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APRIL 11, 2018, NEW YORK -- A Ludwig Cancer Research study has shown that an entirely new type of personalized cancer vaccine induces novel, potent and clinically effective immune responses in patients receiving a combination of standard therapies for recurrent, stage III and IV ovarian cancer.

Led by Lana Kandalaft, George Coukos and Alexandre Harari of the Lausanne Branch of the Ludwig Institute for Cancer Research, the study also found that the vaccine--made from a processed sample of a patient's tumor and delivered via that patient's own immune cells--is well tolerated, safely administered and can be made in sufficient quantities with relative ease. Further, the researchers show that the immune responses it elicits are vigorous and target both known cancer antigens as well as a broad variety of the unique antigens, or "neoantigens", expressed by each patient's cancer cells.

"This is the first time ever that a personalized vaccine made from the contents of whole cancer cells has been shown to produce immune responses against neoantigens," says Kandalaft, who is an adjunct researcher at Ludwig Lausanne. "We've also shown that these immune responses are not just any responses, but the type that kill tumor cells, and that they correlate with better progression-free survival and better overall survival of patients."

The study, reported in the current issue of Science Translational Medicine, addressed a longstanding conundrum of ovarian cancer treatment. Ovarian tumor cells are known to express neoantigens, which are randomly mutated proteins expressed by cancer cells that can be detected as signs of disease by the immune system. Yet the malignancy has so far proved largely resistant to immunotherapies, including traditional cancer vaccines, that stimulate an attack by killer T cells--immune cells that detect and destroy sick and infected cells.

Coukos, who is director of Ludwig Lausanne, has shown that this is at least partly because a factor secreted by tumors, VEGF-A, keeps killer T cells from infiltrating the tumor. Ovarian tumors also harbor T regulatory cells (Tregs), whose job it is to suppress killer T cells.

Many researchers are trying to computationally predict the neoantigens expressed by a patient's tumors and synthesize the bits--or neoepitopes--recognized by T cells to make personalized vaccines. But, while promising, such approaches are labor intensive and time-consuming, and thus, relatively expensive.

Kandalaft and colleagues wondered if, alternatively, the contents of cancer cells taken from tumor samples--or "whole tumor lysates"--might suffice to make vaccines that train the body to detect the neoepitopes expressed on tumors.

"This would be the cost-effective way of producing an individualized cancer vaccine," says Kandalaft.

Kandalaft and Coukos devised a novel method for making a vaccine of this sort while still at the Perelman School of Medicine at the University of Pennsylvania--one in which the lysate from cancer cells is gently treated with acid to turn its antigens into more potent stimulators of immune responses. The researchers applied the method to tumors taken from each patient in the study.

Next, they collected certain immune cells from each patient and coaxed them to turn into dendritic cells, which gobble up suspicious biological detritus and "present" antigens to T cells to help stimulate an immune response.

For the clinical trial, which was conducted at the Perelman School of Medicine at the University of Pennsylvania, the researchers pulsed the dendritic cells from each patient with her tumor lysate to generate living and personalized dendritic cell vaccines. These vaccines were then injected into the lymph nodes of each corresponding patient. "The lymph nodes," explains Kandalaft, "are the headquarters where dendritic cells meet T cells."

One cohort of patients received just the personalized vaccine. A second received vaccine along with bevacizumab, a standard therapy that blocks blood vessel formation in tumors by targeting VEGF-A--the same factor that bars killer T cells from entering tumors. The third got, in addition to bevacizumab, low doses of cyclophosphamide. This chemotherapy, another standard of care for recurrent ovarian cancer, also happens to suppress Tregs--which are recruited into tumors to shut down killer T cells.

"The regimen used for the third cohort really made a difference--first in eliciting an immune response in patients who received it, and then in the progression-free survival and the overall survival of those patients a year and even two years after receiving the therapy," says Kandalaft.

Extensive immunologic analyses, led by Harari and Kandalaft and conducted at Ludwig Lausanne, show that the vaccine stimulated the immune response in unique ways: The T cells elicited by the vaccine not only recognize a broad spectrum of neoantigens but are far more sensitive to lower levels of those antigens, and more fiercely activated.

Although the study met all of its endpoints, it was not a randomized, placebo-controlled trial. The researchers did, however, compare their results with historical patient data of ovarian cancer recurrence and the outcomes recorded in their practice. "At one year, 100% of the patients in cohort 3 were alive, as compared to 60% when patients receive just bevacizumab and cyclophosphamide but no vaccine," says Kandalaft.

Their therapeutic strategy, Kandalaft notes, would also be eminently suited to swift implementation if it passes muster in larger, randomized and placebo-controlled trials.

"We aren't giving patients any completely new drugs in combination with this personalized vaccine," she points out. "Bevacizumab and cyclophosphamide are routinely used to treat recurrent ovarian cancer. All we did was add the vaccine. This means that we should be able to easily integrate this personalized immunotherapy into the current standard of care for recurrent ovarian cancer."

Immunotherapies are treatments that stimulate a patient's immune cells to attack the tumor. They can be very effective in melanoma - a common and aggressive form of skin tumor - but still fail in the majority of the patients. To address this, researchers are trying to identify the factors that enable successful immunotherapy, as well as those that may limit it. The ultimate goal is to open new avenues for immunotherapies that are more broadly effective in melanoma, and potentially other cancer types.

