Culture

A new study looking at data from tens of thousands of children with asthma finds that several widely available interventions are associated with both reduced medical costs and a reduced likelihood that the children will need to visit an emergency room or stay in the hospital.

"This work shows that you can improve the quality of life for children with asthma and you can reduce government spending by implementing these proactive interventions," says Julie Swann, lead author of the study. Swann is the department head and A. Doug Allison Distinguished Professor of the Fitts Department of Industrial and Systems Engineering at North Carolina State University.

The researchers looked at data from 2010 and 2011 on more than 70,000 children with asthma enrolled in the Medicaid programs in New York and Michigan. The researchers focused on four interventions: asthma self-management education (ASME); flu vaccine; the use of spacers, which are low-cost plastic tubes that improve the performance of inhalers; and the use of nebulizers, which are devices that convert liquid medicine into an aerosol that patients can inhale.

Specifically, the researchers analyzed the data to understand the extent to which each of these interventions was associated with three outcomes: asthma-related visits to the emergency room; asthma-related visits to a primary-care physician; and asthma-related stays in the hospital. The researchers also assessed the extent to which each intervention influenced costs associated with each child's asthma medication and so-called "utilization costs" - which are the costs associated with other aspects of a child's asthma treatment, such the cost of visiting a primary-care provider or hospital.

To address these questions, the researchers plugged the healthcare data into models that allowed them to assess the impact of each intervention separately, compared to no intervention.

"One of the key findings, which should be of interest to policymakers, is that all four interventions were associated with lower medication costs and utilization costs," Swann says.

And while the numbers varied between states, the decreases in cost could be substantial. For example, being vaccinated against the flu was associated with a 16.4% reduction in utilization expenses and a 15.6% reduction in medication expenses for children in New York. "There can be significant cost reductions associated with a fairly inexpensive intervention," Swann says.

"Our results suggest that ASME training, and the use of spacers and nebulizers, are also associated with significant decreases in both emergency room visits and hospitalizations," says study co-author Pinar Keskinocak. "And the flu vaccine helps reduce the number of visits to a child's primary care provider." Keskinocak is the William W. George Chair and Professor in Georgia Tech's H. Milton Stewart School of Industrial and Systems Engineering and the director of the Center for Health and Humanitarian Systems at Georgia Tech.

"It's important to note that we looked at the impact of these outcomes separately while accounting for other interventions," Swann says. "You would expect that the more of these pro-active interventions a child has, the greater the positive impact we would expect to see on both their health and on what Medicaid would be asked to spend on their care."

(Vienna, October 13, 2020) A revolutionary endoscopic therapeutic procedure may lead to the discontinuation of insulin treatment in a significant number of people with type 2 diabetes, new research presented today at UEG Week 2020 Virtual has shown.

Researchers from the Netherlands tested a novel, minimally-invasive ablation procedure, which rejuvenates the lining of the duodenum, in combination with daily doses of glucose lowering drugs called glucagon-like peptide agonists (GLP-1 RAs) and mild lifestyle counselling. The study found that 75% of previously insulin-dependent people with type 2 diabetes treated with the ablation technique did not need insulin six months later, with HbA1c (a long-term parameter of glucose control) readings of 7.5% or below. HbA1c readings also fell to 6.7% at 12 months.

Patients who responded to the treatment also saw significant reductions in their body mass index (BMI), which was down from an average of 29.8 kg/m2 at the beginning of the research to 25.5 kg/m2 after 12 months. The percentage of fat in their livers also decreased from 8.1% to 4.6% at 6 months. Obesity and fatty liver are both important risk factors in the development of metabolic syndrome, a term that encompasses diabetes, high blood pressure (hypertension), obesity, and high triglycerides.

In the non-responder patients, who still needed insulin, the median insulin dose they required fell by more than half (from 35 units per day at study entry to 17 units per day at 12 months).

The minimally-invasive technique, called Duodenal Mucosal Resurfacing (DMR), is performed in an outpatient setting and is delivered via an integrated over-the-wire catheter attached to a custom console that performs a synchronized lifting of the duodenal mucosa and then ablation of the treatment area. Although the process is not yet fully understood, mucosal cells are believed to undergo alterations in a response to unhealthy diets, high in fat and sugar. This leads to changes in the production and signalling of key hormones that impact insulin resistance and diabetes. Resurfacing the lining appears to rejuvenate and reset this process.

