Culture

Researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), have produced the first end-to-end DNA sequence of a human chromosome. The results, published today in the journal Nature, show that generating a precise, base-by-base sequence of a human chromosome is now possible, and will enable researchers to produce a complete sequence of the human genome.

"This accomplishment begins a new era in genomics research," said Eric Green, M.D., Ph.D., NHGRI director. "The ability to generate truly complete sequences of chromosomes and genomes is a technical feat that will help us gain a comprehensive understanding of genome function and inform the use of genomic information in medical care."

After nearly two decades of improvements, the reference sequence of the human genome is the most accurate and complete vertebrate genome sequence ever produced. However, there are hundreds of gaps or missing DNA sequences that are unknown.

These gaps most often contain repetitive DNA segments that are exceptionally difficult to sequence. Yet, these repetitive segments include genes and other functional elements that may be relevant to human health and disease.

Because a human genome is incredibly long, consisting of about 6 billion bases, DNA sequencing machines cannot read all the bases at once. Instead, researchers chop the genome into smaller pieces, then analyze each piece to yield sequences of a few hundred bases at a time. Those shorter DNA sequences must then be put back together.

Senior author Adam Phillippy, Ph.D., at National Human Genome Research Institute (NHGRI) compared this issue to solving a puzzle.

"Imagine having to reconstruct a jigsaw puzzle. If you are working with smaller pieces, each contains less context for figuring out where it came from, especially in parts of the puzzle without any unique clues, like a blue sky," he said. "The same is true for sequencing the human genome. Until now, the pieces were too small, and there was no way to put the hardest parts of the genome puzzle together."

Of the 24 human chromosomes (including X and Y), study authors Phillippy and Karen Miga, Ph.D., at the University of California, Santa Cruz, chose to complete the X chromosome sequence first, due to its link with a myriad of diseases, including hemophilia, chronic granulomatous disease and Duchenne muscular dystrophy.

Humans have two sets of chromosomes, one set from each parent. For example, biologically female humans inherit two X chromosomes, one from their mother and one from their father. However, those two X chromosomes are not identical and will contain many differences in their DNA sequences.

In this study, researchers did not sequence the X chromosome from a normal human cell. Instead, they used a special cell type - one that has two identical X chromosomes. Such a cell provides more DNA for sequencing than a male cell, which has only a single copy of an X chromosome. It also avoids sequence differences encountered when analyzing two X chromosomes of a typical female cell.

The authors and their colleagues capitalized on new technologies that can sequence long segments of DNA. Instead of preparing and analyzing small pieces of DNA, they used a method that leaves DNA molecules largely intact. These large DNA molecules were then analyzed by two different instruments. Each of them generates very long DNA sequences - something previous instruments could not accomplish.

After analyzing the human X chromosome in this fashion, Phillippy and his team used their newly developed computer program to assemble the many segments of generated sequences. Miga's group led the effort to close the largest remaining sequence gap on the X chromosome, the roughly 3 million bases of repetitive DNA found at the middle portion of the chromosome, called the centromere.

There is no "gold standard" for researchers to critically evaluate the accuracy of assembling such highly repetitive DNA sequences. To help confirm the validity of the generated sequence, Miga and her collaborators performed several validation steps.

"We have never actually seen these sequences before in our genome, and do not have many tools to test if the predictions we are making are correct. This is why it is important to have specialists in the genomics community weigh in and ensure the final product is high-quality," Miga said.

The effort is part of a broader initiative by the Telomere-to-Telomere (T2T) consortium, partially funded by NHGRI. The consortium aims to generate a complete reference sequence of the human genome.

The T2T consortium is continuing its efforts with the remaining human chromosomes, aiming to generate a complete human genome sequence in 2020.

"We don't yet know what we'll find in the newly uncovered sequences. It is the exciting unknown of discovery. This is the era of complete genome sequences, and we are embracing it wholeheartedly," Phillippy said.

Potential challenges remain. Chromosomes 1 and 9, for example, have repetitive DNA segments that are much larger than the ones encountered on the X chromosome.

"We know these previously uncharted sites in our genome are very different among individuals, but it is important to start figuring out how these differences contribute to human biology and disease," Miga said. Both Phillippy and Miga agree that enhancing sequencing methods will continue to create new opportunities in human genetics and genomics.

Scientists successfully edited RNA in a living animal in such a way that the repaired RNA then corrected a mutation in a protein that gives rise to a debilitating neurological disorder in people known as Rett syndrome.

The advance by researchers at Oregon Health & Science University publishes in the journal Cell Reports.

"This is the first example of using programmable RNA editing to repair a gene in mouse models of a neurological disease," said senior author Gail Mandel, Ph.D., senior scientist in the OHSU Vollum Institute. "This gives us an approach that has some traction."

Rett syndrome is a debilitating neurological disorder caused by mutations in the gene that codes the protein MeCP2. The disease occurs almost exclusively in girls, affecting an estimated 1 in 10,000 live births, due to the fact that it's located on the X chromosome.

Mandel and co-authors, led by postdoctoral fellow John Sinnamon, Ph.D., have been focused on engineering a way to repair the mutated MeCP2 protein at the level of RNA, or ribonucleic acid, which acts as a messenger that carries instructions from DNA to control the synthesis of proteins.

Other scientists have used the programmable RNA editing repair technique to target muscular dystrophy and even hearing loss in genetically engineered mice.

However, this is the first demonstration that the technique holds promise in neurological disorders rooted in genetic mutations spread across thousands of different cell types in the brain. The nervous system poses more challenges for this technique than diseases of other organs, such as muscle or liver, which have much less cellular heterogeneity.

The new study targeted and repaired the MeCP2 protein across a variety of cell types, a scientific first.

