Culture

New research from the Prevention Research Center of the Pacific Institute for Research and Evaluation shows that a community-level alcohol intervention in California resulted in a 17% reduction in alcohol-involved crashes among drivers aged 15-30.

The research study assessed an intervention aimed at reducing excessive drinking and harm among teens and young adults, including driving under the influence. Twenty-four California cities were chosen at random for the study with 12 cities then randomly assigned the intervention and 12 cities assigned as controls.

Interventions included sobriety checkpoints, saturation patrols, and undercover operations to reduce service of alcohol to intoxicated bar patrons, with all interventions accompanied by high visibility to raise public awareness. The effect of these efforts translates into about 310 fewer crashes across the intervention cities.

Says lead author, Dr. Robert Saltz: "The impact of alcohol control policies, whether at the city, state, or national level, ultimately depends on local enforcement. Even though numerous strategies to reduce alcohol-impaired driving have been employed over the years, the study shows that enhanced alcohol interventions involving partnerships of community health and law enforcement agencies can further reduce alcohol-impaired driving and related consequences among young people."

Tsukuba, Japan - Atherosclerosis is the result of a buildup of lipids in the inner walls of blood vessels, and is a major cause of heart disease and stroke. In a new study, researchers from the University of Tsukuba discovered a novel role for cAMP responsive element-binding protein 3 like 3 (CREB3L3) in the development of atherosclerosis and identified a mechanism by which it exhibits protective effects against atherosclerosis.

Atherosclerosis is the detrimental result of long-time high blood lipid levels leading to a thickening of the inner walls of blood vessels through the formation of a so-called plaque. As a result, blood flow to the brain and heart may decrease over time, and once the plaque ruptures, platelets in the blood stream aggregate and clog the blood vessel as they try to repair the damage. While a number of proteins and mechanisms are known to play a part in the development of atherosclerosis, research is ongoing to fully understand this complex process. CREB3L3 is a transcription factor, which is a protein that binds to DNA and regulates gene expression in the liver and small intestine, and plays an important role in the hepatic triglyceride and glucose metabolism.

"Though we have known about atherosclerosis for a long time now, there is still much to learn about the molecular basis for it," corresponding author of the study Professor Hitoshi Shimano says. "The goal of our study was to understand the role CREB3L3 plays in the development of atherosclerosis and whether it lends itself to a therapeutic target against atherosclerosis."

To achieve their goal, the researchers looked into how the absence or the overexpression of CREB3L3 would affect the development of atherosclerosis. To investigate the absence of CREB3L3, the researchers generated knockout mice that were deficient in the protein in the liver or intestines, or both. To investigate the overexpression, the researchers generated a transgenic mouse overexpressing CREB3L3 in the liver. Because atherosclerosis does not naturally occur in mice, the researchers made use of a mouse line, in which the receptor of LDL cholesterol (LDLR), commonly known as "bad" cholesterol, is absent. Because LDL cholesterol circulating in the build cannot be taken up by cells, it builds up in blood vessel walls and leads to the formation of atherosclerosis. By crossing CREB3L3 mice with the LDLR mouse and feeding them with a western diet, the researchers had a system to study the role of CREB3L3 in the development of atherosclerosis.

Interestingly, the researchers found that absence of CREB3L3 in either the liver or intestines resulted in an exacerbation of high blood lipid levels and atherosclerosis formation, and more so in the mice, in which CREB3L3 was knocked out in both organs. Conversely, overexpressing the protein in the liver markedly suppressed blood cholesterol levels and atherosclerosis formation. By looking closer at the molecular mechanism by which CREB3L3 confers protective effects against atherosclerosis, the researchers found that it interacts with sterol regulatory element-binding protein (SREBP) to trap it in a cellular compartment called endoplasmic reticulum and prevent it from inducing the expression of genes important for the formation of atherosclerosis.

"These are striking results that provide a mechanism by which CREB3L3 exhibits anti-atherosclerotic effects, making it an interesting, potential novel target against atherosclerosis," Professors Shimano and Nakagawa, the first author, say.

With almost every aspect of their biology and anatomy adapted to their specialized parasitic lifestyle, fleas have long troubled evolutionary biologists. Their early evolution and position on the insect tree of life remained a mystery even after the first flea genomes were sequenced over the last decade.

Now, however, researchers from the Nanjing Institute of Geology and Palaeontology of the Chinese Academy of Sciences (NIGPAS) and the University of Bristol in the UK have solved this long-standing evolutionary riddle.

Their study was published in Palaeoentomology, the official publication of the International Palaeoentomological Society, on Dec. 21.

Of all the parasites in the animal kingdom, fleas hold a pre-eminent position. After all, the Black Death, caused by a flea-transmitted bacterium, was the deadliest pandemic in the recorded history of mankind.

"Despite their medical significance, the placement of fleas on the tree of life represents one of the most persistent enigmas in the evolution of insects," said Erik Tihelka, undergraduate at the University of Bristol who led the study.

Over the years, researchers have proposed many hypotheses regarding the origin of fleas, most arguing that their closest relatives lie among the flies or scorpionflies, or both.

In this study, the scientists used genome-scale sequences of fleas and all their possible close relatives, then analyzed them using new statistical methods. By employing more sophisticated algorithms to test all historically proposed hypotheses and search for new potential relationships, the team came to an unexpected conclusion - fleas are a group of highly modified, parasitic scorpionflies.

Scorpionflies are a group of small- to medium-sized flying insects distributed worldwide. The new study suggests that the small scorpionfly family Nannochoristidae, which is endemic to the southern hemisphere and whose adults probably feed on nectar, is the closest relative of all living fleas. Despite looking very unlike the flea we know today, the Nannochoristidae in fact share surprising anatomical similarities with fleas such as characteristics of the head and the sperm pump.

Why was the "flea mystery" so hard to solve?

