Culture

HANOVER, N.H. - May 28, 2019 - Parts of Alaska's mountainous Brooks Range were likely transported from Greenland and a stretch of the Canadian Arctic much farther to the east, according to a series of Dartmouth-led studies detailing over 300 million years of Arctic geologic history.

The finding updates the geological evolution of the Arctic Ocean and could help revise predictions about the Arctic's oil, gas and mineral wealth.

By explaining the formation of the Arctic Ocean in the Western Hemisphere - known as the Amerasian Basin - the research provides more clues into the geological history of the rapidly changing region.

"This is arguably the most important place for the United States from the perspective of Arctic economic development," said Justin Strauss, an assistant professor of earth science at Dartmouth. "The geology of this region, which is directly connected to its ancient history, will help revise our knowledge about natural resources in the Arctic."

The existing model for the formation of the Arctic Ocean along the U.S. and Canada border region details how seismic activity, known as faulting, caused Alaska to rotate away from a western band of islands in the Canadian Arctic starting approximately 125 million years ago.

Under this original "rotation" scenario, parts of the Brooks Range should match perfectly with Canada's Banks Island and Victoria Island about 450 hundred miles away.

But after close to ten years studying exposed rocks in the region, the Dartmouth studies show that the area actually contains rocks with origins as far away as 1,200 miles to the east. The results were recently published in a Special Papers series by the Geological Society of America.

"The geology of the northeastern Brooks Range does not match anything that we've studied in the neighboring region of North America," said Strauss, the research lead of the study. "This complicates previous models for how you open this major ocean basin."

Further confirming the findings, researchers in the study area saw signs of mountain-building processes that are not known to have taken place near the present position of the Brooks Range. This collision of ancient land masses dating from 400-450 million years is more closely associated with tectonic activity in the eastern Arctic.

The team believes that the area was formed by a combination of activities including the action of a major strike-slip fault system - similar to the San Andreas Fault of California - that transported part of what is now the Brooks Range from Greenland to the western Canadian Arctic Islands.

A smaller scale rotation of the land mass farther westward that has been previously recorded may complete the explanation of how northern Alaska was transported to its current location.

"Relationships on the northwestern margin of North America have long been poorly understood and poorly documented," said Bill McClelland, a professor of earth and environmental studies at the University of Iowa and co-investigator of the study. "The results of these studies have significantly enhanced our understanding of the tectonic processes that formed the Arctic margin of North America and will be instrumental in pushing forward on new research frontiers."

"Because of its remoteness, the North Slope of Alaska and Yukon has seen limited studies to date," said co-investigator Maurice Colpron, a scientist with the Yukon Geological Survey. "Understanding the area with complete certainty will still take many years of hard work, but these research findings greatly advance our knowledge of the region."

As the Arctic continues to open for the development of oil, gas and mineral resources, this new understanding of the region's history could change predictions of how much resource wealth lies in the area.

The United States Geological Survey currently estimates that about 6 percent of the world's oil and 25 percent of the world's natural gas are in the Arctic. The region studied by the team lies within the Arctic National Wildlife Refuge, an area that some would like to open for oil drilling.

In addition to changing the outlook over how much resource wealth exists in the Arctic and where it sits, the research could impact how countries lay claim to those resources. The United States, Russia, Canada and other Arctic countries are all jostling for extended footholds in the region.

"If countries are going to make legal claims based on geology or geophysics, they should consider these much older boundaries that we are highlighting. Governments will to need to confront the complexities of geology meeting politics," said Strauss.

While magnetic surveys allow researchers to understand how the Arctic's Eurasian Basin over Europe and western parts of Asia was formed, that same data are not as easy to interpret for the Amerasian Basin above North America.

The research, funded by the National Science Foundation, is based on the existence of a major fault system in the northern part of North America that has yet to be completely mapped.

"This is the area of the Arctic Ocean that still baffles researchers. It's one of the last major ocean basins on the planet that we just do not understand," said Strauss.

In future studies, the research team will focus on Canada's Yukon and Ellesmere Island to look for major fault systems. The research will retrace hundreds of millions of years of geological evolution to further explore where this part of Alaska came from and why it landed where it did.

There has been a rapid rise in e-cigarette use, but its health effects have not been well-studied and their effect on vascular health remains unknown. A first of its kind study in endothelial stem cells, published in the Journal of the American College of Cardiology, found acute exposure to flavored e-liquids or e-cigarette use exacerbates endothelial cell dysfunction, which often precedes heart disease.

Endothelial cells are the main type of cell found in the inside lining of blood vessels, lymph vessels and the heart.

The researchers used induced pluripotent stem cells-derived endothelial cells (iPSC-ECs) from three healthy individuals and a subject population consisting of five healthy non-smokers, five active cigarette smokers, two dual users of e-cigarettes and cigarettes, and two sole users of e-cigarettes. All subjects were healthy individuals free of other major cardiovascular risk factors. The researchers examined the effects of e-liquids on endothelial cell viability by treating the iPSC-ECs with a dilution of six commercially available e-liquids at varying nicotine concentrations. They found all six flavored e-liquids had varying effects on cell survival and observed the presence of pro-inflammatory markers that are known to play a critical role in the development of vascular disease.

The researchers observed the fruit-flavored, sweet tobacco with undertones of caramel and vanilla-flavored, tobacco-flavored Red Oak Tennessee Cured, and sweet-flavored Butter Scotch all had moderate toxic effects on the cells, with the strongest toxic effect coming from the cinnamon-flavored Marcado. They also found menthol tobacco-flavored Tundra had a strong toxic effect at 1 percent dose of concentration with or without nicotine.

