Culture

People who live through traumatic experiences in childhood often suffer long-lasting consequences that affect their mental and physical health. But moreover, their children and grand-children can also be impacted as well. In this particular form of inheritance, sperm and egg cells pass on information to offspring not through their DNA sequence like classical genetic heredity, but rather via biological factors involving the epigenome that regulates genome activity. However, the big question is how the signals triggered by traumatic events become embedded in germ cells.

"Our hypothesis was that circulating factors in blood play a role," says Isabelle Mansuy, professor of neuroepigenetics at the University of Zurich's Brain Research Institute and the ETH Zurich's Institute for Neuroscience. Mansuy and her team demonstrated that childhood trauma does have a lifelong influence on blood composition and that these changes are also passed to the next generation. "These findings are extremely important for medicine, as this is the first time that a connection between early trauma and metabolic disorders in descendants is characterized," explains Mansuy.

Traumatic stress leads to metabolic changes across generations

In her study, Mansuy used a mouse model for early trauma that had been developed in her lab. The model is used to study how the effects of trauma in early postnatal life on male mice are transmitted to their offspring. To determine whether these early experiences have an impact on blood composition, the researchers conducted multiple analyses and found large and significant differences between blood from adult traumatized animals and blood from normal, non-traumatized control group.

Changes in lipid metabolism were particularly striking, with certain polyunsaturated fatty acids metabolites appearing in higher concentrations in the blood of traumatized male mice. These same changes were also observed in their offspring. Even more strikingly, when the serum of traumatized males was chronically injected into non-traumatized males, their offspring also developed metabolic symptoms of trauma - providing a direct link between circulating factors and germ cells, thus confirming the hypothesis that blood delivers stress signals to the gametes.

Comparison with traumatized children

The researchers then investigated whether similar effects are present in humans. For this, they assembled a cohort of 25 children from an SOS Children's Village in Pakistan who have lost their father and were separated from their mother, and analyzed their blood and saliva. When compared with children from normal families, the orphans showed higher level of several lipid metabolites - just like the traumatized mice.

"These children's traumatic experiences are comparable to those in our mouse model, and their metabolism show similar changes in blood," explains Mansuy. "This demonstrates the importance of animal research for providing us with fundamental insights into human health." Up to one fourth of children across the world experience violence, abuse and neglect, that can lead to chronic diseases later in their life, highlighting the importance of Mansuy's research.

Receptor interferes with gametes

Further experiments led the team to discover a molecular mechanism by which lipid metabolites can transmit signals to animals' germ cells. PPAR, a receptor at the surface of cells, plays a key role in this process; it is activated by fatty acids and regulates gene expression and DNA structure in numerous tissues. The researchers discovered that this receptor is upregulated in the sperm of traumatized males.

Artificially activating this receptor in male mice led to lower body weight and disturbances in glucose metabolism - an effect that was also seen in their offspring and grand-offspring. These and other experiments led researchers to conclude that PPAR activation in sperm cells plays a significant role in the heritability of metabolic dysfunctions caused by traumatic experiences in ancestors.

Trauma damages the health of offspring

"Our findings demonstrate that early trauma influences both mental and physical health in adulthood and across generations, which can be seen in factors like lipid metabolism and glucose levels," says Mansuy. "This is rarely taken into consideration in clinical settings." Improving the understanding of the underlying biological processes could help medical practitioners prevent the late-onset consequences of adverse life experiences in their patients in the future.

Autonomous vehicles (AV) are the wave of the future in the automobile industry, and there's extensive discussion about the impacts on transportation, society, the economy and the environment.

However, less attention has been focused on the potential health impacts of self-driving vehicles.

Texas A&M University researchers have developed a conceptual model to identify these health impacts systematically. They identified 32 transportation-related risk factors that affected health and concluded that 17 could negatively impact public health, while eight could have a positive impact. There were seven areas of uncertain implications that require further investigation.

The researchers recently published their findings in the December issue of Sustainable Cities and Society.

"A survey on the receptiveness of autonomous vehicles' impacts showed that there is a lack of awareness of the potential health impacts of AVs and low perceptions of the importance of AV health benefits," said Soheil Sohrabi, a doctoral student in the Zachry Department of Civil and Environmental Engineering and a graduate researcher at the Texas A&M Transportation Institute (TTI). "On the other hand, there are some unintended consequences of AVs' implementation that need to be studied before AVs find their way onto the road."

Sohrabi, with Dr. Dominque Lord, professor in the department and A.P. Wiley Faculty Fellow, and Dr. Haneen Khreis with TTI created a conceptual model to systematically identify the pathways through which AVs can affect public health. The proposed model summarizes the potential changes in transportation after AV implementation into seven points of impact: transportation infrastructure; land use and the built environment; traffic flow; transportation mode choice; transportation equity; and jobs related to transportation and traffic safety. The changes in transportation are then attributed to potential health impacts.

