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BOSTON - In the early months of the COVID-19 pandemic, the United States experienced higher rates of heart disease and cerebrovascular disease deaths, relative to the corresponding months the previous year. While a large body of evidence has shown that Black and Hispanic communities have borne a disproportionately high burden of disease and death from COVID-19, little is known about whether the rise in cardiovascular deaths during the pandemic has been disproportionately concentrated among racial and ethnic minority populations.

A new study led by clinician-researchers at the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center (BIDMC) characterized heart disease and cerebrovascular deaths by race and ethnicity during the U.S. COVID-19 pandemic and evaluated whether the relative increases in deaths were more pronounced among racial and ethnic minority groups, compared with non-Hispanic white persons. The team found that the year-over-year increase in deaths due to heart disease and cerebrovascular disease was significantly more pronounced among Black, Hispanic and Asian populations in the United States than in the non-Hispanic white population. The study was published today in the journal Circulation.

"Although the direct toll of COVID-19 on racial and ethnic minority groups has been substantial, our findings suggest that Black, Hispanic and Asian populations have also been disproportionately impacted by the indirect effects of the COVID-19 pandemic," said corresponding author Rishi K. Wadhera, MD, MPP, MPhil, a cardiologist in the Smith Center for Outcomes Research in Cardiology at BIDMC. "Disruptions in access to health care services during the pandemic may have had a larger impact on the health outcomes of Black and Hispanic individuals, as these populations have a higher burden of cardiovascular risk factors and disease, due in part to structural and systemic inequities. In addition, social determinants of health associated with cardiovascular risk, such as poverty and stress, have worsened in these communities as a result of the pandemic."

Wadhera and colleagues obtained monthly cause-of-death data from the National Center for Health Statistics from March 2020 -- when many states began to experience a rapid rise in COVID-19 cases -- through August 2020. Next, the team identified deaths caused by heart diseases and cerebrovascular diseases during this period as well as for the corresponding months in 2019.

Their analysis revealed that Black, Hispanic and Asian populations each experienced about a 19 percent relative increase in heart disease deaths, and a 13 percent relative increase in cerebrovascular disease deaths in 2020 compared to the previous year. The increase in deaths due to heart disease and cerebrovascular disease was significantly more pronounced among racial and ethnic minority populations compared with the non-Hispanic white population, which experienced a two percent and four percent relative increase in deaths due to each of these causes.

The researchers suggest a number of factors may have played a role in the disproportionate rise in cardiac and cerebrovascular deaths among racial and ethnic minorities, including disruptions in healthcare delivery in minority communities especially hard-hit by COVID-19. Although the use of telemedicine increased during the early phase of the COVID-19 pandemic to bridge gaps in care, Black, Hispanic, and Asian patients have also experienced unequal access to video telemedicine. In addition, avoidance of health care systems may have also played a role. A recent survey by the American Heart Association found that Hispanics and Black Americans were most likely to stay home if experiencing a heart attack or a stroke, to avoid the risk of contracting COVID-19 at the hospital.

Racial and ethnic minority groups also disproportionately experience poverty in the United States, a gap that only deepened after the onset of the COVID-19 pandemic. In a recent survey, 60 percent of Black and 72 percent of Hispanic households reported serious financial problems during the pandemic, compared with only 36 percent of white households.

Public policies may have also contributed to worse cardiovascular outcomes during the pandemic. In early 2020, the Trump administration revised immigration rules, leaving some documented immigrants in poor health at risk of being denied permanent residency status. As a result, Hispanic and Asian immigrant families may have avoided seeking care for cardiovascular disease.

"The extent to which disruptions in health care delivery, avoidance of care due to fear of contracting COVID-19 and/or immigration policy, and worsening inequities in social determinants of health have contributed to the increase in heart disease and cerebrovascular deaths remains an important area for future research," said Wadhera. "These data highlight that public health and policy strategies are urgently needed to mitigate the short- and long-term adverse effects of the pandemic on the cardiovascular health of minority populations."

A decade already passed from the first use of bioresorbable vascular scaffold in percutaneous coronary interventions. The first studies - by using surrogate endpoints - showed some superiority of BRS vs. metallic drug-eluting stent in terms of the so-called vascular restoration therapy with recovery of vasomotion and vascular pulsatility when the scaffold was absorbed.

Nevertheless, after these first promising findings, larger and randomized clinical trials and subsequent meta-analyses, powered to hard clinical endpoints, showed that bioresorbable vascular scaffolds, made of poly-lactic polymer, exhibit a higher rate of target lesion revascularization, with in particular a higher rate of scaffold thrombosis as compared with metallic drug-eluting stent. Interestingly, the implantation technique was related to these events rates, as these first generation bioresorbable scaffolds were characterized by a thick strut (150 micron), which made it similar to first generation metallic DES and therefore very much dependent by a very precise implantation technique.