The researchers performed other tests to examine endothelial function in iPSC-ECs after the addition of e-liquids and serum from e-cigarette users, and the effect of acute e-cigarette use and cigarette smoking on serum nicotine levels, among others.

"Although limited by a small sample size, our data suggest that e-cigarette use can lead to acute endothelial dysfunction, which we validated by in vitro exposure to either e-liquid or serum derived from patients using e-cigarettes," said Joseph C. Wu, MD, PhD, professor and director of the Stanford Cardiovascular Institute at the Stanford School of Medicine and the study's senior author. "E-cigarette use in the U.S. and worldwide is rapidly increasing with growing concerns from the scientific, public health and policy making communities. Our findings are an important first step in filling this gap by providing mechanistic insights on how e-cigarettes cause endothelial dysfunction, which is an important risk factor for the development of heart disease."

A study presented at the American College of Cardiology's 68th Annual Scientific Session earlier this year found that adults who report puffing e-cigarettes, or vaping, are significantly more likely to have a heart attack, coronary artery disease and depression compared with those who do not use them or any tobacco products.

LA JOLLA, CA--A decade ago researchers announced development of a cancer immunotherapy called CAR (for chimeric antigen receptor)-T, in which a patient is re-infused with their own genetically modified T cells equipped to mount a potent anti-tumor attack. Since then CAR T approaches (one of several strategies collectively known as "adoptive T cell transfer") have made headlines as a novel cellular immunotherapy tool, most successfully against so-called "liquid cancers" like leukemias and lymphomas.

Sarcomas and carcinomas have proven more resistant to these approaches, in part because engineered T-cells progressively lose tumor-fighting capacity once they infiltrate a tumor. Immunologists call this cellular fatigue T cell "exhaustion" or "dysfunction."

In efforts to understand why, La Jolla Institute for Immunology (LJI) investigators Anjana Rao, Ph.D., and Patrick Hogan, Ph.D., have published a series of papers over the last years reporting that a transcription factor that regulates gene expression, called NFAT, switches on "downstream" genes that weaken T cell responses to tumors and thus perpetrates T cell exhaustion. One set of these downstream genes encodes transcription factors known as NR4A, and a previous graduate student, Joyce Chen, showed that genetic elimination of NR4A proteins in tumor-infiltrating CAR T cells improved tumor rejection. However, the identity of additional players cooperating with NFAT and NR4A in that pathway has remained unknown.

Now a paper published in this week's online edition of the Proceedings of the National Academy of Sciences (PNAS) from the Rao and Hogan labs provides a more complete list of participants in an extensive gene expression network that establishes and maintains T cell exhaustion. The study employs a mouse model to show that genetically eliminating two new factors, TOX and TOX2, also improves eradication of "solid" melanoma tumors in the CAR T model. This work suggests that comparable interventions to target NR4A and TOX factors in patients may extend the use of CAR T-based immunotherapy to solid tumors.

The group began by comparing gene expression profiles in samples of normal versus "exhausted" T cells, searching for factors upregulated in parallel with NR4A as co-conspirators in T cell dysfunction. "We found that two DNA binding proteins called TOX and TOX2 were consistently highly expressed along with NR4A transcription factors," says Hyungseok Seo, Ph.D., a postdoctoral fellow in the Rao lab and the study's first author. "This discovery suggested that factors like NFAT or NR4A may control expression of TOX."

The group then recapitulated a CAR T protocol in mice by first inoculating animals with melanoma tumor cells to establish a tumor, and then a week later infusing mice with one of two collections of T cells: a "control" sample from a normal mouse, versus a sample derived from mouse genetically engineered to lack TOX and TOX2 expression in T cells.

Remarkably, mice infused with TOX-deficient CAR T cells showed more robust regression of melanoma tumors than did mice infused with normal cells. Moreover, mice treated with TOX-deficient CAR T cells exhibited dramatically increased survival, suggesting that loss of TOX factors combats T cell exhaustion and allows T cells to destroy tumor cells more effectively.

Additional analysis led the investigators down a pathway ending with a well-known immune adversary. The researchers showed that TOX factors join forces with both NFAT and NR4A to promote expression of an inhibitory receptor called PD-1, which decorates the surface of exhausted T cells and sends immunosuppressive signals.

PD-1 is blocked by numerous monoclonal antibodies called checkpoint inhibitors, which combat immunosuppression and activate an innate anti-cancer immune response. Convergence of TOX, NFAT, and NR4A on PD-1 makes molecular and immunological sense and puts it at the convergence of both cellular and antibody immunotherapy approaches.

"Currently, CAR T cell therapy shows amazing effects in patients with "liquid tumors" such as leukemia and lymphoma," says Seo. "But they still do not work well in patients with solid tumors due to T cell exhaustion. If we could inhibit TOX or NR4A by treating CAR T cells with a small molecule, this strategy might show a strong therapeutic effect against solid cancers such as melanomas."

The flavoring liquid for electronic cigarettes, or e-cigarettes, may increase the risk of cardiovascular disease when inhaled, according to a study led by researchers at the Stanford University School of Medicine.

The scientists investigated the effect of the e-liquids on cells called endothelial cells that line the interior of blood vessels. They found that, when grown in a laboratory, endothelial cells exposed to the e-liquids -- or to blood collected from e-cigarette users shortly after vaping -- are less viable and exhibit significantly increased levels of molecules implicated in DNA damage and cell death. The cells are also less able to form new vascular tubes and to migrate and participate in wound healing.

