Culture

ROCHESTER, Minn. -- Research by investigators at Mayo Clinic Cancer Center suggests that physicians should screen patients with lung cancer for MET amplification/overexpression before determining a treatment strategy. Their findings are published Cancer Discovery, a journal of the American Association for Cancer Research.

"In our research we found several lung cancer cases that were not responsive to standard chemotherapy," says Zhenkun Lou, Ph.D., a cancer researcher at Mayo Clinic. "Because these lung cancers were positive for PD-L1, a protein that allows some cells to escape attack by the immune system, we then tried treating these patients with anti-PD1 immunotherapy to relieve PD-L1 mediated immune suppression, however this treatment also failed."

Dr. Lou and his colleagues then used cell line animal models and patient tissue samples to study why these lung cancers were not responding to treatment.

"We discovered that in these particular cases, the cancer exhibited a MET oncogene amplification, which creates a hostile environment for immunotherapy," says Dr. Lou. Abnormal MET activation has been implicated as an oncogenic driver in non-small-cell lung cancer.

After analyzing several independent medical databases, Dr. Lou and his colleagues confirmed that MET oncogene amplification should be a factor to be considered when designing lung cancer therapy. In addition, they showed that in animal models, a combination of a MET inhibitor with anti-PD1 immunotherapy was effective in treating cancers with MET amplification.

"Our study suggests that patients with a MET oncogene amplification will not respond to immunotherapy alone and will require treatment with a combination of a MET inhibitor together with immunotherapy," says Dr. Lou. He cautions that this strategy will require confirmation in a prospective clinical trial before becoming a standard of care. In the meantime, Dr. Lou suggests that patients with lung cancer be screened for MET amplification/overexpression before determining an immunotherapy strategy.

A key factor in America's prodigious agricultural output turns out to be something farmers can do little to control: clean air. A new Stanford-led study estimates pollution reductions between 1999 and 2019 contributed to about 20 percent of the increase in corn and soybean yield gains during that period - an amount worth about $5 billion per year.

The analysis, published this week in Environmental Research Letters, reveals that four key air pollutants are particularly damaging to crops, and accounted for an average loss of about 5 percent of corn and soybean production over the study period. The findings could help inform technology and policy changes to benefit American agriculture, and underscore the value of reducing air pollution in other parts of the world.

"Air pollution impacts have been hard to measure in the past, because two farmers even just 10 miles apart can be facing very different air quality. By using satellites, we were able to measure very fine scale patterns and unpack the role of different pollutants," said study lead author David Lobell, the Gloria and Richard Kushel Director of the Center on Food Security and the Environment.

The research highlights the considerable power of satellites to illuminate pollution impacts at a scale not possible otherwise. That power could be of even greater value in countries with less access to air monitors and yield data.

Reading the air

Scientists have long known that air pollution is toxic to plant life in high doses, but not how much farmers' yields are actually hurt at current levels. The impact of pollution on agriculture overall, as well as the effects of individual pollutants, has also remained unknown.

Focusing on a nine-state region (Illinois, Indiana, Iowa, Michigan, Minnesota, Missouri, Ohio, South Dakota and Wisconsin) that produces roughly two-thirds of national maize and soybean output, Lobell and study co-author Jennifer Burney, an associate professor of environmental science at the University of California, San Diego, set out to measure the impact on crop yields of ozone, particulate matter, nitrogen dioxide and sulfur dioxide.

Ozone is the result of heat and sunlight-driven chemical reactions between nitrogen and hydrocarbons, such as those found in car exhaust. Particulate matter refers to large particles of dust, dirt, soot or smoke. Nitrogen dioxide and sulfur dioxide are gases released into the atmosphere primarily through the burning of fossil fuels at power plants and other industrial facilities.

"This has been a tricky problem to untangle because historically our measurements of different types of air pollutants and our measurements of agricultural yields haven't really overlapped spatially at the necessary resolution," explained Burney. "With the new high spatial resolution data, we could look at crop yields near both pollution monitors and known pollutant emissions sources. That revealed evidence of different magnitudes of negative impacts caused by different pollutants."

Lobell and Burney extended their analysis back to 1990, when Congress passed Clean Air Act amendments that resulted in significant air quality improvements across the country. The researchers looked through air pollution data from hundreds of monitoring stations around the region, federal data on power plant emissions, satellite-based observations of nitrogen dioxide around those power plants, crop yield data from federal surveys and satellite imagery, as well as weather data to account for growing season conditions known to explain crop yield variations.

Surprising findings

What Lobell and Burney discovered surprised them. Among their findings: negative effects of each of the four pollutants on corn and soybean yields, and a clear yield increase the farther away from power plants - particularly coal-burning facilities - crops were grown. The unique spatial patterns of each pollutant allowed them to disentangle the effect of each pollutant in a way that past studies could not.

The researchers estimated that total yield losses from the four pollutants averaged 5.8 percent for maize and 3.8 percent for soybean over the past two decades. Those losses declined over time as the air grew cleaner. In fact, the reduction in air pollution contributed to an estimated 4 percent growth in corn yields and 3 percent growth in soybean yields - increases that equal 19 percent of corn's overall yield gains during the timeframe and 23 percent of soybeans' overall yield gains.

"We already know that the Clean Air Act resulted in trillions of dollars of benefits in terms of human health, so I think of these billions in agricultural benefits as icing on the cake," Lobell said. "But even if it's a small part of the benefits of clear air, it has been a pretty big part of our ability to continue pushing agricultural productivity higher."

The number of people who live past the age of 100 has been on the rise for decades, up to nearly half a million people worldwide.

