Culture

One way CBD appears to reduce the "cytokine storm" that damages the lungs and kills many patients with COVID-19 is by enabling an increase in levels of a natural peptide called apelin, which is known to reduce inflammation and whose levels are dramatically reduced in the face of this storm.

Dental College of Georgia and Medical College of Georgia researchers reported this summer CBD's ability to improve oxygen levels and reduce inflammation as well as physical lung damage in their laboratory model of deadly adult respiratory distress syndrome, or ARDS.

Now they have shown that apelin levels go way down with the viral infection, which has killed 1 million people worldwide, and that CBD quickly helps normalize those levels along with lung function.

"It was dramatic in both directions," says Dr. Babak Baban, DCG immunologist and associate dean for research, of shifting apelin levels in both circulating blood and lung tissue.

Blood levels of the peptide dropped close to zero in their ARDS model and increased 20 times with CBD, they report in the Journal of Cellular and Molecular Medicine.

"CBD almost brought it back to a normal level," Dr. Jack Yu, physician scientist and chief of pediatric plastic surgery at MCG, says of the apparent first connection between CBD and apelin.

Apelin is a pervasive peptide made by cells in the heart, lung, brain, fat tissue and blood, and is an important regulator in bringing both blood pressure and inflammation down, says Baban, the study's corresponding author.

When our blood pressure gets high, for example, apelin levels should go up in the right place, like endothelial cells that line blood vessels, to help bring it down. Apelin should do the same to help normalize the significant increases in inflammation in the lungs and related breathing difficulties associated with ARDS.

"Ideally with ARDS it would increase in areas of the lungs where it's needed to improve blood and oxygen flow to compensate and to protect," Baban says. But when they looked at their ARDS model, apelin didn't do either, and instead decreased in both the lung tissue itself and the general circulation. Until they gave CBD.

They reported this summer in the journal Cannabis and Cannabinoid Research that treatment with CBD reduced excessive lung inflammation, enabling improvements in lung function, heathier oxygen levels, and repair of some of the structural damage to the lungs that are classic with ARDS. The investigators said then more work was needed, including finding how CBD produced the significant changes as well as human trials, before it should be included as part of a treatment regimen for COVID-19.

Now they have correlated those improvements with regulation of apelin. While they don't attribute all CBD's benefits to apelin, they say the peptide clearly has an important role in this scenario. They also don't yet know whether the novel coronavirus, or CBD for that matter, have a direct effect on apelin, or if these are downstream consequences, but they are already pursuing answers to those unknowns.

"It is an association; we don't know yet about causative, but it is a very good indicator of the disease," Baban says of the bottom line impact of the viral infection on apelin levels.

The now familiar spiked virus enters human cells via the also pervasive angiotensin-converting enzyme 2, or ACE2, receptor. "The spike proteins have just the right docking mechanism," says coauthor Yu. And there is plenty of common ground between ACE2 and apelin, including the fact that many cell types and tissues have both, including the lungs.

Apelin and ACE2 also normally work together to control blood pressure, and upregulation of both may be helpful in cardiovascular disease, including heart failure, by decreasing blood pressure while increasing the heart's ability to pump. In fact, apelin and ACE2 work together to regulate a healthy cardiovascular system and they are factors in pretty much any condition, like obesity or hypertension, that hurt the cardiovascular system, Baban says.

Like other disease, the novel coronavirus appears to upset their positive partnership. The virus' binding to the receptor for ACE2 has been shown to decrease ACE2 levels and increase levels of the powerful blood vessel constrictor angiotensin II, because less angiotensin II gets degraded and fewer vasodilators get produced, which worsens the patient's prognosis.

"Instead of ACE2 helping blood vessels relax, it helps the virus get into the host where it makes more virus instead of helping the lungs relax and do their job," says Yu.

While the researchers are still putting the pieces together, reduced levels of ACE2 appear to enable less apelin and less protection.

However it happens, their finding of dramatic reductions in apelin in the face of ARDS, makes levels of the protective peptide a potential early biomarker for ARDS and response to treatment efforts, they say.

The new finding was their first in learning more about how CBD produces the beneficial effects they saw in their model of ARDS. Next steps include better understanding the interaction between CBD, apelin and the novel coronavirus including why apelin goes down in the face of the virus and why CBD brings it up. That includes exploring how eliminating apelin affects ARDS and if CBD produces the same lung benefit without apelin.

Likely the virus suppresses something that suppresses apelin, they say and CBD interferes. But they doubt the apelin-CBD interaction is the only way the compound, the second most prevalent found in the marijuana plant, works in this and other scenarios.

The studies were enabled by the investigators' development of a safe, relatively inexpensive model of ARDS by giving a synthetic analog of double-stranded RNA called POLY (I:C). The novel coronavirus also has double-stranded RNA, while ours is single-stranded, so this analog produced a response similar to the virus, including the extreme lung damage that has led to the need for ventilator and other extreme support measures for patients, and is a major cause of death. Much as with the SARS-CoV-2 infection, the result is the "cytokine storm" that reflects an over-the-top immune response in the lungs, which results in an attack rather than protection.

For these studies, a control group received intranasal saline for three consecutive days while the COVID-19 model received POLY (I:C) intranasally for three days. A third group, the treatment group, received POLY ((I:C) and CBD over the same timeframe.

