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DURHAM, N.C. -- The rise of social media and fake news challenge long-held assumptions about the First Amendment and are undermining the functioning of the "the marketplace of ideas," a Duke professor argues in a new article.

"There are a number of very specific ways in which the structure and operation of today's digital media ecosystem favors falsity over truth; and this shifting balance raises some troubling implications for how we think about the First Amendment," says author Philip Napoli, professor at Duke's Sanford School of Public Policy.

Much of our thinking about the First Amendment assumes that the answer to false speech is more speech, or counter-speech, and that the truth will triumph in the marketplace of ideas, he says.

Yet changes in the news media - such as consumption via social media, the speed and targeting capabilities of fake news purveyors and "filter bubbles," where people only see news that reinforces their views -- mean we can no longer assume legitimate news will win, Napoli says.

The article, "What If More Speech Is No Longer the Solution? First Amendment Theory Meets Fake News and the Filter Bubble," was published Monday in the Federal Communications Law Journal.

In the last two decades, technological and economic changes have undermined legitimate news production and enhanced fake news. Despite the flood of news available online, the actual proportion of original reporting is declining.

"Original reporting is costly. Fake news is cheap," says Napoli.

Meanwhile, audiences have increasing difficulty distinguishing between true and false news. Recent surveys suggest people now evaluate news not based on its source, but based on the trustworthiness of the person who shared it.

The 2016 election is a case study of the failure of the marketplace of ideas, Napoli said. Filter bubbles and fake news, including Russia's online propaganda efforts, made it difficult for citizens to access accurate information, Napoli said.

Meanwhile, big social media platforms have considered themselves tech companies, not publishing or media companies. The public service ethos and journalistic standards of traditional media are not part of their business models. Google and Facebook have not acted as gatekeepers keeping out fake news in same way that traditional news outlets such as The New York Times or ABC News do.

Social media companies also bear no legal liability for falsehoods, Napoli notes.

He recommends that social media companies develop a robust public service ethos appropriate to their responsibilities as providers of the news and information essential to a functioning democracy.

The recent Congressional testimony of Facebook founder Mark Zuckerberg shows that Congress has taken an interest in the issue.

"The key question is if or how government intervention might be an appropriate response. Germany recently adopted a law that requires social media platforms to remove stories identified as fake news or face government-imposed fines," Napoli says.

In the U.S., broadcast media adhere to federal regulations about false news reporting, and the Federal Communications Commission can choose to investigate reports of intentional falsification of the news.

"It is important to recognize that concerns about fake news have an established foothold in the U.S. media regulatory framework," Napoli says.

Vigorous physical activity, either in leisure time or in work, may be linked to a heightened risk of developing motor neurone disease, also known as amyotrophic lateral sclerosis, or ALS for short, suggests research published online in the Journal of Neurology Neurosurgery & Psychiatry.

The "new class 1 evidence" prompts the researchers to speculate whether ALS might be a trade-off for the many well known benefits of physical exercise on other aspects of health.

ALS is a progressive, fatal neurodegenerative disease for which there is currently no treatment. Genes account for a proportion of cases, but a role for environmental factors, including physical activity, has also been mooted.

But the evidence to date has been inconclusive, possibly because of the differences in research design and methods, say the researchers.

In a bid to try and plug this gap, they compared the lifestyles of 1557 adults newly diagnosed with ALS in their mid 60s in Ireland, Italy, and The Netherlands with those of 2922 similarly aged people who didn't have the condition.

Each of the participants provided details of their educational attainment; lifestyle, including smoking and alcohol intake; employment history; and lifetime physical activity levels (weekly leisure and workplace quotas).

Physical activity was measured in Metabolic Equivalent of Task (MET) minutes. These express the amount of energy (calories) expended per minute of physical activity.

Analysis of the data showed that lifetime physical activity was associated with a heightened risk of ALS, after taking account of potentially influential factors, such as age, sex, smoking and alcohol intake, and other potential workplace exposures.

The heightened risk was 6 percent for leisure time activities; 7 percent for workplace activities; and 6 percent for all activities combined.The associations were strongest among the Italian and Irish participants.

And the higher the MET score, the greater was the risk of ALS, which adds weight to other studies describing a higher prevalence of motor neurone disease among former professional athletes, say the researchers.

This is an observational study, and as such, it can't establish causation. It was also based on recall, and factors such as diet, trauma or some metabolic or energy deficit induced by activity can't be ruled out, say the researchers.

"An [increased risk of 6%] for all activities combined can be translated into a 26 percent increase in risk when comparing a person who is more active than average and a person who is less [so]," they explain.

While exercise is not likely to be a major factor in the development of ALS, this level of increased risk might be important in those who are genetically predisposed, they suggest.

"Overall, [physical activity] has been demonstrated to be protective against many diseases, including cardiovascular disease, diabetes, and a variety of cancers," they point out, and suggest that "Decreasing the risk of these common conditions may be a trade-off with increasing the risk of a relatively rare disease such as ALS."

In a linked editorial, Professor Michael Swash, of the Royal London Hospital, emphasises that there are "no simple answers" for the potential role of environmental factors in the development of ALS.

"Although it is tempting to construct an hypothesis linking physical activity with increased [central nervous system] excitotoxicity in susceptible persons and, therefore, an increased risk for the onset of ALS, a disorder long recognised to be associated with CNS excitotoxicity, any such suggestion is, at present, purely hypothetical," he cautions.

"Nonetheless, the data are intriguing and deserve closer investigation on a case-by-case basis," he adds.

