Culture

Individual pastures on livestock farms yield surprisingly dissimilar benefits to a farm's overall agricultural income, and those differences are most likely attributable to the varying levels of "soil health" provided by its grazing livestock, reveals a study published today.

The study, produced by an interdisciplinary team of 13 scientists and two PhD students from Rothamsted Research, evaluates how efficiently nutrients are used on a livestock farm, on a field-by-field basis for the first time, and links soil health to animal growth.

The team has developed a method to derive the contribution of individual fields to an animal's growth and, in the process, has opened up the possibility of using field-scale metrics as indicators of animal performance and agricultural productivity. The findings appear in the journal Animal.

"The prospect that commercial livestock producers could improve their productivity by purely changing rotational patterns is exciting," says Taro Takahashi, an agricultural economist at Rothamsted's North Wyke Farm Platform (NWFP) in Devon, who led the study.

"Unlike many alternative technologies, this will not require any capital investment," adds Takahashi, who is also Senior Lecturer in Sustainable Livestock Systems and Food Security at the Bristol Veterinary School of the University of Bristol.

The majority of livestock farms in the UK operate rotational grazing, which involves moving animals from one field to another. While this practice supplies more fresh forage to animals throughout the season, it makes farming systems more difficult to monitor and optimise.

The problem has been the difficulty of linking an animal's performance to field measurements, such as soil health, because animals spend only a fraction of time in each field, which is also used to produce silage for winter. Under such complexity, collating required information manually was almost infeasible. The latest method provides a shortcut.

The NWFP team found that animal performance on individual fields was positively associated with the level of soil organic carbon, a common measure of "soil health" for sustainable farming. The team also discovered that fields grazed more intensively had healthier soils and were less prone to water and nutrient losses.

"Without our unique experimental design to separate hydrological flows from individual grazing fields, you couldn't accurately quantify any nutrients being lost as the majority would be dissolved in water," notes Paul Harris, one of the study's authors and the Principal Investigator at North Wyke, which consists of three instrumented farms over 63 hectares.

With the UK preparing to leave the EU, the new study comes as Rothamsted increases its efforts to contribute to the creation of a well-designed food supply chain, both through enhanced ecosystem services and reduced environmental impacts.

"The correlation between soil health and animal performance is a major finding that confirms the huge amount of anecdotal evidence linking soil parameters and liveweight gain," says Michael Lee, Head of the Department of Sustainable Agriculture Sciences at North Wyke.

"This study illustrates the multifaceted interactions between soil health, ecological surroundings and grazing animals that are so often overlooked in favour of more simplistic narratives," adds Lee, who is also Professor of Sustainable Livestock Systems at Bristol Veterinary School.

BUFFALO, N.Y. -- Each year, farmers in the U.S. purchase tens of millions of pounds of antibiotics that are approved for use in cows, pigs, fowl and other livestock.

When farmers repurpose the animals' manure as fertilizer or bedding, traces of the medicines leach into the environment, raising concerns that agriculture may be contributing to the rise of antibiotic-resistant bacteria.

New research holds troublesome insights with regard to the scope of this problem.

According to a pair of new studies led by Diana Aga, PhD, Henry M. Woodburn Professor of Chemistry in the University at Buffalo College of Arts and Sciences, two of the most elite waste treatment systems available today on farms do not fully remove antibiotics from manure.

Both technologies -- advanced anaerobic digestion and reverse osmosis filtration -- leave behind concerning levels of antibiotic residues, which can include both the drugs themselves and molecules that the drugs break down into.

In addition, the study uncovered new findings about solid excrement, which is often filtered out from raw, wet manure before the treatment technologies are implemented.

Researchers found that this solid matter may contain higher concentrations of antibiotics than unprocessed manure, a discovery that is particularly disturbing because this material is often released into the environment when it's used as animal bedding or sold as fertilizer.

"We were hoping that these advanced treatment technologies could remove antibiotics. As it turns out, they were not as effective as we thought they could be," Aga says.

She does offer some hope, however: "On the positive side, I think that a multistep process that also includes composting at the end of the system could significantly reduce the levels of antibiotics. Our earlier studies on poultry litter demonstrated that up to 70 percent reduction in antibiotics called ionophores can be achieved after 150 days of composting. Testing this hypothesis on dairy farm manure is the next phase of our project, and we are seeing some positive results."

The research on reverse osmosis filtration was published online in January in the journal Chemosphere. The study on advanced anaerobic digestion -- a collaboration between UB and Virginia Tech -- appeared online in March in the journal Environmental Pollution.

Waste treatment systems are not designed to remove antibiotics

According to the U.S. Food and Drug Administration, more than 30 million pounds of antibiotics approved for use in food-producing livestock were sold or distributed in the United States in 2016. And these are just a fraction of the total antibiotics used annually around the world in humans and animals.

Though the new research focuses on dairy farms, the findings point to a larger problem.

"Neither of the treatment systems we studied was designed to remove antibiotics from waste as the primary goal," Aga says. "Advanced anaerobic digestion is used to reduce odors and produce biogas, and reverse osmosis is used to recycle water. They were not meant to address removal of antibiotic compounds.

"This problem is not limited to agriculture: Waste treatment systems today, including those designed to handle municipal wastewater, hospital wastes and even waste from antibiotic manufacturing industries, do not have treatment of antibiotics in mind. This is an extremely important global issue because the rise of antibiotic resistance in the environment is unprecedented. We need to start thinking about this if we want to prevent the continued spread of resistance in the environment."

Aga is a proponent of the "One Health" approach to fighting antimicrobial resistance, which encourages experts working in hospitals, agriculture and other sectors related to both human and animal health to work together, as humans and animals are often treated with the same or similar antibiotics.

Aga was an invited presenter at an international forum last week on the latest research about antimicrobial resistance. The event, in Vancouver, Canada, was co-chaired by representatives of the UK Science and Innovation Network, Wellcome Trust and U.S. Centers for Disease Control and Prevention.

Poop has different parts -- and all need to be treated

To conduct the research, scientists visited two dairy farms in Upstate New York.

