Culture

New research from a group of Vanderbilt biomedical engineers reveals that while cancer cells move quickly in metastasis, they're rather lazy in which paths they choose.

According to the researchers, migrating cancer cells decide which path in the body to travel based on how much energy it takes, opting to move through wider, easier to navigate spaces rather than smaller, confined spaces to reduce energy requirements during movement. These findings suggest energy expenditure and metabolism are significant factors within metastatic migration, which lends credence to recent clinical interest in the study of metabolomics and the targeting of cellular metabolism as a way to prevent metastasis.

The discoveries appear in a new paper, "Energetic costs regulated by cell mechanics and confinement are predictive of migration path during decision-making," published today in the journal Nature Communications.

Led by Cynthia Reinhart-King, Cornelius Vanderbilt Professor of Engineering, the paper is the first study to quantify the energetic costs of cancer cells during metastasis - enabling the prediction of specific migration pathways. These new findings build on similar research from the Reinhart-King Lab, published earlier this year, which discovered "drafting" techniques used by cancer cells to conserve energy during migration.

"These cells are lazy. They want to move, but they will find the easiest way to do it," noted Reinhart-King. "By manipulating many different variables, we were able to track and build predictions of cellular preference for these paths of least resistance in the body based on how much energy a cell would need to move."

Lead author on the paper, graduate student Matthew Zanotelli, used a variety of methods to test and map out cellular movement, including tracking cells through a constructed maze of pathways as they manipulated the mechanical properties of each cancer cell, and even the physical properties of the paths themselves.

While the scope of the new research focuses on metastatic cancer cells, Zanotelli noted that the results of this study could soon have broader implications for a variety of situations beyond cancer.

"This type of cellular movement happens in other instances - for example, during inflammation and around healing wounds," said Zanotelli. "We're excited to have this initial understanding of energy and cell migration and hope it will prove foundational for future, broader research."

For male Trinidad Guppies applies: if you are hungry, seek female company. A recent study led by scientists of the the Leibniz-Institute of Freshwater Ecology and Inland Fisheries (IGB) and the Leibniz Institute for Zoo and Wildlife Research (IZW) together with other research institutions provides evidence that male guppy fish in the presence of females more often ended up at novel food patches. In contrast, female food discovery was independent of male presence.

Trinidad guppies (Poecilia reticulata) live in small watercourses in the rainforests of Trinidad. They have a preference for sporadic high-quality food resources, like fruits and insects, falling into the water- so it is usually uncertain when and where they encounter food. In this study, behavioural ecologist Lysanne Snijders and her team set up a field experiment and manipulated guppy sex compositions (all male, all female or mixed) in the wild using individually colour-marked guppies. They conducted social observations, followed by foraging trials.

Males reached more food patches when there were females around. Yet, females reached a similar number of patches either with or without males present. Males also spent less time social in absence of females, but the absence of males had no effects for females. The researchers analysed if this time spent socially was linked to patch discovery success. Indeed, in agreement with a previous study, more social guppies ended up at more food patches.

"Life in the group can be advantageous. You have to share the food with your peers, but it is also easier to find it if you use the information of others," explains Lysanne Snjiders. Guppies, for example, react to the typical behaviour of successful food finders, which is: swim faster, grab food, stay there and eat.

The researchers can only guess why males behave differently in the absence of females than in sexually mixed groups. "In this case, males among themselves are more likely to be in a state of competition than cooperation and therefore spend less time together and miss out on important information," says Lysanne Snijders.

The head of the study, IGB-researcher Prof. Jens Krause, is investigating the dynamics of swarm behaviour and collective intelligence in animals. He explains the importance of this field of research: „If we are able to understand the interactions of animals within a group, we can derive from this knowledge information about the spread of diseases, reproduction and predator-prey relationships. The structure of social networks may also be a decisive factor concerning the stability of a population. Such knowledge may help wildlife managers and conservationists, for example, to optimise disease management, breeding programmes or reintroduction activities."

An international collaboration of scientists in Iceland, Denmark and the Netherlands has for the first time used ancient DNA analyses and C14-dating to demonstrate the past existence of a unique population of Icelandic walrus that went extinct shortly after Norse settlement some 1100 years ago. Walrus hunting and ivory trade was probably the principal cause of extinction, being one of the earliest examples of commercially driven overexploitation of marine resources.

The presence of walruses in Iceland in the past and its apparent disappearance as early as in the Settlement and Commonwealth periods (870-1262 AD) has long puzzled the scientific world. In a study recently published in the journal Molecular Biology and Evolution scientists from Denmark, Iceland and Holland have addressed the question by analysing ancient and contemporary DNA along with carbon-14 dating of walrus remains, supplemented with detailed studies of finding localities of the remains, place names and references to walrus hunting in the Icelandic Mediaeval literature, including the Icelandic Sagas.