LOS ANGELES - For most people, it's better to start taking drugs for multiple sclerosis (MS) early on rather than letting the disease run its course, according to a new guideline for treating MS from the American Academy of Neurology. The guideline is published in the April 23, 2018, online issue of Neurology®, the medical journal of the American Academy of Neurology, and presented at the 70th AAN Annual Meeting in Los Angeles, April 21 to April 27, 2018. The guideline is endorsed by the Multiple Sclerosis Association of America and the National Multiple Sclerosis Society.

"The treatment landscape for people with MS has changed dramatically over the last decade," said lead author Alexander D. Rae-Grant, MD, FAAN, of Cleveland Clinic in Cleveland, Ohio, and a Fellow of the American Academy of Neurology. "We now have a number of disease-modifying therapies to choose from that may help treat MS by changing how the disease affects people over time by slowing the disease process."

Multiple sclerosis affects about 400,000 Americans and is a leading cause of disability among young adults. It is a chronic inflammatory condition that affects the central nervous system, causing substantial disability and increasing the risk of mortality. People living with MS experience symptoms such as vision problems, muscle weakness, bladder or bowel dysfunction, tremors, trouble with coordination, and cognitive and emotional problems.

Unlike some treatments, which only help manage symptoms, disease-modifying therapies are drugs that can alter or change the course of MS for patients. While they are not a cure, they can reduce the number of relapses a person has and slow the process of MS.

For the guideline, experts from the American Academy of Neurology carefully reviewed available scientific studies on the use of MS drugs.

They found that starting to use an MS drug as early as possible may be better than letting MS run its course. This is because the disease is known to get worse over time. According to the guideline, several MS drugs have either strong or moderate evidence supporting their use for slowing certain disease processes.

While MS drugs may help slow and stabilize the disease process, some people with MS may experience a return of disease activity while using an MS drug. According to the guideline, if that happens, they may need to switch to another MS drug shown to have less risk of returning disease activity.

The guideline experts also note that some people whose MS is stable may think about stopping their MS drug use since they have no signs of the disease. According to the guideline, very few studies have been done on the benefits or risks of stopping MS drugs.

Currently, there is no blood test that can determine whether a person's MS drug is working and there is no universally accepted method to determine which MS drug to use in which order or in which individuals.
Some MS drugs have risks for the reproductive health of both men and women, and the guideline offers recommendations regarding pregnancy and disease-modifying therapies for women with MS, including that their doctors monitor any plans for pregnancy.

According to the guideline authors, it is important to be aware of the potential risks of these medicines, and they recommend that people weigh the benefits and risks with their physician before deciding to start, switch or stop using an MS drug.

Increased awareness of the health consequences of eating too much sugar has fueled a dramatic uptick in the consumption of zero-calorie artificial sweeteners in recent decades. However, new research finds sugar replacements can also cause health changes that are linked with diabetes and obesity, suggesting that switching from regular to diet soda may be a case of 'out of the frying pan, into the fire.'

Artificial sweeteners are one of the most common food additives worldwide, frequently consumed in diet and zero-calorie sodas and other products. While some previous studies have linked artificial sweeteners with negative health consequences, earlier research has been mixed and raised questions about potential bias related to study sponsorship.

This new study is the largest examination to date that tracks biochemical changes in the body--using an approach known as unbiased high-throughput metabolomics--after consumption of sugar or sugar substitutes. Researchers also looked at impacts on vascular health by studying how the substances affect the lining of blood vessels. The studies were conducted in rats and cell cultures.

"Despite the addition of these non-caloric artificial sweeteners to our everyday diets, there has still been a drastic rise in obesity and diabetes," said lead researcher Brian Hoffmann, PhD, assistant professor in the department of biomedical engineering at the Medical College of Wisconsin and Marquette University. "In our studies, both sugar and artificial sweeteners seem to exhibit negative effects linked to obesity and diabetes, albeit through very different mechanisms from each other."

Hoffmann will present the research at the American Physiological Society annual meeting during the 2018 Experimental Biology meeting, held April 21-25 in San Diego.

The team fed different groups of rats diets high in glucose or fructose (kinds of sugar), or aspartame or acesulfame potassium (common zero-calorie artificial sweeteners). After three weeks, the researchers saw significant differences in the concentrations of biochemicals, fats and amino acids in blood samples.

The results suggest artificial sweeteners change how the body processes fat and gets its energy. In addition, they found acesulfame potassium seemed to accumulate in the blood, with higher concentrations having a more harmful effect on the cells that line blood vessels.

"We observed that in moderation, your body has the machinery to handle sugar; it is when the system is overloaded over a long period of time that this machinery breaks down," Hoffmann said. "We also observed that replacing these sugars with non-caloric artificial sweeteners leads to negative changes in fat and energy metabolism."

So, which is worse, sugar or artificial sweeteners? Researchers cautioned that the results do not provide a clear answer and the question warrants further study. It is well known that high dietary sugar is linked to negative health outcomes and the study suggests artificial sweeteners do, too.

"It is not as simple as 'stop using artificial sweeteners' being the key to solving overall health outcomes related to diabetes and obesity," Hoffmann added. "If you chronically consume these foreign substances (as with sugar) the risk of negative health outcomes increases. As with other dietary components, I like to tell people moderation is the key if one finds it hard to completely cut something out of their diet."

Brian Hoffmann will present this research on Sunday, April 22, from 10 a.m.-noon in the San Diego Convention Center Exhibit Hall (poster A322) (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.

Barcelona, Spain: Radiotherapy given in high doses over a shorter period of time is safe and effective for prostate cancer patients, according to research presented at the ESTRO 37 conference today.

The treatment, called ultrahypofractionated radiotherapy, involves hospital treatment every other day for two and half weeks, compared to every week day for eight weeks for standard radiotherapy.