At light of these findings, BRS made of polylactic acid were withdrawn from the market and only metallic BRS based on a magnesium platform are still used, restricted to a very specific subset of patients included in controlled studies.

Although BRS use is very limited nowadays, the need of a bioresorbable scaffold for treating coronary lesions, leaving nothing behind and allowing the so-called vascular restoration therapy, is still very much alive.

The FUTURE-II trial is a randomized trial comparing a new, thin-strut bioresorbable scaffold - the FIRESORB -poly-L-lactic acid-based sirolimus-eluting vs. everolimus-eluting cobalt-chromium stent (EES). The FIRESORB scaffold may be defined as a second generation bioresorbable scaffold: it is made of poly-lactic polymer, but with a strut thickness of only 100-125 micron, which made it close to second generation drug-eluting metallic stents. The trial wanted to demonstrate non-inferiority of the FIRESORB vs. EES, with a primary surrogate endpoint of late lumen loss at 1-year, which is known to be associated with clinical event rates. Major secondary endpoint is 1-year proportion of covered struts by OCT, which was evaluated in a subgroup of patients.

The trial succeeded to show non-inferiority of FIRESORB vs. EES in terms of 1-year angiographic late lumen loss (0.17 ± 0.27 vs. 0.19 ± 0.37 mm, p for non-inferiority Eventually, no difference was found in terms of target lesion failure between groups with very low rate of events (1.9% vs. 3.3%, p=0.37) and no definite probable device thromboses.

For all these reasons, the results of this trial may revitalize the concept of bioresorbable scaffold or may even stimulate the design of new pivotal studies with this new device. A proper implantation technique together with a device with improved physical and mechanical properties may give the opportunity to have a PLLA-based BRS back in our daily practice in a foreseeable FUTURE.

Postpartum psychosis is a devastating, but rare, mental health problem that affects women in the first few weeks after giving birth. Symptoms vary widely, and can include high mood (mania), depression, confusion, hallucinations and delusions.

Although the disorder affects only one in every 1,000 women who have a baby, it is much more common in mothers with a history of bipolar disorder or schizoaffective disorder (a condition which has symptoms of schizophrenia and bipolar disorder), or women who have suffered a previous episode of postpartum psychosis.

There are currently no biological markers that help to identify women who could go on to develop postpartum psychosis, and the role of brain connectivity - how different areas of the brain talk to each other, measured using brain scans - is yet to be fully explored.

Researchers from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King's College London, and the University of Padova in Italy, found that compared with healthy women, women at risk of postpartum psychosis show altered connectivity in brain networks associated with 'goal-directed behaviour' - i.e. areas of the brain involved in planning, organising and completing short and long-term tasks.

Their study also offers the first evidence that increased connectivity within the brain's executive network (responsible for attention, working memory and decision-making) could represent a marker of resilience to postpartum psychosis relapse.

32 women 'at risk' of postpartum psychosis, and 27 healthy women, were followed up from pregnancy through to eight weeks after giving birth. They were considered 'at risk' of postpartum psychosis if they had a diagnosis of bipolar disorder or schizoaffective disorder, or if they had suffered a previous episode of postpartum psychosis. In the first four weeks after delivery, 15 women became unwell with symptoms indicating postpartum psychosis.

Eight weeks after giving birth, the women had brain scans while resting, followed by further scans during an emotional processing task, to study how different brain areas were activated, and the interplay between them. For the task, participants looked at images of faces expressing different emotions and had to identify that emotion (for example, a face showing a fearful expression). The researchers measured how long it took for them to successfully identify these emotions and analysed how different networks of the brain were activated.

All women at risk of postpartum psychosis, and particularly those who later became unwell, struggled more with understanding and decoding negative emotions, compared to the healthy women. This was indicated by reduced connectivity between certain brain networks during the task, and longer reaction times to the negative emotional images.

While similar connectivity changes have also been revealed in patients with other psychiatric disorders, the King's study found that these changes were more marked specifically in women who become unwell, potentially reflecting the emotional instability women experience during the course of the disorder.

Paola Dazzan, Professor of Neurobiology of Psychosis at King's College London, said: "Although rare, postpartum psychosis is a very serious mental health problem that can be really frightening for new mothers, their partners, friends and family.

"Previously, it's been difficult to spot women at risk of postpartum psychosis or explain why some are more vulnerable than others, as we really haven't known enough about the neurobiology of the illness. Our study is the first step towards a better understanding of brain connectivity as a marker of vulnerability to postpartum psychosis."

