Culture

The gravitational wave (1) detectors LIGO and Virgo have just chalked up their biggest catch yet, a black hole 142 times the mass of the Sun, resulting from the merger of two black holes of 85 and 65 solar masses. The remnant black hole is the most massive ever observed with gravitational waves, and it could give us some clues about the formation of the supermassive black holes that sit at the centres of some galaxies. The mass of one of the merging black holes, 85 solar masses, provides information that could improve our understanding of the final stages in the evolution of massive stars. The discovery, to which several CNRS teams contributed as part of the Virgo collaboration, is published on 2 September 2020 in the journals Physical Review Letters and Astrophysical Journal Letters.

At first sight, there is nothing particularly new about the detection of the birth of a black hole caused by the merger of two others, accompanied by the emission of a huge amount of energy: after all, a succession of similar events have been observed ever since 2015, when the gravitational waves produced by such phenomena were observed for the first time (2). However, GW190521, the signal recorded on 21 May 2019 by the LIGO and Virgo instruments, stands out from the crowd, for the signal is not only the most distant, and therefore the oldest, ever detected (the gravitational wave took seven billion years to reach us), but in addition the black hole resulting from the merger is also the most massive observed so far. Above all, the observation is the first direct evidence of the existence of 'intermediate-mass' black holes, which weigh in at 100 to 100 000 solar masses. Such intermediate-mass black holes are heavier than those resulting from the collapse of high mass stars, but much lighter than the supermassive black holes that sit at the centre of some galaxies. Until now, only indirect evidence obtained from electromagnetic observations hinted at their existence.

Intermediate-mass black holes are interesting since they may hold the key to one of the big puzzles in astrophysics and cosmology: the origin of supermassive black holes. Although the question remains an open one, one of the scenarios proposed to explain the formation of these cosmic monsters is precisely that of repeated mergers of intermediate-mass black holes.

With masses around 65 and 85 times that of the Sun, the two black holes that were observed to merge intrigue astrophysicists as well. This is because, based on our current knowledge, the gravitational collapse of a star cannot form black holes in the approximate range of 60 to 120 solar masses, since the most massive stars are completely blown apart by the supernova explosion that accompanies the collapse, leaving only gas and dust behind them. So, sitting right in the middle of this forbidden range, how did the black hole of 85 solar masses form? Is there something we haven't understood about the way in which massive stars end their lives? If it is not of stellar origin, could it too have resulted from an earlier merger of less massive black holes? Or alternatively, could it be a hypothetical primordial black hole, formed during the Big Bang? The observation of GW190521 clearly raises new questions about the formation of the enigmatic objects we call black holes.

Compared to earlier observations, the GW190521 signal detected by LIGO and Virgo is very short and harder to analyse. Due to its more complex nature, other hypotheses involving more exotic sources were also explored to explain it, and such possibilities are described in the article in Astrophysical Journal Letters. However, the most plausible source of this gravitational wave remains the merger of two black holes.

The populations of common animals are just as likely to rise or fall in number in a time of accelerating global change as those of rare species, a study suggests.

A study of more than 2,000 species reveals animal populations around the world - from the very common to endangered species - are going up and down as global change alters land, sea and freshwater ecosystems.

The findings highlight a need to look beyond only rare species in order to improve efforts to conserve global biodiversity, scientists say.

Critically endangered animals - such as the Hawksbill sea turtle - were previously thought to be at greater risk of decline than common species like red deer, but the study found a wide spectrum of changes in animal numbers.

Findings from the new study suggest the numbers within very common animal species are, in fact, as likely to increase or decrease as rare ones.

However, species with smaller population sizes were shown to be more likely to change from year to year, potentially increasing their extinction risk in the long term.

Until recently, scientists were still compiling data on how animal populations were shifting over time on a global scale across the different regions of the planet.

Making use of the newly available data, a team of University of Edinburgh researchers studied nearly 10,000 animal populations recorded in the Living Planet Database between 1970 and 2014 to provide a new perspective on animal population change. These include records of mammals, reptiles, sharks, fish, birds and amphibians.

The team found that 15 per cent of all populations declined during the period, while 18 per cent increased and 67 per cent showed no significant change.

Amphibians were the only group in which population sizes declined, while birds, mammals and reptiles experienced increases.

The overall decline in amphibians makes them a priority for conservation efforts, researchers say, as their loss could have knock-on effects in food chains and wider ecosystems.

The study, published in the journal Nature Communications, was funded by the Natural Environment Research Council and the Carnegie Trust.

Gergana Daskalova, of the University of Edinburgh's School of GeoSciences, who led the study, said: "We often assume that declines in animal numbers are prevalent everywhere. But we found that there are also many species which have increased over the last half of a century, such as those that do well in human-modified landscapes or those that are the focus of conservation actions."

Dr Isla Myers-Smith, also of the School of GeoSciences, who co-authored the study, said: "Only as we bring together data from around the world, can we begin to really understand how global change is influencing the biodiversity of our planet. The original idea for this study stemmed from a fourth year undergraduate class at the University of Edinburgh. It is so inspiring to see early career researchers tackle some of the big conservation questions of our time using advanced data science skills."

A simple test such as the strength of your handgrip could be used as a quick, low-cost screening tool to help healthcare professionals identify patients at risk of type 2 diabetes. In new research, scientists at the universities of Bristol and Eastern Finland measured the muscular handgrip strength of 776 men and women without a history of diabetes over a 20-year period and demonstrated that the risk of type 2 diabetes was reduced by around 50 per cent for every unit increase in handgrip strength value. The findings are published today in Annals of Medicine.