"Natural History Museum collections provide a remarkable window into the past, which with modern day technology allow us to explore the past effects of human activities and environmental change on species and ecosystems. This can be further put into context by studying the Icelandic Mediaeval literature, historic place names and zooarchaeological sites," explains instigator of the research Hilmar J. Malmquist, Director of the Icelandic Museum of Natural History, Reykjavik, Iceland.

A long-term population of genetically unique walruses in Iceland

The scientists used carbon-14 dating of walrus remains found in Iceland to reveal that walrus inhabited Iceland for thousands of years, but disappeared shortly after the country's settlement around 870 AD by the Norse. DNA was extracted from natural finding sites and archaeological excavations of walrus samples, and compared to data from contemporary walruses, documenting that the Icelandic walrus constituted a genetically unique lineage, distinct from all other historic and contemporary walrus populations in the North Atlantic.

"Our study provides one of the earliest examples of local extinction of a marine species following human arrival and overexploitation. It further adds to the debate about the role of humans in the extinction of megafauna, supporting a growing body of evidence that wherever humans turn up, the local environment and ecosystem suffers," says Morten Tange Olsen, Assistant Professor at Globe Institute, University of Copenhagen.

Walrus ivory was a luxury good

Walrus ivory was a luxury good in high demand and widely traded across Viking Age and Medieval Europe with beautifully ornamented tusks documented as far away as the Middle East and India. Most examples of trade and human overexploitation and extinction of local marine resources are of much more recent date, such as overfishing, and commercial whaling for the past three centuries or so.

"We show that already in the Viking Age, more than 1000 years ago, commercial hunting, economic incentives and trade networks were of sufficient scale and intensity to result in significant, irreversible ecological impacts on the marine environment, potentially exacerbated by a warming climate and volcanism. The reliance on marine mammal resources for both consumption and trade has so far been underestimated," says lead author Xénia Keighley, who is completing a PhD at the GLOBE Institute in Copenhagen and the Arctic Centre in Groningen.

The Large Magellanic Cloud, or LMC, is one of our nearest galactic neighbors, at only 163 000 light years from Earth. With its sibling the Small Magellanic Cloud, these are among the nearest dwarf satellite galaxies to the Milky Way. The LMC is also the home of various stellar conglomerates and is an ideal laboratory for astronomers to study the processes that shape galaxies.

ESO's VISTA telescope, has been observing these two galaxies for the last decade. The image presented today is the result of one of the many surveys that astronomers have performed with this telescope. The main goal of the VISTA Magellanic Clouds (VMC) Survey has been to map the star formation history of the Large and Small Magellanic Clouds, as well as their three-dimensional structures.

VISTA was key to this image because it observes the sky in near-infrared wavelengths of light. This allows it to see through clouds of dust that obscure parts of the galaxy. These clouds block a large portion of visible light but are transparent at the longer wavelengths VISTA was built to observe. As a result, many more of the individual stars populating the centre of the galaxy are clearly visible. Astronomers analysed about 10 million individual stars in the Large Magellanic Cloud in detail and determined their ages using cutting-edge stellar models[1]. They found that younger stars trace multiple spiral arms in this galaxy.

For millennia, the Magellanic Clouds have fascinated people in the Southern Hemisphere, but they were largely unknown to Europeans until the Age of Discovery. The name we use today harkens back to the explorer Ferdinand Magellan, who 500 years ago began the first circumnavigation of the Earth. The records the expedition brought back to Europe revealed many places and things to Europeans for the first time. The spirit of exploration and discovery is ever more live today in the work of astronomers around the world, including the VMC Survey team whose observations led to this stunning image of the LMC.

Disabled people face being marginalised by the very programmes that are designed to help them.

Rather than taking their differences and particular preferences into account, projects and welfare systems established to provide support are normalising disabled people, and unintentionally contributing to their further marginalisation.

Research from Lancaster University Management School (LUMS), published in Organization Studies, investigated a programme that allocated computers to disabled people. Its aim was to help people improve their sociability through electronic interactions. The research focuses on the part played by an assessment form designed to establish whether or not a person qualified for a computer.

The study found that the scheme's assessors did not apply a strict interpretation of the questions and answers on the form, and sometimes ignored responses or shaped answers to better suit the programme's requirements. This allowed some of those involved to receive a computer even though they did not comply with the allocation criteria, but had the unintended effect of glossing over their views and wishes in favour of the pre-set organisational goals of promoting sociability.

Dr Yvonne Latham, of the LUMS Department of Organisation, Work and Technology, who conducted the research, observed that carers, family members and project staff applied their own views and perceptions of what was important for disabled people, while often ignoring their actual preferences.