There are, however, far fewer “supercentenarians,” people who live to age 110 or even longer. The oldest living person, Jeanne Calment of France, was 122 when she died in 1997; currently, the world’s oldest person is 118-year-old Kane Tanaka of Japan.

Such extreme longevity, according to new research by the University of Washington, likely will continue to rise slowly by the end of this century, and estimates show that a lifespan of 125 years, or even 130 years, is possible.

“People are fascinated by the extremes of humanity, whether it’s going to the moon, how fast someone can run in the Olympics, or even how long someone can live,” said lead author Michael Pearce, a UW doctoral student in statistics. “With this work, we quantify how likely we believe it is that some individual will reach various extreme ages this century.”

Longevity has ramifications for government and economic policies, as well as individuals’ own health care and lifestyle decisions, rendering what’s probable, or even possible, relevant at all levels of society.

The new study, published June 30 in Demographic Research, uses statistical modeling to examine the extremes of human life. With ongoing research into aging, the prospects of future medical and scientific discoveries and the relatively small number of people to have verifiably reached age 110 or older, experts have debated the possible limits to what is referred to as the maximum reported age at death. While some scientists argue that disease and basic cell deterioration lead to a natural limit on human lifespan, others maintain there is no cap, as evidenced by record-breaking supercentenarians.

Pearce and Adrian Raftery, a professor of sociology and of statistics at the UW, took a different approach. They asked what the longest individual human lifespan could be anywhere in the world by the year 2100. Using Bayesian statistics, a common tool in modern statistics, the researchers estimated that the world record of 122 years almost certainly will be broken, with a strong likelihood of at least one person living to anywhere between 125 and 132 years.

To calculate the probability of living past 110 — and to what age — Raftery and Pearce turned to the most recent iteration of the International Database on Longevity, created by the Max Planck Institute for Demographic Research. That database tracks supercentenarians from 10 European countries, plus Canada, Japan and the United States.

Using a Bayesian approach to estimate probability, the UW team created projections for the maximum reported age at death in all 13 countries from 2020 through 2100.

Among their findings:

Researchers estimated near 100% probability that the current record of maximum reported age at death — Calment’s 122 years, 164 days — will be broken;
The probability remains strong of a person living longer, to 124 years old (99% probability) and even to 127 years old (68% probability);
An even longer lifespan is possible but much less likely, with a 13% probability of someone living to age 130;
It is “extremely unlikely” that someone would live to 135 in this century.

As it is, supercentenarians are outliers, and the likelihood of breaking the current age record increases only if the number of supercentenarians grows significantly. With a continually expanding global population, that’s not impossible, researchers say.

People who achieve extreme longevity are still rare enough that they represent a select population, Raftery said. Even with population growth and advances in health care, there is a flattening of the mortality rate after a certain age. In other words, someone who lives to be 110 has about the same probability of living another year as, say, someone who lives to 114, which is about one-half.

“It doesn’t matter how old they are, once they reach 110, they still die at the same rate,” Raftery said. “They’ve gotten past all the various things life throws at you, such as disease. They die for reasons that are somewhat independent of what affects younger people.

“This is a very select group of very robust people.”

In Canada, low-income hospital patients under palliative care are less likely to receive medical assistance in dying compared to those who are high income, according to a study published in British Medical Journal Open (BMJ Open).

Medical assistance in dying (MAID) is legal and free under Medicare, Canada's universal health care system. Patients with low socioeconomic status (SES), however, generally tend to experience less access to medical care compared to their high SES counterparts.

Eldar Shafir, professor of psychology and public affairs at the Princeton School of Public and International Affairs, along with a team of researchers from Sunnybrook Hospital in Ontario, investigated whether this trend of decreased care for low-income patients includes medical assistance in dying.

"I have long been interested in SES influences on decision-making," said Shafir. "I often discuss with my friend and collaborator, Dr. Redelmeier, ways to illustrate some of our findings in the medical realm, especially, when possible, among experts. ... In this case MAID was a really interesting domain, since it's a 'big' decision, and finances are not an issue."

Medical assistance in dying was ruled legal in Canada in February 2015 and officially implemented and covered under Medicare by June 2016. To be considered, a patient must have a grievous and irremediable medical condition, such as metastatic cancer, that causes unbearable suffering where death is foreseeable, according to the Government of Canada.

However, one's socioeconomic status can influence how medical care is administered and received by a patient in several ways. "People can be easily susceptible to pitfalls and biases in reasoning," Shafir said.

Low-income patients, for example, may feel less equipped to advocate for their care and to convey dissatisfaction. Clinicians can also succumb to the "thick-skin fallacy," or the harmful perception that low-income people are used to hardship and therefore less impacted by it.

The team explored the association between socioeconomic status and medical assistance in dying by identifying hospital patients aged 65 and older in Ontario, Canada between June 2016 and 2019. At the time of their death, all patients, all of whom had serious medical conditions, were under palliative care, receiving pain-relieving treatment for symptoms. They were then divided into groups based on socioeconomic status, which was calculated using an official algorithm created by Statistics Canada based on home neighborhood location, and whether they received medical assistance in dying.

During the three years, 50,096 patients were given palliative care in their last month of life. Among them, 920 received medical assistance in dying. Only 1.5% of low-income patients identified were given MAID, compared to 2.4% of high-income patients -- a 39% decreased likelihood for those with low socioeconomic status. This disparity in care was found consistently across a variety of patient subgroups that varied in age, sex, home location, type of cancer, health care utilization, and general frailty. It was even replicated with patients treated by the same responsible physician.