Certain immune cells, called CD8 T cells (or cytotoxic T lymphocytes), can recognize and kill melanoma cells, thus have the potential to eradicate the tumor. Immunotherapies stimulate the CD8 T cells to attack the tumor more vigorously. But the activity of CD8 T cells can be suppressed by other immune cells present in the tumor.

Studying a subset of melanoma patients, researchers led by Michele De Palma at EPFL and Daniel Speiser at the University of Lausanne have identified macrophages as culprits driving resistance to a leading immunotherapy, known as PD-1 checkpoint blockade.

"The existence of immune cells that either execute or suppress cytotoxic immune responses is essential for limiting the potentially deleterious effects of an uncontrolled immune response, a condition that may lead to auto-immunity or organ damage," says De Palma. "The problem is that tumors hijack these regulatory mechanisms to their own benefit, so that they can grow largely unchecked by the immune system".

By analyzing samples obtained from the patients' tumors, Speiser and his colleagues found that the CD8 T cells release signals that indirectly attract the macrophages to the tumors, establishing what they refer to as a "dangerous liaison" in melanoma.

"It is a sort of vicious cycle," says Speiser. "The good side of the coin is that the CD8 T cells get activated by certain tumor antigens and initiate a potentially beneficial immune response against the tumor. The bad side is that, when activated, the CD8 T cells also induce the production of a protein in melanoma, called CSF1, which attracts the macrophages." Indeed, melanomas that attract many CD8 T cells frequently end up containing many macrophages, which can weaken the efficacy of PD-1 immunotherapy.

Once recruited en masse to the tumor, macrophages suppress the CD8 T cells and dampen the anti-tumoral immune response. But when the scientists used a drug to specifically eliminate the macrophages in experimental models of melanoma, they found that the efficacy of PD-1 checkpoint blockade immunotherapy was greatly improved.

The findings support the clinical testing of agents that disrupt macrophages in combination with PD-1 immunotherapy in patients whose melanomas contain high numbers of both CD8 T cells and macrophages.

"As opposed to targeted therapies that hit specific oncogenes responsible for the growth of the tumor, immunotherapies largely lack biomarkers that can predict whether a patient will respond or not to the treatment", says De Palma. "Our study suggests that assessing the abundance of macrophages and the contextual presence of CD8 T-cells - for example by measuring genes that are specifically expressed by these cells - may serve to stratify patients who are amenable to more effective immunotherapy combinations," concludes Speiser.

ANN ARBOR--In an advance that could grime-proof phone screens, countertops, camera lenses and countless other everyday items, a materials science researcher at the University of Michigan has demonstrated a smooth, durable, clear coating that swiftly sheds water, oils, alcohols and, yes, peanut butter.

Called "omniphobic" in materials science parlance, the new coating repels just about every known liquid. It's the latest in a series of breakthrough coatings from the lab of Anish Tuteja, U-M associate professor of materials science and engineering. The team's earlier efforts produced durable coatings that repelled ice and water, and a more fragile omniphobic coating. The new omniphobic coating is the first that's durable and clear. Easily applied to virtually any surface, it's detailed in a paper published in ACS Applied Materials & Interfaces.

Tuteja envisions the new coating as a way to prevent surfaces from getting grimy, both in home and industry. It could work on computer displays, tables, floors and walls, for example.

"I have a 2-year-old at home, so for me, this particular project was about more than just the science," Tuteja said. "We're excited about what this could do to make homes and daycares cleaner places, and we're looking at a variety of possible applications in industry as well."

He says the new coating is the latest result of the team's systematic approach, which breaks with the traditional materials science "mix-and-see" approach. By mapping out the fundamental properties of a vast library of substances, they're able to mathematically predict how any two will behave when they're combined. This enables them to concoct a nearly endless variety of combinations with very specifically tailored properties.

"In the past, researchers might have taken a very durable substance and a very repellent substance and mixed them together," Tuteja said. "But this doesn't necessarily yield a durable, repellent coating."

They discovered that even more important than durability or repellency is a property called "partial miscibility," or the ability of two substances to mix together in exactly the right way. Chemicals that play well together make a much more durable product, even if they're less durable individually.

Tweaking the miscibility of this particular coating posed a special challenge. To make a versatile coating that's optically clear and smooth enough to repel oils and alcohols, the team needed to find a repellent ingredient and a binder with exactly the right amount of miscibility, as well as the ability to stick to a wide variety of substrates. They also needed a coating that would stay smooth during processing and drying.

"You can repel water with a rough surface that creates tiny pockets of air between the water and the surface, but those surfaces don't always repel oils or alcohols because of their lower surface tension," Tuteja said. "We needed a very smooth surface that interacts as little as possible with a variety of liquids, and we also needed ingredients that mix together very well, because too much phase separation between ingredients will scatter light."

Ultimately, the team discovered that a mix of fluorinated polyurethane and a specialized fluid-repellent molecule called F-POSS would do the job. Their recipe forms a mixture that can be sprayed, brushed, dipped or spin-coated onto a wide variety of surfaces, where it binds tightly. While the surface can be scratched by a sharp object, it's durable in everyday use. And its extremely precise level of phase separation makes it optically clear.

"The repellent and binder mix together well enough to make a clear coating, but there's a very small amount of phase separation between them," said Mathew Boban, a materials science and engineering graduate researcher and an author on the paper. "That separation allows the F-POSS to sort of float to the surface and create a nice repellent layer."