In optimistic views, AVs are expected to prevent 94% of traffic crashes by eliminating driver error, but AVs' operation introduces new safety issues such as the potential of malfunctioning sensors in detecting objects (pedestrians, bikes and cyclists, vehicles, obstacles, etc.), misinterpretation of data and poorly executed responses, which can jeopardize the reliability of AVs and cause serious safety consequences in an automated environment.

Another possible safety consideration is the riskier behavior of users because of their overreliance on AVs -- for example, neglecting the use of seatbelts due to an increased false sense of safety.

AVs have the potential to shift the people from public transportation and active transportation such as walking and biking to private vehicles in urban areas, which can result in more air pollution and greenhouse gas emissions and create the potential loss of driving jobs for those in the public transit or freight transport industries.

The model serves researchers in the fields of transportation engineering and urban planning as well as automotive makers, health sectors and policymakers to identify the potential pathways through which AVs can affect public health, and to investigate the impacts, quantify them and develop policies to mitigate them.

"Given the very fast-paced research related to AVs, this work provides very good preliminary guidelines about how AVs can negatively and positively affect the general health of people before their full deployment," Lord said. "Hence, engineers, planners and policymakers can already examine measures and policies that could mitigate the negative health effects."

"This study can urge public health sectors to enter the discussion about AVs and contribute to supporting policies that address the potential negative impacts," Sohrabi said. "It also increases the public awareness of the health impacts of AVs that can facilitate the acceptance of AV regulations and motivate them to use this new technology and ultimately, benefit the greater good."

In the future, Sohrabi said more research is needed to clarify public health impacts of AVs more accurately. This study was primarily focused on urban areas and does not take into account the affects of AVs in rural areas.

"The discussion about the health implications of AVs is new and limited," he said. "Next, we will be working on quantifying the health implications of AVs."

Researchers at the University of Colorado Boulder and the University of Colorado Anschutz Medical Campus have developed a new way to diagnose diseases of the blood like sickle cell disease with sensitivity and precision and in only one minute. Their technology is smaller than a quarter and requires only a small droplet of blood to assess protein interactions, dysfunction or mutations.

The team published its results Oct. 15 in the journal Small.

"In Africa, sickle cell disease is the cause of death in 5% of children under 5-years-old for lack of early diagnosis," said Angelo D'Alessandro, a coauthor of the study and associate professor in the departments of Biochemistry and Molecular Genetics and Medicine, Division of Hematology at CU Anschutz. "This common, life-threatening genetic disorder is most prevalent in poor regions of the world where newborn screening and diagnosis are rare."

Sickle cell disease affects hemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body. In some areas of the world where malaria is endemic, variants of hemoglobin have evolved that can cause red blood cells to assume a crescent, or sickle, shape.

"Almost all life activities involve proteins," said study coauthor Xiaoyun Ding, an assistant professor in the Paul M. Rady Department of Mechanical Engineering at CU Boulder. "We thought if we could measure the protein thermal stability change, we could detect these diseases that affect protein stability."

Proteins have a specific solubility at a specific temperature. When one bonds to another, or when the protein is mutated, the solubility changes. By measuring solubility at different temperatures, researchers can tell whether the protein has been mutating.

Before recent developments, study coauthor Michael Stowell, an associate professor in the Department of Molecular, Cellular and Developmental Biology (MCDB) at CU Boulder, and his colleagues used Thermal Shift Assays (TSAs) to assess protein stability under varying conditions. Such tests took about a day to run. Now, with the new technology, an Acousto Thermal Shift Assay (ATSA), they can do the same but faster and with greater sensitivity.

The ATSA utilizes high-amplitude sound waves, or ultrasound, to heat a protein sample. The tool then measures data continuously, recording how much of the protein has dissolved at every fraction of change in degrees Celsius.

"Our method is seven to 34 times more sensitive," said Ding. "The ATSA can distinguish the sickle cell protein from normal protein, while the traditional TSA method cannot."

Another benefit of the ATSA is cost reduction in terms of human labor and equipment.

"The traditional methods for thermal profiling require specialized equipment such as calorimeters, polymerase chain reaction machines and plate readers that require at least some technical expertise to operate," said Kerri Ball, a coauthor of the new study and a researcher who works with Stowell at CU Boulder. "These instruments are also not very portable, requiring samples to be transported to the instruments for analysis."

Ball said the ATSA requires only a power source, a microscope and a camera as simple as the one on your smart phone. Because the protein is concentrated, there is also no need to apply a florescent dye as is sometimes required to highlight protein changes in a traditional TSA.

A unique study conducted by University of Georgia entomologists led to the discovery of a distinctive supergene in fire ant colonies that determines whether young queen ants will leave their birth colony to start their own new colony or if they will join one with multiple queens.

Researchers also found that ants were more aggressive toward queens who don't possess the supergene, causing main colony workers to kill them. This critical finding opens the door to new pest control methods that may be more efficient in eradicating problematic fire ant colonies.

"Learning about the way fire ants behave is very important baseline information," said Ken Ross, a professor of entomology at UGA. "This information is key to helping us manage pest populations and predict what dissimilarities can happen in their environment."