Diabetes in all forms is the ninth major cause of death in the world. Around 90 per cent of people with diabetes have type 2 diabetes. In the UK alone, one in ten people over 40 are now living with a diagnosis of type 2 diabetes. It is expected that if nothing changes, more than five million people will have developed diabetes by 2025.

Though older age, obesity, family history and lifestyle factors such as physical inactivity, smoking, unhealthy diet and excessive alcohol contribute substantially to the risk of developing type 2 diabetes, these factors alone do not explain all of the risk for type 2 diabetes. It appears other factors may be involved. Reduced muscular strength, which can be measured by handgrip strength, has consistently been linked to early death, cardiovascular disease, and disability.

Until recently, there was inconsistent evidence on the relationship between handgrip strength and type 2 diabetes. In a recent literature review of ten published studies on the topic the same researchers demonstrated that people with higher values of handgrip strength had a 27 per cent reduced risk of developing type 2 diabetes.

However, while findings from this review suggested handgrip strength could potentially be used to predict type 2 diabetes, researchers needed to test this formally using individual patient data.
In this latest study, the researchers from Bristol Medical School and Eastern Finland's Institute of Public Health and Clinical Nutrition followed 776 men and women aged 60-72 years without a history of diabetes over a 20-year period and measured the power of their hand grip strength using a handgrip dynamometer. Patients were asked to squeeze the handles of the dynamometer with their dominant hand with maximum isometric effort and maintain this for five seconds.

An analysis of the results demonstrated that the risk of type 2 diabetes was reduced by about 50 per cent for every unit increase in handgrip strength value. This association persisted even after taking into account several established factors that can affect type 2 diabetes such as age, family history of diabetes, physical activity, smoking, hypertension, waist circumference and fasting plasma glucose. When information on handgrip strength was added to these established factors which are already known to predict type 2 diabetes, the prediction of type 2 diabetes improved further.

According to lead author Dr Setor Kunutsor from Bristol's Musculoskeletal Research Unit: "These findings may have implications for the development of type 2 diabetes prevention strategies. Assessment of handgrip is simple, inexpensive and does not require very skilled expertise and resources and could potentially be used in the early identification of individuals at high risk of future type 2 diabetes."

Importantly, the findings appeared to be marked in women compared to men in sex-specific analyses, suggesting that women are likely to benefit from the use of this potential screening tool.

Principal investigator, Professor Jari Laukkanen from the University of Eastern Finland, added: "These results are based on a Finnish population. Given the low number of events in our analyses, we propose larger studies to replicate these findings in other populations and specifically in men and women."
The authors add that further research is needed to establish whether efforts to improve muscle strength such as resistance training are likely to reduce an individual's risk of type 2 diabetes.

The Korea Institute of Science and Technology (KIST) has announced that a research team led by Dr. Joong-Kee Lee of the Center for Energy Storage Research had developed a next-generation secondary battery that uses zinc metal as an electrode without any risk of explosion or fire. This battery is safe enough to be worn on the body and can be manufactured in the form of fiber shape, which means it may potentially be applied as a power source for wearable devices in the future.

Recently, the demand for safe batteries has been rising dramatically, mainly due to fires occurring in various electronic devices using lithium-ion batteries. The primary cause of such fires is the highly flammable electrolytes, but since Zn-ion secondary batteries use water-based electrolytes, there is no risk of explosion. This is why they are considered one of the more promising candidates to replace Li-ion batteries.

However, zinc anodes, which are the core material of existing Zn-ion batteries, present an inherent problem in that they undergo continuous corrosion in water-based electrolytes. Not only that, when zinc ions are stored on a metal surface, they accumulate as crystals in the form of branches (dendrites)* and trigger a short circuit between electrodes, resulting in a sharp decline in efficiency. Various studies have been carried out to come up with a solution to this problem through the means of a zinc metal complex, surface coating, and shape change, for example, but there have been major limitations in relation to processing cost and time.

The team headed by Dr. Lee from KIST developed a periodic anodizing method, which involves repeatedly permitting and blocking a flow of current on the surface of the metal electrode, thereby successfully controlling the surface coating morphologies and shape pattern array of the zinc oxide film simultaneously.

Using this method, the KIST research team inhibited the generation of dendrites during the electrochemical reaction by forming a functionalized shape in which hexagonal pyramids were arranged on the surface of zinc metal. According to the periodic anodizing method, the zinc oxide covering the upper part of the hexagonal pyramid is thick, whereas it is thin on the sides. The variation in thickness induces the zinc metal to accumulate on the side with a relatively thinner layer of zinc oxide. Dendrites are a problem as they accumulate vertically on the metal surface, but the newly developed technology in question induces the zinc metal film to grow in a horizontal direction on the electrode surface, and it was able to effectively suppress the generation of dendrite. As for the zinc oxide film that formed on the surface, direct contact with electrolytes was blocked, thereby preventing corrosion and side reaction at the same time.

The Zn-ion secondary battery developed through this study maintained nearly 100% of its capacity over 1,000 cycles, even though it was repeatedly charged and discharged under extreme conditions (9,000 mA/g, fully charged and discharged for about 2 minutes each), attributed to its structural and electrochemical stability.

