Culture

Non-violent offenders serving time for drug use or possession should be freed immediately and their convictions erased, according to research published in the peer-reviewed The American Journal of Bioethics.

More than 60 international experts including bioethicists, psychologists and drug experts have joined forces to call for an end to the war on drugs which they argue feeds racism.

All drugs currently deemed illicit - even crack cocaine and heroin - should be decriminalized as a matter of urgency, according to this new alliance. Legalisation and regulation should then follow with restrictions on age, advertising and licensing, they say.

They have analysed evidence from over 150 studies and reports, concluding that prohibition unfairly affects Black people, damages communities, and violates the right to life as illustrated by the killing of medical worker Breonna Taylor in March 2020.

"The 'war on drugs' has explicitly racist roots and continues to disproportionately target certain communities of color," say lead study authors Brian D. Earp from the University of Oxford and Jonathan Lewis from Dublin City University.

"Drug prohibition and criminalization have been costly and ineffective since their inception. It's time for these failed policies to end.

"The first step is to decriminalize the personal use and possession of small amounts of all drugs currently deemed to be illicit, and to legalize and regulate cannabis. Policymakers should pursue these changes without further delay."

Their research adds to growing calls for drug policy reform at a time of renewed focus on injustices faced by Black people, and cannabis legalisation for recreational use by a growing list of US states.

The study is based on evidence from existing research into how drug prohibition affects users, communities and human rights, and the impact of decriminalisation by governments.

The authors found that prohibition motivates individuals to commit offences such as burglaries to fund their habit. This lowers life expectancy because people end up in prison, and triggers a 'multitude' of health-related costs from unsafe drug use.

Communities are damaged by illicit markets which undermine drug purity, with Black and Hispanic men more likely to end up in the criminal justice system. The war on drugs makes people more vulnerable to violations of their rights including what they choose to put in their bodies.

In contrast, the study highlights the liberal approach of countries such as Portugal where drug-related deaths have fallen and where users are encouraged to seek treatment.

An estimated £43.5bn ($58bn) could be generated in federal, state and local tax revenues through the legalization of drugs, according to the findings. This compares with an annual federal, state and local spend of more than £35bn ($47bn) on prohibition.

The authors stress that non-violent prisoners found with a small amount of illegal substances should be released.

A new computational analysis suggests that a vaccine or medication that could shorten the infectious period of COVID-19 may potentially prevent millions of cases and save billions of dollars. The study was led by Bruce Lee along with colleagues in the Public Health Informatics, Computational, and Operations Research (PHICOR) team headquartered at the CUNY Graduate School of Public Health and Health Policy and the Lundquist Research Institute at Harbor-UCLA Medical Center, and publishes in the open-access journal PLOS Computational Biology.

While much of the public conversation surrounding COVID-19 vaccines and medications has focused on preventing or curing the infection, the vaccines and medications that may emerge could have subtler effects. Those that can't necessarily prevent or cure may still reduce how long someone is contagious.

To clarify the potential value of shortening the infectious period, Lee and colleagues created a computational model that simulates the spread of SARS-CoV-2, the virus that causes COVID-19. They used the model to explore how a vaccine or medication that can reduce the contagious period might alleviate the clinical and economic impact of the disease.

The simulations suggest that reducing the contagious period by half a day could avert up to 1.4 million cases and over 99,000 hospitalizations, saving $209.5 billion in direct medical and indirect costs--even if only a quarter of people with symptoms were treated--and incorporating conservative estimates of how contagious the virus may be. Under the same circumstances, cutting the contagious period by 3.5 days could avert up to 7.4 million cases. Expanding such treatment to 75 percent of everyone infected could avert 29.7 million cases and save $856 billion.

These findings could help guide research and investments into development of vaccines or medications that reduce the infectious period of SARS-CoV-2. They could also help government agencies plan rollout of such products and provide cost insights to guide reimbursement policies for third-party payers.

"There may be a tendency to overlook vaccines and other treatments that don't prevent a COVID-19 infection or cure disease," says Lee. "But this study showed that even relatively small changes in how long people are contagious can significantly affect the transmission and spread of the virus and thus save billions of dollars and avert millions of new cases."