Both facilities extract much of the solid matter from cow manure before subjecting the remaining sludge to high-tech waste management techniques. To process the remaining goop, one farm uses advanced anaerobic digestion, which employs microorganisms and pasteurization to break down and convert organic matter into products that include biogas, while the other farm uses reverse osmosis, which passes the slurry through a series of membranes to purify water.

Both technologies reduced antibiotic residues in liquid manure, but did little to cut down levels in the remaining solid matter. This is particularly worrisome as the research also revealed that antibiotic compounds tend to migrate from the liquid parts of the manure into the solids during treatment, making it arguably more important to treat than the latter.

The concern over solid excrement is heightened by the fact that the treatment techniques are implemented only after most solids are already separated from the raw manure, meaning that the bulk of the solid matter may go untreated.

Some key findings from each study:

The research on advanced anaerobic digestion examined a popular class of antibiotics called tetracyclines, finding that these drugs and their breakdown products migrated from the fluid part of the sludge into the solid part during treatment. At the end of the process, the solids contained higher levels of tetracycline antibiotics than the original raw manure. The study also found that both the liquid and solid parts of the sludge contained genes that confer resistance to these antibiotics.

The study on reverse osmosis looked at how well this water purification technique removed synthetic antimicrobials called ionophores, which are used to promote growth in dairy cows and to treat coccidiosis, a costly, parasitic disease in the cattle industry that affects mostly young calves. The research found that reverse osmosis effectively filtered ionophores from the liquid portion of manure. However, low levels of the drugs persisted in "purified" water after treatment due to the deterioration of membranes used in the filtration process. Also, solid matter extracted from the water during reverse osmosis still harbored high levels of ionophores. Finally, the study found that prior to treatment, many of the ionophores appear to have already migrated into the solid part of the raw manure that is removed before the reverse osmosis even begins.

"Both of the systems we studied are a good first step in reducing the spread of antibiotics and potentially reduce resistance in the environment, but our study shows that more must be done," Aga says. "We need to look at different waste management practices that, maybe in combination, could reduce the spread of antibiotic compounds and resistance in the environment."

Aga points to composting as one area to explore. Her team is studying how advanced anaerobic digestion can be used in conjunction with composting of solid materials to remove antibiotics and their breakdown products from manure. The preliminary results of the research, not yet published, are promising, Aga says.

Things are getting real for researchers in the UC Santa Barbara John Martinis/Google group. They are making good on their intentions to declare supremacy in a tight global race to build the first quantum machine to outperform the world's best classical supercomputers.

But what is quantum supremacy in a field where horizons are being widened on a regular basis, in which teams of the brightest quantum computing minds in the world routinely up the ante on the number and type of quantum bits ("qubits") they can build, each with their own range of qualities?

"Let's define that, because it's kind of vague," said Google researcher Charles Neill. Simply put, he continued, "we would like to perform an algorithm or computation that couldn't be done otherwise. That's what we actually mean."

Neill is lead author of the group's new paper, "A blueprint for demonstrating quantum supremacy with superconducting qubits," now published in the journal Science.

Fortunately, nature offers up many such complex situations, in which the variables are so numerous and interdependent that classical computers can't hold all the values and perform the operations. Think chemical reactions, fluid interactions, even quantum phase changes in solids and a host of other problems that have daunted researchers in the past. Something on the order of at least 49 qubits -- roughly equivalent to a petabyte (one million gigabytes) of classical random access memory -- could put a quantum computer on equal footing with the world's supercomputers. Just recently, Neill's Google/Martinis colleagues announced an effort toward quantum supremacy with a 72-qubit chip possessing a "bristlecone" architecture that has yet to be put through its paces.

But according to Neill, it's more than the number of qubits on hand.

"You have to generate some sort of evolution in the system which leads you to use every state that has a name associated with it," he said. The power of quantum computing lies in, among other things, the superpositioning of states. In classical computers, each bit can exist in one of two states -- zero or one, off or on, true or false -- but qubits can exist in a third state that is a superposition of both zero and one, raising exponentially the number of possible states a quantum system can explore.

Additionally, say the researchers, fidelity is important, because massive processing power is not worth much if it's not accurate. Decoherence is a major challenge for anyone building a quantum computer -- perturb the system, the information changes. Wait a few hundredths of a second too long, the information changes again.

"People might build 50 qubit systems, but you have to ask how well it computed what you wanted it to compute," Neill said. "That's a critical question. It's the hardest part of the field." Experiments with their superconducting qubits have demonstrated an error rate of one percent per qubit with three- and nine-qubit systems, which, they say, can be reduced as they scale up, via improvements in hardware, calibration, materials, architecture and machine learning.

Building a qubit system complete with error correction components -- the researchers estimate a range of 100,000 to a million qubits -- is doable and part of the plan. And still years away. But that doesn't mean their system isn't already capable of doing some heavy lifting. Just recently it was deployed, with spectroscopy, on the issue of many-body localization in a quantum phase change -- a quantum computer solving a quantum statistical mechanics problem. In that experiment, the nine-qubit system became a quantum simulator, using photons bouncing around in their array to map the evolution of electrons in a system of increasing, yet highly controlled, disorder.

"A good reason why our fidelity was so high is because we're able to reach complex states in very little time," Neill explained. The more quickly a system can explore all possible states, the better the prediction of how a system will evolve, he said.

If all goes smoothly, the world should be seeing a practicable UCSB/Google quantum computer soon. The researchers are eager to put it through its paces, gaining answers to questions that were once accessible only through theory, extrapolation and highly educated guessing -- and opening up a whole new level of experiments and research.

"It's definitely very exciting," said Google researcher Pedram Roushan, who led the many-body quantum simulation work published in Science in 2017. They expect their early work to stay close to home, such as research in condensed matter physics and quantum statistical mechanics, but they plan to branch out to other areas, including chemistry and materials, as the technology becomes more refined and accessible.

"For instance, knowing whether or not a molecule would form a bond or react in some other way with another molecule for some new technology... there are some important problems that you can't roughly estimate; they really depend on details and very strong computational power," Roushan said, hinting that a few years down the line they may be able to provide wider access to this computing power. "So you can get an account, log in and explore the quantum world."

