Culture

Charles Lieber and his group are rewriting the rules of how scientists study retinal cells, and they're doing it with a single injection.

For decades, scientists hoping to understand how the retina interprets visual input have often had to resort to invasive techniques to dissect the retina from the animal in an effort to record the cells' activity, but a new system developed by Lieber, the Joshua and Beth Friedman University Professor and Chair of the Department of Chemistry and Chemical Biology, and Guosong Hong, a post-doctoral fellow working in Lieber's lab, make it possible to track the firing patterns of dozens of cells chronically in awake animals.

The system uses ultraflexible mesh electronics developed in Lieber's lab which can be non-invasively injected and interact with tissue at a cellular level, allowing scientists to record the activity of a variety of retinal cell types simultaneously for weeks.

In a new study, Lieber and Hong not only demonstrated that the system offers new opportunities to track the activity of retinal cells, but were also able to use the system to reveal new information about how retinal ganglion cells behave over the course of multiple circadian cycles. The study is described in a June 29 paper published in Science, in collaboration with Joshua Sanes, the Paul J. Finnegan Family Director of Harvard Center for Brain Science and the Jeff C. Tarr Professor of Molecular and Cellular Biology, with other leading authors Tian-Ming Fu, a former graduate student in the Lieber lab, and Mu Qiao, a former graduate student in the Sanes lab.

"Now we can do things that were a dream before," Lieber said, of the technique. "Since the 1970s, the only way to measure this fundamental sensory input has been with invasive, surgical procedures to remove the eye from the animal, (so) I think this opens up completely new opportunities for vision research. Even as we were documenting this new methodology, we were able to find new biology...so I think this will be an important new tool that can transform what people thought they could do in this field."

The mesh electronics used in the system were developed by Lieber and colleagues several years ago, comprising macroporous and ultraflexible electronic network that can be injected into soft tissue where it interacts with the nervous system on a single-neuron level.

The ability to inject the mesh was a key to the development of the system to monitor retinal ganglion cells, Lieber said.

"That's one of the unique things about this work," he said. "Because these mesh (probes) are injectable, we can do something that just isn't possible with rigid probes, which is a non-coaxial implantation. Normally, when you use a probe, you insert it and pull it out along a single axis, but Guosong and Tian-Ming (or Hong and Fu) developed this non-coaxial technique to trace the curvature of the retinal cup so the mesh can unfold and conformally coat the retina...so in a way you could ultimately think of this as an artificial receptor layer."

And because the tissue-like mesh electronics interact with retina at a biological level, the authors were able to track the activity of specific cells not over hours, but over weeks, gaining new insight into the circadian cycles of the cells experience over the day.

"What we showed is that the firing rate of certain cells changes dramatically at different times in the circadian cycle," Hong said. "We summarized the activity for different cells for three circadian cycles, from day one to day seven, and for some cells, the firing rate increased during the day, between 8 am and 8 pm, but different cells showed the complete opposite behavior with increased firing rates at night."

Without the injectable mesh, Hong said, the discovery would not be possible. In part, that's because researchers needed to monitor the cells for multiple complete circadian cycles - something that's impossible with traditional, rigid probes.

And though researchers had previously observed increased activity in bipolar retinal cells during daylight hours, those measurements were based on observing large populations of cells, Hong added. The discovery that some cells increase their activity at night was only possible due to the mesh's ability to observe and chronically track individual cells.

"This is new biology that we can see using this tool, but this is only one of many possibilities," Hong said.

In future studies, he plans to collaborate with Joshua Sanes and Zhigang He, Professor of Neurology and Professor of Ophthalmology at Harvard Medical School to explore a model for understanding glaucoma.

"The hope is that they might one day be able to develop some type of treatment, but until they understand the timing of how the disease progresses, we can't know what's going on," Hong said. "So already we can see there's a very important medical application for this tool that a lot of people can identify with."

Going forward, Lieber said, he believes the new system can be used to study any number of processes that occur during development, as well as understanding how firing patterns in retinal cells are passed on to and interpreted by the brain.

"We've already been able to measure the input to the retina, but with one or two more injections, we can measure the connections to the next relay station in the brain," Lieber said. "So we will be able to see the interactions between these neurons."

Genetic ancestry tests are often advertised as a tool to uncover new connections to diverse cultures and ancestries, but new research from the University of British Columbia has found people tend to pick and choose which races they identify with based on preconceived biases.

Ancestry testing is part of a rapidly growing, billion-dollar industry that claims to use DNA to tell people about the parts of the world from which their ancestors originated. In research published this week in the American Journal of Sociology, sociologists found that, rather than embrace all their test results, people who use genetic ancestry tests tend to selectively identify with ethnicities they view as positive while disregarding others.

"People often buy these genetic ancestry tests because they're looking for a sense of belonging or to confirm a story that's been passed down in their family," said Wendy Roth, associate professor in the department of sociology and the study's lead author. "But if the test results don't support what they want to believe, we found that people will often ignore the results or criticize them. We tend to cherry-pick the parts of our family story that we like most and want to emphasize."

For the study, researchers interviewed 100 American genetic ancestry test users who said they identified before the test as white, black, Hispanic/Latino, Asian, or Native American. Study participants were asked questions about their ethnic and racial identities over their lifetime. The participants were interviewed a second time, 18 months after genetic testing, to examine how they made sense of test results and how their identities had changed over time.

