Culture

Stone tools move back the arrival of humans in America thousands of years

Findings of stone tools move back the first immigration of humans to America at least 15,000 years. This is revealed in a new international study from the University of Copenhagen, where researchers have analysed ancient material from a Mexican mountain cave.

The first humans arrived in America at least 30,000 years ago, approximately 15,000 before science was hitherto able to render it probable. This is the conclusion in new study published in the scientific journal, Nature.

The team behind the article consists of archaeologists and DNA experts from the University of Copenhagen and universities in Mexico, the UK, the US and Brazil, among others.

"The article in Nature is a scientific hand grenade. The fact that it moves back the time of early immigration to America significantly is guaranteed to ignite a heated debate," says Eske Willerslev, Professor and Head of Lundbeck Foundation Centre for GeoGenetics, Globe Institute at the University of Copenhagen.

Eske Willerslev and his two colleagues, Associate Professor Mikkel Winther Pedersen and Assistant Professor Martin Sikora, made up the Danish contribution to the international team of researchers.

The three scientists from UCPH have conducted the DNA analyses of ancient remains from animal and plant material found during the excavations of the Chiquihuite Cave in Northern Mexico.

1,900 stone tools

As far back as 30,000 years ago, humans had already developed techniques for producing tools. In the Mexican cave, researchers found 1,900 stone tools.

The unique feature of the Chiquihuite Cave is the "floor", which consists of six layers of detritus and dust - all in all, a ten-foot column of ancient remains - which is so compressed and stable that by using various advanced measuring methods, it has been possible to date the layers one by one, from top to bottom.

Each layer has contained deposits of stone tools such as knives, scrapers and arrowheads, which the researchers have also been able to date.

"The cave finds are extremely interesting. These archaeological finds are so far the oldest in America. And the excavated stone tools are of a type unique to America," Professor at Universidad Autónoma de Zacatecas, Mexico, Ciprian F. Ardelean, states.

Ice Cap Across North America

Until now, science has assumed that the earliest immigration to America took place approx. 15,000 years ago. At the time, a narrow opening in the ice along the northern Pacific coastline was created, which made it possible to walk from Siberia onto the American continent.

At the time, there were no other access routes to the continent, because North America was covered by a thick ice cap, which only later - approx. 13,000 years ago - melted enough to enable passage.

30,000 years ago, when the first stone tools were left in the Chiquihuite Cave, the massive ice cap had not yet covered all of North America, which means that it would have been possible to walk from Siberia and down through the American continent, Eske Willerslev explains.

"And that's how we must understand the presence of these humans in Mexico at this particular time - unfortunately though, we have no idea who they were. Because although we searched very thoroughly for human DNA in the samples we gathered during the ten days we spent at the Chiquihuite Cave, there were no human traces to be found. However, we may still be able to find some in the hundreds of earth samples we gathered, because we've not yet had time to analyse all of them."

According to Mikkel Winther Pedersen who was in charge of the DNA analyses, their finds contain DNA samples from numerous plants as well as animals. He elaborates:

"For example, we found DNA from an American black bear, a wide range of rodents, several types of bats as well as sparrow and falcon. These are all animals we would expect to find in Mexico at the time. Simultaneously, we were able to ascertain

CORVALLIS, Ore. - The discovery of the first active methane seep in Antarctica is providing scientists new understanding of the methane cycle and the role methane found in this region may play in warming the planet.

A methane seep is a location where methane gas escapes from an underground reservoir and into the ocean. Methane seeps have been found throughout the world's oceans, but the one discovered in the Ross Sea was the first active seep found in Antarctica, said Andrew Thurber, a marine ecologist at Oregon State University.

"Methane is the second-most effective gas at warming our atmosphere and the Antarctic has vast reservoirs that are likely to open up as ice sheets retreat due to climate change," Thurber said. "This is a significant discovery that can help fill a large hole in our understanding of the methane cycle."

The researchers' findings were published today in the journal Proceedings of the Royal Society B. Co-authors are Sarah Seabrook and Rory Welsh, who were graduate students at OSU during the expeditions. The research was supported by the National Science Foundation.

Methane is a greenhouse gas that is 25 times more powerful than carbon dioxide at warming the planet. Most methane in the ocean water and sediment is kept out of the atmosphere by microbes that consume it.

Thurber and his colleagues discovered that the microbes around the Antarctic seep are fundamentally different that those found elsewhere in the world's oceans. This helps researchers better understand methane cycles and the factors that determine whether methane will reach the atmosphere and contribute to further warming, Thurber said.

The Ross Sea seep was discovered in an area that scientists have studied for more than 60 years, but the seep was not active until 2011, said Thurber, an assistant professor in Oregon State's College of Earth, Ocean, and Atmospheric Sciences and the College of Science's Department of Microbiology.

An expansive microbial mat, about 70 meters long by a meter across, formed on the sea floor about 10 meters below the frozen ocean surface. These mats, which are produced by bacteria that exist in a symbiotic relationship with methane consumers, are a telltale indication of the presence of a seep, said Thurber.

"The microbial mat is the road sign that there's a methane seep here," Thurber said. "We don't know what caused these seeps to turn on. We needed some dumb luck to find an active one, and we got it."

Thurber happened to be in Antarctica in 2012 when another researcher told him about a "microbial waterfall" and thought it was something he should look at. Thurber was able to confirm the seep's presence, collect samples and analyze the seep and its environment. When he returned to the site in 2016 to conduct further study, he also discovered a second seep nearby.

Antarctica is believed to contain as much as 25 percent of Earth's marine methane. Having an active seep to study gives researchers new understanding of the methane cycle and how that process might differ in Antarctica compared to other places on the planet, Thurber said.

For example, researchers have found that the most common type of microbe that consumes methane took five years to show up at the seep site and even then those microbes were not consuming all of the methane, Thurber said. That means some methane is being released and is likely working its way into the atmosphere.

