Culture

Scientists at the University of Waterloo have developed a new tool to protect women from HIV infection.

The tool, a vaginal implant, decreases the number of cells that the HIV virus can target in a woman's genital tract. Unlike conventional methods of HIV prevention, such as condoms or anti-HIV drugs, the implant takes advantage of some people's natural immunity to the virus.

HIV infects the body by corrupting T cells that are mobilized by the immune system when the virus enters a person's body. When the T cells stay resting and do not attempt to fight the virus they are not infected and the HIV virus is not transmitted between people. When the T cells stay resting, it's referred to as being immune quiescent.

"We know that some drugs taken orally never make it to the vaginal tract, so this implant could provide a more reliable way to encourage T cells not to respond to infection and therefore more reliably and cheaply prevent transmission," said Emmanuel Ho, a professor in the School of Pharmacy at Waterloo. "What we don't know yet is if this can be a stand-alone option for preventing HIV transmission or if it might be best used in conjunction with other prevention strategies. We aim to answer these questions with future research."

Ho's implant was inspired by previous research involving sex workers in Kenya. In Kenya, Ho and research partner Keith Fowke of the University of Manitoba, observed that many of these women who had sex with HIV positive clients but did not contract the virus. They later found the women possessed T cells that were naturally immune quiescent.

"Observing this, we asked ourselves if it was possible to pharmacologically induce immune quiescence with medication that was better assured of reaching the point of infection," said Ho. "By delivering the medication exactly where it's needed, we hoped to increase the chances of inducing immune quiescence."

The implant is composed of a hollow tube and two pliable arms to hold it in place. It contains hydroxychloroquine (HCQ) which is disseminated slowly through the porous material of the tube and absorbed by the walls of the vaginal tract.

The implants were tested in an animal model and the team observed a significant reduction in T cell activation, meaning that the vaginal tract was demonstrating an immune quiescent state.

The article recently appeared in the Journal of Controlled Release.

DARIEN, IL - April 16, 2018 - A position statement from the American Academy of Sleep Medicine (AASM) concludes that fatigue and sleepiness are inherent safety risks in the ridesharing industry.

Both sleep deprivation and circadian influences leave ridesharing drivers at risk for drowsy driving. The typical schedule for workers in the ridesharing industry may lead to driving after extended periods of wakefulness or during nights. These drivers also are often independent contractors who are not screened for medical problems that can reduce alertness, such as obstructive sleep apnea.

"We are dealing with a public safety issue, where low fares and salary incentives compel drivers to continue driving past their safety limits. They may be unaware of the huge risks they are taking or have the false belief that sleep is overrated. Their customers, meanwhile, usually aren't asking themselves, 'How alert is my driver right now?' They aren't even thinking about drowsy driving. This is a formula for disaster," said senior author Dr. Indira Gurubhagavatula, an associate professor of medicine in the Perelman School of Medicine at the University of Pennsylvania in Philadelphia. "We need to raise awareness and gather information. Without accurate estimates of how common this is, or regulation, it's the wild west of transportation out there."

The position statement is published in the April 15 issue of the Journal of Clinical Sleep Medicine.

The AAA Foundation for Traffic Safety estimates that an average of 328,000 annual crashes in the U.S. involve a drowsy driver, including 109,000 that result in injuries and 6,400 that involve a fatality. The National Transportation Safety Board also included "reduce fatigue-related accidents" on its 2017-2018 Most Wanted List of the 10 most critical changes needed to reduce transportation accidents and save lives.

In February, ridesharing company Uber announced that it is requiring drivers to go offline for six straight hours after a total of 12 hours of driving time. Similarly, Lyft requires its drivers to take a six-hour break for every 14 hours of driving. However, the AASM considers these limits to be insufficient since many ridesharing drivers work multiple jobs or drive for more than one ridesharing company, and they often drive late at night and early in the morning when sleepiness may peak.

"The American Academy of Sleep Medicine calls on ridesharing companies, government officials, medical professionals, and law enforcement officers to work together to address fatigue and sleepiness in the ridesharing industry," said AASM President Dr. Ilene Rosen. "A collaborative effort is necessary to reduce this public safety risk."

Visit the Awake at the Wheel campaign page for tips from the National Healthy Sleep Awareness Project to help you recognize the warning signs of drowsy driving.

DARIEN, IL - April 16, 2018 - Medical cannabis and synthetic marijuana extracts should not be used for the treatment of obstructive sleep apnea, according to a position statement from the American Academy of Sleep Medicine (AASM).

In November 2017 the Minnesota Department of Health announced the decision to add obstructive sleep apnea as a new qualifying condition for the state's medical cannabis program. However, the AASM has concluded that sleep apnea should be excluded from the list of chronic medical conditions for state medical cannabis programs due to unreliable delivery methods and insufficient evidence of treatment effectiveness, tolerability and safety.