One study participant, "Eduardo," identified as a white Mexican-American before the test, but his genetic ancestry test results reported Native American, Celtic and Jewish ancestries. The researchers found that Eduardo disregarded his Celtic ancestry but embraced his Jewish identity, explaining: "I always looked up to the Jewish people... I thought of them as higher than me." Another participant, "Shannon," was adopted and always believed she had Native American lineage through her birth parents. When her test results revealed no Native American ancestry, she decided the test was incorrect and continued to identify as Native American.

White respondents were more likely to embrace new racial identities, as long as they felt others would still accept them, the researchers found.

"White identity is something that lots of people around them have, so it doesn't feel special," said Roth. "Part of it may be guilt about being white and feeling somewhat privileged. They want something that makes them feel unique, whereas for many people of colour, they've known all along that they have some racial mixture in their ancestry, and it's not as surprising."

Roth noted there are at least 74 companies that have sold genetic ancestry tests, but she warned that their tests should be taken with a grain of salt.

"There are many ways in which genetic tests that tell you the percentages of your ancestry are misleading and they're often misunderstood," said Roth. "Some tests can be useful for helping people track down long-lost relatives who are genetic matches, if they're lucky. But people who use these tests to determine their race or inform their sense of identity should be aware that this isn't the right way to think about it."

Spiders are ubiquitous within our forests, fields, and backyards. Although you may be used to seeing the beautiful yellow and black spiders of the genus Argiope in your garden, large ground-scurrying wolf spiders in your yard, or spindly cellar spiders in your basement, this new sheet-web-building spider is probably one you haven't seen before. The reason is that it's known from a single cave in the world, Stygeon River Cave, in southern Indiana.

The University of Indianapolis assistant professor, Dr. Marc Milne, described the rare species in the open access journal Subterranean Biology with the help of a University of Indianapolis alumnus, Elizabeth Wells, who illustrated the spider for the manuscript.

Sheet weavers, also known as dwarf spiders or money spiders, are minute creatures growing no larger than a few centimetres in length, which makes them particularly elusive. Their peculiar webs are flat and sheet-like, hence their common English name.

The new spider, Islandiana lewisi, is an homage. Milne was shown the spider by a fellow scientist, Dr. Julian Lewis, who noticed the critter on one of his many cave expeditions. In appreciation for his help, Milne and Wells named the spider after Lewis.

This is the fifteenth species in its genus (Islandiana) and the fifth known to live exclusively in caves. It has been over 30 years since the last species has been added to this group.

At about 2 mm in size, Islandiana lewisi is thought to feed on even smaller arthropods, such as springtails living in the debris on the cave floor. It is unknown when it reproduces or if it exists anywhere else. The spider is likely harmless to humans.

The collectors of the spider, Milne and Lewis, described the hostile conditions within the cave, which the new species calls home: "because the cave floods from time to time, the insides were wet, muddy, slippery, and dangerous to walk on without the proper equipment."

Milne and Lewis found the spider in small, horizontal webs between large, mud-caked boulders in the largest room in the cave. It was collected in October 2016 with the permission of the landowner.

Milne hypothesized that he had collected something special, stating, "I didn't know what the spider was at first, I just thought it was odd that so many were living within this dark cave with no other spider species around."

After returning to the lab and inspecting the spider under a microscope, Milne initially misidentified the species. However, when he re-examined it months later, he realized that the species was indeed new to science.

Around 25 percent of Medicare spending in the U.S. occurs in the last year of people's lives. This is sometimes discussed as a questionable use of resources: Is society throwing large amounts of medical treatment at some patients in a futile, if noble, effort to extend lives that are bound to end soon?

A new study co-authored by an MIT health care economist offers a resounding answer: No.

After examining millions of medical records, the study found that although Medicare spending is concentrated among people who die, there is very little Medicare spending on patients whose death within the year is highly likely. For example, the researchers discovered, less than 5 percent of Medicare spending is applied to the single highest-risk percentile of all individuals -- and their predicted one-year mortality rate is still just 46 percent.

"What we discovered is, very little money is spent on people who we know with high probability are going to die in a short amount of time," says Amy Finkelstein, a professor in MIT's Department of Economics and co-author of a paper in the journal Science that details the study's findings. To the extent that such cases exist, she adds, "they're just not the drivers of spending" in bulk.

The study also illuminates the general circumstances of late-in-life mortality. Fewer than 10 percent of people who die in a given year have a predicted one-year mortality rate over 50 percent. As the researchers found, even when people are admitted to a hospital in what turns out to be their last year of life, fewer than 4 percent of those patients have a predicted one-year mortality rate of 80 percent or higher at the time of admission.

In a sense, the study shows, the apparent concentration of spending on last-year-in-life patients is a byproduct of the fact that even relatively low-mortality health scenarios for the elderly will include a certain number of deaths -- not that the individual treatment decisions represent longshot cases.

"I do hope we stop pointing to end-of-life spending as an obvious problem," Finkelstein says. "That's not to say there aren't problems in the U.S. health care system, but this is not a symptom of them."

The paper, "Predictive modeling of U.S. healthcare spending in late life," is being published in Science. The authors are Liran Einav, a professor of economics at Stanford University; Finkelstein, the John and Jennie S. MacDonald Professor at MIT; Sendhil Mullainathan, a professor in the economics department at Harvard University; and Ziad Obermeyer, an assistant professor at Harvard Medical School.