"A close relationship between Nannochoristidae and the fleas has been proposed in several past molecular analyses but was treated as likely an error. Ancient evolutionary radiations leave behind subtle clues in organisms' genomes that can only be recovered with sophisticated models of molecular evolution. Moreover, the nannochoristids are a quite rare and little-studied group that only occurs in New Zealand, southeastern Australia, Tasmania, and Chile, so they are easy to overlook," explained Tihelka.

"The new results suggest that we may need to revise our entomology textbooks. Fleas no longer deserve the status of a separate insect order, but should actually be classified within the scorpionflies," said CAI Chenyang, associate professor at NIGPAS and expert on Mesozoic insects.

The new findings agree with fossil evidence. "We have exceptionally preserved fossil fleas from the Jurassic and Cretaceous. In particular, some Jurassic fleas from China, about 165 million years old, are truly giant and measure up to two centimeters. They may have fed on dinosaurs, but that is exceedingly difficult to tell. What is more interesting is that these ancient fleas share important characteristics with modern scorpionflies," said CAI.

"Sometime between the Permian and Jurassic, a group of scorpionflies started feeding on the blood of vertebrates. This group gave rise to fleas as we know them today," added Prof. HUANG Diying of NIGPAS.

"It is interesting," commented Mattia Giacomelli, a Ph.D. student at the University of Bristol who participated in the study. "We used to think that all blood-feeding parasitic insects basically started off by either being predators or living in close association with their vertebrate hosts, like in their nests. The case of fleas shows that blood feeding can evolve in groups that originally fed on nectar and other plant secretions. It seems that the elongate mouthparts that are specialized for nectar feeding from flowers can become co-opted during the course of evolution to enable sucking blood."

Hospital in-patients from lower socioeconomic backgrounds are less likely to receive prompt cardiopulmonary resuscitation (CPR) after their hearts stop beating and less likely to survive than patients from higher socioeconomic backgrounds.

These are the findings of a new study in over 24,000 patients in Sweden, published in the European Heart Journal [1] today (Monday). It is the first European study to investigate this and the first to show that socioeconomic status (SES), rather than other factors, is important. The authors believe their findings could hold true for other European countries as well.

It is known that people with lower SES are less likely to survive a sudden cardiac arrest outside the hospital setting compared to those of higher SES but, until now, it has not been clear whether this was the case for patients already in hospital where they could expect to receive the same standard of care regardless of their backgrounds.

In the current study, Professor Jens Agerström, from Linnaeus University in Kalmar and Växjö, Sweden, and his Swedish colleagues, found that patients in hospital with higher incomes and education were significantly less likely to experience a delay in receiving CPR after a cardiac arrest, and significantly more likely to survive until discharge from hospital and for 30 days after the cardiac arrest.

Prof. Agerström said: "The good news is that for most of the cardiac arrest cases in this study, socioeconomic status didn't seem to matter. Nevertheless, there seems to be a significant number of deaths that can still be attributed to socioeconomic factors, even when we take account of things that could affect the results such as gender, age, ethnicity, other health conditions, cause of the cardiac arrest, and the specific hospital providing the treatment.

"The study investigated several outcomes but, for example, if we look at survival for 30 days after the cardiac arrest, approximately 280 people in 1000 from a low socioeconomic background will survive; however, for patients from a high socioeconomic background approximately 320 people may survive to 30 days."

The researchers also found that patients with higher SES were significantly more likely to have their heart rhythm monitored before they suffered a cardiac arrest and this was associated with less delay before CPR, a shorter duration of CPR and increased survival immediately afterwards and 30 days later. This could partially explain the differences in survival.

Prof. Agerström said: "Even when we took account of patients' other medical conditions, we found that patients with higher income and education were more likely to receive heart rhythm monitoring. In fact, we found that patients from high socioeconomic backgrounds were more likely to be monitored even if their health status was better than patients from low socioeconomic backgrounds. This suggests that there may be a bias in the way treatment is provided. Although doctors make the decision whether or not to monitor heart rhythm, we cannot rule out that patients from high socioeconomic backgrounds may request more monitoring."

The researchers write in their paper: "The finding that SES difference remain after controlling for major demographic, clinical and contextual factors suggests the presence of treatment bias/discrimination. Such bias, where patients are treated differently due to their SES, may stem from prejudiced attitudes among hospital staff."

They continue: "Reassuringly, however, most of the uncovered associations between patient SES and the studied outcomes are small, meaning that a large majority of IHCA [in-hospital cardiac arrest] patients with low SES is not subjected to disparate treatment. However, because human lives are at stake, a SES-related survival odds difference of approximately 21% (our effect size for 30-day survival) should not be ignored. This would mean that 818 of the 14,714 IHCA deaths of the lowly educated patients . . . could be attributed to education." They suggest that hospitals may want to consider enrolling their cardiac arrest teams in equality training programmes to help them be aware of their possible bias and how this could translate into discriminatory treatment.

The researchers analysed data from the Swedish National Registry of Cardiopulmonary Resuscitation for 24,217 cardiac arrests that occurred in patients aged 40 or over in Swedish hospitals between 2005 and 2018. They obtained socioeconomic data on patients from a second database and they used highest level of education and annual income as indicators of SES. They adjusted their results to take account of factors that could affect them, such as age, gender, ethnicity, other medical conditions, hospital where they were treated, heart rhythm and the cause of the cardiac arrest.

Prof. Agerström said: "The current study only examined cases where resuscitation was started because these are the cases that appear in the Swedish National Registry of CPR. It's possible that SES disparities are more pronounced when the medical staff decide whether or not to initiate CPR in the first place."

Other limitations of the study include that it can show only that the SES is associated with CPR and survival, not that SES causes fewer CPR attempts and lower survival rates among people with low SES. The researchers did not have access to smoking habits and other lifestyle factors and, because the study was conducted in Sweden, it might not be possible to generalise to other countries.

"Because it has been shown that people with low SES face prejudiced attitudes in many societies and cultures, it is possible that there are SES disparities in in-hospital cardiac arrest care and outcome in other European countries too. This, of course, rests on the assumption that prejudice plays an important role in the observed differences," said Prof. Agerström.