This time they looked and also found significantly reduced apelin levels in the mice that developed COVID-like symptoms compared to controls. Treatment with CBD normalized the immune response and apelin levels, along with oxygen levels and swelling and scarring in the lungs characteristic of the deadly ARDS.

"The apelinergic system is a very, very ubiquitous signaling system," Yu says. While it has diverse jobs in different places, and levels may rise and fall depending on what is needed, its levels are consistently measurable in the lungs, one of the reasons it should be a good biomarker, and it's also generally considered protective, they say.

Apelin's important, diverse roles include helping ensure the placenta is well supplied with blood and the oxygen and nutrients it carries during a pregnancy. In fact, DCG and MCG investigators decided to look at apelin because of the work of Dr. Évila Lopes Salles, a postdoctoral fellow with Baban in the DCG Department of Oral Biology and the study's first author, who was looking at the peptide's significant impact in gestation and clear anti-inflammatory role, Baban says.

Synthetic agonists that increase apelin levels exist and are showing promise in the laboratory for cardiovascular disease, including slowing the growth rate of weak points in blood vessels called aneurysms. CBD appears to be a natural apelin agonist, the researchers say.

Ants are one of the most successful groups of animals on the planet, occupying anywhere from temperate soil to tropical rainforests, desert dunes and kitchen counters. They're social insects and their team-working abilities have long since been identified as one of the key factors leading to their success. Ants are famously able to lift or drag objects many times their own weight and transport these objects back to their colony. But with previous research having focused on the social aspects of an ant colony, looking at an individual ant has been somewhat neglected.

Now, researchers at the Okinawa Institute of Science and Technology Graduate University (OIST) and Sorbonne University in Paris have investigated why individual worker ants are so strong by taking X-ray images and creating 3D models of their thorax - the central unit of their bodies - to analyze their muscles and internal skeleton. Their study, published in Frontiers in Zoology, examines the hypothesis that loss of flight in worker ants is directly connected to the evolution of greater strength.

"Worker ants evolved from flying insects," said Professor Evan Economo, who leads OIST's Biodiversity and Biocomplexity Unit. "We've always assumed that losing flight helped to optimize their bodies for working on the ground, but we have much to learn about how this is achieved."

Being able to fly might be a common dream amongst people but the reality of flight is that it puts strong constraints on the build of a body. In flying insects, the wing muscles occupy a major part of the thorax - sometimes more than 50%. This means that other muscles, which are used to support and move the head, legs, and abdomen are constrained and squeezed up against the exoskeleton.

But once the constraints of flight are removed, all that space in the thorax is open, which, the researchers surmised, would allow the remaining muscles to expand and reorganize.

Previous research in this area had focused on the external structure of ants but, with the technology available at OIST, the researchers were able to gain a highly detailed picture of what was going on inside the thorax. The aim was to analyze the general features common across all ants, rather than focus on the specialization of certain species. To do this, the researchers did a detailed analysis of two distantly related ant species, including both the wingless workers and the flying queens, and confirmed their findings across a broader sample of species.

They used advanced X-ray technology to scan the internal and external anatomy, like CT scans used in a hospital, but at much higher resolution. From these scans, the researchers mapped all the different muscles and modeled them in 3D. The result was a comprehensive image of the inside of the thorax. They then compared findings from these two species to a range of other ants and wingless insects.

As predicted, the researchers found that loss of flight had allowed for clear-cut reorganization of the thorax. "Within the worker ant's thorax, everything is integrated beautifully in a tiny space," said the late Dr. Christian Peeters, lead author of this paper, who was a research professor at Sorbonne University. "The three muscle groups have all expanded in volume, giving the worker ants more strength and power. There has also been a change in the geometry of the neck muscles, which support and move the head. And the internal attachment of muscles has been modified."

Interestingly, when looking at wingless wasps, the researchers found that these insects had responded to the loss of flight in a completely different way. Wingless wasps are solitary and consume food as they find it. On the other hand, ants are part of a colony. They hunt or scavenge for food that then needs to be carried back to the nest for the queen and younger nestmates, so it makes sense that there was a selection pressure to promote carrying ability.

Ants have been studied for centuries in terms of their behavior, ecology, and genetics but, the researchers emphasized, this story of strength has, so far, been somewhat overlooked. The next step is to develop more detailed biomechanical models of how different muscle groups function, do similar research on the mandible and legs, and explore the diversity seen between ant species.

"We're interested in what makes an ant an ant and understanding the key innovations behind their success" explained Professor Economo. "We know that one factor is the social structure, but this individual strength is another essential factor."

Beijing, China 19 Oct 2020: Elevated birth weight is linked with developing atrial fibrillation later in life, according to research presented at the 31st Great Wall International Congress of Cardiology (GW-ICC).

GW-ICC 2020 is a virtual meeting during 19 to 25 October. Faculty from the European Society of Cardiology (ESC) will participate in joint scientific sessions with the GW-ICC as part of the ESC Global Activities programme.

Study author Dr. Songzan Chen of Zhejiang University, Hangzhou, China said: "Our results suggest that the risk of atrial fibrillation in adulthood may be higher for large newborns (over 4,000 grams or 8 pounds 13 ounces) than those with normal birth weight. Preventing elevated birth weight could be a novel way to avoid atrial fibrillation in offspring - for example with a balanced diet and regular check-ups during pregnancy, particularly for women who are overweight, obese or have diabetes."

He added: "People born with a high weight should adopt a healthy lifestyle to lower their likelihood of developing the heart rhythm disorder."