The pilot study, undertaken in 16 patients, was led by Dr Suzanne Meiring, Dr. Annieke van Baar, and Professor Jacques Bergman from the Amsterdam University Medical Center in the Netherlands.

Dr Meiring explained: "This could be a game-changing approach in the treatment of metabolic syndrome. A single endoscopic DMR ablation with GLP-1 drugs and lifestyle counselling can lead to discontinuation of insulin therapy in a subset of patients with type 2 diabetes, while improving their blood glucose control and overall metabolic health. Many patients with type 2 diabetes are very happy to be able to discontinue insulin therapy, since insulin therapy comes with weight gain and hypoglycaemic events. Our earlier study, (Revita-1) with patients that used only oral medication for their diabetes type 2, showed that the effect of a single DMR was comparable to adding one glucose lowering drug."

There are about 60 million people in Europe with diabetes and the vast majority (around 90%) of cases are type 2. As well as age and a family history of the condition, high blood pressure and being overweight are major risk factors for type 2 diabetes.

"Based on the results of this study, a large international randomised controlled trial, called Revita T2Di Pivotal, will soon start to further investigate its effectiveness in greater numbers", added Dr Meiring.

In Alzheimer's disease, impaired blood flow to brain regions coincides with tau protein buildup. This relationship strengthens as cognition declines, according to new research published in JNeurosci.

Vascular function declines and amyloid-β and tau protein accumulate as Alzheimer's disease progresses, resulting in neuron death. Like the proverbial chicken and egg, it remains unclear if impaired blood flow causes or is caused by errant protein buildup, or if the two symptoms occur for unrelated reasons.

Albrecht et al. used MRI and PET to compare blood flow and tau buildup in the brains of older adults, with cognition ranging from cognitively normal to showing signs of mild cognitive impairment. Areas with increased tau levels had diminished blood flow, particularly in the inferior temporal gyrus, one of the first regions to show tau buildup in Alzheimer's disease, even before cognitive symptoms manifest. The relationship held true for a separate data pool from the Alzheimer's Disease Neuroimaging Initiative, which included people with mild cognitive impairment and Alzheimer's dementia. The correlation between tau and vascular function was stronger in people with greater cognitive impairment and higher amyloid-β levels. It also appeared in more brain regions as the disease progressed in severity. These findings suggest targeting vascular function could be key to preventing and treating Alzheimer's dementia.

Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.

1. Nearly 1 in 8 patients receive unexpected out-of-network bills after colonoscopy

Abstract: https://www.acpjournals.org/doi/10.7326/M20-2928
URL goes live when the embargo lifts

Nearly 1 in 8 commercially insured patients nationwide who underwent an elective colonoscopy between 2012 and 2017 performed by an in-network provider received potential "surprise" bills for out-of-network expenses, often totaling hundreds of dollars or more. These findings are concerning, as federal regulations eliminate consumer cost-sharing when screening colonoscopies are performed in-network. A brief research report is published in Annals of Internal Medicine.

Colonoscopy is the most effective colorectal cancer prevention strategy. However, researchers suggest that surprise billing may deter patients from getting recommended screening.

Researchers from the University of Virginia and the University of Michigan reviewed 1.1 million claims from a large national insurer to estimate the prevalence, amount, and source of out-of-network claims for commercially insured patients having an elective colonoscopy when all of the endoscopists and facilities were in-network. The researchers found that 12.1 percent of cases received out-of-network claims, with an average surprise bill of $418. The bills often came because of the use of out-of-network anesthesiologists and out-of-network pathologists.

The researchers suggest that to spare patients surprise bills, endoscopists and hospitals should partner with anesthesia and pathology providers who are in-network, and they should consider cost-saving strategies such as endoscopist-provided sedation rather than use of deeper anesthesia. They also suggest that not all low-risk polyps need to be sent for pathological evaluation, which could offer further savings.