Studying the site over a five-year time span allowed researchers to see how microbes respond to the formation of a seep, said Seabrook, who earned her doctorate at OSU and is now a post-doctoral scholar at the National Institute of Water and Atmospheric Research in Wellington, New Zealand.

"What was really interesting and exciting was that the microbial community did not develop as we would have predicted based on other methane seeps we have studied around the globe," she said.

Researchers had assumed that microbes should respond really quickly to changes in the environment, but that wasn't reflected in what OSU's team saw in Antarctica, Thurber said.

"To add to the mystery of the Antarctic seeps, the microbes we found were the ones we least expected to see at this location," he said. There may be a succession pattern for microbes, with certain groups arriving first and those that are most effective at eating methane arriving later.

"We've never had the opportunity to study a seep as its forming or one in Antarctica, because of this discovery we can now uncover whether seeps just function differently in Antarctica or whether it may take years for the microbial communities to become adapted," Thurber said.

"Animals in Antarctica are very different than elsewhere in the world as the continent has been separated from the rest of the globe for more than 30 million years - a long time for evolution to act," he said. "That has resulted in a remarkable diversity of fauna that we only find there. That may also contribute to the differences in microbes there."

It is important to understand how methane seeps behave in this environment so researchers can begin factoring those differences into climate change models, Thurber said. He hopes to return to the site to monitor its evolution and conduct further research.

Adoptive cell transfer immunotherapy is one of the most promising new treatments for people with hard-to-treat cancers. However, the process is complex and needs fine-tuning in order to develop more treatment strategies that will work for more people.

In a new study looking at adoptive cell transfer products bearing a transgenic T-cell receptor (TCR), researchers at the UCLA Jonsson Comprehensive Cancer Center have identified a discordant phenomenon in which a subset of patients displayed profoundly decreased expression of the transgenic TCR over time, despite the transgenic TCR being present at the DNA level. This gave rise to the observation that structural changes to the DNA via DNA methylation make it inaccessible for transcription and translation, which is an influential step in the flow of genetic information from DNA to RNA. This can be one clue into why some patients stop responding to this type of immunotherapy.

"The issue is this phenomenon happens over time," said lead author Theodore Scott Nowicki, MD, PhD, clinical instructor of pediatrics and hematology/oncology at the David Geffen School of Medicine at UCLA. "We're hoping this can help inform the design of future generations of these types of therapies and pinpoint different vectors that might be more or less vulnerable to this phenomenon."

JOURNAL

The study was published online in Cancer Discovery, a journal of the American Association for Cancer Research.

BACKGROUND

Adoptive cell transfer immunotherapy works by taking a patient's own T cells, which are one of the components of the immune system, and genetically modifying them in the laboratory to target tumor-specific antigens on the surface of the tumor. The new army of tumor-specific T cells are then reinfused back into the patient to help attack the cancer.

A key component of adoptive cell transfer therapy requires genetically modifying T cells to target cancer cells. This is often done with viral transduction agents with either lentivirus- or retrovirus-based products to express either a cancer antigen-specific TCR or chimeric antigen receptor (CAR).

In order to develop more efficient cell therapies, Nowicki and colleagues are studying the genetic mutations of T cells to understand the structural changes to DNA over time. This could reveal why adoptive cell transfer therapy is more likely to work in some patients versus others and help inform the future design of next-generations of the therapy.

METHOD

The team analyzed 16 clinical transgenic adoptive cell therapy samples collected before and during treatment from patients with melanoma and sarcoma. This allowed the team to look at the expression of the transgenic TCR at the DNA and protein level. It gave them insight into what proportion of the cells displayed impaired expression of the transgenic TCR. They were then able to assess the degree of DNA methylation present in the retroviral vector's promoter region over time, and correlate this degree of DNA methylation with repression of the transgenic TCR.

IMPACT

The study can help researchers in the design of future generations of cellular immunotherapies to help treat people with advanced cancers.

The ability of the human brain to process and store information is determined to a large extent by the connectivity between nerve cells. Chemical synapses are very important in this context as they constitute the interface for the transmission of information between individual nerve cells. Abnormalities in the formation of synapses cause many neurological disorders such as autism. Neurobiologists at Johannes Gutenberg University Mainz (JGU) have found new evidence that specific calcium channel subunits play a crucial role in the development of excitatory and inhibitory synapses.

α2δ subunits have different effects on the formation of new synapses

Autism spectrum disorder is a condition involving impaired development that begins with birth and is usually manifested when the individual in question exhibits difficulties in social interaction and communication. It is postulated that the main underlying cause is disruption of synapse-mediated interaction between nerve cells.

The results of several studies indicate that so-called α2δ subunits of calcium channels are involved in the formation and fine-tuning of excitatory and inhibitory nerve cells, but little has been known to date about when and how specifically the four forms of α2δ subunits are involved. It is this aspect that the research team led by Professor Martin Heine of the Institute of Developmental Biology and Neurobiology at Mainz University has now addressed. What is particularly interesting is their research finding that the two dominant α2δ subunits in the hippocampus, α2δ1 and α2δ3, have different effects on synaptogenesis in neuronal networks.

In order to investigate the underlying mechanism, the researchers prepared isolated networks of hippocampal neurons. The results show that during the early phase of the development of neural networks, subunit α2δ3 promotes the release of an inhibitory neurotransmitter, triggers the formation of inhibitory synapses, and boosts the growth of axons from inhibitory neurons. "The α2δ3 subunit is obviously an important factor with regard to the early development of neural networks," explained Heine. At later development phases and in more mature neuronal networks, it is subunit α2δ1 that fosters excitatory stimulus transmission and synaptogenesis.