"Until we have further evidence on the efficacy of medical cannabis for the treatment of sleep apnea, and until its safety profile is established, patients should discuss proven treatment options with a licensed medical provider at an accredited sleep facility," said lead author Dr. Kannan Ramar, professor of medicine in the division of pulmonary and critical care medicine at Mayo Clinic in Rochester, Minnesota.

The position statement is published in the April 15 issue of the Journal of Clinical Sleep Medicine.

Nearly 30 million adults in the U.S. have obstructive sleep apnea, a chronic disease that involves the repeated collapse of the upper airway during sleep. Common warning signs include snoring and excessive daytime sleepiness. After early animal studies demonstrated that the synthetic cannabis extract dronabinol improved respiratory stability, recent studies in humans have explored the potential use of dronabinol as an alternative treatment for sleep apnea.

However, dronabinol has not been approved by the U.S. Food and Drug Administration for the treatment of sleep apnea, and its long-term tolerability and safety are still unknown. Furthermore, there have been no studies of the safety and efficacy of other delivery methods such as vaping or liquid formulation. Treatment with the use of medical cannabis also has shown adverse effects such as daytime sleepiness, which may lead to unintended consequences such as motor vehicle accidents.

"Until there is sufficient scientific evidence of safety and efficacy, neither marijuana nor synthetic medical cannabis should be used for the treatment of sleep apnea," said AASM President Dr. Ilene Rosen. "Effective and safe treatments for sleep apnea are available from licensed medical providers at accredited sleep facilities."

There are more than 2,500 AASM-accredited sleep facilities across the U.S. Treatment options for sleep apnea include CPAP therapy, which uses mild levels of air pressure, provided through a mask, to keep the throat open while you sleep.

New research published in The Journal of Physiology has indicated why people with paralysis of their limbs and torso are more likely to suffer from sleep apnoea. This knowledge could be used to develop much-need targeted therapies.

Obstructive sleep apnoea (OSA) is a sleep disorder in which the upper airway (ranging from the back of the nose to the to the throat area) narrows and closes repetitively during sleep. This can result in major sleep disruption and serious health consequences, including increased risk of high blood pressure and diabetes. In people with tetraplegia, which is paralysis caused by illness or injury that results in the partial or total loss of use of all four limbs and torso, the rate of OSA is over 70%. Currently, the reasons for this particularly high rate are unknown. The development of new therapies could potentially have a large positive impact on health and quality of life.

This new research sought to understand the way throat muscles react in those with tetraplegia and sleep apnoea. This will help discern why obstructive sleep apnoea is so prevalent in individuals with tetraplegia. Volunteers with OSA (with and without tetraplegia) were studied in sleep physiology laboratories in Sydney (NeuRA) and Melbourne (IBAS). Brief pulses of suction were delivered to participants via a breathing mask to simulate the airway narrowing characteristic of OSA, with electrodes inserted into the largest muscle surrounding the upper airway, genioglossus, enabling the measurement of key reflex responses.

It was expected that the reflexes would be similar for all those with OSA, whether they were tetraplegic or not, as it was believed that they only involved processes above the injury site. However, this study showed that in several cases of individuals with tetraplegia and sleep apnoea, key protective throat reflexes were absent, or indeed led to the switching off (instead of activation) of the genioglossus muscle. These findings help to explain why OSA is so common in those with tetraplegia and sleep apnoea.

Due to the fact that this research was conducted in wakefulness and not sleep, the researchers cannot be certain that their findings translate to sleep. Regardless, their observations provide valuable insight into upper airway reflex responses, and pave the way for future physiological sleep reflex studies looking to develop effective and tolerable targeted therapies for those with tetraplegia and sleep apnoea.

Laura Gainche, one of the research investigators, commended the resilience, optimism, tolerance and willingness of all the research's volunteers, characterised especially by their first participant, JV, who sustained his spinal injury aged 16:

"We were worried that nobody would take part in our long, tedious protocol. However, he just brushed it off like it was nothing: "a 2mm wide catheter in the nose? What a joke compared to the feeding tubes I had before"!

"The experimental day was intense to say the least; six people wheeled his bed up a steep slope to a test room about 100m away from the main hospital. Somehow we made it through the lengthy protocol together, and it was mostly thanks to him, our first rockstar patient! These participants gave us confidence that this project was feasible, and in the future the data produced will hopefully make their lives a tiny bit easier".

14 April 2018, Paris, France: A single treatment using an optimized, targeted form of faecal microbiota transplantation (FMT) produces sustained clinical and cognitive improvements, according to the results of a long-term follow-up of patients with liver cirrhosis and hepatic encephalopathy (HE) who had participated in a short-term study. The original, randomized, open label study, which enrolled 20 outpatient men with cirrhosis and recurrent HE receiving standard-of-care (SOC) treatment, had previously reported that a single FMT enema after antibiotic pretreatment improved cognitive function at Day 20 and reduced HE episodes and hospitalizations over the following 5 months compared with SOC.1 The long-term outcomes of this study, which were presented today at The International Liver Congress™ 2018 in Paris, France, demonstrated sustained and statistically significant reductions in the number of HE episodes and hospitalizations as well as improvements in cognitive function over 1 year in the men who received FMT compared with the control group.

