Culture

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.

The risk of preterm infants developing necrotizing enterocolitis (NEC) is higher when they are fed formula than when they feed on breast milk. Of the many reasons why breast milk protects preterm infants from this serious condition better than formula, not all of them are well understood. In a study published in the journal Microbiome, a team of researchers at the USDA-ARS Children's Nutrition Research Center at Baylor College of Medicine and Texas Children's Hospital, and the Mead Johnson Pediatric Nutrition Institute report an association between the type of carbohydrates in formula; the products of metabolism or metabolites; and the risk of NEC in a piglet model of the human condition. The researchers suggest that further study of the metabolite profiles could provide a better understanding of the development of the disease and potentially lead to improved treatments.

"NEC is a devastating, serious disease that causes an inflammatory process that leads to intestinal damage and sometimes death. It is rare in full term babies, but it occurs more often in preterm infants. The earlier before full term the infant is born, the higher the risk of developing the disease," said corresponding author Dr. Douglas Burrin, research physiologist at the USDA-ARS Children's Nutrition Research Center and professor of pediatrics at Baylor College of Medicine. "Although this condition has been known for more than 50 years, we still don't understand exactly how it develops. In this study we worked with a premature piglet model of NEC that closely reproduces the characteristics observed in human infants."

The researchers had previously shown that the type of carbohydrate or sugar in the diet of preterm piglets affected the risk of developing NEC. Preterm infant formulas contain two main sugars, lactose and corn syrup solids. The main carbohydrates in human milk are lactose and oligosaccharides. The researchers previously showed that feeding formula containing the sugar lactose protected preterm piglets from NEC. In comparison, piglets fed formula containing corn syrup solids had a higher risk of developing the condition. In this study, the researchers took a closer look at the effect of these two different sugars on the development of NEC using a more detailed analysis than had been done in previous studies: they characterized the bacterial communities, or microbiome, of the gut, and the metabolite profiles found in the gut and the blood.

"We asked, how does the diet interact with the microbiome in the developing piglet gut, and how does that interaction shape not only the community of bacteria but also the metabolites found in the gut and blood of the piglets," Burrin said. "To identify the metabolites produced by the piglets, we partnered with Metabolon, a company that specializes in the analysis of all the main products of metabolism and their intermediates in a cell, tissue or organism. We also partnered with the Alkek Center for Metagenomics and Microbiome Research at Baylor College of Medicine to conduct the microbiome analysis in the piglets, comparing the effects the two diets have on the profiles of bacteria growing in their gut."

The researchers confirmed that formula with lactose can protect piglets from developing NEC better than formula with corn syrup solids. Fourteen percent of the piglets in the lactose-containing formula developed NEC, while 44 percent of the piglets in the corn syrup solids-containing formula presented with the condition.

"We determined that the communities of bacteria were not dramatically different between the lactose and the corn syrup solids group, but the metabolite profiles were quite different," said Burrin. "We found a clear association between the metabolite profile, the sugar in the diet and the risk of developing NEC. This suggested that the metabolite profile is perhaps an early determinant of the development of this disease, as the microbiome begins to develop."

"We think that the metabolite profiles we identified correlating with disease are going to be useful for generating and testing new hypotheses to better understand how this disease happens," said first author Lee Call, a graduate student in the Burrin lab.

The researchers' next plan is to study in more detail what these metabolites that correlate with the disease are doing to lead to the condition, for instance, what biological pathways they are triggering or how they interact with cells in the gut.

Tuesday, June 26st, Rockville, MD - Today, Insilico Medicine, Inc., a Rockville-based next-generation artificial intelligence company specializing in the application of deep learning for target identification, drug discovery and aging research announces the publication of a new research paper "Reinforced Adversarial Neural Computer for De Novo Molecular Design" in The Journal of Chemical Information and Modeling. The authors presented an original deep neural network architecture named Reinforced Adversarial Neural Computer (RANC) for the de novo design of novel small-molecule organic structures utilizing the generative adversarial network (GAN) and reinforcement learning (RL) methods.

"In this work, we introduced RANC architecture for de novo molecular design. Our engine generates more unique and diverse structures as well as clusters with the lengths close to the reference samples, keeping the distributions of key molecular descriptors as in the training sets. As a result, many of the generated structures meet the crucial criteria used in medicinal chemistry of today and are able to pass medical chemistry filters. I hope this approach will become a starting point to making perfect molecules for specific targets and multiple targets that will have a much higher chance of becoming great drugs", said Evgeny Putin, the deep learning lead at Insilico Medicine.

In silico modeling is a crucial milestone in modern drug design & development. Although computer-aided approaches in this field are well-studied, the application of deep learning methods in this research area is at the beginning facing a lot of challenges.