Connectivity relies on concerted cooperation between α2δ1 and α2δ3

In their article in The Journal of Neuroscience, the researchers proposed "that formation of connectivity in neuronal networks is associated with a concerted interplay of α2δ1 and α2δ3 subunits of calcium channels". Dr. Artur Bikbaev, one of the lead authors from JGU, further concluded that the calcium channel subunits are molecules that are relevant to the development of the brain. New data has confirmed the assumption that there is a link between an aberration in the genes that code for subunits α2δ1 and α2δ3 and autistic spectrum disorders. An imbalance in the ratio of excitatory to inhibitory neurons is also thought to be the cause of the epileptic seizures which very frequently accompany autism spectrum disorder.

In addition to the team at JGU, researchers at the Leibniz Institute for Neurobiology, the University of Münster, and the Medical University of Innsbruck were also involved in the project.

For-profit status is associated with the extent of an outbreak of coronavirus disease 2019 (COVID-19) in long-term care (LTC) homes and the number of resident deaths from COVID-19, but not the likelihood of an outbreak, which was related to the infection rate in the surrounding local public health unit and the total number of beds in the home, found new research published in CMAJ (Canadian Medical Association Journal).

"Our findings suggest that the incidence of COVID-19 in the public health unit region surrounding an LTC home and the size of the home -- but not for-profit status -- are important risk factors for outbreaks of COVID-19 in LTC homes, whereas for-profit status (with for-profit homes more commonly having outdated design standards and chain ownership) is an important risk factor for transmission of SARS-CoV-2 after an outbreak has been established in a home," writes Dr. Nathan Stall, Sinai Health and the University of Toronto, with coauthors.

The study looked at all 623 long-term care homes in Ontario from March 29 to May 20, 2020, and their 75 676 residents. It excluded retirement residences, which are privately funded and not administered by the Ministry of Long-term Care. For-profit homes were usually smaller, housed fewer residents, and had older design standards from before 1972 with multiple-occupancy rooms and chain ownership.

About 30% (190) of long-term care homes in Ontario experienced outbreaks during the study period, with 110 (30.6%) occurring in for-profit homes, 55 (34%) in nonprofit homes and 25 (24.8%) in municipal homes.

For-profit status of LTC homes was associated with about a two-fold increase in the extent of a COVID-19 outbreak (number of resident cases) and a 178% increase in the number of resident deaths compared with homes with non-profit status. These associations were mediated in large part by the higher proportion of outdated design standards (which meet or fall below standards set in the year 1972) and chain ownership in for-profit homes. Of the 10 homes with the highest death rates, 7 were for-profit-homes with older design standards and chain ownership.

"Newer design standards provide for larger and more private room accommodations, as well as less crowded and self-contained common spaces, whereas older design standards can have ward-style accommodation and centralized common spaces in which all residents can interact. Beyond promoting quality of life, newer design standards promote infection prevention and control, given that they limit infection both within resident bedrooms and among areas of a facility," write the authors.

"With governments such as Ontario's already committing to independent commissions and inquiries into their LTC systems, it is important that policy recommendations and changes consider all root causes of the present crisis, including supporting capital projects to retrofit or rebuild older LTC homes," the authors write.

CHICAGO --- A new Northwestern Medicine study in mice found a widely used class of drugs to treat patients with hypertension, cardiovascular disease and diabetic kidney disease - many of whom are elderly -- does not increase the risk of developing a severe and potentially fatal COVID-19 infection, as previously feared.

There have been concerns by the medical community worldwide that the drugs -- ACE inhibitors and angiotensin receptor blockers (ARB) -- might have caused an increase in ACE2, the main receptor for SARS-CoV-2, which could possibly increase the risk for this infection and its severity.

But the new findings revealed a decrease, not an increase, in ACE2 in mice kidney membranes and no change in lung membranes. The study supports the safety of these drugs in the face of the COVID-19 pandemic.

This study is the first to examine the effect of ACE2 and ARBs in the lungs, which are considered one of the main targets for SARS-CoV-2 entry into the body.

"This study supports the concept that there is no increased risk for COVID-19 infection by using ACE inhibitors and angiotensin receptor blockers," said Daniel Batlle, the Earle, del Greco, Levin Professor of Medicine at Northwestern University Feinberg School of Medicine and a Northwestern Medicine nephrologist.

The paper was published recently in the Journal of the American Society of Nephrology.

ACE inhibitors and ARBs are a category of drugs called RAS blockers. These drugs, by different mechanisms, block the actions of a peptide that causes narrowing of blood vessels and fluid retention by the kidneys, which result in increased blood pressure. The drugs help blood vessels relax and expand and decrease fluid retention, both of which lower blood pressure.

To examine this issue, Northwestern Medicine scientists measured ACE2 in isolated kidney and lung membranes of mice that were treated with either captopril, a widely used ACE inhibitor, or telmisartan, an ARB also widely prescribed.

Since the recognition that ACE2 is the main receptor for SARS-CoV-2, there have been multiple studies discussing the potential risk (or lack of) for susceptibility and worse clinical course of COVID-19 in patients treated with RAS blockers. Much of the speculation comes from previous animal studies where some RAS blockers were reported to upregulate ACE2 in the heart and kidney vasculature.

"My lab has long worked with ACE2, and this was a critical question that needed to be addressed," Batlle said. First author Jan Wysocki said, "We had no bias one way or another, and the kidney findings showing lower ACE2 in treated animals were a bit unexpected."

RENO, Nev. - Summit Lake in remote northwest Nevada is home to the only self-sustaining, robust, lake population of Lahontan Cutthroat Trout, North America's largest freshwater native trout species. Research to understand the reasons why this population continues to thrive, where others have not, will be used to protect the fish and its habitat - as well as to apply the knowledge to help restore other Nevada lakes that once had bountiful numbers of the iconic fish that historically reached 60 pounds.

A team of researchers from the University of Nevada, Reno and the Summit Lake Paiute Tribe has been studying the watershed ecosystem and recently authored two papers published in scientific journals describing their findings about the relatively small desert terminal lake.