Liver cirrhosis is a leading cause of morbidity and mortality, with complications such as HE resulting in recurrent emergency hospitalizations, irreversible brain injury, and a poor prognosis.2-5 There is some evidence that HE patients have a reduced relative abundance of certain beneficial gut microbiota (e.g. Lachnospiraceae and Ruminococcaceae) and an enrichment of potentially pathogenic Enterobacteriaceae ¬- a microbial profile that has been linked to cognitive impairment and systemic inflammation in cirrhotic patients with HE.1 Faecal microbiota transplants have been used successfully to correct dysbiotic conditions such as recurrent Clostridium difficile and ulcerative colitis,6-8 and a preliminary report suggested that FMT may be promising in the management of HE.9

'In conducting the original study, we primarily wanted to evaluate whether FMT was safe in patients with recurrent HE compared with SOC alone', explained Dr Jasmohan Bajaj from Virginia Commonwealth University and McGuire VA Medical Center in Richmond, USA, and lead author of the study. 'We identified a single stool donor from a universal donor bank who had the highest relative abundance of Lachnospiraceae and Ruminococcaceae, and FMT enemas were prepared using a single stool specimen provided by this donor'.

The long-term analysis of this study followed all participants from the original 5-month study1 who were still alive and without liver transplant for an additional 6 months, assessing both cognitive and clinical outcomes. At 1 year after randomization, one participant in the FMT arm and three in the SOC arm had died or undergone liver transplant. Amongst the remaining participants, a median of 1.5 (IQR 0.75-2.75) HE episodes and 3.0 (IQR 0.75-5.75) hospitalizations were reported during the subsequent 6 months of the study in the SOC arm compared with 0 (range 0-1.0) and 0 (range 0-1.5) in the FMT arm (p'Although this was a small randomized trial, we believe it confirms that FMT from a rationally selected donor was safe and associated with substantial long-term improvements in both clinical and cognitive outcomes in patients with cirrhosis and recurrent HE', said Dr Bajaj. 'These findings now need to be confirmed in a larger patient population'.

'Hepatic encephalopathy is a debilitating condition and a major burden to patients and caregivers, and new therapies are urgently needed', said Prof. Annalisa Berzigotti from the University of Bern, Switzerland, and EASL Governing Board Member. 'This study provides an important piece of evidence. The encouraging long-term results of FMT in HE strongly support the need for a larger, multicentre study of this intervention'.

The hippocampus is an area of the brain commonly linked with memory and dementia.

But new U of T Scarborough research finds that it may also yield important clues about a range of mental health illnesses including addiction, anxiety and depression.

The research, authored by a team of neuroscientists, found that a specific part of the hippocampus could play an important role in emotional regulation, a finding that calls into question our understanding of how exactly this part of the brain works.

"What this shows is that we may need to rethink how the hippocampus processes information," says Rutsuko Ito, an associate professor in the Department of Psychology.

The hippocampus is a seahorse-shaped structure located deep inside the brain. As part of the limbic system, it plays an important role in memory processing and spatial cognition, including how mammals learn to understand and navigate their environment.

Researchers have long looked at the hippocampus for its role in memory and dementia, especially in relation to Alzheimer's disease. In Alzheimer's patients for instance, this region is one of the first areas of the brain to suffer damage.

But there's been a few studies that suggest the anterior hippocampus, a sub-region located at the front, could play a role in emotional regulation, including anxiety.

For this study, Ito and her team looked at the ventral hippocampus in rats, a sub-region that correlates to the anterior hippocampus in humans. They wanted to see what role two further subareas of the ventral hippocampus -- called the CA1 and CA3 -- play in terms of approach-avoidance conflict processing.

Approach-avoidance conflict is a model used in psychology to test how animals deal with regulating fear and anxiety. It basically offers a situation that involves a decision about whether to pursue or avoid something that could have both positive and negative aspects to it.

"One good example is imagine going to a restaurant you love, but the moment you walk in you see someone you can't stand - do you go in, or avoid going in?" says Associate Professor Andy Lee, who collaborated on the research.

What they found is that after temporarily inactivating the CA1, it increased avoidance of the conflict. Meanwhile, inactivating the CA3 increased approach behaviour to the conflict.

Ito says this finding is important because the conventional thinking is that these areas, along with another part called the dentate gyrus, form a circuit through which information flow occurs in one direction. Information processed by the dentate gyrus gets passed along to the CA3, and then on to CA1. In other words, the CA1 and CA3 should carry out the same function because they're both part of the same information processing circuit.

"But that's not the case, the CA1 and CA3 in the ventral hippocampus seem to do very opposite things in relation to conflict processing," says Ito.

"It's this strange bi-directional or oppositional effect, and that goes against traditional thinking of how information processing takes place in this part of the brain," she says.