"This study shows that vaccine and medication development efforts for COVID-19 should focus on the impact to actually help curb the spread of the COVID-19 pandemic, not just benefits of a single patient," says James McKinnell, a co-author of the study. "Widespread treatment, in combination with other prevention efforts, could prove to be the tipping point."

Using stem cells to regenerate parts of the skull, scientists corrected skull shape and reversed learning and memory deficits in young mice with craniosynostosis, a condition estimated to affect 1 in every 2,500 infants born in the United States, according to the Centers for Disease Control and Prevention. The only current therapy is complex surgery within the first year of life, but skull defects often return afterward. The study, supported by the National Institute of Dental and Craniofacial Research (NIDCR), could pave the way for more effective and less invasive therapies for children with craniosynostosis. The findings were published Jan. 7, 2021 in Cell. NIDCR is part of the National Institutes of Health.

"This is a pivotal study demonstrating both structural regeneration and functional restoration in an animal model of craniosynostosis, said Lillian Shum, Ph.D., director of NIDCR's Division of Extramural Research. "It holds great potential for translation to treatment of the human condition."

Healthy infants are born with sutures--flexible tissue that fills the space between the skull bones--that allow the skull to expand as the brain grows rapidly in the first few years of life. In craniosynostosis, one or more sutures turn into bone too early, closing the gap between skull plates and leading to abnormal growth. The resulting increase in pressure inside the skull may cause physical changes in the brain that lead to thinking and learning problems.

"The connection between changes in the skull and the development of cognitive deficits had not been fully explored," said Yang Chai, D.D.S., Ph.D., director of the Center for Craniofacial Molecular Biology and associate dean of research at the Herman Ostrow School of Dentistry at the University of Southern California, Los Angeles, who led the study. "We wanted to know if restoring sutures could improve neurocognitive function in mice with mutations in a gene that causes craniosynostosis in both mice and humans."

That gene, called TWIST1, is thought to be important for suture formation during development. In humans, mutations in this gene can lead to Saethre-Chotzen syndrome, a genetic condition characterized by craniosynostosis and other skeletal abnormalities.

To see if flexible sutures could be restored in mice with craniosynostosis due to Twist1 mutations, the scientists focused on a group of stem cells normally found in healthy sutures. Previous studies by the group indicated that these stem cells--called Gli1+ cells--are key to keeping skull sutures of young mice intact. The team had also found that Gli1+ cells are depleted from the sutures of mice that develop craniosynostosis due to Twist1 mutations. Chai and his colleagues reasoned that replenishing the cells might help regenerate the flexible sutures in affected animals.

To test this idea, the researchers added Gli1+ cells from healthy mice to a biodegradable gel. They deposited the mixture into grooves meant to re-create the space where skull sutures had been in mice with craniosynostosis.

Skull imaging and tissue analysis revealed that after six months, new fibrous sutures had formed in treated areas and that the new tissue remained intact even after a year. In contrast, the same grooves closed in mice that received a gel that lacked Gli1+ cells.

Closer analysis showed that Gli1+ cells in the regrown sutures had different origins: some were descended from the cells that had been implanted, while others were the animals' own, having migrated from nearby areas. The findings suggest that Gli1+ cell implantation leads to suture regeneration in part by recruiting native Gli1+ stem cells to help in the process.

Further experiments showed that untreated mice with craniosynostosis had increased pressure inside their skulls and poor performance on tests of social and spatial memory and motor learning. After treatment, these measures all returned to levels typical of healthy mice. The skull shapes of treated mice were also partially corrected.

The treatment also reversed the loss of brain volume and nerve cells in areas involved in learning and memory. According to the scientists, this finding sheds light on the mechanisms underlying impaired brain function and its improvement after suture regeneration.

"We have discovered that Gli1+ stem-cell-based suture regeneration restores not only skull shape but also neurocognitive functions in a mouse model of craniosynostosis," said Chai.

The scientists note that more work remains before such an intervention can be tested in humans, including studies to determine the optimal timing of surgery and the ideal source and amount of stem cells.

"This study provides a foundation for efforts to develop a less-invasive, stem cell-based therapeutic strategy that can benefit patients who suffer from this devastating disorder," Chai said.