Professor Dazzan added: "We recently published another paper looking at the role of stress in postpartum psychosis, which found that higher levels of cortisol (the main stress hormone) in the third trimester of pregnancy predicted postpartum psychosis relapse. If subtle alterations in the brain's executive network, and its interaction with other brain areas, were also detectable in pregnancy, these could offer vital clues to the development of postpartum psychosis. Potentially, this could enable us to intervene earlier, allowing clinicians to provide the best possible support for new mothers, before the onset of symptoms."

The researchers are now planning to study how these brain scan changes are related to the interaction between the mothers and their babies, and also how the babies develop during their first years of life.

The first-ever discovery of an extraterrestrial radioactive isotope on Earth has scientists rethinking the origins of the elements on our planet.

The tiny traces of plutonium-244 were found in ocean crust alongside radioactive iron-60. The two isotopes are evidence of violent cosmic events in the vicinity of Earth millions of years ago.

Star explosions, or supernovae create many of the heavy elements in the periodic table, including those vital for human life, such as iron, potassium and iodine.

To form even heavier elements, such as gold, uranium and plutonium it was thought that a more violent event may be needed, such as two neutron stars merging.

However, a study led by Professor Anton Wallner from The Australian National University (ANU) suggests a more complex picture.

"The story is complicated - possibly this plutonium-244 was produced in supernova explosions or it could be left over from a much older, but even more spectacular event such as a neutron star detonation," lead author of the study, Professor Wallner said.

Any plutonium-244 and iron-60 that existed when the Earth formed from interstellar gas and dust over four billion years ago has long since decayed, so current traces of them must have originated from recent cosmic events in space.

The dating of the sample confirms two or more supernova explosions occurred near Earth.

"Our data could be the first evidence that supernovae do indeed produce plutonium-244," Professor Wallner said

"Or perhaps it was already in the interstellar medium before the supernova went off, and it was pushed across the solar system together with the supernova ejecta."

Professor Wallner also holds joint positions at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and Technical University Dresden in Germany, and conducted this work with researchers from Australia, Israel, Japan, Switzerland and Germany.

The VEGA accelerator at Australian Nuclear Science and Technology Organisation, (ANSTO) in Sydney was used to identify the tiny traces of the plutonium-244.

The study has been published in Science.

An international team of scientists from the Menzies Health Institute Queensland (MHIQ) at Griffith University and from City of Hope, a research and treatment center for cancer, diabetes and other life-threatening diseases in the U.S., have developed an experimental direct-acting antiviral therapy to treat COVID-19.

Traditional antivirals reduce symptoms and help people recover earlier. Examples include Tamiflu®, zanamivir and remdesivir.

This next-generation antiviral approach used gene-silencing RNA technology called siRNA (small-interfering RNA) to attack the virus' genome directly, which stops the virus from replicating, as well as lipid nanoparticles designed at Griffith University and City of Hope to deliver the siRNA to the lungs, the critical site of infection.

"Treatment with virus-specific siRNA reduces viral load by 99.9%. These stealth nanoparticles can be delivered to a wide range of lung cells and silence viral genes,'' said co-lead researcher Nigel McMillan, Ph.D., professor and director of the Infectious Diseases & Immunology Program at MHIQ.

"Treatment with the therapy in SARS-Cov-2 infected mice improved survival and loss of disease. Remarkably, in treated survivors, no virus could be detected in the lungs,'' McMillan said.

Kevin Morris, Ph.D., professor and associate director of the Center for Gene Therapy at City of Hope and co-lead researcher from both City of Hope and Griffith University said, "This treatment is designed to work on all betacoronaviruses such as the original SARS virus (SARS-CoV-1) as well as SARS-CoV-2 and any new variants that may arise in the future because it targets ultra-conserved regions in the virus' genome."

McMillan added, "We have also shown that these nanoparticles are stable at 4°C for 12 months and at room temperature for greater than one month, meaning this agent could be used in low-resource settings to treat infected patients."

The results suggest that siRNA-nanoparticle formulations can be developed as a therapy to treat COVID-19 patients, as well as used for future coronavirus infections by targeting the virus' genome directly.

"These nanoparticles are scalable and relatively cost-effective to produce in bulk," Professor Morris said.

"This work was funded as an urgent call by Medical Research Futures Fund and is the type of RNA medicine that can be manufactured locally in Australia,'' McMillan said.