Atrial fibrillation is the most common heart rhythm disorder, affecting more than 40 million individuals globally.1 People with atrial fibrillation have a five times greater risk of having a stroke. The relationship between birth weight and atrial fibrillation is controversial.2-5 This study investigated the lifetime causal effect of birth weight on the risk of atrial fibrillation.

The researchers conducted a naturally randomised controlled trial - a technique called Mendelian randomisation. First, they used data from 321,223 individuals in a genome-wide association study (GWAS) to identify 132 genetic variants associated with birth weight.6 Next, they identified which of those variants play a role in atrial fibrillation using data from 537,409 participants of the Atrial Fibrillation Consortium (of whom 55,114 had atrial fibrillation and 482,295 did not).7

To conduct the naturally randomised controlled trial, the 132 genetic variants were randomly allocated to the 537,409 participants at conception, giving each individual a birth weight in grams. The investigators then analysed the association between birth weight and atrial fibrillation.

Elevated birth weight was associated with an increased risk of atrial fibrillation later in life. Specifically, participants with a birth weight that was 482 grams (about 1 standard deviation) above the average (3,397 grams) were 30% more likely to develop the heart rhythm disorder (odds ratio = 1.30; 95% confidence interval 1.18-1.44; p=0.0000004).

Dr. Chen said: "A major strength of our study is the methodology, which allows us to conclude that there may be a causal relationship between high birth weight and atrial fibrillation. However, we cannot discount the possibility that adult height and weight may be the reasons for the connection. Birth weight is a robust predictor for adult height, and taller people are more likely to develop atrial fibrillation. Previous research has shown that the link between birth weight and atrial fibrillation was weaker when adult weight was taken into account."2

Professor Guosheng Fu of Sir Run Run Shaw Hospital (SRRSH), affiliated with the Zhejiang University School of Medicine, and one of the Scientific Committee Chairmen of GW-ICC 2020, said: "This study provides genetic evidence for the association between elevated birth weight and the increased risk of atrial fibrillation. From this research, we can see that reducing the number of newborns with elevated birth weight is probably considered as a feasible prevention to ease the burden of atrial fibrillation. Therefore, pregnant women should pay more attention to the diet control and regular check-ups, especially for those with obesity or diabetes. Equally important, people born with a high birth weight should be aware of reducing other risk factors to prevent atrial fibrillation."

Professor Michel Komajda, a Past President of the ESC and Global Affairs regional Ambassador for Asia at GW-ICC 2020, said: "Atrial fibrillation is a devastating illness that causes avoidable strokes if left untreated. We know that people with unhealthy lifestyles are more likely to develop atrial fibrillation, and risk can be lowered through physical activity and keeping body weight under control. This study is a welcome addition to our knowledge about how to prevent atrial fibrillation."

Tokyo, Japan - Researchers from Tokyo Metropolitan University studied the biodiversity of wetland plants over time in rice paddies in the Tone River basin, Japan. They found that paddies which were more likely to have been wetland before agricultural use retained more wetland plant species. On the other hand, land consolidation and agricultural abandonment were both found to negatively impact biodiversity. Their findings may one day inform conservation efforts and promote sustainable agriculture.

The Asian monsoon region is home to a vast number of rice paddies. Not only have they fed its billions of inhabitants for centuries, they are also an important part of the ecosystem, home to a vast array of wetland plant species. But as the population grows and more agricultural land is required, their sheer scale and complexity beg an important question: what is their environmental impact?

A team from Tokyo Metropolitan University led by Associate Professor Takeshi Osawa and their collaborators have been studying how rice paddies affect local plant life. In their most recent work, they investigated the biodiversity of wetland plants in rice paddies around the Tone River basin Japan. The Tone River is Japan's second longest river, and runs through the 170,000 square kilometer expanse of the Kanto plains. Previous studies have looked at how a particular species or group of species fare in different conditions. Instead, the team turned their attention to the range of species that make up the plant community, with a particular focus on the number of wetland and non-wetland species present. Changes were tracked over time using extensive survey data from 2002, 2007 and 2012.

They found that not all rice paddies are equal when it comes to how well they support original wetland species. In fact, there was a correlation between how likely it was that the land was wetland before it was put to agricultural use, and the number of wetland species which were retained over time. Here, the team measured this using flow accumulation values (FAVs) for different plots of land, a simple metric which showed how easily water could accumulate. Importantly, this kind of approach might help us predict how amenable new rice paddies might be to the local wetland flora by calculating a simple number using the local terrain. However, they also found that things like land consolidation and agricultural abandonment could also have a negative impact. The emerging story is that both current human usage and original geographical conditions play an important role in deciding how 'friendly' rice paddies could be for the original wetland ecosystem.

The team believe that the same approach could be applied to different locations such as plantation forests which were (or were not) originally woodland. After all, many nations are turning to large scale tree planting to offset carbon emissions. The ability to systematically 'assign' how new land usage might impact local ecosystems is sure to greatly help restoration and conversation efforts.

Droplets of fat inside our cells are helping the body's own defence system fight back against infection, University of Queensland researchers have discovered.

The international collaboration between UQ Institute for Molecular Bioscience researchers Professor Robert Parton and Professor Matt Sweet, and the University of Barcelona's Professor Albert Pol found that these fat droplets are both a food source and weapon against bacterial invaders.

"It was previously thought that bacteria were merely using the lipid droplets to feed on, but we have discovered these fatty droplets are involved in the battle between the pathogens and our cells," Professor Parton said.

