Culture

Renewable technologies are a promising solution for addressing global energy needs in a sustainable way.

However, widespread adoption of renewable energy resources from solar, wind, biomass and more have lagged, in part because they are difficult to store and transport.

As the search for materials to efficiently address these storage and transport needs continues, University of Delaware researchers from the Catalysis Center for Energy Innovation (CCEI) report new techniques for characterizing complex materials with the potential to overcome these challenges.

The researchers recently reported their technique in Nature Communications.

Seeing the parts, as well as the whole

Currently technologies exist for characterizing highly ordered surfaces with specific repeating patterns, such as crystals. Describing surfaces with no repeating pattern is a harder problem.

UD doctoral candidate and 2019-2020 Blue Waters Graduate Fellow Josh Lansford and Dion Vlachos, who directs both CCEI and the Delaware Energy Institute and is the Allan and Myra Ferguson Professor of Chemical and Biomolecular Engineering, have developed a method to observe the local surface structure of atomic-scale particles in detail while simultaneously keeping the entire system in view.

The approach, which leverages machine learning, data science techniques and models grounded in physics, enables the researchers to visualize the actual three-dimensional structure of a material they are interested in up close, but also in context. This means they can study specific particles on the material's surface, but also watch how the particle's structure evolves -- over time -- in the presence of other molecules and under different conditions, such as temperature and pressure.

Put to use, the research team's technique will help engineers and scientists identify materials that can improve storage technologies, such as fuel cells and batteries, which power our lives. Such improvements are necessary to help these important technologies reach their full potential and become more widespread.

"In order to optimize electrochemical storage technologies, such as fuel cells and batteries, we must understand how they work and what they look like," said Lansford, the paper's lead author, who is advised at UD by Vlachos, the project's principal investigator.

"We need to understand the structure of the materials we are generating, in detail, so that we can recreate them efficiently at a large scale or modify them to alter their stability."

Computational modeling

Lansford concedes that it is too costly and time-consuming to model complex structures directly. Instead, they take data, generated from a single spot on the surface of a material, and scale it to be representative for a variety of catalysts on many surfaces of many different materials.

Imagine a cube made up of many atoms. The atoms located on the corners of the cube will have different properties than, say, the atoms located on one side of the cube. This is because on the corners, fewer atoms will be connected to each other and atoms may be spaced closer together. While on the side of the cube, more atoms will be connected even though they may be spaced farther apart from each other.

The same is true for catalyst materials. Even if we can't see them with the naked eye, the particles that make up a catalyst are adsorbed onto many different sites on the material -- and these sites have different edges, bumps and other variations that affect how materials located there will behave. Because of these differences, scientists can't just use a single number to try to quantify what's happening across a material's entire surface, so they have to estimate what these surfaces look like.

According to Lansford, this is where computational modeling can help.

The research team used experimental measurements of different wavelengths of infrared light and machine learning to predict and describe the chemical and physical properties of different surfaces of materials. The models were trained entirely on mathematically generated data, allowing them to visualize many different options under many different conditions.

They developed special open-source software to apply the technique on different metals, materials and adsorbates. The methodology is flexible enough to be used with other spectroscopic techniques beyond infrared light, so that other scientists and engineers can modify the software to advance their own work.

"This work introduces an entirely new way of thinking on how to bridge the gap between real-world materials and well-defined model systems, with contributions to surface science and machine learning that stand on their own," said Lansford.

One of the most commonly used diagnostic tools, particularly during this pandemic, is the reverse transcriptase polymerase chain reaction test (RT-PCR), which uses a person's respiratory sample to detect viral particles and determine if the person may have been exposed to a virus. Laboratory professionals across the U.S. and the globe have used RT-PCR to find out if a person has been infected with SARS-CoV-2, the virus that causes COVID-19. These tests have played a critical role in our nation's response to the pandemic. But, while they are important, researchers at Johns Hopkins have found that the chance of a false negative result -- when a virus is not detected in a person who actually is, or recently has been, infected -- is greater than 1 in 5 and, at times, far higher. The researchers caution that the predictive value of these tests may not always yield accurate results, and timing of the test seems to matter greatly in the accuracy.

In the report on the findings published May 13 in the journal Annals of Internal Medicine, the researchers found that the probability of a false negative result decreases from 100% on Day 1 of being infected to 67% on Day 4. The false negative rate decreased to 20% on Day 8 (three days after a person begins experiencing symptoms). They also found that on the day a person started experiencing actual symptoms of illness, the average false negative rate was 38%. In addition, the false negative rate began to increase again from 21% on Day 9 to 66% on Day 21.