Researchers say this method of giving radiotherapy saves time for patients. It also frees up radiotherapy equipment, saving money and benefiting other patients on the waiting list for treatment.

The study was presented by Professor Anders Widmark, a senior consultant based in the department of radiation sciences and cancer centre at Umeå University, Sweden.

He said: "We already know that radiotherapy can destroy cancer cells in the prostate and that it has advantages over surgery and hormone therapy because it is less likely to cause impotence or incontinence. However, radiotherapy requires expensive specialist equipment and patients can end up on a waiting list for treatment.

"Ultrahypofractionated radiotherapy offers a number of practical benefits to patients as well as time and cost-savings for hospitals, so we wanted to test if it is as safe and effective as standard radiotherapy."

The researchers conducted a trial with 1,200 patients who were treated at ten hospitals in Sweden and two in Denmark between July 2005 and November 2015. All had been diagnosed with medium or high-risk cancer, where clinical factors suggest there was a risk that the cancer could spread if it was not treated. None had received treatment to block the male hormone testosterone, which can stimulate prostate tumours to grow.

Half of patients received standard radiotherapy of 39 treatments each with a standard radiation dose of two Gray (Gy), spread over eight weeks (78 Gy in total). The other half received ultrahypofractionated radiotherapy with seven treatments of high dose radiation of 6.1 Gy, every other week day for two and half weeks (42.7 Gy in total). Patients were monitored for an average of five years following treatment to see whether their cancer returned, indicated by a rising level of prostate specific antigen (PSA) and whether they suffered any side-effects.

Researchers found that at five years after treatment 83.8% of patients treated with standard radiotherapy had no signs of their cancer returning and in patients treated with ultrahypofractionated radiotherapy the figure was 83.7%.

Although patients who had the ultrahypofractionated treatment suffered slightly worse side-effects at the end of treatment, long-term side-effects were the same as those experienced by patients who had the standard treatment.

Professor Widmark added: "Previous research has already shown that it's possible to increase individual doses and give them over four to five weeks. Now we have shown that we can condense the therapy further, raising the dose at each hospital visit so that the whole schedule lasts only two and half weeks.

"This is the first large patient trial of this kind and it shows that ultrahypofractionated radiotherapy is just as effective as standard radiotherapy at stopping prostate cancer from returning. Importantly, it also shows that patients treated in this way do not suffer any more side-effects than those treated with conventional radiotherapy."

The researchers plan to continue to study the patients in the trial to check whether there are differences in their survival or side-effects in the longer-term.

President of ESTRO, Professor Yolande Lievens, head of the department of radiation oncology at Ghent University Hospital, Belgium, said: "Advances in radiotherapy mean that we are better able to locate and target tumours while minimising damage to nearby organs. In prostate cancer, this can mean men retaining urinary and sexual function. This also means that we can consider giving higher individual doses over a shorter time, as in this study.

"Results of this trial suggests that ultrahypofractionated radiotherapy is equal to conventional radiotherapy. For patients, that could mean they have to spend much less time travelling to and from hospital for treatment. For health services this could help them save resources and get more patients treated sooner."

Research into cancer can provide new insight into how this disease works and how it can be stopped. The Experimental Biology 2018 meeting (EB 2018) will showcase innovative research that could lead to new ways to treat and prevent cancer.

Potential treatment for pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC), which makes up 90 percent of all pancreatic cancers, has a 5-year survival rate of less than five percent. The cancer is not only difficult to detect but treatment is often complicated by mutations in the p53 tumor suppressor gene that make the cancer cells resistant to chemotherapy. Researchers from the Human BioMolecular Research Institute, University of California San Diego and ChemRegen, Inc. developed a new compound that could be useful for treating pancreatic cancer. They previously showed that the compound killed PDAC cells with and without mutant p53 and strongly inhibited tumor growth in an invasive PDAC tumor mouse model. In new work, the researchers showed that the compound works by uniquely targeting two human cell death pathways: programmed cell death, or apoptosis, and the intracellular degradation system known as autophagy. They also showed that the compound's potency comes from its ability to induce crosstalk between PDAC cell death pathways.

Jiongjia Cheng will present this research at the American Society for Pharmacology and Experimental Therapeutics (ASPET) annual meeting from 12:30-2:30 p.m. Tuesday, April 24, in Exhibit Halls A-D (poster C197) (abstract).

Insights into chemotherapy-associated pain

Patients receiving anti-cancer drugs often experience debilitating pain because of a condition known as chemotherapy-induced peripheral neuropathy. Scientists don't fully understand why the drugs cause this condition, which currently has no treatment. In a new study, researchers from the University of Texas Health Science Center at San Antonio discovered that exposure to vinca alkaloids and taxanes chemotherapy drugs was associated with an immediate pain response activated through the peripheral nerves that detect pain stimuli. Their experiments revealed that the chemotherapy drugs cause overexcitation of sensory neurons by specifically activating the an ion channel (TrpA1) involved in pain perception. The study represents the first demonstration of direct activation of sensory neurons by anti-cancer drugs and supports a role for TrpA1 in the development of chemotherapy-induced peripheral neuropathy. The findings could lead to new treatments for pain associated with chemotherapy drugs.

Nina Boiko will present this research at the American Physiological Society annual meeting from 7-8:30 p.m. Saturday, April 21, in the Sails Pavilion (poster SH16) (abstract); from 9:45-10 a.m. Monday, April 23, in Room 25C; and from 10 a.m.-noon Monday, April 23, in the Exhibit Hall (poster A518).