"We repaired the MeCP2 protein in three different distinct populations of neurons," Mandel said. "So it's possible that it would work throughout the brain, assuming we can deliver the editing components in a widespread manner."

Previous landmark research led by Adrian Bird, Ph.D., with the University of Edinburgh revealed it was possible to reverse Rett-like symptoms in mice, suggesting it may be possible in people, too.

"For that reason, Rett syndrome is an ideal test case for this technique," Mandel said.

While the OHSU research shows that RNA repair holds promise as a proof of concept, Mandel emphasized that much more research needs to be done to test whether it reverses Rett-like behaviors in mice, and to improve the efficiency and specificity of the repair.

Chikungunya virus, once confined to the Eastern Hemisphere, has infected millions of people in the Americas since 2013, when mosquitoes carrying the virus were discovered in the Caribbean. About half of all people infected with chikungunya virus never show symptoms, while some develop fever and joint pain that lasts about a week, and 10% to 30% develop debilitating arthritis that persists for months or years.

Scientists have understood little about why the severity of the illness varies so widely. A study from researchers at Washington University School of Medicine in St. Louis indicates, in mice, that gut bacteria may play a role. The research shows that mice with faulty gut microbiomes were less able to control chikungunya virus infection. Further, giving the mice a single species of bacteria - or a chemical compound produced by that species - improved the mice's immune responses, lowered levels of the virus in their blood and reduced the chances that a mosquito that fed on blood from infected mice would acquire the virus.

The findings, published July 14 in the journal Cell, suggest that a healthy microbiome could help reduce the chance of severe chikungunya disease and possibly even reduce community spread by disrupting the transmission of virus from person to mosquito to another person.

"In many viral diseases, only a subset of the people who get infected become symptomatic, and we don't really understand why," said senior author Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine. "There might be things that happen during your lifetime that shape your immune system and influence whether you can stop the infection early and have minimal symptoms, or fail to stop it and develop severe disease. We found that when mice don't have a healthy gut microbiome, not only do they get sicker, but mosquitoes that sample their blood are more likely to get infected. Promoting a healthy microbiome could be important not just for individuals who might get infected but for the whole community in breaking or reducing the cycle of transmission."

The gut microbiome is the community of bacteria that live in the intestines. Gut bacteria metabolize and chemically modify some of the material that comes through the digestive tract, generating vitamins and other compounds as byproducts that then are absorbed by cells or other microbes, and help regulate inflammation and the body's response to infection.

To find out if the gut microbiome affects the severity of chikungunya infection, Diamond, first author Emma Winkler, a graduate student in Diamond's lab, and colleagues studied mice without normal gut microbiomes. They used two kinds of mice: germ-free mice, which had been kept under sterile conditions since birth and therefore never developed a gut microbiome, and ordinary laboratory mice treated with a cocktail of two commonly used antibiotics to reduce the complexity of their gut microbiomes.

The researchers infected groups of germ-free and antibiotic-treated mice with chikungunya virus, as well as a group of laboratory mice with normal microbiomes for comparison. The virus multiplied and spread rapidly in the mice that lacked gut microbes, reaching high levels in the blood and in tissues far from the site of infection. Further experiments showed that key immune cells were impaired in the mice without a normal gut microbiome.

Introducing just one bacterial species - a normal member of the human gut microbiome known as Clostridium scindens - rescued the mice's ability to fight the infection. C. scindens is not typically found in mice. But it is common in people, where it modifies a bile acid produced in the liver, generating a compound that affects immune cells. When the researchers gave the modified bile acid alone to mice that lacked normal microbiomes, it improved their immune responses and reduced viral levels in the blood and tissues.

"If having an unhealthy microbiome affects the virus levels in your blood, that raises an interesting question for a blood-borne pathogen: Does the health of your microbiome impact transmission?" said Diamond, who is also a professor of molecular microbiology, and of pathology and immunology. "It stands to reason that if there is more virus in the blood, a mosquito would be more likely to get infected when it takes a blood meal."

To test this idea, Diamond and Winkler infected three groups of mice with chikungunya virus. One group was treated with antibiotics to eliminate their gut bacteria, a second was treated with antibiotics and later given C. scindens to repopulate such bacteria in their intestines, and the third group didn't receive antibiotics at all, leaving them with normal gut microbiomes. The researchers drew blood one day after infection and offered the blood to mosquitoes to feed on. More than half of the mosquitoes that sampled the blood of the antibiotic-treated mice became infected, compared with less than a third of the mosquitoes that fed on blood from the mice with normal microbiomes or with only C. scindens.

"There are plenty of people walking around with unhealthy microbiomes and varying levels of conjugated bile acids in their guts," said Diamond. "There may be other bacteria that might be even better than C. scindens at modifying bile acids that could be used to rebalance microbiomes. If a probiotic like that were created, it might be one way to not only minimize disease in individuals, but reduce community spread at the same time."

In a discovery with important implications for criminal justice, a team of scientists from USC and other Southern California research institutions has developed a unique way to measure the reliability of an eyewitness trying to pick a culprit from a police lineup.

It's a new forensic approach that attempts to gauge the strength of witness memory while minimizing the influence of unwitting bias in an attempt to explain -- and solve -- why so many innocent people get convicted of crimes. The method challenges police lineup techniques that've been entrenched for nearly a century.

"Our new lineup method uncovers the structure of eyewitness memory, removes decision bias from the identification process and quantifies the performance of individual witnesses. This study is a great example of using laboratory science to bring about criminal justice reform," said Sergei Gepshtein, an expert in perceptual psychology and neuroscience at the USC School of Cinematic Arts and a corresponding author of the study.