The study, which analyzed seven previously published studies on RT-PCR performance, adds to evidence that caution should be used in the interpretation of negative test results, particularly for individuals likely to have been exposed or who have symptoms consistent with COVID-19.

More than 1.7 million Americans develop sepsis each year, and more than 270,000 die from it. The condition--which happens when the body has an extreme response to a bacterial or viral infection, causing a chain reaction that can lead to organ failure and death--has few strategies for treatment.

That's what Savas Tay found a few years ago, when his mother died from sepsis. "I learned that there is very little they can do to really monitor and diagnose these patients," said Tay, associate professor of molecular engineering at the Pritzker School of Molecular Engineering (PME) at the University of Chicago. "A good percentage of them will ultimately die, which is unacceptable, considering the high-quality facilities, physicians, and therapies we have available. I was kind of enraged with the situation."

So Tay set out to do something about it. Now, he and his collaborators have developed a new, extremely sensitive method that can quantify bacteria, an antibiotic resistant gene, and immune molecule levels within sepsis patients, far more rapidly than current protocols.

By deploying these tests at intervals, the researchers also found that it wasn't the absolute levels of these markers that mattered--it was the change in the levels. Using machine learning, they accurately predicted which patients with sepsis would recover quickly, recover later, or ultimately succumb to the condition. That information could ultimately help physicians diagnose and treat patients in a more personalized way.

"Our findings provide a new approach to the diagnosis of sepsis with the potential to identify the causal pathogen early," said Gokhan Mutlu, professor of medicine and chief of pulmonary and critical care medicine at UChicago and co-author of the research. "This will allow us to use the appropriate antibiotics earlier before the culture results are available and minimize the use of antibiotics that are needed to treat the infection. By combining the pathogen-related and host response data, we are able to predict outcomes in patients with sepsis."

The results were published May 25 in the journal Nature Communications.

Understanding how to treat sepsis

Because sepsis is often caused by microbial infections, the condition is usually initially treated with antibiotics. Treatment must happen quickly--any delay in the administration of correct antibiotics increases the chances of the patient dying. But doctors often aren't sure which bacteria is causing the infection, and growing cultures to pinpoint the bacteria can take days.

Even if doctors can treat the infection directly, the condition can cause the body's immune response to become exaggerated. By attacking the pathogens, the immune system can release too many immune system proteins called cytokines, which can ultimately overwhelm the body and kill the patient. Anti-inflammatory drugs can help treat this, but often physicians do not know when this "cytokine storm" is taking place until it's too late.

"The immune system has a gas and a brake," Tay said. "You need the gas to kill the pathogens, but you need the brake so you don't overshoot inflammation and harm the patient. In all of this, timing is critical. We wanted to know if we could monitor bacterial load and cytokines at the same time, and monitor their changes, to provide better guidance about who should get certain treatments."

Creating an extremely sensitive test

Tay, an expert in single-cell analysis and microfluidics, and his team developed a digital polymerase chain reaction (PCR) test that uses digital proximity litigation assays to quantify the levels of certain genes and proteins in the blood.

Specifically, the test uses a blood sample to test for gram-negative (GN) and gram-positive (GP) bacterial DNA, which is abundant in many septic patients. It also tests for levels of the IL-6 and TNF proteins, the cytokines that the immune system releases to attack pathogens. In addition, it tests for the blaTEM gene, which signifies antibiotic resistance.

The test is extremely sensitive--able to quantify very small changes in the concentrations of these molecules--and provides results within a few hours. Tay worked with pulmonologists at University of Chicago Medicine to try out the test on samples from septic patients.

The researchers took samples once a day for two days from 32 patients and tested their bacterial and protein levels. They found that the bacterial levels of the patients who lived decreased as time went on.

However, in almost every patient that died, IL-6 levels increased throughout their time at the hospital. Even patients who had low bacterial levels to begin with still died if their IL-6 levels increased, showing that the immune system potentially overshot and attacked their own body.

Though IL-6 has been considered a major biomarker in sepsis before, previous researchers did not realize that it was the change in the levels--not the levels themselves--that predicted this outcome.

In addition, the researchers found several patients with the gene that indicates antibiotic resistance, which would be helpful information for the physicians treating them.

"Sepsis manifests itself differently in each person, therefore having a test like this to shed light on that variation could one day be used by providers to identify which patients may respond better to certain treatments or interventions," said Krysta Wolfe, a pulmonologist and assistant professor of medicine at UChicago, and co-author of the research.

Using machine learning algorithms, the researchers could ultimately use these biomarkers to predict who would recover early, recover late, or die, with nearly 100% accuracy.