Because of its possible role in basic motivational behaviour, it may also offer important insights into a range of mental health illnesses. Addiction, for example, could be linked to deficits of approach motivation. Anxiety and depression on the other hand could be linked to avoidance behaviours, all of which could manifest itself in this part of the brain.

The research, which was published in the journal Current Biology, received funding from the Natural Sciences and Engineering Research Council of Canada, and the Canada Institutes for Health Research.

Ito says the next step is to explore which connections to the CA1, CA3, or other parts of the brain could be responsible for this effect.

Meanwhile, Lee is investigating the role sub-regions of the hippocampus play in conflict processing in humans.

"Some patients have lesions to certain areas of this part of the brain, so hopefully we can assess them to see what particular aspects of approach avoidance behaviour may or may not be impacted," he adds.

Losing just one night of sleep led to an immediate increase in beta-amyloid, a protein in the brain associated with Alzheimer's disease, according to a small, new study by researchers at the National Institutes of Health. In Alzheimer's disease, beta-amyloid proteins clump together to form amyloid plaques, a hallmark of the disease.

While acute sleep deprivation is known to elevate brain beta-amyloid levels in mice, less is known about the impact of sleep deprivation on beta-amyloid accumulation in the human brain. The study is among the first to demonstrate that sleep may play an important role in human beta-amyloid clearance.

"This research provides new insight about the potentially harmful effects of a lack of sleep on the brain and has implications for better characterizing the pathology of Alzheimer's disease," said George F. Koob, Ph.D., director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, which funded the study.

Beta-amyloid is a metabolic waste product present in the fluid between brain cells. In Alzheimer's disease, beta-amyloid clumps together to form amyloid plaques, negatively impacting communication between neurons.

Led by Drs. Ehsan Shokri-Kojori and Nora D. Volkow of the NIAAA Laboratory of Neuroimaging, the study is now online in the Proceedings of the National Academy of Sciences. Dr. Volkow is also the director of the National Institute on Drug Abuse at NIH.

To understand the possible link between beta-amyloid accumulation and sleep, the researchers used positron emission tomography (PET) to scan the brains of 20 healthy subjects, ranging in age from 22 to 72, after a night of rested sleep and after sleep deprivation (being awake for about 31 hours). They found beta-amyloid increases of about 5 percent after losing a night of sleep in brain regions including the thalamus and hippocampus, regions especially vulnerable to damage in the early stages of Alzheimer's disease.

In Alzheimer's disease, beta-amyloid is estimated to increase about 43 percent in affected individuals relative to healthy older adults. It is unknown whether the increase in beta-amyloid in the study participants would subside after a night of rest.

The researchers also found that study participants with larger increases in beta-amyloid reported worse mood after sleep deprivation.

"Even though our sample was small, this study demonstrated the negative effect of sleep deprivation on beta-amyloid burden in the human brain. Future studies are needed to assess the generalizability to a larger and more diverse population," said Dr. Shokri-Kojori.

It is also important to note that the link between sleep disorders and Alzheimer's risk is considered by many scientists to be "bidirectional," since elevated beta-amyloid may also lead to sleep disturbances.

RIVERSIDE, Calif. -- A team of researchers at the University of California, Riverside have isolated three previously unknown bacterial species from wild bees and flowers. The bacteria, which belong to the genus Lactobacillus, may play a role in preserving the nectar and pollen that female bees store in their nests as food for their larvae.

The results were published Thursday in the International Journal of Systematic and Evolutionary Microbiology. The study was led by Quinn McFrederick, an assistant professor of entomology in UCR's College of Natural & Agricultural Sciences.

Symbiotic bacteria that live in bee guts are believed to promote bee health by helping to digest food and boost immunity. Compared to honeybees and bumblebees, little is known about the microbial communities associated with wild bees, despite the important role these insects play in the pollination of flowering plants.

To study the bacteria associated with wild bees, McFrederick and co-authors collected wild bees and flowers from two sites in Texas and on the UCR campus. Genomic DNA sequencing coupled with traditional taxonomic analyses confirmed the isolation of three new Lactobacillus species, which are closely related to the honeybee-associated bacteria Lactobacillus kunkeei. The news strains are:

Lactobacillus micheneri, named after Charles D. Michener to honor his contributions to the study of bees in natural habitats.
Lactobacillus timberlakei, named after Philip Timberlake to honor his work on the taxonomy of native bees, especially at UC Riverside.
Lactobacillus quenuiae, named after Cécile Plateaux-Quénu to honor her contribution to our understanding of the social biology of halictid bees.
Lactobacilli are often used by humans to preserve dairy products, fermented vegetables and other foods. The study by McFrederick's group suggests the newly identified species may help bees in a similar way, inhibiting the growth of fungi inside pollen provisions. McFrederick's group is currently conducting research to further explore this hypothesis.

"Wild bees lay their eggs inside chambers filled with nectar and pollen," McFrederick said. Once an egg has been laid, it may take several days to hatch and an additional week for the larvae to eat through all the nectar and pollen, so it is important that these provisions don't spoil during this period."