A supergene is a collection of neighboring genes located on a chromosome that are inherited together due to close genetic linkage. Studying these unique genes is important to understanding the potential causes for differences among the social structure of fire ants, specifically for controlling the species and building on the existing knowledge base.

Researchers focused on young queen fire ants embarking on nuptial flights. They compared the supergene's impact on the fire ants' two primary types of social structures: monogyne, which is reproduction from queens that form a new nest, and pologyne, reproduction from queens that join an existing nest.

Ross initially worked alongside colleagues in his lab to discover a remarkable example of genetically encoded differences in social organization within the fire ant species Solenopsis invicta. The next step was to understand how these genetic differences result in complex behavioral and physiological variations among ants from single queen colonies versus colonies with multiple queens. Compounding this knowledge helps scientists further understand patterns of development in the species, increasing alternatives to combat invasive populations.

Led by a pair of UGA entomology graduate alumni, Joanie King, who earned her master's degree in 2017, and Samuel Arsenault, who earned his doctoral degree in 2020, the team developed an experimental design that utilized a collection of samples from two fire ant organs -- brain and ovarian tissues -- and the complete range of social chromosome genotypes and social forms within this fire ant species.

The innovative study incorporated various scientific methods, leading to a collaboration of tools and resources throughout many areas of the institution.

"UGA was a very supportive environment to conduct this research," said Brendan Hunt, associate professor of entomology. "We received help preparing samples for RNA sequencing from Dr. Bob Schmitz's lab in the genetics department, performed the sequencing at the Georgia Genomics and Bioinformatics Core, and utilized computational resources from the Georgia Advanced Computing Resource Center to analyze the data."

These types of student-led projects give young researchers the chance to grow in a hands-on environment with mentorship and guidance from scientists with proven track records in the field.

"The graduate students gained experience that helped them transition to the next stages of their careers," said Hunt. "Both have gone on to continue their studies of ant genetics."

TALLAHASSEE, Fla. -- Researchers are learning more about the brightly colored bacterial mats threatening the ecological health of coral reefs worldwide. In new research released this month, a Florida State University team revealed that these mats are more complex than scientists previously knew, opening the door for many questions about how to best protect reef ecosystems in the future.

FSU Assistant Professor of Biological Science Sophie McCoy and doctoral student Ethan Cissell published their findings in the journal Science of the Total Environment.

"By targeting the full biological diversity of these mat communities on reefs, and by studying the transcriptome, which gives us information about which biochemical processes are being used by those organisms, we're opening the door to a more complete understanding of the entire ecological role of mats," McCoy said.

Though these cyanobacterial mats have been examined in the past, scientists focused on characterizing the cyanobacteria. Cissell and McCoy found that cyanobacteria only made up about 47.57% of the mats. Their analysis showed that mats also contained a type of algae called diatoms, fungi, a single cell organism called archaea, viruses and other forms of bacteria.

"We know from other well-characterized systems that cyanobacteria, even in bloom-forming scenarios, associate with a diversity of other microorganisms that make significant and unique contributions to the overall dynamics and ecophysiology of these cyanobacteria-dominated consortia," Cissell said. "We set out to determine if similar associations are found in proliferating cyanobacterial mats on coral reefs."

Cyanobacterial mats have posed a huge problem for coral reef health. Coral reef bacteria have always played an important role in these ecological communities, but the growth -- largely attributed to local and global climate stressors -- has threatened to totally snuff out the life of precious corals.

Previously, the bacteria covered about 1% of reefs, but that has grown to 20 to 30% in some places.

Researchers said this greater understanding of the communities comprising the mats leads to more questions about how the mats form and grow.

"What this means is that the mechanisms controlling mat bloom dynamics on coral reefs are likely more complex than previously thought," Cissell said. "These data we present provide important baselines for future mechanistic-based exploration of the processes driving the growth, persistence, and decline of benthic cyanobacterial mats."

McCoy and Cissell conducted 29 diving expeditions in Bonaire, an island municipality of the Netherlands off the coast of Venezuela, for the project. They are currently conducting genetic sequencing on mat samples to get a better understanding of daily patterns of the communities comprising the mat. They are also examining samples taken from a dying mat to better understand compositional and functional shifts associated with mat death.

CHICAGO, Oct. 15, 2020 -- Although assumed to be at high risk for COVID-19, fewer than one percent of dentists nationwide were found to be COVID-19 positive, according to a first-of-its-kind report in the U.S. based on data collected in June 2020. The result is far below that of other health professionals in the U.S. In addition, 99 percent of dentists are using enhanced infection control procedures such as screening protocols and enhanced disinfection practices when treating patients. The report, published online ahead of print by The Journal of the American Dental Association, is the first large-scale collection and publication of U.S. dentists' infection rates and infection control practices related to COVID-19.
"This is very good news for dentists and patients," said American Dental Association (ADA) Science and Research Institute Chief Executive Officer Marcelo Araujo, D.D.S., M.S., Ph.D., the senior author of the report. "This means that what dentists are doing - heightened infection control and increased attention to patient and dental team safety - is working."