"All of the sudden we have this method that allows us to really understand how these patients are going to fare," Tay said. "If there are patients that are going to do badly, then you can start treating these patients in different ways, perhaps with drugs that will help block the immune system from overshooting."

Extending the test to other diseases

Right now, the test happens in a lab, but Tay and his group are developing a machine that can quickly test samples on site at ICUs. They are proceeding with a clinical trial and hope to extend the test to include more groups of bacteria beyond just the GN and GP levels, to help physicians better understand which antibiotics are needed in order to help reduce antibiotic resistance.

This test could also be extended to other infections where cytokines can overtake the body, including viral infections like COVID-19.

"A rapid test like this is needed in many situations and could really change the game for treatment of sepsis," Tay said. "This is a disease that can kill everybody, regardless of your situation."

May 26, 2020 - Early in the pandemic, American Indian Reservations have experienced a disproportionately high incidence of COVID-19 infections: four times higher than in the US population, reports a study in the July/August issue of the Journal of Public Health Management and Practice. The special issue of JPHMP focuses on COVID-19, with commentaries and scientific articles describing the pandemic in the United States and globally. The journal is published in the Lippincott portfolio by Wolters Kluwer.

Lack of indoor plumbing is a strong risk factor for COVID-19 in tribal communities, while the incidence appears lower in households that speak English only, according to the new research led by Desi Rodriguez-Lonebear, PhD, of UCLA. "These key findings have implications for communication, implementation, and success of recommendations such as hand washing and state/tribal stay-at-home orders in American Indian Reservation communities," the researchers write.

Insights on Factors Affecting COVID-19 Incidence on American Indian Reservations

Using publicly reported information on COVID-19 cases, along with reservation-level data from a previous national survey, Dr. Rodriguez-Lonebear and colleagues analyzed household and community characteristics associated with rates of COVID-19 in tribal communities. The study focused on 287 American Indian Reservations and tribal homelands (in Oklahoma) with an average population of about 12,500.

As of April 20, 2020, these communities had a total of 861 COVID-19 cases. About 60 percent of cases were in the Navajo Nation. At that time, the incidence of COVID-19 was more than four times higher for people living on a reservation, compared to the United States as a whole: 0.24 versus 0.057 cases per 1,000 people.

On analysis of household and community factors, the number of COVID-19 cases was substantially higher on American Indian Reservations where a higher percentage of homes lacked complete indoor plumbing. The researchers write, "While some reservation communities have elected not to pursue full plumbing facilities for historical, cultural and environmental reasons, there are certainly solutions, like providing potable water and hand sanitizer, that could improve critical sanitation needs."

The number of COVID-19 cases was lower on reservations with a high percentage of English-only households - highlighting the need for public health campaigns in Indigenous languages. "This is of particular concern given there are 150 different Indigenous languages spoken by more than 350,000 people in the US today," according to the authors.

Along with household plumbing and language, overcrowding has been identified as a potential infection risk factor. However, at least early in the pandemic, overcrowding - defined as more than one person per room - was not related to COVID-19 incidence on American Indian reservations.

Due to its timing, the study could not address how reservation-level conditions affect the risk of death from COVID-19. Any such analysis would have to consider the unique circumstances surrounding healthcare access and infrastructure in tribal communities. "With inadequate public health infrastructure, limited medical resources, and high rates of poverty, communities on Indian reservations are poorly equipped to manage a pandemic like COVID-19," Dr. Rodriguez-Lonebear and coauthors write.

The researchers outline the implications for policy and practice addressing the impact of COVID-19 on American Indian reservations - including the need for access to potable water and communication of critical health information in Indigenous languages. Dr. Rodriguez-Lonebear and colleagues conclude: "In the long-term, increase direct public health funding to tribes for infrastructure development and secure American Indian household access to environmental health infrastructure such as indoor plumbing, where desired."

CHAPEL HILL, NC - May 26, 2020 - How hepatitis A virus (HAV) manages to enter liver cells called hepatocytes and initiate infection had remained a mystery for fifty years until now. University of North Carolina School of Medicine researchers designed experiments using gene-editing tools to discover how molecules called gangliosides serve as de facto gatekeepers to allow the virus entry into liver cells.

The research, published in Nature Microbiology, has revealed gangliosides as a key player in HAV and has led to several other questions, such as how exactly viral RNA transitions between different compartments in human liver cells to replicate and cause disease.