Gepshtein and collaborators from the University of California and the Salk Institute for Biological Studies in La Jolla, Calif., where he is also a member of the Center for the Neurobiology of Vision, conducted the study, which appears today in Nature Communications.

At its core, the new method accounts for mistakes in witness decision making, scores a witness' responses based on paired comparisons of photos instead of a traditional lineup and assigns a probability value to the testimony. Among the advantages, the technique minimizes biases that confound memory and inserts elements of the scientific method into eyewitness testimony.

"What's at stake is the confidence people have in their criminal justice system. People want the criminal justice system to use the best methods available for prosecuting crime," Gepshtein said.

When police round up suspects to appear in a lineup, the outcome isn't always accurate, as misidentification by eyewitnesses can lead to false arrests and imprisonments. In recent years, more than 350 people -- many serving lengthy prison sentences -- have been exonerated in the United States because their DNA was found to be incompatible with evidence collected from crime scenes. Eyewitness misidentification accounts for 70% of verified erroneous convictions, the study says.

The study also comes at a time of increased racial tensions across the United States, as police practices come under scrutiny, mass protests support the Black Lives Matter movement and some municipalities consider defunding local law enforcement.

In the experiment, the researchers used neuroscience and psychology to parse how the eyewitness's mind captures events and then retrieves impressions from memory -- two distinct brain functions that sometimes can lead to erroneous recollections.

Like in the movies, lineups occur when a suspect and several other people, known as "fillers," are shown to a witness, either by photos or in person. But the process can muddle a correct identification because of ambiguity about two factors that underlie human decision-making: strength of memory and decision criterion.

Decision criterion is the mental yardstick a witness uses to assess the resemblance of a suspect to the memory of the culprit; it's a measure of similarity that the witness deems sufficient for identification. An individual assured in their strong memory may make a selection using a rigid criterion, concluding there's a high similarity to identify the culprit. But another individual might have a weak memory and use a laxer criterion to claim that a suspect is the culprit, even if there's little similarity. In both instances, the witness could potentially finger a perpetrator erroneously.

The problem is exacerbated by law enforcement's binary yes-or-no imperative that the witness identifies the bad guy, Gepshtein explained.

To extract a more accurate memory, the scientists employed a science called sensory psychophysics. Their experiment involved 202 college students shown a movie clip of a single criminal act. Later, the scientists asked the subjects to view photos of possible culprits. Some subjects viewed photos in sequence and other subjects in a simultaneous batch, just like in a police lineup. Other subjects were presented the photos using a new method where the same photos were shown in pairs.

The latter group of subjects reported which of images in a pair was more similar to the culprit in the film clip. Then the scientists tallied the scores, a method called "perceptual scaling."

"It's like when you go to the optometrist and you're asked, 'which image is clearer: this one or that one?' as the optometrist flips the contrasting lenses," Gepshtein said. A similar technique is used in product marketing, preference testing and hearing aid tests.

In the end, the researchers obtained a relative ranking for every photo -- rather than an absolute identification of a culprit -- and could assign a probability score to each image, thus quantifying the perceived similarity of each face to the perpetrator. Using this method, they found that the culprit's face was most consistently ranked correctly; the photo received more than double the positive identifications than could be expected by chance, the study says. Moreover, the new process led to significantly fewer rejections of the lineup than the traditional methods, which is important because it indicates the bad guy is less likely to go free.

"Using these scaled measures of similarity to estimate recognition memory strength for each face in a lineup removes decision bias from the process of eyewitness identification and replaces the yes-or-no absolute identification by providing a more detailed relative judgment," Gepshtein said.

The new identification method has profound implications for law enforcement investigations. It means that, for the first time, investigators can measure the strength of the memory of an eyewitness. It also helps to create a fairer lineup in which the fillers are similar to the suspect to a known degree, whereas traditional methods could not measure that, Gepshtein explained.

In addition, the method is novel because it leads to a new manner of presenting eyewitness testimony in a court of law. It involves a forensic expert to interpret the reliability of an eyewitness, similar to how other experts weigh the value of other evidence such as DNA, ballistics or physical items from a crime scene.

But whether the criminal justice system is ready to change an investigative practice embedded in cop culture and immortalized in pulp fiction and crime thriller cinema is another matter.

"Generally speaking, criminal justice reform is an uphill battle, partly because there are many concepts and methods that are deeply embedded in the culture of those who work in our legal and law enforcement systems," said Thomas Albright, a study co-author, director of the Vision Center Laboratory at the Salk Institute and a member of the National Academy of Sciences. "On the other hand, there are compelling principles of fairness at stake here and science is a largely unmined source of new ideas to mitigate injustice."

A team of researchers at the Nanyang Technological University, Singapore (NTU Singapore) has created a perovskite solar mini module that has recorded the highest power conversion efficiency of any perovskite-based device larger than 10 cm2.

Perovskites are new materials that have emerged as promising alternatives to silicon in solar cell applications. The material offers power conversion efficiencies similar to silicon solar cells but can also be used to create light-weight flexible and semi-transparent cells ideal for applications in buildings and a variety of urban spaces. Perovskite technologies are progressing rapidly towards industrialisation, with stability and scalability to larger sizes seen by researchers as the last hurdles to overcome.

Now NTU researchers report that they have adopted a common industrial coating technique called 'thermal co-evaporation' and found that it can fabricate solar cell modules of 21 cm2 size with record power conversion efficiencies of 18.1 per cent. These are the highest recorded values reported for scalable perovskite solar cells.

Thermal evaporation is an established coating technique currently used to produce electronics including Organic Light Emitting Diode (OLED) TVs.