The study's results support past findings by other countries about the relationship between medical assistance in dying and patients' socioeconomic status. In countries like the United States, the Netherlands, Switzerland, and Belgium, people who received MAID or MAID equivalents tended to be highly educated, financially secure, or live in wealthy neighborhoods.

The researchers, however, suspect that this difference in patient care may be influenced by factors that exist outside of financial capabilities. "I suspect most of what happens here is a function of the doctor-patient interaction," explained Shafir. "I think, all else equal, that doctors might see low-SES patients as less in urgent need of MAID."

Certain study limitations, such as biased and imperfect socioeconomic status measures, warrant further research exploring the link between social class and medically assisted death. "Both perspectives, the doctors' and the patients', need to be better understood by the medical community in order to provide low-SES patients with same care afforded those of higher SES," said Shafir.

The observations made by Shafir and his team address an earlier misconception in Canada that medical assistance in dying may harmfully target low-income individuals. The researchers are optimistic that their findings may help promote greater patient-clinician communication and engagement.

LA JOLLA, CA--Researchers at La Jolla Institute for Immunology (LJI) have found that T cells from people who have recovered from COVID-19 or received the Moderna or Pfizer-BioNTech vaccines are still able to recognize several concerning SARS-CoV-2 variants.

Their new study, published online on July 1, 2021 in Cell Reports Medicine, shows that both CD4+ "helper" T cells and CD8+ "killer" T cells can still recognize mutated forms of the virus. This reactivity is key to the body's complex immune response to the virus, which allows the body to kill infected cells and stop severe infections.

"This study suggests that the impact of mutations found in the variants of concern is limited," says LJI Professor Alessandro Sette, Dr.Bio.Sci., study senior author and member of the LJI Center for Infectious Disease and Vaccine Research. "We can presume that T cells would still be available as a line of defense against viral infection."

The researchers emphasize that the study only addresses how the body's T cells respond to Variants of Concern (VOCs). The researchers emphasize that several of these variants, are linked to lower levels of virus-fighting antibodies.

The current study includes data on four of the most prevalent VOCs. Ongoing studies have been expanded to a larger panel of variants, including the Delta (B.1.617.2) variant, which became prevalent after this study had been initiated. The team has also established relationships with more than 20 different laboratories around the world to help monitor T cell reactivity to VOCs.

"These variants are still a concern, but our study shows that even if there is a decrease in antibodies, as other studies have shown, the T cells remain largely unaffected," says LJI Instructor Alba Grifoni, Ph.D. "The vaccines still work."

The Johnson & Johnson/Janssen COVID-19 vaccine was not part of this study because it was not available at the time the study was launched.

LJI findings guide COVID-19 vaccine efforts

This study was previously published online as a pre-print in March 2021. The findings were then highlighted by National Institutes of Allergy and Infectious Diseases Director Anthony Fauci, M.D., in a March 31 White House press briefing.

"We're learning more and more that these CD4+ and CD8+ T cells are very important in that they cross-react against certain viral variants," Fauci said.

In the time since the paper was first published, the researchers nearly tripled their patient cohort and performed an additional method of stringent statistical analysis. "We've also added an unexposed donor cohort," says study first author Alison Tarke, a Ph.D. student of the University of Genoa, guested in the Sette Lab at LJI.

For the new study, the researchers analyzed T cells from three different groups: people who had recovered from COVID-19, people who had received either the Moderna or Pfizer-BioNTech vaccines, and people never exposed to SARS-CoV-2 (from samples taken before the pandemic).

Both the recovered subjects and the vaccinated subjects were likely to have T cells that recognized the "ancestral lineage" of SARS-CoV-2. This was the original strain that emerged at the beginning of the pandemic; however, the virus has mutated since December 2019, and several variants have been identified as VOCs.

The question was whether people with T cells trained to recognize the ancestral strain would also recognize the new variants. The researchers tested T cell responses from the donor groups against four prominent VOCs: Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Epsilon (B.1.427/B.1.429).

The researchers found that both vaccinated individuals and the recovered patients had cross-reactive T cells that could target these variants. That is good news for anyone who has received one of the two mRNA vaccines and for anyone who has recovered from any variant of the virus.

"With this study, the underlying message is optimistic," adds Tarke. "At least, as far as the T cell response goes, your immune system is still able to recognize these new variants and your T cells will be able to respond."

Similar results reporting largely unaffected T cell reactivity has now been presented through independent studies published in Nature and Science Immunology.

Study co-author and LJI Professor Shane Crotty, Ph.D., says this research highlights the importance of enlisting T cells in fighting SARS-CoV-2.

"COVID vaccines do a fantastic job of making antibodies that stop SARS-CoV-2 infections, but some of the vaccines do less well at stopping infections from variants," Crotty says. "You can think of T cells as a backup system: if the virus gets past the antibodies--if you have vaccine T cells the T cells can probably still stop the variant coronavirus infection before you get pneumonia."

Researchers are now looking for ways to take advantage of how flexible the T cells response appears to be. With T cells already working hard to recognize SARS-CoV-2 variants, Grifoni says future "booster" shots could increase immunity by prompting the body to produce more antibodies against the variants and/or by adding additional parts of the virus recognized by T cells.

"T cell epitopes are well conserved among SARS-CoV-2 variants, so incorporating T cell targets into future COVID vaccines could be a clever way to make sure future variants can't escape the vaccines," adds Crotty.

There is also the possibility that current SARS-CoV-2 research may one day lead to a universal, "pan-coronavirus" vaccine. This kind of vaccine would train the body to recognize the structural details, such as elements of the spike protein, that all coronaviruses have in common.

