Wednesday, November 11, 2020

Group size and makeup affect how social birds move together

Scientists have used high-resolution GPS tracking methods to provide new insights into how differently sized animal groups move and interact with their environment

ELIFE

Research News

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IMAGE: THIS PHOTO SHOWS SOME OF THE VULTURINE GUINEAFOWL FROM THE STUDY BY DANAI PAPAGEORGIOU AND DAMIEN FARINE view more 

CREDIT: DAMIEN R FARINE (CC BY 4.0)

Scientists have shown that the size and makeup of groups of social birds can predict how efficiently they use and move through their habitat, according to new findings published today in eLife.

The study suggests that intermediate-sized groups of vulturine guineafowl - a ground-dwelling social bird found in east African savannahs - exhibit the most effective balance between a decreased ability to coordinate movements and increased accuracy of navigation.

These findings add to our understanding of a key question in animal sociality - namely, whether groups have an optimal size - by showing that the number of individuals in a group determines the ability of that group to make the most effective use of their environment.

"For many social animals, larger groups benefit from information pooling, where inputs from multiple individuals allow for more accurate decisions about navigation," explains first author Danai Papageorgiou, IMPRS Doctoral Student at the Department of Collective Behaviour, Max Planck Institute of Animal Behavior, and at the Centre for the Advanced Study of Collective Behaviour, University of Konstanz, Germany. "However, as groups become larger they start to face challenges in coordinating their actions, such as reaching a consensus about where to go next or maintaining cohesion as they move through vegetation."

Papageorgiou and her PhD advisor, Professor Damien Farine, investigated the relationship between the size and collective movement of groups of vulturine guineafowl. They predicted that the optimal group size of these birds would be determined by the balance between their ability to coordinate movement and their ability to make accurate decisions when navigating.

The team fitted individual birds from 21 distinct social groups with GPS tags and collected movement data over five two-month-long seasons. They used these data to calculate the groups' habitat use, including their home-range size, the distance that they travelled each day and their movement speed while 'on the go'. By observing the groups each week, they could also measure the size of each group and record their makeup. Specifically, they recorded the number of chicks in each group, as they predicted that the birds' movement abilities may be restricted when there are more chicks because they are slower and much more vulnerable to predators.

The researchers found that intermediate-sized groups, consisting of 33-37 birds, ranged over larger areas and achieved this by travelling shorter distances each day, compared to smaller and larger groups. They also explored the most new areas. These results suggest that intermediate-sized groups were more efficient in using the space, potentially encountering more resources while spending less energy and lowering their chances of being tracked by predators. Additionally, data collected on the birds' reproductive success reinforced the fact that intermediate-sized groups benefited from these movement characteristics, as they also had more chicks.

However, the study also found interesting consequences of having a beneficial group size for movements. Groups with many chicks, despite being the optimal size, had more restricted home ranges. This was likely because the chicks needed more protection from predators, and therefore stayed in the protected vegetation for longer periods of time, and their small sizes slowed down the group while moving.

As a result, the study showed that intermediate-sized groups were in fact rarer than smaller and larger groups. Papageorgiou and Farine suggest this is because the benefits of being in an optimal-sized group makes the size of these groups less stable. For example, higher reproductive success inevitably pushes the group past its optimal group size.

"Our study highlights how all groups are not equal, with the effects of group size and composition playing a major role in shaping how social species use their habitat," Farine says. "What is particularly interesting is that optimally sized groups are not expected to be common. Future studies should investigate whether these relationships change across different environmental conditions, and how animal groups cope with the different challenges that each season brings."

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Reference

The paper 'Group size and composition influence collective movement in a highly social terrestrial bird' can be freely accessed online at https://doi.org/10.7554/eLife.59902. Contents, including text, figures and data, are free to reuse under a CC BY 4.0 license.

Media contact

Emily Packer, Media Relations Manager
eLife
e.packer@elifesciences.org
01223 855373

About eLife

eLife is a non-profit organisation created by funders and led by researchers. Our mission is to accelerate discovery by operating a platform for research communication that encourages and recognises the most responsible behaviours. We work across three major areas: publishing, technology and research culture. We aim to publish work of the highest standards and importance in all areas of biology and medicine, including Ecology, while exploring creative new ways to improve how research is assessed and published. We also invest in open-source technology innovation to modernise the infrastructure for science publishing and improve online tools for sharing, using and interacting with new results. eLife receives financial support and strategic guidance from the Howard Hughes Medical Institute, the Knut and Alice Wallenberg Foundation, the Max Planck Society and Wellcome. Learn more at https://elifesciences.org/about.

To read the latest Ecology research published in eLife, visit https://elifesciences.org/subjects/ecology.

Treating opioid addiction in primary care helps patients and cash-strapped medical practices

AMERICAN ACADEMY OF FAMILY PHYSICIANS

Research News

Buprenorphine-based treatment for opioid addiction is in short supply in many areas of the United States. And while many physicians want to offer it, clinics are unsure how to offer buprenorphine therapy in a financially sustainable way. A team of researchers at Harvard Medical School conducted financial cost and revenue analysis for four different approaches to delivering buprenorphine-based treatment in primary care practices. The approaches differed based on who in the clinic delivered the majority of face-to-face care, the presence of nurse care managers, and whether care was delivered in traditional one-on-one or group settings.

