Radical new approach to schizophrenia treatment begins trial

Exclusive: as evidence emerges that schizophrenia could be an immune system disease, two-year trial will use antibody drug currently used for MS

British scientists have begun testing a radically new approach to treating schizophrenia based on emerging evidence that it could be a disease of the immune system.

The first patient, a 33-year old man who developed schizophrenia after moving to London from Cameroon a decade ago, was treated at Kings College Hospital in London on Thursday, marking the start of one of the most ambitious trials to date on the biology of the illness and how to treat it.

During the next two years, 30 patients will receive monthly infusions of an antibody drug currently used to treat multiple sclerosis (MS), which the team hopes will target the root causes of schizophrenia in a far more fundamental way than current therapies.

The trial builds on more than a decades work by Oliver Howes, a professor of molecular psychiatry at the MRC London Institute of Medical Sciences and a consultant psychiatrist at the Maudsley Hospital in south London. Howess team is one of several worldwide to have uncovered evidence that abnormalities in immune activity in the brain may lie at the heart of the illness for some patients, at least.

In the past, weve always thought of the mind and the body being separate, but its just not like that, said Howes. The mind and body interact constantly and the immune system is no different. Its about changing the way we think about mental illnesses.

Recent work by Howes and colleagues found that in the earliest stages of schizophrenia, people experience a surge in the number and activity of immune cells in the brain. As well as fighting infection, these cells, called microglia, have a gardening role, pruning unwanted connections between neurons. But in schizophrenia patients, the pruning appears to become more aggressive, leading to vital connections being lost.

We studied people in that [initial] phase of the illness and saw microglial changes, said Howes. It shows that its something [happening] very early on and seems to be driving the illness.

The most extensive pruning appears to occur in the frontal cortex, the brains master control centre, and also the auditory regions, which could explain why patients often hear voices. The frontal cortex indirectly controls the brains levels of dopamine a surge in this brain chemical is thought to explain the delusions and paranoia experienced by those with schizophrenia.

Nearly all existing medications work by blocking dopamine, which can bring psychotic symptoms under control, but fail to protect the brains basic architecture from damage.

The current drugs are based on 1950s technology; they all still work in exactly the same way, said Howes. They are only able to target the delusion side of things. Its like getting a sledgehammer and squashing it down.

Microglial
Microglial cells, outlined in green stain, have thin processes that reach out around brain cells, stained in red. Photograph: Bloomfield et al

There is a growing appreciation that other, perhaps less well-known, symptoms associated with schizophrenia memory and cognitive problems, and lack of motivation can have an equally profound impact on patients, and existing drugs do little to help this side of the disease. Its typically [these other] symptoms that are the most disabling, said Toby Pillinger, a psychiatrist and Kings College London researcher involved in the study.

The latest trial, a collaboration between MRC scientists and Kings College London, involves treating patients with a monoclonal antibody drug, called Natalizumab, that is already licensed for MS. In MS, the brains immune cells go awry by attacking a different aspect of the brains wiring. And although the diseases manifest in very different ways, apparent parallels in the underlying biology raise the possibility that the MS drug might help schizophrenia patients.

The drug works by targeting microglia and restricting their movement around the brain, which scientists hope could prevent the over-pruning of vital connections. In doing so, it could potentially address the diseases full spectrum of symptoms.

The first participant, Leopold Fotso, 33, received his first dose of treatment on Thursday. Fotso, who lives in south London after moving from Cameroon in 2007, was diagnosed with schizophrenia four years ago. He has been admitted to hospital several times with psychotic episodes. His illness also forced him to abandon his studies in accountancy which he had moved to the UK to pursue and his part-time kitchen job.

Leopold
Leopold Fotso undergoes the first treatment of a new therapy for schizophrenia. Photograph: Teri Pengilley for the Guardian

He currently has monthly injections of an antipsychotic drug, and his condition is now stable. He feels on the way to being himself again and is looking to slowly start working again. Its quite hard, he said.

At some time during their life about 1 in 100 people will suffer an episode of schizophrenia. In the UK, about 220,000 people are being treated for the condition by the NHS at any one time.

In total, in this first trial, 60 patients will be treated for three months, attending clinic once a month for hour-long infusions half will receive the antibody, half a placebo. The patients symptoms will be tracked and, along with 30 healthy volunteers, they will be given a series of brain scans, cognitive assessments and tests of immune activity. The hope is that, even if symptoms do not improve, the study should also answer fundamental questions about the role of the immune system in the illness.

Belinda Lennox, senior clinical lecturer in psychiatry at the University of Oxford, whose work also focuses on the role of the immune system in schizophrenia, said the concept behind the latest study was exciting although at a very experimental stage. Theres a lot of emerging evidence that the immune system is going wrong [in schizophrenia], she said. If reducing inflammation acts to improve psychosis in this study it will open a new range of treatment possibilities, which is very exciting for the field, and desperately needed.