This project is part of a 9-year collaboration to conserve habitats and promote a healthy ecosystem for the lake. University researchers Sudeep Chandra and Zeb Hogan - as well as students from their aquatics ecosystems lab and Global Water Center - work with the tribe's Natural Resources Department, formerly led by fish biologist William Cowan before he retired from the U.S. Fish and Wildlife Service.

"An objective to implement holistic management at Summit Lake is to blend science with traditional knowledge to protect and conserve natural ecologic processes, species diversity and tribal cultural practices," Cowan said. "The partnership with the Global Water Center, as well as many other researchers, agencies, and organizations has complemented this objective by implementing science-based research and technological advances to investigate the viability of trout in the Summit Lake watershed."

Monitoring data, including climate, hydrology, fish and wildlife population trends and habitat integrity, is used to develop, revise or validate the tribe's management plans and regulations. This approach is a stark contrast to when the lake ecosystem and associated resources were at risk of irreversible impacts caused by non-point source pollution, irrigation diversions, livestock grazing, and the unknown affects caused by exporting trout eggs for establishment or supplementation of other populations.

"Our team at the University wants to support the efforts initiated by the Summit Lake Tribe," Chandra, a professor in the College of Science, said. "Our goals are to assist them in developing their science-based program to protect Nevada's only strong, self sustaining lake population of Lahontan Cutthroat Trout. We believe that investigations in this robust ecosystem like Summit, where there is little human impact, could improve recovery efforts in other lake systems that are less fortunate and that have lost their trout like the Walker and Tahoe. Surprisingly there are still few comparative investigations of these lake ecosystems and how they could support trout during a time for increasing global changes."

The Lahontan Cutthroat Trout, with its crimson red-orange slash marks on the throat under the jaw and black spots scattered over steel gray to olive green scales, is Nevada's state fish and holds a cultural significance to the Summit Lake Paiute Tribe while providing the tribe with bountiful food and fish resources.

As an important traditional food source, Lahontan Cutthroat Trout composed a large part of Tribal member's diets and were the focus of many gatherings held to honor the fish and to learn oral history, traditional practices, and cultural resources from elders of the tribe.

"The tribe has exercised their sovereignty to protect, manage and enhance tribal homelands, including the lake ecosystem and associated resources by working with federal agencies and other organizations that enable the tribe to holistically manage and protect the land, water and resources that fish, wildlife and tribal members depend on for survival," Cowan said.

Climate Change, drought impacts watershed

The lake is about one square mile of surface area, has a mean depth of 20 feet with the southern end generally deeper with about 50 feet of depth at the deepest. The lake elevation decreased about 13 feet during the severe drought in the western United States that lasted from 2012 to 2016.

"One thing we learned is that the climatically induced drought can change the hydrology, or flow of water and connections of stream to lake, but even with these changes, the trout populations remain relatively stable in the lake," Chandra said. "They look for the opportunity to spawn every year and likely wait for better conditions with higher flows for better access to upstream spawning grounds.

"So it is critical to support the tribe's efforts to protect the watershed and understand how the long term changes in water resources, like the flow of water, will change with pending climate change projections for the Great Basin."

James Simmons, doctoral student with the Ecology, Evolution and Conservation Biology program at the University said the population appears resilient to today's climate disturbances/drought, which is very positive, but should the frequency and severity of drought increase in the future, will the population remain resilient in the face of continued low abundance, survival, spawners and a skewed sex ratio.

"I think the key going forward will be for the tribe to try to understand how the long-term flow of water in the watershed will be impacted by the future changing climate in the Great Basin - so that the tribe can formulate a game plan to get ahead of any potential negative repercussions," he said. "Like cutthroat populations across the western U.S., this population faces unknown impacts from climate change.

"Declining abundance and diverging male and female abundance under changing drought cycles and conditions may have negative long term consequences. The prediction of increased frequency, severity and duration of drought and an increased percentage of rain may decrease abundance, reduce the effective population size and skew the sex ratio at Summit Lake."

The research team found that connections between the upper watershed and the lake are essential for maintaining a healthy population during a drought. During the drought of 2012-2016, Summit Lake had a strong, stable population of naturally reproducing Lahontan Cutthroat Trout. The numbers of trout spawning up Mahogany Creek, one of the lake's only inflow streams, was also relatively stable in number. Some of the trout in the lake migrated all the way to the upper watershed, about eight miles.

"Lahontan Cutthroat Trout can live in streams and lakes," Chandra said. "The trout that live in lakes need rivers to spawn to keep their populations healthy. The numbers do show with little to no major changes to the watershed by human development, there is still a highly variable amount of spawning from lake to stream."

Stream flow studied

Adequate stream flow is necessary for spawning and movement to the lake-dwelling component of the population. In rivers where flow is regulated, enough flow must be preserved in the spring to allow "lake spawners" to come upstream and in the fall to allow juveniles to migrate to the lake.

"Healthy habitat and ecological connectivity between habitats, such as no man-made migration barriers and adequate stream flow, should be preserved throughout as much of the watershed as possible (and of course between the stream and the lake) to facilitate movement for both stream- and lake-dwelling fish, and to support a robust overall population," Teresa Campbell, a biologist and staff researcher in the University's Global Water Center and lead author of one of the scientific papers, said.

"Strong connectivity between healthy stream and lake habitats is crucially important to the long-term survival of the Summit Lake Lahontan Cutthroat Trout because it seems that the exchange of individual fish across habitats contributes to the resilience and vitality of the population as a whole."

The study also found that in drought-prone systems, streams should have adequate pool habitat and cover such as trees and woody debris to provide a refuge area from the drought and cooler temperatures for trout.

"During the drought, in the stream, these refuge pools with structure in the form of wood, cobbles, or boulders supported higher densities of stream-dwelling trout," Campbell said. "Therefore, this habitat type is an important component of healthy stream habitat for trout."