Based on such stability, the KIST researchers made a Zn-ion secondary battery in the form of flexible fibers. In addition to being bent can be bent easily, it can be used incorporated into clothing, a bag if it is made into fabric. (ACS Appl. Mater. Interfaces 2020, 12, 5, 5820-5830)

Dr. Lee, a senior researcher at KIST, said, "The high-performance Zn-ion secondary battery developed in this study does not present any potential risks associated with Li-ion batteries coming into contact with the human body. At the same time, we expected it to garner attention as a next-generation secondary battery that is safe for the human body and doesn't present any risks of explosion or fire, along with its excellent electrochemical performance that is comparable to the existing commercial batteries in terms of battery capacity. (Advanced Functional Materials, 2020, 202004210, DOI: 10.1002/adfm.202004210) It appears that based on excellent stability, improved electrochemical performance, and simple processes, it will be possible to make the manufacturing process practical for real-life application."

The most massive black hole collision ever detected has been directly observed by the LIGO and VIRGO Scientific Collaboration, which includes scientists from The Australian National University (ANU).

The short gravitational wave signal, GW190521, captured by the LIGO and Virgo gravitational wave observatories in the United States and Europe on 21 May last year, came from two highly spinning, mammoth black holes weighing in at a massive 85 times and 66 times the mass of the Sun, respectively.

But that is not the only reason this system is very special. The larger of the two black holes is considered `impossible'. Astronomers predict that stars between 65 - 130 times the mass of the Sun undergo a process called pair instability, resulting in the star being blown apart, leaving nothing behind.

With a mass of 85 solar masses, the larger black hole falls squarely in that forbidden range, referred to as the upper black hole mass gap, and should be `impossible'. So if it wasn't created by the collapse of a star, how did it form?

"We think of black holes as the vacuum cleaners of the Universe. They suck in everything in their paths, including gas clouds and stars," said Professor Susan Scott?from the ANU Research School of Physics, a co-author on the publication.

"They also suck in other black holes and it is possible to produce bigger and bigger black holes by the ongoing collisions of earlier generations of black holes. The heavier `impossible' black hole in our detected collision may have been produced in this way."

The two black holes merged when the Universe was only about seven billion years old, which is roughly half its present age. They formed an even larger black hole weighing a whopping 142 times the mass of the Sun, by far the largest black hole ever observed through gravitational wave observations.

Black holes of mass 100 to 100,000 solar masses are called intermediate mass black holes (IMBHs). They are heavier than stellar mass black holes but lighter than supermassive black holes often located at the centres of galaxies. There have been no conclusive electromagnetic observations for IMBHs in the mass range 100 to 1,000 solar masses.

"The `impossible' black hole formed by the collision lies in the black hole desert between 100 and 1,000 times the mass of the Sun," Professor Scott, who is also the Chief Investigator with the ARC Centre of Excellence for Gravitational Wave Discovery (OzGrav), said.

"We are very excited to have achieved the first direct observation of an IMBH in this mass range. We also saw how it formed, confirming that IMBHs can be produced through the merger of two smaller black holes."

Another recent study suggests scientists using Caltech's Zwicky Transient Facility may have spotted a light flare from the collision. This is surprising, as black holes and their mergers are normally dark to telescopes. One theory is the system may have been orbiting a supermassive black hole. The newly formed black hole may've received a kick from the collision, shooting off in a new direction and surging through the disk of gas surrounding the supermassive black hole, causing it to light up.

"There are a number of different environments in which this system of two black holes could have formed, and the disk of gas surrounding a supermassive black hole is certainly one of them," OzGrav postdoctoral researcher, Dr Vaishali Adya from ANU, said.

"But it is also possible that this system consisted of two primordial black holes that formed in the early Universe.

"Every observation we make of two black holes colliding gives us new and surprising information about the lives of black holes throughout the Universe. We are beginning to populate the black hole mass gaps previously thought to exist, with `impossible' black holes that have been revealed through our detections."

Recent estimates indicate a prevalence of autism spectrum disorder (ASD) in the United States of 1 in 59 children with a well-established 4:1 male predominance. Individual costs for care are estimated at about $2.4 million, yielding a societal burden that is expected to exceed $400 billion by 2025. Currently, there are no FDA-approved medications that improve the core symptoms of ASD.

Neuroscientists in the laboratory of Randy D. Blakely, Ph.D., professor of biomedical science in Florida Atlantic University's Schmidt College of Medicine and executive director of the FAU Brain Institute, are focused on serotonin, a mood-regulating molecule in the brain that regulates many brain synapses -- the gaps between nerve cells where signals are sent and received. The supply of serotonin is tightly regulated by a protein called the serotonin transporter (SERT), which sweeps away serotonin from synapses to limit its action. Shifts in the transporter's activity can significantly impact the ability of serotonin to act in the brain.

Changes in signaling by the neurotransmitter serotonin has been connected to autism for more than 50 years, dating back to findings of elevated serotonin levels in the blood of some people with the disorder, a feature termed hyperserotonemia. Since this time, multiple rare changes in the genetic code that impact SERT have been observed.

Recent studies of mice expressing the most common of these gene variants, called SERT Ala56, induces behavioral changes in animals that scientists connect to alterations in people with autism - repetitive behavior, altered communication, and atypical social interactions, as well as hyperserotonemia. Although the effects of the SERT Ala56 mutation are paralleled by other mutations in the SERT gene, none of these mutations are common enough to account for the number of individuals with autism demonstrating hyperserotonemia.

Blakely and collaborators have published a study in the journal Frontiers in Molecular Neuroscience, which now offers a possible explanation for this puzzle.

"We have known for some time that the activity and regulation of the SERT protein is critically dependent on a number of other proteins that tell the protein where to locate on nerve cells and how to act," said Blakely, lead author.