He said he was prompted to carry out the research because of his own experiences. "After having studied discrimination in the labour market for many years with Dr. Magnus Carlsson, one of my co-authors, we thought that a natural next step would be to look at the health care system and possible treatment discrimination, which is much less researched. My own medical visits also played a role, as I got the impression that the staff often became more thorough after they had asked me about my profession."

A study of more than 1,400 protein-coding genes of fleas has resolved one of the longest standing mysteries in the evolution of insects, reordering their placement in the tree of life and pinpointing who their closest relatives are.

The University of Bristol study, published in the journal Palaeoentomology, drew on the largest insect molecular dataset available. The dataset was analysed using new statistical methods, including more sophisticated algorithms, to test all historically proposed hypotheses about the placement of fleas on the insect tree of life and search for new potential relationships.

The findings overturn previously held theories about fleas, the unusual anatomy of which has meant that they eluded classification in evolutionary terms. According to the authors of the study, contrary to popular belief, fleas are technically scorpionflies, which evolved when they started feeding on the blood of vertebrates sometime between the Permian and Jurassic, between 290 and 165 million years ago.

The closest living relatives of fleas are the members of the scorpionfly family Nannochoristidae, a rare group with only seven species native to the southern hemisphere. Unlike the blood-thirsty fleas, adult nannochoristid scorpionflies lead a peaceful existence feeding on nectar.

"Of all the parasites in the animal kingdom, fleas hold a pre-eminent position. The Black Death, caused by a flea-transmitted bacterium, was the deadliest pandemic in the recorded history of mankind; it claimed the lives of possibly up to 200 million people in the 14th century," says lead author and undergraduate student Erik Tihelka from the School of Earth Sciences.

"Yet despite their medical significance, the placement of fleas on the tree of life represents one of the most persistent enigmas in the evolution of insects."

It used to be thought that all blood-feeding parasitic insects began life as either predators or by living alongside vertebrate hosts in their nests. In actual fact, blood feeding can evolve in groups that originally fed on nectar and other plant secretions.

"It seems that the elongate mouthparts that are specialized for nectar feeding from flowers can become co-opted during the course evolution to enable sucking blood," says Mattia Giacomelli, a PhD student at the University of Bristol who participated in the study.

Previous studies had suggested a connection between fleas and anatomically unusual groups of scorpionflies, but their exact relationships remained unresolved. The mystery was prolonged by the fact that flea genomes underwent rapid evolution, which makes reconstructing ancient evolutionary relationships challenging. Moreover, the nannochoristids are a quite rare and little-studied group that only occurs in New Zealand, southeastern Australia, Tasmania, and Chile, so they are easy to overlook.

"The new results suggest that we may need to revise our entomology textbooks. Fleas no longer deserve the status of a separate insect order, but should actually be classified within the scorpionflies," says Chenyang Cai, associate professor at the Nanjing Institute of Geology and Palaeontology (NIGP) and a research fellow at the University of Bristol specialising on Mesozoic insects.

"We have exceptionally preserved fossil fleas from the Jurassic and Cretaceous. In particular, some Jurassic fleas from China, about 165 million years old, are truly giant and measure up to two centimetres. They may have fed on dinosaurs, but that is exceedingly difficult to tell. What is more interesting is that these ancient fleas share important characters with modern scorpionflies."

Lower rates of hospital attendance for urgent heart problems during the initial phase of the COVID-19 pandemic may have contributed to avoidable deaths in England, finds a new study led by UCL researchers.

In the wake of the coronavirus pandemic, a marked decline* in patient visits to Emergency Departments (EDs) was observed in England and the US, including for people with heart problems.

In this study, published online in the journal Circulation cardiovascular quality and outcomes, researchers at UCL's Institute of Health Informatics estimated the effect of reduced ED visits for suspected cardiac disease on non-COVID-19 related cardiac mortality in England.

To quantify the number of excess deaths due to cardiac disease, the team used mortality counts from the Office of National Statistics (ONS) for England. To quantify the change in daily ED visits, researchers used data from the Public Health England (PHE) Emergency Department Syndromic Surveillance System (EDSSS): a network of sentinel EDs across England. To explore how the reduction in ED visits may have affected cardiac mortality, researchers implemented causal inference methodology.

Lead author Dr Michail Katsoulis (UCL Institute of Health Informatics) said: "During the initial phase of the pandemic, between March 12** and April 15, 2020, there was an estimated fewer ED visits of 2,750 per week for suspected cardiac disease; this is around a 35% decrease compared to the pre-pandemic period this year.

"Our analysis suggested that one cardiac death might have been prevented or delayed for every additional 12 ED visits for suspected cardiac conditions. We estimated that the excess cardiac mortality due to non-attendance at EDs, during the initial phase of the pandemic, may have been as high as 232 deaths per week."

Senior author Dr Tom Lumbers (UCL Institute of Health Informatics) said: "While the decline of patients accessing hospital care during the pandemic has been well documented, here we provide an estimate of the health consequences of this change in healthcare utilisation.

"The public health messaging to protect the NHS may have led to patients not attending ED out of fear or public-mindedness or difficulty accessing services due to the pandemic.

"Our results suggest that the pandemic response may have led to the undertreatment of non-COVID-19 diseases, including heart conditions, with important impacts on the excess mortality observed during this period."

Dr Lumbers added: "These results provide evidence of the stark indirect effects of the COVID-19 pandemic on mortality in England. There is a need to better understand how the pandemic response resulted in a decline in attendance to EDs with suspected cardiac disease and other serious medical conditions to inform future strategies to mitigate both the direct and indirect effects of the pandemic."

Study limitations

The research team's estimates rest upon the assumption that the COVID-19 pandemic only affects excess deaths from cardiac disease through the reduction in ED admissions, and not as a result of other factors, such as increased stress and anxiety.

Another potential limitation of this study is the possible misclassification of cardiac deaths as not related to COVID-19, since SARS-CoV-2 viral infection was excluded on clinical grounds and not through systematic viral ribonucleic acid testing.