Highly unpredictable

To conduct the study, the research team examined a random sample of almost 6 million Medicare enrollees who were in the program as of Jan. 1, 2008. For survivors, the study examines health care spending for all of 2008; for people who died in 2008, it examines spending over the year prior to death. The analysis produces mortality predictions as of Jan. 1, 2008, using data on demographics, health care use, and more.

The analysis also deployed a standard form of machine learning to evaluate the impact of a wide range of variables on health care trajectories, and to produce a probability of death within one year for every enrollee in the study.

The overarching result, as the authors write in the paper, is simple: "Death is highly unpredictable."

Take, for instance, that top percentile of high-risk Medicare enrollees, those whose one-year predicted mortality rate is 46 percent: Of those patients, 44 percent survived for at least one year after the start of the study. Similarly, the predicted one-year mortality rate at the 95th percentile of people in the study is just 25 percent.

Moreover, the study finds, the basic fact that we spend more money on people who are sick -- in the study, both those who recovered and those who died -- accounts for 30 to 50 percent of the concentration of spending on people in their last 12 months of life.

"I think the typical narrative is: 'Wow, the U.S. spends so much on health care and a quarter of that is in the last 12 months of life. That money is obviously a waste; we spent all this money and they died,'" says Finkelstein. "But that's not the right way to look at it. We don't know in advance who's going to die this year, and some of the people we spend money on survive."

"Let's not get distracted by misleading statistics"

The paper's authors suggest that productive new avenues for research on efficiency and medical spending will look concretely at more specific parts of the picture. Or, as they write in the paper, "a focus on end-of-life spending is not, by itself, a useful way to identify wasteful spending."

Instead, Finkelstein contends, it would be more productive to zoom in on particular kinds of treatments and procedures, among other things, to assess their effectiveness, rather than generalizing about efficiency based on massive aggregate numbers such as the last-year-of-life Medicare figure.

"What we need to do is engage in the challenging task of figuring out which kinds of spending are yielding health benefits, and what types aren't," Finkelstein says. "Let's focus on the real problem and not get distracted by misleading statistics. There's a lot of hard work ahead of us, not easy answers."

Finkelstein adds: "The policy upshot is: It's important we understand the things we're talking about."

When playing an economic game those that were assigned as 'lower status' were more likely to share their wealth than their 'higher status' counterparts, according to a new study at Queen Mary University of London.

The social experiment involved a series of economic games in which people played with other people for real money. The games involved participants deciding how much money they kept and how much they gave to a group pot. The money in the pot was always shared out to the players.

Participants were assigned a status, either 'higher status' or 'lower status'. This determined how much more or less money they were allotted compared to a group of other others that they played with. In some experiments participants were allocated high or low status based on chance and in other experiments they were allocated high or low status based on effort.

The study found that overall, the low status participants contributed more than the high status participants. Also, high status participants contributed even less when they had earned their wealth through effort compared to those who had acquired their riches through chance.

The study, published in the journal Basic and Applied Social Psychology, demonstrates under laboratory conditions that once we gain access to more resources, the way in which we gain access will determine how we behave with others.

Lead author Dr Magda Osman from Queen Mary's School of Biological and Chemical Sciences, said: "For the high status individuals, the way in which wealth was achieved, whether through chance or effort, appeared to be the key factor determining the level of cooperation observed. This wasn't the case for the low status individuals. How they got to their low status made no difference to their behaviour in the game.

"If you gain high status through effort, rather than chance, you are even more likely to want to keep what you own. When you have limited status one obvious strategic way to increase it, is through cooperation. The point here being that even if one is acting cooperatively, there is no reason to think that this is purely for altruistic reasons."

She added: "There is an element of risk in this game, because if you contribute anything to the shared pot there is no way of knowing, and no guarantee that anyone else from the group will do the same. So what is surprising is that low status individuals are willing to take a bigger risk, with fewer resources than the high status individuals. In other words, you take a risk by being pro-social because you have no idea if it will be reciprocated."

The study also goes to show that we can't rely on empathy as a way to improve the good will of those that are in high status positions, this consistently failed to work in the experiments.

Dr Osman said: "The other surprising finding is that empathy has next to no impact on promoting pro-social behaviour, in other words contributing money to the group pot. This matters because there are a lot of claims that empathy is the glue that binds people to act socially. What we show is that when money matters, empathy plays virtually no role in improving pro-social behaviours."

Although it's far from perfect by virtually any measure - whether poverty rates, violence, access to education, racism and prejudice or any number of others - the world continues to improve. Why, then, do polls consistently show that people believe otherwise?

The answer, Daniel Gilbert says, may lie in a phenomenon called "prevalence induced concept change."

As demonstrated in a series of new studies, Gilbert, the Edgar Pierce Professor of Psychology, his post-doctoral student David Levari, and several other colleagues, show that as the prevalence of a problem is reduced, humans are naturally inclined to redefine the problem itself. The result is that as a problem becomes smaller, people's conceptualizations of that problem become larger, which can lead them to miss the fact that they've solved it. The studies are described in a paper in the June 29th issue of Science.

"Our studies show that people judge each new instance of a concept in the context of the previous instances," Gilbert said. "So as we reduce the prevalence of a problem, such as discrimination for example, we judge each new behavior in the improved context that we have created."