The severity of the damage, aspects of which occur even in the absence of nicotine, varies among popular flavors, the researchers said. Cinnamon and menthol were found to be particularly harmful.

"Until now, we had no data about how these e-liquids affect human endothelial cells," said Joseph Wu, MD, PhD, director of the Stanford Cardiovascular Institute and professor of cardiovascular medicine and of radiology. "This study clearly shows that e-cigarettes are not a safe alternative to traditional cigarettes. When we exposed the cells to six different flavors of e-liquid with varying levels of nicotine, we saw significant damage. The cells were less viable in culture, and they began to exhibit multiple symptoms of dysfunction."

The researchers studied human endothelial cells generated in the laboratory from what are called induced pluripotent stem cells, or iPS cells. Human iPS cells can become many different cell types, and they provide an ideal way for researchers to closely study cells that would be difficult to isolate directly from a patient.

This study was the first to use endothelial cells derived from iPS cells to directly investigate the effect of e-liquids with and without nicotine on their viability and function.

A paper describing the findings will be published online May 27 in the Journal of the American College of Cardiology. Wu is the senior author. Former postdoctoral scholars Won Hee Lee, PhD, now an assistant professor at the University of Arizona, and Sang-Ging Ong, PhD, now an assistant professor at University of Illinois-Chicago, are the lead authors.

E-cig use has skyrocketed

In the United States, cardiovascular disease is responsible for about one-third of smoking-associated deaths in smokers, and secondhand smoke causes approximately 34,000 early deaths from heart disease each year in nonsmokers. Endothelial cells line the interior surface of blood vessels and play a critical role in heart and cardiovascular health. Although some studies have suggested that e-cigarettes deliver lower levels of carcinogens to users than do conventional cigarettes -- perhaps decreasing the risk of cancer -- the effect of e-cigarette use on vascular health has been unclear.

Despite these uncertainties, the use of e-cigarettes has skyrocketed since their introduction about a decade ago, particularly among young people. The Food and Drug Administration estimated that more than 3.5 million middle and high school students used e-cigarettes in 2018, though sales to minors are prohibited. In 2018, the FDA restricted the sale of flavored e-cigarettes to adults-only venues, with the exception of tobacco, menthol and mint flavors, which can be sold wherever traditional cigarettes are sold.

"One in five high school students have tried e-cigarettes, perhaps because they feel they are relatively safe," Lee said. "But we found the e-liquids caused changes in the endothelial cells that are closely related to those seen during the development of cardiovascular disease."

The researchers investigated the effect of six different popular e-liquid flavors -- fruit, tobacco, sweet tobacco with caramel and vanilla, sweet butterscotch, cinnamon, and menthol -- with nicotine levels of 0, 6, and 18 milligrams per milliliter on endothelial cells derived from human iPS cells. They found that while several of the liquids were moderately toxic to the endothelial cells, the cinnamon- and menthol-flavored e-liquids significantly decreased the viability of the cells in culture even in the absence of nicotine.

Exposure to the e-liquids also increased the relative levels of reactive oxygen species -- molecules that can cause DNA damage -- and the levels of molecules associated with programmed cell death.

The researchers also found that exposure to the cinnamon and menthol flavored e-liquids significantly disrupted the ability of the cultured cells to form capillary-like tubular structures associated with the growth of new blood vessels. The e-liquid flavored with caramel and vanilla also disrupted growth, but not as severely. The cells exposed to cinnamon flavor and caramel and vanilla flavors exhibited an increased uptake of low-density lipoproteins and lipids -- processes commonly associated with inflammation and endothelial dysfunction -- and a reduction in their ability to migrate to heal wounds or scratches.

Some of the effects of exposure to the various e-liquids were dependent on the nicotine concentration, but others, like cellular migration and decreases in cell viability, were independent of nicotine, suggesting a combined effect of nicotine concentrations and flavoring components.

Finally, the researchers compared the levels of nicotine in the blood serum of people after they had vaped e-cigarettes with the levels in people who smoked traditional cigarettes. They found that the amounts of nicotine in the blood were similar between the two groups after 10 minutes of smoking at a constant rate.

"When you're smoking a traditional cigarette, you have a sense of how many cigarettes you're smoking," Wu said. "But e-cigarettes can be deceptive. It's much easier to expose yourself to a much higher level of nicotine over a shorter time period. And now we know that e-cigarettes are likely to have other significantly toxic effects on vascular function as well. It's important for e-cigarette users to realize that these chemicals are circulating within their bodies and affecting their vascular health."

A combination of visual training and a recently developed brain stimulation technique boosts learning in healthy adults and cortically blind patients, according to research published in JNeurosci.

Lorella Battelli at the IIT-Istituto Italiano di Tecnologia and collaborators Krystel Huxlin and Duje Tadin at the University of Rochester demonstrate enhanced learning in healthy men and women with only 10 days of training. Transcranial random noise stimulation of early visual areas resulted in twice as much improvement on a visual motion task compared to other stimulation techniques or training alone. Surprisingly, the study found this enhanced learning persists for at least six months.

By extending their findings to patients who suffered a stroke or traumatic brain injury affecting their visual cortex, the researchers suggest this safe and painless two-pronged approach could lead to faster visual recovery and improved quality of life for this underserved patient population.