"Fat is part of the cell's arsenal--cells manufacture toxic proteins, package them into the lipid droplets, then fire them at the intruders.

"This is a new way that cells are protecting themselves, using fats as a covert weapon, and giving us new insights into ways of fighting infection."

With antibiotic-resistant superbugs on the rise, researchers are determined to find alternative ways to fight infection.

One possibility is ramping up the body's natural defences.

"We showed that upon infection of white blood cells called macrophages, lipid droplets move to the part of the macrophage where the bacteria are present," Professor Sweet said.

The bacterial infection also changed the way that white blood cells used energy.

"Lipid droplets can be used as a fuel source for mitochondria when there aren't enough other nutrients," Professor Sweet said.

"During an infection, lipid droplets move away from the mitochondria and attack the bacteria instead, altering metabolism of the cell."

Cell biologist Professor Parton was inspired to continue this research after the phenomenon was seen in fruit flies.

"Most people thought the lipid droplets were 'blobs of fat', only useful for energy storage but now we are seeing that they act as metabolic switches in the cell, defend against infection and much more--there are now entire scientific conferences of researchers working on them," he said.

"Our next step is to find out how the lipid droplets target the bacteria.

"By understanding the body's natural defences, we can develop new therapies that don't rely on antibiotics to fight drug-resistant infections."

LA JOLLA--Your pancreas is studded with cell clusters called islets. In most people, special beta cells live snug in the islets, happily making the insulin that the body uses to regulate blood sugar. But in people with type 1 diabetes, the body's T cells mistakenly move into the islets and kill the beta cells.

It's long been thought that having "autoreactive" T cells in the pancreas was a sure sign of type 1 diabetes. Yet a new study led by scientists at La Jolla Institute for Immunology (LJI) shows that even healthy people have these cells lurking in the pancreas--in surprisingly high numbers.

"These T cells are like predators," says LJI Professor Matthias von Herrath, M.D., senior author of the new study, published October 16, 2020, in Science Advances. "And we always thought that beta cells would die if the predator was there. But it turns out the T cells are already there. They just seem to be waiting for a signal to attack."

These "predator" cells are called CD8+ T cells, and they specifically target a molecule called preproinsulin, a precursor to insulin. Previous studies have shown that healthy people do have some of these T cells in their bloodstream. No one knew if these cells would travel to the pancreas though--partly because of the challenge of obtaining pancreas samples.

In work spearheaded by Christine Bender, Ph.D., first author of the study and a postdoctoral fellow in the von Herrath Lab, the researchers used a new staining technique to show where these cells gathered in precious human tissue samples. They were surprised to see that even healthy people had proproinsulin-specific T cells swarming in the pancreas.

It appears that high numbers of these T cells in the pancreas are the default--whether you have type 1 diabetes or not. "We were surprised," says Bender. "Of course, every donor is different, but in general, the numbers are pretty high."

Of course, people with type 1 diabetes had it worse. Their tissue samples showed the T cells very close to--and even infiltrating--the islets.

"We can't say that these are the only culprits in type 1 diabetes," says von Herrath. "But these T cells are the prime suspects."

These results add evidence for the theory that type 1 diabetes is not caused by malfunctioning T cells attacking beta cells. Instead, the body is already making these T cells and something in the pancreas is triggering the attack. Von Herrath thinks this could mean that an effective type 1 diabetes therapy would need to be local to the pancreas.

Going forward, the researchers plan to take a closer look at how the preproinsulin-specific T cells behave. The team also hopes to investigate other proteins in islets that might attract T cell attacks.

"We still have so many questions," says Bender.

New research suggests that conditions such as attention deficit hyperactivity syndrome (ADHD), bipolar disorder, and even aggressive behaviors may be linked with sugar intake, and that it may have an evolutionary basis.

The research, out today from the University of Colorado Anschutz Medical Campus and published in Evolution and Human Behavior, presents a hypothesis supporting a role for fructose, a component of sugar and high fructose corn syrup, and uric acid (a fructose metabolite), in increasing the risk for these behavioral disorders.

"We present evidence that fructose, by lowering energy in cells, triggers a foraging response similar to what occurs in starvation," said lead author Richard Johnson, MD, professor at the University of Colorado School of Medicine on the CU Anschutz Medical Campus.

Johnson outlines research that shows a foraging response stimulates risk taking, impulsivity, novelty seeking, rapid decision making, and aggressiveness to aid the securing of food as a survival response. Overactivation of this process from excess sugar intake may cause impulsive behavior that could range from ADHD, to bipolar disorder or even aggression.

"While the fructose pathway was meant to aid survival, fructose intake has skyrocketed during the last century and may be in overdrive due to the high amounts of sugar that are in the current Western diet," Johnson adds.

The paper looks at how excessive intake of fructose present in refined sugars and high fructose corn syrup may have a contributory role in the pathogenesis of behavioral disorders that are associated with obesity and Western diet.

Johnson notes, "We do not blame aggressive behavior on sugar, but rather note that it may be one contributor."

Johnson recommends further studies to investigate the role of sugar and uric acid, especially with new inhibitors of fructose metabolism on the horizon.

"The identification of fructose as a risk factor does not negate the importance of genetic, familial, physical, emotional and environmental factors that shape mental health," he adds.