Highly potent NSAID inhibits colon cancer

Indomethacin is a highly potent nonsteroidal anti-inflammatory drug (NSAID) that has shown anticancer properties in people and animal models. To find out if this drug inhibits colon cancer, researchers from University of Texas Health Sciences Center in Houston conducted a study involving unmodified indomethacin and indomethacin modified with phosphatidylcholine to protect against NSAID injury in the gastrointestinal tract. In cultured cancer cells from mice, doses of both indomethacin formulations significantly inhibited colon cancer cell growth in culture, with the phosphatidylcholine formulation showing slightly more potency at the lowest dose tested. Similarly, in mice injected with colon cancer cells, treatment with both forms of indomethacin brought significant reductions in the number of tumors compared to mice receiving no treatment. The researchers conclude that indomethacin and phosphatidylcholine-indomethacin are strong and effective inhibitors of colon cancer cell growth and hold potential for preventing, and possibly treating, colorectal cancer in people.

Lenard Lichtenberger will present this research at the ASPET annual meeting from 12:30 p.m.-2 p.m. Monday, April 23, in Exhibit Halls A-D (poster C243 701.9) (abstract).

Understanding what drives breast cancer growth

Cold-inducible RNA binding protein (CIRP) plays an important role in regulating gene expression and how cells respond to stress. To better understand CIRP's role in breast cancer, researchers from the University of New Mexico Health Sciences Center are studying a mouse model of breast cancer that expresses CIRP at levels that are higher than normal. The researchers report that the increased levels of CIRP inhibited growth, progression and metastasis of tumors. These anti-cancer effects were associated with changes in immune system signals known as cytokines. Specifically, the mice exhibited decreased levels of cytokines that promote an environment favorable for tumor growth and increased levels of cytokines that create an antitumorigenic environment. The researchers continue to study the mechanisms involved in CIRP's ability to influence signaling between cancer and immune cells so that this information could be used to improve standard therapies and immunotherapeutic approaches for treating breast cancer.

Daniel Lujan will present this research at the American Association of Anatomists annual meeting during the Cell Biology Award Hybrid Symposium at 11:30 a.m. Sunday, April 22, in Room 11A (abstract).

EB 2018 is the premier annual meeting of five scientific societies to be held April 21-25 at the San Diego Convention Center. Contact the media team for abstracts, images and interviews, or to obtain a free press pass to attend the meeting.

New research overturns a myth that has persisted for nearly four decades - that competing in endurance sports, like this weekend's London Marathon, suppresses the body's immune system and makes competitors more susceptible to infections.

Research from the 1980s, which focused on events such as the Los Angeles Marathon, asked competitors if they had symptoms of infections in the days and weeks after their race. Many did, leading to a widespread belief that endurance sports increase infection risk by suppressing our immune system.

Now a new article, from researchers in the Department for Health at the University of Bath published in the journal Frontiers in Immunology, reinterprets scientific findings from the last few decades and emphasises that exercise - instead of dampening immunity - may instead be beneficial for immune health.

In a detailed analysis of research articles that have been published since the 1980s, this new review of the literature has reinterpreted findings, based on fundamental principles of immunology and exercise physiology, to clarify misconceptions and misinterpretations that have formed over the years.

In their study, the authors from the University of Bath explain that, for competitors taking part in endurance sports, exercise causes immune cells to change in two ways. Initially, during exercise, the number of some immune cells in the bloodstream can increase dramatically by up to 10 times, especially 'natural killer cells' which deal with infections. After exercise, some cells in the bloodstream decrease substantially - sometimes falling to levels lower than before exercise started, and this can last for several hours.

Many scientists previously interpreted this fall in immune cells after exercise to be immune-suppression. However strong evidence suggests that this does not mean that cells have been 'lost' or 'destroyed', but rather that they move to other sites in the body that are more likely to become infected, such as the lungs.

Scientists know that these cells are not 'destroyed' for three main reasons. First, most evidence shows that cells return to normal levels within several hours, which is far too quick for them be 'replaced' with new cells. Second, studies in humans have shown that these cells have the ability to leave the bloodstream and travel to other body sites.

Third, studies with laboratory animals have shown by labelling immune cells, that following exercise, these labelled cells accumulate in the lungs, and other places, because they go there to look for infections.

The authors therefore suggest that low numbers of immune cells in the bloodstream in the hours after exercise, far from being a sign of immune-suppression, are in fact a signal that these cells, primed by exercise, are working in other parts of the body.

Prize Fellow Dr John Campbell from the University's Department for Health explained: "It is increasingly clear that changes happening to your immune system after a strenuous bout of exercise do not leave your body immune-suppressed. In fact, evidence now suggests that your immune system is boosted after exercise - for example we know that exercise can improve your immune response to a flu jab."

Co-author, Dr James Turner added: "Given the important role exercise has for reducing the risk of cardiovascular disease, cancer and type II diabetes, the findings from our analysis emphasise that people should not be put off exercise for fear that it will dampen their immune system. Clearly, the benefits of exercise, including endurance sports, outweigh any negative effects which people may perceive."

The authors suggest that although a strenuous exercise bout itself will not increase the likelihood of catching an infection, other factors might.

First, attending any event where there is a large gathering of people, increases your chance of infection. Second, public transport, particularly airline travel over long distances, where sleep is disrupted, may also increase your infection risk. Other factors, like eating an inadequate diet, getting cold and wet, and psychological stress, have all been linked to a greater chance of developing infections.

Previous studies have demonstrated a decreased risk of Alzheimer's disease (AD) in individuals with various cancers, including non-melanoma skin cancers (including squamous cell cancers and basal cell cancers). A new Journal of the European Academy of Dermatology & Venereology study finds that this inverse relationship also holds true for malignant melanoma.