Forward thinking on the part of the tribe led to early habitat protections for the stream and the lake that now contribute to the success of this population. The tribe took measures to protect much of the stream habitat, erecting grazing enclosures in the 70s that prevented cattle from trampling the stream and allowed the stream to recover into the healthy habitat it is now. This is one of the reasons that trout are thriving here.

"The lake and surface water on the Reservation are further protected by restricting public access and monitoring resources necessary to sustain endemic species diversity in the area," Cowan said.

The Summit Lake Paiute Tribe Reservation is the most remote Native American reservation in Nevada. Located in the northwest corner of Nevada, the reservation is 50 miles south of the Oregon border and 70 miles east of the California border.

Veterans who have served in the U.S. military since the 9/11 attacks have a high level of need for both substance use treatment and mental health care, yet many do not receive appropriate help for their co-occurring disorders, according to a new RAND Corporation report.

While the availability of services has expanded in recent years, more effort is needed to encourage providers to adopt evidence-based treatments and structured programs to make them more assessible and appealing to veterans, according to the report.

Among the RAND recommendations are offering evidence-based integrated treatments that target substance use and co-occurring mental health disorders concurrently, evaluating veterans regularly throughout treatment to make sure both substance use and mental health outcomes are adequately addressed, and incorporating veterans' treatment preferences into decisions about their care.

"Despite federal and community efforts to improve the quality and availability of
care for veterans, they remain at high risk of developing both mental health disorders
and substance use disorders," said Eric Pedersen, lead author of the study, an adjunct researcher at RAND and an associate professor of psychiatry and behavioral sciences at the Keck School of Medicine of USC.

"More work is needed to explore in more detail not only the quality of care available to these high-risk veterans, but also their ability to access it and their treatment outcomes over the short and long terms," Pedersen said.

RAND was asked by the Wounded Warrior Project to examine the state of care provided to post-9/11 veterans who experience both substance use and mental health disorders, and provide recommendations for how to improve care for the group.

"We must continue the work to meet the mental health needs of post-9/11 veterans," said Mike Richardson, Wounded Warrior Project's vice president of mental health. "This important research will help us support veterans by supporting programs that can help those suffering from both substance use disorders and mental health challenges."
Veterans with co-occurring substance use disorders and mental health disorders may have poor functioning in multiple areas of their lives, such as in their relationships, and are likely to have other behavioral health and physical health problems.

Frequently, these veterans do not seek behavioral health care, and even when they do they generally have poorer treatment outcomes than those with just a single behavioral health disorder. This may be because both issues are not addressed concurrently and/or with evidence-based approaches.

RAND researchers reviewed the research literature on effective approaches to treating substance use disorders alone and alongside mental health disorders, and analyzed the approaches used at treatment centers that offer substance use disorder treatment by conducting a series of interviews and site visits with treatment providers.

Using information from two federal databases about treatment programs and information about the locations of the post 9/11 veterans who belong to the Wounded Warrior Project, the study found that alumni of the Wounded Warrior Project have relatively convenient access to mental health and substance use treatment facilities with specialized programs for co-occurring disorders and that also offer specialty programs for veterans.

However, despite access to these facilities, visits and telephone interviews with representatives from a sample of treatment facilities revealed that evidence-based practices and data-driven decision making were not standardized across facilities.

Although some facilities prioritized innovation, the weight of clinical experience in others perhaps precluded some clinic leaders and providers from implementing novel treatment approaches or adapting current approaches based on the most current evidence.

"Across the board, there was a need for more data and systematic tracking of treatment outcomes over time," said Terri Tanielian, co-author of the report and a senior behavioral scientist at RAND.

The report also notes that the coronavirus pandemic in the United States has made it clear that telehealth and self-help approaches are a necessary option for mental health and substance use disorder care for veterans when access to in-person care is limited or risky.

The Wounded Warrior Project is a nonprofit organization established to support veterans of the post 9/11 era with significant injuries.

The report, "Improving Substance Use Care for Post-9/11 Veterans: Addressing Barriers to Expanding Integrated Treatment Options," is available at http://www.rand.org. Other authors of the report are Kathryn E. Bouskill, Stephanie Brooks Holliday, Jonathan Cantor, Sierra Smucker, Matthew L. Mizel, Lauren Skrabala and Aaron Kofner.

RAND Health Care promotes healthier societies by improving health care systems in the United States and other countries.

To ensure survival, living organisms are equipped with defensive systems that detect threats and respond with effective counter measures.

Plants are known to mount quick defenses against a variety of threats--from attacking insects to invading pathogens. These intricate immune response mechanisms operate through a complex network that plant biologists have sought to untangle.

Crucial to these defenses is the timing and duration of immune responses. Humans are equipped with a strong and rapid inflammation response that is essential to ward off disease, but chronic and persistent inflammation can be harmful to our health. Similarly, plants feature defenses that are timed for rapid and effective responses against pathogens, yet tightly controlled to avoid threatening the host organism.

Keini Dressano, Alisa Huffaker and their colleagues at the University of California San Diego's Division of Biological Sciences have discovered a critical "on-off" switch in the plant immune response system. As described July 20 in their report published in Nature Plants, they identified a new regulatory switching mechanism--an RNA-binding protein--that helps turn on immune responses a few minutes after attack. Hours later, the switch follows with a deactivation "off" signal to avoid self-inflicted damage to the plant.

"These findings have provided new insights into how the complex intricacies of plant immune responses are orchestrated to successfully fight off pathogens, and lay a path forward for improving plant disease resistance to ensure future food stability," said Huffaker, an assistant professor in the Section of Cell and Developmental Biology.

The novel switch was found in Arabidopsis plants to control splicing of mRNA transcripts that encode signaling protein regulators of the plant immune response. To turn immune defenses on, the researchers say, a simple chemical modification of the RNA-binding protein reverses mRNA splicing that normally keeps immune responses deactivated. To turn the immune response back off, a second chemical modification of the RNA-binding protein returns mRNA splicing to "normal," and the immune response is back to being held in check.