In 2013, the Nobel Prize in Physiology or Medicine was awarded to three scientists for their contributions to uncovering the mechanisms governing vesicle transport in cells. Their explanations provided both a conceptual and a mechanistic understanding of basic processes at the most fundamental level.

At the heart of this Nobel Prize-winning intracellular process lies SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptors), a superfamily of 60 proteins in mammalian cells that transport lipids and membrane proteins across the cells by facilitating the fusion of vesicles to their target membranes.

Biologists at UC Santa Barbara have now discovered a surprising, additional function for syntaxin 3S, a soluble form of a SNARE protein. The researchers found a new signaling pathway widely used by human and other mammalian cells. The team's results appear in the Journal of Biological Chemistry.

"What we found was very unorthodox and hadn't been known before," explained corresponding author Thomas Weimbs, a professor in UCSB's Department of Molecular, Cellular, and Developmental Biology. "Syntaxin 3S binds to transcription factors -- proteins involved in converting DNA into RNA -- and regulates the expression of the genes controlled by those factors. In fact, our initial results suggest that these genes play a role in cancer progression, but that remains to be definitively proved."

In a scientific first, the UCSB researchers showed that besides the well-established role of syntaxin 3 in membrane fusion, its novel soluble version is transported to the cell's nucleus and carries out a completely different function. In nature, many proteins have more than one function -- a phenomenon known as protein moonlighting.

That syntaxins -- and SNARE proteins in general -- are capable of moonlighting was unknown until now. Given that syntaxins are present in all cells and responsible for a large number of essential cell functions, the discovery that these proteins can carry out additional functions suggests that much more is yet to be discovered.

"Finding that syntaxin 3S functions as a nuclear regulator is the beginning of a story that opens up a new field of research," Weimbs said. "It's like a field of snow with no footsteps on it because nobody has done research on this, so we can pick and choose the most exciting directions to follow."

Weimbs and his colleagues identified similar nuclear-targeted soluble forms of other syntaxins, which indicates that this signaling pathway is a conserved, novel function common among these membrane-trafficking proteins.

In the future, the UCSB biologists would like to delineate how far-reaching the functions of these new soluble syntaxin versions are. Are there other unidentified forms of syntaxin that bind to similar nuclear import factors? Do they bind to different or similar transcription factors? Do they regulate different genes?

Researchers at the University of Washington have designed a convenient and natural product that uses proteins to rebuild tooth enamel and treat dental cavities.

The research finding was first published in ACS Biomaterials Science and Engineering.

"Remineralization guided by peptides is a healthy alternative to current dental health care," said lead author Mehmet Sarikaya, professor of materials science and engineering and adjunct professor in the Department of Chemical Engineering and Department of Oral Health Sciences.

The new biogenic dental products can -- in theory -- rebuild teeth and cure cavities without today's costly and uncomfortable treatments.

"Peptide-enabled formulations will be simple and would be implemented in over-the-counter or clinical products," Sarikaya said.

Cavities are more than just a nuisance. According to the World Health Organization, dental cavities affect nearly every age group and they are accompanied by serious health concerns. Additionally, direct and indirect costs of treating dental cavities and related diseases have been a huge economic burden for individuals and health care systems.

"Bacteria metabolize sugar and other fermentable carbohydrates in oral environments and acid, as a by-product, will demineralize the dental enamel," said co-author Sami Dogan, associate professor in the Department of Restorative Dentistry at the UW School of Dentistry.

Although tooth decay is relatively harmless in its earliest stages, once the cavity progresses through the tooth's enamel, serious health concerns arise. If left untreated, tooth decay can lead to tooth loss. This can present adverse consequences on the remaining teeth and supporting tissues and on the patient's general health, including life-threating conditions.

Good oral hygiene is the best prevention, and over the past half-century, brushing and flossing have reduced significantly the impact of cavities for many Americans. Still, some socio-economic groups suffer disproportionately from this disease, the researchers said. And, according to recent reports from the Centers for Disease Control and Prevention, the prevalence of dental cavities in Americans is again on the rise, suggesting a regression in the progress of combating this disease.

Taking inspiration from the body's own natural tooth-forming proteins, the UW team has come up with a way to repair the tooth enamel. The researchers accomplished this by capturing the essence of amelogenin -- a protein crucial to forming the hard crown enamel -- to design amelogenin-derived peptides that biomineralize and are the key active ingredient in the new technology. The bioinspired repair process restores the mineral structure found in native tooth enamel.

"These peptides are proven to bind onto tooth surfaces and recruit calcium and phosphate ions," said Deniz Yucesoy, a co-author and a doctoral student at the UW.

The peptide-enabled technology allows the deposition of 10 to 50 micrometers of new enamel on the teeth after each use. Once fully developed, the technology can be used in both private and public health settings, in biomimetic toothpaste, gels, solutions and composites as a safe alternative to existing dental procedures and treatments. The technology enables people to rebuild and strengthen tooth enamel on a daily basis as part of a preventive dental care routine. It is expected to be safe for use by adults and children.

UCLA biochemists have achieved a first in biology: viewing at near-atomic detail the smallest protein ever seen by the technique whose development won its creators the 2017 Nobel Prize in chemistry. That technique, called cryo-electron microscopy, enables scientists to see large biomolecules, such as viruses, in extraordinary detail.

Until now, this method has not worked with the thousands of much smaller proteins, which can cause diseases if defective, that are inside cells. A team led by Todd Yeates, a UCLA professor of chemistry and biochemistry, reports results that hold the promise of using cryo-electron microscopy to better understand many important proteins. The research is published in the journal Proceedings of the National Academy of Sciences.

"This new method should be useful broadly," said Yeates, who is a member of the Institute for Genomics and Proteomics and the California NanoSystems Institute at UCLA.

Yeates' research team published the first research, in 2001, in the scientific field of designing molecular cages built from protein molecules. In the new research, his team used "protein engineering" to attach 12 copies of a small protein to a cube-shaped molecular cage, which was designed by a former graduate student of Yeates'. The small protein, called a DARPin, is too small to analyze using cryo-electron microscopy alone. But when the researchers attached the copies to the protein cage, they succeeded in seeing the DARPin with cryo-electron microscopy.