"Another way to say this is that solving problems causes us to expand our definitions of them," he said. "When problems become rare, we count more things as problems. Our studies suggest that when the world gets better, we become harsher critics of it, and this can cause us to mistakenly conclude that it hasn't actually gotten better at all. Progress, it seems, tends to mask itself."

The phenomenon isn't limited to large, seemingly intractable social issues, Gilbert said. In several experiments described in the paper, it emerged even when participants were asked to look for blue dots.

"We had volunteers look at thousands of dots on a computer screen one at a time and decide if each was or was not blue," Gilbert said. "When we lowered the prevalence of blue dots, and what we found was that our participants began to classify as blue dots they had previously classified as purple."

Even when participants were warned to be on the lookout for the phenomenon, and even when they were offered money not to let it happen, the results showed they continued to alter their definitions of blue.

Another experiment showed similar results using faces. When the prevalence of threatening faces was reduced, people began to identify neutral faces as threatening.

Perhaps the most socially relevant of the studies described in the paper, Gilbert said, involved participants acting as members of an institutional review board, the committee that reviews research methodology to ensure that scientific studies are ethical.

"We asked participants to review proposals for studies that varied from highly ethical to highly unethical," he said. "Over time, we lowered the prevalence of unethical studies, and sure enough, when we did that, our participants started to identify innocuous studies as unethical."

In some cases, Gilbert said, prevalence-induced concept change makes perfect sense, as in the case of an emergency room doctor trying to triage patients.

"If the ER is full of gunshot victims and someone comes in with a broken arm, the doctor will tell that person to wait," he said. "But imagine one Sunday where there are no gunshot victims. Should that doctor hold her definition of "needing immediate attention" constant and tell the guy with the broken arm to wait anyway? Of course not! She should change her definition based on this new context."

In other cases, however, prevalence-induced concept change can be a problem.

"Nobody thinks a radiologist should change his definition of what constitutes a tumor and continue to find them even when they're gone," Gilbert said. "That's a case in which you really must be able to know when your work is done. You should be able to see that the prevalence of tumors has gone to zero and call it a day. Our studies simply suggest that this isn't an easy thing to do. Our definitions of concepts seem to expand whether we want them to or not."

Aside from the obvious questions it raises about how we might go about fixing problems both large and small, the studies also point to issues of how we talk about addressing those problems.

"Expanding one's definition of a problem may be seen by some as evidence of political correctness run amuck," Gilbert said. "They will argue that reducing the prevalence of discrimination, for example, will simply cause us to start calling more behaviors discriminatory. Others will see the expansion of concepts as an increase in social sensitivity, as we become aware of problems that we previously failed to recognize."

"Our studies take no position on this," he added. "There are clearly times in life when our definitions should be held constant, and there are clearly times when they should be expanded. Our experiments simply show that when we are in the former circumstance, we often act as though we are in the latter."

Ultimately, Gilbert said, these studies suggests that there may be a need for institutional mechanisms to guard against the prevalence-induced concept change.

"Anyone whose job involves reducing the prevalence of something should know that it isn't always easy to tell when their work is done," he said. "On the other hand, our studies suggest that simply being aware of this problem is not sufficient to prevent it. What can prevent it? No one yet knows. That's what the phrase 'more research is needed' was invented for."

Researchers have identified a new gene-activation pathway caused by lipids associated with coronary artery disease, a finding that could help identify new directions in research and drug development. The study was published in June in Nature Communications.

The discovery that exposure to lipids activates a gene called MTHFD2 in the walls of blood vessels was made by researchers from the Institute for Cardiovascular Physiology of Goethe University in Frankfurt, Germany, and the Department of Genetics and Genomic Sciences of the Icahn School of Medicine at Mount Sinai in New York. The researchers used a computational model of the cells lining blood vessels in the human heart developed at Mount Sinai.

Atherosclerosis is caused by the buildup of a complex mixture of components, commonly referred to as plaque, within the inner lining of arteries. Oxidized phospholipids are abundant in this arterial plaque and are thought to promote atherosclerosis progression. However, the specific cellular processes caused by these lipids on the arterial surface are still not well understood. The cells composing the inner surface of blood vessels, called endothelial cells, are at the forefront of the atherosclerotic process and therefore are a major focus of research into coronary artery disease.

"Endothelial cell response to lipids has been studied extensively over the years, but it was still unknown that MTHFD2 was even functional in these cells," said Jun Zhu, PhD, Professor of Genetics and Genomic Sciences at the Icahn School of Medicine; Head of Data Science at Sema4, a patient-centered predictive health company that is a Mount Sinai venture; and co-senior author of the study. "Computational biological models such as the one we used in this study are allowing us to uncover a wealth of knowledge about complex diseases that we never could before."

The international research team predicted and validated in follow-up experiments that the MTHFD2 gene plays a key role in endothelial cell response to oxidized phospholipids. They found that MTHFD2 was also activated in endothelial cells in response to other factors, such as inflammation or a change in amino acid concentration. This underscores the many factors involved in the development of atherosclerosis that must be understood and taken into consideration when approaching disease therapies.