The study included patients aged 60-88 years with a clinic follow-up of at least 1 year and no diagnosis of AD or skin cancer at the beginning of the study. Of 1147 patients who were later diagnosed with malignant melanoma, 5 were diagnosed with subsequent AD. Of 2506 who were diagnosed with basal cell cancer, 5 had a subsequent AD diagnosis, and of 967 who were diagnosed with squamous cell cancer, only 1 had a subsequent AD diagnosis.

After adjustments, a diagnosis of malignant melanoma was associated with a 61% reduced risk of developing AD. For basal cell and squamous cell carcinomas, the reduced risks were 82% and 92%, respectively.

DALLAS - April 19, 2018 - After testing more than 200,000 chemical compounds, UT Southwestern's Simmons Cancer Center researchers have identified 170 chemicals that are potential candidates for development into drug therapies for lung cancer.

The 5-year project set out to identify new therapeutic targets for non-small cell lung cancer as well as potential drugs for these targets - a significant step forward toward personalizing cancer care.

"For the large majority of compounds, we identified a predictive biomarker - a feature that allows the development of 'precision medicine,' or individualized treatment for each patient, which is a major goal of the Simmons Cancer Center," said Dr. John Minna, Director of the Hamon Center for Therapeutic Oncology Research at UT Southwestern Medical Center.

Lung cancer is the most common cause of cancer deaths in the U.S. for both men and women, according to the National Cancer Institute. Non-small cell lung cancer, the type of cancer studied in this research, comprises approximately 85 percent of all lung cancers. In 2017, lung cancer caused 26 percent of all cancer deaths.

For more information

Tips: Should I be screened for lung cancer?
Cancer Care: Lung cancer services
News: Double-drug lung cancer strategy
Labs: Hamon Center for Therapeutic Oncology Research
Research Article: Cell

Using UT Southwestern's unique lung cancer cell library that is now the world's largest, the researchers searched for compounds that would kill cancer cells but not harm normal lung cells.

"We began an ambitious project with the goal of identifying 'therapeutic triads': chemicals that kill cancer cells, biomarkers that predict who would respond, and the therapeutic targets on which those active chemicals work," said Dr. Minna, Professor of Internal Medicine and Pharmacology who holds the Sarah M. and Charles E. Seay Distinguished Chair in Cancer Research and the Max L. Thomas Distinguished Chair in Molecular Pulmonary Oncology.

Continuing to uncover the mechanism of action for the majority of the 170 chemicals will be a key focus of future research. Follow-up work will also include testing the chemicals on other types of cancer. Preliminary work shows some of the compounds are likely effective against certain breast and ovarian cancers as well.

Results of this complex project, led by Dr. Michael White, former Professor of Cell Biology and now Vice President for Oncology Drug Development at Pfizer Inc., involved members of the Harold C. Simmons Comprehensive Cancer Center and the Departments of Cell Biology, Biochemistry, Pharmacology, and Internal Medicine, and appear in the journal Cell.

Dr. Minna, along with his research partner Dr. Adi Gazdar, Professor of Pathology and with the Hamon Center for Therapeutic Oncology, have carefully developed and curated a collection of lung cancer cell lines since the 1970s that is now recognized as the world's largest - and upon which this research was based. Dr. Minna was named a "Giant of Cancer Care" in 2015 in recognition of this work developing lung cancer cell lines.

What made this work unusual was that they began with the chemical compounds.

"Almost all cancer research is gene-first, or target-first. We began with the potential drugs," said Dr. Michael Roth, Professor of Biochemistry and a member of the Simmons Cancer Center.

Using UT Southwestern's High-Throughput Screening Core Facility, the team of scientists began by testing 200,000 chemicals against 12 lung cancer cell lines.

"The initial screen gave us 15,000 chemical 'hits,' way too many to work with in detail, but with repeat testing we eventually narrowed the number down to 170. We called this the UT Southwestern 'Precision Oncology Probe Set,' or POPS," said Dr. Bruce Posner, Professor of Biochemistry and Director of the High-Throughput center.

The set of 170 chemical compounds was then tested across 100 lung cancer lines.

At the same time, researchers conducted in-depth molecular analyses of the lung cancer lines, including identification of genome mutations and protein expression. This information, paired with whether or not an individual cancer cell line was sensitive to a particular chemical, allowed the researchers to develop a set of biomarkers - indicators that could be used to determine if a particular cancer will respond to one of the 170 chemical compounds.

The final step of the study was determining how the drugs acts on the cancer. "We scoured existing knowledge and were able to come up with the target for several examples to complete the third leg of the triad," said Dr. Roth, who holds the Diane and Hal Brierley Distinguished Chair in Biomedical Research at UT Southwestern, which is recognizing its 75th anniversary this year.

Barcelona, Spain: A simple test of handgrip strength is a good indicator of short- and long-term survival in patients with early, stage I non-small cell lung cancer (NSCLC), according to new findings to be presented at the ESTRO 37 conference tomorrow (Saturday).

In a study of 226 patients who were about to be treated with stereotactic body radiotherapy (SBRT) at the MAASTRO Clinic in Maastricht (The Netherlands), researchers found that weak handgrip strength was an independent indicator of life expectancy providing additional information to the World Health Organisation (WHO) performance status, which is used routinely at present to measure this as well as patients' general well-being and ability to manage the activities of daily life.

Patients with weak handgrips were 1.5 times more likely to die within five years, compared to those with strong handgrips. Handgrip strength was even able to indicate life expectancy within one year of the measurement being taken.

Dr Stéphanie Peeters, a radiation oncologist at the MAASTRO Clinic, said: "We have found that handgrip strength is an objective, cheap and easy way to measure short- and long-term overall survival in stage I patients with non-small cell lung cancer who are being treated with stereotactic body radiotherapy with the aim of curing them. The WHO performance status measurement is quantified by a physician, and therefore may be prone to subjectivity. The handgrip test, on the other hand, is a more objective measure that may provide additional information on the general condition of a patient. Our analysis shows that handgrip strength is a valuable additional measure for predicting overall survival."