"This work went beyond simply identifying a new regulator of plant immunity," said Huffaker, of the detailed mechanisms uncovered. "We discovered specific chemical modifications that control regulatory function, transcriptional targets of the regulator, differential splicing of the targets and precise effects of splicing on both target function and overall plant immune responses and disease resistance."

It might be no surprise that sugar in sweetened coolers helps to mask the taste of alcohol and make it more appealing to novice consumers, including young people.

Based on the first study to look at the role of high-fructose corn syrup - the main ingredient in most coolers - a University of Guelph professor suggests that these sweetened beverages can actually promote harmful alcohol consumption.

The results should prompt caution particularly among university-age drinkers and their parents about the potential of coolers to encourage consumption of other alcoholic beverages, said psychology professor Francesco Leri.

"The more sweetened drinks that an adolescent drinks, the more likely they are to drink alcohol that is not sweetened," said Leri, who conducted the study with master's student Samantha Ayoub and psychology professor Linda Parker

As with earlier studies of how sweetened alcoholic beverages affect adolescent drinking behaviour, he said, this study suggests that these beverages act as "a gateway - a way to get introduced and then like alcohol itself."

Other researchers have found that sweeteners such as sucrose and glucose encourage rats to drink more alcohol.

Published recently in the journal Alcohol, the U of G study is the first to look at the effects of high-fructose corn syrup (HFCS), which makes up about one-quarter of the volume of many sweetened alcoholic beverages.

Using rats able to self-administer liquids, the researchers tested consumption of different proportions of alcohol mixed with 25-per-cent HFCS. Adding the corn syrup increased rats' intake and the palatability of the beverage. Palatability was measured by observing behaviours such as rats licking their snouts. Rats given alcohol normally show facial signs of disgust.

"Most rats don't voluntarily drink alcohol by itself. The moment we added HFCS, there was a huge increase in consumption," said Leri.

Beverages containing 10 per cent alcohol and 25 per cent corn syrup encouraged some rats to drink an amount equivalent to an average adult human consuming 4.5 beers in 30 minutes. Although the researchers didn't measure blood alcohol levels, consuming that much alcohol would cause blood alcohol levels in people to spike to "binge drinking" amounts.

Mixing alcohol with saccharin (a non-caloric sweetener) also prompted more consumption but less than with HFCS.

In earlier studies, Leri looked at the effects of HFCS on the brain. This time, he wanted to see how sweeteners might affect consumption of other addictive drugs such as alcohol.

He said someone drinking sweetened coolers can grow accustomed to the taste of alcohol, even if they initially dislike the latter on its own. 

"Most people that don't like the taste of alcohol in a drink will drink sweetened coolers. We think they get an introduction to alcohol via sweeteners."

Leri said beverage manufacturers might be persuaded to use more natural sweeteners such as regular cane sugar or to refrain from marketing their products to younger consumers.

He encourages parents to discuss coolers with young people.

"Because it's sweet and tastes like pop doesn't make it any safer than a straight can of beer or glass of wine. Alcohol is alcohol no matter what. Because alcohol is sweet, there's a danger of over-drinking. It's important to monitor the amount taken, especially when it's mixed with other substances. It's just another drug of addiction, that's all it is."

GAINESVILLE, Fla. --- A large fruit-eating bird from Tonga joins the dodo in the lineup of giant island pigeons hunted to extinction.

Fossils show that Tongoenas burleyi, a newly described genus and species, inhabited the Pacific islands for at least 60,000 years, but vanished within a century or two of human arrival around 2,850 years ago.

Unlike the dodo and the extinct Viti Levu giant pigeon of Fiji, however, T. burleyi could fly. This canopy-dwelling species co-evolved with fruit-bearing trees in the mango, guava and chinaberry families, acting as an essential forest cultivator by spreading seeds to new locations. The size of a large duck, Tongoenas burleyi was likely capable of swallowing fruit as big as a tennis ball, said study lead author David Steadman, curator of ornithology at the Florida Museum of Natural History.

"Some of these trees have big, fleshy fruit, clearly adapted for a big pigeon to gulp whole and pass the seeds," Steadman said. "Of the fruit-eating pigeons, this bird is the largest and could have gulped bigger canopy fruit than any others. It takes co-evolution to the extreme."

The absence of T. burleyi from the Tongan islands could threaten the long-term survival of local trees that depended on the pigeon as a seed transporter, said study co-author Oona Takano, a doctoral student at the University of New Mexico.

"T. burleyi provided an important service by moving seeds to other islands," said Takano, who was previously a research assistant at the Florida Museum. "The pigeon species on Tonga today are too small to eat large fruits, which imperils certain fruit trees."

When Steadman first found T. burleyi fossils in a cave on the Tongan island of 'Eua, he was immediately impressed by their size: The bird was about 20 inches long, not including the tail, and weighed at least five times as much as the average city pigeon.

"I said, 'Oh my God, I've never seen a pigeon that big,'" Steadman said. "It was clearly something different."

Once he and archaeologist David Burley of Simon Fraser University - who is also the species's namesake - began excavating charred and broken remains of T. burleyi at archaeological sites, "we knew it was another human-caused extinction," Steadman said. "Pigeons and doves just plain taste good."

Columbids, the family that includes pigeons and doves, had few predators or competitors before people reached the Pacific islands, he said. The region was devoid of primates and carnivores such as cats, dogs and weasels, and hawks and owls were absent from many islands. The birds flourished in this nurturing environment, diversifying over the past 30-40 million years.

Today, the Pacific islands are the global epicenter of pigeon and dove diversity, with more than 90 species, ranging from fruit doves as light as a handful of raisins to the turkey-sized, ground-dwelling crowned pigeon of New Guinea. But the number and distribution of birds in the region is a shadow of what it once was, Steadman said. Tonga's four remaining species of pigeons and doves represent less than half of the islands' historic diversity.