Microsimulation modelling found that all four approaches to care produced positive net revenue after the first year, and net revenues were consistently highest for rural practices. Physician-led treatment and shared medical visits, both of which relied on nurse care managers, consistently produced the greatest net revenue gains. Additionally, net revenues were positive for all primary care practices that had at least nine patients in buprenorphine treatment per provider at any given time and no-show rates less than 34 percent. The findings suggest that in the current fee-for-service-dominated environment, offering office-based therapy for opioid addiction with buprenorphine can be a financially sustainable choice for cash-strapped primary care practices, despite hurdles.

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Financing Buprenorphine Treatment in Primary Care: A Microsimulation Model

Sanjay Basu, MD, PhD, et al
Harvard Medical School, Center for Primary Care, Boston, Massachusetts
https://www.annfammed.org/content/18/6/535

Taking a scalpel to opioid painkiller risks: New studies show progress and opportunity

Surgery studies show progress and opportunity to reduce prescribing and better support pain care across many types of operations

MICHIGAN MEDICINE - UNIVERSITY OF MICHIGAN

Research News

Having surgery means placing complete trust in a team of professionals, and counting on them to fix what's wrong while keeping surgical risks as low as possible.

But one of those risks, surgery experts have begun to realize, has nothing to do with what happens in the operating room. Instead, it has to do with treating post-surgery pain without raising the chance that the patient will get hooked, or more dependent, on opioids.

It's a risk that affects a minority of patients - maybe 1% to 10% at most, depending on the operation. But it's not easy to tell in advance which patients will continue to seek opioid painkiller refills months after their surgery pain should have subsided.

Meanwhile, patients who already took opioids for pain before their operation face other risks from increased doses taken after surgery.

A wave of new studies led by surgeons and trainees at Michigan Medicine, the University of Michigan's academic medical center, add to the understanding of these risks. They also show what happens when surgical teams work together to reduce the emphasis on, and supply of, opioid painkillers while still seeking to ease surgery patients' pain.

Sustained success

It's already been several years since a U-M team published some of the first evidence about the risks of long-term post-surgical opioid use. The team also took the novel step of contacting patients to find out how many opioid pills they had actually taken for their surgical pain, compared with what they'd been prescribed.

That led them to develop prescribing guidelines for sharp reduction in opioid prescribing, and use of other pain medications and patient education. They formed the Michigan Opioid Prescribing and Engagement Network, or Michigan OPEN, to help spread the word about the guidelines and about the need for proper disposal of leftover pain medicines to keep them from being diverted to recreational use.

A trial of the guidelines at Michigan Medicine's hospitals showed opioid prescribing declined without increasing patients' pain. That was enough to convince dozens of hospitals across the state of Michigan to adopt the guidelines, and work together to refine them, through the Michigan Surgical Quality Collaborative funded by Blue Cross Blue Shield of Michigan.

Now, a new paper published in BMJ Quality & Safety shows the long-term effects of that statewide effort. It includes data from 36,022 patients who received a prescription for an opioid painkiller to help them with the pain associated with one of 9 operations between February 2017 and May 2019 in 69 hospitals across Michigan.

In all, the average surgical opioid prescription size was cut in half over this time, from an average of 30 tablets to about 15. The amount of opioids patient took from those prescriptions also dropped, from an average of 13 tablets to an average of 6, and the percentage of patients who sought a refill for their opioid prescription went down.

Despite the reduction in prescribing and consumption, there was no increase in the amount of pain patients reported in follow-up surveys, or decrease in their satisfaction with their surgery experience. These follow-up data are available for more than 15,000 of the patients.

Prescribing was more in line with guidelines instead of varying greatly by surgeon and procedure, especially for less commonly performed operations that had previously varied widely.

"This project illustrates the power of engaging and empowering physicians, nurses, and other healthcare workers across the state to help improve care for all of our patients," says Craig Brown, M.D., the general surgery resident who is the first author of the new paper. "There's still room to improve opioid prescribing, but teamwork like that exhibited through this MSQC and M-OPEN partnership has made a lasting impact on post-operative prescribing and made a huge difference in our communities."

Surgery professor Michael Englesbe, M.D., who co-leads Michigan OPEN and leads MSQC, is the study's senior author. "We are fortunate in Michigan that our physicians, nurses, state policy makers, and major private payer are able to partner, coordinate efforts and rapidly improve care for patients in our State," he says.

Opioids and hernia surgery

Every year, nearly 800,000 Americans - most of them men - have surgery for the most common kind of hernia, called an inguinal hernia. And according to results of a new study, about 12,000 of them might end up using opioid painkillers long-term, months after the pain from their operation should have subsided.

The study led by U-M surgery resident Ryan Howard, M.D., and surgery associate professor Dana Telem, M.D., M.P.H., is published ahead of print in the Annals of Surgery. It looked at national data on hernia operations done from 2008 to 2016, on patients who got their insurance through a major private insurer including through jobs and Medicare Advantage plans. It only included patients who were "opioid-naïve," meaning they were not already using opioid at the time of surgery.

The team found that of all the patients who received an opioid prescription around the time of surgery, 1.5% of these patients continued refilling opioid prescriptions for at least 3 months after their hernia repair. This means that these patients are continuing to use opioids - medications that carry many risks -long after the surgical pain should have subsided. While this is a lower percentage than those seen in other studies of post-surgery chronic opioid use, it's still concerning because the operation is so common, the authors say.