Tuteja believes that the coating will be inexpensive by the time it sees the mass market--fluorinated polyurethane is an inexpensive, common ingredient. And while F-POSS is rare and expensive today, manufacturers are in the process of scaling it up to mass production, which should dramatically lower its cost.

The research team is also doing further studies to ensure that the coating is nontoxic for use in places like daycare centers. Tuteja estimates that the coating could go to market within the next two years, and he believes childproof coatings are just the beginning.

The coating could also be used in refrigeration, power generation and oil refining--all industries that depend on the condensation of liquids. The new coating could enable equipment to slough off condensed water and chemicals more quickly, increasing efficiency by up to 20 percent. That's a game changer, as those industries are some of the world's most high-volume and energy-intensive.

DALLAS, April 11, 2018 -- Smoke from wildfires may send people - particularly seniors - to hospital emergency rooms (ERs) with heart, stroke-related complaints, according to new research in the Journal of the American Heart Association, the Open Access Journal of the American Heart Association/American Stroke Association.

Previous studies have shown that wildfire smoke exacerbates respiratory conditions but yielded inconsistent results for effects on the heart, brain or blood vessels.

The study was the product of a collaboration between researchers at the University of California San Francisco, California Department of Public Health and the U.S. Environmental Protection Agency. Researchers reviewed more than one million ER visits in northern and central California during intense wildfires in the summer of 2015. They examined the relative risk of daily heart-, brain- and blood vessel-related ER visits on light, medium and dense smoke days relative to days without wildfire smoke exposure.

They found that smoke exposure was associated with increased rates of ER visits, not just for breathing trouble, but also ischemic heart disease, irregular heart rhythm, heart failure, pulmonary embolism and stroke. The risk was greatest for adults age 65 and older.

The greatest increased relative risk was noted within a day of dense wildfire smoke. During these times, researchers found rates of ER visits among adults 65 and older increased:

42 percent for heart attack; and

22 percent for ischemic heart disease.

Overall, ER visits for all cardiovascular and cerebrovascular causes were elevated across all smoke days, with the greatest increase on dense smoke days and among adults age 65 and older. Respiratory conditions also were increased, as anticipated.

"This is one of the most extensive studies of wildfire health impacts in California to date," said Ana Rappold, Ph.D., study senior author and statistician with the U.S. Environmental Protection Agency in Durham, North Carolina.

Wildfire smoke contains many pollutants including ozone, carbon monoxide and fine particulate matter - which is linked to cardiovascular risk. People with underlying cardiovascular disease risk factors may be at risk for an acute heart, brain or blood vessel event when exposed to wildfire smoke.

A 2010 AHA statement on air pollution noted that particulate matter has been associated with increased risks of heart attack, stroke, irregular heart rhythm and heart failure exacerbation within hours to days of exposure in susceptible individuals. In addition, long term exposure to particulate matter can reduce life expectancy by a few years.

"The findings have public health and clinical implications," said Wayne E. Cascio, M.D., study author and acting director for the National Health and Environmental Effects Research Laboratory in the EPA's Research and Development Office. "I think it will have a significant impact on how clinicians and public health officials view future wildfire events and the smoke that's generated from them."

Research has shown that wildfire season in North America is increasing in intensity and duration. As wildfires likely become a bigger problem, it is important to continue research for wider-ranging health impacts from smoke exposure and ways to help people prevent these health outcomes, said Zachary S. Wettstein, B.A., study first author and graduating medical student from the University of California San Francisco.

"We need to study effective interventions that might decrease exposure to smoke and the associated health impacts," Wettstein said. "These findings urge us to study these impacts over longer periods of time and within susceptible populations."

The study did not examine the effect of personal traits such as past medical history, race, socioeconomic status and other factors that might affect the association between smoke exposure and ER visits but did examine differences by sex and age.

TORONTO, April 11, 2018 - Higher cigarette prices would save millions of people from extreme poverty and poor health around the world, while also cutting health treatment costs for families across the globe, suggests a comprehensive study published today in The BMJ.

The analysis, led by Dr. Prabhat Jha and Patricio V. Marquez, concludes that those with lower incomes would benefit the most from higher cigarette prices. Examining 500 million male smokers in 13 countries, they found that a 50 per cent price increase in cigarettes would result in 67 million men quitting smoking, with the biggest benefit in low-income men.

The higher price would also lead to 15.5 million men avoiding catastrophic health spending in the seven countries studied without universal health coverage. This would result in 8.8 million men avoiding extreme poverty, half of whom are in the bottom income group.

"Our study debunks the current narrative that higher cigarette prices would negatively impact the poorest among us," said Dr. Jha, director of the Centre for Global Health Research of St. Michael's Hospital. "This analysis shows the opposite - a higher price would encourage cessation, lead to better health, and save money much more strongly for the poor than the rich."

Cessation would result in 449 million years of life gained, the study showed. Higher tobacco costs would also benefit households globally, with about $157-billion USD averted to treat the four main tobacco-attributable diseases examined: chronic obstructive pulmonary disease, stroke, heart disease and cancer.

Despite more awareness of the risks, Dr. Jha said, if we don't deflect the current trends, smoking will be responsible for one billion deaths in the 21st century. Most of these will be in low and middle-income countries. Previous research by Dr. Jha, who is also a professor in the Dalla Lana School of Public Health at the University of Toronto, has shown that raising taxes on tobacco is the single most effective intervention to lower smoking rates and to deter future smokers.