Media contacts: For an embargoed PDF, please contact Lauren Evans at laevans@acponline.org. To reach the corresponding author, James M. Scheiman, MD., please contact Joshua Barney at JDB9A@hscmail.mcc.virginia.edu.

2. Excess Days in Acute Care provide a more comprehensive picture of hospital performance compared to 30-day readmission rates
Using the EDAC measurement would change penalty status for about one-quarter of hospitals

Abstract: https://www.acpjournals.org/doi/10.7326/M19-3486
Editorial: https://www.acpjournals.org/doi/10.7326/M20-6254
URL goes live when the embargo lifts

The Excess Days in Acute Care (EDAC) measure provides a more comprehensive assessment of hospital performance compared to the 30-day readmission measure, which is currently used by the Centers for Medicare and Medicaid Services (CMS) to evaluate quality in the Hospital Readmissions Reduction Program (HRRP). Using the EDAC measure in the HRRP would change penalty status for about one-quarter of hospitals. These findings are published in Annals of Internal Medicine.

CMS currently uses 30-day readmission rates to evaluate hospital performance and to issue penalties to those that underperform. Hospitals have been penalized more than $3 billion to date under the HRRP. However, the 30-day readmission measure has increasingly been scrutinized because it provides an incomplete picture of hospital visits after discharge. In contrast, the EDAC measure captures all hospital encounters - inpatient, Emergency Department, and observation stays - that occur within 30-days of discharge and provides a more comprehensive picture of performance.

Researchers from Beth Israel Deaconess Medical Center studied more than 3,100 hospitals that participated in the HRRP in fiscal year 2019 to compare whether using the EDAC measure instead of readmissions would change hospitals' penalty status for three conditions targeted by the HRRP. They found that one-quarter of hospitals' penalty status would change if the EDAC measure were used instead of the readmission measure in the program. In addition, fewer small hospitals and rural hospitals would receive financial penalties if the EDAC measure were used. According to the study authors, these findings suggest that CMS should consider using the EDAC measure rather than the 30-day readmission measure to evaluate health care system performance under federal quality reporting and value-based programs.

Media contacts: For an embargoed PDF, please contact Lauren Evans at laevans@acponline.org. To speak with the corresponding author, Rishi K. Wadhera, MD, MPP, please contact Lindsey Diaz-MacInnis at ldiaz2@bidmc.harvard.edu.

PRINCETON, N.J.--As the planet continues to warm, people living in the world's most vulnerable regions -- like arid or low-lying nations -- must contend with the decision to stay in a place where livability is decreasing or leave for countries with more stable climate and economic conditions.

New Princeton University research suggests that restrictive border policies could increase many people's vulnerability to extreme climate conditions and weaken economic prosperity by limiting their ability to emigrate from countries that are facing worsening conditions due to climate change, such as drought, heat waves, and rising seas.

When allowed to move freely, however, both migrants and the developing countries from which they came are less vulnerable and better off financially, the researchers reported in the journal the Proceedings of the National Academy of Sciences.

The researchers built migration into a standard model typically employed by policymakers to estimate the social cost of carbon and other climate change effects, explained co-lead author Hélène M. Benveniste, a Ph.D. candidate at the Princeton School of Public and International Affairs (SPIA).

"In discussions about international migration and global climate policy, it seemed that many were looking through the lens of the people coming in, focusing only on the destination country, and not what it would mean for both the migrant population and origin countries," said Benveniste, who was supported by the Princeton Energy and Climate Scholars program based in the Princeton Environmental Institute (PEI). "Our work shows these conversations need to be brought closer together."

Benveniste conducted the work with Michael Oppenheimer, the Albert G. Milbank Professor and Geosciences and International Affairs and the PEI, and Marc Fleurbaey, a professor at the Paris School of Economics who conducted the work as a Princeton professor.

The researchers centered their work around two questions: What does exposure to climate change mean for people around the world, as well as their ability to deal with the impacts? And who would be able to move, and who would be constrained to stay?

They employed a standard climate-global economy model known as the Integrated Assessment Models, which typically includes a simplified representation of migration. In their version of the model, they included dynamics for both migration and remittance, cash being exchanged between people in the two countries. Remittance is an important feature of the model, as cash received from family members abroad can be a powerful resource in developing countries.