A critical finding of this study was that patients who filled an opioid prescription in the month before their operation were four times more likely to become persistent opioid users after surgery. Importantly, over half of these preoperative prescriptions were provided by surgeons. The study team believes this may reflect the practice of "convenience prescribing," where a provider makes sure a patient has their prescription filled and ready before they even have their operation. Given that this dramatically increases the risk of persistent opioid use, it may be time for surgeons to abandon this practice.

Additionally, patients who had a major complication of their operation, or who had anxiety, disruptive mood disorder, alcohol or substance abuse disorders or pain disorders were more likely to go on to become chronic opioid users.

Opioids after cancer surgery

One of the key goals of surgical opioid prescribing research is to "right size" the painkiller prescriptions that patients receive before or immediately after their operations so that they have the pills they need to control their pain once they get home, but don't have so many that leftovers pose a risk to them or someone in their household.

A new study in the Journal of Surgical Oncology by a team led by U-M medical student Nicholas Eyrich, M.S., and general surgery chief resident Jay S. Lee, M.D., shows what breast cancer and melanoma surgery patients at a major medical center actually reported receiving and using.

They interviewed 439 patients within a few months of their operation, and found that on average patients took just two of the opioid tablets they were prescribed, no matter what operation they had or whether they received a prescription of 5, 10 or 20 tablets.

While the vast majority of patients said they received instructions for taking opioids, less than half said a member of the care team had talked with them about using non-opioids first or about the risk of addiction to opioids. Less than a third said they were told about the risks of having unused opioids in the home, and only a quarter said they had discussed safe disposal of unused opioids with a member of the care team.

Persistent use leads to higher costs

Another new paper, led by Lee and Michigan OPEN co-leader and plastic surgeon Jennifer Waljee, M.D., M.P.H., M.S., shows that patients who become persistent opioid users for the first time after surgery cost the health system more.

Writing in the Annals of Surgery, they report data from more than 133,000 people nationwide who did not take opioids before they had surgery, of whom 8,100 continued refilling opioid prescriptions for months after their operations.

The average health care bills for each of those patients were $2,700 higher than for those who didn't develop persistent use. The increased spending kept going for at least six months after surgery, at an average rate of $200 a month.

Outpatient surgery risks for those already taking opioids

Older patients who take high doses of opioids, and then go on to have outpatient operations, are more likely to die within a few months of surgery than those who weren't taking opioids, according to a recent study published in JAMA Surgery.

The team, led by Katherine Santosa, M.D., M.S., U-M chief resident in plastic surgery, and Waljee, looked at data from Medicare enrollees over 65 who had common outpatient procedures between 2009 and 2015. They included people who had gallbladder, thyroid, hernia, carpal tunnel, hemorrhoid, varicose vein and prostate surgery, among others.

The team did the study because opioid use is known to be associated with falls, fractures and breathing issues in older adults, especially those who also take medications called benzodiazepines for anxiety or sleep issues.

Although only a small percentage of patients died within 90 days of their outpatient operation - just 471 of the more than 99,000 studied, or 0.5% - the researchers were able to see a difference based on opioid use. It was visible even after adjusting the results for differences in age, sex, race, type of surgery, and multiple measures of health.

The authors call for more attention to be paid to the risks of surgery for people who take opioids on a long-term basis, especially those taking higher doses. Helping them reduce their opioid use before their operation could reduce their risk, and also help them respond better to any opioids prescribed for pain control after surgery. The authors also note that prescribing naloxone, a drug that can "rescue" someone from an opioid overdose, might be wise.

Englesbe, Telem and Waljee are faculty in the U-M Department of Surgery and members of the U-M Institute for Healthcare Policy and Innovation. Waljee directs the Center for Healthcare Outcomes and Policy, where Brown and Howard are current fellows and Lee is a former fellow.

Learn more about the full spectrum of opioid-related research and scholarship at U-M through the Opioid Solutions Initiative.

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Mindfulness interventions can change health behaviors -- integrated model helps to explain how they work

WOLTERS KLUWER HEALTH

Research News

November 10, 2020 - A growing body of evidence supports the effectiveness of mindfulness approaches to promote positive changes in health behaviors. New neurobiologically based models of "mindful self-regulation" help to explain the how mindfulness-based interventions (MBIs) work to help people make healthy behavior changes, according to a review in the November/December issue of Harvard Review of Psychiatry. The journal is published in the Lippincott portfolio by Wolters Kluwer.

Mindfulness approaches can help patients with a wide range of physical and mental health conditions to initiate and sustain changes in health behaviors, according to the article by Zev Schuman-Olivier, MD, of Harvard Medical School and colleagues. They present an integrated model that "synthesizes the neuroscience of mindfulness and integrates motivation and learning mechanisms within a mindful self-regulation model for understanding the complex effects of mindfulness on behavior change." Dr. Schuman-Olivier is Director of the Center for Mindfulness and Compassion at the Cambridge Health Alliance.