A challenge the researchers overcame was getting the copies of the protein to attach in a rigid manner. Their new method, which Yeates calls "scaffolding," can be modified easily to bind to many different proteins as a "universal protein scaffold."

"The small protein we attached can itself be made to bind to other proteins, which can then be studied by cryo-electron microscopy," said Yeates, whose research team is currently working on doing this.

The development of cryo-electron microscopy earned Jacques Dubochet, Joachim Frank and Richard Henderson the 2017 Nobel Prize in Chemistry.

Why is it so important to see a protein in such detail?

"The last 50 years of structural biology has been about trying to get detailed pictures of all the parts of the cell to understand them thoroughly," Yeates said. "A picture is worth 1,000 words, and very often, getting a first three-dimensional view of a component of the cell gives you valuable insight -- often surprising and unexpected -- that you could not anticipate. When you see it, you frequently think, now I see how it does what it does."

Many diseases are due to a mutation or defect in a protein. Seeing the defect can provide an understanding of what causes diseases, which can lead to new pharmaceuticals and treatments for diseases.

About a year and a half ago, a 6-year-old boy arrived at Children's Emergency Department after accidently removing his own gastrointestinal feeding tube. He wasn't a stranger to Children's National Health System: This young patient had spent plenty of time at the hospital since birth. Diagnosed in infancy with an intestinal pseudo-obstruction, a rare condition in which his bowels acted as if there were a blockage even though one was not present, parts of his intestine died and had been removed through multiple surgeries.

Because of this issue and associated health problems, at 4 years old he had a central line placed in a large vein that leads to his heart. That replaced other central lines placed in his neck earlier after those repeatedly broke. This latest central line in his chest als0 had frequent breaks. It also had become infected with multidrug-resistant Klebsiella bacteria two years before he was treated at Children's National for inadvertently removing his feeding tube.

On that day, he seemed otherwise well. His exam was relatively unremarkable, except for a small leak in his central line and a slight fever. Those findings triggered cultures taken both from blood flowing through his central line and the surrounding skin.

"No one expected him to grow anything from these cultures, especially from a child who looked so healthy," explains Madan Kumar, a fellow in Children's division of Pediatric Infectious Disease and a member of the child's care team. But a mold grew prolifically. Further investigation from a sample sent to the National Institutes of Health showed that it was a relatively new species known as Mucor velutinosus.

Because such an infection had never been reported in a child whose immune system wasn't extremely compromised from cancer, Kumar and team decided to publish a case report. The study appeared online Jan. 24, 2018, in the Journal of the Pediatric Infectious Diseases Society.

Kumar notes that this patient faced myriad challenges. Not only did he have a central line, but the line also had numerous problems, necessitating fixes that could increase the chance of infection. Additionally, because of his intestinal issues, he had a chronic problem with malabsorption of nutrients. Patients with this issue often are treated liberally with antibiotics. Although this intervention can kill "bad" bacteria that can cause an infection, they also knock out "good" bacteria that keep other microorganisms--like fungi--in check. On top of all of this, the patient was receiving a nutrient-rich formula in his central line to boost his caloric intake, yet another factor associated with infections.

Patients who develop this specific fungal infection are overwhelmingly adults who are immunocompromised, Kumar explains, including those with diabetes, transplant recipients, patients with cancer and those who have abnormally low concentrations of immune cells called neutrophils in their blood. The only children who tend to get this infection are preterm infants of very low birth weight who haven't yet developed a robust immune response.

Because there was only one other published case report about a child with M. velutinosus--a 1-year-old with brain cancer who had undergone a bone marrow transplant--Kumar notes that he and colleagues were at a loss as to how best to treat their patient. "There's a paucity of literature on what to do in a case like this," he says.

Fortunately, the treatment they selected was successful. As soon as the cultures came back positive for this mold, the patient went on a three-week course of an antifungal drug known as amphotericin B. Surgeons also removed his infected central line and placed a new one. These efforts cured the patient's infection and preventing it from spreading and potentially causing the multi-organ failure associated with these types of infections.

This case taught Kumar and colleagues quite a bit--knowledge that they wanted to share by publishing the case report. For example, it reinforces the importance of central line care. It also highlights the value of thoroughly investigating potential problems in a patient with risk factors, even one who appears otherwise healthy.

Finally, Kumar adds, the case emphasizes the importance of good antibiotic stewardship, which can help prevent patients from developing sometimes deadly secondary infections like this one. "This is not an organism that you see growing in a 6-year-old very often," he says. "The fact that we saw it here speaks to the need to be judicious with broad-spectrum antibiotics so that we have a number of therapeutic options should we see unusual cases like this one."

Deep space is not as silent as we have been led to believe. Every few minutes a pair of black holes smash into each other. These cataclysms release ripples in the fabric of spacetime known as gravitational waves. Now Monash University scientists have developed a way to listen in on these events. The gravitational waves from black hole mergers imprint a distinctive whooping sound in the data collected by gravitational-wave detectors. The new technique is expected to reveal the presence of thousands of previously hidden black holes by teasing out their faint whoops from a sea of static.

Last year, in one of the biggest astronomical discoveries of the 21st century, LIGO Scientific Collaboration (LSC) and Virgo Collaboration researchers measured gravitational waves from a pair of merging neutron stars.

Drs Eric Thrane and Rory Smith, from the ARC Centre of Excellence for Gravitational Wave Discovery (OzGrav) and Monash University, were part of the team involved in last year's discovery and were also part of the team involved in the detection of first gravitational-wave discovery in 2015, when ripples in the fabric of space time generated by the collision of two black holes in the distant Universe were first witnessed, confirming Albert Einstein's 1915 general theory of relativity.

To date, there have been six confirmed, or gold plated, gravitational-wave events announced by the LIGO and Virgo Collaborations. However there are, according to Dr Thrane, more than 100,000 gravitational wave events every year too faint for LIGO and Virgo to unambiguously detect. The gravitational waves from these mergers combine to create a gravitational-wave background. While the individual events that contribute to it cannot be resolved individually, researchers have sought for years to detect this quiet gravitational-wave hum.