Money can also help people prepare for the effects of climate change. The researchers measured "exposure" to climate change by quantifying how people might be affected by it, where they are and where they might go, as well as how much money they might have.

First, they tested the accuracy of the model by looking at different border policies, making them both easier and more difficult to cross than they are today. They also investigated the effects of these border policies on different income levels and on people's ability to relocate.

Then, using actual migration flows compiled by past researchers and derived from the World Bank, they made projections up until the year 2100. Using what scientists call a "gravity model," they took into account economics, demography, migration and income differences between places to determine the number of people moving.

They found that exposure and vulnerability to impacts of climate change tend to be higher in developing countries. Over the 21st century, most migrants from these developing countries tend to move to areas where they are less exposed to such impacts than where they came from. The researchers can't say how many of these migrants moved because of climate change, as many relocated for other financial reasons as well.

The results also show that open borders have a positive impact on developing countries themselves, especially in places like Central America, Southeast Asia, and small island nations. When people are allowed to move freely, they tend to send more money "back home," which provides an important source of income for the origin country. This income could also be used to reduce vulnerability to climate change.

Researchers at SPIA have been studying the relationship of climate change to migration for more than a decade using a variety of modeling approaches. "Our motivation in projecting climate-related migration is to provide a basis for public policy that will improve outcomes for migrants and for people at migration destinations as well as the communities they left behind," Oppenheimer said.

Fewer college-age Americans drink alcohol, compared to nearly 20 years ago, according to a new study.

Between 2002 and 2018, the number of adults aged 18-22 in the U.S. who abstained from alcohol increased from 20% to 28% for those in college and from about 24% to 30% for those not in school, say researchers at the University of Michigan and Texas State University. And alcohol abuse among both groups decreased by roughly half.

However, the study found that the number of young adults using marijuana, as well as co-using alcohol and marijuana, has increased.

Overall, the mixed findings show more positive than negative trends for alcohol and marijuana use and misuse among this age group, but the progression still bears close monitoring, the researchers say.

The study, appearing in JAMA Pediatrics Oct. 12, examined how alcohol and marijuana abstinence, co-use and use disorders have changed in 18-to-22-year-olds as a function of college status, using data from a nationally representative survey of 182,722 young adults. It also looked at prescription drug use and misuse as a function of alcohol and marijuana use, from 2015 to 2018.

The researchers were particularly surprised at the drop in alcohol use and misuse.

"We're encouraged by the significant decreases in alcohol use disorder--for both college and noncollege students," said lead author Sean Esteban McCabe, director of the Center for the Study of Drugs, Alcohol, Smoking and Health at the U-M School of Nursing.

"The prevalence of alcohol use disorder in both groups in 2018 was roughly half of what it was in 2002. We are excited to learn about these drops in disordered drinking, as alcohol-related consequences are one of the leading causes of mortality and morbidity for young adults."

Co-author Ty Schepis, professor of psychology at Texas State, said "even with increases in marijuana use disorder and co-use of alcohol and marijuana, there is a lot of hope in our study's results."

"Points of concern that deserve more attention are the rise in co-use of alcohol and marijuana, as we know that polysubstance use can have more negative consequences and be more difficult to treat," he said.

The study also found that more than three-fourths of those who had disordered use of both alcohol and marijuana reported past-year prescription drug use and illicit drug use, while the majority reported prescription drug misuse.

The findings indicate that the substance use landscape has changed over the past 20 years, with more young adults using or misusing several different substances, as opposed to just marijuana or alcohol.

"For example, from 2015 to 2018, only 2.5% of young adults who abstained from both alcohol and marijuana reported misusing prescription drugs, while 25.1% of co-users misused prescription drugs," Schepis said. "That is a tenfold difference with potentially dangerous consequences."

Abusing multiple substances is often more dangerous than abusing a single substance.

"Interventions that focus solely on one substance will be less effective than interventions that take a more holistic polysubstance use perspective," McCabe said. "The findings of our study reinforce the complex task health professionals have of detecting and developing effective interventions to reduce consequences associated with polysubstance use, such as co-use of alcohol and marijuana."