"This is another example of how looking at the modern fauna doesn't yield a complete picture of a region's diversity," he said.

Steadman and Takano analyzed the features of columbid hindlimbs, dividing them into three groups: tree-dwelling species, ground-dwellers and those that live both on the ground and in trees. Pigeons and doves that spend most of their time in the canopy tend to have shorter legs, more suitable for perching and gripping in high winds. Those that forage for seeds on the ground have longer legs adapted for walking and running. Birds that flit between the understory and the forest floor have legs that are a blend of the characteristics of the other two groups.

The researchers found surprising agreement between the groupings based on leg characteristics and molecular data: In other words, canopy-dwelling pigeons tend to be more closely related to one another than to birds in the other two groups.

"Given that there are 350 species of pigeons and doves, people might suspect these big changes in lifestyle evolved independently many times," Steadman said. "But right now, we don't have evidence that it happened more than once - at least in the tropical Pacific."

The relatively short hindlimbs of T. burleyi mark it as a canopy-dwelling species. Steadman hypothesized the species featured the bright, even gaudy, plumage of other pigeons that live in treetops, where intense colors provide better camouflage than the muted browns and grays of pigeons that live on the ground.

The researchers dedicated the study to the memory of W. Arthur "Art" Whistler, whose expertise in West Polynesian botany was unsurpassed, Steadman said. Whistler died from COVID-19 in April.

"There wasn't a plant on Fiji or Tonga that Art didn't know, including all of the pigeon-dispersed fruits," Steadman said. "He was a true plant nerd and complete salt of the earth. He always made time for people."

In a new study, University of Colorado Denver researchers found when people have access to the food stamp program, they are less likely to frequent a physician for medical care. The findings were published in the American Journal of Health Economics by two CU Denver assistant professors of economics, Chloe East, PhD, and Andrew Friedson, PhD.

According to the study, which used changes in eligibility rules for documented immigrants in the 1990-2000s to learn about the program, those who were eligible for the food stamp program saw a reduction in health care utilization, specifically fewer office visits to physicians. The reductions were concentrated among locations with a higher prevalence of common communicable illnesses, such as cold or stomach illness. This suggests improved immune response could be an important mechanism.

"This is a program that has been a target of cuts in the Executive Budget--but if Supplemental Nutrition Assistance Program (SNAP) reduces health care utilization, a dollar of cuts will not be a dollar of budgetary savings as spending will likely ramp up in other programs such as Medicaid as former SNAP enrollees start to use more care," says study co-author Andrew Friedson.

About 44 percent of food stamp recipients in the United States also receive health insurance coverage through the Medicaid program. Since there is a reduction in the need for medical treatment, government health care spending is reduced, and there's an increase in savings for the individuals who pay out of pocket.

The researchers also calculated a rough (but likely lower bound) estimate of the magnitude of these savings, using the Colorado Medicaid payment for a 15-minute office visit: $64 in 2017, the most billed type of office visit. Based on that number, and the results of the study, providing food stamps reduces healthcare expenditures by $9 per enrolled person, or roughly 4% of the cost of the SNAP program.

"There have been many proposed cuts to the Food Stamp program in recent years, including reducing immigrants' access further," said study co-author Chloe East. "Our findings show there would be important costs of these cuts, to both individuals and the federal government, due to increased health care costs."

DUARTE, Calif. -- In order for cancer to form in the human body, normal cells must acquire multiple mutations before they develop toward the disease. It was previously believed that these mutations acted in concert in the progression of cancer. But a new Nature study led by City of Hope's Markus Müschen, M.D., Ph.D., chair of the Department of Systems Biology and The Norman and Sadie Lee Foundation Professor in Pediatrics, uncovered a new aspect of this theory.

In a paper published today, Müschen and an international team of researchers outline their findings that individual mutations only promote progression toward leukemia if they converge on one single pathway. In addition, some mutations actually generate "noise" that drown out central elements of cancer development.

"Surprisingly, mutations that are not aligned with the central cancer pathway but instead promote growth and survival in divergent directions are counterproductive and even prevent overt transformation into cancer," said Müschen, who is the corresponding author of the new study. "The concept of multistep cancer progression suggested that acquisition of additional mutations would invariably promote cancer, but we found that many of these mutations, in fact, lead to a dead end and stop cancer progression rather than promoting it."

The team reached this conclusion after analyzing 1,148 patient-derived B cell leukemia samples to see how mutations either cooperated or antagonized each other. Current targeted therapies in cancer are based mainly on suppressing the principal driver of cancer, but the study's findings offer a previously unrecognized strategy to enhance treatment responses.

As a strategy for preventing drug resistance and relapse, Müschen and his colleagues explored an alternative approach based on reactivating suppressed pathways in order to interfere with the principal oncogenic driver and potentially amplify treatment responses.

"We have developed drug combinations that would mimic these effects," Müschen said. "Like a mutation that activates a divergent pathway, we found drugs to reactivate pathways that diverge from the central oncogenic driver to disrupt oncogenic signal transduction in these cells."

Müschen and his team are now testing various drug combinations.

"In these combinations, one drug directly inhibits the central oncogenic driver, while the second drug reactivates divergent pathways that were silenced during the transformation process," Müschen said. "If successful for leukemia, we may be able to test this approach for the treatment of other cancers."

Studies through the decades have linked higher wages to education, with the greatest returns in developing countries. However, the correlation between higher wages and education doesn't always account for an individual's innate cognitive abilities, or the mental processes of gathering and processing information to solve problems, adapt to situations and learn from experiences.

How much of those wage gains come from schooling, and how much from cognitive abilities developed long before the student sets foot in a classroom?

Data on measures of cognitive performance have been limited historically, particularly in developing countries. Using data sets that only became available in recent years, Binghamton University Assistant Professor of Economics Plamen Nikolov, and graduate students, Nusrat Jimi and Jerray Chang, analyzed the wage impact of cognitive skills in "The Importance of Cognitive Domains and the Returns to Schooling in South Africa: Evidence of Two Labor Surveys" in the August 2020 edition of Labour Economics.