In a landmark paper in the US journal, Physical Review X, the two researchers have developed a new, more sensitive way of searching for the gravitational-wave background.

"Measuring the gravitational-wave background will allow us to study populations of black holes at vast distances. Someday, the technique may enable us to see gravitational waves from the Big Bang, hidden behind gravitational waves from black holes and neutron stars," Dr Thrane said.

The researchers developed computer simulations of faint black hole signals, collecting masses of data until they were convinced that - within the simulated data - was faint, but unambiguous evidence of black hole mergers. Dr Smith is optimistic that the method will yield a detection when applied to real data. According to Dr Smith, recent improvements in data analysis will enable the detection of "what people had spent decades looking for." The new method is estimated to be one thousand times more sensitive, which should bring the long-sought goal within reach.

Importantly the researchers will have access to a new $4 million supercomputer, launched last month (March) at the Swinburne University of Technology. The computer, called OzSTAR, will be used by scientists to look for gravitational waves in LIGO data.

According to OzGRav Director, Professor Matthew Bailes, the supercomputer will allow OzGrav's researchers to attempt these kind of landmark discoveries.

"It is 125,000 times more powerful than the first supercomputer I built at the institution in 1998."

The OzStar computer differs from most of the more than 13,000 computers used by the LIGO community, according to Dr Smith, including those at CalTech and MIT. OzStar employs graphical processor units (GPUs), rather than more traditional central processing units (CPUs). For some applications, GPUs are hundreds of times faster. "By harnessing the power of GPUs, OzStar has the potential to make big discoveries in gravitational-wave astronomy," Dr Smith said.

First study to show 'owls' have higher risk of mortality

Switch to daylight savings time is much harder for them

They suffer from more diseases and disorders than morning larks

Employers should allow greater flexibility in working hours

Consider abolishing daylight savings time, scientists say

CHICAGO --- "Night owls" -- people who like to stay up late and have trouble dragging themselves out of bed in the morning -- have a higher risk of dying sooner than "larks," people who have a natural preference for going to bed early and rise with the sun, according to a new study from Northwestern Medicine and the University of Surrey in the United Kingdom (UK).

The study, on nearly half a million participants in the UK Biobank Study, found owls have a 10 percent higher risk of dying than larks. In the study sample, 50,000 people were more likely to die in the 6½ -year period sampled.

"Night owls trying to live in a morning lark world may have health consequences for their bodies," said co-lead author Kristen Knutson, associate professor of neurology at Northwestern University Feinberg School of Medicine.

Previous studies in this field have focused on the higher rates of metabolic dysfunction and cardiovascular disease, but this is the first to look at mortality risk.

The study will be published April 12 in the journal Chronobiology International.

The scientists adjusted for the expected health problems in owls and still found the 10 percent higher risk of death.

"This is a public health issue that can no longer be ignored," said Malcolm von Schantz, a professor of chronobiology at the University of Surrey. "We should discuss allowing evening types to start and finish work later, where practical. And we need more research about how we can help evening types cope with the higher effort of keeping their body clock in synchrony with sun time."

"It could be that people who are up late have an internal biological clock that doesn't match their external environment," Knutson said. "It could be psychological stress, eating at the wrong time for their body, not exercising enough, not sleeping enough, being awake at night by yourself, maybe drug or alcohol use. There are a whole variety of unhealthy behaviors related to being up late in the dark by yourself."

In the new study, scientists found owls had higher rates of diabetes, psychological disorders and neurological disorders?

Can owls become larks?

Genetics and environment play approximately equal roles in whether we are a morning or a night type, or somewhere in between, the authors have previously reported.

"You're not doomed," Knutson said. "Part of it you don't have any control over and part of it you might."

One way to shift your behavior is to make sure you are exposed to light early in the morning but not at night, Knutson said. Try to keep a regular bedtime and not let yourself drift to later bedtimes. Be regimented about adopting healthy lifestyle behaviors and recognize the timing of when you sleep matters. Do things earlier and be less of an evening person as much as you can.

Society can help, too

"If we can recognize these chronotypes are, in part, genetically determined and not just a character flaw, jobs and work hours could have more flexibility for owls," Knutson said. "They shouldn't be forced to get up for an 8 a.m. shift. Make work shifts match peoples' chronotypes. Some people may be better suited to night shifts."

In future research, Knutson and colleagues want to test an intervention with owls to get them to shift their body clocks to adapt to an earlier schedule. "Then we'll see if we get improvements in blood pressure and overall health," she said.

The switch to daylight savings or summer time is already known to be much more difficult for evening types than for morning types.

"There are already reports of higher incidence of heart attacks following the switch to summer time," says von Schantz. "And we have to remember that even a small additional risk is multiplied by more than 1.3 billion people who experience this shift every year. I think we need to seriously consider whether the suggested benefits outweigh these risks."

How the study worked

For the study, researchers from the University of Surrey and Northwestern University examined the link between an individual's natural inclination toward mornings or evenings and their risk of mortality. They asked 433,268 participants, age 38 to 73 years, if they are a "definite morning type" a "moderate morning type" a "moderate evening type" or a "definite evening type." Deaths in the sample were tracked up to six and half years later.

Analyzing the famous academic aphorism "publish or perish" through a modern digital lens, a group of emerging ecologists and conservation scientists wanted to see whether communicating their new research discoveries through social media--primarily Twitter--eventually leads to higher citations years down the road.

Turns out, the tweets are worth the time investment.

"There's a compelling signal that citation rates are positively associated with science communication through social media. Certainly, Twitter provides an accessible and efficient platform for scientists to do a majority of that communication," said Clayton Lamb, a University of Alberta PhD student and lead researcher on a new study out today.

"The good papers that get pushed on social media are what end up on people's minds and eventually as PDFs in their reference manager," he said.

As is common among scientists, what started as a personal curiosity turned into a full-scale study. Along with Sophie Gilbert, a former U of A post-doc now working in the Department of Fish and Wildlife Sciences at the University of Idaho, and Adam Ford, an assistant professor at UBC (Okanagan), Lamb explored the phenomenon of science communication in the social media age, measuring the association of altmetrics--alternative impact factors, which consider, amongst other avenues, social media attention surrounding science discoveries--with eventual citation of 8,300 ecology and conservation papers published between 2005 and 2015.