Dr Annalisa Bruno, lead author of the research findings published on the cover page of scientific journal Joule, and Senior Scientist at the Energy Research Institute @ NTU (ERI@N) explained the roadblock in the large-scale adoption of perovskite solar modules.

"The best-performing perovskite solar cells have so far been realised in the laboratory at sizes much smaller than 1 cm2, using a solution-based technique, called 'spin-coating'. However, when used on a large surface, the method results in perovskite solar cells with lower power conversion efficiencies. This is due to the intrinsic limitations that include defects and lack of uniformity over large areas, making it challenging for industrial fabrication methods" she said.

"By using thermal evaporation to form the perovskite layer, our team successfully developed perovskite solar cells with the highest recorded power conversion efficiency reported for modules larger than 10 cm2.

"Our work demonstrates the compatibility of perovskite technology with industrial processes, and its potential for market entry. This is good news for Singapore, which is looking to ramp up the use of solar energy for its power needs."

First author and research fellow at ERI@N, Dr Li Jia said, "We have demonstrated the excellent scalability of co-evaporated perovskite solar cells for the first time. This step will accelerate the transition of this technology from laboratory to industry."

More surface areas to harness sunlight with coloured perovskite solar cells

Utilising the same technique, the researchers then fabricated coloured semi-transparent versions of the perovskite solar cells and mini modules, which achieved similar measures of power conversion efficiency across a whole range of different colours.

These results demonstrate the versatility of the thermal evaporation method in producing a variety of perovskite-based solar devices for a variety of optoelectronic applications.

NTU Associate Vice President (Strategy & Partnerships), Professor Subodh Mhaisalkar, who is the co-lead author of the paper, said the findings open doors for Singapore and urban environments in other countries to harness the power of sunlight more efficiently than ever before.

"The solar mini modules can be used on facades and windows in skyscrapers, which is not possible with current silicon solar panels as they are opaque and block light. Building owners will be able to incorporate semi-transparent coloured solar cells in the architectural designs to harvest even more solar energy without compromising the aesthetic qualities of their buildings" said Prof Mhaisalkar who is also Executive Director of the Energy Research Institute @ NTU (ERI@N).

Associate Professor Nripan Mathews, who is co-lead author and from the School of Materials Science & Engineering at NTU said, "This work highlights the breadth and depth of perovskite research at NTU. There is no other team in the world which pursues the various possibilities that perovskites provide under one roof. From large area solar cells for buildings, high efficiency perovskite-silicon tandem devices, to light emitting diodes - our team is inspired to tackle the key challenges involved to expedite technological deployment."

Providing an independent view, Professor Armin Aberle, Chief Executive Officer of the Solar Energy Research Institute of Singapore (SERIS) at the National University of Singapore (NUS) said, "This work represents the first demonstration of highly efficient large-area perovskite solar cells fabricated by an industrially compatible process. We are working closely with NTU in the future development of 30% efficient perovskite-on-silicon tandem solar cells in Singapore."

The NTU team is now looking at integrating perovskite and silicon solar cells to create a tandem solar cell. Such a configuration fabricated using cost-effective and scalable processes can substantially increase the solar electricity production per unit area while keeping production costs low.

Barcelona, July 14, 2020-. An analysis of a series of maternal deaths in Maputo's central hospital, in Mozambique, reveals a major diagnostic error in almost 40% of the deaths. The results, published in Lancet Global Health, show there has been scarce improvement over the last ten years. The study was led by the Barcelona Institute for Global Health (ISGlobal), an institution supported by the "la Caixa" Foundation, in collaboration with Manhiça Health Research Centre (CISM) in Mozambique.

Although the number of women in low- and middle-income countries that give birth in health centres has increased over the last years, maternal mortality remains extremely high in these countries: more than 300,000 women die during pregnancy, delivery or puerperium every year worldwide, and 99% of these deaths occur in poor countries.

"It is not only about increasing access to health services, but also increasing the quality of the care provided," says Clara Menéndez, director of the Maternal, Child and Reproductive Health Initiative at ISGlobal and first author of the study. "A key - and often neglected- element for improving healthcare quality is the correct diagnosis of diseases that can lead to death in pregnant women," she adds.

In this study, the team led by Jaume Ordi, ISGlobal researcher and pathologist at the Hospital Clinic, retrospectively analysed a series of deaths that occurred in Maputo's central hospital, in southern Mozambique, between November 2013 and March 2015. They compared the clinical diagnosis with diagnosis by complete autopsy and they observed that in almost 40% of the deaths there was a major diagnostic error where, if a correct diagnosis had been made, death could possibly have been avoided.

"If we compare these results with a similar study done ten years earlier, we can see that the diagnostic capacity has barely improved and has even worsened for some pathologies such as puerperal infections," says Ordi.

These results highlight the need to improve diagnostic capacities through the access to better diagnostic tests and strengthening clinical skills among the healthcare workers. "The practice of autopsies and the joint analysis of the diagnostic discrepancies with clinicians and pathologists could be of great help for the medical staff providing care for pregnant women," concludes Menéndez.

The death of a twin, especially earlier in life, can increase the risk of their surviving twin being diagnosed with a psychiatric disorder, finds a new study published today in eLife.

Losing a loved one is always difficult but losing a twin may be particularly so. By virtue of being the same age, twins share many common experiences and may have strong emotional bonds. The new study suggests those who lose a co-twin may require extra support in both the short and longer term.

"Losing a co-twin by death may be a particularly devastating life stressor with considerable health implications for surviving twins, yet there have been few studies on this type of bereavement," says lead author Huan Song, a senior researcher at West China Hospital, Sichuan University, China, and also at the University of Iceland and Karolinska Institute, Sweden.