Schools and employers may require more resources to scale interventions to address both young adults with and without a disorder, including screening and brief interventions for co-use of alcohol and marijuana, McCabe said.

"The finding that abstinence is increasing among college students and young adults not in college is very important for U.S. colleges and universities to take into account moving forward," he said. "These findings reinforce the importance of the need to support those young adults in recovery and abstinence for other reasons. There are over 1 million U.S. young adults in recovery and a wide variety of resources are needed to support these individuals."

In first-of-their-kind observations in the human brain, an international team of researchers has revealed two well-known neurochemicals -- dopamine and serotonin -- are at work at sub-second speeds to shape how people perceive the world and take action based on their perception.

The discovery shows researchers can continually and simultaneously measure the activity of both dopamine and serotonin -- whose receptor and uptake sites are therapeutic targets for disorders ranging from depression to Parkinson's disease -- in the human brain.

Furthermore, the neurochemicals appear to integrate people's perceptions of the world with their actions, indicating dopamine and serotonin have far more expansive roles in the human nervous system than previously known.

Known as neuromodulators, dopamine and serotonin have traditionally been linked to reward processing -- how good or how bad people perceive an outcome to be after taking an action.

The study online today in the journal Neuron opens the door to a deeper understanding of an expanded role for these systems and their roles in human health.

"An enormous number of people throughout the world are taking pharmaceutical compounds to perturb the dopamine and serotonin transmitter systems to change their behavior and mental health," said P. Read Montague, senior author of the study and a professor and director of the Center for Human Neuroscience Research and the Human Neuroimaging Laboratory at the Fralin Biomedical Research Institute at Virginia Tech Carilion. "For the first time, moment-to-moment activity in these systems has been measured and determined to be involved in perception and cognitive capacities. These neurotransmitters are simultaneously acting and integrating activity across vastly different time and space scales than anyone expected."

Better understanding of the underlying actions of dopamine and serotonin during perception and decision-making could deliver important insight into psychiatric and neurological disorders, the researchers said.

"Every choice that someone executes involves taking in information, interpreting that information, and making decisions about what they perceived," said Kenneth Kishida, a corresponding author of the study and an assistant professor of physiology and pharmacology, and neurosurgery, at Wake Forest School of Medicine. "There's a whole host of psychiatric conditions and neurological disorders where that process is altered in the patients, and dopamine and serotonin are prime suspects."

Lack of chemically specific methods to study neuromodulation in humans at fast time scales has impeded understanding of these systems, according to Montague, who is an honorary professor at the Wellcome Center for Human Neuroimaging at University College London and a professor of physics at the Virginia Tech College of Science.

But now, in first-ever measurements, scientists used an electrochemical method called "fast scan cyclic voltammetry," which employs a small carbon fiber microelectrode that has low voltages ramped across it for real-time detection of dopamine and serotonin activity.

In the study, researchers recorded fluctuations in dopamine and serotonin using specially designed electrodes in five patients undergoing deep brain stimulation electrode implantation surgery to treat essential tremor or Parkinson's disease. Patients were awake during surgery, playing a computer game designed to quantify aspects of thought and behavior while the measurements were taken.

On each round of the game, patients briefly viewed a cloud of dots and were asked to judge the direction they were moving. The method, designed by corresponding author Dan Bang, a Sir Henry Wellcome Postdoctoral Fellow, and Steve Fleming, a Sir Henry Dale/Royal Society Fellow, both at the Wellcome Center for Human Neuroimaging at University College London, helped indicate that dopamine and serotonin were involved in simple perceptual decisions, outside of the traditional context of rewards and losses.

"These neuromodulators play a much broader role in supporting human behavior and thought, and in particular they are involved in how we process the outside world," Bang said. "For example, if you move through a room and the lights are off, you move differently because you're uncertain about where objects are. Our work suggests these neuromodulators -- serotonin in particular-- are playing a role in signaling how uncertain we are about the outside environment."

Montague and Kishida, along with Terry Lohrenz, a research assistant professor, and Jason White, a senior research associate, now both at the Fralin Biomedical Research Institute, started working on a new statistical approach to identify dopamine and serotonin signals while still at the Baylor College of Medicine in Houston, Texas.