The three scientists, who use Twitter to communicate daily about their science (see @ClaytonTLamb, @SophieLGilbert, and @adamthomasford), found a positive correlation between social media engagement and traditional measures of scholarly activity.

"There's a big hype when a paper comes out, but then there is this underwhelming lull for a year or two as you wait for citations to accumulate, so you don't really know whether your science is reaching people. We quantified whether science communication may correlate with more citations. In the case of ecology and conservation science, it looks like it does," said Lamb, who is completing his PhD tracking grizzly bear population patterns with supervisors Stan Boutin in the Faculty of Science and Scott Nielsen in the Faculty of Agricultural, Life, & Environmental Sciences.

Science communication is viewed as critical to ecology and conservation, where research findings are often used to shape public policy and mainstream media attention. Lamb said though much of scientists' communication on social media is directed at other scientists, by virtue of the medium, information is making its way to the broader community, noting statistics showing that nearly half of ecologists' followers on Twitter are non-scientists, environmental groups and the media.

"Ecologists and conservation scientists are dealing with applied problems that the public cares a lot about. So when science gets stuck in the circles of academia and doesn't make it out to the public, it's doing that publicly funded research and its potential applications, a disservice," said Lamb.

"In this era of alternative facts and some mixed messaging surrounding science, data-driven scientific information offers a light of truth. Twitter is one of the ways we can help share science with policy-makers, other scientists and the public."

NEW YORK, April 11, 2018 - Salaries for U.S. physicians edged higher this past year, with compensation increasing modestly for most specialties, while jumping 16% for psychiatrists. Still, the gender gaps in compensation remain unchanged and failed to budge for African-American physicians, according to the results of the 2018 Medscape Physician Compensation Report. Yet, despite concerns regarding pay equity and skyrocketing bureaucratic demands, the majority of physicians remain committed to the profession and are happy they chose to be doctors.

The Report is the most comprehensive and widely used physical salary survey in the U.S. Now in its 8th year, it has been used by more than 470,000 physicians in the U.S. to assess information on compensation, hours worked, time spent with patients, and what they find most rewarding -- and challenging -- about their jobs. More than 20,000 U.S. physicians across 29 specialties responded to the survey.

"We're seeing the impact of supply and demand on physicians' salaries in this year's report," said Leslie Kane, MA, Senior Director, Medscape Business of Medicine. "The growing need for more doctors as the population ages is pushing salaries higher. At the same time, the amount of paperwork and bureaucratic demands escalate, leaving doctors with less time to see patients. We also see the influence of the opioid epidemic and the demand for psychiatrists to treat aging patients leading to increased salaries."

Regarding the continued gender pay disparity, one leading family practice physician is calling for greater salary transparency in the medical profession, so that women would know how much their male colleagues are earning.

"You would think that as we narrow the gap of representation of women in medicine, that would narrow the wage gap, but it's not happening," says Ranit Mishori, MD, professor of family medicine at Georgetown University School of Medicine. "The lack of salary transparency adds to the challenges of addressing gender-based pay disparities. Women don't even know what targets to shoot for."

Physician salaries average $299,999 in this year's report, up from $294,000 in 2017; specialists earn about $100,000 more than primary care physicians ($329,000 versus $223,000), and plastic surgeons ranked highest in salary at $501,000 -- outpacing orthopedists ($497,000) for the first time since the report has been conducted, which may be a reflection of greater demand fueled by increased popularity of cosmetic procedures. Pediatricians and family practice physicians report the lowest compensation, at $212,000 and $219,000 respectively.

The amount of time physicians spend on paperwork and administrative tasks continues to increase, with nearly three quarters (71%) spending more than 10 hours per week on paperwork -an increase of 13 percentage points in one year.

"Although physicians put paperwork and long hours at the top of their list of professional challenges, we continue to see an abiding sentiment across all specialties that being a physician is rewarding, despite the issues," said Medscape Chief Medical Director Michael Smith, M.D. "The majority of physicians feel fairly compensated, and even though about 40% might have chosen another specialty in hindsight, 77% are satisfied with their decision to become a doctor. It's important to note the rewards come from making a difference and gratitude from patients. Money ranks lower on the list of genuine rewards."

Additional Report Highlights

Gender Disparities Remain in Primary Care and Specialties

Male primary care doctors earned almost 18% more than female primary care doctors, and men in specialties earned 36% more than women this year versus 31% last year. Male primary care physicians' compensation averaged $239,000 versus $203,000 for women, and males in specialties earned an average $358,000 versus $263,000 for women.

Race/Ethnicity and Physician Income

Racial disparities in compensation remained unchanged, with African-American/black physicians earning an average $50,000 less per year than white physicians ($308,000 for white physicians versus $258,000 for black physicians). African-American/black women made nearly $100,000 less than male African-American physicians ($322,000 for men versus $225,000 for African American/black women). Asian-American physicians earned an average $293,000 per year and Hispanic/Latino physicians earned an average $278,000.

Location Makes a Difference

Less populated states continue to be more lucrative than more densely populated regions, with physicians in the North Central region earning the highest, at $319,000, and the Northeast the lowest, at $275,000. The states with the highest average physician salaries are Indiana, Oklahoma and Connecticut; New Mexico, Maryland and Washington DC rank lowest. The number of physicians in a region, percent of insured patients and the overall concentration of specialists play a role in regional compensation differences.

To view the full Medscape 2018 Physician Compensation Report, visit:
https://www.medscape.com/slideshow/2018-compensation-overview-6009667?faf=1

To view the 2018 report before the embargo, please use this link:
https://www.staging.medscape.com/slideshow/2018-compensation-overview-6009667?faf=1

Medscape Survey Methods:

The 2018 Medscape Physician Compensation Survey was completed by more than 20,000 physicians representing 29 specialty areas, including Medscape members and nonmembers. Respondents were invited to respond to the online survey. The margin of error for the survey was +/- 0.69% at a 95% confidence level.