Read more: https://www.theguardian.com/society/2017/nov/03/radical-new-approach-to-schizophrenia-treatment-begins-trial

Acid reflux drug linked to more than doubled risk of stomach cancer study

There are more than 50m prescriptions for proton pump inhibitors in the UK, though they have previously been linked to side-effects and increased risk of death

A drug commonly used to treat acid reflux is linked to a more than doubled risk of developing stomach cancer, researchers have claimed.

Proton pump inhibitors (PPIs) reduce the amount of acid made by the stomach and are used to treat acid reflux and stomach ulcers.

A study published in the journal Gut identified an association between long-term use of the drug and a 2.4 times higher risk of developing stomach cancer. In the UK, there are more than 50m prescriptions for PPIs every year but they have been linked to side-effects and an increased risk of death.

A link between PPIs and a higher stomach cancer risk has previously been identified by academics but never in a study that first eliminates a bacteria suspected of fuelling the illnesss development.

Research by the University of Hong Kong and University College London found that after the Helicobacter pylori was removed, the risk of developing the disease still rose in line with the dose and duration of PPI treatment.

They compared the use of PPI against another drug which limits acid production known as H2 blockers in 63,397 adults. The participants selected had been treated with triple therapy, which combines PPI and antibiotics to kill off the H pylori bacteria over a week, between 2003 and 2012.

Scientists then monitored them until they either developed stomach cancer, died or reached the end of the study at the end of 2015.

During this period, 3,271 people took PPIs for an average of almost three years, while 21,729 participants took H2 blockers. A total of 153 people developed stomach cancer, none of whom tested positive for H plyori but all had long-standing problems with stomach inflammation, the study found.

While H2 blockers were found to have no link to a higher risk of stomach cancer, PPIs was found connected to an increased risk of more than double.

Daily use of PPIs was associated with a risk of developing the illness that was more than four times higher (4.55) than those who used it weekly. Similarly, when the drug was used for more than a year, the risk of developing stomach cancer rose five-fold, and as high as eight-fold after three or more years, the findings showed.

The study concluded no firm cause and effect could be drawn, but doctors should exercise caution when prescribing long-term PPIs even after successful eradication of H plyori.

Responding to the study, Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, said: Many observational studies have found adverse effects associated with PPIs.

The most plausible explanation for the totality of evidence on this is that those who are given PPIs, and especially those who continue on them long-term, tend to be sicker in a variety of ways than those for whom they are not prescribed.

Read more: https://www.theguardian.com/science/2017/oct/31/acid-reflux-drug-linked-to-more-than-doubled-risk-of-stomach-cancer-study

Americans Are Retiring Later, Dying Sooner and Sicker In-Between

The U.S. retirement age is rising, as the government pushes it higher and workers stay in careers longer.

But lifespans aren’t necessarily extending to offer equal time on the beach. Data released last week suggest Americans’ health is declining and millions of middle-age workers face the prospect of shorter, and less active, retirements than their parents enjoyed.

Here are the stats: The U.S. age-adjusted mortality rate—a measure of the number of deaths per year—rose 1.2 percent from 2014 to 2015, according to the Society of Actuaries. That’s the first year-over-year increase since 2005, and only the second rise greater than 1 percent since 1980.

 

At the same time that Americans’ life expectancy is stalling, public policy and career tracks mean millions of U.S. workers are waiting longer to call it quits. The age at which people can claim their full Social Security benefits is gradually moving up, from 65 for those retiring in 2002 to 67 in 2027.

Almost one in three Americans age 65 to 69 is still working, along with almost one in five in their early 70s.

Postponing retirement can make financial sense, because extended careers can make it possible to afford retirements that last past age 90 or even 100. But a study out this month adds some caution to that calculation.

Americans in their late 50s already have more serious health problems than people at the same ages did 10 to 15 years ago, according to the journal Health Affairs.

University of Michigan economists HwaJung Choi and Robert Schoeni used survey data to compare middle-age Americans’ health. A key measure is whether people have trouble with an “activity of daily living,” or ADL, such as walking across a room, dressing and bathing themselves, eating, or getting in or out of bed. The study showed the number of middle-age Americans with ADL limitations has jumped: 12.5 percent of Americans at the current retirement age of 66 had an ADL limitation in their late 50s, up from 8.8 percent for people with a retirement age of 65.

At the current retirement age of 66, a quarter of Americans age 58 to 60 rated themselves in “poor” or “fair” health. That’s up 2.6 points from the group who could retire with full benefits at 65, the Michigan researchers found.

Cognitive skills have also declined over time. For those with a retirement age of 66, 11 percent already had some kind of dementia or other cognitive decline at age 58 to 60, according to the study. That’s up from 9.5 percent of Americans just a few years older, with a retirement age between 65 and 66.

While death rates can be volatile from year to year, Choi and Schoeni’s study is part of a raft of other research showing the health of Americans deteriorating.