"This research shows that a pan-coronavirus vaccine is feasible," says Grifoni.

The group is now studying a much larger group of 12 different Variants of Concern (VOCs) and Variants of Interest (VOIs), including the Delta variant (B.1.617.2), Eta (B.1.525), Iota (B.1.526), Kappa (B.1.617.1), Lambda (C37) and the variants B.1.526.1, B.1.617.3, R1 and B.1.1.519.

Sette says he'd also like to study T cells from people who have been infected with the variants and see how those T cells react to the ancestral strain of the virus.

Minority-ethnic medical students must have more role-models in senior leadership positions if they are to engage with academia. This is one of the conclusions drawn by a group of medical students writing in the Journal of the Royal Society of Medicine about the drivers and barriers to engaging with academia.

Barriers currently hampering the chances of minority-ethnic medical students accessing formal pathways into academia, they write, include differential attainment and unconscious bias, difficulties forming meaningful mentor-mentee relationships, as well as the lack of role models from minority-ethnic backgrounds.

Drawing on their own experiences, the medical students write that while progress has been made to increase the number of academics from minority ethnic backgrounds, the same progress has not been made celebrating them as people or their contributions to science, especially given the inspirational impact individuals such as Mary Seacole or Charles Richard Drew have had on future generations of students.

Co-author Carlos Curtis-Lopez, of the University of Manchester medical school, said: "Nationally, major research funders and policymakers could start by making a real statement of intent addressing this problem. They should also ensure a proportion of those in senior leadership positions reflect the entire population that they serve and that there is diverse representation across committees, selection and award panels."

He added: "By having medical students from minority-ethnic backgrounds see something of themselves among those in senior leadership roles, it could be enough of a nudge to push them into having a conversation with academics in their institutions about pursuing a career in academia."

Senior author Dr Rakesh Patel, Clinical Associate Professor in Medical Education at the University of Nottingham, said: "Given diversity of thinking and representation are associated with greater scientific impact and growth, not having minority-ethnic students consider academia is a lost opportunity for all."

In an article appearing in Nature Biomedical Engineering, a team of scientists from the UCLA David Geffen School of Medicine and UCLA School of Engineering report real-world results on SwabSeq, a high-throughput testing platform that uses sequencing to test thousands of samples at a time to detect COVID-19. They were able to perform more than 80,000 tests in less than two months, with the test showing extremely high sensitivity and specificity.

SwabSeq uses sample-specific molecular barcodes to simultaneously analyze thousands of samples for the presence or absence of SARS-CoV-2, the virus that causes COVID-19. SwabSeq was granted FDA Emergency Use Authorization in October and is currently deployed at UCLA in a high-complexity CLIA laboratory, which has performed over 150,000 tests since December 2020. SwabSeq is a flexible protocol and can rapidly scale up testing for novel pathogens, including COVID-19 and future emerging viruses.

"We have optimized SwabSeq to prioritize scale and low cost, key factors that are missing from current COVID-19 diagnostics," the authors write.

"These results demonstrate the potential of SwabSeq to be used for SARS-CoV-2 testing on an unprecedented scale," said Dr. Valerie Arboleda, Assistant Professor and lead scientist on the project. "SwabSeq offers a potential solution to the need for population-wide testing to stem the pandemic." In the months since, the team has continued to use the test, and as of this date has performed more than 150,000 tests.

The groundbreaking technology was developed in a collaboration between scientists at the Department of Computational Medicine affiliated with both the David Geffen School of Medicine and the Samueli School of Engineering at UCLA, the Department of Human Genetics, the Department of Pathology and Laboratory Medicine, and Octant, a start-up company founded and incubated at UCLA. SwabSeq is a modification of Octant's technology that is being applied toward drug discovery and has been made available broadly to fight the pandemic. UCLA scientists have been leading a broader coalition of academic and industrial labs around the country and the world to develop the technology to scale up COVID-19 testing.

1 July 2021: Despite only limited evidence that fertility add-ons increase the odds of having a baby, the majority of women (82%) have used one or more of these treatments as part of their IVF.

This is the conclusion of a retrospective study of 1,590 Australian patients which also found more than seven in 10 (72%) had incurred additional costs for these unproven additional therapies and techniques which range from Chinese herbal medicine to endometrial scratching.

The results based on an online survey into prevalence of these optional extras will be presented today by principal investigator Dr Sarah Lensen, a researcher from the University of Melbourne, Australia, at the 37th virtual Annual Meeting of ESHRE.

The findings, says Lensen, suggest that patients "may not be adequately informed" about the lack of evidence to support "the effectiveness and safety of add-ons". She adds that "accessible and transparent information" is needed - and large high-quality randomised trials - to help women make decisions and minimise the regret felt by those whose IVF has been unsuccessful.

This report into add-ons is based on a questionnaire advertised on Facebook, distributed to women undergoing IVF, and completed between June and July 2020. Gestational surrogates or patients who used a surrogate were excluded as were those who donated eggs or underwent elective egg freezing.

Participants were asked about their IVF and medical history, and details about add-on use over the past 3.5 years including specific treatments and cost. They were also questioned about what importance they placed on evidence around safety and effectiveness.

In addition to cost and prevalence of add-ons, the results showed that the most commonly used of these optional extras was acupuncture (45%) followed by preimplantation genetic testing for aneuploidy (PGT-A) (28%) then Chinese herbal medicine (26%).