McFrederick said it is interesting that the bacteria were able to live on both wild flowers and bees.

"The species we isolated have fairly small genomes and not as many genes as you would expect considering they survive in two different environments," McFrederick said.

The researchers within the groups of Prof Dr Lars Schäfer and Prof Dr Enrica Bordignon, who work together in the Excellence Cluster Ruhr explores Solvation, Resolv in short, report in the Journal of the American Chemical Society of 16 March 2018.

"ABC transporters are fascinating biological nanomachines", says Lars Schäfer, head of the Molecular Simulation research group. These proteins couple the binding and chemical cleavage of ATP molecules, the chemical energy unit of the cell, with the transport of molecules through biological membranes.

Resistance of tumour cells and bacteria

A particular characteristic of the so-called ABC exporters is that they transport a very wide range of molecules out of the cell: from lipids and peptides to chemotherapeutic agents. "ABC exporters therefore play an important role, including with regard to multi-drug resistance of cancer cells and antibiotic resistance of bacteria", explains Schäfer.

The research groups of Lars Schäfer and Enrica Bordignon combined detailed computer simulations with spectroscopic experiments to shed light on the functional mechanism of an ABC exporter in atomic detail.

Hope for new therapy approaches

"Our results show how the binding of ATP molecules induces structural changes in the transporter that are ultimately required to carry substrate molecules through the membrane", explains Hendrik Göddeke, co-author and doctoral researcher in Lars Schäfer's group. "We conduct basic research", says Enrica Bordignon, head of the EPR Spectroscopy research group. In the long term, however, these findings could contribute to the development of new therapeutic approaches. "The goal would be to specifically influence or inhibit these processes", says Bordignon.

IF you want to know how to pour the perfect pint or create the ultimate cup of coffee, then you really need a mathematician.

That might not be the most obvious choice, but major companies are increasingly aware that they can solve conundrums and improve their products by calling on specialists in the burgeoning discipline known as industrial mathematics. They include William Lee, recently appointed professor in the subject at the University of Huddersfield.

Two of his most high-profile research projects were triggered by drinks giant Diageo - which wanted Professor Lee to investigate the strange behaviour of bubbles in a glass of Guinness - and by electrical goods conglomerate Philips, which commissioned research on how to obtain the best results from filter coffee machines.

He has also carried research for major companies in fields that include pharmaceuticals, using mathematics to investigate topics such as arterial disease.

The Guinness bubbles research has created widespread media interest over recent years and earned light-hearted plaudits such as The Economist Babbage Award for Bizarre Boffinry. But it has also proved to be highly productive academically, resulting in a sequence of scientific articles. The latest is Sinking Bubbles in Stout Beers, published by the American Journal of Physics.

It was while Professor Lee was based at the University of Limerick that he was asked to investigate the counter-intuitive behaviour of bubbles in a glass of Guinness - they sink rather than rise. After simulations and experiments, which he completed following a move to the University of Portsmouth, it was decided that the shape of the glass, with its sloping walls, was the determining factor.

The latest article describes how a mathematical model - which provides greater focus than computer simulation - was used in order to provide conclusive proof.

"People think that the Guinness glass is designed to optimise the settling time," said Professor Lee. "But now we have a better understanding of the theory behind it, we might be able to make an even better glass so that it settles faster. Unfortunately, the ideal shape would look like a giant cocktail glass!"

Mathematical ideas

Professor Lee was drawn to industrial mathematics when he realised the research potential it offered. At the University of Limerick - where he remains an Adjunct Professor - he founded its Industrial Mathematics Unit, which carries out consultancy work in mathematical and statistical modelling for industry. At the University of Huddersfield, he is establishing an Institute for Mathematics and Data Science.

"There are two basic places you can look for new mathematical ideas," said Professor Lee. "One is just digging deeper into existing mathematics and the other is to go out and look for new phenomena, and industry is full of those."

"It's much more rewarding to work on a problem where you know someone is interested in the solution!"

Specialists in industrial mathematics hold study groups that resemble academic conferences, but also invite industry figures to come and present their problems. This is how Professor Lee and his collaborators were first enlisted by Diageo to work on issues around bubbles in stout and the serving of Guinness.

It was also the point of contact for another high-profile strand of Professor Lee's research - the quest for a perfect cup of coffee from the filter machines manufactured by Philips. The result was a mathematical model of coffee brewing that could be used to aid the design of machines. There were also significant findings about the processes by which coffee is extracted from beans.

This led to the co-authored 2016 article Coffee extraction kinetics in a well mixed system, in the Journal of Mathematics in Industry. Now, Professor Lee is moving from filter coffee to espresso, investigating the link between strength and flavour.

April 13, 2018--Even the briefest increase in airborne fine particulate matter PM2.5, pollution-causing particles that are about 3 percent of the diameter of human hair, is associated with the development of acute lower respiratory infection (ALRI) in young children, according to newly published research. Increases in PM2.5 levels also led to increased doctor visits for these lung infections.