Dysfunctional neurons in the hippocampus of adult female mice modeling dementia can be repaired and reconnected to distant parts of the brain, reports a new study published in JNeurosci. The similarity between the mouse model and the human condition underscores the therapeutic potential of targeting these cells in dementia patients.

The hippocampus generates new brain cells throughout life and is implicated in neurodegenerative diseases. María Llorens-Martín and colleagues at the Centro de Biología Molecular "Severo Ochoa" (CBMSO, CSIC-UAM) used a mouse model of frontotemporal dementia to investigate the effects of the disease on dentate granule cells.

Compared to control subjects, the researchers observed strikingly similar alterations in newborn neurons from their mouse model and from human brain tissue of patients with frontotemporal dementia. In mice, chemically activating the cells and placing animals in a stimulating environment with running wheels and toys reversed the alterations and restore some of the connectivity disrupted by dementia. If translated to humans, these results suggest potential new directions for combating cognitive decline in the elderly.

A new analysis of global fishing data has found the world's fishing fleet doubled in size over the 65-years to 2015 but for the amount of effort expended the catch fell more than 80 per cent.

Published in the journal Proceedings of the National Academy of Sciences, the study by researchers from the University of Tasmania and CSIRO found the global fishing fleet grew from 1.7 million vessels in 1950 to 3.7 million in 2015.

However, despite better technology and increased motorisation, modern fishing vessels take only one fifth of the catch per unit of effort (CPUE) that the 1950s fishing fleet achieved.

IMAS and CMS PhD student Yannick Rousseau, who led the study, said the findings reflect growing pressure on marine resources and a fall in the abundance of fish.

"What we have seen over the last 65 years is more and more fishing vessels chasing fewer fish," Mr Rousseau said.

"Since 1950 a dramatic increase in the size of the fishing fleet in Asia has more than off-setting small declines in North America and Western Europe.

"Most of the increase in vessel numbers has been in motorised fishing boats, a change from the unpowered 'artisanal' fishing vessels that once characterised Asian and African fishing fleets.

"But, despite its advanced technology and increased numbers, the modern motorised fleet is having to work much harder to catch fewer fish," he said.

Mr Rousseau said fisheries scientists use a measure of catch per unit of effort (CPUE) to assess fisheries management and the well-being of fish stocks.

"CPUE reflects how many fish are caught for the amount of effort expended, such as during a day's fishing, and this measure paints a dark picture of the state of the ocean's resources.

"In recent years a sharp drop in CPUE in Southeast Asia, Latin America and the Southern Mediterranean indicates their fisheries expanded at a much faster rate than fish stocks could support."

The study found that in developed countries such as Australia more effective fisheries management and a sharp fall in the size of the fishing fleet over the last decade has led to a recent stabilisation of CPUE.

"However, on current worldwide trends we can expect to see a further one-million vessels on the water by mid-century and the average engine power of the global fleet continues to increase," Mr Rousseau said.

"These changes will further challenge the sustainable use of fisheries resources in coming years.

"This is a particular concern for populations in regions such as Southeast Asia, where a high proportion of people rely on fish for sustenance.

"Our findings suggest that additional management measures are urgently warranted to ensure the future sustainability of global marine resources," Mr Rousseau said.

Researchers from Sweden's Chalmers University of Technology and the University of Gothenburg present a new method which can double the energy of a proton beam produced by laser-based particle accelerators. The breakthrough could lead to more compact, cheaper equipment that could be useful for many applications, including proton therapy.

Proton therapy involves firing a beam of accelerated protons at cancerous tumours, killing them through irradiation. But the equipment needed is so large and expensive that it only exists in a few locations worldwide.

Modern high-powered lasers offer the potential to reduce the equipment's size and cost, since they can accelerate particles over a much shorter distance than traditional accelerators - reducing the distance required from kilometres to metres. The problem is, despite efforts from researchers around the world, laser generated proton beams are currently not energetic enough. But now, the Swedish researchers present a new method which yields a doubling of the energy - a major leap forward.

The standard approach involves firing a laser pulse at a thin metallic foil, with the interaction resulting in a beam of highly charged protons. The new method involves instead first splitting the laser into two less intense pulses, before firing both at the foil from two different angles simultaneously. When the two pulses collide on the foil, the resultant electromagnetic fields heat the foil extremely efficiently. The technique results in higher energy protons whilst using the same initial laser energy as the standard approach.

"This has worked even better than we dared hope. The aim is to reach the energy levels that are actually used in proton therapy today. In the future it might then be possible to build more compact equipment, just a tenth of the current size, so that a normal hospital could be able to offer their patients proton therapy," says Julien Ferri, a researcher at the Department of Physics at Chalmers, and one of the scientists behind the discovery.

The unique advantage of proton therapy is its precision in targeting cancer cells, killing
them without injuring healthy cells or organs close by. The method is therefore crucial for treating deep-seated tumours, located in the brain or spine, for example. The higher energy the proton beam has, the further into the body it can penetrate to fight cancer cells.

Although the researchers' achievement in doubling the energy of the proton beams represents a great breakthrough, the end goal is still a long way off.

"We need to achieve up to 10 times the current energy levels to really target deeper into the body. One of my ambitions is to help more people get access to proton therapy. Maybe that lies 30 years in the future, but every step forward is important," says Tünde Fülöp, Professor at the Department of Physics at Chalmers.