Dr. Araujo added that the authors of the report, researchers from the ADA Science and Research Institute and Health Policy Institute based in Chicago, are continuing to collect and will report infection rate data on dentists and have added hygienists to their ongoing survey, in collaboration with the American Dental Hygienists Association.
This report focused on nearly 2,200 dentists in June, finding that 82 percent of dentists were asymptomatic for one month prior to the survey and 16.6 percent reported getting a COVID-19 test. Those who tested positive were not clustered in any particular geographic region. Among those not tested, less than one percent (0.32) were given a probable COVID-19 diagnosis by a physician. The authors weighted the results to align with U.S. dentists demographically and geographically and found an estimated prevalence of less than one percent (0.9) with a margin of error of 0.5 percent.

"Understanding the risks associated with COVID-19 transmission in the dental setting is critical to improving patient and dental team safety," said Dr. Araujo. "This study brings us another step forward in understanding what works. Dentists are following ADA and U.S. Centers for Disease Control and Prevention (CDC) guidance, and it's helping to keep the dental team and their patients as safe as possible."

In March, The New York Times listed dentistry as one of the professions at highest risk of COVID-19 based on data from O*NET, a database maintained by the U.S. Department of Labor. It was presumed that virus transmission could occur because of the close proximity between dental professionals and patients and because many dental procedures generate aerosols that may contain viral particles from infected individuals.

This newly-published report, with the extremely low rate of COVID-19 infection among dentists, supports the effectiveness of the recommendations from the CDC and ADA in preventing virus transmission.

The ADA's guidance calls for the highest level of personal protective equipment (PPE) available--masks, goggles and face shields. The ADA's interim guidance also calls for the use of rubber dams and high velocity suction whenever possible and hand scaling when cleaning teeth rather than using ultrasonic scaling to minimize aerosols.

"The fact that dentistry was named one of the most at-risk professions for infection, but has a far lower prevalence of infection compared to other health professions, is not a coincidence," said Chief Economist and Vice President of the ADA Health Policy Institute Marko Vujicic, Ph.D. "The profession has taken this issue extremely seriously, and it shows. We will continue to track the rate of COVID-19 among dentists and other facets of the pandemic affecting dentistry so it can help inform the dental profession and other industries as well."

Of the six or more different species of early humans, all belonging to the genus Homo, only we Homo sapiens have managed to survive. Now, a study reported in the journal One Earth on October 15 combining climate modeling and the fossil record in search of clues to what led to all those earlier extinctions of our ancient ancestors suggests that climate change--the inability to adapt to either warming or cooling temperatures--likely played a major role in sealing their fate.

"Our findings show that despite technological innovations including the use of fire and refined stone tools, the formation of complex social networks, and--in the case of Neanderthals--even the production of glued spear points, fitted clothes, and a good amount of cultural and genetic exchange with Homo sapiens, past Homo species could not survive intense climate change," says Pasquale Raia of Università di Napoli Federico II in Napoli, Italy. "They tried hard; they made for the warmest places in reach as the climate got cold, but at the end of the day, that wasn't enough."

To shed light on past extinctions of Homo species including H. habilis, H. ergaster, H. erectus, H. heidelbergensis, H. neanderthalensis, and H. sapiens, the researchers relied on a high-resolution past climate emulator, which provides temperature, rainfall, and other data over the last 5 million years. They also looked to an extensive fossil database spanning more than 2,750 archaeological records to model the evolution of Homo species' climatic niche over time. The goal was to understand the climate preferences of those early humans and how they reacted to changes in climate.

Their studies offer robust evidence that three Homo species--H. erectus, H. heidelbergensis, and H. neanderthalensis--lost a significant portion of their climatic niche just before going extinct. They report that this reduction coincided with sharp, unfavorable changes in the global climate. In the case of Neanderthals, things were likely made even worse by competition with H. sapiens.

"We were surprised by the regularity of the effect of climate change," Raia says. "It was crystal clear, for the extinct species and for them only, that climatic conditions were just too extreme just before extinction and only in that particular moment."

Raia notes that there is uncertainty in paleoclimatic reconstruction, the identification of fossil remains at the level of species, and the aging of fossil sites. But, he says, the main insights "hold true under all assumptions." The findings may serve as a kind of warning to humans today as we face unprecedented changes in the climate, Raia says.

"It is worrisome to discover that our ancestors, which were no less impressive in terms of mental power as compared to any other species on Earth, could not resist climate change," he said. "And we found that just when our own species is sawing the branch we're sitting on by causing climate change. I personally take this as a thunderous warning message. Climate change made Homo vulnerable and hapless in the past, and this may just be happening again."

Along with the woolly mammoth and the giant ground sloth, the sabre-toothed cats were probably among the most famous animals that lived during the Pleistocene Epoch and went extinct before the end of last ice age. Over the years, sabre-toothed cats have also been the subject of many research projects.

Now, for the first time, researchers from the University of Copenhagen have succeeded in mapping the entire nuclear genome of a sabre-toothed cat, the scimitar-toothed cat "Homotherium latidens". Their DNA study reveals what genes were highly selected upon and important in evolution of the species.