The groundbreaking study, "Short-Term Elevation of Fine Particulate Matter Air Pollution and Acute Lower Respiratory Infection," is the largest to date on this health concern, involving more than 100,000 patients.

The research was undertaken by a team from Intermountain Healthcare, Brigham Young University and University of Utah and is published online in the American Journal of Respiratory and Critical Care Medicine, an American Thoracic Society journal.

"The most important finding of this study is that infectious processes of respiratory disease may be influenced by particulate matter pollution at various levels," said lead author Benjamin Horne, PhD, director of cardiovascular and genetic epidemiology at the Intermountain Medical Center Heart Institute in Salt Lake City, Utah. "The exact biological implications of the study's findings require further investigation."

Dr. Horne and colleagues studied 146,397 individuals who were treated for ALRI between 1999 and 2016 at Intermountain Healthcare facilities throughout Utah's Wasatch Front region. The Wasatch Front is approximately 80 miles long and 10-20 miles wide, bordered on both sides by mountains. It consists primarily of suburbs, but also includes the cities of Salt Lake City, Ogden and Provo/Orem.

PM2.5 levels were estimated based on data from air quality monitoring stations along the Wasatch Front, where approximately 80 percent of Utah's population resides. Measurements were also made at secondary locations. Short-term periods of PM2.5 elevation were matched with the timing of increases in health care visits for ALRI.

The primary aim of the study was to determine if there was an association between these fine particulates and ALRI in very young children, with a secondary objective of finding the same associations for older children, adolescents and adults.

The research team found ALRI associated with elevated levels of PM2.5 in both children and adults - even in newborns and toddlers up to age two, who represented 77 percent (112,467) of those who had an ALRI diagnosis.

Nearly 60 percent of U.S. children live in counties with PM2.5 concentrations above air quality standards. This study was performed in a location where the average daily PM2.5 level is lower than places like Los Angeles and New York. Due to the topography of the region, though, air pollution may become trapped in the high mountain valleys of the Wasatch Front--especially during temperature inversions, which typically occur in the winter months. When PM2.5 becomes trapped in the valleys, this often leads to sharp increases in PM2.5 to levels considered to be unhealthy (>35 micrograms per cubic meter, and at times approaching 100 ug/m3).

"In many places that have higher average PM2.5, the PM2.5 level does not vary as much as it does on the Wasatch Front, so it is not clear how this study's findings may transfer to those locales where the air pollution exposure is higher over the long term but short term spikes do not occur," said Dr. Horne. "It may be, though, that long-term exposure to air pollution makes people more susceptible to ALRI on a routine basis, although additional studies will be required to test this hypothesis."

Bronchiolitis, a condition in which small breathing tubes in the lungs called bronchioles become infected and clogged with mucus, is the most common acute lower respiratory infection in children.

Fifty to 90 percent of bronchiolitis cases are caused by respiratory syncytial virus (RSV), which is the most common cause of hospitalization in the first two years of life. Sixty-four percent of individuals studied had a diagnosis of bronchiolitis.

"Overall, it took about 2-3 weeks for the ALRI hospitalizations or clinic visits to occur in this study after the rapid rise in PM2.5 had been observed," said Dr. Horne. In an analysis of death rates among the study population, 17 children ages 0-2, 9 children ages 3-17 and 81 adults (? age 18) died within 30 days of diagnosis with ALRI.

In theorizing about the connection between PM2.5 and ALRI, Dr. Horne said: "The air pollution itself may make the human body more susceptible to infection or may impair the body's ability to fight off the infectious agents. It may be that PM2.5 causes damage to the airway so that a virus can successfully cause an infection or that PM2.5 impairs the immune response so that the body mounts a less effective response in fighting off the infection. This could lead to longer periods of ALRI symptoms or more severe symptoms requiring a higher intensity of medical care for the infected individual. It may also be that periods of acute increases in PM2.5 lead people to stay indoors more where they are in closer contact with others who carry infectious agents and can transmit the infection to them."

Motor vehicles contribute about 48 percent of emissions that lead to the formation of fine particulates. Small industry and businesses such as gas stations and dry cleaners, as well as home heating, emit about 39 percent of all fine particulates. Large manufacturing accounts for 13 percent.

"The practical implications for prevention of ALRI and amelioration of symptoms include that when an acute increase in the level of PM2.5 occurs, people may be able to prevent infections or decrease ALRI symptom severity or duration by reducing their exposure to the air pollution," said Dr. Horne. "Furthermore, a substantial elevation in PM2.5 may also serve as a nudge that reminds or alerts people to avoid areas and activities where other people may share an infection with them, to not touch their face with dirty hands, to be vigilant about washing their hands when reasonably possible or prudent, and to engage in other preventive behaviors that are known to reduce infection risk."

SCIENTISTS at the University of Huddersfield have been using world-class new facilities to carry out experiments that could aid the development of nuclear fusion reactors, widely regarded as the "Holy Grail" solution to future energy needs.