"Discovering that gangliosides are essential receptors for HAV infection adds an interesting plot twist to the hepatitis A story," said senior author Stanley Lemon, MD, professor of medicine and microbiology at the UNC School of Medicine and member of the UNC Institute for Global Health and Infectious Diseases. "Gangliosides are structurally similar across mammalian species, unlike proteins, which helps explain cross-species transmission of ancient hepatoviruses. Understanding what helps a virus jump from one animal species to another is incredibly important, as evidenced so plainly by the current Covid-19 pandemic."

HAV was discovered nearly 50 years ago, and although there is a vaccine, there is no treatment. The virus still infects more than 1.4 million people globally each year, and in recent years has been causing increasing numbers of hepatitis cases in the United States, some fatal. Many people experience very mild or no symptoms, especially children. Patients with symptoms, which can last eight weeks and sometimes longer, often experience nausea, vomiting, diarrhea, jaundice, fever, and abdominal pain. After initial infection, 10 to 15 percent of infected individuals experience a recurrence of symptoms during the first six months. Acute liver failure is rare, but more common in elderly people.

HAV infects people through mechanisms similar to other viruses; it interacts with receptor molecules on the surface of human cells to gain entry. Knowing the receptor for a virus not only helps researchers understand how the virus enters cells, but also creates opportunities to design antivirals to block the interaction to prevent or treat disease.

Among the five known hepatitis viruses that cause acute or chronic liver disease in humans, receptors have been identified for hepatitis C virus and hepatitis B virus. For hepatitis A, the identity of the receptor remained elusive. The black sheep of the picornavirus family, it uniquely exists in two modes: as nonenveloped (naked) viruses (nHAV), comprised of a protein shell called a capsid surrounding an RNA genome; or as 'quasi-enveloped' viruses (eHAV), in which capsids containing the viral genome are cloaked inside host cell membranes.

Once inside the liver, eHAV is released from infected hepatocytes to circulate in the blood, whereas naked nHAV particles are shed in feces. Both virus types are infectious. Being cloaked with host-derived membranes gives eHAV an advantage in evading antibody responses, while the naked virion is extraordinarily stable and spreads readily in the environment. But how did each virus get into liver cells and the blood in the first place?

Years ago, the human protein TIM1 was reported to be a receptor for HAV. The gene that encodes this protein even bears the official name HAV cellular receptor 1 (HAVCR1). But recent studies in Lemon's laboratory showed that cells lacking TIM1 still allow HAV infection.

To find a more likely culprit for the receptor, Anshuman Das, PhD, a postdoc in the Lemon lab at the time of this research and now at Duke University., used CRISPR-Cas9 gene editing to knock out approximately 20,000 genes in cultured cells to find which human genes are essential for the virus to invade. They identified five particular genes, all of which were required by the virus. Turns out, these genes encode enzymes or transporters that make possible the synthesis of gangliosides. (Transporters are molecules that traffic chemicals across channels inside cells.)

Gangliosides are sugary fatty acid molecules. The enzyme ceramide glucosyltransferase creates gangliosides. And the gene UGCG encodes for that enzyme.

"UGCG was the lead culprit of the five genes that lit up our screen using CRISPR-Cas9," Lemon said.

The researchers then knocked out UGCG, which prevented HAV infection. They also treated liver-derived cells with a chemical inhibitor of ceramide glucosyltransferase to prevent both eHAV and nHAV infection.

The researchers then injected synthetic HAV RNA directly into cells to discover that the viral RNA replicated well, suggesting that gangliosides were required for entry of the virus into cells, but not needed for it to make copies of its genome, or new virus particles, once it gets into cells.

Subsequent experiments revealed that - in the absence of gangliosides - both naked and quasi-enveloped HAV particles do in fact get part way into the cell, but they end up getting stuck in a compartment called the lysosome. Viral replication does not occur. When the researchers added back gangliosides, the accumulated viruses used the gangliosides to exit the lysosome and continue their invasion of the cell, ending up releasing their genomes into the cell cytoplasm where the virus then began to replicate.

"This means gangliosides are essential for a late-step entry of HAV into cells," said Anshuman Das, PhD, a postdoc in the Lemon lab at the time of this research and now at Duke University. "They function as true receptors."

Although questions remain, the researchers say that understanding the role of gangliosides may open up new avenues for prevention and possibly even treatment of hepatitis A.

The COVID-19 pandemic has magnified the social, educational and health care disparities already plaguing the nearly 40 million Americans the U.S. Census Bureau estimates are living in poverty. Perhaps the hardest hit members of that population, say three pediatricians at Johns Hopkins Children's Center and Children's National Hospital, are children from low-income households who are experiencing major disruptions in already inconsistent routines and less-than-adequate resources critical to learning, nutrition and social development because of restrictions in place to curb the spread of the disease.