"Ken rose to the challenge of doing fast neurochemistry in human beings during active cognition," Montague said. "A lot of other good groups of scientists were not able to do it. Aside from the computation of enormous amounts of data, there are complicated issues to solve, including great, fundamental algorithmic tasks."

Until recently, only slow methodologies such as PET scanning could measure the impact of neurotransmitters, but they were nowhere near the frequency or volume of the second-to-second measurements of fast scan cyclic voltammetry.

The measurements in the new study were taken at the Wake Forest Baptist Medical Center, and involved neurosurgical teams led by Adrian W. Laxton and Stephen B. Tatter.

"The enthusiasm the neurosurgeons have for this research is derived from the same reasons that drove them to be doctors -- first and foremost, they want to do the best for their patients, and they have a real passion for understanding how the brain works to improve patient outcomes," said Kishida, who oversaw the data collection in the operating room during the surgeries. "Both are collaborative scientists along with Charles Branch, the chair of the neurosurgery department at Wake Forest, who has been an amazing advocate for this work."

Likewise, Montague said, "You can't do it without the surgeons being real, shoulder-to-shoulder partners, and certainly not without the people who let you make recordings from their brains while they are having electrodes implanted to alleviate the symptoms of a neurological disorder."

Montague had read a study in the Proceedings of the National Academy of Sciences that prompted him to approach colleagues Bang and Fleming at University College London to tailor a task for patients to perform during surgery that would reveal sub-second dopamine and serotonin signaling in real-time inference about the external world - separate from their often-reported roles in reward-related processes.

"I said I have this new method to measure dopamine and serotonin, but I need you to help with the task," Montague said. "They ended up in the study. The research really took a lot of hard work and an integrated a constellation of people to obtain these results."

The research was funded by grants to various researchers from the Wellcome Trust, the National Institutes of Health including the National Institute on Drug Abuse, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke.

CHAPEL HILL, N.C.--A treatment that uses immune system T cells, combined with an immune-boosting drug packaged in an injectable gel, was found to preserve the vision of mice implanted with tissue from a human eye cancer known as retinoblastoma. The cancer is treatable in early stages but can still lead to the loss of vision in about 5% of cases.

The research findings from scientists at the University of North Carolina Lineberger Comprehensive Cancer Center were published is Nature Cancer on Oct. 12, 2020.

Retinoblastoma is primarily diagnosed in infants and young children. It is considered rare, with approximately 200-300 children diagnosed with the cancer each year in the U.S. Current treatments for retinoblastoma use cold, heat, chemotherapy, lasers or radiation but vision loss still occurs, so the UNC researchers wanted to search for methods that could preserve vision.

"Based on our mouse study and the existence of an active cell immunotherapy program at UNC Lineberger, along with infrastructure for generation of CAR-Ts for clinical use, we feel confident that our efforts could be translated into a phase I clinical study in people," said Zongchao Han, MD, PhD, an associate professor in the UNC School of Medicine and UNC Eshelman School of Pharmacy and a UNC Lineberger member.

The researchers used an incremental process to determine the best method for treatment of retinoblastoma. First, the researchers turned to chimeric antigen receptor-T (CAR-T) cell therapy, a type of immunotherapy where T cells that comprise the immune system are modified in the laboratory to express chimeric antigen receptors, CARs, that target surface proteins on cancer cells. In a lab test, they found that a molecule, GD2, is expressed in retinoblastoma but the possibility to target this molecule to safely eliminate the tumor in the eye was unknown.

Next, to test the safety and benefit of targeting GD2, the investigators injected the CAR-T that recognizes this molecule into the retina of mice implanted with retinoblastoma cancer cells and found the therapy delayed tumor development but did not eradicate the tumor. Then they combined the CAR-Ts with interleukin (IL)-15, a protein that can boost immune response, and found that 60% of mice were tumor-free for up to 70 days.

Finally, they injected a water-based gel containing the CAR-Ts and IL-15 into the retinas of the mice. The CAR-Ts and IL-15 retained an extended ability to attack the cancer cells, control tumor growth and prevent tumor recurrence. They corroborated the lack of tumor growth with several imaging exams of the retina.