Building on his earlier research, Dr. Jha and the team undertook this new analysis to understand the true impact of higher cigarette prices around the world. They conducted an assessment across 13 middle-income countries with diverse socioeconomic characteristics, tobacco use and health care coverage. Focusing on male smokers - who make up 90 per cent of smokers in the selected countries - the researchers used mathematical models to quantify the effect of a 50 per cent increase in prices.

"The findings of our new analysis will have a far-reaching impact," said Marquez, lead health specialist at The World Bank. "Not only does increasing tobacco taxation reduce smoking and its health consequences, but the study's findings are also relevant to the United Nations sustainable development goals to reduce poverty and improve health."

This study will add to a growing body of knowledge that higher cigarette pricing, though not yet universally adopted, has significant health benefits. Small steps taken by governments can lead to unprecedented health gains and poverty reduction, Dr. Jha said.

In a two-year community randomised trial involving more than 15,000 children in Tanzania, a long lasting insecticidal net treated with piperonyl butoxide (PBO LLIN) reduced the prevalence of malaria by 44% and 33% in the first and second year respectively, compared to a standard long lasting insecticidal net (LLIN) treated with pyrethroid only.

The study, led by the London School of Hygiene & Tropical Medicine (LSHTM), also showed unprecedented malaria control through indoor residual spraying (IRS) with the insecticide pirimiphos methyl, which after a single spray round reduced malaria infection by 48% for an entire year.

LLINS and IRS are the cornerstones of malaria control in sub-Sahara Africa, and have been estimated to reduce malaria disease by 41% and malaria deaths by 62% between 2000 and 2015 globally. Despite this public health success, malaria still kills nearly half a million people annually, and for the first time in many years the World Health Organization (WHO) reported an increase in malaria cases and no change in the number of malaria deaths in 2017.

There is concurrent evidence that resistance to pyrethroid insecticide is growing in the Anopheline mosquitoes which transmit the disease. Only a limited range of alternative insecticides are available, particularly for LLINs for which pyrethroids are the only class of insecticide fully recommended by the WHO.

Anticipating the possible failure of current control tools due to resistance, WHO and LSHTM have been collaborating with the chemical industry for almost 20 years to develop new types of LLIN and new insecticides for IRS. One of these is a novel LLIN which incorporates piperonyl butoxide (PBO), a chemical which blocks the natural defence mechanisms of insects - the oxidase enzymes that would otherwise metabolise insecticide - which means the pyrethroid on the LLIN remains potent against mosquitoes despite resistance. This chemical synergist stops insects from breaking down the pyrethroid within their bodies, so the insecticide stays toxic to the insect.

Dr Natacha Protopopoff from the London School of Hygiene & Tropical Medicine who led the field research operations in Muleba, Tanzania, said: "It's imperative we try and remain one step ahead of insecticide resistance which threatens to reverse the great gains made in combating malaria. We must develop an improved strategy based on new classes of LLIN to control malaria transmitted by pyrethroid resistant mosquitoes."

This new study involved randomly selected children aged six months to 14 years from villages in Muleba district of North West Tanzania, where high levels of resistance to pyrethroids have been reported. In 2015, 48 villages were randomised into four groups with different preventative measures. Altogether 45,000 standard LLINs and 45,000 PBO LLINs were distributed. Children were then tested for malaria at the end of each rainy season.

After nine months, malaria infection was considerably lower in the group that received just the net treated with piperonyl butoxide - PBO LLIN - (31.1%, 275/883) and the group that received indoor residual spraying and standard LLIN (28.7%, 252/877), compared to the group that received standard LLIN alone (55.3%, 515/932). Twelve months later, the PBO LLIN effect was still persisting relative to the standard LLIN.

To strengthen the evidence for the interventions, mosquito traps were placed in each study arm. The number of malaria infected mosquitoes captured in the PBO LLIN villages was reduced by 87% and 67% during the first and second years respectively compared to the standard LLIN villages.

Professor Mark Rowland from LSHTM and Principal Investigator, said: "This project is a game-changer. The trial is the first clear evidence that nets treated with piperonyl butoxide can significantly improve personal and community protection from malaria compared to standard pyrethroid-only nets in areas where there is high pyrethroid resistance. It also demonstrated that pyrethroid resistance is now a significant problem in some areas and standard LLIN are less effective than before, and that the new IRS controlled malaria for an entire year before needing to be re-sprayed."

As a direct consequence of the trial, WHO revised its reccomendations on LLIN in September 2017, giving an interim policy recommendation to PBO LLIN as a new class of LLIN1.

Dr Jan Kolaczinski, Coordinator for Entomology and Vector Control in the WHO Global Malaria Programme said: "WHO recommends PBO LLINs should be deployed for malaria prevention in areas where mosquitoes are pyrethroid resistant, provided that full coverage is maintained. This would include many endemic areas in Africa where standard LLINs are currently used."

Professor Rowland said: "We are pleased that the WHO has already revised policy on the basis of this trial. This will ensure insecticide treated nets will remain an effective intervention for malaria control, and justifies the continued investment and research on alternative insecticides for use on nets."

The authors acknowledge the study does have limitations, including the short buffer distance between villages; however, any spill-over between villages would tend to underestimate the intervention effect rather than increase it.

The authors also stress that it is important to always sleep under a bed net in areas of malaria transmission, and until PBO LLIN are deployed more widely in areas of resistance, standard pyrethroid-only nets will be more protective than non-use of nets and should continue to be used.

