Culture

Commercially important seafood species are at greater risk of microplastic contamination depending how they clump together in the marine environment, new research suggests.

In the first study of its kind, scientists from the University of Plymouth used a series of experiments to assess whether the reefs formed by blue mussel (Mytilus edulis) affected their exposure and consumption of tiny microplastic particles.

They found that when mussels were clumped together forming reefs, as they do in nature, the reef structure slowed the sea water flowing over them, increased turbulence, and resulted in a three-fold rise in the amount of ingested plastic.

Writing in Environmental Research Letters, researchers say the study suggests that the arrangement and surface roughness (complexity) of natural reef structures - such as that constructed by mussel populations - create conditions that make them natural sinks for plastics and other forms of human pollution.

They also believe species like the blue mussel, which are important for human consumption but susceptible to microplastic pollution, may be useful indicators of the problem and its potentially harmful biological impacts.

The research was led by recent graduate Marine Biology and Oceanography graduate Hyee Shynn Lim from the University's Marine Biology and Ecology Research Centre and School of Biological and Marine Sciences.

Dr Antony Knights, Associate Professor in Marine Ecology and senior author on the study, said: "Species such as the blue mussel are both commercially valuable as seafood but also environmentally important. They form natural reefs within marine and coastal settings which enhance biodiversity to such a degree that they are commonly protected under conservation actions. If they are particularly susceptible to microplastic pollution, there are many potential knock-on effects that we need to be aware of.

"Often we look to protect reef-forming species based on who they are. However, we are not aware of any research that has shown that the physical structure of reef itself - which we have shown can help these filter-feeding organisms to be more effective feeders - might also inadvertently increase their exposure to pollutants like microplastic. With no means of addressing this issue, due to our increasing awareness of the quantity of microplastic in the marine environment, this study offers the first evidence that forming a reef is a double-edged sword for individuals."

For the research, mussels were placed in controlled aggregations in a water flume and exposed to different wave speeds. Quantities of microplastics added to the water, ordinarily used to characterise the physical properties of the fluid itself (including the density of plastic in and around the reef structure), allowed the team to also assess particle ingestion risk under different environmental scenarios.

The study is the latest innovative project from the University examining the causes and impacts of microplastics within the marine environment.

It is work which, earlier in 2020, saw the University presented with the Queen's Anniversary Prize for Higher and Further Education for its pioneering research into microplastics pollution and its policy impact in the UK and globally.

CORVALLIS, Ore. - Hop-based dietary supplements that many women use to ease the night sweats and hot flashes commonly reported during menopause aren't likely to cause drug interactions, new research from Oregon State University's Linus Pauling Institute and College of Pharmacy shows.

The findings are important because while hormone replacement therapy remains the standard of care for menopausal patients, not all women are good candidates for it. Some studies have suggested hormone replacement therapy puts women at an increased risk for breast cancer and cardiovascular disease, sparking interest in alternative treatments.

Hops are the flowers of the hop plant and are what give beer its bitter flavor. Supplements made from hops can be effective for alleviating menopausal symptoms because hops contain phytoestrogens. Phytoestrogens are plant-based compounds that mimic the action of female sex hormones, whose deficiency is at the root of symptoms often felt by women in menopause, which also include sleep disturbances, fatigue and vaginal dryness.

"There are reports from other lab studies that compounds from hops may inhibit or deactivate certain drug-metabolizing enzymes," said the study's lead investigator and corresponding author, Richard van Breemen, director and principal investigator of the Linus Pauling Institute. "There is additional concern because we know the compounds in hops have a long half-life in humans, possibly more than 20 hours after taking them."

The long half-life means hops supplements may still be found in the bloodstream when women take drugs they are prescribed. Because these botanical supplements are made from plants, many people don't think of the possibility of drug interactions when they take them.

To determine hops' effect on drug-metabolizing enzymes, the scientists gave 16 research subjects a cocktail of four drugs, each one primarily metabolized by a different enzyme in a family of enzymes known as cytochrome P450s. The drugs were caffeine; alprazolam, an anti-anxiety medicine sold under the trade name Xanax; dextromethorphan, an over-the-counter cough suppressant; and tolbutamide, a medicine used to treat type 2 diabetes.

"We did each drug trial twice. Once to see how these women metabolized the drugs normally," van Breemen explained. "Then we repeated the trial with hops after the participants took a hops extract twice daily for two weeks. Thankfully, no enzyme inhibition was detected."

Guidelines for clinical studies of drug interactions involving CYP enzymes have been set by the U.S. Food and Drug Administration, he noted.

"Under FDA guidelines, the hop dietary supplement caused no clinically relevant pharmacokinetic interactions" said co-author Luying Chen, a Ph.D. student in van Breemen's lab. "So we can say that hop dietary supplements are not expected to produce any harmful drug interactions, at least with respect to the enzymes probed during this investigation. More research is needed, but these findings are good news for women who take hops for relief of menopause symptoms."

CORVALLIS, Ore. - Standup comedian Jon the Robot likes to tell his audiences that he does lots of auditions but has a hard time getting bookings.

"They always think I'm too robotic," he deadpans.

If raucous laughter follows, he comes back with, "Please tell the booking agents how funny that joke was."

If it doesn't, he follows up with, "Sorry about that. I think I got caught in a loop. Please tell the booking agents that you like me ... that you like me ... that you like me ... that you like me."

Jon the Robot, with assistance from Oregon State University researcher Naomi Fitter, recently wrapped up a 32-show tour of comedy clubs in greater Los Angeles and in Oregon, generating guffaws and more importantly data that scientists and engineers can use to help robots and people relate more effectively with one another via humor.