Using the Swedish health registers and the Swedish Twin Registry, Song and colleagues identified all Swedish twins who experienced the death of a co-twin between 1973 and 2013. They then compared the rates of psychiatric diagnoses in these bereaved twins with their non-twin siblings, and with 22,640 twins whose co-twin was still alive.

"We showed that the risk of being diagnosed with a psychiatric disorder increased by 55% to 65% after the death of a co-twin," Song says. This risk was highest in cases where a co-twin had died during childhood or young adulthood.

Surviving twins were most likely to receive a new psychiatric diagnosis in the first month after the death, when their risk of such a diagnosis was sevenfold higher than non-bereaved twins. But they continued to have a higher risk for more than 10 years after the loss.

The findings also revealed that the risk of being diagnosed with a psychiatric disorder after a co-twin's death was particularly high for identical twins, who share all the same genes. These individuals had about a 2.5-times higher risk compared to their non-twin siblings. Surviving fraternal twins, who are as genetically similar to their twin as their non-twin siblings, had about a 30% higher risk of a psychiatric diagnosis after the death of their twin than their non-twin siblings.

Senior author Unnur Valdimarsdóttir, Professor of Epidemiology at the University of Iceland explains that because of their genetic similarities and shared experiences, twins often develop a sense of shared identity, which may compound their grief after the loss of their co-twin.

"Our results suggest that both genetic similarity and early-life attachment may contribute to the subsequent risk of psychiatric disorders among surviving twins after the death of their co-twin," Valdimarsdóttir concludes.

From climate and biodiversity to public health and law enforcement, public goods benefit all. They are produced or maintained through widespread participation in public-goods provision that is vulnerable to low participation rates. Avoiding this vulnerability has spurred a continuing search for better ways to promote participation.

Now, a study by an international group of researches shows that the ability to freely choose preferred public goods adds to their value by increasing participation rates. The findings offer surprising insights into human decision making, while also suggesting that societies may profit from bottom-up approaches to public-goods provision.

Decades of experiments on human behavior and public goods games have consistently confirmed that initial participation rates hover around 50%, but then decrease due to free riding (the act of piggybacking on the goodwill of others). Recent theoretical research suggests that social networks are instrumental in offsetting free riding but so far, large-scale experiments have failed to support these theoretical predictions.

To investigate factors affecting public-goods provision, a research team coordinated by Marko Jusup from Tokyo Institute of Technology (Tokyo Tech) in Japan and Zhen Wang from Northwestern Polytechnical University in China conducted a social-dilemma experiment designed specifically to reveal what drives participation rates. Is it global characteristics of social networks or local circumstances of each individual?

The team organized a game experiment played by 596 students who were equally distributed across three social-network configurations and two experimental conditions. Under control conditions, players could only decide whether to participate in public goods provision or not. A decision to participate implied contributing one unit of wealth to each public good within their reach. The total contribution would then be multiplied by an interest rate and divided equally not only between actual contributors, but also free riders who could have contributed, but chose not to. Free riders could thus piggyback on the effort of contributors to gain benefits without sharing costs. Players under treatment conditions could additionally decide how much to contribute to each of the public goods within their reach.

A player with access to five different public goods would, by opting to participate under control conditions, contribute one unit of wealth to each of the public goods for a total contribution of five units. The same player under treatment conditions would also contribute a total of five units of wealth, but with a caveat that how much goes to each of the five public goods is subject to free will.

The study found that local circumstances are more important than the global characteristics of social networks. Changing the network configuration does not appear to affect player decisions in any significant way, whereas letting players distribute their wealth freely increases participation in public goods provision, motivates better provisioning, and thus adds value to public goods.

Remarkably, treatment conditions jump-started participation from the very beginning to form a cooperative milieu that is independent of social-network characteristics. Jusup comments: "This is surprising! We expected initial participation to be similar under both control and treatment conditions. Only later in the game did we expect gradual learning and optimization from players who could choose freely. We observed that increased participation in public-goods provision happens from the very first round of the game, as if the players could feel that extra freedoms weaken the underlying dilemma of whether to participate or not. Over time, more participation leads to more wealth, generating something akin to a free lunch for players under treatment conditions."

The study identified three behavioral types that account for the results: prosocial, antisocial, and conditional cooperators. Prosocial players participate almost unconditionally, antisocial players mostly forgo participation, and conditional cooperators refuse participation when there are no other participators around. Notably, freedom of choice seems to foster conditional cooperation, as evidenced by the fact that conditional cooperators are mostly absent under control conditions but predominate under treatment conditions. This occurs because in the latter case, players receive much clearer signals from their surroundings, and can then better gauge the overall cooperativeness of their neighbors.

There are many interesting implications for socio-economic settings. "Policymakers, for instance, could facilitate raising residential taxes by offering a portfolio of public goods for taxpayers to choose from," write the researchers in their study published in Proceedings of the National Academy of Sciences.

"And by doing so, voters could decouple long-term, life-improving, public-goods projects from the whims and fancies of political election cycles," adds Ivan Romi?, a co-author of the study. "Going beyond the politics, private companies might be able to motivate customers to pay premium product prices if the premium could be directed toward a public good of customers' choosing, thus stepping up the corporate social responsibility while remaining profitable."

Scientists from Trinity College Dublin have discovered a new link between impaired brain energy metabolism and delirium - a disorienting and distressing disorder particularly common in the elderly and one that is currently occurring in a large proportion of patients hospitalised with COVID-19 [15th of July 2020].

While much of the research was conducted in mice, additional work suggests overlapping mechanisms are at play in humans because cerebrospinal fluid (CSF) collected from patients suffering from delirium also contained tell-tale markers of altered brain glucose metabolism.