Accelerated protons are not only interesting for cancer treatment. They can be used to investigate and analyse different materials, and to make radioactive material less harmful. They are also important for the space industry. Energetic protons constitute a large part of cosmic radiation, which damages satellites and other space equipment. Producing energetic protons in the lab allows researchers to study how such damage occurs, and to develop new materials which can better withstand the stresses of space travel.

Together with research colleague Evangelos Siminos at the University of Gothenburg, Chalmers researchers Julian Ferri and Tünde Fülöp used numerical simulations to show the feasibility of the method. Their next step is to conduct experiments in collaboration with Lund University.

"We are now looking at several ways to further increase the energy level in the proton beams. Imagine focusing all the sunlight hitting the Earth at a given moment onto a single grain of sand - that would still be less than the intensity of the laser beams that we are working with. The challenge is to deliver even more of the laser energy to the protons." says Tünde Fülöp.

The new scientific results have been published in the respected journal Communications Physics, part of the Nature family. Read the scientific article "Enhanced target normal sheath acceleration using colliding laser pulses".

Athens, Greece - 26 May 2019: Elderly patients with heart failure who see a pharmacist once a week are more likely to take their tablets and be active in daily life, according to late breaking results from the PHARM-CHF randomised controlled trial presented today at Heart Failure 2019, a scientific congress of the European Society of Cardiology (ESC).1

"Adhering to a complex medication regimen is a huge challenge for elderly patients with heart failure," said co-principal investigator Professor Martin Schulz, of the Department of Clinical Pharmacy, Freie Universitaet Berlin, Germany. "It is estimated that 30% to 50% of patients in Europe are nonadherent to heart failure medications, which results in increased frequency and severity of symptoms such as breathlessness, worsening heart failure and consequent hospitalisations, and higher mortality."

Nonadherence includes not collecting a prescription, taking a lower dose or less pills than prescribed, drug holidays (during weekends or holidays, or when feeling better), or completely stopping one or more drugs.

The PHARM-CHF trial investigated whether regularly seeing a pharmacist improves adherence to heart failure medications.2 A total of 237 ambulatory chronic heart failure patients aged 60 years and older were randomly allocated to usual care or a pharmacy intervention and followed-up for a median of two years. The average age was 74 years, 62% were male, and the median number of different drugs was nine.

The intervention started with a medication review. Patients brought their drugs to a pharmacist who made a medication plan, checked for drug interactions and double medications, and contacted the physician about any risks. Patients then visited the pharmacy every 8-10 days to discuss adherence and symptoms, and have blood pressure and pulse rate measurements. Drugs were provided in a pillbox with compartments for morning, noon, evening, and night on each day. The pharmacist updated the medication plan if needed and contacted the doctor with new drug-related problems or significant changes in vital signs.

The primary efficacy endpoint was the proportion of days three heart failure medications were collected (using pharmacy claims data) in the year after randomisation. The drugs were beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and mineralocorticoid receptor antagonists. Compared to usual care, the intervention resulted in a significant 5.7% absolute increase in collection.

The researchers also calculated the proportion of patients who collected the three drugs at least 80% of the days under study (defined as adherent) compared to baseline.3 The proportion of adherent patients increased from 44% to 86% in the pharmacy group and from 42% to 68% in the usual care group - a significant 18%-points difference between groups. Patients in the pharmacy group were three times more likely to become adherent compared to the usual care group. Six patients would need to receive the intervention to achieve at least 80% adherence in one patient.

There was no difference between groups in the primary composite safety endpoint of days lost in the year following randomisation due to unplanned cardiovascular hospitalisations or all-cause death.

Improvement in quality of life was more pronounced in the pharmacy group after one year and significantly better compared to the usual care group after two years. This meant patients in the pharmacy group were less limited in their daily activities and less worried about their disease.

Professor Schulz, who is also director of the Department of Medicine at ABDA - Federal Union of German Associations of Pharmacists, said patients would need to see the pharmacist every week lifelong for the benefits to continue: "The key point is that pharmacy visits need to be used as an opportunity to provide structured care."

Co-principal investigator Professor Ulrich Laufs, director of the Department of Cardiology, Leipzig University, Germany, said: "Cardiologists and general practitioners would welcome this type of intervention since it does not change the medication that is prescribed but helps patients to follow the treatment strategy."

Concentrations of antibiotics found in some of the world's rivers exceed 'safe' levels by up to 300 times, the first ever global study has discovered.

Researchers looked for 14 commonly used antibiotics in rivers in 72 countries across six continents and found antibiotics at 65% of the sites monitored.

Metronidazole, which is used to treat bacterial infections including skin and mouth infections, exceeded safe levels by the biggest margin, with concentrations at one site in Bangladesh 300 times greater than the 'safe' level.

In the River Thames and one of its tributaries in London, the researchers detected a maximum total antibiotic concentration of 233 nanograms per litre (ng/l), whereas in Bangladesh the concentration was 170 times higher.

The most prevalent antibiotic was trimethoprim, which was detected at 307 of the 711 sites tested and is primarily used to treat urinary tract infections.

The research team compared the monitoring data with 'safe' levels recently established by the AMR Industry Alliance which, depending on the antibiotic, range from 20-32,000 ng/l.

Ciproflaxacin, which is used to treat a number of bacterial infections, was the compound that most frequently exceeded safe levels, surpassing the safety threshold in 51 places.

The team said that the 'safe' limits were most frequently exceeded in Asia and Africa, but sites in Europe, North America and South America also had levels of concern showing that antibiotic contamination was a "global problem."