"Social robots and autonomous social agents are becoming more and more ingrained in our everyday lives," said Fitter, assistant professor of robotics in the OSU College of Engineering. "Lots of them tell jokes to engage users - most people understand that humor, especially nuanced humor, is essential to relationship building. But it's challenging to develop entertaining jokes for robots that are funny beyond the novelty level."

Live comedy performances are a way for robots to learn "in the wild" which jokes and which deliveries work and which ones don't, Fitter said, just like human comedians do.

Two studies comprised the comedy tour, which included assistance from a team of Southern California comedians in coming up with material true to, and appropriate for, a robot comedian.

The first study, consisting of 22 performances in the Los Angeles area, demonstrated that audiences found a robot comic with good timing - giving the audience the right amounts of time to react, etc. - to be significantly more funny than one without good timing.

The second study, based on 10 routines in Oregon, determined that an "adaptive performance" - delivering post-joke "tags" that acknowledge an audience's reaction to the joke - wasn't necessarily funnier overall, but the adaptations almost always improved the audience's perception of individual jokes. In the second study, all performances featured appropriate timing.

"In bad-timing mode, the robot always waited a full five seconds after each joke, regardless of audience response," Fitter said. "In appropriate-timing mode, the robot used timing strategies to pause for laughter and continue when it subsided, just like an effective human comedian would. Overall, joke response ratings were higher when the jokes were delivered with appropriate timing."

The number of performances, given to audiences of 10 to 20, provide enough data to identify significant differences between distinct modes of robot comedy performance, and the research helped to answer key questions about comedic social interaction, Fitter said.

"Audience size, social context, cultural context, the microphone-holding human presence and the novelty of a robot comedian may have influenced crowd responses," Fitter said. "The current software does not account for differences in laughter profiles, but future work can account for these differences using a baseline response measurement. The only sensing we used to evaluate joke success was audio readings. Future work might benefit from incorporating additional types of sensing."

Still, the studies have key implications for artificial intelligence efforts to understand group responses to dynamic, entertaining social robots in real-world environments, she said.

"Also, possible advances in comedy from this work could include improved techniques for isolating and studying the effects of comedic techniques and better strategies to help comedians assess the success of a joke or routine," she said. "The findings will guide our next steps toward giving autonomous social agents improved humor capabilities."

The studies were published by the Association for Computing Machinery/Institute of Electrical and Electronics Engineering's International Conference on Human-Robot Interaction.

DOI

10.1145/3319502.3374780

Most people with severe coronavirus infections (ie, SARS, MERS, and COVID-19) appear to recover without experiencing mental illness.

Delirium may feature in the acute stages of COVID-19, and clinicians should be aware of potential long-term mental health effects such as depression, anxiety, fatigue, and PTSD in the wake of the COVID-19 pandemic.

With only 12 low-to-moderate quality COVID-19 studies (including seven non-peer reviewed preprints) to draw on, and no post-recovery data, continued research will be needed.

Experts note that findings from past coronavirus outbreaks are useful, but may not perfectly predict prevalence of psychiatric complications from current pandemic.

Most people admitted to hospital with severe COVID-19 should recover without experiencing mental illness if infection with SARS-CoV-2 follows a similar course to the coronavirus epidemics of severe acute respiratory syndrome (SARS) in 2002 and Middle East respiratory syndrome (MERS) in 2012, according to the first systematic review and meta-analysis looking at the psychiatric consequences of coronavirus infections in over 3,550 patients hospitalised with SARS, MERS, and COVID-19, published in The Lancet Psychiatry journal.

Nevertheless, the findings suggest that delirium (a mental state characterised by changes in consciousness, behavioural disturbance, and sometimes hallucinations) may be common in hospitalised patients in the acute stages of SARS, MERS, and COVID-19 illness.

The study looks at severe cases in which individuals have been treated in hospital, and does not apply to milder cases or asymptomatic cases.

In the longer-term, the analysis suggests that SARS and MERS survivors may be at risk for mental illnesses such as depression, anxiety, fatigue, and post-traumatic stress disorder (PTSD) in the months and years following discharge from hospital. While there are no available data on these diagnoses in COVID-19 patients, the authors say that the medical community should be aware of the potential for high rates of these common mental problems in the aftermath of the current pandemic.

The authors caution that given that the majority (68/72) of studies included in the analysis were of either low or medium quality, and mainly involved data on patients with SARS and MERS treated in hospital, the true mental health effects of COVID-19 infection cannot be precisely predicted and will require ongoing research.

"Our analysis of more than 3,550 coronavirus cases suggests that most people will not suffer from mental health problems following coronavirus infection", says Dr Jonathan Rogers from University College London, UK, who co-led the research. "While there is little evidence to suggest that common mental illnesses beyond short-term delirium are a feature of COVID-19 infection, clinicians should monitor for the possibility that common mental disorders such as depression, anxiety, fatigue, and PTSD could arise in the weeks and months following recovery from severe infection, as has been seen with SARS and MERS." [1]

He continues, "With few data yet for COVID-19, high quality, peer-reviewed research into psychiatric symptoms of patients infected with SARS-CoV-2 as well as investigations to mitigate these outcomes is needed. Monitoring for the development of symptoms should be a routine part of the care we provide." [1]

There are several reasons why severe coronavirus infections might have psychiatric consequences, including possible direct effects of viral infection (including on the central nervous system), the degree of physiological compromise (eg, low blood oxygen), the immune response, and medical interventions. Other reasons relate to the wider social impact, including social isolation, the psychological impact of a novel severe and potentially fatal illness, concerns about infecting others, and stigma.

Although the COVID-19 pandemic has affected a large proportion of the world's population, relatively little is known about its potential effects on mental health.