In a viewpoint article published in the May 13 issue of JAMA Pediatrics, the physicians provide examples of how efforts to keep COVID-19 in check have disproportionally impacted the nearly 1 in 5 U.S. children whose family incomes are below the poverty level.

"For example, many school districts are engaging in distance learning during the pandemic, but there is wide variability in the ability to access quality educational instruction, digital technology and internet service, especially by rural and urban students," says Megan Tschudy, M.D., M.P.H., assistant medical director at the Harriet Lane Clinic of Johns Hopkins Children's Center and assistant professor of pediatrics at the Johns Hopkins University School of Medicine. "In some urban areas, as many as one-third of students are not participating in online classes because of challenges accessing the internet."

The authors cite other difficulties that COVID-19 policies and regulations have placed on children from low-income households, including missing months of school by a student population commonly burdened by chronic absenteeism, the inability to get nutritious meals previously provided before and during school hours, and removal of key resources available at schools such as "consistent and caring adults who can help build resiliency and offer holistic support."

To counter the increased disparities brought about by the pandemic and help prevent children from low-income households "experiencing consequences for a lifetime," the authors recommend that future COVID-19 legislation target child health and well-being. They say that this effort should include expanding services and increasing funding for health and nutrition assistance programs, improving child tax credits, and expanding access to high-speed internet and versatile electronic devices so that all children can participate in distance learning.

Beneficial strains of bacteria residing in our guts, genital tracts, and skin have been shown to play a role in human health, and now, researchers publishing May 26 in the journal Cell Reports suggest that some of these "good" bacteria also have a niche in our noses. They found that people with chronic nasal and sinus inflammation had fewer lactobacilli in their upper respiratory tract than healthy controls and were able to identify a specific strain of the bacteria that has evolved to better survive the oxygen-rich environment of the nose. As a part of their study, the researchers developed a proof-of-concept nasal spray that could deliver lactobacilli to the nose, where the bacteria were able to colonize the upper respiratory tract of healthy volunteers.

Senior author Sarah Lebeer of the University of Antwerp became interested in the microbiota of the nose when her mother underwent a surgery for lifelong problems with headaches and chronic rhinosinusitis. "My mother had tried many different treatments, but none worked. I was thinking it's a pity that I could not advise her some good bacteria or probiotics for the nose," recalled Lebeer, who was previously studying gut and vaginal probiotics. "No one had ever really studied it."

To see whether the bacteria we associate with gut health also play a role in the health of the upper respiratory tract, Lebeer and her Procure team (http://www.procureproject.be/) compared nose bacteria between 100 healthy individuals and 225 chronic rhinosinusitis patients. They looked at the prevalence of 30 different families of bacteria in the upper respiratory tract of their participants and found that the healthy people had a greater abundance of lactobacilli than the patients--up to 10 times more in some parts of the nose. Lactobacilli are well-known beneficial, rod-shaped bacteria that have pathogen-inhibiting properties because they produce lactic acid through sugar fermentation, but these bacteria had never been studied in detail in the nose.

The researchers took a closer look and discovered a specific strain of the Lacticaseibacillus that not only showed some anti-inflammatory and antimicrobial effects against pathogens but also unique features that enables the strain to better adapt to the environment of the nose. Although most lactobacilli prefer to grow in the absence of oxygen, the identified strain showed unique genes making it able to cope with the higher oxidative stress levels in the nose. Moreover, the researchers observed the bacteria covered with flexible, hair-like tubes called fimbriae, which allow them to adhere to the surface cells in the nose, indicating an interaction between the bacteria and host.

The researchers then sought to verify their findings in vivo. However, "one limitation is that there are actually no real good animal models or mechanistic models to study the interaction of nose bacteria and human host," says Lebeer. "The microbiome of the nose of mice compared with humans, it's certainly different. Also, mice are nose breathers and they don't get chronic rhinosinusitis; they have fewer allergies and inflammations."

But the results from the lab, and the long history of safe use of lactobacilli, allowed the researchers to study the bacteria in humans instead of animal models. The team created a kind of "probiotic nasal spray" with a selected lactobacillus strain in a special formulation for 20 healthy volunteers. Introducing bacteria to the nose can be challenging, because it's so good at filtering out foreign substances; any substance introduced to the nose usually disappears within 15 minutes. However, after two weeks of administering the spray twice daily, the bacteria stayed in the nose longer than 15 minutes--they colonized the nose for up to two weeks without adverse effects. The study of the spray was not set up to look at beneficial effects, although anecdotally some participants mentioned having fewer nasal problems and said they could breathe better.