Sites where antibiotics exceeded 'safe' levels by the greatest degree were in Bangladesh, Kenya, Ghana, Pakistan and Nigeria, while a site in Austria was ranked the highest of the European sites monitored.

The study revealed that high-risk sites were typically adjacent to wastewater treatment systems, waste or sewage dumps and in some areas of political turmoil, including the Israeli and Palestinian border.

The project, which was led by the University of York, was a huge logistical challenge - with 92 sampling kits flown out to partners across the world who were asked to take samples from locations along their local river system.

Samples were then frozen and couriered back to the University of York for testing. Some of the world's most iconic rivers were sampled, including the Chao Phraya, Danube, Mekong, Seine, Thames, Tiber and Tigris.

Dr John Wilkinson, from the Department of Environment and Geography, who co-ordinated the monitoring work said no other study had been done on this scale.

He said: "Until now, the majority of environmental monitoring work for antibiotics has been done in Europe, N. America and China. Often on only a handful of antibiotics. We know very little about the scale of problem globally.

"Our study helps fill this key knowledge gap with data being generated for countries that had never been monitored before.”

Professor Alistair Boxall, Theme Leader of the York Environmental Sustainability Institute, said: "The results are quite eye opening and worrying, demonstrating the widespread contamination of river systems around the world with antibiotic compounds.

"Many scientists and policy makers now recognise the role of the natural environment in the antimicrobial resistance problem. Our data show that antibiotic contamination of rivers could be an important contributor."

"Solving the problem is going to be a mammoth challenge and will need investment in infrastructure for waste and wastewater treatment, tighter regulation and the cleaning up of already contaminated sites."

The finds are due to be unveiled during two presentations at the annual meeting of the Society of Environmental Toxicology and Chemistry (SETAC) in Helsinki on 27 and 28 May.

Athens, Greece - 26 May 2019: Heart failure patients who consume more dietary fibre tend to have healthier gut bacteria, which is associated with reduced risk of death or need of a heart transplant. The fibre study was presented today at Heart Failure 2019, a scientific congress of the European Society of Cardiology (ESC).1

"Our gut microbiota is composed of trillions of microorganisms that have the potential to affect our health," said study author Dr Cristiane Mayerhofer, of Oslo University Hospital, Norway. "Previous research has reported reduced biodiversity of microbes in the gut of patients with heart failure patients. Today we show for the first time that this is related to low fibre intake."

The study also linked meat intake to higher levels of trimethylamine-N-oxide (TMAO) in patients with heart failure. Prior research has shown that increased TMAO levels are associated with a greater risk of cardiovascular events, and that gut microbes play a role in its formation.

"We show an important pathway that connects diet, microbial activity, and cardiovascular disease," said Dr Mayerhofer. "It would be prudent for patients with heart failure to limit their meat intake to two to three times a week."

To conduct the study, the investigators recruited 84 well-treated patients with chronic heart failure and 266 healthy people. The composition of gut microbes was assessed by sequencing the bacterial 16S rRNA gene in stool samples and compared between the two groups.

Heart failure patients had lower biodiversity of intestinal microbes than healthy controls, with differences in the two main phyla of bacteria present in the human gut. Patients with heart failure had a lower ratio of Firmicutes/Bacteroidetes (F/B) compared to controls, and this difference was even more pronounced when the cause of heart failure was non-ischaemic

Dietary and outcome analyses were performed in heart failure patients. Patients who had a heart transplant or died had lower biodiversity and a lower F/B ratio than controls. Regarding diet, bacterial diversity and Firmicutes levels were positively associated with fibre intake.

"Our findings suggest that the altered microbiota composition found in patients with chronic heart failure might be connected to low fibre intake," said Dr Mayerhofer. "If these findings are confirmed in future studies, my advice will be to choose foods high in fibre such as cereals, fruits and vegetables to stimulate a healthy gut flora."

"We are still just in the beginning of mapping and understanding the microbiota, how it works, and its potential for the clinical setting," noted Dr Mayerhofer.

She is currently involved with GutHeart, the first randomised controlled trial on the effect of a probiotic and an antibiotic on the composition of gut bacteria, heart function, and inflammation in patients with heart failure.2 "The trial will show the potential clinical effects of modulating our gut bugs in the setting of heart failure," she said.

Athens, Greece - 26 May 2019: Less than 10% of heart failure patients comply with advice on salt and fluid restrictions, daily weighing, and physical activity, reports a study presented today at Heart Failure 2019, a scientific congress of the European Society of Cardiology (ESC).1

"Loneliness is the most important predictor of whether patients adopt the advice or not," said senior author Professor Beata Jankowska-Polaska, of Wroclaw Medical University, Poland. "Patients who are alone do worse in all areas. Family members have a central role in helping patients comply, particularly older patients, by providing emotional support, practical assistance, and advice."

Failure to adhere to lifestyle recommendations or regularly take medications contributes to worsening heart failure symptoms and a raised risk of hospitalisation. Breathlessness, swollen ankles and legs, and tiredness occur because the heart can no longer pump effectively. Fluid backs up in the lungs and is retained in parts of the body, and the muscles receive insufficient blood and oxygen.

Daily weighing flags up worsening fluid retention, while salt and fluid restrictions help keep fluid retention under control. Physical activity improves energy levels and quality of life. This study examined adherence to these four recommendations in 475 patients with chronic heart failure using the Revised Heart Failure Compliance Scale.