To provide more evidence, the authors of the new study conducted a systematic review and meta-analysis of all studies and preprint articles (reporting data on the psychiatric and neuropsychiatric features of individuals with suspected or laboratory-confirmed coronavirus infection (SARS, MERS, or SARS-CoV-2) [2].

In total, 65 peer-reviewed studies up to March 18, 2020, and seven preprints between January 1 and April 10, 2020, reporting outcomes for patients admitted to hospital were included in the analyses. Pooled point prevalence (the proportion of people affected at a given time) from seven articles were included in the meta-analysis.

Analysis of data from two studies that systematically assessed common symptoms of patients admitted to hospital with SARS and MERS found that confusion occurred in 28% (36/129) of patients, suggesting delirium was common during acute illness (table 2). There were also frequent reports of low mood (42/129; 33%), anxiety (46/129; 36%), impaired memory (44/129; 34%), and insomnia (34/208; 12%) during the acute stage.

Twelve studies focusing on COVID-19 seemed to show a similar picture, with evidence of delirium (confusion in 26/40 intensive care unit patients, 65%; agitation in 40/58 ICU patients, 69%; and altered consciousness in 17/82 patients who subsequently died, 21%) while acutely ill (table 5).

Six studies looking at SARS and MERS patients after recovery from initial infection found frequent reports of low mood (35/332 patients, 11%), insomnia (34/208, 12%), anxiety (21/171, 12%), irritability (28/218, 13%), memory impairment (44/233, 19%), fatigue (61/316, 19%), and frequent recall of traumatic memories (55/181, 30%) over a follow-up period ranging from 6 weeks to 39 months (table 2).

The researchers estimate that the prevalence of PTSD among SARS and MERS survivors was 33% at an average of 34 months after the acute stage of illness (121/402 cases in four studies), whilst rates of depression and anxiety disorders was around 15% at an average of 23 months (77/517 cases from five studies) and one year (42/284 cases from three studies) after the acute stage respectively (figure 2).

However, the authors warn that these may be overestimates of the true mental health burden resulting from these outbreaks.

"It is likely that the apparently high rates of anxiety disorders, depression, and PTSD seen in SARS and MERS patients overestimate the actual burden", says co-lead author Dr Edward Chesney from King's College London, UK. "The lack of adequate comparison groups or assessment of patients' previous psychiatric history means that it is hard to separate the effects of coronavirus infections from pre-existing conditions, the impact of an epidemic on the population as a whole, or that selection bias (the possibility that patients were recruited into studies on the basis of factors that were associated with subsequent development of psychiatric illness) led to high prevalence figures."[1]

The authors note several limitations in the methodology and reporting of studies in the analysis, including the use of preprint articles that had not been subject to peer review; the exclusion of non-English-language articles; and the small sample size of several studies. Additionally, systematic assessment of psychiatric symptoms was rare, and the use of self-reported data (which might not be accurate) was common, whilst few studies included objective biological measures, such as blood markers of genetic, inflammatory, and immune function, or brain imaging. Finally, follow-up time for the post-illness studies varied between 60 days and 12 years, which makes direct comparison between studies difficult.

Writing in a linked Comment, lead author Dr Iris Sommer (who was not involved in the study) from the University Medical Centre Groningen in the Netherlands, says, "Findings from previous coronavirus outbreaks are useful, but might not be exact predictors of prevalences of psychiatric complications for patients with COVID-19. The warning from Rogers and colleagues that we should prepare to treat large numbers patients with COVID-19 who go on to develop delirium, posttraumatic stress disorder, anxiety, and depression is an important message for the psychiatric community."

She goes on to explain, "Treatment of patients admitted to the hospital for SARS-CoV-2 infection seems to be different from treatment of those admitted for SARS-CoV and MERS-CoV infections. Furthermore, the social situation to which COVID-19 survivors return is completely different from that of SARS and MERS survivors. These differences are relevant for the prevalence of psychiatric disorders in both acute and post-illness stages."

People taken ill by coronavirus infections may experience psychiatric problems while hospitalised and potentially after they recover, suggests an analysis of past research led by the UCL Institute of Mental Health with King's College London collaborators.

The systematic review paper, published in The Lancet Psychiatry, compiled results from short- and long-term studies of people hospitalised by recent coronaviruses, namely SARS (Severe acute respiratory syndrome) in 2002-2004, MERS (Middle East respiratory syndrome) in 2012, as well as COVID-19 this year.

COVID-19 is caused by the SARS-CoV-2 virus, a type of coronavirus. Some coronaviruses only cause mild symptoms of the common cold, but SARS-CoV-2 can cause severe respiratory illness, as did SARS-CoV-1 (the virus implicated in the 2002-2004 SARS epidemic) and MERS-CoV, which caused MERS in 2012.

The analysis found that one in four people hospitalised with COVID-19 may experience delirium during their illness, a known problem among hospital patients, which can increase risk of death or extend time in hospital.

The post-recovery effects of COVID-19 are not yet known, so long-term risks such as post-traumatic stress disorder (PTSD), chronic fatigue, depression, and anxiety are based on SARS and MERS studies, which may or may not apply to COVID-19 as well.

Co-lead author Dr Jonathan Rogers (UCL Psychiatry and South London and Maudsley NHS Foundation Trust) said: "Most people with COVID-19 will not develop any mental health problems, even among those with severe cases requiring hospitalisation, but given the huge numbers of people getting sick, the global impact on mental health could be considerable.

"Our analysis focuses on potential mental health risks of being hospitalised with a coronavirus infection, and how psychiatric conditions could worsen the prognosis or hold people back from returning to their normal lives after recovering."