Researchers have offered many theories for why Americans’ health is getting worse. Princeton University economists Anne Case and Angus Deaton, a Nobel Prize winner, have argued that an epidemic of suicide, drug overdoses and alcohol abuse have caused a spike in death rates among middle-age whites.

Higher rates of obesity may also be taking their toll. And Americans may have already seen most of the benefits from previous positive developments that cut the death rate, such as a decline in smoking and medical advances like statins that fight cardiovascular disease.

Declining health and life expectancy are good news for one constituency: Pension plans, which must send a monthly check to retirees for as long as they live.

According to the latest figures from the Society of Actuaries, life expectancy for pension participants has dropped since its last calculation by 0.2 years. A 65-year-old man can expect to live to 85.6 years, and a woman can expect to make it to 87.6. As a result, the group calculates a typical pension plan’s obligations could fall by 0.7 percent to 1 percent.

    Read more: http://www.bloomberg.com/news/articles/2017-10-23/americans-are-retiring-later-dying-sooner-and-sicker-in-between

    The FDA Warns One of New York’s Most Expensive Restaurants

    One of New York’s most expensive restaurants is in some trouble with the Food and Drug Administration over its fresh fish.

    Masa, which earned three Michelin stars for its $595 tasting menu (before drinks and tax), received a warning letter from the FDA dated Oct. 16 alleging violations of federal rules that govern seafood imports. “Your fresh trevally and fresh Katsuwonus pelamis (Katsuo), also known as skipjack tuna or bonito,” the agency wrote in a letter published online this week, “have been prepared, packed, or held under insanitary conditions whereby they may have been rendered injurious to health.”

    “We take FDA regulations very seriously and, of course, food safety is always a priority. We are working closely with our purveyors in Japan to get this resolved quickly,” said Tina Clabbers, a representative for Masa, in an email.

    While the the FDA doesn’t typically regulate individual restaurants, the agency has jurisdiction over seafood importers. Inspectors visited Masa on June 22, according to the letter, which redacted the name of the restaurant’s fish supplier.

    The letter doesn’t specify the precise nature of the violation, and a spokesperson in the FDA’s New York district office was not available for comment.

    The regulation for which Masa was cited requires fish importers to ensure that foreign suppliers meet the same standards for safety that domestic processors must adhere to. The FDA warning letter says the restaurant “must implement an affirmative step” to comply with the seafood import rules but failed to do so for the aforementioned fresh trevally and Katsuo.

    Affirmative steps could include getting records from foreign suppliers about their compliance with FDA standards, inspecting the foreign facility or other actions to verify that the fish is up to code.

    High-end sushi chefs have clashed with regulators before over rules that require that fish intended for raw consumption be frozen before serving. The freezing process is intended to kill pathogens. Masa’s 20-plus course omakase menu uses ingredients “only in their freshest most delicious state,” according to its website.

    New York City health inspectors gave Masa an A grade in July 2016. The health department did not cite any violations regarding fresh fish.

      Read more: http://www.bloomberg.com/news/articles/2017-10-25/the-fda-warns-one-of-new-york-city-s-most-expensive-restaurants

      Dyslexia: scientists claim cause of condition may lie in the eyes

      In people with the condition, light receptor cells are arranged in matching patterns in both eyes, which may confuse the brain

      French scientists claim they may have found a physiological, and seemingly treatable, cause for dyslexia hidden in tiny light-receptor cells in the human eye.

      In people with the condition, the cells were arranged in matching patterns in both eyes, which may be to blame for confusing the brain by producing mirror images, the co-authors wrote in the journal Proceedings of the Royal Society B.

      In non-dyslexic people, the cells are arranged asymmetrically, allowing signals from the one eye to be overridden by the other to create a single image in the brain.

      Our observations lead us to believe that we indeed found a potential cause of dyslexia, said the studys co-author, Guy Ropars, of the University of Rennes.

      It offers a relatively simple method of diagnosis, he added, by simply looking into a subjects eyes.

      Furthermore, the discovery of a delay (of about 10 thousandths of a second) between the primary image and the mirror image in the opposing hemispheres of the brain, allowed us to develop a method to erase the mirror image that is so confusing for dyslexic people using an LED lamp.

      Like being left- or right-handed, human beings also have a dominant eye. As most of us have two eyes, which record slightly different versions of the same image, the brain has to select one of the two, creating a non-symmetry.

      Many more people are right-eyed than left, and the dominant eye has more neural connections to the brain than the weaker one. Image signals are captured with rods and cones in the eye the cones being responsible for colour.

      The majority of cones, which come in red, green and blue variants, are found in a small spot at the centre of the retina of the eye known as the fovea. But there is a small hole (about 0.1-0.15 millimetres in diameter) with no blue cones.

      In the newstudy, Ropars and colleague Albert le Floch spotted a major difference between the arrangement of cones between the eyes of dyslexic and non-dyslexic people enrolled in an experiment.