By simulating the damage caused by high energy neutrons and alpha particles produced during the fusion process, the Huddersfield researchers have discovered that tungsten -- a favoured choice of metal within the reactor -- is liable to become brittle, leading to failure.

"At this moment in time, even though tungsten is a leading candidate, we don't see how we can use it as a structural material. We can use it as a barrier, but not for anything structurally sound," states Dr Robert Harrison, who is a Research Fellow at the University of Huddersfield's Electron Microscopy and Materials Analysis Research Group (EMMA).

The answer will be to develop a new alloy that combines tungsten -- which has desirable properties of extreme hardness and exceptionally high melting temperature -- with some other material that can prevent its embrittlement from radiation damage and nuclear transmutation reactions, which would have significant safety implications for the operation of the reactor.

Dr Harrison and his colleagues have access to the University of Huddersfield's Microscope and Ion Accelerator for Materials Investigation (MIAMI) facilities. These combine ion irradiation with transmission electron microscopy. Newly-opened MIAMI-2 - developed with an award of £3.5 million from the Engineering and Physical Sciences Research Council - has dual ion beams and is one of the world's leading facilities of its kind.

By using both helium and tungsten ions to safely replicate the alpha particles created during a fusion reaction and the neutron bombardment, the EMMA researchers have been able to replicate the damage caused to tungsten. The findings are described in a new article in the journal Scripta Materialia, authored by Dr Harrison with Dr Jonathan Hinks and Professor Stephen Donnelly.

Progress is being made towards the development of nuclear fusion, which fuses atoms rather than splits them as in a conventional fission reactor. Under construction in France is the International Experimental Fusion Reactor, which aims to be the first reactor that produces more energy than it consumes.

At the Culham Centre for Fusion Energy in Oxfordshire, the Joint European Torus (JET), is the world's largest operational magnetic confinement plasma physics experiment, intended to open the way to future nuclear fusion grid energy.

Advocates for nuclear fusion state that it has the potential to generate almost limitless, clean energy that is "too cheap to meter". Research such as the University of Huddersfield investigation of tungsten could help bring the breakthrough closer.

People in crowded urban areas - especially poor areas - see fewer songbirds such as tits and finches, and more potential "nuisance" birds, such as pigeons, magpies and gulls, new research shows.

The University of Exeter and the British Trust for Ornithology examined ratios of birds-to-people and found areas of high-density housing have fewer birds overall - and the birds people do see are just as likely to cause a nuisance as to make them happy.

Meanwhile, people in green and leafy suburbs see up to three and a half times more songbirds and woodpeckers - which are associated with a positive impact on human wellbeing - than birds whose behaviours can cause a nuisance.

Previous research has suggested that people living in neighbourhoods with more birds, shrubs and trees are less likely to suffer from depression, anxiety and stress.

"For most people, birds provide their most common encounter with wild animals," said research fellow Dr Daniel Cox, of the Environment and Sustainability Institute at the University of Exeter's Penryn Campus in Cornwall.

"Understanding the relationship between the numbers of birds and people is important for how we manage nature and wildlife in towns and cities to promote positive nature experiences, while minimising the potential for conflict.

"There are many ways for people to attract birds to the garden to gain positive nature experiences, not only for you and your family but also for the households around you who will also have an increased chance of seeing these birds.

"We are not saying that all individuals of species such as pigeons, gulls, crows and magpies cause problems - many will provide people with positive experiences - but the behaviours of some individuals of these species can cause problems, such as noise, mess and smell."

The study conducted extensive bird surveys across three towns in England: Milton Keynes, Luton and Bedford.

The researchers then analysed how the numbers and types of birds varied with human population density.

They looked at the ratios of birds to people of species that are generally positive for our wellbeing, such as species that can be attracted to garden bird feeders like tits and finches, and species of bird whose behaviours can cause a nuisance.

Overall, they found 1.1 birds per person that make us happy, and 0.4 birds per person whose behaviours commonly cause a nuisance.

"Many people have different favourite birds, of course, but some species are more popular than others and we all benefit from having species that we perceive positively nearby," added Dr Gavin Siriwardena of the British Trust for Ornithology.

"As well as individual people attracting birds directly by feeding them, a novel approach to planning and development could see design of green spaces to maximize interactions with the wildlife they like.

"This could mean habitats like ponds and woodland integrated with new developments, but avoiding features that support nuisance species."

The study, published in the Journal of Applied Ecology, was funded by the Natural Environment Research Council and conducted as part of the Fragments, Functions, Flows and Ecosystem Services project.