Collectively, the research, which has just been published in the Journal of Neuroscience, suggests that therapies focusing on brain energy metabolism may offer new routes to mitigating delirium.

Delirium

When the body experiences high levels of inflammation - such as during bacterial or viral infections - the way our brains function changes, which in turn affects our mood and motivation. In older patients such acute inflammation can produce a profound disturbance of brain function known as delirium. Despite the disorder being relatively common, the mechanisms by which it arises are poorly understood.

In the new research the scientists found that artificially inducing peripheral inflammation in mice triggered sudden onset cognitive dysfunction, and that this is mediated by a disturbance to energy metabolism.

In these experiments, inflammation left the mice with lower levels of blood sugar (glucose), which the brain requires for maintaining normal function. When the animals were supplemented with glucose, their cognitive performance returned towards normal, despite the continued inflammation.

Professor Colm Cunningham, who leads the Trinity Biomedical Science Institute lab where the work was performed, said: "An important feature of these experiments was that mice with early stages of pre-existing neurodegenerative disease were far more susceptible to dysfunction when these metabolic changes occurred.

"Our collaborators in Oslo also detected evidence of altered brain glucose metabolism in cerebrospinal fluid taken from people experiencing delirium, which argues for overlapping mechanisms in humans and mice. In other words, the signs are that similar processes are at work in people."

Dr Wes Ely, a critical care physician from Vanderbilt University, who wasn't involved with the study, added:

"The finding that the neurodegenerative animals are less resilient to this disturbance of energy metabolism really resonates with what we see in our intensive care unit patients with delirium."

Given the frequency of delirium during hospitalised members of the elderly population and, given that these episodes can accelerate the progress of underlying dementia treatments are desperately needed.

Professor Cunningham added: "Simply providing glucose to patients is not likely to treat delirium in most cases but collectively our data emphasise that an appropriate supply of both oxygen and glucose to the brain becomes especially important in older patients and in those with existing dementia. Therefore, we believe that focusing on brain energy metabolism may offer routes to mitigating delirium."

A range of video game practices have potentially dangerous links to problem gambling, a study has revealed.

Building on previous research by the same author, which exposed a link between problem gambling and video game loot boxes, the new study suggests that a number of other practices in video games, such as token wagering, real-money gaming, and social casino spending, are also significantly linked to problem gambling.

The research provides evidence that players who engage in these practices are also more likely to suffer from disordered gaming - a condition where persistent and repeated engagement with video games causes an individual significant impairment or distress.

Author of the study, Dr David Zendle from the Department of Computer Science at the University of York, said: "These findings suggest that the relationship between gaming and problem gambling is more complex than many people think."

"When we go beyond loot boxes, we can see that there are multiple novel practices in gaming that incorporate elements of gambling. All of them are linked to problem gambling, and all seem prevalent. This may pose an important public health risk. Further research is urgently needed"

For the study, a group of just under 1,100 participants were quota-sampled to represent the UK population in terms of age, gender, and ethnicity. They were then asked about their gaming and gambling habits.

The study revealed that a significant proportion (18.5%) of the participants had engaged in some behaviour that related to both gaming and gambling, such as playing a social casino game or spending money on a loot box.

Dr Zendle added: "There are currently loopholes that mean some gambling related elements of video games avoid regulation. For example social casinos are 'video games' that are basically a simulation of gambling: you can spend real money in them, and the only thing that stops them being regulated as proper gambling is that winnings cannot be converted into cash.

"We need to have regulations in place that address all of the similarities between gambling and video games. Loot boxes aren't the only element of video games that overlaps with gambling: They're just a tiny symptom of this broader convergence"

Last year, University of York academics, including Dr David Zendle, contributed to a House of Commons select committee inquiry whose report called for video game loot boxes to be regulated under gambling law and for their sale to children to be banned. Dr Zendle also provided key evidence to the recent House of Lords select committee inquiry that likewise produced a report recommending the regulation of loot boxes as gambling.

Small amounts of plutonium (Pu) were released from the damaged Fukushima Daiichi Nuclear Power Plant (FDNPP) reactors into the environment during the site's 2011 nuclear disaster. However, the physical, chemical, and isotopic form of the released Pu has remained unknown.

Now, recent work published in the journal Science of the Total Environment has shown that Pu was included inside cesium-rich microparticles (CsMPs) that were emitted from the site. CsMPs are microscopic radioactive particles that formed inside the Fukushima reactors when the melting nuclear fuel interacted with the reactor's structural concrete. Due to loss of containment in the reactors, the particles were released into the atmosphere; many were then deposited across Japan.

Studies have shown that the CsMPs are incredibly radioactive and that they are primarily composed of glass (with silica from the concrete) and radio-cesium (a volatile fission product formed in the reactors). Whilst the environmental impact and distribution of the CsMPs is still an active subject of debate, learning about the chemical composition of the CsMPs has been shown to offer a much-needed insight into the nature and extent of the FDNPP meltdowns.

The study published in Science of the Total Environment, involving scientists from Japan, Finland, France, Switzerland, the UK, and USA, was led by Dr. Satoshi Utsunomiya and graduate student Eitaro Kurihara (Department of Chemistry, Kyushu University). The team used a combination of advanced analytical techniques (synchrotron-based micro-X-ray analysis, secondary ion mass spectrometry, and high-resolution transmission electron microscopy) to find and characterize the Pu that was present in the CsMP samples.

The researchers initially discovered incredibly small uranium-dioxide inclusions, of less than 10 nanometers in diameter, inside the CsMPs; this indicated possible inclusion of nuclear fuel inside the particles. Detailed analysis then revealed, for the first-time, that Pu-oxide concentrates were associated with the uranium, and that the isotopic composition of the U and Pu matched that calculated for the FDNPP irradiated fuel inventory.