This gel-encapsulated therapy is currently being tested in clinical trials in children with neuroblastoma, an embryonal tumor that can progress rapidly and has some of the same genetic characteristics of retinoblastoma.

"We are always looking to improve the lives of children at Lineberger," said Barbara Savoldo, MD, PHD, professor of pediatric Hematology/Oncology at UNC School of Medicine and UNC Lineberger member. "Therefore, we hope to look at the safety of gel injection in a clinical trial of retinoblastoma in children, and if that proves safe, we could move on to see if our methodology can reduce or eliminate these tumors."

To calculate the true value of a forest, we need to know how people benefit from it, according to new research published in Nature Sustainability. A healthy forest holds a treasure trove of benefits for people -- it can filter water for downstream communities, supply timber for building, and provide a place for people to connect with nature. But a forest -- or any other ecosystem -- won't necessarily provide the same things to everyone.

"Context matters," says Lisa Mandle, lead scientist at the Stanford Natural Capital Project and lead author on the paper. "If we want to protect the critical natural assets we all depend on, we need actionable policies that incorporate people's diverse needs. It shouldn't be a one-size-fits-all approach when we're talking about people and nature."

There's a growing global movement to invest in nature in order to protect vital resources and improve climate resilience. But for nature to be factored into policies, sustainable development plans, and other management decisions, the researchers say the science behind them needs to be more inclusive and people-centric.

They also say a focus on equity is crucial. People benefit from nature in different ways -- a forest might provide valuable timber for one group while providing deep cultural significance for another. When all the individuals or groups receiving those benefits aren't considered, the people who depend on nature the most can be left behind.

"If you don't know who specifically would benefit from which ecosystems, how can you prioritize where and how to conserve?" said Taylor Ricketts, director of University of Vermont's Gund Institute for Environment and co-author on the paper. "We want to make sure the benefits of ecosystems are shared equitably, so that we don't make existing racial and social inequality even worse."

Nature-based solutions can create triple-win scenarios for economies, ecosystems, and people. From securing local water supplies to informing coastal development plans, understanding the values that nature provides to people can be a powerful tool for decision-makers. But too often, the research doesn't pay enough attention to the people part.

"People need to see themselves -- their values and needs -- supported in conservation efforts. Often, research will try to assign an overall dollar value to nature without thinking about who will benefitting from it. That's like saying you have $50 of food in your pantry, but you don't know what kind of food it is or who will be eating. You can't plan your meal without knowing what you have and what your diners need," said Mandle.

The researchers recommend actions for their own scientific community that focus on building understanding around who is benefitting from nature in the communities they're hoping to serve. They emphasize direct engagement with people, so that science and policy can be better equipped to meet societal needs, increase equity, and protect vital resources.

"This is a call for us all to do a better job. We can better deliver the information needed to move towards a more sustainable and equitable future," said Mandle. "And that's what we're all working toward."

What The Article Says: This devastating pandemic has affected nearly every aspect of daily life. While nations struggle to manage the initial waves of the death and disruption associated with the pandemic, accumulating evidence indicates another "second wave" is building: rising rates of mental health and substance use disorders.

Authors: Charles R. Marmar, M.D., of the NYU Langone Medical Center in New York, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jama.2020.19632)

Editor's Note: The article includes conflicts of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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What The Study Did: This study updates a previous report of the estimated number of excess deaths in the U.S. during the COVID-19 pandemic through August 1 and describes causes of those deaths and relationships with lifting of coronavirus restrictions.

Authors: Steven H. Woolf, M.D., MP.H., of  the Virginia Commonwealth University School of Medicine in Richmond, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jama.2020.19545)

Editor's Note: The article includes conflicts of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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Media advisory: The full study is attached to this news release.

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What The Study Did: COVID-19 deaths and excess all-cause mortality in the U.S. are compared with 18 countries with diverse COVID-19 responses in this study.

Authors: Ezekiel J. Emanuel, M.D., Ph.D., of the University of Pennsylvania in Philadelphia, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jama.2020.20717)

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What The Article Says: This Viewpoint aggregates mortality, morbidity, mental health conditions, and direct economic losses to estimate the total cost of the pandemic in the U.S. on the optimistic assumption that it will be substantially contained by the fall of 2021.