The comparative results have shown that RANC trained on the SMILES string representation of the molecules outperforms the other methods by several metrics relevant to drug discovery: the number of unique structures, passing medicinal chemistry filters, Muegge criteria and high quantitative estimate of drug-likeness scores. RANC is able to generate structures that match the distributions of the key chemical features/descriptors (e.g. MW, logP, TPSA) and lengths of the SMILES strings in the training dataset. Therefore, RANC can be reasonably regarded as a promising starting point to develop novel molecules with activity against different biological targets or pathways.

This work was carried out in collaboration with one of the most prominent groups in AI-enabled chemistry and quantum chemistry, lead by Prof. Alan Aspuru-Guzik. One of the co-authors of the paper is Benjamin Sanchez-Lengeling - the author of the Objective-Reinforced Generative Adversarial Networks (ORGAN), one of the first objective--reinforced molecular generators.

From a medicinal chemistry perspective, it would be very interesting to investigate how the results of modeling depend on the carefully selected reference compounds as well as the application of the model for the generation of structures with biological activity toward specific targets.

For its work in the field of artificial intelligence for drug discovery and development, Insilico Medicine received the Frost & Sullivan 2018 North American Artificial Intelligence for Aging Research and Drug Development Technology Innovation Award. The company plans to use GAN-RL systems to target age-related diseases and aging itself.

"Technology leadership in artificial intelligence for drug discovery and biomarker development, academic excellence, extensive collaborations with pharmaceutical and consumer companies, novel methods of attracting top talent, and increasing global reach have allowed Insilico Medicine to build a credible and sustainable business model in the nascent longevity biotechnology industry," noted Neelotpal Goswami. "In recognition of its pioneering research and ability to introduce novel products and solutions for age management, Frost & Sullivan is pleased to present it with the 2018 Technology Innovation Award."

Refraining from bad behavior toward a significant other during stressful life events is more important than showing positive behavior, according to a Baylor University study.

Compared with positive gestures, negative ones tend to trigger more intense and immediate responses, according to the study. And how a couple works together during trying times is associated with individual well-being as well as satisfaction with the relationship.

"When people face stressful life events, they are especially sensitive to negative behavior in their relationships, such as when a partner seems to be argumentative, overly emotional, withdrawn or fails to do something that was expected," said researcher Keith Sanford, Ph.D., professor of psychology and neuroscience in Baylor's College of Arts & Sciences.

"In contrast, they're less sensitive to positive behavior -- such as giving each other comfort," he said.

The study also found that low doses of a behavior are most important, and over time, more extreme levels have less impact.

"Because people are especially sensitive to negative relationship behavior, a moderate dose may be sufficient to produce a nearly maximum effect on increasing life stress," Sanford said. "After negative behavior reaches a certain saturation point, it appears that stress is only minimally affected by further increases in the dose of relationship problems."

The study -- "Negative Relationship Behavior Is More Important Than Positive: Correlates of Outcomes During Stressful Life Events" -- is published in Journal of Family Psychology. Sanford and co-researcher Alannah Shelby Rivers, doctoral candidate in psychology and neuroscience, surveyed couples experiencing stressful life events to measure their behavior, relationship satisfaction, personal well-being and quality of life.

The research consisted of two studies done using data from Internet samples.

In the first study, 325 couples who were married or living with a partner all reported experiences of at least one of six possible stressful events within the past month, including: losing a job, becoming a primary caregiver of an older relative, experiencing a parent's death, experiencing a child's death, not having enough resources to afford basic necessities, and experiencing bankruptcy, foreclosure or repossession of a house or car.

The second study included 154 people who were either married or living with a partner and experiencing a serious medical issue meeting one or more of these criteria: a condition requiring hospitalization or a trip to the emergency room, a serious chronic condition and a life-threatening condition. All participants reported that they had visited a medical practitioner within the past year for treatment of their conditions.

Researchers used a scale that included 18 items -- nine for negative and nine for positive behavior. Participants were asked to remember the past month, then write a few words describing different memories of interactions occurring in their relationships and indicate how often specific types of interactions occurred in their relationships.

All participants also were asked questions about how rewarding their relationships were, their general well-being (such as being active and vigorous) and their quality of life (such as health). Those in the first study also were asked about stress, their coping strategies in general and their coping style in the relationship.

The second study, examining couple's behavior during stressful medical events, showed lower levels of negative behavior than the first study dealing with other types of stressful issues.

"It is possible that couples facing stressful medical situations are less likely to blame each other," researchers wrote.

"When people face stressful life events, it's common to experience both positive and negative behavior in their relationships," Sanford said. "When the goal is to increase feelings of well-being and lessen stress, it may be more important to decrease negative behavior than to increase positive actions."