It turns out that the SERT Ala56 mutation changes the structure of the transporter in ways that keep these partner proteins from interacting with the transporter, a protein that Blakely's laboratory identified thirty years ago.

Last year, Blakely's former graduate student Meagan Quinlan, Ph.D., first author and a post-doctoral fellow at the University of Washington, demonstrated that the SERT Ala56 mutation impacts the structure of the SERT protein in cells in culture, revving up the transporter into a state of abnormally high activity.

"We think that this high-activity state results in removal of too much serotonin from sites in the brain where serotonin is needed, both during development and in adults," said Quinlan. "I suspect that the structural changes we have observed likely reflected changes in the regulatory ability of SERT-associated proteins to maintain serotonin inactivation at normal levels."

To test this concept, Quinlan purified the mutant transporter from the brain of SERT Ala56 expressing mice, as well as from normal mice, and then determined whether proteins normally bound to SERT were still attached.

"We found that only a few proteins seemed to interact with SERT Ala56 more than they should. In contrast, many more proteins appeared no longer tethered to the transporter, including some proteins we already knew to be SERT regulators and others that have been linked to ASD," said Quinlan.

Blakely was actually quite surprised at the findings. "It is quite amazing that one of the smallest changes you can make in SERT can alter its interactions with partners," said Blakely.

According to Blakely, further work could reveal more extensive links between SERT and other genes known to associate with autism, broadening the impact of SERT Ala56 to other neurotransmitter systems.

"Following the scent of serotonin may well take us to molecules and medications we had no clue about just a few years ago," said Blakely.

Blakely's team recently reported a new small molecule that can tone down SERT activity and normalize behaviors in the SERT Ala56 mouse, a molecule that he hopes may lead to a new therapeutic.

"A goal moving forward with this drug is to see if it can reverse the changes in SERT Ala56 protein associations, tying the molecular changes we see with the mutant to how the drug may work," said Blakely.

ASD is a serious developmental disorder with increased prevalence that impairs the ability to communicate and interact and impacts the nervous system. The range and severity of symptoms can vary widely and common symptoms can include difficulty with communication and social interactions, obsessive interests, and repetitive behaviors. No current medications treat the core features of ASD.

A blood test on hospital admission showing the presence or absence of SARS-CoV-2 can identify patients at a high risk of severe COVID-19. Admitted patients without virus in their blood have a good chance of rapid recovery. This according to researchers at Karolinska Institutet and Danderyd Hospital in a new study published in the scientific journal Clinical Infectious Diseases.

Blood samples were taken from patients with a confirmed COVID-19 infection within three days of admission to the Department of Infectious Diseases, Danderyd Hospital, Sweden. Patients with measurable levels of the new coronavirus SARS-CoV-2 in their blood were seven times more likely to develop critical symptoms and eight times more likely to die within 28 days.

"This readily available test allows us to identify patient groups at high or low risk of severe COVID-19, which enables us to better guide the treatment and monitoring of these patients", says the study's lead author Karl Hagman, infectious diseases consultant at Danderyd Hospital and doctoral student at Karolinska Institutet's Department of Clinical Sciences at the same hospital.

The researchers analysed the presence of viral RNA in the blood using a standard hospital technique called PCR on samples taken from a total of 167 patients. Sixty-one patients had measurable levels of the virus in their blood and 15/61 (25 per cent) died within 28 days of blood sampling. This can be compared with three deaths (three per cent) amongst the 106 patients who did not have measurable levels of virus in their blood. The presence of virus in the blood increased with age and was much more common in patients over the age of 60.

The researchers received no specific funding for this study. The paper's last author, Johan Ursing, has a clinical research position financed by Region Stockholm. One of the co-authors has reported receipt of payment from pharmaceutical company Pfizer outside this current study. No other potential conflicts of interest are declared in the paper.

The bacterium Helicobacter pylori is linked to increased risk of stomach cancer, and is genetically highly variable. A new study by researchers of Ludwig-Maximilians-Universitaet (LMU) in Munich explores the role played by this diversity in the early phase of infection in adult humans.

It is estimated that about half of the world's population is infected with the bacterium Helicobacter pylori. Most primary infections occur in childhood. In many cases, it causes no overt symptoms in the human host, although it can give rise to a variety of gastrointestinal problems. However, if the infection becomes chronic, approximately 1% of its victims go on to develop stomach cancer. One of the most striking features of the pathogen is the range of its genetic variability, which makes it highly adaptable. - Moreover, as a new report now shows, this versatility becomes apparent within weeks of the initial infection. Led by Professors Sebastian Suerbaum and Christine Josenhans of LMU's Max von Pettenkofer Institute, the study appears in the online journal mbio.

The researchers were able to make use of a unique set of samples obtained in the course of a vaccine trial performed in collaboration with colleagues from the Max Planck Institute for Infection Biology in Berlin in which adult volunteers were infected with H. pylori. Ten weeks later, bacterial samples were isolated from two different regions of the stomach in each case, and the donors were then treated with antibiotics to eliminate the pathogen. Complete genome sequences of single-cell isolates obtained from these samples were determined using state-of-the-art single-molecule, real-time (SMRT) sequencing methods and compared with that of the H. pylori strain with which the volunteers had been infected nearly 3 months previously.