MBIs help patients regulate attention, emotions, and thoughts

Changing unhealthy behaviors can be "exceptionally difficult" - but it's the key to prevention and treatment of many chronic medical and psychiatric illnesses. Mindfulness has been described as "the awareness that arises when paying attention to the present moment nonjudgmentally." The process for cultivating mindfulness often includes various approaches to mindfulness meditation - although the authors emphasize that "not all meditation is mindfulness and not all mindfulness is meditation."

In their comprehensive review of the field, Dr. Schuman-Olivier and colleagues seek to "describe and expand existing models of mindful self-regulation based on neurobiological mechanisms of mindfulness, motivation, and learning." Self-regulation refers to the ability to adapt one's attention, emotions, thoughts, and behavior to respond effectively to internal and external demands.

The article gives an updated account of current neuroscientific understanding of the systems involved in healthy self-regulation - including attentional and cognitive control, emotion regulation, and self-related processes - and the way these neural systems interact with those involved in motivation and learning.

In the authors' proposed model, MBIs can help patients regulate their attention, emotions, and thoughts. Mindfulness training increases the capacity for interoceptive awareness: the ability to identify, access, understand, and respond appropriately to the patterns of internal bodily signals. Patients become aware of negative and self-critical thought patterns, and better able to respond kindly to themselves when they are suffering, make mistakes, or have difficulty (self-compassion).

The authors differentiate between a traditional "cool" pathway for teaching mindfulness, focused solely on attention; and an emerging "warm" pathway that may aid in preventing adverse events and increasing accessibility to MBIs for those who have experienced trauma. The "warm" pathway encourages finding a "window of tolerance" and cultivating inner warmth and self-kindness - alongside attentional and interoceptive awareness training. This approach helps patients learn, develop, and integrate key self-regulatory capacities for "warmly being with present-moment experience."

Dr. Schuman-Olivier and colleagues highlight some key areas of research on mindfulness and behavior change, including alcohol and substance abuse disorders. In addition to general changes in self-regulation, MBIs can address disease-specific issues such as cravings for alcohol and drugs.

Research finds MBIs effective for food-related behaviors and weight loss, including reductions in binge eating and emotional eating. Studies of tobacco smoking suggest that MBIs may provide better outcomes than other accepted treatments. Mindfulness interventions have also led to improvements in self-care for patients with chronic illness and show promise in reducing aggressive behavior, suicide, and self-injury.

The authors draw attention to the need to monitor adverse events and to ensure that mindfulness programs are trauma-informed and accessible to diverse populations. Dr. Schuman-Olivier and colleagues conclude: "While evidence supports the impact of mindfulness on behavior change for key health behaviors related to psychiatric practice, more high-quality research is needed, especially with objective measures, larger samples, replication studies, active controls, and formal monitoring of adverse events."

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Note: This work and effort was funded by grants through the NIH Science of Behavior Change Initiative (funded by the NIH Common Fund and National Center for Complementary and Integrative Health) and also supported by the National Center's HEAL (Helping to End Addiction Long-term) Initiative.

Click here to read "Mindfulness and Behavior Change."

DOI: 10.1097/HRP.0000000000000277

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About the Harvard Review of Psychiatry

The Harvard Review of Psychiatry is the authoritative source for scholarly reviews and perspectives on a diverse range of important topics in psychiatry. Founded by the Harvard Medical School Department of Psychiatry, the journal is peer reviewed and not industry sponsored. It is the property of Harvard University and is affiliated with all of the Departments of Psychiatry at the Harvard teaching hospitals. Articles encompass major issues in contemporary psychiatry, including neuroscience, epidemiology, psychopharmacology, psychotherapy, history of psychiatry, and ethics.

About Wolters Kluwer

Wolters Kluwer (WKL) is a global leader in professional information, software solutions, and services for the clinicians, nurses, accountants, lawyers, and tax, finance, audit, risk, compliance, and regulatory sectors. We help our customers make critical decisions every day by providing expert solutions that combine deep domain knowledge with advanced technology and services.

Wolters Kluwer reported 2019 annual revenues of €4.6 billion. The group serves customers in over 180 countries, maintains operations in over 40 countries, and employs approximately 19,000 people worldwide. The company is headquartered in Alphen aan den Rijn, the Netherlands.

Wolters Kluwer provides trusted clinical technology and evidence-based solutions that engage clinicians, patients, researchers and students with advanced clinical decision support, learning and research and clinical intelligence. For more information about our solutions, visit https://www.wolterskluwer.com/en/health and follow us on LinkedIn and Twitter @WKHealth.

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Lack of positivity bias can predict relapse in bipolar disorder

New findings could provide a tool for people with bipolar disorder and clinicians to predict relapse and intervene in a timely manner

ELIFE

Research News

Relapse in people with bipolar disorder can be predicted accurately by their tendency towards having pessimistic beliefs, according to a study published today in eLife.

The results could provide an urgently needed tool for doctors to predict upcoming relapse and provide timely treatment.

Bipolar disorder is characterised by successive periods of elation (mania) and depression, interspersed with asymptomatic phases, called euthymia. People who have shorter periods of asymptomatic euthymia are more likely to suffer disability, unemployment, hospitalisation and increased suicidal feelings. However, predicting relapses using existing clinical diagnostic tools or demographic information has proven largely ineffective in bipolar disorder.