'Their genetic makeup hints towards scimitar-toothed cats being highly skilled hunters. They likely had very good daytime vision and displayed complex social behaviours. They had genetic adaptations for strong bones and cardiovascular and respiratory systems, meaning they were well suited for endurance running. Based on this, we think they hunted in a pack until their prey reached exhaustion with an endurance-based hunting-style during the day light hours,' says co-first author Michael Westbury, Postdoc at the Section for Evolutionary Genomics, GLOBE Institute, University of Copenhagen.

Abundant species

The researchers extracted DNA from a Homotherium fossil recovered from Pleistocene permafrost sediments near Dawson City, Yukon Territory, Canada. This specimen was so old it could not be dated using conventional radio-carbon dating meaning that it was at least 47.5 thousand years old.

They then used a variety of modern genomic sequencing techniques to map the entire genome of the fossil. They used complex comparative analyses to modern living cat species such as lions and tigers and showed that this sabre-toothed cat were very genetically diverse, relative to modern cat species.

'We know that genetic diversity correlates to how many of a given species that exists. Based on this, our best guess is that there were a lot of these big cats around. This also makes perfect sense given that their fossils have been found on every single continent except Australia and Antarctica,' says Michael Westbury.

Synergies with medical research and bioinformatics

Their analysis also showed that the sabre-toothed cat is very distantly related to all modern cats. They diverged from them around least 22.5 million years ago. In comparison, humans and gibbons split between 15 and 20 million years ago.

'This was an extremely successful family of cats. They were present on five continents and roamed the earth for millions of years before going extinct. The current geological period is the first time in 40 million years that earth has lacked sabretooth predators. We just missed them' says co-first author Ross Barnett.

The researchers also emphasize that their study is an example of how different fields of research can benefit from each other. They hope to see similar bioinformatics methods used on many other extinct animals in the future.

'Modern advancements within medicine and genetic research means that the sequencing methods are a lot better for us now than they were just a few years ago. On top of that, we know what specific genes are associated with in animals and humans from medical research. This means that we can infer a lot of things about extinct animals as we have done here. You could say that the fast progression of medical research has made this study possible,' says professor Tom Gilbert.

What The Article Says: This review synthesizes the literature regarding tracheostomy and laryngectomy management in the context of the COVID-19 pandemic.

Authors: José Vergara, B.Sc., S.L.P., of the University of Campinas in São Paulo, Brazil, 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/jamaoto.2020.3720)

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

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WASHINGTON - A worldwide survey conducted during the first wave of the COVID-19 pandemic found that people with certain common personality traits were less likely to shelter at home when government policies were less restrictive, according to research published by the American Psychological Association.

"We found that people who scored low on two personality traits - openness to experience and neuroticism - were less likely to shelter at home in the absence of stringent government measures, but that tendency went away when more restrictive government policies were implemented," said Friedrich Götz, MPhil, a doctoral candidate at the University of Cambridge and lead author of the study. "Initially, this was a bit astounding, as open individuals have traditionally been shown to be prone to risk taking, willing to deviate from cultural norms and likely to seek out and approach novel and unfamiliar things - all of which would arguably put them at greater risk to ignore sheltering-in-place recommendations. However, at the same time, openness is also related to accurate risk perceptions, universalism and humankind identification. Thus, in the digitalized world in which the current pandemic occurred, these qualities may have led open individuals to follow the COVID-19 outbreak in other countries, realize its severity and act accordingly."

The researchers used data from the "Measuring Worldwide COVID-19 Attitudes and Beliefs" project, a global survey that sought to assess participants' behaviors and perceptions of others' behaviors during the COVID-19 crisis as the pandemic unfolded. Götz and his colleagues analyzed responses from more than 101,000 participants in 55 countries where at least 200 people responded to the survey between March 20 and April 5, 2020. In addition to providing information on behavior, participants also provided sociodemographic data and answered a series of questions designed to measure the so-called Big Five personality traits: conscientiousness, neuroticism, agreeableness, extraversion and openness.

To assess each country's national policy stringency, the researchers used the COVID-19 Government Response Stringency Index, which assigns stringency scores based on seven policy measures - school closing, workplace closing, cancellation of public events, suspension of public transport, implementation of public information campaigns, restrictions on internal movement and international travel controls.

"Our analyses reveal that both governmental stringency and personality independently predicted sheltering-in-place rates. Not surprisingly, in areas where government policies were more stringent, people were more likely to shelter in place," said Götz.

The researchers also found that, regardless of the stringency of government policy measures, personality traits were associated with shelter-in-place behavior. For instance, people who scored high on extraversion were significantly less likely to shelter in place, while higher scores on the other four personality traits were associated with greater likelihood to shelter in place, irrespective of how strictly the government enforced its policies.

But, while people who scored low on openness and neuroticism were less likely to shelter in place when government policies were lenient, that tendency was reduced when stricter government policies were in place.