"The assumptions of those who organised the project were that disabled people are lacking something that can be 'fixed' so as to make their lives similar to those of the able-bodied," said Dr Latham. "Forms will often have yes or no answers to questions which demand more complicated responses. Consequently, welfare worked treat issues such as whether individuals are able to wash, dress or use the toilet by themselves - capabilities that are forever changing, often on a daily basis -with limited importance as they try to render impaired bodies more predictable than is plausible.

"In our case, while the form itself had implications for disabled people, the filling in of the questions and responses, and the results thereof, are also affected by the assumptions of those carrying out the questioning. Everyone has pre-conceived ideas, and these are evident with how they would violate both the spirit and the letter of the form - often normalising assumptions of the needs and desires of those people with whom they are speaking."

For example, among the disabled people interviewed was Ron. During his interview, Ron revealed that he did not want to use the computer for which he was being assessed to increase his social connectivity, but rather for activities such as buying and selling shares. He answered: 'I don't want to increase my social interactions because I'm miserable, like my brother'. He felt that people looking to fill out the form in a certain way were not listening to him.

The interviewer eventually decided that Ron would benefit from using the computer with internet access and would see a boost to his independence as a result, and thus was allocated a computer despite his not fitting the prior organisational criteria of a suitable user.

Other examples included Chloe, a 25-year-old wheelchair user, whose mother was adamant she would not let her use the computer for online shopping (one of the criteria of 'fit' for the programme), as she wanted to continue to take her out shopping. Chloe was not seen as socially isolated so much as lacking independence as a result of her mother's control over her life.

Polly, a woman in her 60s with Lupus, Angina and Arthritis, gave the expected responses, thus allowing a straightforward and positive form filling process. As a result of the cost of broadband and the discomfort she had while trying to sit and use the allocated computer, Polly later returned it because she said it was causing her stress, and because she had not really wanted it in the first place.

Co-author Professor David Knights added: "These examples show how the responses on the form can both be shaped by the interviewer to gain the expected response, but also how the interviewee can give responses they feel are what is expected, even if the result is not what they desire.

"The form and the project were designed to help overcome the marginalisation of disabled people through increasing their sociability, but these assumptions and the form's usage were reconfigured by those involved, glossing over the actual discussions that took place during the interviews and, on occasion, leading the interviewees to feel their views were being ignored.

"Imposing norms on disabled people and expecting them to fit in with preconceived ideas can have the unintended consequence of marking them out as being in need of special attention. There is a fine line in welfare between care and patronising power."

Researchers from Clemson University and University of Kentucky published a new paper in the Journal of Marketing, which examines several means by which suppliers can enhance their competitiveness when selling to barricaded buyers.

The study, forthcoming in the November issue of the Journal of Marketing, is titled "Selling to Barricaded Buyers" and authored by Kevin Chase and Brian Murtha.

To ensure fair and competitive purchase processes, most states and many leading organizations limit the amount of contact suppliers have with buying team members once RFPs are released. Accordingly, the researchers refer to these buyers as "barricaded buyers" because it is difficult for suppliers to communicate with them. How can suppliers effectively sell to buyers who are sheltered by these barricades?

In the typical RFP process, there are fewer restrictions placed on communicating with buyers during the development of the RFP (i.e., the "pre-RFP" phase). In this phase, buyers involve suppliers to help clarify their needs so they can develop more appropriate RFP specifications. One frequent and efficient way to involve suppliers is commonly referred to as a "pre-RFP" meeting. These meetings (some of which require attendance) bring together competing suppliers who participate in facilities walk-throughs, inspections, and clarifying Q&A sessions. Chase explains that "We discovered that while some suppliers remained silent during these meetings, other suppliers took the opportunity to engage in what we call "peacocking" behavior. Peacocking is when a supplier signals or "shows off" the strength of its knowledge about, or its connections to individuals within, the buying firm. Our findings indicate that doing so can substantially demotivate one's competitors from responding to the buyer's RFP."

In addition to demotivating competitors through peacocking, suppliers can demotivate competitors by embedding their unique capabilities and language into buyers' RFPs during the pre-RFP phase. To do so, shrewd suppliers often shared facilitating documentation (e.g., marketing materials or sample RFPs) that included their unique capabilities and language. Buyers, some of whom had less experience developing RFPs, appreciated the help and used suppliers' facilitating documentation to help develop RFPs of their own. Other suppliers were quick to notice the unique capabilities and language of their competitors and lamented about the biased nature of the RFPs (whether the bias was intended or not).

In the post-RFP phase (i.e., once the formal RFP is released), buyer-supplier interactions are much more restricted. A common approach to developing an RFP response was to meet requirements exactly as requested. Buyers, however, often mentioned that the RFP requirements are really just the minimum requirements. "We discovered that more competitive suppliers not only met the requirements of the RFPs, but also went above and beyond the requirements in two critical ways--by also providing innovative solutions and/or by providing solutions buyers hadn't thought of. Doing so signals to buyers a sincere effort by the supplier to claim their business and that the supplier may provide additional value going forward in the relationship," explains Murtha.