"It is already known that people with depression tend to give negative information more weight than positive information, leading to pessimistic views that may make symptoms worse," explains lead author Paolo Ossola, Research Fellow at the Department of Medicine and Surgery, University of Parma, Italy. "We wanted to test the idea that, before symptomatic relapse occurs in bipolar disorder, patients show a specific pattern in the way they update their beliefs according to new information, and this pattern makes them more vulnerable to relapse."

The team carried out a belief update task with 36 people with bipolar disorder and then monitored them every two months for five years to see when they developed symptoms of a relapse. In the belief update task, patients were given information about 40 adverse life events, such as robbery or credit card fraud. They were asked to estimate how likely they thought the event was to happen to them.

Next, they were given information on the real probability of the event happening. In some cases, they received bad news (for example, a higher chance of a robbery than they thought) and in some cases, good news (for example, they were less likely to be a victim of card fraud than they thought). In a second later session they were asked again to estimate their own likelihood of encountering the event. The difference between how much they updated their beliefs in response to good or bad news (called the belief update bias) was then compared with how soon they had a relapse.

The analysis showed that people who had a greater change in their beliefs in response to positive information, and were more likely to take an optimistic view, had a longer time period before the next onset of symptoms. However, the task did not predict whether the next episode was likely to be mania or depression.

When tested against other clinical features, such as age, history of psychotic symptoms, and duration of illness, only belief update bias was strongly linked to more time spent in the eurythmic phase, and taking antidepressants was linked with a shorter time spent in eurythmia.

"Our findings show that the extent to which bipolar patients updated their beliefs in response to positive information, compared with negative information, was predictive of when they would relapse," concludes senior author Tali Sharot, Professor of Cognitive Neuroscience at the Department of Experimental Psychology, University College London, UK. "The way patients update their beliefs could be introduced in future as a risk prediction tool for bipolar disorder, allowing patients and clinicians to step up vigilance to recognise symptoms and intervene where necessary."

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Reference

The paper 'Belief updating in bipolar disorder predicts time of recurrence' can be freely accessed online at https://doi.org/10.7554/eLife.58891. Contents, including text, figures and data, are free to reuse under a CC BY 4.0 license.

Media contact

Emily Packer, Media Relations Manager
eLife
e.packer@elifesciences.org
01223 855373

About eLife

eLife is a non-profit organisation created by funders and led by researchers. Our mission is to accelerate discovery by operating a platform for research communication that encourages and recognises the most responsible behaviours. We work across three major areas: publishing, technology and research culture. We aim to publish work of the highest standards and importance in all areas of biology and medicine, including Neuroscience, while exploring creative new ways to improve how research is assessed and published. We also invest in open-source technology innovation to modernise the infrastructure for science publishing and improve online tools for sharing, using and interacting with new results. eLife receives financial support and strategic guidance from the Howard Hughes Medical Institute, the Knut and Alice Wallenberg Foundation, the Max Planck Society and Wellcome. Learn more at https://elifesciences.org/about.

To read the latest Neuroscience research published in eLife, visit https://elifesciences.org/subjects/neuroscience.

'Diseases of despair' have soared over past decade in US

Suicidal thoughts/behaviors among under 18s up by 287%, and by 210% among 18-34 year olds

BMJ

Research News

'Diseases of despair', such as substance abuse, alcohol dependency, and suicidal thoughts and behaviours, have soared in the US over the past decade, reveals an analysis of health insurance claims data published in the online journal BMJ Open.

And they now affect all ages, with suicidal thoughts and behaviours among the under 18s rocketing by 287% between 2009 and 2018, and by 210% among 18-34 year olds, the analysis shows.

Between 2015 and 2017, life expectancy fell year on year in the USA, the longest sustained decline since 1915-18. And deaths among middle-aged white non-Hispanic men and women rose sharply between 1999 and 2015.

These premature deaths are largely attributable to accidental overdose, alcohol-related disease, and suicide.

Such 'deaths of despair' have coincided with decades of economic decline for workers, particularly those with low levels of educational attainment; loss of social safety nets; and stagnant or falling wages and family incomes in the US, all of which are thought to have contributed to growing feelings of despair.

Despair may in turn trigger emotional, behavioural and even biological changes, increasing the likelihood of diseases that can progress and ultimately culminate in deaths of despair, say the researchers.

To characterise trends in diseases of despair over the past decade and identify associated demographic risk factors, they drew on detailed claims data extracted from Highmark, a large US-based health insurance company.

Highmark members are concentrated in states that have been disproportionately affected by deaths of despair: Pennsylvania; West Virginia; and Delaware.

In all, the researchers analysed information for 12 million people enrolled in a Highmark health insurance plan between 2007 and 2018, and who had valid details on file.

Diseases of despair were defined as diagnoses related to alcohol dependency, substance misuse, and suicidal thoughts/behaviours, and analysed among the following age groups: under the age of 12 months; 1-17 year olds; 18-34 year olds; 35-54 year olds; 55-75 year olds; and those aged 75+.

Overall, 1 in 20 (515,830; just over 4%) of those insured were diagnosed with at least one disease of despair at some point during the monitoring period. Some 58.5% were male, with an average age of 36.

Of these, over half (54%) were diagnosed with an alcohol-related disorder; just over 44% with a substance related disorder; and just over 16% with suicidal thoughts/behaviours. Just under 13% were diagnosed with more than one type of disease of despair.