The cost associated with some of the add-ons used such as aspirin and heparin, says Lensen, is likely to be negligible. However, she points out that expenses are likely to be "significant" for PGT-A, or for repeated add-on treatments over multiple cycles.

Overall, relatively few (18%) women using add-on fertility treatments reported that they first raised the issue, with more than half (54%) saying they had first heard about them from their fertility specialist. The majority (71%) said their specialist generally raised add-on options during consultations.

What also emerged from the study is that women placed significant importance on scientific evidence supporting the use of add-ons. More than half (55%) scored over 90 (out of 100) that they think it's important there is evidence that add-ons improve live birth rates, and 73% gave the same score for their use being safe. This is despite associations to the contrary, says Lensen, as most add-ons are not supported by evidence that they increase live birth rates (LBRs), and some such as immune therapies have been linked with low birth weight and other issues.

Around a third (30%) of women experienced moderate to severe regret about using add-ons compared with 34% who had no regret at all. The level of misgivings about their decision was higher in women who had not conceived or achieved a live birth. In addition, those who reported their fertility specialist had more than 50% input into their decision to use an add-on had more regret than those whose doctor had a lesser role.

The study results come at a time when adjunct treatments are under increasing scrutiny. UK regulator the Human Fertilisation and Embryology Authority (HFEA) has introduced a traffic light system to rate add-ons but none has been awarded a green signal.

The use of some adjunct therapies, says Lensen, is likely to be "associated with a significant financial burden" and may even "potentially pose risk to patient." Therefore, she says impartial evidence-based information like the HFEA's should be available in other countries.

Sophia Antipolis - 1 July 2021: Heart failure patients aged 80 and above are less likely to receive recommended therapies and dosages compared to their younger counterparts, according to research presented today at Heart Failure 2021, an online scientific congress of the European Society of Cardiology (ESC).1

"Guidelines recommend the same treatments for all heart failure patients regardless of age," said study author Dr. Davide Stolfo of the Karolinska Institute, Stockholm, Sweden.2 "Our analysis adjusted for other conditions that might justify withholding therapy or reducing the dose - for example impaired kidney function - and age was independently associated with undertreatment."

The study investigated the prescription of evidence-based therapy in patients with heart failure according to three age categories: under 70, 70 to 79, and 80 years or older. The analysis was limited to heart failure with reduced ejection fraction since it is the only subtype with treatments proven to benefit prognosis. The researchers used data from the nationwide Swedish Heart Failure Registry linked with other national registries in 2000 to 2018.

The study included 27,430 patients with heart failure. The average age was 74 years and 27% were women. Regarding the age categories, 31% were under 70, 34% were 70 to 79, and 35% were 80 years or above. Patients in the oldest age category were more likely to be women than men, and had more severe heart failure and more co-existing conditions compared to the other age groups.

Prescription of treatments progressively decreased with increasing age. Regarding medications, RASi (renin angiotensin system inhibitor)/ARNi (angiotensin receptor neprilysin inhibitor), beta-blockers, and MRA (mineralocorticoid receptor antagonist), respectively, were prescribed in 95%, 95% and 54% in patients aged under 70? 90%, 93% and 47% in patients aged 70 to 79; and 80%, 88% and 35% in those aged 80 or above.

Regarding device therapies, the use of implantable cardioverter defibrillators (ICDs) and cardiac resynchronisation therapy (CRT), respectively, among eligible patients was 22% and 50% in patients under 70; 17% and 42% in the 70 to 79 group; and 5% and 23% in those aged 80 or above.

Patients aged 80 or above were also less likely to be treated with the recommended dose of medications or to receive all three recommended types of medications (RASi/ARNI, beta-blocker and MRA). Half of those under 70 met both recommendations compared to just 42% of the 70 to 79 age group, and 26% of those aged 80 or above.

The researchers analysed the association of age with the prescription of each medication and device, and the use of recommended doses. The analysis was extensively adjusted for other conditions including diabetes, previous cancer, kidney function, low blood pressure and anaemia. With the exception of CRT, age was independently and inversely associated with the odds of receiving recommended treatments and dosages.

Dr. Stolfo said: "Our analysis shows that even after statistical adjustment for many other variables included in the registries, nearly all treatments are underused in older patients. This was an observational study so it is not possible to determine the reasons, but one possibility is that clinicians believe treatments are less effective in older people with heart failure."

Dr. Stolfo noted that older patients, particularly those with co-existing conditions, are often excluded from clinical trials. He said: "Studies in older age groups with heart failure are needed to provide clinicians with greater certainty about the effectiveness of full-dose treatment. We should follow the example of a study investigating this question according to gender, which suggested that women with heart failure might need lower doses of some medications than men."3

He concluded: "In younger patients with heart failure, the primary goal of treatment is to improve survival, while in older patients we aim to reduce symptoms, improve quality of life and prevent hospitalisations. Strategies are needed to ensure that all patients with heart failure are optimally treated."

New research from marine biologists offers answers to a fundamental puzzle that had until now remained unsolved: why are some fish warm-blooded when most are not?

It turns out that while (warm-blooded) fish able to regulate their own body temperatures can swim faster, they do not live in waters spanning a broader range of temperatures.

The research therefore provides some of the first direct evidence as to the evolutionary advantage of being warm-blooded as well as underlining that species in this demographic - such as the infamous white shark and the speedy bluefin tuna - are likely just as vulnerable to changing global ocean temperatures as their cold-blooded relatives.

Lucy Harding, PhD Candidate in Trinity College Dublin's School of Natural Sciences, is the first author of the associated research article, which has just been published in the journal, Functional Ecology. She said:

"Scientists have long known that not all fish are cold-blooded. Some have evolved the ability to warm parts of their bodies so that they can stay warmer than the water around them, but it has remained unclear what advantages this ability provided.