For the first time, researchers have provided physiological evidence that a pervasive neuromodulation system - a group of neurons that regulate the functioning of more specialized neurons - strongly influences sound processing in an important auditory region of the brain. The neuromodulator, acetylcholine, may even help the main auditory brain circuitry distinguish speech from noise.

"While the phenomenon of these modulators' influence has been studied at the level of the neocortex, where the brain's most complex computations occur, it has rarely been studied at the more fundamental levels of the brain," says R. Michael Burger, professor of neuroscience at Lehigh University.

Burger and Lehigh Ph.D. student Chao Zhang?along with collaborators Nichole Beebe and Brett Schofield of Northeast Ohio Medical University and Michael Pecka of Ludwig-Maximilians University Munich?conducted the research. The findings have been described in an article, "Endogenous Cholinergic Signaling Modulates Sound-evoked Responses of the Medial Nucleus of the Trapezoid Body," published earlier this month in The Journal of Neuroscience. The journal's editors designated the article as "noteworthy" and it was included in "featured research" for its particular significance to the scientific community.

"This study will likely bring new attention in the field to the ways in which circuits like this, widely considered a 'simple' one, are in fact highly complex and subject to modulatory influence like higher regions of the brain," says Burger.

The team conducted electrophysiological experiments and data analysis to demonstrate that the input of the neurotransmitter acetylcholine, a pervasive neuromodulator in the brain, influences the encoding of acoustic information by the medial nucleus of the trapezoid body (MNTB), the most prominent source of inhibition to several key nuclei in the lower auditory system. MNTB neurons have previously been considered computationally simple, driven by a single large excitatory synapse and influenced by local inhibitory inputs. The team demonstrates that in addition to these inputs, acetylcholine modulation enhances neural discrimination of tones from noise stimuli, which may contribute to processing important acoustic signals such as speech. Additionally, they describe novel anatomical projections that provide acetylcholine input to the MNTB.

Burger studies the circuit of neurons that are "wired together" in order to carry out the specialized function of computing the locations from which sounds emanate in space. He describes neuromodulators as broader, less specific circuits that overlay the more highly-specialized ones.

"This modulation appears to help these neurons detect faint signals in noise," says Burger. "You can think of this modulation as akin to shifting an antenna's position to eliminate static for your favorite radio station."

"In this paper, we show that modulatory circuits have a profound effect on neurons in the sound localization circuitry, at very low foundational level of the auditory system," adds Zhang.

In addition, during the course of this study, the researchers identified for the first time a set of completely unknown connections in the brain between the modulatory centers and this important area of the auditory system.

Burger and Zhang think these findings could shed new light on the contribution of neuromodulation to fundamental computational processes in auditory brainstem circuitry, and that it also has implications for understanding how other sensory information is processed in the brain.

DURHAM, N.C. - Mechanical engineers at Duke University have devised a method for spinning individual droplets of liquid to concentrate and separate nanoparticles for biomedical purposes. The technique is much more efficient than traditional centrifuge approaches, working its magic in under a minute instead of taking hours or days, and requires only a tiny fraction of the typical sample size. The invention could underline new approaches to applications ranging from precision bioassays to cancer diagnosis.

The results appear online on December 18 in the journal Science Advances.

"This idea originated from a very exciting recent finding that you can use surface acoustic waves to spin a droplet of liquid," said Tony Jun Huang, the William Bevan Distinguished Professor of Mechanical Engineering and Materials Science at Duke. "We decided to investigate whether we could use this method to create a point-of-care system that can separate and enrich nanoparticles quickly and efficiently."

Huang and his doctoral student Yuyang Gu began their investigation by building a device capable of spinning individual droplets of liquid. In the center of a piezoelectric surface sits a ring of polydimethylsiloxane, a type of silicon commonly used in microfluidic technologies, which confines the droplet's boundaries and keeps it in place. The researchers then placed a sound wave generator called a interdigitated transducer (IDT) on each side and slanted them so that sound waves with different frequencies travel through the piezoelectric surface to enter the droplet.

When turned on, the IDTs create surface acoustic waves that push on the sides of the droplets like Donald Duck getting blown over by a gigantic pair of speakers. At low power settings, the top of the droplet begins to wobble around the ring like a muffin top made of Jell-O. But when the power gets turned up to 11, the balance between the surface tension of the droplet and its centrifugal force causes it to take on the shape of a pill and begin spinning in place.

The researchers then investigated how fluorescent nanoparticles of different sizes behaved within the spinning droplets. Because the droplet is spinning, the nanoparticles themselves also got dragged along in a helical pattern. Depending on their size and the frequency of sound, they were also pushed toward the center of the droplet due to the incoming force of the sound waves and hydrodynamics.

The researchers found that by using different frequencies, they could specifically concentrate particles as small as tens of nanometers. These sizes correlate to biologically important molecules such as DNA and exosomes -- biological nanoparticles released from every type of cell in the body that are thought to play an important role in cell-to-cell communication and disease transmission.

But they were still faced with another problem. While nanoparticles of one size flocked to the center of the droplet, nanoparticles of other sizes were still flying randomly about, making it difficult to access the concentrated bounty.

Their solution? A second spinning droplet.

"We set up two droplets of different sizes next to each other so that they'd be spinning at different speeds," said Gu. "By connecting them with a small channel, any nanoparticles not concentrating in the first end up spinning off and getting trapped in the second."

To further show how useful their dual-droplet centrifugal system could be, the researchers showed that it could successfully separate subpopulations of exosomes from a sample. And unlike common centrifugation methods that require large amount of samples and can take overnight to work, their solution only needed a much smaller sample volume--such as five microliters--and less than a minute.

"We envision this work simplifying and speeding up sample processing, detection and reagent reactions in various applications such as point-of-care diagnostics, bioassays and liquid biopsies," said Gu.