About Medscape

Medscape is the leading source of clinical news, health information, and point-of-care tools for health care professionals. Medscape offers primary care physicians, subspecialists, and other health professionals the most robust and integrated medical information and educational tools. Medscape Education (medscape.org) is the leading destination for continuous professional development, consisting of more than 30 specialty-focused destinations offering thousands of free C.M.E. and C.E. courses and other educational programs for physicians, nurses, and other health care professionals.

PHILADELPHIA - A new type of cancer vaccine has yielded promising results in an initial clinical trial conducted at the Perelman School of Medicine at the University of Pennsylvania and the Abramson Cancer Center of the University of Pennsylvania. The personalized vaccine is made from patients' own immune cells, which are exposed in the laboratory to the contents of the patients' tumor cells, and then injected into the patients to initiate a wider immune response. The trial, conducted in advanced ovarian cancer patients, was a pilot trial aimed primarily at determining safety and feasibility, but there were clear signs that it could be effective: About half of the vaccinated patients showed signs of anti-tumor T-cell responses, and those "responders" tended to live much longer without tumor progression than those who didn't respond. One patient, after two years of vaccinations, was disease-free for another five years without further treatment. The study is published today in Science Translational Medicine.

"This vaccine appears to be safe for patients, and elicits a broad anti-tumor immunity--we think it warrants further testing in larger clinical trials," said study lead author Janos L. Tanyi, MD, an assistant professor of obstetrics and gynecology at Penn Medicine.

The study was led by Lana Kandalaft, PharmD, PhD, MTR, George Coukos, MD, PhD, and Alexandre Harari, PhD, of the Lausanne Branch of the Ludwig Institute for Cancer Research. Kandalaft and Coukos devised a novel method for making a vaccine of this sort while at the Perelman School of Medicine at the University of Pennsylvania.

Most cancer vaccines developed to date have been designed to recognize and attack a specific known molecule--such as a cell-surface receptor--that is likely to be found on cancerous cells in any patient with that type of tumor. The approach taken by the Lausanne-Penn team is more ambitious. Each vaccine is essentially personalized for the individual patient, using the patient's own tumor which has a unique set of mutations and thus a unique presentation to the immune system. It is also a whole-tumor vaccine, meant to stimulate an immune response against not just one tumor-associated target but hundreds or thousands.

"The idea is to mobilize an immune response that will target the tumor very broadly, hitting a variety of markers including some that would be found only on that particular tumor," Tanyi said.

The vaccine harnesses the natural process of T-cell immunity to tumors, but enhances it to help overcome tumors' formidable defenses. Tanyi and colleagues made each patient's vaccine by sifting through the patient's own peripheral blood mononuclear cells for suitable precursor cells, and then growing these, in the lab, into a large population of dendritic cells. Dendritic cells are essential for an effective T-cell immune response. They normally ingest infectious pathogens, tumor cells, or anything else considered "foreign," and re-display pieces of the invader to T-cells and other elements of the immune system, to trigger a specific response. The researchers exposed the dendritic cells to specially prepared extracts of the patient's tumor, activated the cells with interferon gamma, and injected them into the patient's lymph nodes, in order to prime a T-cell response.

The team tested this strategy on a total of 25 patients, each of whom received a dose of tumor-exposed dendritic cells every three weeks, in some cases for more than six months. Half of the patients that could be evaluated showed big increases in the numbers of T-cells specifically reactive to tumor material, indicating a good response to vaccination.

"The 2-year overall survival rate of these responder patients was 100 percent, whereas the rate for non-responders was just 25 percent," Tanyi said.

One patient, a 46-year old woman, started the trial with stage 4 ovarian cancer--which generally has a very poor prognosis--following five prior courses of chemotherapy. She received 28 doses of her personalized vaccine over a two-year period, and thereafter remained disease-free for five years.

Also promising was the finding, in tests on several of the responders, of vaccine-induced T-cells that showed high affinity for unique structures ("neoepitopes") on their tumors. In principle, an attack by such T-cells on tumors should be particularly powerful as well as highly tumor-specific and thus sparing of healthy cells.

Tumors typically have a repertoire of molecular defenses they can use to suppress or evade immune attacks, which is why cancer vaccines and immunotherapies have had mixed results in clinical trials to date. Tanyi and colleagues therefore hope in future to enhance the effectiveness of their vaccine by combining it with other drugs that deactivate tumor anti-immune defenses.

(Millbrook, NY) Road salt applied during the winter lingers in the environment, where it can pollute drinking water supplies. In a recent study in the Journal of Environmental Quality, researchers identify landscape and geological characteristics linked to elevated well water salinity in a suburban township in Southeastern New York.

Victoria Kelly, lead author and Environmental Monitoring Program Manager at the Cary Institute of Ecosystem Studies, explains, "Each year, millions of metric tons of road salt are applied to roads in the US. Some of this salt seeps into the soil, where it accumulates and contaminates groundwater. We wanted to understand why some wells were more at risk than others, to inform management that protects water quality."

Kelly and colleagues analyzed publicly available data on water samples taken from 956 private drinking water wells in East Fishkill, New York between 2007 and 2013. More than half of the wells sampled exceeded US Environmental Protection Agency health standards for sodium. Distance to the nearest road and amount of nearby pavement strongly influenced well water salinity. Surprisingly, well depth and road type -- ranging from interstate highways to back roads -- did not have a significant impact.

GIS analysis of sodium and chloride concentrations was used to describe the pattern of road salt distribution in the aquifers tapped for drinking water, and to compare surface features in the surrounding area of each well location. The team assessed neighborhood-scale variables, including well depth, proximity to roads, well elevation relative to nearby roads, impervious surface, surface geology, and soil type to discern relationships between development and well salinity.

Findings linking pavement and other impervious surface cover to well salinity support a growing body of evidence that development and urbanization cause groundwater salinization. Proximity to a road increased a well's chloride concentration, yet road type - major or minor - did not have an impact. Well depth did not significantly impact saltiness and elevation in relation to nearby roads only affected wells when the roads were more than 30 meters from the nearest well.