Between 2009 and 2018, the rate of diseases of despair diagnoses increased by 68%. The rate of alcohol-related, substance-related, and suicide-related diagnoses rose by 37%, 94%, and 170%, respectively.

The largest increase in alcohol and substance-related diagnoses was seen among 55-74 year olds: 59% and 172%, respectively.

Among infants, substance-related diagnoses, which were attributable to neonatal abstinence syndrome linked to maternal drug abuse--for example opioid addiction--rose by 114%.

While the absolute numbers of suicide-related diagnoses were lower than for other types of diseases of despair, the relative increases were large. Among 1-17 year olds, the rate increased by 287%, and by 210% among 18-34 year olds. A relative increase of at least 70% occurred in all other age groups.

Diseases of despair diagnoses were associated with significantly higher scores for coexisting conditions, higher rates of anxiety and mood disorders, and schizophrenia for both men and women across all age groups.

The researchers acknowledge that it wasn't possible to find out about potentially influential social determinants of health from the claims data, added to which, given that an estimated 87 million working adults in the US are uninsured or underinsured, it is hard to gauge the true scope of the diseases of despair, they say.

Nevertheless, they urge: "While the opioid crisis remains a top public health priority, parallel rises in alcohol-related diagnoses and suicidality must be concurrently addressed."

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Externally peer reviewed: Yes
Evidence type: Observational; healthcare claims
Subjects: People

As cancer has evolved, it is time for cancer research to do the same

Analysis of cancer research funding and outputs associated with xenograft models reveals that the poorly predictive animal models still largely outnumber the more predictive, human biology-based organoids.

HUMANE SOCIETY INTERNATIONAL

Research News

London, UK (10 Nov 2020) -- The observance of Lung Cancer Awareness Month in November affords an opportunity to take stock of current approaches to lung cancer research, and to cancer research more widely. While there have been improvements in understanding, prevention and overall survival, it is still shocking to note that more than 1.7 million people died of lung cancer in 2018 alone This is the case despite the fact that lung cancer research has been relatively well-funded, and this suggests that an urgent need to rethink how we prioritise the funding available for cancer research. As the former European Commissioner for Research, Enterprise and Science said, "cancer has evolved and we need new tactics to match it."

For cancer, in particular, more than 95% of potential drugs fail in clinical trials.

Animal testing, with its poorly predictive preclinical models of human efficacy and safety, represents a major obstacle in the drug development pipeline and is the main reason that drug attrition rates are so high. It is still more frustrating to consider that predictive, human biology-based tools are increasingly available, yet receive only a meagre proportion of current research funding.

To investigate the extent to which modern, human-based non-animal approaches are supplanting animal models, research at Humane Society International led by Drs Lindsay Marshall and Marcia Triunfol compared studies using animal-dependent methods--so-called "xenograft" models in which patient tumour biopsies are injected into an animal--and human "organoids", which use patient tumour samples to create in vitro models that more closely resemble a patient's tumour.

Their preliminary analysis showed that for human organoids, there has been a modest increase in outputs, as measured by number of publications, funding, and publications associated with clinical trial. However, when the authors compared this to xenograft research, they found that animal-dependent research is still favoured and that publications, funding and clinical trials associated with xenografts all outnumber organoids by at least 10 to 1.

Human organoid models recapitulate key characteristics of the original cancer and maintain the structure seen in the patient's tumour. This makes human organoid models better for studying how the patient will respond to specific drugs, and how the tumour will progress. Considering this, and the promise of human organoids for studying cancer, the authors of this research expressed their disappointment in learning that the U.S. National Institutes of Health awarded over five times more funding to animal xenograft-based research programs than to those involving human organoids.

The authors contend that, "There is a great need to level the 'playing field' for the human cell-based technologies compared to animals, given that, in the European Union, only 0.036% of the research budget is dedicated to these more human relevant, non-animal approaches. This deficit is adding hugely to the obstacles preventing animal replacement in human health research." They go on to say, "We would like to stress that funding should be made available to assess the capacity of the organoids in predicting patient responses or for evaluating novel, possibly combination therapies, and not for comparative studies aiming to 'validate' organoids against animals, given that the animal models are, and remain, unvalidated." A number of studies have described the pitfalls of using animal xenografts as a proxy model for a patient's tumour. These models are time-consuming, very expensive, and some studies have shown that they do not faithfully replicate the changes and abnormalities first seen in the original tumour, but rather create new ones.

With at least half of European cancer research funding coming from the public via charity donations, and U.S. taxpayers contributing heavily to their own government's research budget, there is certainly a case to be made for the responsibility scientists have to the public. Given the disapproval of many citizens concerning the use of animal in research, this might include reducing reliance on animal testing and accelerating the discovery and development of new, effective and affordable medicines.

Overall, it appears that the transition to more effective and more human-relevant non-animal technologies is proceeding at a very slow pace. Yet the work of Dr Marshall and colleagues indicates that a faster transition is entirely possible, as long as dedicated support for human biology-based approaches, more agile regulatory requirements and smarter clinical trials are put in place.The authors make several recommendations to accelerate this change, including the establishment of training programs for researchers, and greater transparency regarding the use of organoids/other human cell-based tools to develop drug testing regimes for patients. With lung cancer, together with breast and colorectal cancers, accounting for almost a third of all cancer mortality annually worldwide, and cancer research consuming millions of animals' lives, these would surely be small efforts for the potential gains to be made.