"Our study showed that when the MTHFD2 gene is activated in endothelial cells in response to oxidized lipids, it sends out molecular 'danger signals' promoting inflammation and stimulating the atherosclerotic process," said Ralf Brandes, MD, Director of the Institute for Cardiovascular Physiology and Professor of Physiology at Goethe University. "These findings suggest that MTHFD2 could be a novel target to disrupt development and progression of atherosclerosis."

While the role of MTHFD2 in the vascular system was unknown before this study, the gene is known to be consistently activated in cancer, making it a promising target for cancer therapies. MTHFD2 inhibitors are already in clinical trials as anti-cancer therapies. "It's possible that these therapies could also help prevent coronary artery disease, but more research into the specific role of MTHFD2 in atherosclerosis is needed first before proposing it as a target for potential therapy," said Dr. Zhu.

BLOOMINGTON, Ind. -- Researchers at Indiana University have found early evidence that tiny snippets of genetic material called microRNA may help with early detection of conditions such as Alzheimer's disease.

The study, published June 18 in Nature Scientific Reports, found that changes in microRNA are detectable in mice long before they start to show symptoms from neurodegeneration. These microRNA changes may represent an early warning sign, or "biomarker," for the condition.

"Identifying biomarkers early in a disease is important for diagnosing the condition, and following its progression and response to treatment," said Hui-Chen Lu, a professor in the Linda and Jack Gill Center for Biomolecular Science and the Department of Psychological and Brain Sciences, a part of the IU Bloomington College of Arts and Sciences, who led the study. "You need something that can predict your future."

There is currently no treatment to stop or reverse the effects of neurodegenerative diseases such as Alzheimer's, Parkinson's, ALS or Huntington's. It's also estimated that Alzheimer's disease alone, which is the most common of these disorders, will affect 14 million Americans and cost taxpayers $1.1 trillion by 2050.

Unlike regular "messenger RNA," which direct cells to produce specific proteins, microRNA plays a regulatory role, increasing or decreasing the number of proteins that messenger RNAs encode. A single snippet of microRNA can impact the function of tens or hundreds of proteins in the body.

Due to their stability in urine and blood, there is growing interest in using microRNA as biomarkers for disease prediction and diagnosis. Lu's study is an early step to learn whether microRNA can be used to detect neurodegenerative disorders.

To explore this question, Lu and colleagues analyzed microRNA and messenger RNA in two groups: a healthy group and a group genetically modified to develop symptoms of dementia. The team found the highest level of "dysregulation" -- or deviation from normal levels -- in the microRNA of the dementia group before their physical symptoms developed.

"Higher levels of pre-symptomatic microRNA dysregulation are significant because it strongly suggests that it may have a role in changes in the brain in later stages," Lu said.

The team then compared the microRNA changes to the messenger RNA changes to identify biological pathways affected by microRNA dysregulation. Their analysis suggested that changes in microRNA affected pathways related to immunity in the dementia-prone model.

In response, the team then conducted additional tests to study a specific type of microRNA that was elevated in the dementia model. The microRNA -- called microRNA 142 -- is known to play a major role in inflammation, a part of the immune response.

They found that introducing this microRNA into the brain triggered a significant neuroinflammation. The result is important since many other studies have shown that chronic inflammation contributes to many types of disease, including neurodegeneration, Lu said.

She added that the next step will be to learn whether microRNA 142 is easily detectable through a blood test, a key quality for a truly non-invasive biomarker.

In-game purchasing systems, such as 'loot boxes', in popular online games resemble gambling and may pose financial risks for vulnerable players, according to gambling psychology researchers at the University of Adelaide.

The researchers have examined a range of popular online games that include the option of paying small fees ('microtransactions') to access additional features or content that enhance the player's experience.

In an editorial published today in the journal Addiction, the researchers say some online games enable endless spending behaviours and employ systems that disguise or withhold the long-term cost of these microtransactions. The true financial cost of such games may not be obvious until the player is financially or psychologically committed and then finds it more difficult to stop.

"These schemes may entice some players to spend more money than they may have intended or can afford, especially when using credit cards or virtual currency that makes it hard to keep track of spending," says Dr Daniel King, Senior Research Associate in the University of Adelaide's School of Psychology.

He and fellow author Professor Paul Delfabbro, also from the School of Psychology, focus on a purchasing scheme called the 'loot box', an in-game reward system in which players can repeatedly buy a random selection of virtual items. The loot box feature has recently been the subject of regulatory attention across many jurisdictions, with the Belgian Gambling Commission announcing in April this year that loot boxes were an illegal form of gambling.

"Players hoping to win a particular item may end up repeatedly buying loot boxes at significant personal expense," says Dr King. "Because loot boxes require no player skill and have a randomly determined outcome or prize, they function similarly to scratch tickets or gambling slot machines."

The editorial follows the World Health Organization's announcement last week that it plans for the first time to include 'gaming disorder' in its diagnostic manual, the International Classification of Diseases. The authors hope that drawing further attention to these new financial aspects in games may contribute to continuing debates on the nature and extent of gaming-related harms.

The researchers call loot boxes and similar schemes 'predatory monetisation' because they encourage repeated spending using tactics that may involve limited disclosure of the product, unavoidable solicitations, and manipulation of reward outcomes to encourage purchasing behaviours over skilful play.

They liken some of these schemes to a form of psychological 'entrapment' where players spend an escalating amount of money because they believe they have invested too much to quit. There are also sometimes pressuring tactics, incentivising purchases such as so-called 'limited time' offers.