Several hotspots, where salinization was especially high, were identified. Suggested contributing factors included sharp turns and steep grades that required heavier road salt application, and narrow streets that only accommodate older, less efficient salt trucks. There was only one cold spot, in an area of low housing density, reinforcing the relationship between urbanization, salt application, and freshwater salinization.

"Understanding the landscape features that lead to increased groundwater salinization can inform targeted salt application," explains Stuart Findlay, a freshwater ecologist at the Cary Institute of Ecosystem Studies. "The time to act is now, as we know it can take decades or more for the salt currently in groundwater to flush out."

Kelly adds, "In planning efforts to minimize road salt impacts, our findings tell us that smaller roads should not be overlooked and areas with a lot of pavement and porous, well-drained soils are most at risk of experiencing salinization. Road salting is not one-size-fits-all undertaking. More targeted approaches will keep roads safe while reducing unintended consequences to drinking water supplies."

Our emotional state in a given moment may influence what we see, according to findings published in Psychological Science, a journal of the Association for Psychological Science. In two experiments, researchers found that participants saw a neutral face as smiling more when it was paired with an unseen positive image.

The research shows that humans are active perceivers, say psychological scientist Erika Siegel of the University of California, San Francisco and her coauthors.

"We do not passively detect information in the world and then react to it - we construct perceptions of the world as the architects of our own experience. Our affective feelings are a critical determinant of the experience we create," the researchers explain. "That is, we do not come to know the world through only our external senses - we see the world differently when we feel pleasant or unpleasant."

In previous studies, Siegel and colleagues found that influencing people's emotional states outside of conscious awareness shifted their first impressions of neutral faces, making faces seem more or less likeable, trustworthy, and reliable. In this research, they wanted to see if changing people's emotional states outside awareness might actually change how they see the neutral faces.

Using a technique called continuous flash suppression, the researchers were able to present stimuli to participants without them knowing it. In one experiment, 43 participants had a series of flashing images, which alternated between a pixelated image and a neutral face, presented to their dominant eye. At the same time, a low-contrast image of a smiling, scowling, or neutral face was presented to their nondominant eye - typically, this image will be suppressed by the stimulus presented to the dominant eye and participants will not consciously experience it.

At the end of each trial, a set of five faces appeared and participants picked the one that best matched the face they saw during the trial.

The face that was presented to participants' dominant eye was always neutral. But they tended to select faces that were smiling more as the best match if the image that was presented outside of their awareness showed a person who was smiling as opposed to neutral or scowling

In a second experiment, the researchers included an objective measure of awareness, asking participants to guess the orientation of the suppressed face. Those who correctly guessed the orientation at better than chance levels were not included in subsequent analyses. Again, the results indicated that unseen positive faces changed participants' perception of the visible neutral face.

Given that studies often show negative stimuli as having greater influence on behavior and decision making, the robust effect of positive faces in this research is intriguing and an interesting area for future exploration, the researchers note.

Siegel and colleagues add that their findings could have broad, real-world implications that extend from everyday social interactions to situations with more severe consequences, such as when judges or jury members have to evaluate whether a defendant is remorseful.

Ultimately, these experiments provide further evidence that what we see is not a direct reflection of the world but a mental representation of the world that is infused by our emotional experiences.

(New York, NY- April 11, 2018) --Researchers from Mount Sinai and Sema4, a health information company and Mount Sinai venture, have discovered that giving metastatic bladder cancer patients simultaneous chemotherapy and immunotherapy is safe and that patients whose tumors have certain genetic mutations may respond particularly well to this combination approach, according to the results of a clinical trial published in European Urology.

Though chemotherapy and immunotherapy have become standard options for the treatment of metastatic bladder cancer, it was previously unknown whether these therapies could be given together and whether chemotherapy's side effect of weakening the immune system would inhibit immunotherapy. The phase 2 trial was conducted at six cancer centers, and patients in the trial did not show any additional or more severe side effects than patients given chemotherapy or immunotherapy alone, a finding that showed the combination therapy is a safe alternative.

Researchers also generated evidence showing that immunotherapy could boost immune cells in the blood of patients receiving concurrent chemotherapy, allaying previous concerns that chemotherapy might counteract the effects of immunotherapy.

"Because chemotherapy and immunotherapy are the two pillars of treatment for metastatic bladder cancer, we sought to better understand how these treatments might be best given together," said Matthew Galsky, MD, Director of Genitourinary Medical Oncology and Professor of Urology, Medicine, Hematology and Medical Oncology at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, and Principal Investigator of the study. "Already the results of this trial have inspired the creation of two more trials that seek to better the treatment of bladder cancer patients by combining chemotherapy with immunotherapy."

One of the new trials, which Dr. Galsky is heading at Mount Sinai and other centers, gives chemotherapy and immunotherapy to a subset of patients with earlier-stage bladder cancer to determine if this combination can head off the need for surgery to remove the bladder, a standard treatment but one with quality-of-life-altering implications that include wearing a urostomy bag outside the body to collect urine. The other trial combines two different chemotherapy regimens with immunotherapy to determine the best types of chemotherapy drugs to combine with immunotherapy.

Dr. Galsky said that the current trial epitomizes the importance of team science. Dr. Galsky, as well as Andrew Uzilov, PhD, Director of Cancer Genomics for Sema4, and Huan Wang, PhD, Sema4 bioinformatics scientist, and other researchers hypothesized that patients with tumors with particular genetic mutations might respond best to the combination of chemotherapy and immunotherapy. And indeed, they found that certain types of mutations in DNA damage response (DDR) genes were associated with better response to the combined chemotherapy and immunotherapy. If validated in subsequent studies, these findings could add a novel biomarker to the "precision oncology toolbox" and refine the selection of patients who might benefit from concurrent administration of chemotherapy and immunotherapy.

"Our work is an example of using genomics to enable precision medicine. By looking for loss-of-function mutations in DDR genes, we may be able to predict who will do well on a combined chemotherapy plus immunotherapy regimen," explained Dr. Uzilov. "In our study, we looked at a pool of 55 DDR genes as predictive biomarkers. We are now exploring further which of these genes, and what types of mutations within them, best predict treatment response, as well as the interplay of DDR status with other predictors of immunotherapy response."