"Some believed being warm-blooded allowed them to swim faster, as warmer muscles tend to be more powerful, while others believed it allowed them to live in a broader range of temperatures and therefore be more resilient to the effects of ocean warming as a result of climate change."

Lucy and her international team of collaborators assessed these two possibilities by collecting data from wild sharks and bony fish, as well as using existing databases.

By attaching biologging devices to the fins of the animals they caught, they were able to collect information such as water temperatures encountered by the fish in their habitats; the speeds at which the fish swam for most of the day; and the depths of water the fish swam in.

The results showed that warm-blooded fishes swim approximately 1.6 times faster than their cold-blooded relatives, but they did not live in broader temperature ranges.

Nick Payne, Assistant Professor in Zoology in Trinity's School of Natural Sciences, said:

"The faster swimming speeds of the warm-blooded fishes likely gives them competitive advantages when it comes to things like predation and migration. With predation in mind, the hunting abilities of the white shark and bluefin tuna help paint a picture of why this ability might offer a competitive advantage.

"Additionally, and contrary to some previous studies and opinions, our work shows these animals do not live in broader temperature ranges, which implies that they may be equally at risk from the negative impacts of ocean warming. Findings like these - while interesting on their own - are very important as they can aid future conservation efforts for these threatened animals."

As the COVID-19 pandemic exploded across the globe in early 2020, the world's leaders were faced with a flurry of tough moral dilemmas. Should schools and businesses shut down, and if so, for how long? Who should receive scarce resources, such as ventilators, when there wouldn't be enough for everyone? Should people be required to practice contact tracing to control the spread of infection? Should life-saving medicine be held for a country's own citizens or shared with those in greater need?

Some global leaders advocated for a utilitarian approach to these dilemmas: impartially maximizing the greatest good for the greatest number of people, even if that would come at the cost of harming a minority of the population. Utilitarianism, however, is a controversial way of making moral decisions and those who use this approach might not be viewed as trustworthy.

In a new study, Molly Crockett, an associate professor of psychology at Yale, examined whether people trust leaders who make utilitarian decisions during a pandemic. To find out, she and her co-first authors -- Yale's Clara Colombatto and the University of Kent's Jim Everett -- assembled a multidisciplinary team of 37 international researchers to study people's trust in leaders around the globe. In a series of online experiments conducted as cases surged late in 2020, the team asked nearly 24,000 people in 22 countries whether the endorsement or rejection of utilitarian policies impacted their trust in leaders.

The results, published July 1 in the journal Nature Human Behavior, show people had a nuanced view when judging the policy decisions of leaders. People tended to trust utilitarian leaders who sought to save the most lives around the globe, rather than favoring their own citizens. But they were far less willing to trust those whose policy decisions would sacrifice the well-being of some for the benefit of others.

For instance, a shortage of ventilators led some leaders to propose reserving them for younger people more likely to survive a severe case of COVID-19. People tended to distrust leaders who accepted this form of utilitarianism, known as instrumental harm. However, they bestowed more trust in those who would share scarce medicine in regions globally where it is most needed, an aspect of utilitarianism called impartial beneficence.

The results were consistent across the countries studied, which included Australia, Brazil, Canada, Chile, China, Denmark, France, Germany, India, Israel, Italy, the Kingdom of Saudi Arabia, Mexico, the Netherlands, Norway, Singapore, South Africa, South Korea, Spain, the United Arab Emirates, the United Kingdom, and the United States of America.

These patterns held regardless of whether or not people personally agreed with the leader's policy decision. "People do prefer leaders who agree with them on policies, but even after we control for individual policy preferences, people generally trust leaders who endorse impartial beneficence and distrust leaders who accept instrumental harm," said Colombatto, a Ph.D. student in the Department of Psychology.

Everett concluded, "When communicating during a crisis, leaders should be aware that utilitarian approaches to moral dilemmas can both erode and enhance trust -- even when the leaders themselves doesn't have the power to resolve them."

Pandemic choices: Do you trust leaders who make these?

Researchers asked almost 24,000 people in 22 countries to read about moral dilemmas leaders faced during the COVID-19 pandemic. Two examples of those tough moral choices are below. After learning about the leaders' decisions, respondents were asked to rate how trustworthy they thought those leaders were, and to make decisions about whether to trust each leader with control of a group's financial resources. Subjects were also asked whether they would vote for a leader who took a particular policy position.

A demonstration of the trust rating survey is available here:

https://yalesurvey.ca1.qualtrics.com/jfe/form/SV_ekzXerwo4NHMzyK

Medicine Dilemma

Non-Utilitarian Leader

Imagine that the mayor of a major city in your region is arguing that U.S.-made medicine should be reserved for treating American citizens.

This mayor said, "We have a right to use our own resources to help our own citizens before everyone else. Other countries can produce their own treatments for COVID-19."

Average self-reported trust: 3.93 out of 7; votes: 38.93%

Utilitarian Leader

Imagine that the mayor of a major city in your region is arguing that U.S.-made medicine should be given to whoever needs it most, even if that means sending it to other countries.

This mayor said, "COVID-19 is a global pandemic that affects all humans equally. We need to be impartial and send treatment where it can achieve the greatest good."

Average self-reported trust: 4.57 out of 7; votes: 61.07%

Ventilators Dilemma

Non-Utilitarian Leader

Imagine that the mayor of a major city in your region is arguing that doctors should give everyone equal access to COVID treatment.