"The ability to separate and enrich exosome subpopulations and other biological nanoparticles is extremely important." added Huang. "For example, while the recent discovery of exosome subpopulations has excited biologists and researchers due to their potential to revolutionize the field of non-invasive diagnostics, exosome sub-populations have yet to be utilized in clinical settings. This is largely due to the difficulties associated with separating exosome subpopulations because of their small size. Our approach offers a simple, automated approach for separating exosome sub-populations in a fast and biocompatible manner. As a result, we believe that it is critical to unlocking the clinical utility of exosome subpopulations."

December 18, 2020--(BRONX, NY)--People hospitalized with COVID-19 and neurological problems including stroke and confusion, have a higher risk of dying than other COVID-19 patients, according to a study published online today by researchers at Montefiore Health System and Albert Einstein College of Medicine in the journal Neurology®, the medical journal of the American Academy of Neurology. These findings have the potential to identify and focus treatment efforts on individuals most at risk and could decrease COVID-19 deaths.

The study looked at data from 4,711 COVID-19 patients who were admitted to Montefiore during the six-week period between March 1, 2020 and April 16, 2020. Of those patients, 581 (12%) had neurological problems serious enough to warrant brain imaging. These individuals were compared with 1,743 non-neurological COVID-19 patients of similar age and disease severity who were admitted during the same period.

"This study is the first to show that the presence of neurological symptoms, particularly stroke and confused or altered thinking, may indicate a more serious course of illness, even when pulmonary problems aren't severe," said David Altschul, M.D., chief of the division of neurovascular surgery at Einstein and Montefiore and associate professor in the Leo M. Davidoff Department of Neurological Surgery and of radiology at Einstein. "Hospitals can use this knowledge to prioritize treatment and, hopefully, save more lives during this pandemic."

Among people who underwent brain imaging, 55 were diagnosed with stroke and 258 people exhibited confusion or altered thinking ability. Individuals with stroke were twice as likely to die (49% mortality) compared with their matched controls (24% mortality)--a statistically significant difference. People with confusion had a 40% mortality rate compared with 33% for their matched controls--also statistically significant.

More than half the stroke patients in the study did not have hypertension or other underlying risk factors for stroke. "This highly unusual finding agrees with other studies of people with COVID-19 in suggesting that infection with the novel coronavirus is itself a risk factor for stroke," said Dr. Altschul, who is also surgical director of the Montefiore Comprehensive Center for Stroke Care, and the study co- author, along with Emad Eskandar, M.D., M.B.A., chair of neurological surgery at Einstein and Montefiore, professor in the Leo M. Davidoff Department of Neurological Surgery, the department of psychiatry and behavioral sciences, in the Dominick P. Purpura Department of Neuroscience at Einstein. Dr. Eskandar also holds the Jeffrey P. Bergstein Chair and the David B. Keidan Chair in Neurological Surgery.

A group of more than 300 leading scientists across the globe are calling for European governments to work together in managing the pandemic and make a clear commitment to COVID-19 case number targets.

The letter, co-authored by Dr Deepti Gurdasani from Queen Mary University of London and coordinated by Viola Priesemann from the Max Planck Institute for Dynamics and Self-Organization in Göttingen, is published today in The Lancet.

"Across Europe, the COVID-19 pandemic is causing excess deaths, placing a burden on societies and health systems, and harming the economy," they write. "Yet European governments have yet to develop a common vision to guide the management of the pandemic."

The letter outlines the need for a pan-European commitment to reducing and maintaining case numbers for COVID-19 at very low levels to protect people's health, society and economies. It highlights how uncontrolled spread in one region can put the successful management of the pandemic in other regions at risk, suggesting a common vision is needed to achieve this goal.

"With open borders across Europe, a single country alone cannot keep the number of COVID-19 cases low; thus joint action and common goals among countries are essential," the authors write. "We therefore call for a strong, coordinated European response and clearly defined goals for the medium and long term."

To better manage the COVID-19 pandemic, the scientists are proposing a strategy with three core elements:

1) Achieve low case numbers - aiming for a target of no more than ten new COVID-19 cases per million people per day, with synchronisation across all European countries so that SARS-CoV-2 infections are not imported across borders.

2) Keep case numbers low - with continued and improved mitigation measures (such as mask wearing, hygiene, moderate contact reduction, testing and contact tracing), a strategy for delivering at least 300 tests per million people per day, and rapid response to local outbreaks.

3) Develop a longer-term common vision - with context-sensitive regional and national action plans as well as European level goals, strategies for elimination, screening, vaccination, protection of those at high risk, and support for those most affected by the pandemic.

The authors conclude: "We urge governments throughout Europe to agree on clearly formulated common goals, to coordinate their efforts, to develop regionally adapted strategies to reach the goals, and thereby work resolutely towards low case numbers."

There is light at the end of the COVID-19 pandemic tunnel. Several vaccines against the SARS-CoV-2 virus that causes COVID-19 are now in clinical trials, with one — developed by Pfizer/BioNTech — already having been approved for emergency use in the United States. This has been the fastest development and rollout of any vaccine in history, starting with the first gene sequence released in January. (The previous record was held by the mumps vaccine, which took four years.)

“There is light at the end of the COVID-19 pandemic tunnel. Several vaccines against the SARS-CoV-2 virus that causes COVID-19 are now in clinical trials, with two — developed by Pfizer/BioNTech and Moderna — already having been approved for emergency use in the United States.” Case in point: five of the vaccines, including those developed by Pfizer/BioNTech and Moderna, contain genetic mutations that increase their effectiveness, mutations based upon work dating back more than 10 years using the resources of the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science User Facility at DOE’s Argonne National Laboratory.

“The previous work allowed us to move very quickly. Vaccine development usually takes a decade. The RSV vaccine we created in 2013 is just now entering phase 3 clinical trials. COVID-19 went from a genome sequence to first immunization in less than a year.” — Jason McLellan, University of Texas at Austin

The APS has been at the forefront of the field of structural biology since its ultrabright X-ray beams first started shining in 1995. Scientists use those powerful beams of light to illuminate the structures of viruses, producing detailed pictures of the makeup of their proteins. Those pictures are then used to design techniques, drugs and vaccines that fight the virus more effectively.