      In non-dyslexic people, the blue cone-free spot in one eye the dominant one, was round and in the other eye unevenly shaped. In dyslexic people, both eyes have the same, round spot, which translates into neither eye being dominant, they found.

      The lack of asymmetry might be the biological and anatomical basis of reading and spelling disabilities, said the studys authors.

      Dyslexic people make so-called mirror errors in reading, for example confusing the letters b and d.

      For dyslexic students their two eyes are equivalent and their brain has to successively rely on the two slightly different versions of a given visual scene, they added.

      The team used an LED lamp, flashing so fast that it is invisible to the naked eye, to cancel one of the images in the brains of dyslexic trial participants while reading. In initial experiments, dyslexic study participants called it the magic lamp, said Ropars, but further tests are required to confirm the technique really works.

      About 700 million people worldwide are known to have from dyslexia about one in 10 of the global population.

      Read more: https://www.theguardian.com/society/2017/oct/18/dyslexia-scientists-claim-cause-of-condition-may-lie-in-the-eyes

      Antibiotic apocalypse: doctors sound alarm over drug resistance

      The terrifying prospect that even routine operations will be impossible to perform has been raised by experts alarmed by the rise of drug-resistant genes

      Scientists attending a recent meeting of the American Society for Microbiology reported they had uncovered a highly disturbing trend. They revealed that bacteria containing a gene known as mcr-1 which confers resistance to the antibiotic colistin had spread round the world at an alarming rate since its original discovery 18 months earlier. In one area of China, it was found that 25% of hospital patients now carried the gene.

      Colistin is known as the antibiotic of last resort. In many parts of the world doctors have turned to its use because patients were no longer responding to any other antimicrobial agent. Now resistance to its use is spreading across the globe.

      In the words of Englands chief medical officer, Sally Davies: The world is facing an antibiotic apocalypse. Unless action is taken to halt the practices that have allowed antimicrobial resistance to spread and ways are found to develop new types of antibiotics, we could return to the days when routine operations, simple wounds or straightforward infections could pose real threats to life, she warns.

      That terrifying prospect will be the focus of a major international conference to be held in Berlin this week. Organised by the UK government, the Wellcome Trust, the UN and several other national governments, the meeting will be attended by scientists, health officers, pharmaceutical chiefs and politicians. Its task is to try to accelerate measures to halt the spread of drug resistance, which now threatens to remove many of the major weapons currently deployed by doctors in their war against disease.

      The arithmetic is stark and disturbing, as the conference organisers make clear. At present about 700,000 people a year die from drug-resistant infections. However, this global figure is growing relentlessly and could reach 10 million a year by 2050.

      The danger, say scientists, is one of the greatest that humanity has faced in recent times. In a drug-resistant world, many aspects of modern medicine would simply become impossible. An example is provided by transplant surgery. During operations, patients immune systems have to be suppressed to stop them rejecting a new organ, leaving them prey to infections. So doctors use immunosuppressant cancer drugs. In future, however, these may no longer be effective.

      Or take the example of more standard operations, such as abdominal surgery or the removal of a patients appendix. Without antibiotics to protect them during these procedures, people will die of peritonitis or other infections. The world will face the same risks as it did before Alexander Fleming discovered penicillin in 1928.

      Routine surgery, joint replacements, caesarean sections, and chemotherapy also depend on antibiotics, and will also be at risk, says Jonathan Pearce, head of infections and immunity at the UK Medical Research Council. Common infections could kill again.

      As to the causes of this growing threat, scientists point to the widespread misuse and overuse of antibiotics and other drugs and to the failure of pharmaceutical companies to investigate and develop new sources of general medicines for the future. Western doctors are over-prescribing antibiotics to patients who expect to be given a drug for whatever complaint they have. In many countries, both land and fish farmers use antibiotics as growth promoters and indiscriminately pour them on to their livestock. In the latter case the end result is antibiotics leaching into streams and rivers with alarming results, particularly in Asia.

      In the Ganges during pilgrimage season, there are levels of antibiotics in the river that we try to achieve in the bloodstream of patients, says Davies. That is very, very disturbing.

      The creation of these soups of antibiotic-laden waters and banks of drug-soaked soils is ideal for the development of superbugs. Rare strains that are resistant to antibiotics start to thrive in farm animals that are raised in these artificial environments and emerge as highly potent infectious agents that then spread across the planet with startling speed. Examples of these include tuberculosis, which was once easily treated but which, in its modern multi-drug-resistant form, known as MDR-TB, now claims the lives of 190,000 people a year.

      Another even more revealing example is provided by colistin. Colistin was developed in the 50s, says Matthew Avison, reader in molecular biology at Bristol University. However, its toxic side-effects made it unpopular with doctors. So it was taken up by vets and used in animals. But as resistance in humans to other antibiotics has spread, doctors have returned to colistin on the grounds that it was better than nothing.