The results revealed that the bacterial genomes had undergone a surprising degree of diversification within this relatively short time span. Many of the mutations detected were located in genes that are directly involved in molecular interactions between the pathogen and host cells. The set of proteins affected included polypeptides that are expressed on the cell wall of the bacterium, as well as transport proteins that are found in its outer membrane. These findings suggest that specific genes are being positively selected to enable the bacterium to exploit metabolites that are available in different cellular niches in the lining of the stomach. In addition to these genetic mutations (which alter gene products), the authors noted a variety of epigenetic changes (which alter gene regulation) in the bacterial DNA during the early phase of infection. H. pylori possesses many enzyme systems that attach methyl groups to specific DNA sequences. The authors identified 24 such systems, and at least some of these may serve to regulate the expression of sets of genes in the bacterium. These results further support the notion that alterations in gene products and patterns of gene activity during the weeks and months following the primary infection play an important role in enabling the bacterium to adapt to, and become established in different niches in the stomach.

Viruses are often thought of as a human problem, however they are the most abundant biological entities on the planet. There are millions of viruses in every teaspoon of river, lake or seawater, they are found everywhere there is life and probably infect all living organisms. Most are completely harmless to humans and infect microscopic animals, plants and bacteria, which they hijack and reprogram to produce new virus particles, most often destroying these cells in the process. Every day, viruses destroy huge number of microorganisms in the environment, which changes the flow of energy in food webs on global scales. "Understanding how viruses evolve and function allows us to predict their role in the environment and how they interact with their hosts", says Christopher Bellas from the Department of Ecology at the University of Innsbruck. Together with colleagues from the Universities of Bristol, Reading and Aberystwyth in the UK, the University of Minnesota, USA, and Aarhus University in Denmark, he has sequenced and compared genomes (their total DNA) of viruses which infect microbes found on the surface of glaciers. The study, now published in the journal Nature Communications, shows that the viruses on glaciers in the Alps, Greenland and Spitsbergen have genomes which are nearly identical between these isolated locations, this contradicts what we know about the rapid evolution of viruses.

Evolutionary arms race

It is known from laboratory studies that viruses evolve rapidly in order to keep up with their hosts, which are also simultaneously evolving defenses against virus infection, this evolutionary arms race means that they should remain in balance relative to each other. This is known as the 'Red Queen' hypothesis after the character from Alice in Wonderland who states: It takes all the running you can do, to keep in the same place. "This means that when we sequence the genomes of viruses from two, long-term, isolated places, we should never find exactly the same virus genomes twice", says Christopher Bellas. The viruses studied by the research team originate in very unusual habitats on the surface of glaciers and ice sheets, called cryoconite holes. These small pools of meltwater on glaciers are ideal places to test how viruses evolve because they are miniature, replicated communities of microbes which are found on widely separated glaciers around the world.

A genetic fruit machine

When the researchers looked at the virus genomes from isolated cryoconite holes, thousands of kilometers apart, they expected to find that they would each contain different viruses only distantly related to one another. What they actually found was that most bacterial infecting viruses (bacteriophages) were nearly identical between the Arctic and the Alps. However, when they looked closer at their stable genomes, they saw that there were many small sections in each genome where DNA from other related viruses was repeatedly swapped in and out, in a known process called recombination. In each different location, the viruses shuffled the genes present in these swappable regions like a kind of genetic fruit machine. "This means that in the natural environment, gene swapping between viruses by recombination creates much diversity in the virus population, specifically in genes which are involved in recognising and attaching to different hosts, this probably gives viruses the potential to quickly adapt to different hosts in the environment", explains Christopher Bellas.

In 2019, the number of registered campylobacter infections increased by almost a fifth and studies show that many of the campylobacter outbreaks recorded that year were caused by chicken meat. These are some of the findings from the annual report on the incidence of zoonoses in Denmark for 2019.

Campylobacter has long been the bacteria that is to blame for the highest number of foodborne illnesses cases in Denmark. This trend continued in 2019 where 5,389 illness cases were registered. This is an 18.5% increase compared to the previous year and it is the third consecutive year that the number of campylobacter cases has increased.

This is one of the findings from the 2019 annual report on the incidence of zoonoses--disesases that can be transmitted from animals and food to humans. The report was prepared by the National Food Institute, Technical University of Denmark, in cooperation with Statens Serum Institut and the Danish Veterinary and Food Administration.

An increase in registered campylobacter outbreaks

The large increase in campylobacter cases is due to an unusually large outbreak related to Danish chicken meat. Chicken meat was also the source in five other outbreaks, while the source is unknown in three further outbreaks. The remaining campylobacter cases in 2019 are registered as sporadic--that is, they have no identifiable connection.

During 2019, Statens Serum Institut and the Danish Veterinary and Food Administration continuously analyzed and compared campylobacter from both patients and Danish chicken meat. Data show that campylobacter cases are more often related to outbreaks than previously thought, and as such the number of disease outbreaks related to campylobacter is higher than in previous years. According to the data, almost one third of all patients have a campylobacter infection that can be attributed to chicken meat.

"We are surprised that analyses of patient samples using whole genome sequencing show that the campylobacter cases to a greater extent are part of outbreaks, which can be traced back to the same food source, and that the majority of these outbreaks can be attributed to chicken. This knowledge provides new opportunities to prevent infection in Denmark," Head of Unit Eva Møller Nielsen at Statens Serum Institut says.

The large number of illness cases has led the industry to initiate a range of initiatives aimed at reducing the occurrence of campylobacter in the food production chain.