Which is exactly what these mutations do. They were developed by Jason McLellan, now an associate professor at the University of Texas at Austin, and Barney Graham, currently the deputy director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH). The pair’s current work on COVID-19 vaccines was heavily influenced by their research into an entirely different disease: respiratory syncytial virus (RSV), which affects thousands per year.

“We started that work in 2009,” said McLellan, who was then a postdoctoral researcher in Peter Kwong’s lab at NIH. “It took a while, but we had success developing a vaccine candidate for RSV in 2013.”

The key to that vaccine, which is now entering phase 3 trials, was a better understanding of one of the virus’s proteins. The F protein in RSV adorns the surface of the virus and makes first contact with human cells, infecting them. This protein has two shapes: prefusion, a smaller mushroom-like form that first makes contact with cells, and postfusion, an extended form that initiates entry of the virus into those cells. Once the protein is in its postfusion shape, infection has begun, and it is more difficult for the immune system to fight the virus off.

McLellan and Graham worked on the theory that a vaccine directed at the F protein in its prefusion mode should be more effective. They created more than 100 different variants of that protein to find a version that they could stabilize in the prefusion form. This would provide a target for the immune system, helping it to develop neutralizing antibodies against the virus. Parts of that work were done at the Southeast Regional Collaborative Access Team (SER-CAT) beamline at the APS, operated by the University of Georgia.

In May 2013, the pair and their colleagues reported success, publishing their work in Science. In November 2013, they reported a vaccine candidate for RSV that neutralized the F protein, stabilizing it in its prefusion form. That paper was also published in Science, and included structural work performed at SER-CAT. In 2019 McLellan, Graham and their colleagues published the clinical proof-of-concept in Science that showed the prefusion molecule was a better vaccine antigen.

McLellan and Graham soon learned that the technique they discovered could be applied to coronaviruses.

“Barney and I started thinking about what to look at next, and coronaviruses in general were similar to RSV,” McLellan said. “Both contain a similar protein: the spike in coronaviruses is like the F protein in RSV, except that the spike is about two and a half times the size. It’s like the F protein on steroids.”

In 2013, McLellan and his colleagues, including Nianshuang Wang, now at Regeneron Pharmaceuticals, began working with Graham and his NIH colleague Kizzmekia Corbett on a vaccine for the Middle East Respiratory Syndrome coronavirus (MERS-CoV). The team applied the same technique to MERS-CoV, and in 2017 reported similar success. This time they performed some of their work at the Structural Biology Center (SBC) at the APS, and published results in the Proceedings of the National Academy of Sciences.

“Both McLellan and Graham are longtime users of the APS, and their work to understand RSV and MERS-CoV led to an effective technique to neutralize both viruses,” said Argonne’s Bob Fischetti, group leader and life sciences advisor to the APS director. “The structural work performed at the APS played a key role in the discovery of this technique, and we are now seeing how important it might be.”

When SARS-CoV-2 emerged, McLellan, Wang and graduate student Daniel Wrapp, now at the University of Texas at Austin, joined with Graham and Corbett to see if the same technique would work to inhibit this new virus's spread. And once they were able to examine the structure of the spike protein, they discovered that it did.

“Being able to solve the structure of the SARS-CoV-2 spike protein and know that it was in the desired conformation within three weeks of sequence release was critical for rapidly advancing vaccine development and antibody discovery programs,” Graham said.

The initial results of their work, a mutation called S-2P, is now in SARS-CoV-2 vaccines developed by Moderna, Pfizer/BioNTech, Novavax, Johnson & Johnson and CureVac, McLellan confirmed. Pfizer’s and Moderna’s vaccines use messenger RNA (mRNA) to instruct human cells to make the mutant of the spike protein that the immune system then develops antibodies against. If a person is infected with the virus, the immune system then recognizes it before infection and the antibodies neutralize the spike protein, by binding to it and preventing it from infecting the cell.

“The U.S. Food and Drug Administration granted an emergency use authorization for Pfizer’s vaccine on Dec. 12, and did the same for Moderna’s vaccine on Dec. 18. Both vaccines are now being administered in the United States.”

“The previous work allowed us to move very quickly,” McLellan said. “Vaccine development usually takes a decade. The RSV vaccine we created in 2013 is just now entering phase 3 clinical trials. COVID-19 went from a genome sequence to first immunization in less than a year. We played a role in the development of the antigen. There was a massive response to this coronavirus. Lots of labs and companies contributed.”

McLellan and his colleagues published further work on SARS-CoV-2 in Science in September. Again the scientists tested more than 100 variations of the spike protein, this time using a technique called cryogenic electron microscopy at their own labs. They ended up with a molecule called HexaPro that could be 10 times as potent as the S-2P spike protein in the current COVID-19 vaccines. It is currently being evaluated for use by several companies.

While the prospect of several COVID-19 vaccines is exciting, McLellan is similarly heartened by what this accelerated development process means for the future. We don’t know what the next pathogens are going to be, he notes, and the tools and techniques being developed now will play an important role.

“We have learned a lot about the different steps involved in a pandemic response,” he said. “The vaccine development platform will continue to mature. The speed and new technology saves us days and weeks, and helps with the game plan to respond to future pandemics.”

Graham and Corbett were recently named recipients of a Golden Goose Award for their work on COVID-19 research, and McLellan’s work is recognized in the announcement.

The APS has dedicated more than 10,000 hours of time to research into the structure of SARS-CoV-2 this year, and has made its resources available to more than 80 groups of researchers from across the country, in addition to the work done by Argonne scientists there. With more than 100 structures of the virus made available to the world scientific community — more than any other U.S. light source — the APS has been an important factor in the effort to combat COVID-19.