The authors of the new paper analysed 65 peer-reviewed studies and seven recent pre-prints that are awaiting peer review, which included data from over 3,500 people who have had one of the three related illnesses. The review only included results from people who were hospitalised, and not people with more mild cases. The findings cover both acute symptoms during the illness, and long-term outcomes from two months to 12 years.

Almost one in three people hospitalised with SARS or MERS went on to develop PTSD, at an average follow-up time of almost three years, especially if they had ongoing physical health problems. Rates of depression and anxiety were also high, at roughly 15% one year or longer after the illness, with a further 15% also experiencing some symptoms of depression and anxiety without a clinical diagnosis. More than 15% also experienced chronic fatigue, mood swings, sleep disorder or impaired concentration and memory.

While in hospital, a significant minority of people with coronavirus infections experienced delirium symptoms such as confusion, agitation and altered consciousness. Almost 28% of people hospitalised for SARS and MERS experienced confusion, and early evidence from the ongoing pandemic suggests that delirium could be similarly common in COVID-19 patients. The authors found some preliminary evidence that delirium may have been associated with raised mortality during the MERS outbreak.

Co-lead author Dr Edward Chesney (Institute of Psychiatry, Psychology & Neuroscience, King's College London and South London and Maudsley NHS Foundation Trust) said: "We need more research on how to prevent mental health problems in the long term. One possibility might be to reduce social isolation by allowing patients to communicate with their loved ones by using video links."

The body of research also identified some of the risk factors associated with worse mental health outcomes. Researchers found that worrying a lot about the illness was associated with worse mental health in the long run, and healthcare workers had worse long-term mental health outcomes than other groups, while making a good physical recovery predicted better long-term mental health.

Senior author Professor Anthony David (UCL Institute of Mental Health) said: "To avoid a large-scale mental health crisis, we hope that people who have been hospitalised with COVID-19 will be offered support, and monitored after they recover to ensure they do not develop mental illnesses, and are able to access treatment if needed.

"While most people with COVID-19 will recover without experiencing mental illness, we need to research which factors may contribute to enduring mental health problems, and develop interventions to prevent and treat them."

People living in low-income, disadvantaged communities across much of urban Los Angeles lack the means to cool their homes, posing a growing threat to their health -- and their lives -- from extreme heat waves due to global warming, new USC research shows.

The communities across southern L.A. are most vulnerable, underscoring social inequities as a warming world affects populations differently. The USC research aims to help prepare the megalopolis for big disruptions, manifest in the coronavirus crisis today and climate change tomorrow.

"We studied how residential electricity use may increase in a warming world," said Kelly Sanders, an author of the study and associate professor of civil and environmental engineering at the USC Viterbi School of Engineering. "These will be the people and neighborhoods least likely to be resilient to climate change because it's harder for people in low-income communities to adapt."

COVID-19 adds urgency, Sanders said, because "it has underscored the importance of preparing for shocks, particularly those that disproportionately impact underserved populations. We know that extreme heat events are increasing over time, and we hope that our work can be used to direct resources towards building resilience to warming in the vulnerable communities that might suffer most."

The study was published May 19 in Environmental Research Letters.

Hot cities pose serious challenges for policymakers in a warming planet. Heat is already a big killer, accounting for more deaths each year in the United States than storms, floods and lightning combined, the study says.

Last year was the second hottest year on record, according to the World Meteorological Organization. The United Nations reports thousands of heat-related deaths or hospitalizations annually, raising concern among public health officials as extreme temperature events grow in intensity, frequency and duration.

Cities are becoming more crowded, too, as more than half of the world's population now lives in metro areas. The portion is forecast to grow to nearly 70% in 30 years. And cities face a double whammy due to an urban heat island effect, which occurs because the built environment retains more heat than natural environments.

Those trends pose challenges for electricity infrastructure and peak electricity management, underscoring the need to identify vulnerable communities. To anticipate future cooling needs, the study quantifies where urban warming is expected to increase air conditioning and energy use.

The USC research team turned to big data to tackle the problem.

First, they utilized smart meter data for 180,476 households in Southern California. Then, they quantified the increases in residential electricity use per degree of warming for census tracts in the region; that resulted in analyzing 3 billion electrical consumption records. They also created a method to estimate the prevalence of air conditioning units, which showed that the units are less common in poorer census tracts. Next, they utilized global warming projections for the region for 2070-2099.

"Our research suggests that more than half (55%) of the census tracts identified as most vulnerable are expected to experience more than 16 extreme heat days above 95 F per year by the end of the century," said George Ban-Weiss, an author of the study and professor of civil and environmental engineering at USC Viterbi.

Many communities clustered in southern L.A. -- including Lynwood, Compton, Inglewood and South Gate -- lack the advantages to cope with hot temperatures found in other parts of the region, making them more vulnerable to extremes, the study shows.

The study offers rich detail and data, as the analysis accounts for census tracts across Southern California -- data only made possible by advances in electricity meters.

"Before we had these household-level smart meter data, we couldn't locate the most vulnerable communities and where help is needed most," said Mo Chen, lead author of the study and a doctoral student at USC Viterbi.

The study underscores a growing body of research that shows the uneven impacts of global warming. For example, across Southern California, coastal communities are somewhat buffered by the ocean while wealthy communities can afford more energy use and many homes in inland valleys mostly have air conditioners installed.

"The findings are useful from a policy perspective because they give policymakers information to direct resources -- such as public funding, weatherization programs and cooling centers -- towards the vulnerable populations that will be most negatively affected by extreme events in the future," Sanders said.

With the continuing rise of China as a global economic and trading power, there is no barrier to prevent Chinese from becoming a global language like English, according to Flinders University academic Dr Jeffrey Gil.