NSCLC patients who were about to be treated with SBRT between 2006 and 2012 were asked to grip the handle of a device that measures grip strength as hard as they could for three seconds. This was measured three times for each hand. Fifty-nine per cent of the patients were men and 41% were women. They had a mean (average) age of 72. The results of the test were adjusted to take account of gender, age and height. Handgrip weakness was seen in 31% of patients, whereas 69% had no weakness. Handgrip strength varied between 17kg and 39kg (mean of 28kg), and weakness was defined according to what was normal in the general population, taking into account age and gender.

Among those with handgrip weakness, only 12% were still alive five years later, while 40% of patients without weakness were still alive.

Other factors that were associated with an increased risk of dying within five years were being male, being older and having a lower body mass index (BMI).

"It is not always easy for a physician to get a good idea about the general condition of a patient based on one, or only a few, doctor's visits. In this study we have shown that handgrip strength provides additional information to help evaluate survival, which may guide the physician in how to manage the lung tumour. In patients with poor prognosis, it may be decided not to give an active treatment, and having an objective measure such as the handgrip test may give more weight to this important decision. Close surveillance may then be an option," said Dr Peeters.

Further work needs to be performed to validate the test in other groups of patients in order to justify the widespread use of the test. In addition, the researchers do not know whether improving a patient's general health and fitness might help improve their life expectancy. "Future studies could explore the impact on survival of improving the handgrip strength in patients with weakness before the start of a curative treatment," she said.

President of ESTRO, Professor Yolande Lievens, head of the department of radiation oncology at Ghent University Hospital, Belgium, said: "Patients with early-stage, inoperable non-small cell lung cancer who are treated with stereotactic body radiotherapy often die from other diseases and conditions and not from their cancer. In order to give patients the best quality of life while also treating their cancer as effectively as possible, doctors have to weigh the pros and cons of the treatments; in other words, the potential survival gain against the potential adverse effect on quality of life. This interesting study shows that a simple handgrip test provides doctors with an objective, cheap and easy way to assess their patients' overall health, which will help them in deciding on the best way of managing the cancer. While the test already provides interesting information for this population of early-stage lung cancer, it may prove even more interesting in more advanced tumour stages, the risk of toxicity from combined chemo-radiotherapy schemes being more important than after SBRT."

CHAPEL HILL, NC - A new study published today in the journal PLOS ONE details how a compound called EP055 binds to sperm proteins to significantly slow the overall mobility of the sperm without affecting hormones, making EP055 a potential "male pill" without side effects.

"Simply put, the compound turns-off the sperm's ability to swim, significantly limiting fertilization capabilities," said lead investigator Michael O'Rand, PhD, retired professor of cell biology and physiology in the University of North Carolina at Chapel Hill School of Medicine, and president/CEO of Eppin Pharma, Inc. "This makes EP055 an ideal candidate for non-hormonal male contraception."

Currently, condoms and surgical vasectomy are the only safe forms of birth control currently available for men. There are hormonal drugs in clinical trials that target the production of sperm, but these affect the natural hormones in men much like female contraceptives affect hormones in women.

During the study, thirty hours following a high-dose intravenous infusion of EP055 in male rhesus macaques, O'Rand and researchers in the Oregon National Primate Research Center at OHSU in Portland, Oregon, found no indication of normal sperm motility. Further, no physical side effects were observed.

"At 18 days post-infusion, all macaques showed signs of complete recovery, suggesting that the EP055 compound is indeed reversible," said study co-investigator Mary Zelinski, PhD, research associate professor at the ONPRC at OHSU and associate professor of obstetrics and gynecology in the OHSU School of Medicine.

O'Rand and Zelinski indicate that more work is needed before EP055 becomes available for human use. They and their teams have begun to test a pill form of the compound and will eventually conduct a mating trial of EP055's effectiveness against pregnancy.

New research published today by the Journal of the Royal Society of Medicine finds that general practices in England with the worst prescribing quality scores are 2.1 times more likely to prescribe homeopathy than practices with the best prescribing quality scores.

Researchers from the University of Oxford and Exeter University looked at practices that prescribe homeopathy to see if they differ in their prescribing of other drugs. They found that even infrequent homeopathy prescribing is strongly associated with poor performance on a range of prescribing quality measures, but not with overall patient recommendation or quality outcomes framework score.

Lead researcher Dr Ben Goldacre, Senior Clinical Research Fellow at the Nuffield Department of Primary Care Health Sciences, University of Oxford, said: "Despite the lack of evidence for homeopathy, and its lack of a plausible mechanism, some NHS doctors still prescribe it. We set out to explore whether general practices prescribing homeopathic remedies also behave differently on other measures of general practitioner behaviour."

The researchers identified 644 practices that had issued at least one homeopathy prescription in a six-month period (December 2016 to May 2017). There were 2,720 homeopathy prescriptions in total costing £36,532 (mean £13,43 per item).

They found that prescribing any homeopathy is associated with poorer performance at practice level on a range of standard prescribing measures. The association is unlikely to be a direct causal relationship, say the researchers, but may reflect deeper underlying practice features, such as the extent of respect for evidence-based practice, or poorer stewardship of the prescribing budget.

Dr Goldacre said: "Although NHS expenditure on homeopathy is low, we believe the strong association between homeopathy use and poorer prescribing in general is more important than cost. It should raise concerns and may be of interest to those seeking to understand variation in clinical styles and the use of alternative medicine by clinicians."

Increasing numbers of people worldwide are suffering life-long disability and dying prematurely due to the ineffective treatment of people with multiple health conditions, a new report suggests.

