon dioxide and additional hydrogen. In the last step, pressure-swing adsorption, carbon dioxide and other impurities are removed, leaving behind pure hydrogen.

"Compared to natural gas reforming, the use of electricity from renewable sources to split water for hydrogen is cleaner and more sustainable," Feng said. "However, the efficiency of water-splitting is low, mainly due to the high overpotential - the difference between the actual potential and the theoretical potential of an electrochemical reaction - of one key half-reaction in the process, the oxygen evolution reaction or OER."

A half-reaction is either of the two parts of a redox, or reduction-oxidation, reaction in which electrons are transferred between two reactants; reduction refers to gaining electrons, oxidation means losing electrons.

The concept of half-reactions is often used to describe what goes on in an electrochemical cell, and half-reactions are commonly used as a way to balance redox reactions. Overpotential is the margin between the theoretical voltage and the actual voltage necessary to cause electrolysis - a chemical reaction driven by the application of electric current.

"Electrocatalysts are critical to promoting the water-splitting reaction by lowering the overpotential, but developing high-performance electrocatalysts is far from straightforward," Feng said. "One of the major hurdles is the lack of information regarding the evolving structure of the electrocatalysts during the electrochemical operations. Understanding the structural and chemical evolution of the electrocatalyst during the OER is essential to developing high-quality electrocatalyst materials and, in turn, energy sustainability."

Feng and collaborators used a set of advanced characterization tools to study the atomic structural evolution of a state-of-the art OER electrocatalyst, strontium iridate (SrIrO3), in acid electrolyte.

"We wanted to understand the origin of its record-high activity for the OER - 1,000 times higher than the common commercial catalyst, iridium oxide," Feng said. "Using synchrotron-based X-ray facilities at Argonne and lab-based X-ray photoelectron spectroscopy at the Northwest Nanotechnology Infrastructure site at OSU, we observed the surface chemical and crystalline-to-amorphous transformation of SrIrO3 during the OER."

The observations led to a deep understanding of what was going on behind strontium iridate's ability to work so well as a catalyst.

"Our detailed, atomic-scale finding explains how the active strontium iridate layer forms on strontium iridate and points to the critical role of the lattice oxygen activation and coupled ionic diffusion on the formation of the active OER units," he said.

Feng added that the work provides insight into how applied potential facilitates the formation of the functional amorphous layers at the electrochemical interface and leads to possibilities for the design of better catalysts.