This mayor said, :It's not our place to choose who lives. Everyone has the same right to receive equal access to treatment, and we cannot abandon our most vulnerable in an effort to save more lives."

Average self-reported trust: 5.41 out of 7; votes: 85.15%

Utilitarian Leader

Imagine that the mayor of a major city in your region is arguing that younger and healthier people should be prioritized for COVID treatment.

This mayor said, "We have to think about how we can do the most good with the resources we have, and that means prioritizing those people who have the best chance of recovering and living a long and healthy life."

Average self-reported trust: 2.97 out of 7; votes: 14.85%

Nanosized molecules of a particular chemical element can inhibit the formation of plaque in the brain tissues. This new discovery by researchers at Umeå University, Sweden, in collaboration with researchers in Croatia and Lithuania, provides renewed hope for novel treatments of, for instance, Alzheimer's and Parkinson's disease in the long run.

"This is indeed a very important step that may form the basis of new and efficient treatments of neurodegenerative diseases in the future," says Professor Ludmilla Morozova-Roche at Umeå University.

When proteins misfold they form insoluble fibrils called amyloids, which are involved in several serious diseases such as Alzheimer's and Parkinson's, Corino de Andrade's and the mad cow disease. Amyloid aggregates kill neuronal cells and form amyloid plaques in the brain tissues.

What researchers in Umeå in Sweden, Vilnius in Lithuania and Rijeka in Croatia have discovered is that a particular nanosized molecules can hinder the amyloid formation of pro-inflammatory protein S100A9. These molecules are able even to dissolve already pre-formed amyloids, which has been shown by using atomic force microscopy and fluorescence techniques. The molecules in question are nanosized polyoxoniobates, which is so-called polyoxometalate ions with a negative charge containing the chemical element niobium.

"Further research is needed before we can safely say that functioning treatments can be derived from this, but the results so far have proven very promising," says Ludmilla Morozova-Roche.

The researchers have been working with two different polyoxoniobate molecules, Nb10 and TiNb9. Both turned out to inhibit SI00A9 amyloids by forming ionic interactions with the positively charged patches on the protein surface, which are critical for amyloid self-assembly. The polyoxoniobate molecules that have been studied are relatively chemically stable and water-soluble. The molecules are nanosized, which means that they are extremely small. These nanomolecules can also be of interest for other medical applications such as implants thanks to their high biocompatibility and stability.

At Umeå University, two research groups, from the Faculty of Medicine and the Department of Chemistry, have collaborated by addressing the issue from different angles and by applying a wide spectrum of biophysical and biochemical techniques and through molecular dynamics simulations.

Economists at RMIT University in Melbourne, Australia, economists found passers-by often donated more when paying via a digital platforms like apps, QR codes, PayPal and even Bitcoin, compared to the centuries' old payment method of loose coins.

Using data from the online platform The Busking Project, the study analysed individual payments to over three and half thousand active buskers from 121 countries to predict the characteristics of performers who were more likely to receive online donations.

The study found North America and Europe were home to the most active buskers and audiences on the platform, with buskers registered in the UK and USA having significantly higher prospects of receiving a donations.

The study also found:

Circus performers received the biggest donations;

Musicians were most likely to receive donations, but received smaller amounts compared to other types of artists;

The number of other onlookers influenced if and how much passers-by donated;

The artist's location and social media profile also impacted and influenced receiving a donation

Artists who joined the platform after the World Health Organisation (WHO) announcement that COVID-19 was a pandemic in March 2020 were more likely to receive a donation, which ranged from US$1 to over US$500 and averaged at just over US$14.

Lead author Dr Meg Elkins said street performers had a critical role to play as cities looked to bring back the buzz to their CBDs in the wake of the COVID-19 pandemic.

"Buskers often exist on the cultural fringes and get little, if any funding, but can bring vibrancy to streets, squares and shopping strips as people walk from the train to their office or duck out during their lunch hour," Elkins said.

"Europe and America have well-established busking cultures from Covent Gardens in London, Mauerpark in Berlin, to the many and varied roving performers in New York's Washington Square Park and subway stations, and this time of year when the northern summer is beginning is when it's often at its finest.

"Buskers performing in public for coin is a centuries old practice, but they have to move online as our society becomes increasingly cashless.

"We know many street performers become personalities in their own right and we wanted to uncover how they could use digital payment systems to increase their online earnings and create more sustainable careers.

"Circus performers being more likely to attract online donations might be because they're better at incorporating that 'hat line' into their performance compared to musicians who are traditionally much more static."

Elkins, a Senior Lecturer in the School of Economics, Finance and Marketing at RMIT University and its the Behavioural Business Lab, said the findings were important as artists and the creative and cultural industries had to become more entrepreneurial to survive.

"In the future, we could see QR codes as part of the street performance, which would simplify the payment process even further," she said.

"More than 40 QR code trails are underway across Europe, the US and Australia.

"Digital platforms can potentially allow street performers to generate more generous donations beyond cash tips.

"They're also a great way for artists to interact with supporters and build that all important fan base, which can ultimately help sustain a career."

There is a significant discrepancy between theoretical and observed amounts of lithium in our universe. This is known as the cosmological lithium problem, and it has plagued cosmologists for decades. Now, researchers have reduced this discrepancy by around 10%, thanks to a new experiment on the nuclear processes responsible for the creation of lithium. This research could point the way to a more complete understanding of the early universe.