The report from the Academy of Medical Sciences, published today (00.01hrs BST 19 April 2018), points to an alarming lack of information about multimorbidity, a scenario where a patient suffers several diseases simultaneously.

While it is well known that multimorbidity is common and on the rise, the exact extent of the problem and the rate at which it is growing is not understood. It is reported to affect anywhere between 13-95% of patients globally, a range so wide that it indicates just how little is known about this global burden. The causes of multimorbidity are poorly understood and strategies for its prevention are lacking.

The report, produced by a working group of 17 international health experts, is the first to address the problem of multimorbidity on a global scale and highlights the inadequacy of the evidence required to guide health policy and medical practice. The project was supported in part by the UK Department for Business, Energy and Industrial Strategy.

Most health services, including the NHS, are not designed to care for patients with multiple illnesses. This is likely to contribute to the increasing pressures on health systems and budgets worldwide, the report suggests. It concludes that without a better understanding of multimorbidity, it will not be possible for any country to plan future healthcare resources and redesign services effectively.

Health conditions that frequently group together include heart disease, high blood pressure, diabetes, cancer, depression, anxiety, chronic obstructive pulmonary disease (COPD) and chronic kidney disease. However, it is unclear why some of these conditions cluster together, making it difficult to predict which patients may be most in need of preventive steps or increased care.

Evidence suggests multimorbidity is most common in women and people with low income, and is increasingly common in young people as well as in older people.

Professor Stephen MacMahon FMedSci, Chair of the Academy of Medical Sciences multimorbidity working group, said:

"While we know multimorbidity is very common, we don't know precisely how many people live with multiple serious illnesses. From what we do know, I estimate tens of millions of Britons suffer from multimorbidity, and globally the number could be a billion. Similarly, while we know multimorbidity is increasing, we don't know how quickly or which groups are experiencing the biggest increases.

"This report should be the tipping point of recognising that multimorbidity is an enormous threat to global health. It is a priority to get the evidence we need to develop effective strategies for prevention and treatment."

The scientific community does not have an agreed definition of multimorbidity, which has hindered essential research needed to improve prevention and treatment. The report provides a new definition of multimorbidity and recommends that this be adopted by researchers globally.

Physical and mental health conditions often cluster together. Poor mental health can negatively affect quality of life and life expectancy more so than having multiple physical illnesses. The report highlights evidence that mental health conditions can lead to reduced physical health and vice versa. For example, type 2 diabetes has been reported to increase the risk of depression, and adults with depression are 37% more likely to develop type 2 diabetes. However, the division between health services treating mental and physical health often means that patients suffering from both physical and mental conditions are at particular risk of poor care.

Clinical trials of new medicines often exclude patients with multiple conditions, leaving significant gaps in knowledge about effective treatments of those with multimorbidities. This could raise questions about the applicability of the evidence on which drugs are used, given that many long-term diseases do not exist in isolation.

The scale of multimorbidity also raises questions about the suitability of healthcare systems which are organised around treating single diseases or individual organs, the norm in most major hospitals. It also raises questions about the way in which general practice is organised - specifically whether individual GP consultations are generally too short to enable comprehensive management of multiple conditions.

Professor Stephen MacMahon added:

"How to prevent and manage multiple diseases is a challenge that GPs face every day, yet we have almost no evidence on which to provide guidance as to how to do this most effectively.

"We are facing a tidal wave of patients living with multiple long-term health conditions, and our report demonstrates how little we know about how to manage this. Outcomes appear to be worse in these patients and yet there is growing evidence that people with multimorbidity are less likely to receive appropriate care for the individual diseases they have. We face a situation where those in greatest need are least likely to receive appropriate care.

"For too long we've focussed almost exclusively on the management of single diseases, such as cancer and HIV. This means we have neglected the reality that most people with any one long-term disease typically have others."

Professor Melanie Davies, member of the report working group, said:

"We are all familiar with multimorbidity in the older population, but as a diabetes doctor I am seeing many type 2 diabetes patients under the age of 40 years with multiple serious illnesses which is a real concern.

"Our healthcare system is traditionally arranged around caring for single illnesses. With increasing recognition that treatment for patients with multimorbidity is often less effective, we are in desperate need of information to help us reorganise health services to deal with this challenge."

Professor Sir Robert Lechler PMedSci, President of the Academy of Medical Sciences said:

"People living with more than one illness often have more medical appointments and medications to manage, and doctors can struggle to balance their care. The toll of this can have a big impact on the quality of life of patients and their families.

"Multimorbidity is not an intangible problem. Research can give us the evidence needed to tackle this major health challenge and improve patients' lives across the globe.

"So far medicine has excelled in treating single illnesses, but if we are to improve the quality of life for the millions living with multiple health conditions we must get better at treating the whole person and all of their illnesses."

The report suggests tackling multimorbidity will be essential to reach the Sustainable Development Goals set out by the United Nations, and to progress towards the WHO framework on 'integrated people-centred' health services.

As the European Commission considers whether to introduce a partial ban on use of the epilepsy drug valproate in pregnancy over risks to unborn babies, researchers in The BMJ discuss the arguments and the implications for patients and healthcare professionals.

Valproate is an effective treatment for epilepsy, bipolar disorder and migraine. For some women with epilepsy, it may be the only effective treatment option.

But the drug carries a 10% chance of causing physical abnormalities and a 30-40% risk of developmental problems such as autism and developmental delay in children born to mothers who take it. In the UK alone, around 20,000 children have been harmed since valproate was introduced in the 1970s.