The next step for the researchers is to understand whether the fimbriae and the ability to endure oxidative stress are key to beneficial anti-inflammatory properties of the strain, as well as to identify which antimicrobial molecules the strain produces in addition to lactic acid. Ultimately, the team's goal is to develop therapeutics based on nasal probiotics to improve the symptoms of sinusitis patients.

"Sinusitis patients don't have a lot of treatment options," says Lebeer, and with the treatments that are available, problems such as antibiotic resistance and side effects often arise. "We think that certain patients would benefit from remodeling their microbiome and introducing beneficial bacteria in their nose to reduce certain symptoms. But we still have a long way to go with clinical and further mechanistic studies."

What The Study Did: The fit and filtration efficiency of disposable N95 masks after sterilization by cobalt-60 gamma irradiation are examined in this quality improvement study.

Authors: Avilash Cramer, M.S., of the Harvard-MIT Division of Health Sciences and Technology in Charlestown, Massachusetts, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.9961)

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

Bottom Line: The U.S. Preventive Services Task Force (USPSTF) has concluded that current evidence is insufficient to make a recommendation regarding primary care-based behavioral counseling interventions to prevent illicit drug use (including nonmedical use of prescription drugs) in children, adolescents and young adults. The USPSTF routinely makes recommendations about the effectiveness of preventive care services and this recommendation is consistent with its 2014 statement, although it now includes young adults ages 18-25. Illicit drug use, defined as the use of substances (not including alcohol or tobacco products) that are illegally obtained or involve nonmedical use of prescription medications, contributes to the leading causes of death among young people ages 10-24.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jama.2020.6774)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Note: More information about the U.S. Preventive Services Task Force, its process, and its recommendations can be found on the newsroom page of its website.

What The Study Did: This randomized clinical trial evaluated the effect of a workplace wellness program that included health screenings, wellness activities and financial incentives on employee health, health beliefs and medical use after 12 and 24 months among 4,800 employees at a large U.S. university.

Authors: David Molitor, Ph.D., of the University of Illinois at Urbana-Champaign, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2020.1321)

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

The UK has the highest level of obesity in Europe, in fact it's estimated half the population could be obese by 2050. Obesity is a significant risk factor for increased morbidity and mortality

Fasting, has been a trend in recent years to maintain a healthy weight, the body responds to fasting using autophagy, a cellular self-recycling process

The proteins required for autophagy to work during fasting have been identified by researchers from the School of Life Sciences at the University of Warwick

Understanding how the proteins work means researchers can activate autophagic pathways to help people maintain a normal body weight

As modern life-styles and high calorie diets drive the UK's obesity levels up, researchers from the University of Warwick have found how cells respond to fasting and activate the process called autophagy, which means a healthier lifestyle can be promoted to help people maintain a healthy body weight.

The UK has the highest level of obesity in Western Europe, with its levels having more than trebled in the last 30 years, it is estimated that more than half of the population could be obese by 2050 in UK. Obesity is a significant risk factor for increased morbidity and mortality. The cause of the rapid rise in obesity has been blamed on modern lifestyles, including high-calorie diet.

Intermittent fasting, alternate-day fasting, and other forms of periodic caloric restriction are beneficial to maintain a healthy body weight and have gained popularity during the last few years. To respond to fasting, cells use autophagy, a cellular self-recycling process.

A team of researchers led by Professor Ioannis Nezis from the School of Life Sciences, University of Warwick, discovered how cells activate autophagy genes during fasting. In the paper titled 'Regulation of expression of autophagy genes by Atg8a-interacting partners Sequoia, YL-1 and Sir2 in Drosophila', published in the journal Cell Reports on the 26th May, Dr Anne-Claire Jacomin, Dr Stavroula Petridi, PhD student Marisa Di Monaco and Professor Ioannis Nezis have discovered proteins which are required for the transcription of autophagy genes.

The proteins are called Sequoia, YL-1 and Sir2, these proteins interact with the cytoplasmic autophagy-related protein Atg8a. These interactions recruit Atg8a in the nucleus to control the transcription of autophagy genes. This is the first study that uncovers a nuclear role of the cytoplasmic protein Atg8a.

Lead author of the research Professor Ioannis Nezis, from the School of Life Sciences at the University of Warwick, comments:

"Understanding the molecular mechanisms of activation of autophagy genes during fasting will help us to use interventions to activate the autophagic pathways to maintain a normal body weight and promote healthy well-being."

WASHINGTON, May 26, 2020 -- Affecting up to 4% of patients older than 65 years, atrial fibrillation ranks among the most common heart conditions. Described by health professionals as an "irregularly irregular" heart rhythm, episodes of atrial fibrillation continue to prove difficult to predict.