Scientists have detected new early-warning signals indicating that the central-western part of the Greenland Ice Sheet may undergo a critical transition relatively soon. Because of rising temperatures, a new study by researchers from Germany and Norway shows, the destabilization of the ice sheet has begun and the process of melting may escalate already at limited warming levels. A tipping of the ice sheet would substantially increase long-term global sea level rise.

"We have found evidence that the central-western part of the Greenland ice sheet has been destabilizing and is now close to a critical transition," explains lead author Niklas Boers from the Potsdam Institute for Climate Impact Research (PIK) and the Free University, Berlin, Germany. "Our results suggest there will be substantially enhanced melting in the future - which is quite worrying."

A key mechanism determining the overall stability of the Greenland ice sheet is the melt-elevation feedback. Essentially, increasing temperatures causes melting, which reduces the ice sheet's height. On a mountain, it's cold on top and less cold at the bottom. Hence, as the ice sheet's surface is melting, it sinks into lower, warmer surrounding air - which in turn leads to accelerated melting and additional height loss - a vicious circle. "This mechanism is long known, and it is one of the prime suspects for the detected destabilization of the central-western parts of the Greenland ice sheet. But we cannot exclude that other feedbacks, for example related to the albedo of the ice sheet, play an important role too," Boers explains.

Unsettling warning signs

For their analysis Boers and his co-author Martin Rypdal from the Arctic University of Norway factored in sea-level temperatures from weather stations, melt intensities from ice cores in central-west Greenland, as well as corresponding computer model simulations - and found unsettling early warning signs in the fluctuations of ice sheet heights, suggesting that a tipping of this part of the ice sheet is approaching. "The warning signs are caused by characteristic changes in the dynamics of the Greenland ice sheet, which reflect how well the ice sheet can resist against and recover from disruptions", Rypdal explains.

According to previous model results the melting of Greenland Ice Sheet is inevitable beyond a critical global mean temperature brink ranging from 0.8 to 3.2 degrees Celsius above pre-industrial levels. Once this threshold is crossed, the whole ice sheet could melt entirely over hundreds or thousands of years, potentially leading to a global sea-level rise of more than 7 meters and a collapse of the Atlantic Meridional Overturning Circulation (AMOC), which is responsible for the relative warmth in Europe and North America. But in addition to several positive feedbacks that accelerate melting, there exist negative feedbacks that might stabilize the Greenland ice sheet at intermediate heights levels, mostly via increasing accumulation. "We urgently need to better understand the interplay of the different positive and negative feedback mechanisms that determine the current stability and the future evolution of the ice sheet", says Boers.

The future of the ice sheet is uncertain

The study suggests that at least in the central-western part of the Greenland ice sheet a critical temperature threshold is close. Yet how this affects the ice sheet as a whole remains unclear: "Given the signs we detect in ice cores from the central-western part, we have to increase our efforts to gather more observation and to increase our understanding of the mechanisms at play, for more reliable estimates of the future evolution of the Greenland ice sheet," says Rypdal. "The main problem is the so-called hysteresis," Boers continues. "Regardless of the precise interplay of the different feedbacks, we would have to considerably reduce temperatures below pre-industrial to get back to the ice sheet height levels of the last centuries. So practically, the current and near-future mass loss will be largely irreversible. That's why it is high time we rapidly and substantially reduce greenhouse gas emissions from burning fossil fuels and re-stabilize the ice sheet and our climate."

FRANKFURT. There are currently only a few synthetic agents that bind to and block the widespread membrane transport proteins, ATP-binding cassette transporters (ABC). Scientists at Goethe University and the University of Tokyo identified four of these macrocyclic peptides as models for a novel generation of active substances. They used methods for which the scientists involved are considered world leaders.

Thanks to deep sequencing, an extremely fast and efficient read-out procedure, the desired macrocyclic peptides could be filtered out of a "library" of macrocyclic peptides comprising trillions of variants (1 with 12 zeroes) - a number that exceeds the number of stars in the Milky Way. The fact that such an enormous amount exists at all is related to a novel procedure: By reprogramming the genetic code, amino acids can be used specifically as active components that are not otherwise used in the cell. In particular, their circular, closed structure distinguishes them from natural proteins. "Because these therapeutics are cyclic, they break down less rapidly in the cell," explains Robert Tampé, Director of the Institute of Biochemistry at Goethe University. "In addition, the ring-shaped active substances are restricted in their spatial structure, so they bind to the target molecule without major rearrangements." A third distinguishing feature makes macrocyclic peptides particularly attractive for scientists: When the active substances are produced, their building instructions are supplied as a "barcode". If certain therapeutics are selected from among a trillion synthetically produced ones, they carry their "name tags" with them, so to speak.