Earlier this year, the European Medicines Agency recommended that valproate should not be used in pregnancy unless the woman has epilepsy that has not responded to alternative medications. It should not be prescribed to women of childbearing age unless they use contraception. But surveys show that many women with epilepsy are still unaware of the risks.

Responses from expert advisory groups and regulators have varied, from those advocating shared decision making and informed patient choice about taking valproate in pregnancy, to restricted use when other treatments have failed, to prohibition of valproate in pregnancy coupled with a pregnancy prevention programme in all women taking it.

Consultant neurologists Heather Angus-Leppan and Rebecca Liu say, despite international consensus on the harmful effects of valproate during pregnancy, its use may be warranted in certain situations.

They explain that valproate may be the only effective treatment in certain patients and that untreated epilepsy also carries serious risks to both mother and unborn child.

Banning valproate "imposes less effective treatment for some female patients than for other people with a similar life threatening or serious condition, without their consent." they write, while mandating contraception for all women taking valproate "could be considered an infringement of patient autonomy and liberty."

They warn that the unknown number of women taking long term valproate who are not under specialist care are at particular risk, and publicity that generates fear and anxiety without guidance "may result in women stopping their treatment without support."

Further research into alternatives to valproate may help guide treatment in the future, they say. In the meantime, women need specialist information about the risks and benefits of valproate and its alternatives to help them make truly informed decisions, while regulatory guidance "should reflect the full range of risks and benefits of valproate and be based on both ethical and practical considerations for the individual, not just the population."

In a linked editorial, consultant perinatal psychiatrists Angelika Wieck and Sarah Jones explain that, if the European Commission accepts the recommendations, all women of childbearing age who are being prescribed valproate will require regular review and must follow a pregnancy prevention programme.

Valproate packaging will also carry a visual warning of the pregnancy risks and patients will receive a warning card with each prescription. Patients who are already pregnant and taking valproate should be reviewed urgently by a specialist.

"It has taken half a century since valproate was first introduced to understand the full extent of harm to unborn children," they write. "Current regulatory systems are clearly inadequate at identifying and assessing the reproductive risks of medicines."

Although challenging to achieve, "we urgently need a regulatory system for the

standardised and timely collection of pregnancy outcome data for new and existing drugs that may harm offspring," they add. "Mandatory pregnancy registers, targeted data mining of other resources, and regular evaluation of all available evidence would be key elements to achieve this aim."

A rear-ender in which the driver's head slams against the steering wheel or a helmet-to-helmet tussle with an opponent on the football field may increase one's risk for Parkinson's disease if concussion results, say researchers from UCSF and the San Francisco Veterans Affairs Medical Center.

In their study, which publishes April 18, 2018, in the online issue of Neurology®, the researchers looked at the prevalence of Parkinson's among close to one-third of a million veterans, comparing its incidence in those who had experienced a traumatic brain injury - such as concussion - with those who had not. They found that veterans who had had concussion faced a 56 percent increased risk for Parkinson's.

Concussion was defined as loss of consciousness for up to 30 minutes, altered consciousness or amnesia for up to 24 hours.

Results Relevant to More Than Vets

"While the participants had all served in the active military, many if not most of the traumatic brain injuries had been acquired during civilian life," said senior author and principal investigator Kristine Yaffe, MD, of the UCSF departments of neurology, psychiatry, medicine, and epidemiology and biostatistics. "As such, we believe it has important implications for the general population."

The mechanism in which concussion leads to Parkinson's is not fully understood, but recent studies have pointed to abnormal brain deposits of a protein called alpha-synuclein in traumatic brain injuries. This protein is a hallmark of Parkinson's.

Previous research has demonstrated a strong link between Parkinson's disease and moderate-to-severe traumatic brain injury, but this is the first large-scale, nationwide study to show its association with concussion, said first author Raquel Gardner, MD, of the UCSF Department of Neurology.

For the study, researchers identified 325,870 veterans from three U.S. Veterans Health Administration medical databases. Half of the participants had been diagnosed with concussion or the more serious moderate-to-severe traumatic brain injury and half had not. The participants, who ranged in age from 31 to 65, were followed for an average of 4.6 years.

A total of 1,462 of the participants were diagnosed with Parkinson's, with an average time to diagnosis of 4.6 years. Some 949 of the participants with traumatic brain injury, or 0.58 percent, developed Parkinson's, compared to 513 of the participants with no traumatic brain injury, or 0.31 percent.

In total, 360 out of 76,297 with concussion, or 0.47 percent, developed the disease and 543 out of 72,592 with the more serious moderate-to-severe traumatic brain injury, or 0.75 percent, developed the disease.

More Serious Brain Injuries Linked to Higher Parkinson's Risk

After researchers adjusted for age, sex, race, education and other health conditions such as diabetes and high blood pressure, they found that those with concussion had a 56 percent increased risk of Parkinson's. As expected, the risk was higher among veterans with the more serious moderate-to-severe traumatic brain injury (83 percent).

Researchers also found that those with any form of traumatic brain injury were diagnosed with Parkinson's an average of two years earlier than those without traumatic brain injury.

"This study highlights the importance of concussion prevention, long-term follow-up of those with concussion, and the need for future studies to investigate if there are other risk factors for Parkinson's disease that can be modified after someone has a concussion," said Gardner. "There is increasing recognition that concussion may have long-lasting neurobehavioral consequences, including heightened risk for several psychiatric and neurodegenerative diseases."

Military at Risk for Unique Cause of Concussion

Among servicemen and women, concussion may result from exposure to explosives in combat areas. In the general population, it most commonly occurs from falls in older people and motor vehicle accidents and contact sports in younger people.

Parkinson's affects more than 1 million people in North America, most typically after age 60, according to the National Institutes of Health. It is a progressive disorder of the nervous system that primarily impacts balance and movement.