Following the recommendations was defined as "every day" or "three times a week" for weighing and "most of the time" or "all the time" for salt, fluid, and exercise. Just 7% of patients followed all four non-drug recommendations. Compliance with medication and regular check-ups was higher, at 58%.

Nearly 48% did no physical activity, and 19% very rarely exercised. Some 25% and 17% never or very rarely adhered to fluid restrictions, respectively. While 13% never and 22% very rarely restricted salt intake. More than half of patients (54%) weighed themselves less than once a week, and 17% did it once a week.

"It is worrying that fewer than one in ten patients observed all of the lifestyle advice," said Professor Jankowska-Pola?ska. "We also found that women were less compliant than men, and patients over 65 had poorer scores than younger patients."

Multivariate analysis showed that loneliness, higher number of comorbidities, and more physically limiting heart failure were independent predictors of non-compliance to the four recommendations.

Study author Natalia ?wi?toniowska said: "Patients with comorbid conditions may find it difficult to understand and follow all of the medical advice. For example those with heart failure and kidney disease have more than ten pills to take and some guidance may appear to be conflicting."

Doctors and nurses need to encourage better self-care in their patients with heart failure, said Professor Jankowska-Pola?ska. "Patients need clear written instructions on how to exercise for example, while text messages or phone calls can be used as reminders. It's important to check that patients understand the advice, tailor the recommendations, and assess adherence at every visit," she said.

Patients with heart failure can lead a normal social life, noted Ms ?wi?toniowska, provided friends and family accept their dietary restrictions. "It can be difficult for patients with heart failure to stick to the lifestyle advice. Family members in particular have a big influence and it's a good idea to involve them with meal preparation, physical activity, and reminders to check weight."

About one in five Canadian adolescents uses cannabis (19% of Canadians aged 15-19), and its recent legalization across the country warrants investigation into the consequence of this use on the developing brain. Adolescence is associated with the maturation of cognitive functions, such as working memory, decision-making, and impulsivity control. This is a highly vulnerable period for the development of the brain as it represents a critical period wherein regulatory connection between higher-order regions of the cortex and emotional processing circuits deeper inside the brain are established. It is a period of strong remodeling, making adolescents highly vulnerable to drug-related developmental disturbances. Research presented by Canadian neuroscientists Patricia Conrod, Steven Laviolette, Iris Balodis and Jibran Khokhar at the 2019 Canadian Neuroscience Meeting in Toronto on May 25 featured recent discoveries on the effects of cannabis on the adolescent brain.

Dr. Patricia Conrod, at Université de Montréal, studied the year-to-year changes in alcohol and cannabis use and cognitive function in a sample of adolescents consisting of 5% of all students entering high school in 2012 and 2013 in the Greater Montreal region (a total of 3,826 7th grade students). Students were assessed annually for 4 years on alcohol and cannabis use, and their cognitive function was evaluated using computarized cognitive tests. The researchers found substance use to be linked to low cognitive functioning, a finding that could be indicative of an underlying common vulnerability. Cannabis use was linked to impairments in working memory and inhibitory control, which is required for self-control. Cannabis use was also linked to deficits in memory recall and perceptual reasoning. Alcohol use was not linked to impairments in these cognitive functions, suggesting cannabis could have more long-term effects than alcohol.

More recently Dr. Conrod's team analysed the sex difference in cannabis response in the same sample of adolescents. Preliminary data indicates that cannabis use had a stronger effect on the memory functions of male students than female students. Both sexes were however, equally affected by cannabis on inhibitory control. These results help identify at-risk youth groups and target them for early intervention and information.

Dr. Steven Laviolette presented research on the effect the primary psychoactive component of cannabis, delta-9-tetrahydrocannabinol or THC, on the adolescent brain, in rodent animal models. His team demonstrated that adolescent exposure to THC induces changes in specific a region of the brain called the prefrontal cortex (PFC) and in a brain circuit, the mesolimbic pathway, that closely resemble the abnormalities observed in schizophrenia. Furthermore, adolescent THC exposure also caused affective and cognitive abnormalities including deficits in social interactions, memory processing and anxiety regulation.

Interestingly, Dr. Laviolette's team found that administration of drugs that restore normal PFC function in early adulthood could reverse the effects of adolescent THC exposure. They also demonstrated that co-administering THC with drugs that prevent the THC-induced disruption in brain signaling pathways prevented the development of schizophrenia-like effects. These results offer insights into ways to prevent or reverse THC-induced brain signaling defects in adolescents.

Dr. Iris Balodis, from McMaster University, investigates the mechanisms that motivate individuals to act and make decisions that can go against a person's best interest, as seen in people suffering from addiction. To compare decision-making in individuals suffering from cannabis addiction (also called cannabis use disorder) to healthy controls, Dr. Balodis used an effort-based decision-making test, which explores how much effort and individual is willing to make to receive a given reward. Participants are given a choice between an easy task or a hard task in which they can gain varying amounts of money (for example, pressing a lever a number within a certain time limit). During the administration of this test, Dr. Balodis and her team looked at differences in activity in different brain regions by functional magnetic resonance imaging. Initial findings suggest that there are differences in encoding the value of the reward (money received) and of the effort cost (amount of work done) in individuals addicted to cannabis relative to healthy controls. These were revealed by differences in activation of specific brain regions known to be important for motivation. This information could be key to finding cannabis addiction vulnerability factors.