      Levels
      Levels of antibiotics in major rivers such as the Ganges are cause for alarm, says Englands chief medical officer, Sally Davies. Photograph: Alamy

      But the antibiotics widespread use as a growth promoter for poultry and pigs in Asia had by this time encouraged the evolution of resistant strains and these have now spread to humans. Colistin was a drug we discarded and gave to the vets and now, all of a sudden, we expect that we can take it back again, said Avison. However, the genie is already out of the bottle.

      The position is summed up by Lance Price, an antibiotic researcher at George Washington University in Washington DC. Superbugs are gaining strength because we continue to squander these precious medicines through overuse in human medicine and as cheap production tools in animal agriculture.

      Bans on the agricultural use of antibiotics like colistin are being imposed in Asia but have come far too late to be effective, a problem acknowledged by Lord Jim ONeill, whose report to the UK government on antimicrobial resistance was published last year. When we were putting our report together, colistin resistance was considered to be a problem that would not affect us for some time. Now we find it has already spread all over the place.

      The report that was overseen by ONeill who will be speaking at this weeks conference in Berlin put forward a number of proposals to stop antibiotic resistance from overwhelming health services. In particular, it argued that drug companies should now foot the bill for the development of new antibiotics and that patients should not be allowed to get them without a test to ensure they are needed.

      I find it incredible that doctors must still prescribe antibiotics based only on their immediate assessment of a patients symptoms, just like they used to when antibiotics first entered common use in the 1950s, ONeill said in the report, adding that the development of rapid diagnostic tests on patients which would establish whether an antibiotic was necessary and, if so, which kind must now be an urgent priority.

      The proposal to be debated at the conference this week is popular, although Professor Alastair Hay of Bristol University counselled caution. It is a very good idea, but we should note that a new type of diagnostic test like this will also add time and work for our already overburdened health service, he points out.

      Then there is the issue of travel, one of the biggest problems we face over the spread of antimicrobial resistance, according to Davies, who has spearheaded Britains part in the battle to fight its spread around the world.

      One Swedish study followed a group of young backpackers who went off on holiday to different parts of the world. None had resistant bacteria in their guts when they left. When they returned a quarter of them had picked up resistant bugs. That shows the pervasive nature of the problem we face, she said.

      Tourism, personal hygiene, farming, medical practice all are affected by the issue of antibiotic resistance, and it will be the task of the conference to highlight the most effective and speedy solutions to tackle the crisis.

      In the end, the problem posed to the planet by antimicrobial resistance is not that difficult, says ONeill. All that is required is to get people to behave differently. How you achieve that is not so clear, of course.

      Read more: https://www.theguardian.com/society/2017/oct/08/world-faces-antibiotic-apocalypse-says-chief-medical-officer

      Nobel prize for medicine awarded for insights into internal biological clock

      825,000 prize shared between American scientists Jeffrey C Hall, Michael Rosbash and Michael W Young for work on the internal clock of living organismsLive reaction to medicine Nobel prize announcement

      The Nobel prize in physiology or medicine has been awarded to a trio of American scientists for their discoveries on the molecular mechanisms controlling circadian rhythms in other words, the 24-hour body clock.

      According to the Nobel committees citation, Jeffrey C Hall, Michael Rosbash and Michael W Young were recognised for their discoveries explaining how plants, animals and humans adapt their biological rhythm so that it is synchronised with the Earths revolutions.

      The team identified a gene within fruit flies that controls the creatures daily rhythm, known as the period gene. This gene encodes a protein within the cell during the night which then degrades during the day.

      The Nobel Prize (@NobelPrize)

      Our biological clock helps to regulate sleep patterns, feeding behavior, hormone release and blood pressure #NobelPrize pic.twitter.com/NgL7761AFE

      October 2, 2017

      When there is a mismatch between this internal clock and the external surroundings, it can affect the organisms wellbeing for example, in humans, when we experience jet lag.

      The announcement was met by disbelief by the winners. You are kidding me, Rosbash replied when he got the call. Halls reaction was similar: I said, is this a prank? he told the Guardian.

      All three winners are from the US. Hall, 72, has retired but spent the majority of his career at Brandeis University in Waltham, Massachussetts, where fellow laureate Rosbash, 73, is still a faculty member. Young, 68, works at Rockefeller University in New York.

      While all three laboured to isolate the period gene, publishing was something of a race. While Hall and Rosbash collaborated, Young was working on the puzzle independently. Both teams reported their findings in 1984.

      It was very unpleasant competition in the early 80s, although we settled down. I think its possible we just started to act more like grown-ups because we got older, said Hall.