“Just as what we learned from previous outbreaks helped to create vaccines and treatments at record speed, what we are learning about SARS-CoV-2 at the APS will help fight not only this outbreak, but future ones,” said Stephen Streiffer, Argonne’s deputy laboratory director for science and technology and the interim director of the APS.

Land ecosystems currently play a key role in mitigating climate change. The more carbon dioxide (CO2) plants and trees absorb during photosynthesis, the process they use to make food, the less CO2 remains trapped in the atmosphere where it can cause temperatures to rise. But scientists have identified an unsettling trend - as levels of CO2 in the atmosphere increase, 86 percent of land ecosystems globally are becoming progressively less efficient at absorbing it.

Because CO2 is a main 'ingredient' that plants need to grow, elevated concentrations of it cause an increase in photosynthesis, and consequently, plant growth - a phenomenon aptly referred to as the CO2 fertilization effect, or CFE. CFE is considered a key factor in the response of vegetation to rising atmospheric CO2 as well as an important mechanism for removing this potent greenhouse gas from our atmosphere - but that may be changing.

For a new study published Dec. 10 in Science, researchers analyzed multiple field, satellite-derived and model-based datasets to better understand what effect increasing levels of CO2 may be having on CFE. Their findings have important implications for the role plants can be expected to play in offsetting climate change in the years to come.

"In this study, by analyzing the best available long-term data from remote sensing and state-of-the-art land-surface models, we have found that since 1982, the global average CFE has decreased steadily from 21 percent to 12 percent per 100 ppm of CO2 in the atmosphere," said Ben Poulter, study co-author and scientist at NASA's Goddard Space Flight Center. "In other words, terrestrial ecosystems are becoming less reliable as a temporary climate change mitigator."

What's Causing It?

Without this feedback between photosynthesis and elevated atmospheric CO2, Poulter said we would have seen climate change occurring at a much more rapid rate. But scientists have been concerned about how long the CO2 Fertilization Effect could be sustained before other limitations on plant growth kick in.

For instance, while an abundance of CO2 won't limit growth, a lack of water, nutrients, or sunlight - the other necessary components of photosynthesis -- will. To determine why the CFE has been decreasing, the study team took the availability of these other elements into account.

"According to our data, what appears to be happening is that there's both a moisture limitation as well as a nutrient limitation coming into play," Poulter said. "In the tropics, there's often just not enough nitrogen or phosphorus, to sustain photosynthesis, and in the high-latitude temperate and boreal regions, soil moisture is now more limiting than air temperature because of recent warming."

In effect, climate change is weakening plants' ability to mitigate further climate change over large areas of the planet.

Next Steps

The international science team found that when remote-sensing observations were taken into account - including vegetation index data from NASA's Advanced Very High Resolution Radiometer (AVHRR) and the Moderate Resolution Imaging Spectroradiometer (MODIS) instruments - the decline in CFE is more substantial than current land-surface models have shown. Poulter says this is because modelers have struggled to account for nutrient feedbacks and soil moisture limitations - due, in part, to a lack of global observations of them.

"By combining decades of remote sensing data like we have done here, we're able to see these limitations on plant growth. As such, the study shows a clear way forward for model development, especially with new remote sensing observations of vegetation traits expected in coming years," he said. "These observations will help advance models to incorporate ecosystem processes, climate and CO2 feedbacks more realistically."

The results of the study also highlight the importance of the role of ecosystems in the global carbon cycle. According to Poulter, going forward, the decreasing carbon-uptake efficiency of land ecosystems means we may see the amount of CO2 remaining in the atmosphere after fossil fuel burning and deforestation start to increase, shrinking the remaining carbon budget.

"What this means is that to avoid 1.5 or 2°C warming and the associated climate impacts, we need to adjust the remaining carbon budget to account for the weakening of the plant CO2 Fertilization Effect," he said. "And because of this weakening, land ecosystems will not be as reliable for climate mitigation in the coming decades."

- A University of Sheffield-led research programme finds Local Authorities and the Voluntary and Community Sector are best placed to support the response to the Covid-19 crisis locally

Mobilising Volunteers Effectively found local initiatives are best placed to identify and mobilise volunteers

Thousands of members of the public have volunteered, helping their neighbours to stay fed, safe and connected

These volunteers will continue to play a central role during the festive period and into next year, as the socio-economic fallout of the pandemic continues to take hold

During the first national lockdown of the Covid-19 pandemic earlier this year, and subsequent social restrictions, thousands of volunteers provided a vital lifeline for many vulnerable people throughout an unprecedented time of anxiety and social restrictions.

Despite the launch of a new vaccination programme providing hope that the country is nearing the 'beginning of the end' of the health crisis, researchers from the Mobilising Volunteers Effectively (MoVE) project, warn that the socio-economic fallout from Covid-19 means that for many, the crisis is far from over, and that volunteers will continue to be one of many valuable assets needed during the challenging months ahead.

Dr Erica Ballantyne, co-investigator on the MoVE project from the University of Sheffield, said: "Providing access to food was identified as one of the first challenges in the early stages of the pandemic, which created demand for volunteers to aid the supply and distribution of essential food parcels, medication, other essential supplies and even befriending services for those socially isolated as a result of the pandemic.

"Whilst this demand has reduced, the longer-term issue of food poverty remains, which places increased pressure on the voluntary sector, particularly local food banks, who are called upon to provide continued support."

Dr Jon Burchell, Principal Investigator for the project from the University of Sheffield, said: "Whilst the rollout of vaccinations will hopefully lead to a gradual reduction in social restrictions, and thus a return to 'normal' for many, longer-term challenges, namely mental health and food poverty, have been exacerbated and show no signs of abating.

"The new year and the likely continuation of localised social restrictions, volunteers - both formal and informal - will continue to play a critical role in supporting our communities."

The third report of the MoVE project examined how local authorities (LAs) and their voluntary and community sector (VCS) partners worked together to identify and support those in need, reflecting on what can be learnt for the future as the crisis continues into 2021.

The research found that the national volunteering schemes that ran during the first lockdown (e.g. the NHS Volunteer Responders and Ready Scotland) may not have been the best way to achieve this.