Humans feeding leftover lean meat to wolves during harsh winters may have had a role in the early domestication of dogs, towards the end of the last ice age (14,000 to 29,000 years ago), according to a study published in Scientific Reports.

Maria Lahtinen and colleagues used simple energy content calculations to estimate how much energy would have been left over by humans from the meat of species they may have hunted 14,000 to 29,000 years that were also typical wolf prey species, such as horses, moose and deer. The authors hypothesized that if wolves and humans had hunted the same animals during harsh winters, humans would have killed wolves to reduce competition rather than domesticate them. With the exception of Mustelids such as weasels, the authors found that all prey species would have supplied more protein than humans could consume, resulting in excess lean meat that could be fed to wolves, thus reducing the competition for prey.

Although humans may have relied on an animal-based diet during winters when plant-based foods were limited, they were probably not adapted to an entirely protein-based diet and may have favoured meat rich in fat and grease over lean, protein-rich meat. As wolves can survive on a solely protein-based diet for months, humans may have fed excess lean meat to pet wolves, which may have enabled companionship even during harsh winter months. Feeding excess meat to wolves may have facilitated co-living with captured wolves and the use of pet wolves as hunting aids and guards may have further facilitated the domestication process, eventually to full dog domestication.

Policymakers around the world tend to reference new and highly cited COVID-19 research papers in their policy documents regarding the pandemic, Yian Yin and colleagues conclude after analyzing publications of both types from the first half of 2020. "Overall, this result shows that the coronavirus research used by policymakers aligns with what scientists heavily engage themselves," they write in a Policy Forum. Although government agencies produced more COVID-19 documents compared to think tanks and intergovernmental organizations such as the World Health Organization, Yin et al. found that governmental agencies are the least likely to cite science. Organizations like WHO are the most likely institutions to cite science, they write, suggesting that these organizations can act as "central conduits" linking policy and science in the global COVID-19 response. The researchers examined scientific citations in policy documents drawn from a database of 37,725 papers covering most major world economies and populations centers, with the exception of mainland China. The policy documents have an unusually high rate of using the newest science--10 times larger than seen for other policy documents. And policymakers draw heavily from scientific papers that are highly cited in the scientific literature. Papers referenced in the policy documents have collected on average 40 times higher citations than papers not referenced in the documents, the researchers found. Yin et al. also note that policy papers disproportionately reference peer-reviewed research published in top medical and specialty journals, despite the recent abundance and attention given to research released on preprint servers.

Social contact can transfer the feeling of pain or fear in several animal species, including humans, but the exact neural mechanisms for this transmission are still being studied. Now, Monique Smith and colleagues demonstrate that the social transmission of pain and pain relief in mice is mediated by neural projections from the brain's anterior cingulate cortex (ACC) to the nucleus accumbens. The transfer of fear, however, is mediated by the ACC's projections into a different area of the brain called the basolateral amygdala. The findings help untangle the distinct neural circuits involved in empathy, which in its simplest form is the ability to "feel" the affective states of others, say the researchers. A better understanding of how empathy is created in the brain "...may teach us about what goes wrong when empathy becomes maladaptive or is hampered as is the case in several psychiatric diseases," Alexandra Klein and Nadine Gogolla note in a related Perspective. In several experiments with mice, Smith et al. show how pain and fear can be socially transferred between affected and "bystander" mice, using a mix of visual, olfactory, and auditory cues. Using optogenetic methods, among others, they traced neuronal activity in the bystander mice to pinpoint exactly how the ACC induces this effect in the brain. The study also demonstrates for the first time that pain relief via an analgesic drug can be transferred socially, possibly offering an interesting model for socially-induced pain relief among humans, the researchers note.

Richard Tyser and colleagues have mapped the origins of the embryonic mouse heart at single-cell resolution, helping to define the cell types that make up the heart in the earliest days of development. Their techniques allowed them to identify for a first time a pool of progenitor cells that contributes to the formation of heart muscle cells as well as the early epicardium, the outermost layer of the heart. This layer provides cells and other proteins that guide the development and repair of heart tissue, so a better understanding of its origins could better inform regenerative heart therapies as well as improve our understanding of congenital heart defects. Tyser et al. performed a micro-dissection of a portion of the embryonic mouse heart to observe a very early stage streak of cells called the cardiac crescent transform into the linear heart tube. Combining single-cell RNA sequencing to identify cell types with high-resolution imaging and time-lapse microscopy, the researchers were able to follow the development of distinct populations of progenitor heart cells over about 12 hours of development.