In addition to the solutions offered, the study shows that buyers lean heavily on the subtle signals suppliers convey in their RFP response documents. For instance, several suppliers were surprisingly inattentive to the poor tone conveyed in their RFP responses and some used canned responses not tailored to the RFP's buyer. Buyers quickly removed such suppliers from their decision sets. Further, buyers paid particular attention to the similarity of the references suppliers provided. Similar references signaled the requisite experience and ability to handle the buyer's account; dissimilar references either triggered fears of supplier inability to handle their account (when references were smaller or less prestigious) or fears of inattentiveness to their account (when references were larger or more prestigious).

Although price is certainly important when selling to barricaded buyers, this research suggests its importance is largely situational, ranging from zero percent (for some services) to 75 percent (for some commodity products), with the average around 30 percent. As a result, suppliers engaging in the barricaded buying process should acknowledge the important role of price, but also the importance of these other strategies as ways to enhance their competitiveness.

Astronomers using one of the most advanced radio telescopes have discovered a rare molecule in the dust and gas disc around a young star - and it may provide an answer to one of the conundrums facing astronomers.

The star, named HD 163296, is located 330 light years from Earth and formed over the last six million years.

It is surrounded by a disc of dust and gas - a so-called protoplanetary disc. It is within these discs that young planets are born. Using a radio telescope in the Atacama Desert in Chile, researchers were able to detect an extremely faint signal showing the existence of a rare form of carbon monoxide - known as an isotopologue (13C17O).

The detection has allowed an international collaboration of scientists, led by the University of Leeds, to measure the mass of the gas in the disc more accurately than ever before. The results show that disc is much heavier - or more 'massive' - than previously thought.

Alice Booth, a PhD researcher at Leeds who led the study, said: "Our new observations showed there was between two and six times more mass hiding in the disc than previous observations could measure.

"This is an important finding in terms of the birth of planetary systems in discs - if they contain more gas, then they have more building material to form more massive planets."

The study - The first detection of 13C17O in a protoplanetary disk: a robust tracer of disk gas mass - is published today (12/09/2019) in Astrophysical Journal Letters.

The scientists' conclusions are well timed. Recent observations of protoplanetary discs have perplexed astronomers because they did not seem to contain enough gas and dust to create the planets observed.

Dr John Ilee, a researcher at Leeds who was also involved in the study, added: "The disc-exoplanet mass discrepancy raises serious questions about how and when planets are formed. However, if other discs are hiding similar amounts of mass as HD 163296, then we may just have underestimated their masses until now."

"We can measure disc masses by looking at how much light is given off by molecules like carbon monoxide. If the discs are sufficiently dense, then they can block the light given off by more common forms of carbon monoxide - and that could result in scientists underestimating the mass of the gas present.

"This study has used a technique to observe the much rarer 13C17O molecule - and that's allowed us to peer deep inside the disc and find a previously hidden reservoir of gas."

The researchers made use of one of the most sophisticated radio telescopes in the world - the Atacama Large Millimetre/submillimetre Array (ALMA) - high in the Atacama Desert.

ALMA is able to observe light that is invisible to the naked eye, allowing astronomers to view what is known as the 'cold universe' - those parts of space not visible using optical telescopes.

Booth said: "Our work shows the amazing contribution that ALMA is making to our understanding of the Universe. It is helping build a more accurate picture of the physics leading to the formation of new planets. This of course then helps us understand how the Solar System and Earth came to be."

The researchers are already planning the next steps in their work.

Booth added: "We suspect that ALMA will allow us to observe this rare form of CO in many other discs. By doing that, we can more accurately measure their mass, and determine whether scientists have systematically been underestimating how much matter they contain."

WHAT:
Allergy to peanut, which is often severe, is one of the most common food allergies in the United States. Although previous studies have shown that peanut oral immunotherapy (OIT)--ingesting small, controlled amounts of peanut protein--can desensitize adults and children and prevent life-threatening allergic reactions, the optimal duration and dose is unknown. In a study that followed participants after OIT successfully desensitized them to peanut, discontinuing OIT or continuing OIT at a reduced dose led to a decline in its protective effects. The study, published online today in The Lancet, also found that several blood tests administered before OIT could predict the success of therapy. The Phase 2 study was supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, and may inform who may benefit from peanut OIT and what changes in this experimental treatment should be implemented.

Investigators at Stanford University enrolled 120 people aged 7 to 55 with diagnosed peanut allergy in the Peanut Oral Immunotherapy Study: Safety Efficacy and Discovery, or POISED. While otherwise avoiding peanut throughout the trial, 95 participants received gradually increasing daily doses of peanut protein up to 4 grams, and 25 participants received daily placebo oat flour OIT. After 24 months, participants were given gradually increasing amounts of peanut in a controlled environment, to assess their tolerance. Of those participants who received peanut OIT, 83% passed the peanut challenge without an allergic reaction, while only 4% on placebo OIT did so.