      Hall and Rosbash then went on to unpick how the body clock actually works, revealing that the levels of protein encoded by the period gene rise and fall throughout the day in a negative feedback loop. Young, meanwhile, discovered a second gene involved in the system, dubbed timeless, that was critical to this process. Only when the proteins produced from the period gene combined with those from the timeless gene could they enter the cells nucleus and halt further activity of the period gene. Young also discovered the gene that controlled the frequency of this cycle.

      The teams discoveries also helped to explain the mechanism by which light can synchronise the clock.

      Sir Paul Nurse, director of the Francis Crick Institute, who shared the Nobel prize in 2001 for research on the cell cycle, said the work was important for the basic understanding of life.

      Every living organism on this planet responds to the sun, he said. All plant and animal behaviour is determined by the light-dark cycle. We on this planet are slaves to the sun. The circadian clock is embedded in our mechanisms of working, our metabolism, its embedded everywhere, its a real core feature for understanding life.

      We are increasingly becoming aware that there are implications for human disease, Nurse added. There is some evidence that treatment of disease can be influenced by circadian rhythms too. People have reported that when you have surgery or when you have a drug can actually influence things. Its still not clear, but there will almost certainly be some implications for the treatment of disease too.

      The impact of the teams work on medicine is becoming ever more apparent, said Ralf Stanewsky, a professor of molecular behavioural biology at the University of Mnster and a former colleague of Hall. You can see that more and more health issues, human health issues, are boiled down to either genetic defects in the circadian clock or self-imposed problems, by work and jet lag for example, he said. This [internal] timer is constantly struggling to reset to what environment people are exposed to. If you shift your clock every week by six hours or three hours, that puts an enormous pressure on your body.

      The win was welcomed by other experts in the field. I think it is a fantastic development, said professor Hugh Piggins, who works on circadian rhythms at the University of Manchester. But, he added, it was not unexpected, pointing out the work had been tipped for the win for several years.

      Stanewsky agreed: They were winning the prizes that people usually win before they win the Nobel prize, he said.

      Hall and Rosbash struck up their fruitful collaboration after becoming friends on a basketball court, Stanewsky added. The pair were also such fans of the Boston Red Sox baseball team that they once sneaked a portable TV into a conference to keep up with a crucial game.

      Bambos Kyriacou, professor of behavioural genetics at the University of Leicester, who is friends with all three winners and a former colleague of two, said the trio were very different people. Jeff [Hall] is eccentric brilliant but eccentric, he said. Michael [Rosbash], there is no stopping him he is just going 100%, he will die with his boots on in the lab, and Michael Young is the most charming, nicest one of them because he is polite and pleasant, whereas the other two arent like that, they are just crazy, Kyriacou added.

      The winners will share a prize of 9m Swedish kronor (825,000), and each receive a medal engraved with their name.

      Hall told the Guardian he was planning to make large donations, including to the Humane Society of the United States and a Texas-based charity involved in rescuing pets caught in the floods that followed Hurricane Harvey. I have always loved and cared about animals, he said. I didnt even intend to last this long so I still have some [money] left over and Ill have bloated coffers now, he added.

      Last year the prize was won by Yoshinori Ohsumi, a Japanese cell biologist who unpicked the mechanisms by which the body break downs and recycles components of cells a process that guards against various diseases, including cancer and diabetes.

      In total, 107 Nobel prizes for physiology or medicine have been won by 211 scientists since 1901, with just 12 awarded to women. Nonetheless, it remains the science award with the highest such tally so far the physics prize has only been awarded to two women: Marie Curie and Maria Goeppert Mayer.

      This years winners of the physics, chemistry, literature and peace prizes will be announced over the rest of the week, with the economics prize to follow on Monday 9 October.

      Read more: https://www.theguardian.com/science/2017/oct/02/nobel-prize-for-medicine-awarded-for-insights-into-internal-biological-clock

      ‘Western society is chronically sleep deprived’: the importance of the body’s clock

      The 2017 Nobel prize for medicine was awarded for the discovery of how our circadian rhythms are controlled. But what light does it shed on the cycle of life?

      The cycle of day and night on our planet is age-old and inescapable, so the idea of an internal body clock might not sound that radical. In science, though, asking the questions why? and how? about the most day-to-day occurrences can require the greatest leaps of ingenuity and produce the most interesting answers.

      This was the case for three American biologists, Jeffrey Hall, Michael Rosbash and Michael Young, who earlier this week were awarded the Nobel in medicine or physiology, for their discovery of the master genes controlling the bodys circadian rhythms.

      The first hints of an internal clock came as early as the 18th century when the French scientist Jean-Jacques dOrtous de Mairan noticed that plants kept at a steady temperature in a dark cupboard unexpectedly maintained their daily rhythm of opening and closing their leaves. However, De Mairan himself concluded this was because they could sense the sun without ever seeing it.

      It was only when Hall, Rosbash and Young used fruit flies to isolate a gene that controls the rhythm of a living organisms daily life that scientists got the first real glimpse at our time-keeping machinery that explains how plants, animals and humans adapt their biological rhythm so that it is synchronised with the Earths revolutions, the Nobel prize committee said.