The National Human Genome Research Institute (NHGRI) within the National Institutes of Health (NIH) has released a new action agenda for a diverse genomics workforce. This ambitious set of goals, objectives, and implementation strategies details NHGRI's plans for enhancing the diversity of the genomics workforce by 2030.

"To reach its full potential, the field of genomics requires a workforce that better reflects the diversity of the U.S. population," NHGRI Director Eric Green, M.D., Ph.D., said. "Fostering an appropriately diverse genomics workforce of the future requires an immediate and substantial commitment of attention and resources. Our new action agenda aims to bring both short- and long-term changes that will make genomics a more-inclusive discipline."

Accompanying the release of this action agenda today is a commentary authored by Dr. Green and Vence Bonham, J.D., senior advisor to the NHGRI director on genomics and health disparities, in the latest issue of ASHG's American Journal of Human Genetics, which explains the strategic imperative to make the genomics workforce more diverse.

A critical first step in implementing the action agenda is a comprehensive survey announced today by the American Society of Human Genetics, in cooperation with the American College of Medical Genetics and Genomics, the National Society of Genetic Counselors and others, to collect baseline data on the existing demographic landscape of the U.S. human genetics and genomics workforce. The survey will be launched in mid-to-late January.

The action agenda is a direct extension of the 2020 NHGRI Strategic Vision for the future of human genomics. The vision identifies priorities and opportunities for the next decade -- both within research and the research community-at-large -- to improve human health at The Forefront of Genomics.

A key priority that the strategic vision emphasizes is championing a diverse genomics workforce because "the promise of genomics cannot be fully achieved without attracting, developing, and retaining a diverse workforce, which includes individuals from groups that are currently underrepresented in the genomics enterprise."

To develop an overarching plan for this priority area, NHGRI established an internal Genomic Workforce Diversity Working Group last year. Chaired by Bonham, the group worked in earnest to develop the new action agenda.

"We listened to as many voices as possible as we were building the action agenda," Bonham said. "We actively sought broad input by seeking public comments and interviewed research university leaders and early career genomics professionals. This outreach has led to a plan that will propel the genomics field to make a much-needed change to our workforce."

The action agenda highlights groups that have been identified by NIH as underrepresented in biomedical, clinical, behavioral and social sciences. These groups include individuals from underrepresented racial and ethnic groups and disadvantaged backgrounds, persons with disabilities and women at the senior faculty level.

The plan describes four major goals:

Develop and support initiatives that provide early exposure and access to careers in genomics.

Develop and support training programs and networks that connect undergraduate and graduate education to careers in genomics.

Develop and support training, career development and research transition programs that lead to independent research and clinical careers in genomics.

Evaluate progress towards achieving greater diversity in the genomics workforce.

The new action agenda aims to build on NHGRI's history of funding diversity training programs, many of which have successfully helped to increase the number of underrepresented scientists who pursue genomics-related careers. The institute has also supported science education programs that provide genomics training to secondary school teachers, community college staff and tribal college and university faculty.

"With programs in place and new ones to start, the challenging but essential work begins now. Through sustained effort, dedication and creativity, we believe we can make the genomics workforce better reflect our diverse society," Dr. Green said.

Noncognitive skills and cognitive abilities are both important contributors to educational attainment -- the number of years of formal schooling that a person completes -- and lead to success across the life course, according to a new study from an international team led by researchers at Columbia University Mailman School of Public Health, the University of Texas at Austin, and Vrije Universiteit Amsterdam. The research provides evidence for the idea that inheriting genes that affect things other than cognitive ability are important for understanding differences in people's life outcomes. Until now there had been questions about what these noncognitive skills are and how much they really matter for life outcomes. The new findings are published in the journal Nature Genetics.