LAs and the VCS organisations who participated in the study expressed frustration that they could not access these volunteers due to a lack of data sharing, and a general feeling that the resources channeled into these centralised platforms could have been more effectively utilised in supporting local responses.

Dr Erica Ballantyne, said: "Our research highlighted that a centralised service may not be able to understand and reflect the unique needs, assets and resources of different communities. This requires a flexible approach that links with local knowledge and infrastructure.

"The new report offers important insights around the value of informal, local volunteer responses and the principles of mutuality and reciprocity which underpin the most effective volunteering initiatives. Those organised by residents that lived in their community and were able to identify the appropriate responses for their community, whether that came from a good neighbour, a volunteer, or a VCS or LA service."

The findings are all the more significant, as it follows the recent publication of a UK Parliamentary report by Daniel Kruger MP: Levelling up our communities: proposals for a new social covenant commissioned by the Prime Minister.

This 'sets out a vision for a more local, more human, less bureaucratic, less centralised society', yet it continues to focus upon more centralised approaches to volunteering, encouraging all NHS Responders to sign up for a Volunteer Passport and carrying out a national communications campaign.

Volunteer-led community level responses will remain invaluable through the winter months, especially as social restrictions continue and the longer-term challenges of food poverty and social isolation remain. Meeting the needs of these groups will be all the more challenging given the crisis that the VCS is facing.

Professor Joanne Cook, from the University of Hull, said: "VCS capacity is being eroded by the resource squeeze, volunteers returning to work, and staff and volunteer fatigue. Ensuring the sector has the resources it requires to play its critical role in meeting community needs over the coming months, should be a key priority for local and national governments."

As Chile and Argentina witnessed the total solar eclipse on Dec. 14, 2020, unbeknownst to skywatchers, a little tiny speck was flying past the Sun -- a recently discovered comet.

This comet was first spotted in satellite data by Thai amateur astronomer Worachate Boonplod on the NASA-funded Sungrazer Project -- a citizen science project that invites anyone to search for and discover new comets in images from the joint European Space Agency (ESA) and NASA Solar and Heliospheric Observatory, or SOHO.

Boonplod discovered the comet on Dec. 13, the day before the eclipse. He knew the eclipse was coming, and was eager to see whether his new comet discovery might appear in the Sun's outer atmosphere as a small speck in eclipse photographs.

The comet, named C/2020 X3 (SOHO) by the Minor Planet Center, is a "Kreutz" sungrazer. This family of comets originated from a large parent comet that broke up into smaller fragments well over a thousand years ago and continues to orbit around the Sun today. Kreutz sungrazing comets are most commonly found in SOHO images. SOHO's camera works by mimicking total solar eclipses: A solid occulting disk blocks out the otherwise blinding light of the Sun, revealing dimmer features in its outer atmosphere and other celestial objects like comets. To date, 4,108 comets have been discovered in SOHO images, with this comet being the 3,524th Kreutz sungrazer spotted.

Around the time the eclipse image was taken, the comet was traveling at roughly 450,000 miles per hour, about 2.7 million miles from the Sun's surface. The comet was around 50 feet in diameter -- about the length of a semitruck. It then disintegrated to dust particles due to intense solar radiation, a few hours before reaching its closest point to the Sun.

While the pressures of climate change bring a sense of urgency to renewable energy development, a new study serves as a roadmap toward uniting the goals of a low-carbon future with that of ecological sustainability and conservation.

The study, published in the journal Frontiers in Sustainability from the University of California, Davis, and John Hopkins University, aims to help decision-makers avoid the unintended environmental consequences of renewable energy development.

"Renewables aren't always sustainable, but they can be if we think proactively," said co-leading author Sarah Jordaan, an assistant professor at John Hopkins University's School of Advanced International Studies. "There is a huge misalignment between United Nations Sustainable Development Goals and climate goals. This is a call to action for leaders to come together to address it."

To develop the roadmap, the authors assessed public and private investments in renewable energy and analyzed the tradeoffs and synergies of clean energy. They also identified research themes drawn from a two-day workshop held by the Electric Power Research Institute in 2019 with 58 leading experts in the fields of renewable energy and sustainability from across academia, industry, government sectors.

MISSING THE FOREST FOR THE GHGs

Among the key research priorities identified for sustainable solar and wind developments include site selection and understanding interactions with wildlife.

For example, Florida's longleaf pine forests have, for centuries, helped store carbon, protect water quality and provide wildlife habitat. Now, only a fraction of the historical range of longleaf pine forests in the state remain. Yet a sliver of that remaining sliver is slated to be replaced by a solar installation.

Meanwhile, in the same state and just a few miles away, waterbirds squawk, preen their feathers, and hunt for food atop a floating array of solar panels - a "floatovoltaic" installation. Here, both wildlife and greenhouse-gas-reduction goals appear to coexist gracefully.

"We can't pursue climate change mitigation blindly," said co-leading author Rebecca. R. Hernandez, a UC Davis assistant professor and founding director of the Wild Energy Initiative in the John Muir Institute of the Environment. "We must consider the impacts of renewables on the few ecosystems we have left."

Other key considerations and priorities the scientists identified were public acceptance of clean energy projects and the study of end-of-life management for wind and solar. For instance, the composites in wind blades are not recyclable, and solar panels contribute to a growing electronic waste problem.

PUSHING FORWARD

The authors said the work highlights how the field of sustainable renewable energy is in its infancy, with many of the questions and solutions unclear. The roadmap, they emphasize, is a living document, designed to change as the field matures.

"We're pushing forward into maturation something that is really just being born," Hernandez said of renewable energy. "Across its sectors, everyone is trying to figure things out as quickly as possible. This roadmap points to the fact that we all need to get organized and work together to share knowledge, innovation and results."

Jordaan said while the roadmap highlights problems, they are solvable.

"We need to research the things we don't know, implement solutions we do know, and develop technology as needed and ensure accountability," she said.