"Some of the top-earning game publishers have registered patents for microtransaction systems that incentivise the player to spend money, but there are few regulations or consumer protections associated with these systems. I think most experienced gamers will agree: gaming should really be about skilful play, not gambling," says Professor Delfabbro.

The interstellar object Oumuamua was discovered back on October 19, 2017, but the puzzle of its true nature has taken months to unravel, and may never be fully solved.

Meaning "scout from the distant past" in Hawaiian, Oumuamua was found by astronomers working with the University of Hawaii's Pan-STARRS1 survey as it came close to Earth's orbit. But what is it: an asteroid or a comet? As soon as it was spotted, astronomers from around the world were on the case.

The first clue: its trajectory. Extensive follow-up observations by the Canada-France-Hawai?i Telescope (CFHT), the European Space Agency's (ESA) Optical Ground Station telescope in Tenerife, Canary Islands, and other telescopes around the world have helped pin it down.

Oumuamua was first spotted about a month after its closest approach to the Sun, which took it within the orbit of Mercury. Unlike any asteroid or comet observed before, this new object sped past the Sun, approaching from "above" the plabe of the planets on a highly inclined orbit, moving fast enough (70,800 miles per hour as of July 1, 2018) to escape the Sun's gravitational pull and eventually depart our Solar System.

Initially, astronomers assumed Oumuamua was a comet. Current understanding of planet formation predicts more interstellar comets than interstellar asteroids. However, astronomers did not see evidence of gas emission or a dusty environment in the observations. Without these hallmarks of cometary activity, it was classified as the first interstellar asteroid.

But the story has another surprising twist.

Following the initial discovery observations with Pan-STARRS, a team of astronomers, led by Marco Micheli of ESA's SSA-NEO Coordination Centre and Karen Meech of the University of Hawaii Institute for Astronomy, continued to make high precision measurements of the object and its position using many ground-based facilities like CFHT, as well as the Hubble Space Telescope. The final images were taken with Hubble in January, before the object became too faint to observe as it sped away on its outbound orbit.

Contrary to their expectations, the team found that the object was not following the anticipated trajectory if only the gravity of the Sun and the planets were determining its path. "Unexpectedly, we found that Oumuamua was not slowing down as much as it should have due to just gravitational forces," says Marco, lead author of the paper reporting the team's findings published today in the journal Nature. What could be causing this curious behavior?

Rigorous analysis ruled out a range of possible influences, such as radiation pressure or thermal effects from the Sun, or interaction with the Sun's solar wind. Other, less likely scenarios, such as a collision with another body, or Oumuamua being two separate, loosely held-together objects, were also discarded.

Comets contain ices that sublimate, or turn directly from a solid to a gas, when warmed by the Sun. This process drags out dust from the comet's surface to create a fuzzy "atmosphere" and sometimes a tail. The release of gas pressure at different locations and times can have the effect of pushing the comet slightly off-course compared with the expected path if only gravitational forces were at play.

"Thanks to the high quality of the observations we were able to characterize the direction and magnitude of the non-gravitational perturbation, which behaves the same way as comet outgassing," says Davide Farnocchia of NASA's Jet Propulsion Laboratory.

The team has not detected any dusty material or chemical signatures that would typically characterize a comet, even in the deepest images from ESO''s Very Large Telescope, Hubble, and the Gemini South telescope. "Oumuamua is small -- no more than a half a mile long -- and it could have been releasing a small amount of relatively large dust for it to have escaped detection," said Meech. "To really understand Oumuamua we would need to send a space probe to it. This is actually possible, but it would be very expensive and take a long time to get there, so it isn't practical this time. We just have to be ready for the next one."

"It was extremely surprising that Oumuamua first appeared as an asteroid, given that we expect interstellar comets should be far more abundant, so we have at least solved that particular puzzle," says Olivier Hainaut of the European Southern Observatory. "It is still a tiny and weird object that is not behaving like a typical comet, but our results certainly lean towards it being a comet and not an asteroid after all."

Because of its small size and faintness, current observations of Oumuamua do not provide all the information astronomers need to determine important aspects of the comet's surface. "When Oumuamua was discovered, the astronomy community gathered as much data as possible, but ultimately, the object was just not visible long enough to answer all our questions," says Ken Chambers from Pan-STARRS. "With Pan-STARRS monitoring the skies, we hope to discover more Oumuamua-like objects in the future and begin to answer the really interesting questions about this class of objects."

MINNEAPOLIS - While it has been known that estrogen plays a role in migraine for women, new research shows that the female sex hormone may also play a role in migraine for men, according to a small study published in the June 27, 2018, online issue of Neurology®, the medical journal of the American Academy of Neurology.

Migraine is a disabling neurologic disorder marked by frequent attacks of severe headaches. During childbearing years, women are three times more likely to have migraine than men.

"Previous research has found that levels of estrogen can influence when women have migraines and how severe they are, but little is known about whether sex hormones also affect migraine in men," said study author W.P.J. van Oosterhout, MD, of Leiden University Medical Centre in the Netherlands. "Our research found increased levels of estrogen in men with migraine, as well as symptoms of lower levels of testosterone."

The study involved 17 men with an average age of 47 who had a migraine an average of three times a month. None were taking medication known to affect hormone levels. They were compared to 22 men without migraine. All participants were of healthy weight, matched for age and body mass index.