Another explanation for the findings could be political, according to Götz. People who score high on openness tend to be more liberal in their political beliefs, and in the United States - the country with the second highest number of survey responses - compliance with social distancing behaviors during the COVID-19 pandemic appears to be strongly linked to partisanship, with liberals being much more likely to comply than conservatives.

"Taken together, the results reaffirm the power of personality as a central driver of behavior, a force that is not simply eclipsed by governmental policy," said co-author Jon Jachimowicz, PhD, of Harvard University. "Still, stringent governmental policies were able to decrease the influence of two personality traits, demonstrating how macro-level forces can diminish the influence of certain micro-level factors."

Because personality plays such a crucial role as governments continue to relax and reinstate tight government rules in reaction to changes in the spread of disease, it is important to understand why some people flout the rules more than others, according to Jachimowicz. Learning what characterizes such people can be informative in multiple ways, from helping to identify potential super-spreaders to tailoring public health messages to people's personalities in order to increase compliance.

15th October 2020, Hong Kong: Published today in the journal GigaScience is a new open source, cloud-based tool called IDseq that makes it possible to rapidly detect, identify, and track emerging pathogens such as SARS-CoV-2. This tool can identify pathogens before there is an available complete genome sequence; thus, it can be used for current infectious disease outbreaks and also for emerging ones. This will substantially aid in preventing future pandemics.

The coronavirus pandemic demonstrates the importance of global infectious disease monitoring. Finding the cause of an infectious disease outbreak is challenging, especially if it stems from a previously unknown pathogen. IDseq, an open source, cloud-based metagenomic analysis platform, identifies both novel and existing disease-causing pathogens from a given sample -- be it a human, animal, or parasite -- to provide an actionable report of what is happening on the ground in labs and clinics anywhere in the world.

"IDseq can be thought of as an early warning radar for emerging or novel infectious agents," said Joe DeRisi, PhD, Co-President of the Chan Zuckerberg Biohub, who contributed to the identification of the SARS coronavirus in 2003 and whose research lab at the University of California, San Francisco initiated the IDseq tool. It is designed to enable the global health community to leverage the ever-decreasing cost of sequencing for tracking and identifying infectious disease in essentially any sample. "At the beginning of the coronavirus pandemic, researchers in Cambodia used IDseq to help confirm and sequence the whole genome of the country's first case of COVID-19 in a matter of days, and in California, we're providing critical SARS-CoV-2 genomic data to public health officials to inform contact tracing and intervention strategies."

In a study published in GigaScience, scientists use various approaches to demonstrate that the IDseq tool is indeed able to reliably identify emerging pathogens, among them, as proof of principle, a nasal swab from a COVID-19 patient in Cambodia. A partnership between the Chan Zuckerberg Biohub, the Chan Zuckerberg Initiative (CZI), and the Bill and Melinda Gates Foundation enabled these researchers to sequence and confirm the country's first case of COVID-19 in a matter of days -- not the weeks it could typically take. The results demonstrate that IDseq can detect the presence of an emerging pathogen prior to the existence of a full reference genome. IDseq also now contains a new workflow for building SARS-CoV-2 consensus genomes.

"Metagenomic sequencing (mNGS) is an incredibly useful tool for pathogen detection because of its highly sensitive and hypothesis-free nature," said Katrina Kalantar, Computational Biologist at CZI. "We've seen labs that are using IDseq for existing mNGS studies rapidly pivot their focus to more targeted sequencing of SARS-CoV-2, which has helped researchers better understand coronavirus transmission patterns."

In Cambodia, researchers uploaded the genome sequence to open source pathogen data repository GISAID (Global Initiative on Sharing All Influenza Data) and to Nextstrain, so scientists anywhere can see the full genome sequence of the SARS-CoV-2 coronavirus and study it within the broader context of SARS-CoV-2 coronavirus sequences uploaded globally. Researchers at the Cambodian National Center for Parasitology, Entomology and Malaria Control (CNM) and the National Institute of Allergy and Infectious Diseases (NIAID) partnered with the Institut Pasteur Cambodia to complete this research. These researchers are one of several teams around the world receiving molecular biology and bioinformatics training from the infectious disease team at the Biohub; free access, training, and compute on the IDseq platform from CZI; and the necessary equipment and supplies to begin work in their own countries through the Grand Challenges Explorations Grants.

Unlike tests that are specific for a known agent, such as the SARS-CoV-2 PCR test, mNGS is a universal method that can detect novel disease-causing pathogens, which can be especially useful in cases where researchers may not know what is causing an infection, or what pathogens are circulating in a particular area. A mNGS experiment starts with mass-amplifying DNA traces of pathogens from a patient's sample, resulting in millions of small bits of DNA sequences, or reads. This enormous dataset must then be analysed and interpreted using bioinformatic techniques. The aim is to assign individual DNA fragments from the clinical sample to specific pathogens by leveraging knowledge from sequence databases.