RNA interference is a gene regulatory mechanism in which the expression of specific genes is downregulated by endogenous microRNAs or by small interfering RNAs (siRNAs). Although siRNAs have broad potential for gene-silencing therapy, their instability is one of the difficulties to develop siRNA-based agents. To improve their stability, most of the developed siRNA-based drugs are chemically modified in their nucleotides or phosphodiester linkages. However, chemical modification is not a perfect strategy for siRNA stabilisation because extensive modification may interrupt the gene-silencing activity of siRNAs and also induce cytotoxicity.

siRNAs consist of oligonucleotide duplexes of 21-23 bases and form an A-form helix structure in which the major grooves have highly negative potential, therefore cationic molecules that can bind to the major grooves are expected to stabilise the RNA duplexes and protect them against cleavage in the body fluid. Based on this idea, organic chemists at Tokyo University of Science have recently synthesised an artificial cationic oligosaccharide, oligodiaminogalactose 4mer (ODAGal4), that can preferentially bind to the major grooves of RNA duplexes for siRNA stabilisation (Iwata, RI. et al. Org. Biomol. Chem. https://doi.org/10.1039/c6ob02690g (2017)).

Now, Atsushi Irie and his colleague at Tokyo Metropolitan Institute of Medical Science in collaboration with the team at Tokyo University of Science have developed a new strategy for siRNA stabilisation using ODAGal4 combined with phosphorothioate modification of RNAs. In the study published online on 9th September in the Scientific Reports, the researchers have proved that ODAGal4 strongly enhances biological and thermal stability of siRNAs in vitro.

The researchers show that ODAGal4 has several unique characteristics for stabilising siRNAs. Firstly, ODAGal4 can improve stability of various siRNAs independent of nucleotide sequence because ODAGal4 binds to phosphodiester linkages of RNA duplexes but not to nucleobases of the nucleotides. In addition, importantly, ODAGal4 does not compromise gene-silencing activity of any siRNAs. This character of ODAGal4 is in sharp contrast to those of known chemical modifications, which may interrupt gene-silencing activity of siRNAs. ODAGal4, therefore, has great potential for siRNA stabilisation, being widely applicable to various siRNA-based drugs.

Secondly, the effect of ODAGal4 on siRNA stabilisation is further enhanced by chemical modification of the siRNAs; in particularly, ODAGal4 prominently improves stability of RNAs with phosphorothioate linkages. This improvement in siRNA stability is superior to that observed for other chemical modifications (e.g., 2'-O-methyl, locked nucleic acid and 2'-deoxy-2'-fluoro nucleotides) suggesting that ODAGal4 combined with phosphorothioate modification is highly effective for stabilising siRNAs.

Lastly, another striking property of ODAGal4 is its binding specificity to RNA duplexes; ODAGal4 binds to A-form RNA helix but not to B-form DNA helix nor to single-stranded RNA/DNA. Although various gene delivery systems consisting of cationic polymers have been developed to stabilise nucleotides, the molecular structures of the polymers are not designed to specifically bind to nucleotides. The binding of the polymers to nucleotides relies on the ionic interaction between them, and thereby the polycation complexes are prone to induce cytotoxicity due to nonspecific binding of the polymers to other biomolecules. In marked contrast, ODAGal4 escapes from causing cytotoxicity because of its restricted binding with high affinity to RNA duplexes.

"Our goal will be application of ODAGal4 for siRNA-based agents. Although we should study in vivo experiments to confirm and expand our findings, we emphasise that ODAGal4 has a great advantage as improving siRNA stability and has a potential for reducing total dose and frequency of administration of siRNA-based drugs in future application," concludes Atsushi Irie.

Scientists from the University of Surrey have revealed the significant improvements they are making in perovskite-based solar cells.

Perovskite solar cells have shown significant potential in reaching the efficiency limit of the widely used solar cells currently on the market by absorbing light in a broader range of wavelengths. Industry has also been paying close attention to the development of perovskite-based cells thanks to their low-cost and simple fabrication, and their efficient combination with other types of solar cells to produce tandems.

Perovskite solar cells have emerged as the heir apparent to silicon-based solar cells because of their high-power energy conversion efficiency, low development cost, and ability to be ultra-lightweight. Named after a naturally occurring mineral that shares a structurally similar chemical formula, perovskites are synthetic composites that have three-dimensional lattice crystal structures.

In a front-cover paper published by the top American Chemical Society journal Chemical Reviews, the team from Surrey's Advanced Technology Institute (ATI) summarise the recent progress in improving perovskite tandem solar cells power conversion efficiencies, including thickness adjustment of perovskite , improving the transparency of perovskite solar cells, more effective protective layers and much more. The team also highlight measurement techniques, large-scale fabrication, commercialization development and lead-related environmental issues.

In the paper, the team offer a roadmap for further progress, including strategies for the enhancement of the power conversion efficiencies, stability and reliability assessments, and potential applications.

Dr Wei Zhang, the corresponding author and Senior Lecturer in Energy Technology at ATI, said: "Perovskite tandem solar cells are at the forefront of next-generation photovoltaic technologies. Our timely review summarizes the fundamentals of this exciting research field and future applications, which are expected to accelerate the commercialization of this low-cost and high-efficiency photovoltaic product as a major competitor to the traditional crystalline silicon solar cells in the next few years."

Professor Hui Li, first-author and Visiting Professor and Advanced Newton Fellow at ATI, said: "We are excited to offer this review that is showing great potential for moving our planet towards green energy."