Researchers measured the levels of both estradiol, an estrogen, and testosterone in the blood. They took four blood samples from each participant on a single day, each three hours apart. For those with migraine, the first blood samples were taken on a non-migraine day and then each day thereafter until the participant had a migraine.

They found that men with migraine had higher levels of estrogen between migraines, 97 picomoles per liter (pmol/L), compared to 69 pmol/L in men without migraine, while testosterone levels were similar for both groups. This resulted in a lower ratio of testosterone to estrogen between migraines, 3.9, compared with men without migraine, 5.0. Testosterone levels did increase 24 hours before a migraine in men who experienced pre-migraine symptoms like fatigue, muscle stiffness and food cravings.

In addition, participants were surveyed about symptoms that they may have a relative deficiency in testosterone, such as mood, energy and sexual disorders, and researchers found that men with migraine more frequently reported such symptoms and the symptoms were more often severe. A total of 61 percent of men with migraine reported such symptoms, compared to 27 percent of men without migraine.

"Further studies are needed in larger populations to validate our findings," said Van Oosterhout. "The exact role of estrogen in men with migraine, and whether fluctuations in estrogen may be associated with migraine activity, like they are in women, needs to be fully investigated."

A limitation of the study is that participants filled out a questionnaire to be considered for enrollment. It is possible that those with severe migraine were more likely to fill out the questionnaire, meaning results from this study may only apply to people with severe migraine.

Providing care based on need not ability to pay is the NHS's greatest achievement, say readers of The BMJ

'Providing care based on need and free at the point of delivery' has been voted the NHS's greatest achievement in its 70 years by readers of The BMJ.

Over 5,500 readers voted on a shortlist of 12 contenders to find the NHS's greatest achievement since it launched on 5 July 1948.

Providing care based on need received 23% of the votes, closely followed by 'limiting commercial influence on patient care,' which received 18% of the votes. 'General practice as the foundation for patient care' was third, receiving 10% of all votes.

The BMJ's UK Editor Tom Moberly explains that, while many saw the NHS as "a Godsend" in the dark days after the Second World War, its introduction was not universally welcomed when it was launched.

Social insurance was often seen as the best way to fund a national health service, he writes, but Aneurin Bevan believed that it should be funded out of general taxation, in line with the fundamental principle that health was "a basic human right."

As today's vote suggests, the legacy of his belief lives on in popular public opinion.

In second place with 18% of the votes was 'limiting commercial influence on patient care.' Louise Irvine, a GP in Lewisham, London, says this reflects the high value that patients place on knowing clinicians are not encumbered by commercial influences offering advice on treatments.

'General practice as the foundation for patient care' was the third most popular choice, receiving 10% of all votes. Helen Stokes-Lampard, chair of the Royal College of GPs, points out that the trusted relationship a patient and their family has with their GP is unique in healthcare. "It is one of the reasons why we are so effectively able to deliver care to over a million patients every day in the UK," she says.

Commenting on the results, Dr Fiona Godlee, The BMJ's Editor in Chief said: "It is deeply heartening to see a founding and fundamental principle of the NHS topping a list of achievements that makes us most proud - it is a truly deserving winner."

She adds: "I'm delighted that The BMJ has helped to remind everyone of the enormous contribution the NHS has made to our lives. We should celebrate this 70th anniversary with pride as we look ahead and consider the future prospects for our national health service."

Researchers at Nagoya University develop a composite material that, by adjusting its composition and exposing it to different types of light, can mimic animals' changes in color.

Nagoya, Japan - A range of creatures, including chameleons, octopuses, and frogs, can change color in response to changes in the environment. Some insights into the mechanisms behind this at the anatomical, cellular, and molecular levels have been obtained. However, much work is still required to obtain sufficient understanding of this phenomenon and to translate it into useful artificial applications.

As reported in the journal Small, researchers at Nagoya University's Department of Molecular Design and Engineering developed a material containing dyes and crystals that can change the colors and patterns it displays depending on the background color used within it and its exposure to visible or ultraviolet light. You can see a video abstract on this at the website of this journal.

The team was inspired to develop this material by findings obtained in the skin of certain frogs, in which different layers of cells with different properties combine to enable remarkable color changes.

Each component of this novel material plays a key role in its color properties. For example, the dyes contribute their inherent colors to the material's appearance, which can be adjusted by mixing them to different extents. These dyes also include those that change color upon exposure to light.

Spherical crystals were also introduced into the system, which rather than influencing the color through their inherent pigmentation affect it through their microscopic structures that can directly interfere with light. Finally, a black pigment and different background colors were employed to alter the colors the other components of the system display.

"We examined the influences of the different components in the system, such as by changing the size of the crystals, switching the background from white to black, or performing exposure to visible or ultraviolet light," corresponding author Yukikazu Takeoka says. "We found these changes resulted in different colors being displayed across the material, resembling the way in which some organisms can change color in response to various factors in their environment."

"This is an exciting stage in this field of study, as we are increasingly able to adapt the color-changing mechanisms that some animals use to artificial devices," study first author Miki Sakai adds. "If these artificial color-changing materials can equal or surpass the vibrant displays that some animals such as octopuses and frogs make, it could have exciting applications in the development of new display technologies."