Smartphones are an integral part of most people's lives, allowing us to stay connected and in-the-know at all times. The downside of that convenience is that many of us are also addicted to the constant pings, chimes, vibrations and other alerts from our devices, unable to ignore new emails, texts and images. In a new study published in NeuroRegulation, San Francisco State University Professor of Health Education Erik Peper and Associate Professor of Health Education Richard Harvey argue that overuse of smart phones is just like any other type of substance abuse.

"The behavioral addiction of smartphone use begins forming neurological connections in the brain in ways similar to how opioid addiction is experienced by people taking Oxycontin for pain relief -- gradually," Peper explained.

On top of that, addiction to social media technology may actually have a negative effect on social connection. In a survey of 135 San Francisco State students, Peper and Harvey found that students who used their phones the most reported higher levels of feeling isolated, lonely, depressed and anxious. They believe the loneliness is partly a consequence of replacing face-to-face interaction with a form of communication where body language and other signals cannot be interpreted. They also found that those same students almost constantly multitasked while studying, watching other media, eating or attending class. This constant activity allows little time for bodies and minds to relax and regenerate, says Peper, and also results in "semi-tasking," where people do two or more tasks at the same time -- but half as well as they would have if focused on one task at a time.

Peper and Harvey note that digital addiction is not our fault but a result of the tech industry's desire to increase corporate profits. "More eyeballs, more clicks, more money," said Peper. Push notifications, vibrations and other alerts on our phones and computers make us feel compelled to look at them by triggering the same neural pathways in our brains that once alerted us to imminent danger, such as an attack by a tiger or other large predator. "But now we are hijacked by those same mechanisms that once protected us and allowed us to survive -- for the most trivial pieces of information," he said.

But just as we can train ourselves to eat less sugar, for example, we can take charge and train ourselves to be less addicted to our phones and computers. The first step is recognizing that tech companies are manipulating our innate biological responses to danger. Peper suggests turning off push notifications, only responding to email and social media at specific times and scheduling periods with no interruptions to focus on important tasks.

Two of Peper's students say they have taken proactive measures to change their patterns of technology use. Recreation, Parks and Tourism major Khari McKendell closed all of his social media accounts about six months ago because he wanted to make stronger face-to-face connections with people. "I still call and text people but I want to make sure that a majority of the time I'm talking to my friends in person," he said.

Senior Sierra Hinkle, a Holistic Health minor, says she has stopped using headphones while out walking in order to be more aware of her surroundings. When she's out with friends, they all put their phones in the center of the table, and the first one to touch theirs buys the drinks. "We have to become creative and approach technology in a different way that still incorporates the skills we need but doesn't take away from real-life experience," said Hinkle.

Unlike Derek Zoolander, ants don't have any difficulty turning left. New research from the University of Bristol has now found rock ants often have one eye slightly better than the other, which could help explain why most of them prefer to turn left, given the choice.

The research, published in Scientific Reports today [Wednesday 11 April] and led by Dr Edmund Hunt and Emeritus Professor Nigel Franks, studied whether rock ants' turning direction was associated with how well the ants can see in either eye. Previous research on honey bees found a link between lateralization to learn odours better with the right antenna, and more smell sensors on the right antenna than the left.

Behavioural lateralization is the preference to use a certain side of the body for certain tasks. For example, most humans are right-handed. While scientists used to think this was only a human trait, evidence for lateralization in animals, including insects like ants and bees, is becoming increasingly widespread. Research by Bristol in 2014 found that rock ants show a leftward turning bias in branching nest sites. While such lateralization may originate in asymmetrical brain structures, it may also relate to external shape asymmetries - such as the size of eyes or the length of legs.

Ant compound eyes are composed of small structures known as ommatidia which collect light. More ommatidia in an eye contributes to better vision. The researchers found that ants turning left tended to have slightly more ommatidia in their right eye, and vice versa. This may be because they prefer to walk with their inferior eye pointing toward the wall, so when they come to a branch they follow the wall along to the left. This is the first study to report a link between asymmetries in compound eyes and behavioural lateralization in insects.

Dr Edmund Hunt, EPSRC Doctoral Prize Fellow in the Department of Engineering Mathematics' Collective Dynamics research group and corresponding author, said: "It is intriguing that lateralization of behaviour seems to be associated with observable external asymmetries in the body. This suggests that behavioural lateralization is something that is 'hardwired' into these animals as they develop rather than something learned through experience. It also shows that physical indicators of lateralization can be externally observable rather than hidden in the brain - and might be awaiting discovery in all sorts of animals."

Theoretical models of behavioural lateralization suggest that population or colony-level alignment of behavioural biases should develop in social species that would benefit from coordinating their behaviour. In this case, more predictable behaviour would help them cooperate. On the other hand, the costs of being more predictable, such as vulnerability to predators, might outweigh this alignment of lateralization in non-social species.

The researchers suggest a comparative study should be carried out on compound eye asymmetry between social and non-social species of insects of the same family, such as honeybees vs. solitary bees, to see if it is more pronounced in social species.

Science has yet to unravel a complete understanding of the brain and all its intricate workings. It's not for lack of effort.

Over many decades, multiple research studies have sought to understand the dizzying "talk," or interconnectivity, between thousands of microscopic entities in the brain, in particular, neurons. The goal: to one day arrive at a complete brain "mapping" -- a feat that could unlock tremendous therapeutic potential.