There is a famous saying that, "In theory, theory and practice are the same. In practice, they are not." This holds true in every academic domain, but it's especially common in cosmology, the study of the entire universe, where what we think we should see and what we really see doesn't always match up. This is largely because many cosmological phenomena are difficult to study due to inaccessibility. Cosmological phenomena are usually out of our reach because of the extreme distances involved, or often they have occurred before the human brain had even evolved to worry about them in the first place -- such is the case with the big bang.

Project Assistant Professor Seiya Hayakawa and Lecturer Hidetoshi Yamaguchi from the Center for Nuclear Study at the University of Tokyo, and their international team are especially interested in one area of cosmology where theory and observation are very misaligned, and that is the issue of the missing lithium, the cosmological lithium problem (CLP). In a nutshell, theory predicts that in the minutes following the big bang that created all matter in the cosmos, there should be an abundance of lithium around three times greater than what we actually observe. But Hayakawa and his team accounted for some of this discrepancy and have thus paved the way for research that may one day resolve it entirely.

"13.7 billion years ago, as matter coalesced from the energy of the big bang, common light elements we all recognize -- hydrogen, helium, lithium and beryllium -- formed in a process we call Big Bang nucleosynthesis (BBN)," said Hayakawa. "However, BBN is not a straightforward chain of events where one thing becomes another in sequence; it is actually a complex web of processes where a jumble of protons and neutrons builds up atomic nuclei, and some of these decay into other nuclei. For example, the abundance of one form of lithium, or isotope -- lithium-7 -- mostly results from the production and decay of beryllium-7. But it has either been overestimated in theory, underobserved in reality, or a combination of the two. This needs to be resolved in order to really understand what took place way back then."

Lithium-7 is the most common isotope of lithium, accounting for 92.5% of all observed. However, even though the accepted models of BBN predict the relative amounts of all elements involved in BBN with extreme accuracy, the expected amount of lithium-7 is around three times greater than what is actually observed. This means there is a gap in our knowledge about the formation of the early universe. There are several theoretical and observational approaches which aim to resolve this, but Hayakawa and his team simulated conditions during BBN using particle beams, detectors and an observational method known as the Trojan horse.

"We scrutinized more than ever before one of the BBN reactions, where beryllium-7 and a neutron decay into lithium-7 and a proton. The resulting levels of lithium-7 abundance were slightly lower than anticipated, about 10% lower," said Hayakawa. "This is a very difficult reaction to observe since beryllium-7 and neutrons are unstable. So we used deuteron, a hydrogen nucleus with an extra neutron, as a vessel to smuggle a neutron into a beryllium-7 beam without disturbing it. This is a unique technique, developed by an Italian group we collaborate with, in which the deuteron is like the Trojan horse in Greek myth, and the neutron is the soldier who sneaks into the impregnable city of Troy without tipping off the guards (destabilizing the sample). Thanks to the new experimental result, we can offer future theoretical researchers a slightly less daunting task when trying to resolve the CLP."

One year after infection by SARS-CoV-2, most people maintain anti-Spike antibodies regardless of the severity of their symptoms, according to a study with healthcare workers co-led by the Barcelona Institute for Global Health (ISGlobal), the Catalan Health Institute (ICS) and the Jordi Gol Institute (IDIAP JG), with the collaboration of the Daniel Bravo Andreu Private Foundation. The results suggest that vaccine-generated immunity will also be long-lasting.

One of the key questions to better predict the pandemic's evolution is the duration of natural immunity. A growing number of studies suggest that most people generate a humoral (antibody) and cellular (T cells) response that is maintained during several months, maybe years.

During the first wave of the pandemic, the team at ICS/IDIAP JG in collaboration with Carlota Dobaño's team at ISGlobal started a follow-up study of a cohort of healthcare workers with COVID-19 - a total of 173 people working in healthcare centers of central Catalonia. Most infections were mild to moderate, although some cases required hospitalization.

The research team took regular blood samples from September 2020 onwards to measure the level and type of SARS-CoV-2-specific antibodies in these patients. This work was possible thanks to the support of the Daniel Bravo Foundation, which equipped ISGlobal with the latest technology and necessary resources to perform the study and rapidly reach conclusions during the subsequent waves.

"The results obtained until now lead us to believe that immunity to SARS-CoV-2 will last longer than we originally thought. Being a new virus, it is very important to understand how it behaves and affects different people", says Anna Ruiz Comellas, researcher at the Catalan Institute of Health and co-author of the study.

No significant decay in antibody levels was observed over the first five months, and at 9 months, 92.4% of peoples remained seropositive - 90% of them had IgG, 76% had IgA and 61% had IgM recognising the Spike protein or the receptor binding domain (RBD). The results were similar among healthcare workers who had not been vaccinated in April (95% had IgG, 83% IgA and 25% IgM).

"These data confirm that IgG have a longer duration, but IgM levels, which are supposed to last less, were unexpectedly quite sustained over time," says Gemma Moncunill, ISGlobal researcher and senior co-author of the study, together with Ruíz-Comellas. Hospitalization, fever, and loss of smell and taste were associated with higher antibody levels at five or nine months.

Four reinfections were observed among the participants. Two of them were symptomatic and occurred in seronegative individuals. Another asymptomatic reinfection occurred in a subject with very low antibody levels. These results indicate that anti-Spike antibodies protect against symptomatic infections. "They also indicate that people who have not been previously infected should be prioritised for vaccination, since those who have already been infected may be protected for at least one year," says Anna Ramírez-Morros, first co-author of the study.

"Considering that antibody levels achieved upon vaccination are usually higher than those generated upon natural infection, our results suggest that vaccine-induced immunity will also be long-lasting," concludes Carlota Dobaño.