"Genetic studies of educational attainment were initiated with the goal of identifying genes that influenced cognitive abilities. They've had some success in doing that. But it turns out they've also identified genetics that influence a range of other skills and characteristics.," said Daniel Belsky, PhD, assistant professor of epidemiology. "What was most surprising to me about our results was that these noncognitive skills contributed just as much to the heritability of educational attainment as cognitive ability." Of the total genetic influence on educational attainment, referred to as the heritability, cognitive abilities accounted for 43 percent and noncognitive skills accounted for 57 percent.

Similar to the genetics of cognitive abilities, the genetics of noncognitive skills were related to achievements outside of schooling, including holding more prestigious jobs, earning higher incomes, and living longer. And, genes associated with noncognitive skills showed relationships with these other life outcomes that were as strong or stronger than the relationships seen with cognitive genetics. "These results were important proof of concept," observed Belsky, who is also with the Robert N Butler Columbia Aging Center. "They showed us that noncognitive skills genetics have implications for economics and public health similar to the genetics of cognitive abilities."

The study used a method called a "genome-wide association study," or GWAS, to study what economists have called "noncognitive skills,"defined as behaviors and abilities that are not measured by traditional IQ tests but are thought to help people be more successful in school, in their jobs, and in life generally. The study builds on results from a previous study that conducted a GWAS of educational attainment. The researchers applied a new statistical method to develop an understanding of the substance of noncognitive skills, and how genetic correlations with noncognitive skills diverged from genetic correlations with cognitive abilities, as measured by standardized tests of IQ.

"Borrowing a strategy from economists who studied people with the same cognitive ability but different years of education enabled us to associate the variations in how far people go in school above and beyond their association with cognitive test performance. We were able to conduct this type of analysis using a new method we developed called Genomic Structural Equation Modeling, which is a way of combining data from multiple GWASs at the same time," said Michel Nivard, assistant professor of biological psychology at the Vrije Universiteit Amsterdam and co-leader of the study. "This approach allows us to leverage the power of giant genetic databases like UK Biobank to study the genetics of traits and behaviors that were not directly measured in the research participants." Using this novel method, the researchers were able to conduct GWAS of noncognitive skills in data from hundreds of thousands of individuals.

"Our GWAS identified 157 different locations in the human genome that related to noncognitive skills.," said Perline Demange, a PhD candidate in biological psychology at the Vrije University, Amsterdam and a lead author of the paper together with Margherita Malanchini, lecturer in psychology at the Queen Mary University of London. "Our GWAS identified signals from genes that are disproportionately active in brain tissues, similar to what has been found for the genetics of cognitive abilities."

The individual genetic associations discovered in the GWAS were very small in magnitude. "Any individual genetic variant really had a trivial influence on the phenotype.," explained Malanchini, "However, by adding up these tiny associations, we can create composite measures called polygenic scores. These measures can then be applied to genetic data from research participants to estimate how likely someone is to show a particular outcome (or phenotype)." In this paper, polygenic scores were created in six data U.K., and New sets from people born at different times throughout the 20th century in the Netherlands, the U.S., the Zealand. They also calculated genetic correlations between noncognitive skills and other phenotypes that have been the focus of large GWASs, such as obesity, smoking, and psychiatric diseases.

Overall, the genetics of noncognitive skills were associated with higher tolerance of risks, greater willingness to forego immediate gratification, less health-risk behavior, and delayed fertility. Researchers also observed that noncognitive skill genetics were associated with a constellation of personality traits linked with success in relationships and at work, such as being curious and eager to learn, being more emotionally stable, and being more industrious and orderly.

"There has been much debate about what noncognitive skills are and how best to measure them. Motivation, persistence, grit, curiosity, self-control, growth mindset -- these are just a few of the things that people have suggested are important noncognitive skills," observed Paige Harden, professor of psychology at the University of Texas at Austin and a co-leader of the research along with Belsky and Nivard. "For personality and risk behavior, we saw relationships we expected; noncognitive skills genetics were associated with less risky behavior and a personality profile we associate with maturity, and social and professional competency," said Harden. But the results for mental health were a surprise."