      Using fruit flies, the team identified a period gene, which encodes a protein within the cell during the night which then degrades during the day, in an endless feedback cycle.

      Prof Robash, 73, a faculty member at Brandeis University in Waltham, Massachussetts, said that when his paper was published in the 1980s he had no grandiose thoughts about the importance of the discovery. During the intervening years, the picture has changed.

      Its [now] pretty clear that it has its fingers in all kinds of basic processes by influencing an enormous fraction of the genome, he said.

      Scientists discovered the same gene exists in mammals and that it is expressed in a tiny brain area called the suprachiasmatic nucleus, or SCN. On one side, it is linked to the retina in the eye, and on the other side it connects to the brains pineal gland, which pumps out the sleep hormone melatonin.

      Modern lifestyles may no longer be constrained by sunrise and sunset, but light remains one of the most powerful influences on our behaviour and wellbeing. This realisation has fuelled a sleep hygiene movement, whose proponents point out that bright lights before bedtime and spending the whole day in a dimly lit office can dampen the natural circadian cycle, leaving people in a continual mental twilight dozy in the morning, and too alert to fall asleep promptly at night.

      Rosbash welcomes this new awareness. Its been overlooked for a long time as a real public health problem, he said. All of western society is a little bit sleep deprived and, when I say a little bit, I mean chronically.

      There is growing evidence that this decoupling from the natural circadian cycle can have long-term health consequences much more far-reaching than tiredness.

      At first, it was assumed that the brains master clock was the bodys only internal timekeeper. In the past decade, though, scientists have shown that clock genes are active in almost every cell type in the body. The activity of blood, liver, kidney and lung cells in a petri dish all rise and fall on a roughly 24-hour cycle. Scientists have also found that the activity of around half our genes appear to be under circadian control, following undulating on-off cycles.

      In effect, tiny clocks are ticking inside almost every cell type in our body, anticipating our daily needs. This network of clocks not only maintains order with respect to the outside world, but it keeps things together internally.

      Virtually everything in our body, from the secretion of hormones, to the preparation of digestive enzymes in the gut, to changes in blood pressure, are influenced in major ways by knowing what time of day these things will be needed, said Clifford Saper, a professor of neuroscience at Harvard Medical School. The most common misconception is that people think that they do not have to follow the rules of biology, and can just eat, drink, sleep, play, or work whenever they want.

      This discovery explains why jet lag feels so grim: the master clock adapts quickly to changing light levels, but the the rest of your body is far slower to catch up and does so at different speeds.

      Jet lag is so awful because youre not simply shifted, but the whole circadian network is not aligned to each other, said Prof Russell Foster, chair of circadian neuroscience at the University of Oxford. If you were completely aligned but just five hours shifted you wouldnt feel so crappy.

      It is also helps explain the extensive range of health risks experienced by shift workers, who are more likely to suffer from heart disease, dementia, diabetes and some cancers. Theyre having to override their entire biology, said Foster.

      Obesity is also more common among those with irregular sleep patterns. Sapers team has found that animals that dont get enough sleep, but keep their circadian pattern, do not gain weight. But when they are placed on a 20-hour light-dark cycle, they eat more impulsively and develop glucose intolerance.

      I would suggest that for humans, staying up late, watching video screens with high levels of blue light and eating high fat foods, is potentially a major cause of obesity and diabetes, said Saper.

      Evidence is also emerging that our risk of acute illness rises and falls with a predictable regularity. People are 49% more likely to suffer a stroke between 6am and 12 noon than at any other time of the day and a similar pattern is true for heart attacks. This is linked to a circadian rise in blood pressure in the early morning, which happens even if youre lying in bed not doing anything.

      As a result, it makes sense to take certain blood pressure medications first thing, before getting out of bed. By contrast, cholesterol is made more rapidly by the liver at night. So, statins, which lower cholesterol, work best if taken before going to bed.

      Foster said that a failure to consider the circadian influence in past animal experiments may even have led to promising drug candidates being shelved. Toxicity can change from 20% to 80% depending on the time of the day you test a drug, he said.

      As the impact of scientific advance slowly trickles down, the medical profession and society at large are waking up to the power of the biological clock.

      A paper last year showing that jet lag impairs baseball performance, prompted some professional sports teams to take on circadian biologists as consultants on schedules for training and travel. The US Navy has altered its shift system to align it with the 24-hour clock, rather than the 18-hour day used in the old British system. Schools are experimenting with later school days, better aligned with the teenage body clock, which runs several hours later than that of adults.

      As circadian rhythms have journeyed from obscure corner of science to part of the zeitgeist, companies are launching an increasing number of products on the back of a new anxiety around sleep and natural cycles. This is the western world; if somebody can make a buck theyre going to try to do it, said Rosbash.

      The 73-year-old, who describes his own relationship with sleep as borderline problematic, prefers low- tech remedies, however.