So what role do synthetic therapeutics play in antibiotic resistance in bacteria or multidrug resistance in tumour cells? What happens when they encounter the ATP-driven transport molecule that is responsible for resistance by carrying the chemotherapeutic agents out of the cell? In a nutshell: The drugs block the transporter by binding to it. This can happen at the beginning or at the end of a transport process, when the transporter is in a resting state. However, since the scientists can slow down the transport process so that it is carried out in slow motion, they can identify the agents that "enter" in the middle of the transport process and "hold" the membrane protein in its respective position. In this way, the researchers gain an insight into the choreography of the transport process as if through the images of a film strip.

These insights have already led to a "paradigm shift" in science, as Tampé explains: "Until now, we have assumed that ATP hydrolysis (note: an energy-releasing splitting process) provides the energy for transport through the membrane. However, this is only indirectly the case. It is the event of the binding of the ATP molecule that pushes substances out of the cell. The energy of hydrolysis, on the other hand, is used to return the ABC transporter to its initial state." The research groups at Goethe University and the University of Tokyo are convinced that these and other insights into membrane processes will point to the development of future medicines.

Basic research on cellular membranes and membrane proteins already has a long tradition in Frankfurt. Robert Tampé elucidated essential mechanisms of ATP-driven transport proteins and cellular machinery of adaptive immune response and quality control, which together with this new publication can provide approaches for applied drug research. Tampé was head of the Collaborative Research Centre "Transport and Communication across Biological Membranes" (SFB 807) which expired at the end of 2020. Meanwhile the concept for a new research centre on highly dynamic processes related to protein networks and machineries in cellular membranes is already under development. In the long term, the research results should reveal new possibilities for the therapy of molecular diseases, infections and cancer.

One of the projected effects of a warming climate for species living on mountain slopes is moving their distributions upslope as their habits shift upwards. Eventually, since mountains have a limit to their elevation, a species may have no more habitat to move up to and therefore go extinct. Tracking how and where this is happening is tough, though, if you don't have a good idea of where the species are now. That's the situation in places such as Africa, which have tremendous biodiversity but spotty ecological baseline data.

So University of Utah researchers set out to assess the status of bird species in Ethiopia's Bale Mountains through six years' worth of bird banding efforts at five sites. The sites spanned more than a mile of vertical elevation on the tropical mountain slopes. The highest species richness, they found, was near the lowest and intermediate elevation stations, and six species were found at elevations higher than they'd been seen before.

The study, the authors write, establishes baseline observations for tropical birds in East Africa, filling in an important data gap for monitoring biodiversity and tropical ecosystem health in a warming world.

May 17, 2021 - Amid the rising toll of opioid overdoses and deaths in the U.S., several states are considering laws enabling civil commitment for involuntary treatment of patients with substance use disorders (SUDs). Most addiction medicine physicians support civil commitment for SUD treatment - but others strongly oppose this approach, reports a survey study in Journal of Addiction Medicine, the official journal of the American Society of Addiction Medicine (ASAM). The journal is published in the Lippincott portfolio by Wolters Kluwer.

"Civil commitment has emerged as a sometimes compelling yet controversial policy option," according to the new study, led by Abhishek Jain, MD. At the time of the study, Dr. Jain was at Columbia University and New York State Psychiatric Institute. The report is accompanied by a pair of expert commentaries: one discussing the idea of civil commitment in a historical context and another highlighting the dangers of coercive treatment and patient harm.

Physician specialists agree: more education and research needed on civil commitment for SUDs

Most states already have legislation providing for civil commitment of patients with SUDs. "These laws create a mechanism for family members, healthcare practitioners, or select others to seek involuntary court-mandated treatment for individuals suffering from addiction," according to the authors. The opioid crisis has spurred many states to adopt new or expand existing laws, or to implement them more widely.

However, there is little evidence for either beneficial or harmful effects of civil commitment for SUD treatment. To assess the views of addiction medicine physician specialists, Dr. Jain and coauthors sent an online survey to 1,451 members of the ASAM. The analysis included responses from 165 physicians, a rate of 11.4 percent.

Overall, 60.7 percent of the addiction medicine specialists favored civil commitment with involuntary treatment of SUDs. Another 21.5 percent of physicians were opposed to civil commitment for SUDs, while 17.8 percent were unsure. About half of respondents said they would likely consider using civil commitment laws if available in their state, while more than one-third said they were not familiar with such laws.

Nearly 80 percent of respondents believed civil commitment should be permitted for patients who used heroin, while about 75 percent thought it would be appropriate for those who used alcohol or opioids other than heroin. Sixteen percent opposed civil commitment for any type of SUD.