The researchers found that noncognitive skills genetics that were associated with educational attainment were also associated with increased risk for schizophrenia, bipolar disorder, obsessive compulsive disorder, and anorexia nervosa. "This is an example of what geneticists call pleiotropy.," explained Harden. "Our result warns us against a simplistic view of genetic variants being good or bad. The same genetic variant that predisposes someone to go further in school might also elevate their risk of developing schizophrenia or another serious mental disorder."

The authors also released an FAQ to accompany their paper, which warns against using the results of this study - or any genetic research - as evidence that children's educational performance or noncognitive skills cannot be improved with intervention or policy. Harden cautions that, "Genetic influence must always be understood through the lens of history and social structures. These results tell us about what is, not what could be. Nothing about our study should discourage investments in ensuring that all children reach their maximum potential."

What The Study Did: Under a range of assumptions of presymptomatic transmission and transmission from individuals with infection who never develop symptoms, the model presented here estimated that more than half of transmission comes from asymptomatic individuals.

Author: Jay C. Butler, M.D., of the U.S. Centers for Disease Control and Prevention in Atlanta, 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/jamanetworkopen.2020.35057)

Editor's Note: The article includes 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.

What The Study Did: To adapt to broader public health initiatives around COVID-19, researchers developed a drive-through intraocular pressure (IOP) screening clinic to minimize COVID-19 exposure for patients and clinicians by measuring eye pressure in the unconventional setting of a clinic parking lot.

Authors: Miel Sundararajan, M.D., of the University of California, San Francisco, 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/jamaophthalmol.2020.6073)

Editor's Note: The article includes conflict 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.

What The Study Did: The outcomes of a cancer center-wide virtual care program launched in response to the COVID-19 pandemic were examined in this study.

Authors: Alejandro Berlin, M.D., M.Sc., of the Princess Margaret Cancer Centre in Toronto, Ontario, Canada, 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/jamaoncol.2020.6982)

Editor's Note: The article includes conflict 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.

What The Study Did:This cross-sectional study maps a coronavirus research question to illustrate the overlap and shortcomings of the evidence syntheses in this area.

Author: Giordano Pérez-Gaxiola, M.D., M.Sc., of Sinaloa Pediatric Hospital's Cochrane Associate Centre in Culiacan, Mexico, 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/jamanetworkopen.2020.32769)

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

Research from life-saving charity Air Ambulance Kent Surrey Sussex (KSS) in partnership with the University of Surrey has shown the benefits of dispatching HEMS to patients with a sudden, unexplained LOC of medical origin and a high prevalence of acute neurological pathology.

The study - which is believed to be the first published about HEMS dispatch to non-trauma (neuro) cases - also highlights how HEMS dispatchers in dialogue with ambulance personnel are able to select patients requiring HEMS-specific interventions and, based on its findings, identifies opportunities to improve triage for these patients.

Through a retrospective study of all patients with a LOC attended by KSS between 2nd July 2013 and 19th December 2017 the research found:

127 patients with unexplained LOC were attended by KSS, with KSS being dispatched directly to 25% of the patients and 75% on request of the ground ambulance crews

KSS was required to perform a specialist HEMS intervention in 65% of these patients

77% of these patients were conveyed to hospital by KSS

Sudden LOC in the pre-hospital setting in the absence of cardiac arrest and seizure activity presents a challenge from a dispatcher's perspective: the aetiology is varied, with many causes being transient and mostly self-limiting.

However, other causes are potentially life-threatening, with patients requiring the expertise of HEMS. HEMS teams have enhanced knowledge and skills which mean they are able to deliver specific advanced treatments, ordinarily only available in hospital, which can address some of the cause of the LOC. HEMS involvement has been shown to shorten scene times for critically ill patients , and expedite transport times to hospital.

But HEMS is a scarce resource and, as this study shows, there is an opportunity to improve triage for non-trauma patients. This will enable greater accuracy and will potentially help more patients presenting with unexplained life-threatening LOC.

Commenting, Professor Richard Lyon MBE, Associate Medical Director at KSS and Professor in Pre-Hospital Emergency Care at the University of Surrey said:

"We know specialist interventions, like emergency anaesthesia, when delivered at the scene of an accident, can significantly improve the outcome for patients with traumatic brain injury. This study highlights there is a group of patients who suffer sudden neurological emergencies who may also benefit from the air ambulance attending to rapidly deliver hospital-level intensive care."