13 April 2018, Paris, France: The fibroblast growth factor 19 (FGF19) engineered analogue, NGM282, inhibits bile acid synthesis, decreases markers of hepatic inflammation, and significantly improves markers of fibrosis in patients with primary sclerosing cholangitis (PSC), according to the results of a Phase 2, multicentre, randomized, double-blind, placebo-controlled study reported today. The study, which involved 62 patients with PSC diagnosed according to EASL criteria,7 offers hope of a new medical treatment for a condition in which effective drug therapies are currently limited.8

'Primary sclerosing cholangitis is a rare, inflammatory, cholestatic liver disease that is characterized by progressive fibrosis of the bile ducts and liver, and causes progressive liver dysfunction', explained Prof. Gideon Hirschfield from the University of Birmingham in the UK, who presented the results today at The International Liver Congress™ 2018 in Paris, France. 'Liver transplantation is effective for advanced disease, but there are currently no medical treatments that have been shown to prolong transplant-free survival'.8

NGM282 is a non-tumourigenic engineered analogue of FGF19, an endocrine gastrointestinal hormone that regulates bile acid, carbohydrate and energy homeostasis.9,10 In an animal model, NGM282 was shown to suppress the classic pathway of bile acid production, and to inhibit fatty acid synthesis and de novo lipogenesis.11 NGM282 was well tolerated in a healthy volunteer study,12 and the molecule has recently shown potential as a treatment for non-alcoholic steatohepatitis (NASH).13

The study presented today by Prof. Hirschfield randomized 62 patients with PSC and an elevated alkaline phosphatase (ALP) level (?1.5x the upper limit of normal) to receive either a daily subcutaneous injection of NGM282 at a dose of 1 mg or 3 mg, or placebo. The primary endpoint was the change in ALP from baseline to Week 12.

Although there were no significant reductions in serum ALP levels in either active treatment group compared with placebo, at Week 12 significant reductions in serum levels of alanine aminotransferase (ALT) (-40 U/L) and aspartate aminotransferase (AST) (-23 U/L) in the NGM282 3 mg/day treatment group were observed (p'We also saw significant reductions in surrogate markers of fibrogenesis in the patients who received NGM282, with reductions especially pronounced in patients with higher-risk disease (Enhanced Liver Fibrosis Score >9.8 at baseline)', said Prof. Hirschfield. 'These changes are consistent with those observed in patients with non-alcoholic steatohepatitis which were also presented at ILC this year'.

NGM282 was well tolerated in this study, with no differences in PSC-related clinical events between the NGM282 treatment groups and the placebo group. No drug-induced pruritus was observed and no neutralizing anti-drug antibodies were detected during or after treatment with NGM282. The most frequently reported adverse events amongst the NGM282-treated patients were diarrhoea, frequent stools and injection site reactions, the majority of which were mild and resolved while on treatment.

'This study provides good evidence of relevant clinical activity for NGM282 in individuals with PSC and highlights the need to explore NGM282's impact on liver fibrosis in larger studies of a longer duration', said Prof. Hirschfield. 'NGM282 seems to be a promising treatment for patients with PSC, for whom very few medical options currently exist'.

'Studies like this one are key, since they investigate possible novel treatments for PSC, a disease that currently has no effective therapies', said Prof. Marco Marzioni from the University Hospital of Ancona, Italy, and EASL Governing Board Member. 'Although this trial did not achieve fully positive results in terms of reduction of markers of disease progression, it certainly indicates that the manipulation of key molecules involved in the pathophysiology of PSC is the route to cure for our patients'.

Engineers have proposed a coordinated control architecture for motion management in advanced driver assistance systems (ADAS) to increase safety and comfort across all vehicles, regardless of ADAS specifics.

They published their proposal in IEEE/CAA Journal of Automatica Sinica, a joint publication of the IEEE and the Chinese Association of Automation.

"The modern automobile is a complex system of systems. How the functionalities of advanced driver assistance are implemented and coordinated across the systems of the vehicle is generally not made available to the wider research community by the developers and manufactures," wrote Tzu-Chi Lin, a research engineer with the Warwick Manufacturing Group in the United Kingdom, and an author on the paper. "This paper seeks to begin filling this gap by assembling open source physics models of the vehicle dynamics and ADAS command models."

One of the most common ADAS alerts drivers when the car drifts out of their lane, or helps a driver intentionally change lanes.

"Each of the various types of ADAS systems in service today generally provide a unique feature for the user that is implemented through additional control of one of the vehicle's systems, e.g. braking or steering," Lin wrote. "ADAS systems must not be regarded as a substitute for drivers but rather as a co-driver, even if direct involvement in some of the driving tasks is not required."

With that in mind, Lin and his team integrated physics models of vehicle dynamics and ADAS command models. They ran simulations on this combined information, and analyzed how control from different, independent vehicle systems might influence the vehicle trajectory as it changes lanes.

They found that the steering system caused the simulated vehicle to undershoot, while the brake system overshot.

"On the other hand, the 'coordinated control' strategy successfully damped out the deviation errors, and gave much greater precision in following the intended trajectory," Lin wrote.

The researchers will continue to explore the system of systems control architecture to better develop coordinated control in ADAS. They will also examine how new systems interfere with existing systems to fully understand control performance and stability.

Engineers from the Wolfson School of Mechanical, Electrical and Manufacturing Engineering of Loughborough University and systems engineering of Jaguar Land Rover contributed to this research. The work was supported by the Programme for Simulation Innovation at Loughborough University.