Those on OIT who passed the challenge were then randomized to receive either placebo OIT or were switched to a 300-mg daily dose of peanut protein. One year later, more participants on 300-mg peanut OIT (37%) passed the challenge than those on placebo OIT (13%), confirming insights from smaller trials that desensitization is maintained in only a minority of participants after OIT is discontinued or reduced. Participants who passed food challenges also had lower initial levels of allergic antibodies to peanut protein and other indicators of allergic activity in the blood. Future research will focus on identifying optimal OIT regimens that maintain protection after therapy and will allow for regular food consumption without allergic symptoms.

An innovative solution used to prevent common brain infections in patients having surgery for hydrocephalus has been found to significantly reduce infection rates according to a report published in The Lancet today (12 September 2019).

Hydrocephalus is a build-up of fluid on the brain. The excess fluid puts pressure on the brain, which can damage it. Approximately one out of every 500 babies is born with hydrocephalus, making it the most common reason for brain surgery in children.

Babies born with hydrocephalus (congenital) and adults or children who develop it (acquired) usually need prompt treatment to reduce the pressure on their brain. This is usually done with a shunt.

During surgery, a thin tube called a shunt is implanted in the brain. The excess cerebrospinal fluid (CSF) in the brain flows through the shunt to drain into the abdominal cavity where is absorbed. Approximately 1300 new shunts (UK shunt registry) are inserted in the UK each year.

Unfortunately, shunt infection affects up to 15% of patients having shunt surgery, and is more common in children and neonates. Shunt infection is a serious complication that can lead to meningitis, weeks in hospital, prolonged antibiotics, the need for further surgery and irreversible brain injury.

A team of scientists from the University of Nottingham, led by Professor of Surgical Infection Roger Bayston, developed a novel process (Bactiseal®) that allows brain shunts to be impregnated with antibiotics during manufacture.

A team of researchers from the University of Liverpool, Alder Hey Children's NHS Foundation Trust and The Walton Centre NHS Foundation Trust conducted the largest - ever clinical trial for hydrocephalus to test the infection-reducing properties of Bactiseal®. The BASICS trial (British Antibiotic and Silver Impregnated Catheters for ventriculoperitoneal Shunts) was funded by the National Institute for Health Research (NIHR), and cost £2.3M. Over 1600 patients with hydrocephalus took part, across 21 UK neurosurgery centres. The study took seven years (2012-2019) to complete.

The BASICS trial compared antibiotic and silver shunts to standard shunts (without antibiotic or silver coating). The results showed that antibiotic shunts reduce the infection rate from 6% to 2% and saved the NHS approximately £130K per infection averted. If the antibiotic shunts were used in all new patients, this would save the NHS approximately 7 million pounds per year.

The Chief investigators were Professor Conor Mallucci, Paediatric Neurosurgeon at Alder Hey Children's Hospital Trust, and Michael Jenkinson, Reader in Neurosurgery at the University of Liverpool and Consultant Neurosurgeon at The Walton Centre. The study was co-ordinated by Professor Carrol Gamble and run by the University of Liverpool's Clinical Trials Research Centre.

Conor Mallucci, said: "The results of our trial will have an impact on national and international hydrocephalus guidelines and policy. Using these antibiotic shunts will not only reduce potential harm to our patients but are also cost effective and should save Healthcare providers millions of pounds avoiding countless unnecessary days in hospital.'

Michael Jenkinson, said: "The BASICS study shows that antibiotic shunts reduce the risk of infection for all patients having shunt surgery for hydrocephalus. If we use antibiotic shunts routinely we really can 'get it right first time' by avoiding harm and delivering better outcomes for all our patients."

Roger Bayston, said: "The antibiotic shunts have now been shown in a well-designed randomised controlled trial to significantly reduce infection in hydrocephalus shunts. This is a major step forward in treatment of this condition, which can affect newborn babies and adults alike, and will reduce the need for surgery and for antibiotic treatment and will save heathcare costs."

The full paper, entitled 'Antibiotic or silver versus standard ventriculoperitoneal shunts (BASICS): a multicentre, single-blinded, randomised trial and economic evaluation', can be found on The Lancet website once the embargo has lifted.

New findings released Sept. 12 from a groundbreaking gambling study by a University of Massachusetts Amherst research team show that out-of-state casino gambling among Massachusetts residents decreased significantly after the Commonwealth's first slot parlor, Plainridge Park Casino, opened in Plainville in the summer of 2015.

"That suggests that the slot parlor was successful at recapturing people who had been gambling in casinos out of state," says UMass Amherst epidemiologist Rachel Volberg, lead investigator of the Massachusetts Gambling Impact Cohort (MAGIC) study.