Professor Ravi Silva, Director of ATI at the University of Surrey, said: "We are happy to see this wonderful research finally being used for real-world applications and we look forward to continuing our collaboration on perovskite tandem solar cells, which is a research priority area at ATI."

In a series of recommendations to fix the struggling Covid-19 test, trace and isolate system in England, health researchers from University College London and the London School of Hygiene & Tropical Medicine say that pooled testing for Covid-19 could significantly increase testing capacity in a relatively short space of time and help with the identification of asymptomatic cases in key workers.

Writing in the Journal of the Royal Society of Medicine, the researchers say that evaluating samples in batches rather than individually, and re-testing only the groups that come up positive means fewer tests overall would be needed. Several countries, including China, USA, Germany, Portugal, New Zealand, Rwanda, Uruguay, Israel and Vietnam have used pooled testing to considerably increase testing capacity and decrease pressure on lab reagents and operators.

As positivity rates rise, however, pooling becomes less efficient because more samples have to be tested. Co-author Alex Crozier, from the Division of Biosciences at University College London, said: "We are close to missing that window of opportunity in England unless we can control transmission quickly. For now, pooling may be best reserved for surveillance testing and asymptomatic screening of healthcare workers, care homes and hospital pre-admissions."

As well as increased investment in NHS and Public Health England labs to scale up additional testing locally and making use of unused lab capacity in universities and research institutes where possible, the recommendations include the initiation of environmental surveillance by testing wastewater as an early warning system for Covid-19 outbreaks.

The authors also recommend a major investment in people on the ground to support contact tracing. Pointing to Massachusetts where a $44 million contact tracing programme hired and trained 1,000 people to support existing local public health volunteers, the researchers write that this approach is much less costly than the UK government's £100 billion 'Operation Moonshot', and has reached 91.8% of cases and 78.8% of contacts. Recognising the important role played by superspreading events, another of the recommendations is to increase resources to enable a greater focus on identifying clusters using retrospective tracing, as seen in several countries that have been most successful such as Japan, South Korea, and Uruguay.

Another of the authors, Professor Martin Mckee, of the London School of Hygiene & Tropical Medicine, said: "England stands on the edge of a precipice: find, test, trace, isolate and support strategies need to be re-thought to have any chance of avoiding a considerable rise in cases over the coming months requiring a return to stricter social distancing measures nationwide. Our recommendations are feasible, do not require further individual sacrifice and would likely have a significant impact on driving down the reproductive number and reducing the socio-economic impact of the pandemic if they were implemented quickly."

Until mid-March 2020, the WHO, the EU as well as German authorities were convinced that the spread of the virus could not be curbed by border closures. "This belief was fatally mistaken", argues Ruud Koopmans. "Travel restrictions should be given much greater weight", he urges. "This holds true for containing upcoming waves of the COVID-19 pandemic as well as similar pandemics in the future."

The study draws on sociological accounts of network diffusion and shows that countries that are heavily exposed to international travel and tourism - such as France, Italy, and the USA - recorded significantly higher numbers of deaths. At the same time, death rates in countries more at the margins of international travel networks as well in island states remained comparatively low.

In view of this key role of international travel flows, the study examines the effects of entry bans and mandatory quarantines on COVID-19 mortality. The earlier such travel restriction measures were implemented, the greater was their limiting effect on mortality. Crucially, travel restrictions needed to be in place before the local spread of the virus had spiraled out of control. If one compares countries that imposed travel restrictions until early March to countries that implement them from mid-March onward or not at all, mortality within the first group is an estimated62 percentage points lower than in the second group.

Among the early adopters of travel restrictions with significantly lower death rates are countries such as Australia, Israel and the Czech Republic. Germany, which introduced its first travel restrictions on 16 March, belongs to the late-adopter group, but countries such as Great Britain, France or Brazil responded even later.

The study shows that the type of travel restriction also plays a role. Mandatory quarantines for incoming travelers were more effective than entry bans. A plausible explanation is that entry bans often include exceptions for both citizens and permanent residents. By contrast, quarantine measures tend to apply to all incoming travelers, regardless of their nationality or country of residence. The study further shows that targeted travel restrictions (represented in the study by entry bans and mandatory quarantines for travelers from China or Italy) were more effective than restrictions targeted against all foreign countries.

The study has been published as a WZB Discussion Paper:

New research published in Anaesthesia (a journal of the Association of Anaesthetists) reveals the much higher risk of mortality faced by COVID-19 patients in intensive care who have chronic kidney disease (CKD) or, those who develop new (acute) kidney injury (AKI) as a result of developing COVID-19.

CKD is a type of kidney disease in which kidney function declines over a period of months to years, and is more common in older people. There are five stages of the disease, ranging from early stages (1 and 2) in which people initially have no symptoms, through to the more serious stages 3 to 5, which can be associated with complications such as high blood pressure, type 2 diabetes and heart disease. CKD stage 5 is termed end stage kidney failure which must be treated with either dialysis (at home or in hospital), involving complex filtering machinery that takes over the blood-cleaning functions of the kidneys, or with a kidney transplant.

AKI is an abrupt loss of kidney function that takes place over seven days or less, and can have several causes, including the damage and inflammation caused by the COVID-19 virus itself, loss of blood flow to the kidneys, damage from pharmaceutical drugs or other ingested/injected substances, or by anything obstructing the flow of urine in the urinary tract.