Dr Utsunomiya stated "these results strongly suggest that the nano-scale heterogeneity that is common in normal nuclear fuels is still present in the fuel debris that remains inside the site's damaged reactors. This is important information as it tells us about the extent / severity of the melt-down. Further, this is important information for the eventual decommissioning of the damaged reactors and the long-term management of their wastes."

With regards environmental impact, Dr Utsunomiya states "that as we already know that the CsMPs were distributed over a wide region in Japan (up to 230 km from the FDNPP), small amounts of Pu were likely dispersed in the same way."

Professor Gareth Law, a co-author on the paper from the University of Helsinki, indicated that the team "will continue to characterize and experiment with the CsMPs, in an effort to better understand their long-term behavior and environmental impact. It is clear that CsMPs are an important vector of radioactive contamination from nuclear accidents."

Professor Bernd Grambow, a co-author from Nantes/France, states that "while the Pu released from the damaged reactors is low compared to that of Cs; the investigation provides crucial information for studying the associated health impact."

Professor Rod Ewing at Stanford University emphasized that "the study used an extraordinary array of analytical techniques in order to complete the description of the particles at the atomic-scale. This is the type of information required to describe the mobility of plutonium in the environment."

Utsunomiya concluded "It took a long time to publish results on particulate Pu from Fukushima. I would like to emphasize that this is a great achievement of international collaboration. It's been almost ten years since the nuclear disaster at Fukushima," he continued "but research on Fukushima's environmental impact and its decommissioning are a long way from being over."

Kanazawa, Japan - In a study published recently in Communications Biology, researchers led by Kanazawa University explain how a tiny fish could help end painful metabolic and genetic bone diseases.

While pain, swelling, and immobility are the most obvious aftereffects of a broken bone, there is also a flurry of activity going on at the cellular level in an effort to repair the damage. And because bones are usually hidden away under layers of muscle, fat, and skin, it has been difficult for researchers to study in real time how bones regenerate.

"To provide insight into the process of fracture repair, we needed bone that was easily accessible and a model species in which bone growth mimicked that of humans," says lead author Jingjing Kobayashi-Sun. "With transgenic and mutant lines already available, zebrafish scales ticked all the boxes."

Zebrafish scales, although much simpler than mammalian bones, respond and develop in almost the same way as their more complex counterparts, and are conveniently located on the outside of the body. Most importantly though, they contain both osteoclasts and osteoblasts, the cells that respectively clear away broken bone fragments and generate new bone after a fracture.

Explains Kobayashi-Sun, "Recent studies have suggested that molecular packages, called extracellular vesicles (EVs), derived from osteoblasts may deliver signaling molecules to immature osteoclasts, triggering their differentiation into mature, active cells. However, given the difficulty of live imaging in bone, no one has been able to prove this process actually occurs in vivo."

To visualize osteoblasts and osteoclasts in zebrafish scales, the researchers generated a double transgenic line in which the two cell types expressed different color fluorescent labels. After making small cuts in the scales of anesthetized fish, the researchers could identify the different cell types in the healing bone using a fluorescent microscope or flow cytometry.

"We observed that a large number of the green fluorescent osteoclasts at the fracture site contained red fluorescent osteoblast-derived particles in the cytoplasm, confirming the uptake of EVs by immature osteoclasts," says senior author Isao Kobayashi. "In addition, mature osteoclasts were abundant in the damaged scales, indicating that EV uptake triggers the differentiation of osteoclasts."

The EVs contained high levels of a cellular differentiation-associated signaling molecule called RANKL. Knocking out the corresponding gene resulted in a significant reduction in the number of osteoclasts, suggesting that osteoblasts control osteoclast formation via Rankl signaling.

Given that many bone disorders result from a breakdown in communication between osteoblasts and osteoclasts, these findings provide valuable information for the development of novel drug therapies.

What makes a species "smart" and how do strategies for processing information evolve? What goes on in the minds of non-human animals and which cognitive skills can we claim as hallmarks of our species? These are some of the questions addressed by the field of comparative psychology, but a recent review in the Journal of Intelligence joins a growing body of literature that argues that studies of cognition are hampered by anthropocentrism and missing the bigger picture of cognitive evolution.

Based on 40 years of scientific literature and case studies of three non-human animals, the current paper identifies two main problems hindering research in comparative psychology.

First of which is the assumption that human cognition is the standard by which animal cognition should be measured. Human cognition is generally believed to be the most flexible, adaptable form of intelligence, with the abilities of other species evaluated in accordance to the extent they match human cognitive skills. Such an approach tends to overrate human-like cognitive skills and may overlook cognitive skills that play only a small part, or no part at all, in human psychology.

"This approach, whether implicit or explicit, can only produce a restrictive, anthropocentric view of cognitive evolution that ignores the incredible diversity of cognitive skills present in the world," says Juliane Bräuer, leader of the DogLab at the Max Planck Institute for the Science of Human History. Instead, research into the evolution of cognition should take a biocentric approach, considering each species investigated in its own right.

"Applying Darwinian thinking to comparative psychology and removing the 'benchmark' of human intelligence allows us to reveal the evolutionary, developmental and environmental conditions that foster the growth of certain unique abilities and the convergence of skills shared among a species," adds Natalie Uomini, the main co-author of the paper.

To further address this anthropocentric view, the authors also argue for increased focus on cognitive abilities in which animals outperform humans and discuss cases in which various species demonstrate better-than-human abilities in delayed gratification, navigation, communication, pattern recognition and statistical reasoning.