Dr Gil's paper challenges arguments that suggest Chinese faces insurmountable hurdles to become a commonly used international language due to the complexity of Chinese written characters.

His article, titled "Will a character based writing system stop Chinese becoming a global language? A review and reconsideration of the debate", was published in the journal Global Chinese.

The article analyses the language practices, language ideologies and language planning surrounding the Chinese writing system, as well as the characteristics of contemporary global English, to show that Chinese could one day become a global language.

Dr Gil presents four arguments to support the possibility of Chinese one day becoming a global language.

Firstly, he emphasises that universal literacy is not required for global language status.

"There is a flawed assumption that all learners of Chinese must learn to read and write to a native-like level - although this does not reflect the global use of English. People learn as much English as is required for their purposes, and the same would apply if Chinese was a global language."

Dr Gil notes that computers and mobile phones can now convert Pinyin Romanisation (the Chinese phonetic alphabet) into characters, meaning that learners of the language need only learn Pinyin and character recognition, which saves considerable time and effort in regularly communicating in Chinese.

Dr Gil also points to Chinese having previously been a commonly used in other countries.

"There is a historical precedent for the adoption of characters outside of China, with a long-standing use of written Chinese for scholarly and official purposes in Korea, Japan and Vietnam," he says. "This occurred due to China's status as the most powerful country in the region, if not the world, and demonstrates that people in any country will learn and use characters if there is sufficient reason to do so."

The view that Chinese will not be embraced as a global language focuses excessively on linguistic properties, which is not accurate, according to Dr Gil.

"The inconsistencies and irregularities of English's writing system show that linguistic properties alone do not determine whether a language becomes global," says Dr Gil.

"I conclude that a character-based writing system will not prevent Chinese attaining global language status."

The molecular machinery responsible for replicating human DNA has come into sharper focus and deepened understanding of this fundamental biological process and how it can malfunction. An international team led by researchers at KAUST has used cryo-electron micrography to study the structure of the human Pol δ-DNA-PCNA complex.

During replication, the two strands in the DNA helix are unwound, and each serves as the template for a new copy. Pol δ is one of the enzymes responsible for copying one of the strands. It is tethered to the DNA by a molecule known as PCNA, forming a Pol δ-DNA-PCNA complex at the heart of replication.

The team found that the catalytic core of Pol δ--the part that carries out the synthesis reaction--sits on top of PCNA and that its regulatory subunits project to the side. The DNA is threaded through a central channel in PCNA, enabling the molecule to stabilize DNA exiting the reaction area. Further analysis revealed locations in PCNA that are required for the interaction, and results showed that mutating those sites severely reduced the activity of Pol δ.

Muhammad Tehseen, one of the lead authors of the study, explains that "Professor Hamdan's lab has been systematically reconstituting and studying the activities of these proteins by single-molecule imaging, recording molecular movies of these reactions."

Tehseen purified the molecular complex so that the team could create higher resolution static images. "Combining the dynamic information from single-molecule imaging with static images from cryoEM is like bringing an image to life," he explains.

The structure also clarified the role of some of the Pol δ subunits, shedding light on how it interacts with PCNA and DNA. For example, Pol δ interacts with only one monomer of PCNA, and sits in a manner that exposes the two other monomers, freeing them to interact with other proteins that act with Pol δ.

One such protein is FEN1, which processes the short fragment strands of DNA, after they are synthesized by Pol δ, so that they can be stitched together to form a continuous mature strand." The researchers also studied the structure of the Pol δ-DNA-PCNA-FEN1 complex. The interactions they discovered support a "toolbelt" model in which PCNA acts as a platform to which different processing enzymes bind, similar to a toolbelt with an array of tools.

Working out these structures and interactions enables researchers to better understand the dynamics of DNA replication and how it goes wrong, such as mutations in Pol δ linked with tumors.

Menthol cigarettes will be removed from shelves in the UK this Wednesday (20 May 2020), yet new research has found that tobacco companies failed to use the four-year phasing-in period (from 2016) to prepare for this week's ban. Instead they continued to sell and promote menthol products and to develop new products which circumvent the ban.

The University of Bath researchers behind the study - which is out today (Monday 18 May 0001 GMT) in the BMJ's Tobacco Control - argue this highlights how tobacco companies have exploited a delay in the ban to develop new products, keeping menthol products on the market for as long as possible, rather than phasing them out.

A menthol ban was first agreed in 2014 and originally due to be implemented in 2016, alongside accompanying measures such as standardised packaging. However, after intense lobbying, its implementation was put back four years, until this week when it will be implemented in the midst of Covid-19.

For the new study, the researchers from the Tobacco Control Research Group analysed industry analyst data to track menthol market cigarette share from legislation agreement through to 2018. They also analysed documentary evidence - industry documents, websites and retail publications - to understand tobacco industry activities.

Their results show that during the grace period the tobacco industry was given to prepare, the UK market share of menthol cigarettes grew rapidly from 14% of cigarette sales in 2014 to over a fifth (21%) in 2018.

With one in six menthol smokers stating they would quit after the menthol ban, an impact which potentially could reduce UK cigarette sales overall by 3%, the researchers say the menthol ban will be an important driver in the fight against deaths and illness from cigarette smoking.

Dr Rosemary Hiscock, lead author, explains: "Our findings suggest the tobacco industry was driving sales of menthol cigarettes right up to the ban - a product whose serious health implications had led to the ban in the first place."

In the paper, the authors argue that the tobacco industry used the delay to develop and introduce new menthol products that will circumvent the ban once it is implemented: menthol filters and flavour cards which smokers can add to cigarette packs or roll-your-own tobacco pouches to make them minty.