An international team of researchers, led by Boon Leong Lan, at Monash University Malaysia, has proposed a way to define cardiac state and has studied the dynamics of the state before the cardiac rhythm changes from normal sinus to AF rhythm and vice versa. The work, appearing in Chaos, by AIP Publishing, and based on critical transition theory, looks to provide an early warning for those with paroxysmal atrial fibrillation with potential implications for future wearable devices.

The paper points a path forward for better screening for paroxysmal atrial fibrillation and may lead to more successful interventions when an atrial fibrillation episode has started.

"The flickering of the cardiac state could provide an early warning for the onset of paroxysmal atrial fibrillation for patients who are wearing a device that can measure the heartbeats accurately to monitor their cardiac state," said Lan. "This early warning would be useful if there is a medicine that the patient could take to prevent the onset."

It is not obvious how the cardiac state should be defined using just the electrocardiogram time series data. Lan said that their definition of the cardiac state, which is based on the changes between successive beat-to-beat intervals, was inspired by his previous work. He and his collaborator previously discovered that the distribution of the beat-interval changes can discriminate subjects with sustained atrial fibrillation from healthy ones very well.

Their new approach shows the cardiac state flickers back and forth between near normal and near atrial fibrillation states, resulting in a bimodal distribution of states before atrial fibrillation starts or terminates.

Others have proposed that dynamical transitions in a host of different realms from climate to stock markets to medicine are preceded by critical slowing down as the tipping point is reached. In critical slowing down, the rate of recovery from even a small perturbation approaches zero.

Lan and colleagues found that critical slowing down did not precede the onset of atrial fibrillation.

Lan is optimistic their method of defining the state of a complex system can be adapted to study critical transition in other chronic episodic diseases, such as epileptic seizure, asthma and ulcers, and other complex systems like an electrical power system or climate system.

He and his group are currently studying the changes in the brain state before epileptic seizures using their approach.

Early Muslim communities in Africa ate a cosmopolitan diet as the region became a trading centre for luxury goods, the discovery of thousands of ancient animal bones has shown.

Halal butchery practices became common when Islam spread through Ethiopia as vibrant communities developed because of the import and export of products around the Red Sea, and to Egypt, India, and the Arabian Peninsula, archaeologists have found.

New excavations at three sites in the east of the country completed by the University of Exeter and the Ethiopian Authority for Research and Conservation of Cultural Heritage have uncovered around 50,000 animal bones dating from the eighth/ninth centuries onwards, and showing people living there at this early time ate a Muslim diet 400 years before major Mosques or burial sites were built in the 12th century.

The team, led by Professor Timothy Insoll, and involving archaeozoologist Jane Gaastra from the University of Exeter's Institute of Arabic and Islamic Studies, found the first evidence in Africa for ancient halal butchery during the excavations, at Harlaa, Harar, and Ganda Harla.

Previous excavations led by Professor Insoll have revealed the Mosques and burial sites, as well as the remains of luxury materials such as ceramics from China and Egypt, marine shell from the Red Sea and beads from India.

Harlaa was established in the 6th and 7th centuries before Islam arrived in Ethiopia. It was abandoned in the 15th century when Harlaa and Ganda Harlaa were established, possibly because of plague or environmental change, and with the increasing spread of Islam better places to farm could be lived in.

During the period from which the animal bones date people may have been using smaller Mosques not yet discovered by archaeologists, and built larger buildings for worship as Muslim communities grew.

Professor Insoll said: "We didn't expect to find bones of this quality and quantity. They are so well preserved that we can clearly see both cuts and evidence of wear. We've also found bones in both residential areas and places of work.

"This is significant new information about people's religious identity at the time. It shows in the early days of Islam in the region people were just starting to adopt religious practices, so were sometimes pragmatic and didn't follow all of them."

Analysis of wear on the bones show cattle were used for ploughing and turning grinding stones, and other species such as camels, horses, and donkeys, may have been used as pack animals to carry trade goods and other commodities. Analysis of the age data of cattle bones at Harlaa indicated 80 to 90 per cent of animals survived beyond 3 years of age, showing they were kept for milk or for work rather than bred to eat.

Archaeologists found the remains of pigs in Harlaa and Ganda Harlaa, which could have been domesticated or wild, unexpected in an Islamic area, as pigs are haram, ot forbidden in Islamic halal diet. This suggests the region was cosmopolitan, with visitors and residents from different areas and with different religions. Another explanation could be that early Muslims in the area ate pork during this period for practical reasons. No pig remains were found at Harar, which was a city of Muslim scholarship and pilgrimage. Similar halal butchery techniques were used in all three sites, showing the influence of Muslim traders who arrived in the area and the spread of Islam to first Harlaa, and then Harar and Ganda Harla.