Researchers at the RIKEN Center for Brain Science have discovered a circuit in the brain that is necessary for unlearning fear. Published in Nature Communications, the study details the role of dopamine in ensuring that rats stop being afraid when there isn't anything to be afraid of anymore.

Like animals, people develop conditioned responses, especially if strong negative emotions are involved. This fact was used beautifully in the movie Jaws as the simple "da-da ... da-da" frightened millions without anyone needing to actually be chased or killed by a shark. Normally, fearful reactions will lessen over time as the conditioned stimulus (the music) is dissociated from the fearful experience (watching the movie). This is called fear extinction. When fear extinction does not happen normally, it can lead to anxiety disorders such as post-traumatic stress or phobias.

In order to understand how the brain regulates both the normal and pathological situations, the team at RIKEN performed a series of experiments in rats as they extinguished fearful associations. They reasoned that in order for fear to be extinguished, first an animal needs to recognize when an expected fearful event does not happen. As dopamine neurons in some parts of the brain are known to be active when expected unpleasant events don't happen, the team looked at dopamine neurons in a part of the brain called the VTA.

After conditioning rats to associate a specific sound (think of it as their Jaws music) with an aversive experience (a mild footshock), the team then began the extinction process. As expected, when the sound was played many times without the footshock, rats stopped behaving as if they were afraid of the sound. However, when VTA dopamine neurons were silenced just after playing the sound--exactly when the rats expected their feet to be shocked--they could not unlearn the fear response. This showed that without VTA dopamine activity at that specific time, the mental link between the sound and the shock could not be removed.

But what exactly does the VTA dopamine activity do? This was not a simple question to answer because not all VTA dopamine neurons are connected to the same brain regions. Some are connected to brain regions known for their role in storing extinction memories, while others are connected areas related to reward learning. Optogenetics allowed the team to block each of these pathways separately, and they found that they both affected fear extinction, but in opposite ways: blocking the reward pathway prevented fear extinction, while blocking the other pathway enhanced fear extinction.

While the results are simple enough, obtaining them required technological effort. As team leader Joshua Johansen explains, "This finding was possible because we were able to manipulate dopamine neurons based on their unique brain connectivity. We used both genetic and brain-circuit specific technologies coupled with techniques for manipulating neural electrical activity in anatomically and genetically defined cell populations." With this optogenetic setup, they were able to physically shine light into the brain and silence specific dopamine cell populations, which revealed their role in fear extinction.

Now that they have discovered two dopamine pathways that can regulate fear extinction in different ways, the team is working on ways to target these neurons with traditional pharmacology rather than optogenetics. "Pharmacologically targeting the dopamine system will likely be an effective therapy for psychiatric conditions such as anxiety disorders when combined with clinically proven behavioral treatments such as exposure therapy," says Johansen. "In order to provide effective, mechanism-based treatments for these conditions, future pre-clinical work will need to use molecular strategies that can separately target these distinct dopamine cell populations."

Using observations from NASA's Hubble Space Telescope and ground-based observatories, an international team of scientists have confirmed ?Oumuamua (oh-MOO-ah-MOO-ah), the first known interstellar object to travel through our solar system, got an unexpected boost in speed and shift in trajectory as it passed through the inner solar system last year.

"Our high-precision measurements of ?Oumuamua's position revealed that there was something affecting its motion other than the gravitational forces of the Sun and planets," said Marco Micheli of ESA's (European Space Agency) Space Situational Awareness Near-Earth Object Coordination Centre in Frascati, Italy, and lead author of a paper describing the team's findings.

Analyzing the trajectory of the interstellar visitor, co-author Davide Farnocchia of the Center for Near Earth Object Studies (CNEOS) at NASA's Jet Propulsion Laboratory (JPL) found that the speed boost was consistent with the behavior of a comet.

"This additional subtle force on ?Oumuamua likely is caused by jets of gaseous material expelled from its surface," said Farnocchia. "This same kind of outgassing affects the motion of many comets in our solar system."

Comets normally eject large amounts of dust and gas when warmed by the Sun. But according to team scientist Olivier Hainaut of the European Southern Observatory, "there were no visible signs of outgassing from ?Oumuamua, so these forces were not expected."

The team estimates that ?Oumuamua's outgassing may have produced a very small amount of dust particles - enough to give the object a little kick in speed, but not enough to be detected.

Karen Meech, an astronomer at the University of Hawaii's Institute of Astronomy and co-author of the study, speculated that small dust grains, present on the surface of most comets, eroded away during ?Oumuamua's long journey through interstellar space.

"The more we study ?Oumuamua, the more exciting it gets," Meech said. "I'm amazed at how much we have learned from a short, intense observing campaign. I can hardly wait for the next interstellar object!"

?Oumuamua, less than half a mile in length, now is farther away from our Sun than Jupiter and traveling away from the Sun at about 70,000 mph as it heads toward the outskirts of the solar system. In only another four years, it will pass Neptune's orbit on its way back into interstellar space.

Because ?Oumuamua is the first interstellar object ever observed in our solar system, researchers caution that it's difficult to draw general conclusions about this newly-discovered class of celestial bodies. However, observations point to the possibility that other star systems regularly eject small comet-like objects and there should be more of them drifting among the stars. Future ground- and space-based surveys could detect more of these interstellar vagabonds, providing a larger sample for scientists to analyze.