      I havent quite figured out how to do better, he said. I try not to take sleep medication. I dont drink alcohol too late in the evening, I read a good book. The common sense things, I think they help.

      Read more: https://www.theguardian.com/science/2017/oct/06/western-society-is-chronically-sleep-deprived-the-importance-of-the-bodys-clock

      White House Says It Didnt Sign Off on Health Secretarys Private Jet Use

      The White House says it didn’t sign off on what are reportedly at least two dozen private-jet trips taken by Health and Human Services Secretary Tom Price that are now under review by the department’s inspector general.

      Price took at least 24 flights on private airplanes since he became a cabinet secretary in February, Politico reported this week. The trips have cost taxpayers more than $300,000 and were a sharp departure from Price’s predecessors, who typically used commercial flights in the continental U.S., according to Politico.

      “The White House doesn’t sign off for cabinet travel so would direct you to HHS for any comments,” White House press secretary Sarah Sanders said.

      HHS’s Office of Inspector General is reviewing the travel to determine whether it complies with federal regulations, Tesia Williams, a spokeswoman for the OIG, said in an email Friday.

      “We take this matter very seriously, and when questions arose about potentially inappropriate travel, we immediately began assessing the issue,” Williams said. “I can confirm that work is under way and will be completed as soon as possible.”

      Trips Defended

      The health department defended the trips, saying Price’s schedule was difficult and his workdays long.

      “Within an incredibly demanding schedule full of 13+ hour days, every effort is being made to maximize Secretary Price’s ability to travel outside Washington to meet with the American people and carry out HHS’s missions,” said Charmaine Yoest, an HHS spokeswoman. “The travel department continues to check every possible source for travel needs including commercial, but commercial travel is not always feasible.”

      Price is the second official in President Donald Trump’s Cabinet to face scrutiny over travel. Treasury Secretary Steven Mnuchin came under fire earlier this month after news emerged that he sought to use a government plane for his honeymoon in August and the use of an Air Force jet for a trip to Kentucky on Aug. 21 to talk about tax policy and to visit Fort Knox. 

      The Treasury’s inspector general is reviewing all of Mnuchin’s use of and requests for government aircraft.

        Read more: http://www.bloomberg.com/news/articles/2017-09-22/health-secretary-s-private-jet-use-wasn-t-cleared-by-white-house

        Trump Officials Dispute the Benefits of Birth Control to Justify Rules

        When the Trump administration elected to stop requiring many employers to offer birth-control coverage in their health plans, it devoted nine of its new rule’s 163 pages to questioning the links between contraception and preventing unplanned pregnancies.

        In the rule released Friday, officials attacked a 2011 report that recommended mandatory birth-control coverage to help women avoid unintended pregnancies. That report, requested by the Department of Health and Human Services, was done by the National Academies of Sciences, Engineering and Medicine — then the Institute of Medicine — an expert group that serves as the nation’s scientific adviser.

        “The rates of, and reasons for, unintended pregnancy are notoriously difficult to measure,” according to the Trump administration’s interim final rule. “In particular, association and causality can be hard to disentangle.”

        Multiple studies have found that access or use of contraception reduced unintended pregnancies. 

        Claims in the report that link increased contraceptive use by unmarried women and teens to decreases in unintended pregnancies “rely on association rather than causation,” according to the rule. The rule references another study that found increased access to contraception decreased teen pregnancies short-term but led to an increase in the long run.

        “We know that safe contraception — and contraception is incredibly safe — leads to a reduction in pregnancies,” said Michele Bratcher Goodwin, director of the Center for Biotechnology and Global Health Policy at the University of California, Irvine, School of Law. “This has been data that we’ve had for decades.”

        Riskier Behavior

        The rules were released as part of a broader package of protections for religious freedom that the administration announced Friday.

        The government also said imposing a coverage mandate could “affect risky sexual behavior in a negative way” though it didn’t point to any particular studies to support its point. A 2014 study by the Washington University School of Medicine in St. Louis found providing no-cost contraception did not lead to riskier sexual behavior.

        The rule asserts that positive health effects associated with birth control “might also be partially offset by an association with negative health effects.” The rule connects the claim of negative health effects to a call by the National Institutes of Health in 2013 for the development of new contraceptives that stated current options can have “many undesirable side effects.” 

        The rule also describes an Agency for Healthcare Research and Quality review that found oral contraceptives increased users’ risk of breast cancer and vascular events, making the drugs’ use in preventing ovarian cancer uncertain.

        Federal officials used all of these assertions to determine the government “need not take a position on these empirical questions.”

        “Our review is sufficient to lead us to conclude that significantly more uncertainty and ambiguity exists in the record than the Departments previously acknowledged.”

          Read more: http://www.bloomberg.com/news/articles/2017-10-06/trump-officials-dispute-birth-control-benefits-to-justify-rules