Most respondents believed that medications and behavioral therapies - as well as resources to pay for treatment - would be essential for civil commitment laws to be effective. By large majorities, the specialists agreed on the need for more education and research.

Those who opposed civil commitment were more likely to say it would "jeopardize patient rapport" and would be ineffective for unmotivated patients. Whether they favored or opposed civil commitment, addiction medicine specialists agreed on the need for an efficient legal system, available secure treatment facilities, clear consequences for patients who don't follow treatment plans, and ongoing aftercare.

A commentary by William F. Haning III, MD, of the University of Hawai'i at Manoa, Honolulu, discusses reasons for the diverging views of addiction medicine specialists and highlights critical questions for further research: particularly the criteria for civil commitment and the effectiveness of compulsory treatment. He emphasizes the need for "a wider range of supervisory and custodial changes," based on evidence-based approaches.

In another commentary, John C. Messinger, BS, of Harvard Medical School and Leo Beletsky, JD, MPH, of Northeastern University, Boston, call on addiction care providers to "challenge the use of state power to coerce people into treatment settings - especially when such settings often diverge from best clinical practices." They conclude: "Addiction professionals must reject perpetuating punitive structures that harm the individuals we are hoping to serve."

What The Study Did: Hospital discharge rates, hospitalization outcomes and demographic factors were examined among U.S. patients with ischemic stroke before and during the COVID-19 pandemic.

Authors: Adam de Havenon, M.D., of the University of Utah in Salt Lake 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.2021.10314)

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

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Scientists have succeeded in dating some of the oldest stars in our galaxy with unprecedented precision by combining data from the stars' oscillations with information about their chemical composition.

The team led by researchers at the University of Birmingham, surveyed around a hundred red giant stars, and were able to determine that some of these were originally part of a satellite galaxy called Gaia-Enceladus, which collided with the Milky Way early in its history.

The results, published in Nature Astronomy, revealed that the group of stars surveyed all have similar ages, or are slightly younger than the majority of the stars known to have started their lives within the Milky Way. This corroborates existing theories suggesting the Milky Way had already started forming a significant fraction of its stars when the merger with the Gaia-Enceladus (also known as the Gaia Sausage) occurred.

By the time of the collision, the Milky Way was already efficiently forming stars, most of which now reside within its thick disc, one of two disc-like structures that make up the Galaxy.

Josefina Montalbán, lead author on the paper, said: "The chemical composition, location and motion of the stars we can observe today in the Milky Way contain precious information about their origin. As we increase our knowledge of how and when these stars were formed, we can start to better understand how the merger of Gaia-Enceladus with the Milky Way affected the evolution of our Galaxy."

In making the calculations, the team used asteroseismology data from the Kepler satellite in combination with data from the Gaia and APOGEE instruments. All three are set up to gather data to help scientists map and characterise stars in the Milky Way.

Asteroseismology is a relatively new technique, which measures the relative frequencies and amplitudes of the natural modes of oscillation of the stars. This enables scientists to assemble information about the star's size and internal structure, which enables accurate estimations of the star's age to be made.

In this research, the team used information on the individual oscillation modes of each star, rather than averaged properties of their pulsations. They were also able to use asteroseimology in combination with spectroscopy - which enables the chemical composition of the stars to be measured.

Co-author, Professor Andrea Miglio, at the University of Bologna, said: "We have shown the huge potential of asteroseismology in combination with spectroscopy to deliver precise, accurate relative ages for individual, very old, stars. Taken together, these measurements contribute to sharpen our view on the early years of our Galaxy and promise a bright future for Galactic archeoastronomy."

Researchers from Tohoku University have developed a new numerical method that paves the way for simulating landslide tsunamis.

Their research was published in the journal Computational Mechanics on May 13, 2021.

Landslides occurring on land or underneath the sea - known as subaerial and submarine landslides respectively - can cause devastating tsunamis. They also pose other hazards such as severing submarine cables and pipelines.

Yet the mechanisms at play behind these landslides are less well understood, partly due to the multifaceted interactions taking place: a collapse of the seabed and/or the interaction between soil and water. Conventional approaches make it difficult to predict the behaviors of soil and seawater with high accuracy.

The researchers' breakthrough proposes a new hybrid simulation method that can express the complex interaction between soil structures - referred to as granular masses - and liquids.

"Our novel method couples together two computational methods that analyze the interactions of solids and liquids: the finite element method (FEM) along with the material point method (MEM)," said Kenjiro Terada, professor at Tohoku University's International Research Institute of Disaster Science and co-author of the study.

Using the newly created algorithm, the researchers were able to simulate a wave mimicking a submarine granular collapse and a wave induced by a subaerial slide over an inclined plane. To their delight, the simulations were in reasonable agreement with the numerical measurements.