This new study, led by Dr Sanooj Soni from Imperial College London, UK, and colleagues, examined the association between AKI and CKD with clinical outcomes in 372 patients with COVID-19 admitted to four regional intensive care units (ICUs) in the UK between 10 March 23 July 2020 (Hammersmith Hospital, London; St Mary's Hospital, London; Charing Cross Hospital, London; and Queen Elizabeth Hospital, Birmingham). The average age of the patients was around 60 years, and 72% of them were male. Also of note was the fact that the majority of patients were of Black, Asian of Ethnic Minority (BAME) background (281 patients, 76%).

A total of 216 (58%) patients had some form of kidney impairment (45% developed AKI during their ICU stay, while 13% had pre-existing CKD), while 42% had no CKD or AKI. The patients who developed AKI had no history of serious kidney disease before their ICU admission (known from blood tests either at admission to hospital or from their medical records), suggesting that the AKI was directly related to their COVID-19 infection.

The authors found that patients with no kidney injury or disease had a mortality of 21% (32/156 patients). Those with new onset AKI caused by the COVID-19 virus had a mortality of 48% (81/168), whilst for those with pre-existing CKD (Stages 1-4) mortality was 50% (11 /22). In those patients with end-stage kidney failure (i.e. CKD stage 5), where they already required regular out-patient dialysis, mortality was 47% (9 of 19 patients). Mortality was greatest in those patients with kidney transplants, with 6 out of 7 patients (86%) dying, highlighting that these patients are an extremely vulnerable group.

The investigators also examined the rates of renal replacement therapy, a form of hospital dialysis, due to COVID-19 in these ICU patients with kidney injury. Out of 216 patients with any form of kidney impairment, 121 (56%) patients required renal replacement therapy (see Table 2 full paper). Of the 48 survivors who needed dialysis for the first time during their ICU stay, 9 patients (19%) had to continue with dialysis after discharge from ICU, suggesting COVID-19 may lead to chronic kidney problems.

"To the best of our knowledge, this is the first comprehensive analysis of outcomes in critically unwell COVID-19 patients in the UK with kidney failure, particularly in patients with pre-existing chronic kidney disease," say the authors.

The authors note their surprise that mortality in patients with end-stage kidney failure and on dialysis, who normally have worse outcomes in many other diseases, was similar to that in patients with less severe kidney disease and COVID-19 associated AKI. This finding may suggest that such patients benefit equally from ICU admission and thus the threshold for admission should be calibrated accordingly in any future COVID-19 surge. Put another way, these results suggest that patients on dialysis with COVID-19 appear as likely to survive as patients with less serious CKD or AKI and can be considered for admission to an ICU bed.

However, the authors recommend caution interpreting these results due to selection bias - meaning that in this study only patients who were cared for in ICU during the peak of the last surge were included and other patients with end stage kidney failure, who may have been too unwell for admission to ICU, were not. This may have contributed to these findings of similar mortality in patients with end-stage kidney failure compared to those with less serious forms of CKD and AKI.

The reasons for the increased mortality in patients with kidney problems are not clearly understood. There are several theories, including that the COVID-19 virus causes endotheliitis, an inflammation of the blood vessels in the kidneys, which is similar to the problem COVID-19 is known to cause in the lungs. Other reports have suggested that there could be direct kidney injury from the cytokine-induced immune system inflammatory response (where the body is overwhelmed by its own immune response, the so-called cytokine storm), and also death of kidney tissue related to multi-organ failure caused by COVID-19.

The authors conclude: "Our data demonstrate that kidney disease and failure in critically ill patients with COVID-19 are common, and associated with high mortality. However, important differences exist between stages of acute and chronic kidney disease in how they affect mortality in patients with COVID-19 and patients who have had a kidney transplant are an extremely vulnerable group. In view of this, attention needs to be paid to COVID-19 patients with any form of kidney disease or injury, and every effort made to prevent progression of this disease or injury to reduce mortality in this cohort of patients."

Leesburg, VA, October 16, 2020--According to an article in ARRS' American Journal of Roentgenology (AJR), secondary interpretations of body MRI at tertiary care centers identify a high rate of discrepancies--with primary errors being interpretive in origin--suggesting that subspecialty interpretations should be encouraged, and institutions should provide adequate resources for these interpretations to occur.

"We retrospectively identified 395 secondary MRI reports from January 2015 to December 2018 that were labeled as body MRI examinations at a tertiary care center," explained lead author Danielle E. Kostrubiak from the University of Vermont Medical Center.

After exclusions for erroneous categorization and no extant outside report, Kostrubiak and colleagues compared the outside reports with the secondary interpretations, categorizing cases as either discrepancy or no discrepancy. Subdividing the discrepancies according to the most likely reason for error via previously published categories, these categories were further divided into perceptive and cognitive errors.

"Of the 357 cases remaining after 38 exclusions," Kostrubiak et al. wrote, "246 (68.9%; 95% CI, 63.8-73.7%) had at least one discrepancy between the original outside report and the secondary interpretation provided at our institution."

The most common error type contributing to both overall and primary discrepancy was faulty reasoning (a cognitive error characterized by misidentifying an abnormality), which occurred in 34.3% of the total discrepancies (95% CI, 29.0- 40.0%) and 37.8% of the primary discrepancies.

The most common error type contributing to a second discrepancy was a type of perception error called satisfaction of search, which occurred in 37.0% of the second discrepancies and 15.0% (95% CI 11.2- 19.6%) of the overall discrepancies.