Researchers at the University of Southern California Viterbi School of Engineering have developed thin, flexible polymer-based materials for use in microelectrode arrays that record activity more deeply in the brain and with more specific placement than ever before. What's more is that each microelectrode array is made up of eight "tines," each with eight microelectrodes which can record from a total 64 subregions of the brain at once.

In addition, the polymer-based material, called Parylene C, is less invasive and damaging to surrounding cells and tissue than previous microelectrode arrays comprised of silicon or microwires. However, the long and thin probes can easily buckle upon insertion, making it necessary to add a self-dissolving brace made up of polyethylene glycol (PEG) that shortens the array and prevents it from bending.

Professor Ellis Meng of the USC Viterbi Department of Biomedical Engineering and Michelson Center for Convergent Bioscience said that the performance of the new polymer-based material is on par with microwires in terms of recording fidelity and sensitivity. "The information that we can get out is equivalent, but the damage is much less," Meng said. "Polymers are gentler on the brain, and because of that, these devices get recordings of neuronal communication over long periods of time."

As with any prosthetic implant, caution must be exercised in terms of the body's natural immune response to a foreign element. In addition to inflammation, previous microelectrode brain implants made of silicon or microwire have caused neuronal death and glial scarring, which is damage to connective tissue in the nervous system. However, Parylene C is biocompatible and can be microfabricated in extremely thin form that molds well to specific sub-regions of the brain, allowing for exploration with minimal tissue displacement and cell damage.

So far, these arrays have been used to record electrophysiological responses of individual neurons within the hippocampus, a subregion of the brain responsible for memory formation. If injured, the hippocampus may be compromised, resulting in a patient's inability to form new memories. Meng said that the polymer-based material can conform to a specific location in the hippocampus and "listen in on a conversation" between neurons and because there are many such "eavesdroppers" (the microelectrodes), much more information about neural interconnectivity can be gleaned.

"I can pick where I want my electrodes to be, so I can match up to the anatomy of the brain," Meng said. "Along the length of a tine, I can put a group of electrodes here and a group of electrodes there, so if we plant to a certain depth, it's going to be near the neurons I want to record from."

Future research will determine the recording lifetime of polymer-based arrays and their long-term "signal-to-noise" (SNR) stability. Also, the team plans to create devices with even higher density, including a double-sided microelectrode array with 64 electrodes per tine instead of eight -- making for a total of around 4,000 electrodes placed in the brain at once.

Bees could be at risk from climate change because more frequent droughts could cause plants to produce fewer flowers, new research shows.

Droughts are expected to become more common and more intense in many parts of the world, and researchers studied the impact on flowering plants using a field experiment.

They found that drought roughly halved the overall number of flowers. This means less food for bees and other pollinators, which visit flowers for the nectar and pollen that they provide.

The research was carried out by the University of Exeter in collaboration with the University of Manchester and the Centre for Ecology and Hydrology.

"The plants we examined responded to drought in various ways, from producing fewer flowers to producing flowers that contained no nectar," said lead researcher Ben Phillips, of the Environment and Sustainability Institute on the University of Exeter's Penryn Campus in Cornwall.
"But overall there was a very clear reduction in the number of flowers that were available - and obviously this means less food for flower-visiting insects such as bees."

Bees are already under pressure from a variety of threats including habitat loss, the use of particular pesticides, and the spread of diseases and alien species.

"Not only are these insects vital as pollinators of crops and wild plants, but they also provide food for many birds and mammals," said joint lead researcher Dr Ros Shaw, also of the University of Exeter.

The study took place in Wiltshire on chalk grassland, which is an important habitat for UK pollinator species. The plant species studied included meadow vetchling (Lathyrus pratensis), common sainfoin (Onobrychis viciifolia) and selfheal (Prunella vulgaris).

"Previous studies of the impacts of drought on flowers and bees have looked at individual species, often in the laboratory, but we used an experiment with rain shelters to examine the effects on real communities of plant species living in chalk grassland," said Dr Ellen Fry from the University of Manchester, who set up the experiment.

"The level of drought that we looked at was calculated to be a rare event, but with climate change such droughts are expected to become much more common."

The findings suggest that chalk grasslands may support lower pollinator populations in the future, but the scientists warn that the results are likely to be broadly applicable to other regions and habitats.

The research was part of the Wessex Biodiversity and Ecosystem Service Sustainability project, and was funded by the Natural Environment Research Council.

The paper, published in the journal Global Change Biology, is entitled: "Drought reduces floral resources for pollinators."

Commercial adherence to the United States (US) Food and Drug Administration (FDA) 2016 sodium reformulation targets for processed foods will cost-effectively reduce cardiovascular disease (CVD), according to a modeling study published this week in PLOS Medicine. The study, conducted by Jonathan Pearson-Stuttard of the University of Liverpool and Imperial College London, and colleagues, estimates that, over a 20-year period, even modest adherence to the FDA targets will gain 1.1 million discounted quality-adjusted life years (QALYs) [95% Uncertainty Interval (UI) 0.91 m to 1.3 m] from reduced cases of CVD and other causes, and save $19 billion (95% UI $3.4 b to $41 b) in societal costs.

Sodium consumption is a leading modifiable risk factor for high blood pressure and CVD in the US and worldwide. To reduce sodium consumption, the US FDA in 2016 proposed 2-year and 10-year voluntary sodium reformulation targets for commercially processed, packaged, and prepared foods. However, the potential health and economic effects of these proposed targets have not been rigorously estimated.