Due to a loophole in the tobacco display ban legislation, these accessories, unlike cigarettes, can be promoted to customers near the cash till in England and Wales (but not Scotland).

They also find that two tobacco companies have introduced cigarette-like 'cigarillos' (small cigars) with a flavour capsule. Although cigarillos have a small market share of UK tobacco sales at the moment, Euromonitor forecasts that this market will grow, not least because they are subject to lower taxes than cigarettes and are mostly exempt from plain packaging legislation.

Dr Hiscock added: "We recommend loopholes in legislation be closed as soon as possible to prevent tobacco companies undermining the intended public health impacts of the legislation. This includes preventing the display of tobacco accessories and extending the menthol ban to all tobacco products, including cigarillos and heated tobacco products.

"In Canada, the menthol ban stops menthol being used at all, whereas UK legislation only stops menthol's use as a characterising flavour. Banning menthol's use would stop menthol masking the harsh effects of smoking when it is present at undetectable levels."

Finally, the researchers highlight how big tobacco companies have created new websites and sponsored retail industry pieces which effectively undermine the intended public health benefit of the ban. These websites push consumers to switch to other products rather than quitting: a key concern is that they promote new heated tobacco products, such as IQOS, which are still allowed to have a menthol flavour.

Professor Anna Gilmore, Director of the Tobacco Control Research Group, explains: "The way tobacco companies are using the ban on menthol cigarettes to promote new menthol tobacco products which are heated rather than burned undermines the very purpose of this ban. It also flies in the face of tobacco company claims that they wish to reduce the harm from smoking. They realise the menthol ban will trigger smokers to quit. Instead they seek to move the smokers onto new tobacco products which independent evidence indicates are as dangerous as smoking and from which they make even more profit."

The team conclude that the tobacco industry's exploitation of the phase-in of the menthol ban repeats what happened during the 12-month phase-in period of standardised packaging, revealed by previous TCRG work. In both cases, tobacco companies misused the phase-in period to find ways to circumvent legislation and to shore up profits at the expense of public health, say the researchers.

The addition of menthol to cigarettes takes away some of the harsh sensations of smoking. Public health experts suggest this can make them more appealing to younger people and could lead them to become more quickly dependent on nicotine in comparison with non-menthol products. A menthol flavour can be added to cigarettes during the manufacturing process or smokers can add it themselves by crushing a menthol capsule.

Significantly however, menthol can mask early respiratory disease symptoms, so menthol smokers may carry on smoking after they start to become ill, at a time when smokers of other products might be prompted to quit.

Researchers from Sechenov University (Russia) and University of Pittsburgh (USA) discovered that the resistance of innate immune cells, macrophages, to ferroptosis - a type of programmed cell death - depends on the type of their activation. It turned out that cells helping tissues to recover from inflammation were more vulnerable. The researchers identified the mechanisms underlying the cells' resistance and explained how this research would help regulate inflammation in a paper published in Nature Chemical Biology.

When tissues are damaged and bacteria or viruses enter the body, this triggers a defense reaction and starts inflammation. Vasodilation and increased temperature at the site of injury aim to attract macrophages (cells that can 'capture' and digest bacteria and also pick-up and eliminate the remains of dead cells). In this process, macrophages get activated: depending on the stage of inflammation and incoming signals, they can become 'soldiers' (M1-type macrophages), which attack foreign particles and damaged cells of the body, or 'combat medics' (M2-type), that remove cell fragments and regenerate tissues. At the beginning of inflammation, the actions of the first group of macrophages are required, but if they continue their work longer than necessary, the inflammation becomes chronic and the surrounding tissues can suffer, so it is important that the second team get into action on time.

One of the mechanisms that can prevent the transition of acute pro-inflammatory response to the resolution phase is the different resistance of M1-and M2-macrophages to ferroptosis. As the authors of the study found, M2-type cells are much more susceptible to this type of cell death. In addition, the cells debris accumulating during ferroptosis can further provoke inflammation and even worsen the situation.

Ferroptosis allows the body to get rid of damaged and metabolically defective cells; it is necessary for normal development of the body and can serve as a potential new strategy for fighting cancer (activating ferroptosis and killing the cancer cells can slow down tumour growth), but in many cases, cell death as a result of ferroptosis is undesirable, and chronic inflammation is among them. Therefore, scientists try to explore this process as much as possible to understand what makes cells resistant or, on the contrary, vulnerable to it.

The authors conducted many experiments to determine the mechanisms that cause different sensitivity of cells to ferroptosis. Based on their results and new information, a mathematical model has been developed describing the stability of macrophages of different types under different conditions. The model can both describe the observed processes and predict the results of experiments.

This work deepens our understanding of the cellular processes that determine the resistance/sensitivity of macrophages to ferroptosis, thus facilitating the targeted control of this type of cell death.

Robots can be made from soft materials, but the flexibility of such robots is limited by the inclusion of rigid sensors necessary for their control. Researchers created embedded sensors, to replace rigid sensors, that offer the same functionality but afford the robot greater flexibility. Soft robots can be more adaptable and resilient than more traditional rigid designs. The team used cutting-edge machine learning techniques to create their design.

Automation is an increasingly important subject, and core to this concept are the often paired fields of robotics and machine learning. The relationship between machine learning and robotics is not just limited to the behavioral control of robots, but is also important for their design and core functions. A robot which operates in the real world needs to understand its environment and itself in order to navigate and perform tasks.

If the world was entirely predictable, then a robot would be fine moving around without the need to learn anything new about its environment. But reality is unpredictable and ever changing, so machine learning helps robots adapt to unfamiliar situations. Although this is theoretically true for all robots, it is especially important for soft-bodied robots as the physical properties of these are intrinsically less predictable than their rigid counterparts.