Conducted by the Social and Economic Impacts of Gambling in Massachusetts (SEIGMA) research team at UMass Amherst's School of Public Health and Health Sciences, MAGIC is the first major adult cohort study of gambling in the U.S., which examines gambling behaviors by surveying the same individuals over time. The study aims to uncover and understand populations at higher risk of experiencing problem gambling and gambling harm, and to support the development of effective and efficient treatment and prevention programs in Massachusetts.

The new report, prepared by lead author Alissa Mazar and presented to the Massachusetts Gaming Commission at its meeting in Boston, covers "Wave 3," a period from 2015 to 2016, before the state's two large resort-casinos opened in August 2018 and June 2019.

"Although this report focuses on results from before the opening of MGM Springfield and Encore Boston Harbor, we have already learned a great deal about how gambling problems among Massachusetts adults develop, progress and remit - information that will assist the Gaming Commission and the Department of Public Health in crafting the right mix of prevention, intervention, treatment and recovery services to effectively minimize and mitigate gambling harm in the Commonwealth," Volberg says.

In another "very interesting finding," Volberg notes that people who gambled were unlikely to stop gambling over the three years surveyed so far. "That has implications for both prevention and treatment," she says. "On the prevention side, it suggests that it's important to provide people with tools to manage their gambling so it doesn't become problematic."

Other findings:

From 2015 to 2016, the incidence rate of problem gambling, which refers to the proportion of people who newly experience problem gambling over a 12-month period, was 1.2 percent, which is similar to other jurisdictions.

From Wave 2 to Wave 3, the remission rate, which refers to the proportion of people no longer experiencing problem gambling who were experiencing this disorder 12 months prior, was 44 percent. Slightly more individuals remitted compared with the number identified as new problem gamblers.

"When you have people both developing a problem and remitting within a given period, that suggests problem gambling can be reduced by using some resources for treatment and some for preventing people from progressing to a more serious situation in the first place," Volberg says.

Conventional substance abuse and gambling treatment programs, which typically require people to abstain from their problem behavior, may not be the most effective treatment model, the study's data suggest. "Only 3 to 10 percent of problem gamblers ever seek professional treatment," Volberg says. "If you put up that abstinence barrier, it makes it very unattractive for someone who could benefit from the help."

The next MAGIC report, to be released in 2020, will examine the predictors of problem gambling over years and whether racial/ethnic, income, gender and/or regional differences exist in these predictors.

A phase 2 clinical trial has found that combining a molecular targeted drug called temsirolimus with chemotherapy shows promise in the treatment of rhabdomyosarcoma, the most common soft tissue sarcoma in childhood. The Children's Oncology Group trial was led by Leo Mascarenhas, MD, MS, Deputy Director of the Children's Center for Cancer and Blood Diseases at Children's Hospital Los Angeles. Results were recently published online in the Journal of Clinical Oncology.

"Since the early 1990s, there's been no change in the overall survival or risk of recurrence of this disease," explains Dr. Mascarenhas, Section Head, Oncology, in the Division of Oncology, Hematology and Blood and Marrow Transplantation at CHLA. "This trial was pivotal in finding a path forward to potentially break the stalemate."

Rhabdomyosarcoma is a rare childhood cancer that arises in the body's soft tissues, such as muscle. A small group of patients--those whose tumors can be surgically removed at the time of diagnosis--have an over 90% chance of being cured. But for others, the outlook is far less certain. About half are considered "intermediate-risk," with a 60% to 70% chance of long-term survival. Roughly 25% of patients are diagnosed with disease that's already spread; these children have a poor prognosis. In addition, once rhabdomyosarcoma relapses in any patient, long-term survival plummets to under 20%.

The goal of the clinical trial was to see if a targeted drug could be paired with chemotherapy to improve patient outcomes. It was the first-ever randomized trial in rhabdomyosarcoma to test targeted agents in combination with chemotherapy in both treatment groups.

Researchers compared two targeted drugs against each other: bevacizumab, which inhibits the growth of blood vessels that feed tumors, and temsirolimus, which inhibits a pathway often active in rhabdomyosarcoma called mammalian target of rapamycin (mTOR). Both drugs are approved by the Food and Drug Administration for use in other cancers.

The multicenter trial enrolled 86 rhabdomyosarcoma patients who had relapsed for the first time. About half received bevacizumab with chemotherapy; the other half received temsirolimus with chemotherapy. The chemotherapy agents used were vinorelbine and cyclophosphamide.

Enrollment was stopped early because an interim analysis showed that the temsirolimus combination was clearly superior. After six months, the event-free survival rate of patients receiving the bevacizumab treatment was 54.6%--comparable to results expected at this point in treatment with chemotherapy alone. For patients receiving temsirolimus, it was 69.1%.