In their study, Pearson-Stuttard and colleagues quantify the potential impact on CVD, life years and costs of the FDA proposal over a 20-year period. They use a previously validated microsimulation modeling approach, with a close-to-reality synthetic population (the US IMPACT food policy model) comparing 3 different levels of industry compliance. The researchers project that the optimal scenario--100% compliance with the 10-year FDA targets--could gain approximately 2 million QALYs [95% UI 1.7 m to 2.4 m] and produce discounted cost savings of approximately $40 billion [95% UI $14 b to $81 b]. In contrast, the modest scenario (50% compliance with the 10-year FDA targets) and the pessimistic scenario (100% compliance with the 2-year targets but no further progress) could yield health and economic gains half and a quarter as large, respectively. According to model estimates, all 3 scenarios have a greater than 80% probability of being cost-effective by 2021 (incremental cost-effectiveness ratio

Pearson-Stuttard and colleagues' projections use data from interventional and prospective observational studies, which are subject to biases and confounding. However, sensitivity analyses incorporating uncertainty in the prevalence of risk factors, the relative risks associated with these factors, the specific foods to be reformulated, and costs were factored into the reported UIs. The authors state, "suboptimal compliance or a delay in reaching these targets could result in a significant number of preventable CVD cases, CVD deaths, and costs to the wider economy."

It's still easy to tell computer-simulated motions from the real thing - on the big screen or in video games, simulated humans and animals often move clumsily, without the rhythm and fluidity of their real-world counterparts.

But that's changing. University of California, Berkeley researchers have now made a major advance in realistic computer animation, using deep reinforcement learning to recreate natural motions, even for acrobatic feats like break dancing and martial arts. The simulated characters can also respond naturally to changes in the environment, such as recovering from tripping or being pelted by projectiles.

"This is actually a pretty big leap from what has been done with deep learning and animation. In the past, a lot of work has gone into simulating natural motions, but these physics-based methods tend to be very specialized; they're not general methods that can handle a large variety of skills," said UC Berkeley graduate student Xue Bin "Jason" Peng. Each activity or task typically requires its own custom-designed controller.

"We developed more capable agents that behave in a natural manner," he said. "If you compare our results to motion-capture recorded from humans, we are getting to the point where it is pretty difficult to distinguish the two, to tell what is simulation and what is real. We're moving toward a virtual stuntman."

The work could also inspire the development of more dynamic motor skills for robots.

A paper describing the development has been conditionally accepted for presentation at the 2018 SIGGRAPH conference in August in Vancouver, Canada, and was posted online April 10. Peng's colleagues in the Department of Electrical Engineering and Computer Sciences are professor Pieter Abbeel and assistant professor Sergey Levine, along with Michiel van de Panne of the University of British Columbia.

Mocap for DeepMimic

Traditional techniques in animation typically require designing custom controllers by hand for every skill: one controller for walking, for example, and another for running, flips and other movements. These hand-designed controllers can look pretty good, Peng said.

Alternatively, deep reinforcement learning methods, such as GAIL, can simulate a variety of different skills using a single general algorithm, but their results often look very unnatural.

"The advantage of our work," Peng said, "is that we can get the best of both worlds. We have a single algorithm that can learn a variety of different skills, and produce motions that rival if not surpass the state of the art in animation with handcrafted controllers."

To achieve this, Peng obtained reference data from motion-capture (mocap) clips demonstrating more than 25 different acrobatic feats, such as backflips, cartwheels, kip-ups and vaults, as well as simple running, throwing and jumping. After providing the mocap data to the computer, the team then allowed the system - dubbed DeepMimic - to "practice" each skill for about a month of simulated time, a bit longer than a human might take to learn the same skill.

The computer practiced 24/7, going through millions of trials to learn how to realistically simulate each skill. It learned through trial and error: comparing its performance after each trial to the mocap data, and tweaking its behavior to more closely match the human motion.

"The machine is learning these skills completely from scratch, before it even knows how to walk or run, so a month might not be too unreasonable," he said.

The key was allowing the machine to learn in ways that humans don't. For example, a backflip involves so many individual body movements that a machine might keep falling and never get past the first few steps. Instead, the algorithm starts learning at various stages of the backflip - including in mid-air - so as to learn each stage of the motion separately and then stitch them together.

Surprisingly, once trained, the simulated characters are able to deal with and recover from never-before-seen conditions: running over irregular terrain and doing spin-kicks while being pelted by projectiles.

"The recoveries come for free from the learning process," Peng said.

And the same simple method worked for all of the more than 25 skills.

"When we first started, we thought we would try something simple, as a baseline for later methods, not expecting that it was going to work. But the very simple method actually works really well. This shows that a simple approach can actually learn a very rich repertoire of highly dynamic and acrobatic skills."

Silent marine robots that record sounds underwater are allowing researchers at the University of East Anglia (UEA) to listen to the oceans as never before.

The robots are about the same size as a small human diver, but can reach depths of 1000 metres and travel the ocean for months, covering thousands of kilometres. They communicate by satellite with their pilot to build an underwater soundscape of the world's oceans.

Pierre Cauchy, a PhD researcher from UEA's School of Environmental Sciences, has been using one of these autonomous submarines for five years, recording underwater noises in the Mediterranean Sea and the North Atlantic and Southern oceans.

The recordings can be used to measure sea-surface wind speed and monitor storms as well as eavesdropping on marine life.