People also ate and hunted warthog, bushpig, aardvark, porcupine, hare, gennet, mongoose and leopard.

At Harlaa researchers also found evidence of marine fish imported from the Red Sea some 120 kilometres away. These had all been processed prior to being sent to Harlaa, either in dried or salted form to preserve them. This was indicated by the complete absence of fish heads showing these had been removed, probably at the Red Sea coast. No local freshwater fish species were found suggesting the people eating the fish were used to a sophisticated diet.

Similar animal body portions were found at each site, indicating wealth or status may not have been a factor in access to meat.

The study, published in the Journal of African Archaeology, indicates that the discarded remains of meals eaten many hundreds of years ago can provide very important information on diet, but also religious conversion, trade, and the use of animals for transport and work purposes in Islamic societies in Africa which have been largely neglected by archaeologists.

This release has been removed by request of the submitting institution. Please contact Valérie Geneux for more information: valerie.geneux@epfl.ch

Smart devices that measure electrical signals from your skin have the potential to tell you about your stress levels, help your sports performances and allow you to track your emotions.

An international team of researchers from Sweden and the UK have developed an innovative way of interpreting biological signals produced by the conductance of our skin. Using data obtained using a Philips wrist-worn wearable sensor device that also include an accelerometer to measure movement, the researchers’ system displays information in the form of colourful spiral graphics in real time on a smart phone, as well as a recording of data, for the wearer to interpret and reflect on.

Skin conductance is a measure of how much someone sweats, indicating their emotional reactions as well as physical reactions and is the basis for technologies such as lie detectors.

The prototype visualisation system called ‘Affective Health’, was developed by experts in Human-Computer Interaction looking into how new and emerging computer technologies, such as those using data extracted from sensors on the skin, can be used to design engaging visualisations on smart phones.

Dr Pedro Sanches, senior researcher at KTH - Royal Institute of Technology Stockholm, and lead researcher on the study said:

“Our bodies produce a wide range of signals that can be measured. Many useful devices that measure these signals, which we call biodata, have proliferated over the years – such as heart-rate monitors for sports. However, there are other areas of biodata that are yet to be fully developed – such as skin conductance or perspiration levels. Making sense of these kinds of biodata is not easy. People are unfamiliar with this kind of information and it is not clear how people would want to use it, or interact with devices that present this biodata.”

A study group of 23 people were given the Affective Health prototype to use for a month. Importantly, the researchers deliberately did not tell the participants what the devices were useful for. Instead, they gave guidelines that Affective Health could collect information relating to both physical and emotional reactions, how increased sweating increased the conductivity, and how this was represented by different colours. Participants were left to decide the best ways of using the technology.

The researchers found that this open design stage of the study, without providing pre-specified uses, led to some participants using the system as a tool to measure, and help manage, their stress levels.

While others, including elite athletes, used the device to get information on their training and recovery regimes.

Other uses included logging information on their lives, and tracking emotions. But interestingly, few would use the technology for more than one purpose.

Prof Kristina Höök, of Royal Institute of Technology in Sweden said:

“We were surprised at how much the wearers’ initial categorisation of the system coloured how they used it. If they looked upon it as a sports tool, they did not even ’see’ the data that spoke of stress or emotional reactions. If they looked upon it as an emotion measuring tool, they did not see the data that spoke of social processes or exertion due to sports activities.

“It was also interesting to see how some would avoid engaging with data that spoke against their ideas of their personality traits. One person looked upon himself as a calm person, but in the data, there were plenty of peaks. He just could not reconcile those with his impression of himself.”

Although the open design phase helped reveal several different practices Affective Health prototypes could be used for, the prototype lacked some of the functions needed to make it a good tool for a specific role – such as a sports training system, or as a stress management tool.

The researchers found the need for a second, more tailored, step in the design process to make devices specific to particular roles.

The research is part of the AffecTech: Personal Technologies for Affective Health, Innovative Training Network, which is funded through the European Union’s Horizon2020 programme and led by Professor Corina Sas of Lancaster University’s School of Computing and Communications.

Professor Sas, said: “The study revealed insights for designers of emerging wearable technologies, and in particular of biodata-based wearable devices. Design is crucially important to help users understand their bodily responses.

“Our results suggest the value of a two-step approach for designing new technologies that present bio-data that are unfamiliar to users. A deliberately open initial design stage allows users to develop their own ideas of how these kinds of products could be used. This is followed by a second step that tailors the functions of the device for specific activities, such as wellbeing, health or productivity.”