Focus on controlling campylobacter in Denmark and the EU

The importance of controlling campylobacter is also recognized at EU level, where an expert group under the European Food Safety Authority, EFSA, has assessed various options for controlling infection with the bacteria in the production of broilers. The results show that controlling campylobacter on farms is complicated and that no silver bullet exists.

"Given that we in the expert group have not found one single solution to solve the problem, it is paramount that authorities, the industry and researchers have access to reliable data, which can guide efforts to reduce the incidence of illness in humans," Head of Research Group and Senior Advisor at the National Food Institute, Johanne Ellis-Iversen says.

Tick-borne diseases

Data from the annual report stress that it is wise to keep an eye out for ticks after a nature trip: According to a study from the University of Copenhagen of just over 1,000 ticks collected in Gribskov--a forest situated north of Copenhagen--approximately one in four ticks carry the disease borrelia, while one in five ticks carry at least two different zoonoses.

Research suggests that humans are at greater risk if they are bitten by a tick that has been infected with more than one zoonosis. Some of the infections, which an infected tick can cause weaken the human immune system making it easier for other zoonoses to establish themselves in the body.

The study from the University of Copenhagen underlines how important it is for doctors to consider whether a patient may have been infected with other diseases when the patient is diagnosed with and treated for an infection caused by a tick bite.

In the first study of its kind, University of Illinois Chicago researchers have found associations among disrupted sleep, elevated blood pressure and changes in the gut microbiome.

The research aimed to determine whether a 28-day period of disrupted sleep changed the microbiota in rats. The gut microbiota refers to the collection of microorganisms living in the intestines. The researchers also sought to identify biological features associated with undesirable arterial blood pressure changes.

The results were published in Physiological Genomics.

Using rats, the researcher disrupted their sleep periods. Rats are nocturnal, so the experiments were designed to interfere with their daytime sleep periods.

Telemetry transmitters measured the rats' brain activity, blood pressure and heart rate. Fecal matter also was analyzed to examine changes in the microbial content.

The research idea was generated by several of the paper's authors who are or have been health care providers with night-shift schedules.

"When rats had an abnormal sleep schedule, an increase in blood pressure developed -- the blood pressure remained elevated even when they could return to normal sleep. This suggests that dysfunctional sleep impairs the body for a sustained period," Maki said.

Undesirable changes also were found in the gut microbiome -- the genetic material of all bacteria living in the colon.

Contrary to her initial hypothesis, Maki found that the gut microbiome changes did not happen immediately, but instead took a week to show unfavorable responses such as an imbalance among different types of bacteria including an increase in microbes associated with inflammation.

"When the sleep disruption stopped, everything did not come back to normal immediately," Maki said. "This research shows a very complex system with the presence of multiple pathological factors."

This was initial research, and studies will continue to examine pathways involving the gut microbiome and metabolites produced by gut bacteria. The researchers will see exactly how sleep characteristics are changed and how long blood pressure and gut microbiome alterations persist. Researchers will then determine how this information translates to humans.

"We hope to find an intervention that can help people who are at risk for cardiovascular disease because of their work and sleep schedules. People will always have responsibilities that interrupt their sleep. We want to be able to reduce their risk by targeting the microbiome with new therapies or dietary changes," Fink said.

A lopsided merger of two black holes may have an oddball origin story, according to a new study by researchers at MIT and elsewhere.

The merger was first detected on April 12, 2019 as a gravitational wave that arrived at the detectors of both LIGO (the Laser Interferometer Gravitational-wave Observatory), and its Italian counterpart, Virgo. Scientists labeled the signal as GW190412 and determined that it emanated from a clash between two David-and-Goliath black holes, one three times more massive than the other. The signal marked the first detection of a merger between two black holes of very different sizes.

Now the new study, published today in the journal Physical Review Letters, shows that this lopsided merger may have originated through a very different process compared to how most mergers, or binaries, are thought to form.

It's likely that the more massive of the two black holes was itself a product of a prior merger between two parent black holes. The Goliath that spun out of that first collision may have then ricocheted around a densely packed "nuclear cluster" before merging with the second, smaller black hole -- a raucous event that sent gravitational waves rippling across space.

GW190412 may then be a second generation, or "hierarchical" merger, standing apart from other first-generation mergers that LIGO and Virgo have so far detected.

"This event is an oddball the universe has thrown at us -- it was something we didn't see coming," says study coauthor Salvatore Vitale, an assistant professor of physics at MIT and a LIGO member. "But nothing happens just once in the universe. And something like this, though rare, we will see again, and we'll be able to say more about the universe."

Vitale's coauthors are Davide Gerosa of the University of Birmingham and Emanuele Berti of Johns Hopkins University.

A struggle to explain

There are two main ways in which black hole mergers are thought to form. The first is known as a common envelope process, where two neighboring stars, after billions of years, explode to form two neighboring black holes that eventually share a common envelope, or disk of gas. After another few billion years, the black holes spiral in and merge.

"You can think of this like a couple being together all their lives," Vitale says. "This process is suspected to happen in the disc of galaxies like our own."

The other common path by which black hole mergers form is via dynamical interactions. Imagine, in place of a monogamous environment, a galactic rave, where thousands of black holes are crammed into a small, dense region of the universe. When two black holes start to partner up, a third may knock the couple apart in a dynamical interaction that can repeat many times over, before a pair of black holes finally merges.

In both the common envelope process and the dynamical interaction scenario, the merging black holes should have roughly the same mass, unlike the lopsided mass ratio of GW190412. They should also have relatively no spin, whereas GW190412 has a surprisingly high spin.