The second problem addressed is the assumption that cognition evolves as a package of skills similar to those apparent in humans, skills which taken together constitute "one cognition." The authors survey various major hypotheses from psychology, including Social Intelligence Hypothesis, Domestication Hypothesis and Cooperative Breeding Hypothesis, and argue that while each has evidence to support its claims, none account for the whole picture of cognition.

Instead of a cluster of linked skills originating from a single evolutionary pressure, the paper provides a framework for understanding cognitive arrays as the result of species-typical adaptations to the entire ecological and social environment.

"If we want to account for the fascinating variety of animal minds, comparative scientists should focus on skills that are ecologically relevant for a given species," say Bräuer and Uomini.

The paper discusses three distantly related species - chimpanzees, dogs and New Caledonian crows - that are highly sophisticated in one cognitive domain yet perform poorly in others generally believed to be linked.

The paper also lays out recommendations to make future experiments in comparative psychology ecologically relevant to the target species, including differentiating tasks for each species and accounting for diverse senses of perception, such as smell in the case of dogs.

In Germany, where the authors of the paper are based, comparative psychology is a relatively unknown field. The authors hope to stimulate interest and growth in the subject with future research dedicated to the study of each species' cognitive skills for their own sake, leading to a more relevant and holistic perspective on animals' cognitive skills and the recognition that there is not only "one cognition."

A new study from North Carolina State University and Microsoft finds that the technical interviews currently used in hiring for many software engineering positions test whether a job candidate has performance anxiety rather than whether the candidate is competent at coding. The interviews may also be used to exclude groups or favor specific job candidates.

"Technical interviews are feared and hated in the industry, and it turns out that these interview techniques may also be hurting the industry's ability to find and hire skilled software engineers," says Chris Parnin, an assistant professor of computer science at NC State and co-author of a paper on the work. "Our study suggests that a lot of well-qualified job candidates are being eliminated because they're not used to working on a whiteboard in front of an audience."

Technical interviews in the software engineering sector generally take the form of giving a job candidate a problem to solve, then requiring the candidate to write out a solution in code on a whiteboard - explaining each step of the process to an interviewer.

Previous research found that many developers in the software engineering community felt the technical interview process was deeply flawed. So the researchers decided to run a study aimed at assessing the effect of the interview process on aspiring software engineers.

For this study, researchers conducted technical interviews of 48 computer science undergraduates and graduate students. Half of the study participants were given a conventional technical interview, with an interviewer looking on. The other half of the participants were asked to solve their problem on a whiteboard in a private room. The private interviews did not require study participants to explain their solutions aloud, and had no interviewers looking over their shoulders.

Researchers measured each study participant's interview performance by assessing the accuracy and efficiency of each solution. In other words, they wanted to know whether the code they wrote would work, and the amount of computing resources needed to run it.

"People who took the traditional interview performed half as well as people that were able to interview in private," Parnin says. "In short, the findings suggest that companies are missing out on really good programmers because those programmers aren't good at writing on a whiteboard and explaining their work out loud while coding."

The researchers also note that the current format of technical interviews may also be used to exclude certain job candidates.

"For example, interviewers may give easier problems to candidates they prefer," Parnin says. "But the format may also serve as a barrier to entire classes of candidates. For example, in our study, all of the women who took the public interview failed, while all of the women who took the private interview passed. Our study was limited, and a larger sample size would be needed to draw firm conclusions, but the idea that the very design of the interview process may effectively exclude an entire class of job candidates is troubling."

What's more, the specific nature of the technical interview process means that many job candidates try to spend weeks or months training specifically for the technical interview, rather than for the actual job they'd be doing.

"The technical interview process gives people with industry connections an advantage," says Mahnaz Behroozi, first author of study and a Ph.D. student at NC State. "But it gives a particularly large advantage to people who can afford to take the time to focus solely on preparing for an interview process that has very little to do with the nature of the work itself.

"And the problems this study highlights are in addition to a suite of other problems associated with the hiring process in the tech sector, which we presented at ICSE-SES [the International Conference on Software Engineering, Software Engineering In Society]," adds Behroozi. "If the tech sector can address all of these challenges in a meaningful way, it will make significant progress in becoming more fair and inclusive. More to the point, the sector will be drawing from a larger and more diverse talent pool, which would contribute to better work."

The study on technical interviews, "Does Stress Impact Technical Interview Performance?," will be presented at the ACM Joint European Software Engineering Conference and Symposium on the Foundations of Software Engineering, being held virtually from Nov. 8-13. The study was co-authored by Shivani Shirolkar, a Ph.D. student at NC State who worked on the project while an undergraduate; and by Titus Barik, a researcher at Microsoft and former Ph.D. student at NC State.

Until recently, economists, policy makers and workforce experts have relied on outdated and inaccurate snapshots of the U.S. physician workforce, making it especially difficult to predict the need and availability of health care services across the country. Data about each physician's area of specialty is collected at the beginning of their career and is rarely updated, increasing the potential for outdated information about who is providing care for our nation's population. In this study, Wingrove et al examine how machine learning algorithms may allow for more real-time, accurate descriptions of the medical workforce, including professions that do not formally collect specialty data like physician assistants and nurse practitioners. Algorithms also can identify physicians in new and evolving interdisciplinary positions. One such learning model from the Robert Graham Center and the University of Pittsburgh was trained to identify a majority of medical specialties with 95 percent accuracy. The model was fed data from clinical encounters in the form of procedures and prescriptions billed by Medicare from 2014 to 2016. The models were less accurate at predicting some specialties, like neurosurgery and physical medicine and rehabilitation. But overall, the model correctly predicted 70 percent of physician's practice type within five percentage points of their actual count, including primary care and specialties such as emergency medicine, cardiology, gastroenterology and radiology.