Mr Cauchy will present his research at the General Assembly of the European Geosciences Union in Vienna. He will show how the robot - called a Seaglider - can measure the wind speed, listen in to the sounds made by fishes and whales, and pick up human activities, such as marine traffic and seismic surveys.

By recording sounds in remote locations where there are no permanent weather stations, the robots provide valuable information on wind or storm patterns, which can help to finetune climate models.

Mr Cauchy said: "As an acoustician, it is fascinating to listen in to underwater life such as long-finned pilot whales in the North Atlantic, but also to hear the echoes of what is happening in the skies above."

While pilot whales make whistles, buzzes and clicks, pods of hunting dolphins create high- pitched echolocation clicks and larger species such as sperm whales make louder, slower clicks.

High winds raise the background noise level, seismic surveys' intense pulses are unique and easily identifiable, and marine vessels are clearly identified by low-frequency rumbles.

The Seaglider weighs just over 50kg and is 1.5 metres tall. It is remotely controlled by a pilot and is silent, so records only sound from the ocean without adding its own tones.

Mr Cauchy said: "Now that they have been shown to be useful for modelling climate, monitoring storms or protecting marine life, I hope that other researchers will integrate the silent robot divers into their work and their use will broaden."

Philadelphia, April 9, 2018 - Angiogenesis, the formation of new blood vessels, is essential for tumor growth. A new study reported in The American Journal of Pathology describes a vascular stabilization biomarker that can visualize blood vessel activity, thus optimizing the timing of anticancer therapies including anti-angiogenics.

Combination therapy using angiogenesis inhibitors and anticancer drugs can improve drug delivery into tumor tissues and prolong progression-free survival. "Vascular normalization by angiogenesis inhibitors, such as vascular endothelial growth factor (VEGF) signaling inhibitors, is a promising method for improvement of chemotherapy. However, it is unclear how we can recognize the 'window of opportunity' for the tumor vascular normalizing period for effective timing of anticancer drug treatment. Therefore, biomarkers delineating this window are essential," explained Nobuyuki Takakura, MD, PhD, Professor, Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.

Researchers showed that active proliferating vascular endothelial cells (ECs) in mice could be distinguished from dormant ones. They measured the promoter activity of DNA replication factor partner of Sld5-1 (PSF1; official name GINS1) in ECs using enhanced green fluorescent protein (EGFP) that allows visualization of gene activity as fluorescence.

No EGFP signals were observed in normal adult skin vasculature, which was expected as normal skin ECs are dormant. However, after subcutaneous injection of tumor cells, some ECs in and near the tumor shifted to EGFP-positivity. PSF1 promotor activity was also found to correlate well with tumor cell growth. ECs that were high in EGFP expression were larger and had greater intracellular complexity than cells that were EGFP negative. "Our data showed that PSF1-promotor-EGFP mice may be utilized to visualize proliferating ECs by their EGFP expression," commented Dr. Takakura.

"Experimentation on non-proliferative ECs revealed that these quiet cells strongly expressed VEGFR1 and a cell surface protein CD109. CD109 expression in ECs increased three to five days after injection of bevacizumab into human colorectal adenocarcinoma HT29-bearing mice, coinciding with normalization of tumor vessels. Though on day 5 after bevacizumab injection, functional vessels increased and hypoxic regions significantly decreased, by day 8, hypoxic regions increased again."

These results enabled researchers to successfully distinguish between proangiogenic ECs and quiescent ECs by their PSF1 gene promoter activity, which is associated with DNA replication and rapid proliferation of somatic cells. Therefore, CD109 expression in ECs marked normalized or silenced blood vessels in the tumor vasculature.

"Since CD109 is highly expressed in dormant ECs, we suggest it can be used to detect normalized blood vessels, thus allowing identification of the 'window of opportunity' for optimal delivery of chemotherapeutics," remarked Dr. Takakura.

Though angiogenesis therapy is clinically used to suppress tumor growth, unfortunately, monotherapy using anti-angiogenics such as VEGF signaling inhibitors does not effectively suppress tumor growth in patients. Adding an anti-angiogenic drug can boost an anticancer drug's effectiveness. Basic research indicates that anti-angiogenic therapy allows the blood vessels to return to quiescence and "normalize" so that the anticancer drug can penetrate the tumor more effectively.

Blocking the activity of an enzyme that interferes with the blood-brain barrier, contributing to the generation of recurring seizures, may provide a new way to treat epilepsy that is resistant to anti-seizure drugs, according to a study of rats and mice published in JNeurosci.

One-third of people with epilepsy, one of the most common neurological disorders, do not respond well to current treatments for managing seizures. Part of this challenge is that seizures erode the lining of capillaries in the brain that let nutrients in and keeps toxins out. A "leaky" blood-brain barrier, in turn, leads to more seizures. Understanding how this cycle occurs is necessary in order to develop strategies to plug the leak.

In their study of rodent brain capillaries, Björn Bauer and colleagues identified a seizure-triggered pathway that contributes to blood-brain barrier dysfunction in epilepsy. The neurotransmitter glutamate, released during seizures, increased the activity of two types of enzymes belonging to a group called matrix-metalloproteinase (MMP-2, MMP-9) and degraded the tightly-packed proteins that form a critical component of the blood-brain barrier. Blocking another enzyme called cytosolic phospholipase A2 (cPLA2) in rats with induced seizures and genetically deleting cPLA2 in mice prevented these changes and the associated capillary leakage.