"Take for example a robot with pneumatic artificial muscles (PAM), rubber and fiber-based fluid-driven systems which expand and contract to move," said Associate Professor Kohei Nakajima from the Graduate School of Information Science and Technology. "PAMs inherently suffer random mechanical noise and hysteresis, which is essentially material stress over time. Accurate laser-based monitors help maintain control through feedback, but these rigid sensors restrict a robot's movement, so we came up with something new."

Nakajima and his team thought if they could model a PAM in real time, then they could maintain good control of it. However, given the ever-changing nature of PAMs, this is not realistic with traditional methods of mechanical modeling. So the team turned to a powerful and established machine learning technique called reservoir computing. This is where information about a system, in this case the PAM, is fed into a special artificial neural network in real time, so the model is ever changing and thus adapts to the environment.

"We found the electrical resistance of PAM material changes depending on its shape during a contraction. So we pass this data to the network so it can accurately report on the state of the PAM," said Nakajima. "Ordinary rubber is an insulator, so we incorporated carbon into our material to more easily read its varying resistance. We found the system emulated the existing laser-displacement sensor with equally high accuracy in a range of test conditions."

Thanks to this method, a new generation of soft robotic technology may be possible. This could include robots that work with humans, for example wearable rehabilitation devices or biomedical robots, as the extra soft touch means interactions with them are gentle and safe.

"Our study suggests reservoir computing could be used in applications besides robotics. Remote-sensing applications, which need real-time information processed in a decentralized manner, could greatly benefit," said Nakajima. "And other researchers who study neuromorphic computing -- intelligent computer systems -- might also be able to incorporate our ideas into their own work to improve the performance of their systems."

DALLAS, May 15, 2020 -- The Affordable Care Act (ACA) Medicaid Expansion appears to have eased health care inequities among heart failure patients; however, racial and ethnic disparities in heart failure care still exist, according to research presented today at the American Heart Association's Quality of Care & Outcomes Research Scientific Sessions 2020. The virtual conference, to be held May 15-16, is a premier global exchange of the latest advances in quality of care and outcomes research in cardiovascular disease and stroke for researchers, health care professionals and policymakers.

Using the American Heart Association's Get With the Guidelines-Heart Failure registry of nearly 272,000 patients, researchers compared patient information among early-adopter states that approved the ACA Medicaid Expansion by 2014, to states that had not adopted the expansion through 2019. They assessed if patients in underserved racial and ethnic minority groups received heart failure therapies, including guidelines-based medications, heart failure education and heart failure follow-up.

"Lack of insurance contributes to racial and ethnic health inequities among U.S. heart failure patients. We were pleased to find that ACA Medicaid Expansion was associated with increased delivery of cardiovascular care to racial and ethnic minority groups," said study author Khadijah Breathett, M.D., M.S., FAHA, assistant professor of cardiology at the University of Arizona College of Medicine in Tucson, Arizona. "Heart failure education and follow-up appointments can empower patients, contribute to better medical management and may prevent future hospitalizations."

Looking specifically at how the ACA Medicaid Expansion impacted the delivery of recommended medical care to African American, Asian, Hispanic and white patients hospitalized for heart failure, researchers found:

Hispanic patients in ACA Medicaid Expansion states were 146% more likely than Hispanics in non-ACA states to get medications recommended to treat heart failure. These medications include angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and angiotensin receptor-neprilysin inhibitors (ARNIs).

Asian patients in ACA Medicaid Expansion states were 44% more likely than Asians in non-ACA states to receive a heart failure follow-up appointment.

No significant differences were noted for other heart failure therapies among other racial and ethnic groups.

Hispanics living in ACA Medicaid Expansion states were notably more likely to receive all forms of heart failure therapy than Hispanics in non-adopter states, independent of when the states adopted the ACA.

"Today, health care professionals can examine barriers within their individual practices, administrators can examine barriers from a center level, and all of us must engage with policymakers to assure that policy keeps up with the needs of the people," she said. "Based on these findings, increased adoption of the ACA Medicaid Expansion may reduce racial and ethnic disparities in heart failure treatment and outcomes. However, health equity will require substantial changes in policy and additional investigation of interventions that may reduce barriers to care."

For the past 70 years, the best indicator of life expectancy for a patient with glioblastoma (GBM) -- the most common and the most aggressive brain cancer -- has simply been age at diagnosis. Now, an international team of scientists has experimentally validated a predictor that is not only more accurate but also more clinically relevant: a pattern of co-occurring changes in DNA abundance levels, or copy numbers, at hundreds of thousands of sites across the whole tumor genome.

Patients with the genome-wide pattern survive for a median of one year. However, patients without it survive three times as long, for a median of three years. The results came from a retrospective clinical trial that was published today in the journal Applied Physics Letters (APL) Bioengineering.

Having a predictor of a patient's life expectancy can help inform medical decisions. The GBM pattern can, in principle, be used in this way today. For example, when a patient has magnetic resonance imaging results that are inconclusive such information can help doctors decide whether to perform an intervention.

"The information contained in this pattern, and other patterns that we can discover by using the same mathematical methods, can improve the standard of care of GBM and other diseases," said the team leader Orly Alter, Ph.D., Utah Science, Technology, and Research (USTAR) associate professor of bioengineering and human genetics at the Scientific Computing and Imaging Institute and the Huntsman Cancer Institute at the University of Utah.

Personalizing medicine

Having a predictor that encompasses the whole genome could also help drugs progress to regulatory approval. That is because the cumulative effect of all genes is thought to be involved in the drug response.