Analysing the massive amount of data from a typical mNGS experiment often requires a battery of specialized bioinformatic tools, including highly specialized expertise and expensive commercially licenced software -- making mNGS a hard-to-access method. The new user-friendly IDseq software is open source and freely available to the global health community, reducing the barrier of entry to metagenomics. Researchers can reuse and build upon the code, which works via a cloud-based service and a web application designed for collaboration and data sharing. The pipeline starts with raw sequencing data as the input, and then goes through steps of filtering, quality control, alignment, and reporting and visualization.

For more information, visit IDseq.net.

Further Reading
Kalantar KL et al., IDseq - An Open Source Cloud-based Pipeline and Analysis Service for Metagenomic Pathogen Detection and Monitoring. Gigascience. 2020;9(10):giaa085. doi:10.1093/gigascience/giaagiaa111

https://academic.oup.com/gigascience/article-lookup/doi/10.1093/gigascience/giaa111

Preprint available at https://www.biorxiv.org/content/10.1101/2020.04.07.030551v3

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What The Study Did: Testimonials posted on a social media site were analyzed to examine whether individuals are using the cannabis-derived chemical compound cannabidiol (CBD) in an attempt to treat diagnosable conditions that have evidence-based therapies.

Authors: John W. Ayers, Ph.D., M.A., of the University of California, San Diego, 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.2020.20977)

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.

UNIVERSITY PARK, Pa. -- The precise timing of a bird's complex song is driven in part by the often-ignored "wires" connecting neurons in the bird's brain, according to a new study. A team of researchers from Penn State and New York University has deconstructed an important "biological clock" that regulates birdsong and other behaviors, leading to new ways of thinking about the function of neuronal networks.

"Many complex, learned behaviors, like hitting a golf ball or playing the violin, require incredibly precise timing at the level of neural firing," said Dezhe Jin, associate professor of physics at Penn State and an author of the paper. "But how the brain seamlessly regulates our muscles in such a precise way remains unclear. In this study, we created a model based on years of experimental observations which revealed that delays within the circuits of neurons play a critical role in the timing of their firing. We then pinpointed the source of the delays to the wires, or axons, that connect neurons."

In a paper appearing Oct. 15 in the journal Cell, Jin and colleagues address behavioral timekeeping using the zebra finch, a small Australian songbird capable of learning a courtship song with the skill of a master instrumentalist. To enable this vocal display, finches have a dedicated "clock" -- called HVC -- in their brains that regulates the timing of the song. In HVC, groups of neurons fire in a predictable sequence that correspond to the performance of the song.

"HVC is often thought of as a clock because it controls a very complicated movement -- the song -- where precise timing is so critical," said Robert Egger, a postdoctoral fellow at the NYU School of Medicine and lead author on this study. "We used cutting-edge methods to measure the simultaneous activity of up to 70 neurons within HVC during singing. In the past, we had to measure each neuron one by one and align their activity to the song."

To explore how a circuit can be so precise, Jin and his graduate student Eugene Tupikov developed a series of large-scale computational models describing the neuronal circuit. In one case, a cluster of neurons fires at the same time which triggers the next cluster of neurons that fire at the same time, triggering the next cluster, like falling dominos, in what researchers call a synfire chain. In an alternative model, delays in the wires allow neurons to fire at slightly different times. The result is a more precise clock.

"We used to think of each group of neurons firing together as a separate, discrete tick of the second hand," said Michael Long, associate professor of neuroscience and physiology at the NYU School of Medicine and corresponding author of the paper. "But what we actually see is more like a second hand that moves smoothly and continuously. The distribution of delays among the wires allows for higher resolution because you don't get these tick points."

The team found a wide distribution of delays in the circuit, meaning some signals reach other neurons very quickly and some take much longer.

"We knew that delays in neuronal circuits were important over a large distance, but within local circuits, they were thought to be negligible, and for that reason were often ignored," said Jin, who led the modeling effort. "These results suggest that axons play a critical role in the timing of neuronal circuits and should be incorporated into future models."

To determine if axonal delays may play a role in other brain networks, the researchers estimated the delays in an area of the rodent brain used to sense their environment while they move their whiskers.

"Our results were consistent with the delays we saw in the songbird, which suggests that axonal delays may play an important role in shaping neuronal activity across a range of complex behaviors," said Jin. "We need to incorporate axon delays into how we think about the brain and how it works."

Fruit flies may be able to teach researchers a thing or two about artificial intelligence.

University of Michigan biologists and their colleagues have uncovered a neural network that enables Drosophila melanogaster fruit flies to convert external stimuli of varying intensities into a "yes or no" decision about when to act.

The research, scheduled to publish Oct. 15 in the journal Current Biology, offers hints into how these decisions work in other species, and could perhaps even be applied to help AI machines learn to categorize information.

Imagine you are working near an open window. If the outside noise is low enough, you may not even notice it. As the noise level gradually increases, you start to notice it more--and eventually, your brain makes a decision about whether to get up and close the window.

But how does the nervous system translate that gradual, linear increase in intensity to a binary, "yes/no" behavioral decision?

"That's a really big question," said neuroscientist Bing Ye, a faculty member at the University of Michigan Life Sciences Institute and senior author of the study. "Between the sensory input and the behavior output is a bit of 'black box.' With this study, we wanted to open that box."