The goal of this trial was to determine which molecularly targeted agent warranted further investigation. Because the patients studied had already relapsed, most did not survive long-term on either treatment. However, the Children's Oncology Group is now conducting a multicenter, phase 3 clinical trial to study the effectiveness of the temsirolimus-chemotherapy combination in newly diagnosed, intermediate-risk patients.

Researchers are trying to see if giving this therapy early on--when the cancer is most sensitive to treatment--will improve long-term outcomes.

"Prior to these results, there were no compelling ideas on how to improve survival of newly diagnosed patients," says Dr. Mascarenhas, who directs the Sarcoma and Solid Tumor Program at CHLA and is also Associate Professor of Pediatrics at the Keck School of Medicine of USC. "There is a lot more work to be done. But we now may have a way forward."

For the first time, astrophysicists have heard a black hole ringing like a bell. By reanalyzing the first black hole merger ever detected, the astrophysicists measured the gravitational wave 'tones' emitted following the event. The breakthrough comes 10 years earlier than expected and confirms that the properties of black holes are just as Einstein predicted in his theory of general relativity in 1915.

"Previously it was believed these tones were too faint to be detected, yet now we are able to," says study co-author Will Farr. "Just like the measurement of atomic spectra in the late 1800s opened the era of stellar astrophysics and classifying and understanding stars, this is the opening of the era of black hole spectra and understanding black holes and the general relativity that sits behind them."

Farr is an associate professor at Stony Brook University in New York and group leader for gravitational wave astronomy at the Flatiron Institute's Center for Computational Astrophysics in New York City. He and his colleagues present their findings September 12 in Physical Review Letters.

When two black holes merge into one, the resulting supersized black hole wobbles like a struck bell. The reverberations emit gravitational waves at characteristic tones that fade away as the black hole settles. The so-called 'no-hair theory' states that these tones -- and all other external properties of a black hole -- depend only on the black hole's mass and rotation, just as Einstein's general relativity predicts. Some scientists, however, propose that reality is hairier and that effects like quantum mechanics play a role as well.

Scientists knew that detecting a black hole's tones could settle the debate. But the tones were thought to be too quiet to be detected by the current-generation gravitational wave detectors LIGO and Virgo.

In the new study, the astrophysicists combined simulations of black hole mergers with a reanalysis of the first gravitational waves ever detected. Those waves came from the merger of two black holes. The analysis led to the identification of two independent tones emitted by the newly combined black hole. The pitch and decay rates of these tones lined up with Einstein's general relativity. The no-hair theory stood triumphant.

Farr says that with new data analysis and with LIGO and Virgo continuing to observe black hole mergers, tests from the observatories will become more precise. The added precision will likely lead to additional detections of black hole tones and an improved understanding of the exotic objects.

Farr collaborated on the study with Maximiliano Isi of the Massachusetts Institute of Technology and the astrophysicists Matt Giesler, Mark Scheel and Saul Teukolsky of the California Institute of Technology.

Metastasizing breast cancers typically seek out the bones, lung, and brain. Brain metastases are especially dangerous; many women survive for less than a year after diagnosis. How is the cancer able to get past the blood brain barrier? And can it be blocked?

Those questions led PhD candidate Golnaz Morad, DDS, and her mentor Marsha Moses, PhD, to conduct an in-depth investigation of exosomes, also known as extracellular vesicles or EVs, and their role in breast-to-brain metastasis. Their surprising findings appear in the journal ACS Nano.

"Golnaz was able to identify the mechanism by which EVs pass through the blood brain barrier and provide a 'niche' so that breast cancer cells can metastasize to brain," says Moses, who directs the Vascular Biology Program at Boston Children's Hospital and whose lab is interested in women's cancers.

Now that they know the mechanism, Moses and Morad hope to identify therapeutic targets that could stop brain metastases from happening.

EVs and cancer

Simply put, EVs are tiny bubbles released by cells, encapsulating chemical messages they wish to convey. In the case of cancer cells, EVs carry factors that help create a more hospitable environment for both the primary tumor and its metastases, as Moses and Morad detailed recently in a review article. Primary tumors can secrete EVs into the circulation, allowing them to travel to distant organs and help spread the cancer.

"The main question we had was, how can EVs reach the brain in the first place?" says Morad. "The blood brain barrier doesn't allow anything larger than 400 daltons to passively get into brain tissue. Exosomes are more than two thousand times larger than the size cutoff limit."

Hijacking transcytosis

The blood brain barrier (BBB) is a complex structure made up of three kinds of cells. EVs traveling in the blood first encounter tightly joined brain endothelial cells. Pericytes comprise the next layer, followed by astrocytes (the "feet," which connect to the cell bodies). Crosstalk between the cells circles the wagons even tighter: Astrocytes and pericytes send cues to the endothelial cells to tighten up the junctions.