"The bottom line is, both these scenarios, which people traditionally think are ideal nurseries for black hole binaries in the universe, struggle to explain the mass ratio and spin of this event," Vitale says.

Black hole tracker

In their new paper, the researchers used two models to show that it is very unlikely that GW190412 came from either a common envelope process or a dynamical interaction.

They first modeled the evolution of a typical galaxy using STAR TRACK, a simulation that tracks galaxies over billions of years, starting with the coalescing of gas and proceeding to the way stars take shape and explode, and then collapse into black holes that eventually merge. The second model simulates random, dynamical encounters in globular clusters -- dense concentrations of stars around most galaxies.

The team ran both simulations multiple times, tuning the parameters and studying the properties of the black hole mergers that emerged. For those mergers that formed through a common envelope process, a merger like GW190412 was very rare, cropping up only after a few million events. Dynamical interactions were slightly more likely to produce such an event, after a few thousand mergers.

However, GW190412 was detected by LIGO and Virgo after only 50 other detections, suggesting that it likely arose through some other process.

"No matter what we do, we cannot easily produce this event in these more common formation channels," Vitale says.

The process of hierarchical merging may better explain the GW190412's lopsided mass and its high spin. If one black hole was a product of a previous pairing of two parent black holes of similar mass, it would itself be more massive than either parent, and later significantly overshadow its first-generation partner, creating a high mass ratio in the final merger.

A hierarchical process could also generate a merger with a high spin: The parent black holes, in their chaotic merging, would spin up the resulting black hole, which would then carry this spin into its own ultimate collision.

"You do the math, and it turns out the leftover black hole would have a spin which is very close to the total spin of this merger," Vitale explains.

No escape

If GW190412 indeed formed through hierarchical merging, Vitale says the event could also shed light on the environment in which it formed. The team found that if the larger of the two black holes formed from a previous collision, that collision likely generated a huge amount of energy that not only spun out a new black hole, but kicked it across some distance.

"If it's kicked too hard, it would just leave the cluster and go into the empty interstellar medium, and not be able to merge again," Vitale says.

If the object was able to merge again (in this case, to produce GW190412), it would mean the kick that it received was not enough to escape the stellar cluster in which it formed. If GW190412 indeed is a product of hierarchical merging, the team calculated that it would have occurred in an environment with an escape velocity higher than 150 kilometers per second. For perspective, the escape velocity of most globular clusters is about 50 kilometers per second.

This means that whatever environment GW190412 arose from had an immense gravitational pull, and the team believes that such an environment could have been either the disk of gas around a supermassive black hole, or a "nuclear cluster" -- an incredibly dense region of the universe, packed with tens of millions of stars.

"This merger must have come from an unusual place," Vitale says. "As LIGO and Virgo continue to make new detections, we can use these discoveries to learn new things about the universe."

[Lakewood, Colorado; Bridgewater, New Jersey; September 1, 2020] The American Animal Hospital Association (AAHA) and the American Association of Feline Practitioners (AAFP) convened a panel of experts to update the 2013 AAFP Feline Vaccination Advisory Panel Report. The release of the 2020 AAHA/AAFP Feline Vaccination Guidelines provides updated recommendations and the most current information for feline vaccinations.

The Task Force approached the update with evidence-based recommendations and peer-reviewed literature on feline vaccinations. "Working together with these two organizations affords our veterinary community exposure to the wisdom of colleagues who are dedicated to increasing the standard of care for cats," said Amy ES Stone, DVM, PhD, Chair of the 2020 AAHA/AAFP Feline Vaccination Guidelines Task Force.

The guidelines stress the need for an expanded understanding by veterinary professionals of individualized feline risk factors to determine a proper preventive healthcare plan. Practitioners are encouraged to gain better insight into feline patients' risk factors, which may include life stage, environment, and lifestyle.

Veterinarians should use these guidelines in conjunction with their own clinical experience and expert opinion, while considering the needs of the individual patient. "Cats used to be vaccinated for certain diseases based solely on whether they went outside or not. Those times have changed," said AAHA Senior Veterinary Officer Heather Loenser, DVM. "We need to tailor vaccine protocols for individual pets, rather than basing vaccination decisions on a single factor."

"We no longer can simply ask a client if the cat is 'indoors' or 'outdoors,'" said Kelly St. Denis, MSc, DVM, DABVP (Feline Practice), and 2020 AAFP President. "A client may not correctly interpret what they might consider brief or low-risk outdoor access, which may contain information that contributes to your risk assessment. We need to ask if the cat has free access to outdoors; do they ever sit on a patio or in a cateo; do they have access to a balcony or open window; do they go anywhere outside of the home such as a friend's house or boarding facility; are they ever walked on a leash? A risk assessment of the other cats living in the home is also critical as these risks extend to all other cats in the house. By asking these questions you can better review the cat's risk for safety, nutrition, behavior, and zoonotic disease."

The guidelines provide resources for the entire veterinary practice team to utilize including:

A lifestyle-based feline vaccine calculator

FAQs and tips for client and staff education

Recommendations for core and noncore vaccines for pet and shelter-housed cats

A webinar summarizing the must-see and clinically important sections of the guidelines (available in October)

With these new guidelines, the team can educate pet owners about vaccination protocols and the overall importance to feline wellbeing, provide proper vaccine recommendations for pet and shelter cats, and have open conversations to address clients' questions or concerns.