Brain imaging in humans or other mammals can identify certain regions of the brain that respond to particular stimuli. But to determine how and when the neurons transform linear information into a nonlinear decision, the researchers needed a much deeper, more quantitative analysis of the nervous system, Ye said.

They chose to work with the model organism Drosophila, due to the availability of genetic tools that make it possible to identify individual neurons responding to stimuli.

Using an imaging technique that detects neuronal activity through calcium signaling between neurons, the scientists were able to produce 3-D neuroactivity imaging of the flies' entire central nervous system.

"What we saw was that, when we stimulate the sensory neurons that detect harmful stimuli, quite a few brain regions light up within seconds," said Yujia Hu, a research investigator at the LSI and one of the lead authors on the study. "But these brain regions perform different functions. Some are immediately processing sensory information, some spark the behavioral output--but some are more for this transformation process that occurs in between."

When sensory neurons detect the harmful external stimuli, they send information to second-order neurons in the central nervous system. The researchers found that one region of the nervous system in particular, called the posterior medial core, responds to sensory information by either muting less intense signals or amplifying more intense signals, effectively sorting a gradient of sensory inputs into "respond" or "don't respond" categories.

The signals get amplified through increased recruitment of second-order neurons to the neural network--what the researchers refer to as escalated amplification. A mild stimulus could activate two second-order neurons, for example, while a more intense stimulus may activate 10 second-order neurons in the network. The larger network can then prompt a behavioral response.

But to make a "yes/no" decision, the nervous system needs a way not just to amplify information (for a "yes" response), but to also suppress unnecessary or less harmful information (for a "no" response).

"Our sensory system detects and tells us a lot more than we realize," said Ye, who is also a professor of cell and developmental biology in the U-M Medical School. "We need a way to quiet that information, or we would just constantly have exponential amplification."

Using the 3-D imaging, the researchers found that the sensory neurons actually do detect the less harmful stimuli, but that information is filtered out by the posterior medial core, through the release of a chemical that represses neuron-to-neuron communication.

Together, the findings decode the biological mechanism that the fruit fly nervous system uses to convert a gradient of sensory information into a binary behavioral response. And Ye believes this mechanism could have far wider applications.

"There is a dominant idea in our field that these decisions are made by the accumulation of evidence, which takes time," Ye said. "In the biological mechanism we found, the network is wired in a way that it does not need an evidence accumulation phase. We don't know yet, but we wonder if this could serve as a model to help AI learn to sort information more quickly."

Nearly 1 in 8 commercially insured patients nationwide who underwent an elective colonoscopy between 2012 and 2017 performed by an in-network provider received "surprise" bills for out-of-network expenses, often totaling hundreds of dollars or more, new analysis from a team led by a UVA Health doctor shows.

James M. Scheiman, MD, chief of UVA's Division of Gastroenterology and Hepatology, has been deeply concerned that surprise billing may deter patients from getting recommended colonoscopies, increasing the chances that cancer and other digestive disorders remain undetected. So he and his collaborators set out to document the scope of the problem and develop potential solutions.

"Colonoscopy is the most effective colorectal cancer prevention strategy in our medical toolbox," Scheiman said. "We cannot let out-of-pocket costs deter patients from undergoing this potentially lifesaving screening test."

Colonoscopy Insurance Coverage

Scheiman and colleagues at the University of Michigan reviewed 1.1 million claims from a large national insurer for elective colonoscopies that were performed across the country between 2012 and 2017 where both the endoscopists and the hospital facilities were in-network. Of those, 12.1% involved out-of-network claims, with an average surprise bill of $418.

These bills often came because of the use of out-of-network anesthesiologists (64% of cases; median surprise bill of $488) and out-of-network pathologists (40% of cases; median surprise bill of $248). At UVA, colonoscopy anesthesia and pathology services are provided in-house, and there are no out-of-network costs for in-network patients.

"Particularly concerning was that 1 in 12 procedures that did not have an associated intervention had an out-of-network claim," the researchers write in a new Annals of Internal Medicine paper (link here). "This outcome is disconcerting since federal regulations eliminate consumer cost sharing for screening colonoscopy when performed in-network; and 2) a recent Federal Reserve Study reported that 40% of Americans do not have $400 to cover unexpected expenses."

Stopping Surprise Bills

The researchers go on to make important recommendations to spare patients surprise bills: Endoscopists and hospitals should partner with anesthesia and pathology providers who are in-network, and they should consider cost-saving strategies such as endoscopist-provided sedation rather than use of deeper anesthesia. Also, they say considerable healthcare dollars could be saved by adopting a strategy where not all low-risk polyps are sent for pathological evaluation. "In the longer term, we must enhance ongoing reform efforts to remove consumer cost sharing for all clinically indicated care associated with colonoscopy," the researchers write.

"In addition to insurance reform, which is essential to resolve this risk of cost sharing," Scheiman said,"we need tools to accurate predict out-of-pocket responsibilities for patients before the procedure is performed to allow opportunities to limit costs without impact on quality."