Morad, Moses, and colleagues worked with several models of the BBB, including in vitro microfluidic models of the BBB ("BBB on a chip"), as well as static in vitro models and live zebrafish and mouse models. The labs of Donald Ingber, MD, PhD, and Leonard Zon, MD, collaborated in the development of the BBB-on-a-chip and zebrafish models, respectively. The Moses Lab also collaborated with the lab of Christopher Carman, PhD, of Harvard's T.H. Chan School of Public Health for the high-resolution imaging conducted in this study.

Each model and technique provided its own insights. Bottom line, Morad and Moses showed, for the first time, that rather than squeezing in between the cells in the BBB to get into the brain, the EVs trick the endothelial cells into taking them up. Using a standard biological pathway called transcytosis, the cells simply engulfed the EVs, bringing them inside and releasing them into brain tissue like so many Trojan horses.

"EVs can also manipulate endothelial cells to facilitate their own transport across the BBB," says Morad. "They hijack the pathways involved in the uptake and sorting of molecules and change regulation of the pathways."

Ongoing work in the Moses Lab shows that once the EVs have breached the barrier, they trick astrocytes into sending signals to the surrounding environment, making it more receptive to tumor growth. An inventory of these signals, using mass spectrometry and other techniques, identified some that are known to degrade the network of proteins providing structural and biochemical support to brain cells.

EVs as anticancer delivery vehicles?

For the study, Morad had to develop special methods to harvest the EVs in quantity and to verify their identity.

"They are remarkable little vehicles, but it is very challenging to get enough of them," says Moses.

Having discovered what EVs do to help breast cancer metastasize to the brain, the Moses Lab hopes to turn the tables -- and use EVs (or synthetic versions) to deliver anticancer drugs that home to the metastatic site. That work is ongoing.

The work, for which the investigators have filed patents, was supported by the Breast Cancer Research Foundation, the National Institutes of Health (R01 CA185530, K01 DK111790), and the Advanced Medical Foundation. See the paper for a full list of authors.

Patients with sepsis often require surgery or imaging procedures under general anesthesia, yet there is no standard regimen for anesthetizing septic patients. Of volatile (inhaled) anesthetics, sevoflurane and isoflurane are the most commonly used drugs, despite their undetermined mechanisms of action. A novel study in The FASEB Journal suggests that the type of drug used in general anesthesia could be critical to the survival of patients with sepsis.

To conduct the experiment, researchers induced sepsis in a mouse model. They then separated the mice into three groups: the first received sevoflurane, the second received isoflurane, and the third acted as a control, receiving no anesthetic. Compared with the control, the first group exposed to sevoflurane displayed improved survival rates, less bacteria in their organs, and less splenic neutrophil apoptosis (i.e., the process through which immune cells die). The second group exposed to isoflurane, on the other hand, displayed worsened sepsis outcomes than the control.

"With the prevalence of sepsis on the rise and the mortality rates of severe sepsis already extremely high, it is crucial that our findings are validated in a human model," said Koichi Yuki, MD, an associate professor of anesthesia at Boston Children's Hospital, Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division. "We are hopeful that one day, the findings from this study will improve the outcomes of patients with sepsis."

"The clinical importance of this study cannot be overstated," said Thoru Pederson, PhD, Editor-in-Chief of The FASEB Journal.

Songbirds exposed to imidacloprid, a widely used neonicotinoid insecticide, exhibit anorexic behavior, reduced body weight and delays in their migratory itinerary, according to a new study. This is perhaps the first direct evidence of a mechanistic link between the pesticide and declining migratory bird populations. The results suggest that, even in tiny sublethal doses, the presence of these neurotoxic compounds at critical stopover sites refueling birds visit on their cross-continental springtime journeys could be contributing to the overall population declines observed among many migratory species. Neonicotinoids are the most widely used class of agricultural pesticide. However, while the controversial neurotoxic insecticide is advertised to pose a low risk to vertebrates, a growing body of evidence has shown that neonicotinoids may have significant negative impacts on a number of species, including birds. This research has suggested that birds who use agricultural environments as habitats or for foraging stopovers during migration are routinely exposed to neonicotinoid pesticides. Many of these species are also undergoing precipitous population declines. Despite this association, the overall influence of neonicotinoids on wild migratory songbirds remains virtually unknown. Building on previous research, Margaret Eng and colleagues used automated telemetry to track individual white-crowned sparrows they experimentally exposed to sublethal yet field-realistic doses of imidacloprid during migration. The authors found that the pesticide acted as an anorexic agent within the birds, causing rapid losses in body weight and fat. This resulted in extended stays at stopover sites as the birds had to forage longer to restore their greatly depleted fuel stores and to recover from imidacloprid's neurotoxic effects before moving on. According to Eng et al., the use of neonicotinoids along migratory routes throughout North America means that birds may suffer repeated exposure at successive stopover sites, amplifying migration delays and their consequences.