The team from Marien Hospital and the department of Virology of Ruhr-Universität Bochum (RUB) as well as the Clinic for Infectious Diseases, the Clinic of Anesthesiology and the Institute for Virology of University Medicine Essen studied specific antibodies and T cells occurring in recovered, seriously ill and deceased Covid-19 patients. The researchers identified comparable immune reactions in clinical follow up. They report their findings in the journal Cell Reports Medicine from 29 August 2020.

How the immune system fights viruses

Antibodies and T lymphocytes are among the most important elements of the immune defence against viruses. The antibodies prevent viruses from entering the host cell by binding to certain virus receptors. They also mark the infected cells for other players in the immune system, which are able to kill the infected cells. Virus-specific T lymphocytes, on the other hand, can kill infected cells directly and highly efficiently.

During the last weeks, some studies have been published on the analysis of these cell-killing Sars-Cov-2 specific T cells in patients with Covid-19. The studies demonstrated detection of such cells in patients recovered from Covid-19 suggesting their protective antiviral effect. On the other hand, some studies indicate that an excessive immune response might be the cause of severe Covid-19. The role of Sars-Cov-2 specific T-cells in this exaggerated immune response is unclear.

Critically ill patients have the same or stronger immunity as recovered patients

In the current study, the research team analysed immune responses in Covid-19 patients during the disease progress. "This is how we wanted to investigate the role of T cells and antibodies in controlling the infection and the disease," explains Nina Babel, who headed the study. "The novel aspect of our study is that we analysed Sars-Cov-2 specific T-cells and antibodies in relation to disease progression and viral clearance. We found that a strong T-cell and antibody response could be detected not only in patients with mild Covid-19 patients who had recovered from the virus infection." Similar or even stronger immunity to Sars-Cov-2 was found in patients who had been critically ill and who suffered Covid-19-related lung failure.

"The total number of specific immune cells as well as their functionality was not better in patients who survived Covid-19 than in those who died from it," says Dr. Ulrik Stervbo, head of laboratory at the Centre for Translational Medicine. There was also no difference in the strength and functionality of the immune response between patients who still suffered from and those who had cleared a Sars-Cov-2 infection.

Excessive immune response plays an important role

"Even though further studies will be necessary to understand the specific mechanism of Covid-19 development, our data suggest that excessive Sars-Cov-2-specific T cell response can cause immunopathogenesis leading to Covid-19-related lung failure," points out Nina Babel. "The results of current studies on the successful application of immunosuppressive therapies in Covid-19 support this hypothesis," concludes Professor Timm Westhoff, Director of Medical Clinic I at Marien Hospital Herne.

Sophia Antipolis, France - 1 Sept 2020: Heart patients hospitalised with COVID-19 can safely continue taking angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), according to the BRACE CORONA trial presented in a Hot Line session today at ESC Congress 2020.1

ACE inhibitors and ARBs are commonly taken by heart patients to reduce blood pressure and to treat heart failure. There is conflicting observational evidence about the potential clinical impact of ACE inhibitors and ARBs on patients with COVID-19.2 Select preclinical investigations have raised concerns about their safety in patients with COVID-19. Preliminary data hypothesise that renin-angiotensin-aldosterone system (RAAS) inhibitors could benefit patients with COVID-19 by decreasing acute lung damage and preventing angiotensin-II-mediated pulmonary inflammation.

Given the frequent use of these agents worldwide, randomised clinical trial evidence is urgently needed to guide the management of patients with COVID-19.

Membrane-bound angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV-2, the virus responsible for the coronavirus disease 2019 (COVID-19).3 ACE2 expression may increase due to upregulation in patients using ACE inhibitors and ARBs.4

The BRACE CORONA trial was an academic-led, phase 4, randomised study testing two strategies: temporarily stopping the ACE inhibitor/ARB for 30 days versus continuing ACE inhibitors/ARBs in patients who were taking these medications chronically and were hospitalised with a confirmed diagnosis of COVID-19. The primary outcome was the number of days alive and out of hospital at 30 days.

Patients who were using more than three antihypertensive drugs, or sacubitril/valsartan, or who were haemodynamically unstable at presentation were excluded from the study.

The trial enrolled 659 patients from 29 sites in Brazil. All participants were chronically using an ACE inhibitor or ARB and were hospitalised with COVID-19. Patients were randomly allocated to stopping the ACE inhibitor/ARB for 30 days or continuing the ACE inhibitor/ARB.

The average number of days alive and out of hospital was 21.9 days for patients who stopped ACE inhibitors/ARBs and 22.9 days for patients who continued these medications. The average ratio of days alive and out of hospital between the suspending and continuing groups was 0.95 (95% confidence interval [CI] 0.90 to 1.01, p=0.09). The average difference between groups was -1.1 days (95% CI -2.33 to 0.17).

The proportion of patients alive and out of hospital by the end of 30 days in the suspending ACE inhibitor/ARB group was 91.8% versus 95% in the continuing group. A similar 30-day mortality rate was seen for patients who continued and suspended the ACE inhibitor/ARB (2.8% versus 2.7%, respectively with a hazard ratio of 0.97).

"This is the first randomised data assessing the role of continuing versus stopping ACE inhibitors and ARBs in patients with COVID-19," said principal investigator Professor Renato Lopes of Duke Clinical Research Institute, Durham, US. "In patients hospitalised with COVID-19, suspending ACE inhibitors and ARBs for 30 days did not impact the number of days alive and out of hospital."

He concluded: "Because these data indicate that there is no clinical benefit from routinely interrupting these medications in hospitalised patients with mild to moderate COVID-19, they should generally be continued for those with an indication."