Authors: David M. Cutler, Ph.D., of Harvard University in Cambridge, Massachusetts, is the corresponding author.

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(doi:10.1001/jama.2020.19759)

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What The Article Says: Ways the COVID-19 pandemic has compounded existing health, human rights and economic disparities in communities of color are discussed in this Viewpoint, which also proposes a program of restorative justice in response, comprising investments in education and housing, reforms in lending practices and criminal justice, and more.

Authors: Lisa A. Cooper, M.D., M.P.H., the Johns Hopkins Center for Health Equity in Baltimore, is the corresponding author.

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(doi:10.1001/jama.2020.19567)

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Japan -- Researchers in Japan demonstrated for the first time the 'spinal motor module hypothesis' in the primate arm, opening a new pathway for recovery after disease or injury.

The human hand has 27 muscles and 18 joints, which our nervous system is able to coordinate for complex movements. However, the number of combinations -- or degrees of freedom -- is so large that attempting to artificially replicate this control and adjustment of muscle activity in real time taxes even a modern supercomputer. While the method used by the central nervous system to reduce this complexity is still being intensely studied, the "motor module" hypothesis is one possibility.

Under the motor module hypothesis, the brain recruits interneuronal modules in the spinal cord rather than individual muscles to create movement; wherein different modules can be combined to create specific movements. Nearly 40 years ago, research in frogs showed that simultaneously recruiting two modules of neurons controlling leg muscles created the same pattern of motor activity that represents a "linear summation" of the two component patterns.

An international team of researchers, led by Kazuhiko Seki at the National Center of Neurology and Psychiatry's Department of Neurophysiology, in collaboration with David Kowalski of Drexel University and Tomohiko Takei of Kyoto University's Hakubi Center for Advanced Research, attempted to determine if this motor control method is also present in the primate spinal cord. If validated, it would provide new insight into the importance of spinal interneurons in motor activity and lead to new ideas in movement disorder treatments and perhaps even a method to "reanimate" a limb post-spinal injury.

The team implanted a small array of electrodes into the cervical spinal cord in three macaques. Under anesthesia, different groups of interneurons were recruited individually using a technique called intraspinal microstimulation, or ISMS. The team found that, as in the frog leg, the force direction of the arm at the wrist during dual-site simulation was equal to the linear summation of the individually recruited outputs. However, unlike the frog leg, the force magnitude output could be many times higher than that expected from a simple linear summation of the individual outputs. When the team examined the muscle activity, they found that this supralinear summation was in a majority of the muscles, particularly in the elbow, wrist, and finger.

"This is a very interesting finding for two reasons," explains Seki. "First, it demonstrates a particular trait of the primate spinal cord related to the increased variety of finger movements. Second, we now have direct evidence primates can use motor modules in the spinal cord to control arm movement direction and force magnitude both efficiently and independently."

In effect, using paired stimulation in the primate spinal cord not only directly activate two groups of interneurons, INa and INb, which recruit their target muscle synergies, Syn-a and Syn-b, to set the arm trajectory, but can also activate a third set of interneurnons that can adapt the motor activity at the spinal level to change the force of the movement, group INc. This would let the brain plan the path the arm should take while the spinal cord adapts the muscle activity to make sure that path happens.

One example of this "plan and adapt" approach to motor control is the deceptively simple act of drinking from a can of soda. The brain can predetermine the best way to lift the can to your mouth for a sip, but the actual amount of soda in the can -- and therefore the can's weight -- is perhaps unknown. Once your brain has determined the trajectory the can should take -- in this case INa and INb -- the amount of force needed to complete that action can be modulated separately in INc, rather than redetermining which sets of muscles will be needed.

This study experimentally proves for the first time that primate arm movements may be efficiently controlled by motor modules present in the spinal cord. Based on the results of this research, it is expected that the analysis and interpretation of human limb movements based on the motor module hypothesis will further advance in the future.

In the field of robotics, this control theory may lead to more efficient methods to create complex limb movements, while in the field of clinical medicine, it is expected that new diagnostic and therapeutic methods will be created by analyzing movement disorders caused by neurodegenerative diseases and strokes.