The article entitled "Patient-Derived Xenograft vs Organoids: A Preliminary Analysis of Cancer Research Output, Funding and Human Health Impact in 2014-2019" has been published in the journal Animals.


Studies outline key ethical questions surrounding brain-computer interface tech

NORTH CAROLINA STATE UNIVERSITY

Research News

Brain-computer interface (BCI) technologies are no longer hypothetical, yet there are fundamental aspects of the technology that remain unaddressed by both ethicists and policy-makers. Two new papers address these issues by outlining the outstanding ethical issues, offering guidance for addressing those issues, and offering particular insight into the field of BCI tech for cognitive enhancement.

"BCI technologies are devices that detect brain signals conveying intention and translates them into executable output by a computer," says Allen Coin, a graduate student at North Carolina State University and lead author of both papers. "BCI technologies can also provide feedback to the user, reflecting whether he or she attained a goal or completed a desired action."

"BCI devices can be non-invasive devices that users wear, or they can be invasive devices, which are surgically implanted," says Veljko Dubljevi?, an assistant professor in NC State's Science, Technology & Society program and co-author of both papers. "The invasive devices are more efficient, since they can read signals directly from the brain. However, they also raise more ethical concerns.

"For example, invasive BCI technologies carry more associated risks such as surgery, infection, and glial scarring - and invasive BCI devices would be more difficult to replace as technology improves."

Many BCI devices, such as cochlear implants, are already in use. And this field of technology has garnered increased attention due to a company called Neuralink, which is focused on building what it calls a brain-machine interface.

"Neuralink highlights the immediacy of these ethical questions," Dubljevi? says. "We can't put the questions off any more. We need to address them now."

And Dubljevi? would know.

He, Coin and NC State undergraduate Megan Mulder recently published a comprehensive review of the research literature that addresses ethical considerations of BCI. A previous review had been done as recently as 2016, but almost as much research had been done on the ethics of BCI since 2016 as had been done before 2016.

One of the key take-aways from the analysis is that there are two areas that ethicists have not adequately addressed and that should be prioritized for future work: physical effects of BCI and psychological effects.

"On the physical side, there's been little analysis by ethicists of the potential long-term health effects of BCI on users," Coin says. "There's also been inadequate discussion of ethical considerations related to the use of animals in testing invasive BCI technologies. These are, after all, surgical operations."

On the psychological side, researchers found reason for concern - but a lack of ethical analysis. For example, one study evaluated the use of invasive BCI to give patients with epilepsy advanced warning of seizures. While some people adjusted well to the technology, others reported experiencing radical psychological distress.

"This is an issue that must be addressed," Dubljevi? says. "We also need to assess questions on the extent to which users feel the BCI is an empowering extension of their minds, as opposed to challenging their sense of self. These are big questions, not afterthoughts."

"Another thing our review really drove home is that the ethical analysis of BCI has been done by ethicists who are writing almost exclusively for other ethicists," Coin says. "As a result, little of the work is framed in a way that is directly relevant - or even accessible - to policy makers and the public."

The researchers also laid out a constructive framework for guiding future research on the ethics of BCI. At its core is one overarching question: "What would be the most legitimate public policies for regulating the development and use of various BCI neurotechnologies by healthy adults in a reasonably just, though not perfect, democratic society?"

"That question is long, technical, and steeped in scholarship of ethics and policy of new technology, but it's critical to guiding the development of BCIs," Dubljevi? says.

In a separate paper, Coin and Dubljevi? explored issues related to authenticity and machine-augmented intelligence. In this context, authenticity refers to the extent to which an individual feels that their abilities and accomplishments are their own, even if those abilities are augmented by BCI technologies, or their accomplishments were made with the assistance of BCI technologies.

"And machine-augmented intelligence refers to BCI technologies that enhance cognition - which are not yet on the market," Dubljevi? says. "However, they are clearly a goal of BCI developers, including Neuralink."

In this paper, the researchers were focused on the fact that there have been very few concerns about authenticity in the context of cognitive enhancement BCI technologies, despite the fact that these concerns have come up repeatedly in regard to other cognitive enhancement tools - such as drugs that can improve concentration.

In other words, if ethicists care about whether people on "smart drugs" have "earned" their test scores, why don't they have similar concerns about BCIs?

The answer appears to be twofold.

First of all, the majority of the proposed cognitive enhancement BCI devices are therapeutic in nature.

"When a patient receives a cochlear implant, that's a BCI that helps them hear," Coin says. "Nobody questions whether that patient's hearing is authentic. Similarly, cognitive enhancement BCI devices are often presented as similarly therapeutic tools, helping patients overcome a challenge.

"However, we are now hearing more about the potential for BCI devices to enhance cognition in ways that go beyond therapeutic applications, yet there is still limited debate about their authenticity," Coin says. "We think that this is because these BCI technologies are generally envisioned as being implants, which means the device would effectively be a permanent - or semi-permanent - change, or even an extension, to a person's mind. These aren't drugs that wear off. They're there to stay."

"Ultimately, these two papers get at some of the big questions that we need to address as a society about BCI technologies," Dubljevi? says. "The technologies are coming whether we're ready or not. How will we regulate them? Who will have access to them? How can they be used? We need to start thinking about those questions now."