"We expect the GBM pattern, for example, to identify the patients who would benefit from a drug in prospective clinical trials," said Sri Priya Ponnapalli, Ph.D., a senior research affiliate and an alumna of Alter's lab, who is the first author of the paper.

"Even if the drug targets just one gene, a patient's response to the drug would depend on the status of the whole genome and not just that one gene," she added. The successful approval of any additional drug would be significant. In GBM, for example, only one drug, which does not cure GBM, has advanced from trials to standard of care over the last 40 years.

The GBM pattern not only predicts survival, but also includes most DNA copy-number alterations that were known and at least as many that were unrecognized in GBM prior to its discovery, including new druggable targets. This enables drug development efforts to directly focus on gene targets that have been shown to correlate with patient outcome.

Finding relationships between patient outcomes and whole genomes

Alter's team were the first to successfully identify, and now to experimentally validate, a relationship between a GBM tumor's DNA copy numbers and a patient's life expectancy. However, researchers have recognized this type of DNA alteration as a hallmark of cancer for more than a century and have observed them in GBM tumors for decades.

The team uncovered the relationship by developing and using new mathematical methods to compare and contrast tumor and normal whole genomes from the Cancer Genome Atlas (TCGA), a publicly open national database. Repeated previous attempts to associate a tumor's DNA copy numbers with a GBM patient's outcome failed, including previous studies of the same data from TCGA that used other methods.

This is the first predictor that encompasses the whole tumor genome.

The new mathematical methods have overcome three distinct challenges that others had not. First, they found consistent patterns across the hundreds of thousands of sites in whole genomes, which have three billion nucleotides. Second, they were able to do that across the tumor and the matching normal genomes simultaneously. Third, they were able to do so in small cohorts of patients, about 100, that are typical in clinical trials.

"Our mathematical methods succeeded because they use the complex structure of the datasets rather than simplifying or standardizing them as is commonly done," said Alter. "This enables the separation of patterns which occur only in the tumor genomes from those that occur in the genomes of normal cells in the body and variations caused by experimental inconsistencies."

These methods can be used with any kind of data, biological and otherwise. They can therefore be used to inform personalized approaches to various health conditions, including infectious disease.

Quantum entanglement is a process by which microscopic objects like electrons or atoms lose their individuality to become better coordinated with each other. Entanglement is at the heart of quantum technologies that promise large advances in computing, communications and sensing, for example detecting gravitational waves.

Entangled states are famously fragile: in most cases even a tiny disturbance will undo the entanglement. For this reason, current quantum technologies take great pains to isolate the microscopic systems they work with, and typically operate at temperatures close to absolute zero. The ICFO team, in contrast, heated a collection of atoms to 450 Kelvin, millions of times hotter than most atoms used for quantum technology. Moreover, the individual atoms were anything but isolated; they collided with each other every few microseconds, and each collision set their electrons spinning in random directions.

The researchers used a laser to monitor the magnetization of this hot, chaotic gas. The magnetization is caused by the spinning electrons in the atoms, and provides a way to study the effect of the collisions and to detect entanglement. What the researchers observed was an enormous number of entangled atoms - about 100 times more than ever before observed. They also saw that the entanglement is non-local - it involves atoms that are not close to each other. Between any two entangled atoms there are thousands of other atoms, many of which are entangled with still other atoms, in a giant, hot and messy entangled state.

What they also saw, as Jia Kong, first author of the study, recalls, "is that if we stop the measurement, the entanglement remains for about 1 millisecond, which means that 1000 times per second a new batch of 15 trillion atoms is being entangled. And you must think that 1 ms is a very long time for the atoms, long enough for about fifty random collisions to occur. This clearly shows that the entanglement is not destroyed by these random events. This is maybe the most surprising result of the work".

The observation of this hot and messy entangled state paves the way for ultra-sensitive magnetic field detection. For example, in magnetoencephalography (magnetic brain imaging), a new generation of sensors uses these same hot, high-density atomic gases to detect the magnetic fields produced by brain activity. The new results show that entanglement can improve the sensitivity of this technique, which has applications in fundamental brain science and neurosurgery.

As ICREA Prof. at ICFO Morgan Mitchell states, "this result is surprising, a real departure from what everyone expects of entanglement." He adds "we hope that this kind of giant entangled state will lead to better sensor performance in applications ranging from brain imaging to self-driving cars to searches for dark matter."

A Spin Singlet and QND

A spin singlet is one form of entanglement where the multiple particles' spins--their intrinsic angular momentum--add up to 0, meaning the system has zero total angular momentum. In this study, the researchers applied quantum non-demolition (QND) measurement to extract the information of the spin of trillions of atoms. The technique passes laser photons with a specific energy through the gas of atoms. These photons with this precise energy do not excite the atoms but they themselves are affected by the encounter. The atoms' spins act as magnets to rotate the polarization of the light. By measuring how much the photons' polarization has changed after passing through the cloud, the researchers are able to determine the total spin of the gas of atoms.

The SERF regime

Current magnetometers operate in a regime that is called SERF, far away from the near absolute zero temperatures that researchers typically employ to study entangled atoms. In this regime, any atom experiences many random collisions with other neighbouring atoms, making collisions the most important effect on the state of the atom. In addition, because they are in a hot medium rather than an ultracold one, the collisions rapidly randomize the spin of the electrons in any given atom. The experiment shows, surprisingly, that this kind of disturbance does not break the entangled states, it merely passes the entanglement from one atom to another.

What The Study Did: This study compares COVID-19 cases in border counties in Iowa, which didn't issue a stay-at-home order, with cases in border counties in Illinois, which did.

Authors: George L. Wehby, Ph.D., of the University of Iowa in Iowa City, 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.2020.11102)

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.