"We are not aware of any studies that have specifically focused on secondary interpretations of body MRI analyzed by type of likely error, and to our knowledge, ours is the largest MRI sample size published to date," the authors of this AJR article concluded.

Although the innate subjectivity of error classification stands to limit similar studies, Kostrubiak and team acknowledged that related research should become progressively easier to conduct as medical practices adopt more detailed electronic medical records.

"The next step," they wrote, "would be to explore how these discrepancies may impact patient outcomes and overall cost to the system associated with these radiologic errors."

A soil scientist from RUDN University discovered the effect of fertilization on the ability of the soil to retain carbon. To understand this mechanism, he and his team studied the movement of organic carbon in the soil of rice paddies. The results of the study can help increase the fertility of the paddies while at the same time reducing the volume of greenhouse gases in the atmosphere. An article about the study was published in the Soil Biology and Biochemistry journal.

The main reason for global climate change is the increasing amount of carbon dioxide in the atmosphere. CO2 prevents thermal emissions from leaving our planet, and the so-called greenhouse effect occurs. Being able to absorb up to 10% of carbon dioxide from the atmosphere (which amounts to approximately 20,000 megatons of carbon in 25 years), soils could mitigate this effect. A soil scientist from RUDN University studied the mechanism of carbon retention in the soils of rice paddies that account for 40% of natural atmospheric carbon absorption in China. According to him, the ability of the soil to retain carbon depends, among other factors, on its structure and the presence of fertilizers.

"The soils of rice paddies play an important role in mitigating the consequences of global warming and contribute a lot to the retention of carbon. The most effective way to study the processes that lead to the accumulation of organic carbon in the soil is to measure the concentration of its isotopes. We used this method to find out how mineral and organic fertilizers affect carbon flows between fractions of different density in rice paddy soils," said Yakov Kuzyakov, the Head of the Center for Mathematical Modeling and Design of Sustainable Ecosystems at RUDN University.

The team studied three groups of soils with different types of fertilizers: azophoska, or nitrogen-phosphorus-potassium fertilizer, was added to the first group; the second one contained azophoska with straw, and the third--azophoska with organic supplements. The content of carbon in the soils and its movement between density fractions was determined based on the ratio of 13C and 12? isotopes. The second and the third group showed better carbon retention results: after fertilization, their carbon content grew by 69%, while the increase in the first group amounted to 30%.

The scientists also paid attention to the changes in soil structure under the influence of fertilizers and the effect of such changes on carbon retention. Fertilizers consolidate the structural elements of the soil, and the number of large soil particles (over 0.25 mm in diameter) grows. Soils of medium density showed the highest carbon retention efficiency after fertilization: the amount of accumulated carbon increased by 70% compared to unfertilized soils. Less dense soil fractions showed a 21-56% increase, and carbon retention in dust and clay grew by 24-49%.

"We confirmed that fertilizers support organic carbon retention in the soil. Knowing this, we could better understand the processes that lead to the accumulation of soil carbon in rice paddies. These agricultural ecosystems already play an important role in world food security and now can also help us combat climate change," addedYakov Kuzyakov.

Researchers at uOttawa have created a new method to measure the temporal evolution of electric fields with optical frequencies. The new approach, which works in ambient air, facilitates the direct measurement of the field waveform and could lead to breakthroughs in high-speed electronics.

To learn more, we talked to Aleksey Korobenko, a postdoctoral fellow in the Department of Physics at the University of Ottawa, and lead author of "Femtosecond streaking in ambient air", an article recently published in the journal Optica.

Please tell us about this research project.

"The aim of our project is to resolve the electric field oscillations in a light pulse. This allows one to control the motion of electrons in quantum systems on shortest time scales and may lead to important applications such as petahertz electronics -- that are a million times faster than typical modern processors.

Such a measurement was first achieved using a technique called attosecond streaking -- a generalization of the long-known conventional streak camera. When irradiated with a short electromagnetic pulse, the gas molecules give up their electrons that continue their motion, experiencing the pull from the field of a second, "streaking," pulse. Measuring the velocity that the electrons acquire due to this pull allows one to reconstruct the streaking pulse on attosecond time scales."

What did you discover?

"In our work we demonstrated that instead of measuring the velocities of individual electrons in low-density gas samples, which requires high vacuum conditions and/or a complicated setup, one can simply measure the current induced in air plasma under ambient conditions. We probe this current using a pair of metal electrodes. which facilitates a much simpler and faster measurement of a light wave oscillation."

Why is it important?

"We can access the time scales of the optical field oscillations in an inexpensive, fast and robust way. Owing to its simplicity, our method can become a useful tool for the ultrashort lasers research community, aiding the development of a next generation petahertz electronics."

How was this research conducted?

"The experiments were carried out using a unique, state-of-the-art, high-power laser generating ultrashort pulses from the visible to the infrared spectrum. Performing a measurement of these pulses under different experimental conditions, we benchmarked our method against the established measurement techniques."

Is there anything you'd like to add?

"Yes, this study is an international collaboration with researchers from the Ludwig-Maximilian University of Munich, the Max-Planck Institute for Quantum Optics in Germany and the Joint Attosecond Science Lab (NRC and uOttawa). Researchers of Canadian, Russian, German, American, Iranian, Chinese and French nationality participated in the project.

The research was conducted in the Joint Attosecond Science Laboratory, which is jointly operated by the University of Ottawa and the National Research Council."