Adolescent cannabis use is associated with behavioral changes related to reward and motivation in humans. Paradoxically, this use has both been suggested to increase motivation for other drug use (the gateway hypothesis) and a potential "amotivation syndrome" in which individuals are less willing to expend effort to receive a reward. It is not known whether adolescent cannabis use causes either of these responses, or if cannabis use is rather a symptom of a pre-existing state that results in these behaviours. In order to better understand the long-term effects of adolescent cannabis exposure on the brain, Dr. Jibran Khokhar, from the University of Guelph, studied the effect of THC exposure in adolescent rats on their adult behaviour. In this study, adolescent THC exposure differentially impacted instrumental (decreased lever pressing) and Pavlovian learning (increased sign-tracking). These rats also showed differences in other reward-related behaviors. These behavioural changes were accompanied by changes in the connection between different regions of the brain, including those involved in encoding reward and motivation. These results suggest adolescent cannabis exposure in rats can produce long-lasting changes in brain circuitry which might contribute to the behavioral changes observed after cannabis exposure.

Taken together, the research results presented in this symposium help decipher the links between cannabis use and long-lasting changes in the brain, which underlie changes in behaviour in adolescent humans, and in studies reverse-translating these findings to animal models. Research in humans shows that adolescent cannabis use is widespread, and associated with defects in working memory, self-control and motivation. Similar results were obtained in animal studies, through which researchers were also able to test therapies that can reverse the effects of adolescent cannabis use in adulthood. These findings provide keys to prevent and treat the long term effect of adolescent cannabis use.

Crabs from a single species rely on different camouflage techniques depending on what habitat they live in, new research shows.

University of Exeter scientists compared the colour patterns of common shore crabs (Carcinus maenas) from rock pools with those living on mudflats.

They found that crabs from mudflats closely matched the appearance of the mud they live on, while rockpool crabs did not match the background but instead relied on "disruptive colouration" - the use of high-contrast patterns to break up the appearance of the body outline.

Shore crabs are the most common crab found on Britain's coasts, familiar to anyone who goes rock pooling, and the crabs examined in this study came from six sites in Cornwall.

"The crabs are highly variable in colour and pattern, and are often extremely difficult to see," said Professor Martin Stevens, of the Centre for Ecology and Conservation on the University of Exeter's Penryn Campus in Cornwall.

"We used image analysis simulating predator (bird and fish) vision to test how shore crabs camouflage themselves.

"As we predicted, rock pool individuals had significantly higher levels of disruption, and this seems an effective way to disguise the body's outline in the complex rock pool backgrounds where matching the colour of the environment is often not possible.

"In contrast, mudflat crabs closely matched the mud in terms of colour, brightness and pattern but lacked high-contrast disruptive markings that might give them away in the uniform mudflat environment."

While a great deal of work has investigated the use of disruptive and background matching camouflage, most of this has been undertaken in artificial systems. The work here tests the different use of camouflage types by real animals in different habitats.

"Shore crabs are often assumed to be dull and green, but in fact they can be extremely colourful and every individual can look completely different. Our study goes part of the way to explaining why shore crabs are so diverse," said Professor Stevens.

The paper, published in the journal Scientific Reports, is entitled: "Background matching and disruptive coloration as habitat-specific strategies for camouflage."

A technique to stabilise alkali metal vapour density using gold nanoparticles, so electrons can be accessed for applications including quantum computing, atom cooling and precision measurements, has been patented by scientists at the University of Bath.

Alkali metal vapours, including lithium, sodium, potassium, rubidium and caesium, allow scientists to access individual electrons, due to the presence of a single electron in the outer 'shell' of alkali metals.

This has great potential for a range of applications, including logic operations, storage and sensing in quantum computing, as well as in ultra-precise time measurements with atomic clocks, or in medical diagnostics including cardiograms and encephalograms.

However, a serious technical obstacle has been reliably controlling the pressure of the vapour within an enclosed space, for instance the tube of an optical fibre. The vapour needs to be prevented from sticking to the sides in order to retain its quantum properties, but existing methods to do this, including directly heating vapour containers are slow, costly, and impractical at scale.

Scientists from the University of Bath, working with a colleague at the Bulgarian Academy of Sciences, have devised an ingenious method of controlling the vapour by coating the interior of containers with nanoscopic gold particles 300,000 times smaller than a pinhead.

When illuminated with green laser light the nanoparticles rapidly absorb and convert the light into heat, warming the vapour and causing it to disperse into the container more than 1,000 times quicker than with other methods. The process is highly reproducible and, in addition, the new nanoparticle coating was found to preserve the quantum states of alkali metal atoms that bounce from it.

The study is published in Nature Communications.

Professor Ventsislav Valev, from the University of Bath's Department of Physics led the research. He said: "We are very excited by this discovery because it has so many applications in current and future technologies! It would be useful in atomic cooling, in atomic clocks, in magnetometry and in ultra-high-resolution spectroscopy."

"Our coating allows fast and reproducible external control of the vapour density and related optical depth, crucial for quantum optics in these confined geometries."

Assoc. Prof Dimitar Slavov, from the Institute of Electronics in the Bulgarian Academy of Sciences, added "In this proof of principle, it was demonstrated that illuminating our coating significantly outperforms conventional methods and is compatible with standard polymer coatings used to preserve quantum states of single atoms and coherent ensembles."

Dr Kristina Rusimova, a prize fellow in the Department of Physics, added: "Further improvements of our coating are possible by tuning particle size, material composition and polymer environment. The coating can find applications in various containers, including optical cells, magneto-optical traps, micro cells, capillaries and hollow-core optical fibres."