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The first paper, "Ethical Aspects of BCI Technology: What Is the State of the Art?," is published in the journal Philosophies. The second paper, "The Authenticity of Machine-Augmented Human Intelligence: Therapy, Enhancement, and the Extended Mind," is published in the journal Neuroethics.

Sleep loss hijacks brain's activity during learning

Disruption could increase risks for sleepless workers

ELSEVIER

Research News

Philadelphia, November 11, 2020 - Sleep is crucial for consolidating our memories, and sleep deprivation has long been known to interfere with learning and memory. Now a new study shows that getting only half a night's sleep - as many medical workers and military personnel often do - hijacks the brain's ability to unlearn fear-related memories. That might put people at greater risk of conditions such as anxiety or posttraumatic stress disorder.

The study appears in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier.

"This study provides us with new insights into how sleep deprivation affects brain function to disrupt fear extinction," said Cameron Carter, MD, Editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.

The researchers, led by Anne Germain, PhD, at the University of Pittsburgh and Edward Pace-Schott, PhD, at Harvard Medical School and Massachusetts General Hospital, studied 150 healthy adults in the sleep laboratory. One third of subjects got normal sleep, one third were sleep restricted, so they slept only the first half the night, and one third were sleep deprived, so they got no sleep at all. In the morning, all the subjects underwent fear conditioning.

"Our team used a three-phase experimental model for the acquisition and overcoming of fearful memories while their brains were scanned using functional magnetic resonance imaging," said Dr. Pace-Schott. In the conditioning paradigm, subjects were presented with three colors, two of which were paired with a mild electric shock. Following this fear conditioning, the subjects underwent fear extinction, in which one of the colors was presented without any shocks to learn that it was now "safe." That evening, subjects were tested for their reactivity to the three colors, a measure of their fear extinction recall, or how well they had "unlearned" the threat.

Brain imaging recorded during the tasks showed activation in brain areas associated with emotional regulation, such as the prefrontal cortex, in people who got normal sleep. But the brain activity looked very different in people with restricted sleep, said Dr. Pace-Schott. "We found that among the three groups, those who had only gotten half a night's sleep showed the most activity in brain regions associated with fear and the least activity in areas associated with control of emotion."

Surprisingly, people who got no sleep lacked the brain activation in fear-related areas during fear conditioning and extinction. During the extinction recall 12 hours later, their brain activity looked more similar to those with normal sleep, suggesting that a limited night of sleep may be worse than none at all.

The researchers hypothesize that sleeping only half the night results in a loss of rapid eye movement (REM) sleep, which has been shown to be important for memory consolidation and usually happens toward the end of a normal sleep period.

Dr. Carter said the study used "noninvasive brain imaging to give us a novel window into how sleep deprivation disrupts the normal fear extinction mechanisms and potentially increases vulnerability to posttraumatic stress symptoms."

"Medical workers and soldiers often have curtailed or interrupted sleep rather than missing an entire night's sleep," Dr. Pace-Schott said. "Our findings suggest that such partially sleep-deprived individuals might be especially vulnerable to fear-related conditions such as posttraumatic stress disorder."

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This study was funded by the Military Operational Medicine Research Program, Log#11293006; PI: Germain.

Notes for editors

The article is "Partial and Total Sleep Deprivation Interferes with Neural Correlates of Consolidation of Fear Extinction Memory," by Jeehye Seo, Edward Pace-Schott, Mohammed Milad, Huijin Song, Anne Germain (https://doi.org/10.1016/j.bpsc.2020.09.013). It appears as an Article in Press in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier.

Copies of this paper are available to credentialed journalists upon request; please contact Rhiannon Bugno at BPCNNI@sobp.org or +1 254 522 9700. Journalists wishing to interview the authors may contact Edward Pace-Schott, PhD, at epace-schott@mgh.harvard.edu or +1 508 523 4288.

The authors' affiliations and disclosures of financial and conflicts of interests are available in the article.

Cameron S. Carter, MD, is Professor of Psychiatry and Psychology and Director of the Center for Neuroscience at the University of California, Davis. His disclosures of financial and conflicts of interests are available here.

About Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging is an official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal focuses on studies using the tools and constructs of cognitive neuroscience, including the full range of non-invasive neuroimaging and human extra- and intracranial physiological recording methodologies. It publishes both basic and clinical studies, including those that incorporate genetic data, pharmacological challenges, and computational modeling approaches. The 2019 Impact Factor score for Biological Psychiatry: Cognitive Neuroscience and Neuroimaging is 5.335. http://www.sobp.org/bpcnni

About Elsevier

Elsevier is a global information analytics business that helps scientists and clinicians to find new answers, reshape human knowledge, and tackle the most urgent human crises. For 140 years, we have partnered with the research world to curate and verify scientific knowledge. Today, we're committed to bringing that rigor to a new generation of platforms. Elsevier provides digital solutions and tools in the areas of strategic research management, R&D performance, clinical decision support, and professional education; including ScienceDirectScopusSciValClinicalKey and Sherpath. Elsevier publishes over 2,500 digitized journals, including The Lancet and Cell , more than 39,000 e-book titles and many iconic reference works, including Gray's Anatomy. Elsevier is part of RELX, a global provider of information-based analytics and decision tools for professional and business customers. http://www.elsevier.com