"HEMS is a valuable but scarce medical resource so it is crucial the HEMS crew is tasked to those patients likely to have the most benefit. KSS is a charity, reliant upon public donations and fundraising for the £15 million it costs each year to deliver its service for the 4.8 million people it serves."

"Improving triage for these patients is key, so that those patients who need immediate critical care, receive it as quickly as possible. Further research, in partnership with the University of Surrey, is now underway to explore how to improve air ambulance dispatch to medical cases, including exploring using live video footage from 999 callers."

(New York, NY - January 6, 2021) - Researchers at the Icahn School of Medicine at Mount Sinai have identified three major molecular subtypes of Alzheimer's disease (AD) using data from RNA sequencing. The study advances our understanding of the mechanisms of AD and could pave the way for developing novel, personalized therapeutics.

The work was funded by the National Institute on Aging, part of the National Institutes of Health (NIH), and published in Science Advances on January 6, 2021.

RNA is a genetic molecule similar to DNA that encodes the instructions for making proteins. RNA sequencing is a technology that reveals the presence and quantity of RNA in a biological sample such as a brain slice.

Alzheimer's disease is the most common form of dementia, but it is quite diverse in its biological and pathological manifestations. There is growing evidence that disease progression and responses to interventions differ significantly among Alzheimer's patients. Some patients have slow cognitive decline while others decline rapidly; some have significant memory loss and an inability to remember new information while others do not; and some patients experience psychosis and/or depression associated with AD while others do not.

"Such differences strongly suggest there are subtypes of AD with different biological and molecular factors driving disease progression," said Bin Zhang, PhD, the lead author of the study, Director of the Center for Transformative Disease Modeling, and Professor of Genetics and Genomic Sciences at the Icahn School of Medicine.

To identify the molecular subtypes of AD, the researchers used a computational biology approach to illuminate the relationships among different types of RNA, clinical and pathological traits, and other biological factors that potentially drive the disease's progress. The research team analyzed RNA-sequencing data of more than 1,500 samples across five brain regions from hundreds of deceased patients with AD and normal controls, and identified three major

molecular subtypes of AD. These AD subtypes were independent of age and disease stage, and were replicated across multiple brain regions in two cohort studies.

These subtypes correspond to different combinations of multiple dysregulated biological pathways leading to brain degeneration. Tau neurofibrillary tangle and amyloid-beta plaque, two neuropathological hallmarks of AD, are significantly increased only in certain subtypes.

Many recent studies have shown that an elevated immune response may help cause Alzheimer's. However, more than half of AD brains don't show increased immune response compared to normal healthy brains. The analysis further revealed subtype-specific molecular drivers in AD progression in these samples. The research also identified the correspondence between these molecular subtypes and the existing AD animal models used for mechanistic studies and for testing candidate therapeutics, which may partially explain why a vast majority of drugs that succeeded in certain mouse models failed in human AD trials, which likely had participants belonging to different molecular subtypes.

Although the subtyping described by the researchers was performed post mortem using the patients' brain tissue, the researchers said that if the findings were validated by future studies, they could lead to the identification in living patients of biomarkers and clinical features associated with these molecular subtypes and earlier diagnosis and intervention.

"Our systematic identification and characterization of the robust molecular subtypes of AD reveal many new signaling pathways dysregulated in AD and pinpoint new targets," said Dr. Zhang, "These findings lay down a foundation for determining more effective biomarkers for early prediction of AD, studying causal mechanisms of AD, developing next-generation therapeutics for AD and designing more effective and targeted clinical trials, ultimately leading to precision medicine for AD. The remaining challenges for future research include replication of the findings in larger cohorts, validation of subtype specific targets and mechanisms, identification of peripheral biomarkers and clinical features associated with these molecular subtypes."

The AD subtyping study is supported by the NIH National Institute on Aging (NIA) and is part of the NIA-led Accelerating Medicines Partnership - Alzheimer's Disease (AMP-AD) Target Discovery and Preclinical Validation program. This public private partnership aims to shorten the time between the discovery of potential drug targets and the development of new drugs for Alzheimer's disease treatment and prevention.