Several numerical examples also revealed that the proposed method can be applied to other types of potentially dangerous natural events that involve the interaction of air, water, and solids.

Looking ahead, Terada and his team aim to improve the accuracy of their experimental measurements and apply it to larger-scale real data.

An international team of researchers from Japan, the US and the UK has analyzed the function of the histone demethylase KDM5A in multiple myeloma, one of the three major hematological cancers, and clarified the mechanism by which it promotes myeloma cell proliferation. They also developed a novel KDM5 inhibitor and showed that it inhibits cancer cell growth in a myeloma mouse model. The researchers expect that new therapies targeting KDM5A will be developed in the future.

The prognosis for multiple myeloma is improving every year with the introduction of new therapeutic agents, but there is still no cure. Further elucidation of the pathogenesis of this cancer and the development of therapeutic agents are required. The molecular pathogenesis of cancers, including multiple myeloma, is deeply related not only to genetic alterations but also to epigenetic changes. The epigenetic regulator KDM5 family proteins are highly expressed in myeloma cells, but their function is not clear.

To clarify the role of KDM5 family proteins in myeloma cells, researchers from Kumamoto University and the Dana-Farber Cancer Institute used genetic manipulation to suppress the expression of KDM5 in human myeloma cell lines. They found that among KDM5 family members, KDM5A in particular had a strong effect on cell proliferation which prompted them to analyze its molecular mechanisms. They also developed a novel KDM5 inhibitor and validated its efficacy using both myeloma patient cells and myeloma mouse models.

Genetic suppression of KDM5A expression or pharmacological inhibition of KDM5 inhibited the growth of myeloma cells. Furthermore, by using myeloma mouse models in which a human myeloma cell line was transplanted into immunodeficient mice, the researchers demonstrated that their KDM5 inhibitor suppresses myeloma cell growth even in vivo. Functional analysis revealed that KDM5A cooperates with MYC, an important transcription factor in myeloma development and growth, to promote the expression of MYC target genes. Although a high level of histone methylation (H3K4me3) was originally observed near the transcription start site of MYC target genes, this modification level was further increased by repressing KDM5A. This indicates that excess H3K4me3 acts as a barrier to transcription thereby inhibiting transcription contrary to previous theories that H3K4me3 promoted transcription. Further analysis suggested that KDM5A helps switch transcription-associated complexes as they proceed from transcription initiation to transcription elongation by transiently releasing H3K4me3.

This study proposed a new model of epigenetic regulation in which KDM5A regulates histone methylation at the transcription start site to optimal levels during the required phase, thereby promoting the transcription of MYC target genes and leading myeloma cells to proliferation. It also showed that KDM5 inhibitor inhibits the growth of myeloma cells.

"Our research has elucidated part of the mechanism of myeloma cell proliferation mediated by histone modification regulation, and has shown the potential for therapies targeting KDM5A," said Associate Professor Hiroto Ohguchi, who led this study. "It is also becoming clear that the KDM5 family is involved in the growth of other carcinomas. The problem with the KDM5 inhibitors so far is that they have weak cell membrane permeability and are not effective in cells or in vivo. However, if a therapeutic drug is developed based on the KDM5 inhibitor developed in this study, it is expected to develop into a new therapeutic strategy for not only multiple myeloma but also various other types of cancer by combining it with conventional treatment methods."

Scientists from Hokkaido University have used species survey and climate data to identify two marine biodiversity refugia in the Eastern Bering Sea - regions where species richness, community stability and climate stability are high.

Marine biodiversity, the diversity of life in the seas and oceans, supports ecosystem services of immense societal benefits. However, climate change and human activities have been adversely affecting marine biodiversity for many decades, resulting in population decline, community shifts, and species loss and extinction. Developing effective means to mitigate this rapid biodiversity loss is vital.

Scientists from Hokkaido University have identified and characterised regions in the Eastern Bering Sea where biodiversity has been protected from the effects of climate change. Their work was published in the journal Global Change Biology.

Conservation is one of the many approaches by which we have been able to protect biodiversity in various environments from climate change, pollution and human encroachment. Conservation hinges on the identification of areas where the maximum amount of biodiversity is preserved. One such area are refugia, regions that are relatively buffered from the impacts of ongoing climatic changes, which provide favorable habitats for species when the surrounding environment becomes inhospitable.

The scientists tracked the distribution of 159 marine species in the Eastern Bering Sea, off the coast of Alaska, from data collected by the National Oceanic and Atmospheric Administration (NOAA) between 1990 and 2018. Using statistical analysis, they attempted to find regions where there existed persistently high species richness and a stable marine community over a longer period of time. They also, separately, mapped out the changes in climate across the Eastern Bering Sea over the same period.