Economics research dating back to the 1970s links higher wages to more education; however, it wasn't until the 1990s that economists made headway in designing research that could tease out the true causes of such phenomena rather than just the correlation, Nikolov explained.

If non-experimental studies that explore the effects of education on wages don't account for cognitive performance in addition to schooling, the wage effect of school alone will seem higher than it really is, he pointed out. While cognitive skills may be further developed in the classroom, previous economics and psychology research shows that most of these skills are developed before people start elementary school.

In addition to the innate cognitive factor, the quality of education can also impact wages. During the Apartheid period, schools in South Africa were race-based, with those of worse quality attended by Black South Africans; this system was dismantled in 1994, although disparities remain. Black South Africans often had substantially less education than their white counterparts as a result.

"It is possible that people who have better cognitive performance are likely either to do better in school or to get more schooling. In our estimation, our conceptual argument is that both cognition and schooling separately and distinctly exert a positive effect on wages," said Nikolov, the lead author, adding that the empirical analysis already accounts for other factors that could potentially affect wages, such as socio-economic factors.

Cognitive skills and wages

The study used two surveys conducted between 2002 and 2014 in two distinct areas of South Africa: urban and rural. The surveys collected extensive household information, including dimensions of cognition: memory, orientation, numeracy and attention in one, and literacy and numeracy in the other.

Findings show that each additional year of school equates to an earnings increase of 18 to 20 percent. Returns are higher in the urban sector due to the preponderance of service-oriented and technical jobs, compared to rural South Africa, which has mostly low-paying agricultural work, Nikolov said.

Urban and rural environments also show differences in which types of cognitive skills are rewarded, once again connected with the types of jobs available. In rural environments, memory and orientation -- an awareness of one's time, place and person -- are most important when it comes to higher wages. In more urban environments, earnings are connected with higher order cognitive skills, such as arithmetic, literacy and planning.

A standard deviation increase in cognitive skills -- memory in rural areas and numeracy in cities -- is roughly equivalent to one more year of school. However, an extra year of school in a developing country such as South Africa has double the rate of return as an equivalent year in a high-income country such as the United States, according to the research.

While cognitive skills may predate schooling, that doesn't mean that classrooms aren't a worthwhile investment for developing countries -- quite the opposite, in fact.

"This wage effect implies that both cognitive skills and schooling matters, but schooling matters a lot more," Nikolov said.

The European Southern Observatory's Very Large Telescope (ESO's VLT) has taken the first ever image of a young, Sun-like star accompanied by two giant exoplanets. Images of systems with multiple exoplanets are extremely rare, and -- until now -- astronomers had never directly observed more than one planet orbiting a star similar to the Sun. The observations can help astronomers understand how planets formed and evolved around our own Sun.

Just a few weeks ago, ESO revealed a planetary system being born in a
new, stunning VLT image. Now, the same telescope, using the same instrument, has taken the first direct image of a planetary system around a star like our Sun, located about 300 light-years away and known as TYC 8998-760-1.

"This discovery is a snapshot of an environment that is very similar to our Solar System, but at a much earlier stage of its evolution," says Alexander Bohn, a PhD student at Leiden University in the Netherlands, who led the new research published today in the Astrophysical Journal Letters.

"Even though astronomers have indirectly detected thousands of planets in our galaxy, only a tiny fraction of these exoplanets have been directly imaged," says co-author Matthew Kenworthy, Associate Professor at Leiden University, adding that "direct observations are important in the search for environments that can support life." The direct imaging of two or more exoplanets around the same star is even more rare; only two such systems have been directly observed so far, both around stars markedly different from our Sun. The new ESO's VLT image is the first direct image of more than one exoplanet around a Sun-like star. ESO's VLT was also the first telescope to directly image an exoplanet, back in 2004, when it captured a speck of light around a brown dwarf, a type of 'failed' star.

"Our team has now been able to take the first image of two gas giant companions that are orbiting a young, solar analogue," says Maddalena Reggiani, a postdoctoral researcher from KU Leuven, Belgium, who also participated in the study. The two planets can be seen in the new image as two bright points of light distant from their parent star, which is located in the upper left of the frame (click on the image to view the full frame). By taking different images at different times, the team were able to distinguish these planets from the background stars.

The two gas giants orbit their host star at distances of 160 and about 320 times the Earth-Sun distance. This places these planets much further away from their star than Jupiter or Saturn, also two gas giants, are from the Sun; they lie at only 5 and 10 times the Earth-Sun distance, respectively. The team also found the two exoplanets are much heavier than the ones in our Solar System, the inner planet having 14 times Jupiter's mass and the outer one six times.

Bohn's team imaged this system during their search for young, giant planets around stars like our Sun but far younger. The star TYC 8998-760-1 is just 17 million years old and located in the Southern constellation of Musca (The Fly). Bohn describes it as a "very young version of our own Sun."

These images were possible thanks to the high performance of the SPHERE instrument on ESO's VLT in the Chilean Atacama desert. SPHERE blocks the bright light from the star using a device called coronagraph, allowing the much fainter planets to be seen. While older planets, such as those in our Solar System, are too cool to be found with this technique, young planets are hotter, and so glow brighter in infrared light. By taking several images over the past year, as well as using older data going back to 2017, the research team have confirmed that the two planets are part of the star's system.

Further observations of this system, including with the future ESO Extremely Large Telescope (ELT), will enable astronomers to test whether these planets formed at their current location distant from the star or migrated from elsewhere. ESO's ELT will also help probe the interaction between two young planets in the same system. Bohn concludes: "The possibility that future instruments, such as those available on the ELT, will be able to detect even lower-mass planets around this star marks an important milestone in understanding multi-planet systems, with potential implications for the history of our own Solar System."