The scientists identified two distinct refugia in the fishery-rich waters of the Eastern Bering Sea. These regions covered less than 10% of the total study area but harbored 91% of the species analyzed. Most significantly, among the species sheltered in these refugia, commercially important fish and crabs were present in high numbers -- indicating that these refugia conserved high-value resources in addition to supporting high species diversity and community stability. Moreover, these refugia overlapped with regions of high climatic stability over time, where trends in seasonal sea surface temperatures and winter sea ice conditions remained largely unchanged.

Climate buffering and high productivity within the Eastern Bering Sea refugia potentially permit the persistence of stable communities and high biodiversity as well as cushion marine communities from the impacts of fishing. "These biodiversity refugia, albeit small, will be increasingly crucial for preserving communities in this climate-exposed and continually exploited marine ecosystem," says Irene D. Alabia, the lead author of the paper. "At a larger scale, this underpins the need and urgency to identify and manage marine biodiversity refugia to maintain climate-resilient marine ecosystems and fisheries."

Researchers at the University of Adelaide have found several grape varieties native to Cyprus, which tolerate drought conditions better than some international varieties popular in Australia, contain chemical compounds responsible for flavours preferred by Australian consumers.

The study published in OENO One follows earlier research with Cypriot grape varieties Maratheftiko and Xynisteri in particular, which showed they are well adapted to a hot climate and continue to perform well as the climate becomes hotter.

Lead author and PhD student Alexander Copper, from the University of Adelaide's School of Agriculture, Food and Wine, said: "With climate change placing greater strain on the resources needed to sustain viticulture, it is necessary for the global wine industry to investigate alternative grape varieties better suited to hotter climates.

"While the ability to tolerate hotter climates is critical for any alternative varieties considered, they also need to deliver on taste," Mr Copper said.

In the new study, researchers looked at the role of polyfunctional thiols, which are aroma impact compounds generally known for their contribution to the 'tropical' aroma and flavour of Sauvignon blanc and, more recently, in Chardonnay. The study investigated five such thiols in Cypriot wines comprising the white variety Xynisteri, and two red varieties, Maratheftiko and Giannoudhi, comparing them to Australian Pinot Gris, Chardonnay and Shiraz wines.

Researchers found that each white wine contained compounds responsible for 'grapefruit', 'tropical fruit' and 'passionfruit' aromas at well above their sensory threshold, whereas compounds associated with 'struck flint' and 'meaty' characters were much lower in concentration. A compound responsible for aromas likened to 'roasted coffee' was only detected in the Chardonnay and four of the Xynisteri wines. A final thiol, with aroma attributes of 'blackcurrant' and 'boxwood' was only detected in Pinot Gris and three Xynisteri wines.

Overall, researchers found the concentration of flavour compounds in the Cypriot wines was comparable to those in popular Australian wines such as Chardonnay and Sauvignon blanc.

Corresponding author Dr Dimitra Capone, an ARC Research Associate with the ARC Training Centre for Innovative Wine Production at the University of Adelaide, has more than 25 years experience in the area of aroma and flavour chemistry.

Dr Capone said: "Finding the presence of these desirable flavour compounds in Cypriot grape varieties is exciting and opens up further questions regarding their sensory contributions at varying concentrations in Cypriot wines."

Mr Copper added: "In better understanding the thiol composition of Cypriot varieties, producers can better tailor their products to consumer preferences in a changing climate."

The presence of flavour compounds enjoyed by consumers in the Cypriot wines aligns with the findings of the earlier consumer sensory project conducted by the researchers.

"The panel of wine experts in the sensory study identified flavours upon tasting Xynisteri wines that were comparable to Pinot Gris, which aligns with what we found when analysing the compounds present in both Pinot Gris and several varieties of Xynisteri," said Mr Copper.

"In consumer trials, consumers 'liked' the flavour of the Cypriot varieties, and in one segment of consumers, Xynisteri was preferred to Pinot Gris."

Since bringing the Cypriot vines to Australia for research at the University's Waite campus, Mr Copper said they have been approached by several grape growers interested in the varieties, particularly Xynisteri. In recent weeks the project has had discussions with renowned South Australian viticulturist Paul Georgiadis and the project will begin its first vineyard trials at Paulmara Wines in the Barossa Valley later this year.

"This latest research adds further support for considering Cypriot varieties for use in Australia and other hot wine growing regions," he said.

Mr Copper's PhD project is supported by an Adelaide Graduate Research Scholarship and a supplementary scholarship from Wine Australia.