Culture

It's long been known that people who suffer a major concussion can lose their sense of smell temporarily and also develop affective problems, such as anxiety and depression. Now scientists have found that's true even for people who get a minor concussion.

Falling off a bike with a helmet on, having a fender-bender in one's car, taking a tumble on the ski slopes, slipping on ice and hitting one's head - these kinds of minor accidents can provoke the same kinds of olfactory and anxiety problems, the researchers found.

In a study published in Brain Injury, an international team led by Université de Montréal neuropsychologists compared 20 hospital patients who had mild concussions to 22 who'd broken limbs but had no concussion. Within 24 hours of their accident, just over half of those with mild concussions had a reduced sense of smell, versus only 5 per of the patients with broken bones. A year later, although their sense of smell was back to normal, the first group of patients had significantly more anxiety than the control group.

"A lot of people will suffer a mild concussion at some point in their life, so realizing they have trouble smelling is the first step to telling their doctor about it," said lead author Fanny Lecuyer Giguère, who did the research as part of her doctoral thesis in neuropsychology supervised by UdeM associate professor of psychology Johannes Frasnelli. "It's important that patients report any loss of smell, because it's not something their general practitioner or emergency-room physician normally asks about."

Identifying the problem is a short step to getting personalized treatment, she added, with closer follow-up to see if the loss of smell and anxiety persist, indicating the severity of the injury. Physicians should also educate their patients so that they check whether symptoms crop up in the weeks following their accident, she said. "It's a question of raising awareness: the more people are told to watch for signs of olfactory loss and anxiety, the easier it will be for doctors to respond."

To test their capacity to identify smells, Lecuyer Giguère visited hospital patients in the alpine ski resort of Visp, Switzerland between December 2016 and February 2017. Almost all those with mild concussions had had a skiing accident. They were all seen within the first 24 hours following their accident, as were those with fractures but no concussion. With scented "Sniffin' Sticks' (felt-tip pens) to smell, they were asked to identify synthetic odours of roses, garlic, cloves and solvent, and more.

A year later, the patients were sent a follow-up questionnaire and a set of scratch-and-sniff booklets. By comparing the two groups of patients' results in the day following their injury and 12 months later, the researchers were able to determine that most who'd lost their sense of smell gained it back within six months of their accident.

What did not significantly diminish, however, were their symptoms of anxiety: thoughts that made them worry, difficulties to relax, and sudden feelings of panic. About 65 per cent of the concussed patients reported such symptoms.

Future studies should look at a larger sample of patients to better examine the association between anxiety and olfaction, the authors concluded.

A recent study of over 1,000 healthy women with no symptoms of urinary tract infections showed nearly 9 percent carried multi-drug resistant Escherichia coli strains in their guts.

This is of clinical concern because disease-causing E. coli bacteria can transfer from the digestive tract to the female urinary tract via the urethra, the urine duct, which is shorter and positioned differently in females than in males. The bacteria can then make their way into the bladder and other parts of the urinary tract.

More than a third of urine samples provided by those who had fluoroquinolone (Cipro) resistant gut E. coli tested positive for E. coli growth. Of those, nearly 77 percent were Cipro-resistant, and the clonal type of the bacteria matched the fecal sample.

Most of the pathogenic E. coli found belonged to the pandemic, multi-drug resistant ST131-H30R or ST1193 clonal groups that currently cause the majority of drug-resistant urinary tract and bloodstream infections. They were detected twice as frequently in the urine of people who had these specific strains in their gut, compared to other strains of E. coli in general.

In addition, the presence of ST ST131-H30R in the gut in this study was associated with older age.

The researchers also checked to see which participants might have had an antibiotic prescription during the study for any type of infection, including respiratory.

Three months after that earlier urine collection, urinary tract infections were diagnosed in nearly 7 percent of the 45 previously asymptomatic carries who consented to follow-up electronic medical record examination. The study participants were from the Puget Sound area.

"The two pandemic fluoroquinolone-resistant urinary tract pathogenic strains of E. coli found in the clinical specimens are superior gut colonizers and tend to persist there," noted the researchers. "They can also show up, at an unusually high rate, in the urine of healthy women who did not have a documented urinary tract infection diagnosis at the time of sample testing. Both phenomena appear to be interconnected."

The researchers pointed out that it has long been known that a patient's gut microbial flora often harbors urinary tract infection-causing strains. It was not certain whether pandemic, drug-resistant strains have distinct moorage patterns in the gut or lower urinary tract of healthy people.

The study was published in the Oxford University Press journal, Clinical Infectious Diseases.

The findings could have several clinical care and infection control implications, according to Evgeni V. Sokurenko, professor of microbiology at the University of Washington School of Medicine. He was the senior researcher on the study. Several other UW microbiology faculty and Kaiser Permanent Research Institute investigators in Seattle collaborated on the work. The lead researcher was Veronika L. Tchesnokova, of the UW medical school's Department of Microbiology.

The results suggest the specific multi-drug resistant E. coli strains detected in this study take up a much more prolonged residence in the gut than do some other resistant strains, and also can become present in the urine of healthy women without causing burning, urgency, blood in the urine or other warning signs of bacterial infection.

Sokurenko explained that knowing whether or not multiple drug resistant strains are present in a woman's gut could help predict the resistance profile of a subsequent clinical infection. Efforts to get rid of the pandemic E. coli strains in the carriers gut could reduce their rate of multiple drug resistant infections, and perhaps protect their household or other contacts as well.

Sokurenko also said medicine might need to revisit the clinical significance of finding bacteria in the urine, even without symptoms, during this pandemic of multiple antibiotic resistant strains of E. coli, because those strains could put the carriers at risk for a difficult-to-treat bacterial illness.

Fluoroquinolones are the most often prescribed drugs for urinary tract infections. Despite efforts to limit its use, strains resistant to this category of antibiotic are flourishing and spreading globally, according to the researchers.

The superior ability of the two pandemic strains, ST131-H30R and ST119, to take up long-term residence in people's guts may have contributed to their rapid global spread, the researcher surmised. They can be sustained and passed among healthy individuals even in the absence of antibiotic use, which can upset the microbial makeup of gut flora.

This study, the researchers concluded, highlights the likely physiological reasons behind the pandemic of these resistant E. coli strains. It also points out the value of determining female patients' carrier-status to predict future resistant infections, and the need to re-think the clinical significance of bacteria present in the urine without symptoms, especially as these pandemic strains can be superbugs: highly pathogenic to the urinary system and treatment resistant.

Sokurenko has patent applications for detecting E. coli strains and is a major shareholder in ID Genomics

RMIT University researchers have used data from mobile phone accelerometers - the tiny sensors tracking phone movement for step-counting and other apps - to predict people's personalities.

RMIT University computer scientist Associate Professor Flora Salim said previous studies had predicted personality types using phone call and messaging activity logs, but this study showed adding accelerometer data improved accuracy.

"Activity like how quickly or how far we walk, or when we pick up our phones up during the night, often follows patterns and these patterns say a lot about our personality type," said Salim, a leading expert in human mobility data.

Physical activity is proven to have a strong correlation with human personality. Therefore, researchers analysed physical activity features from different dimensions like dispersion, diversity, and regularity.

Key findings from the study:

People with consistent movements on weekday evenings were generally more introverted, while extroverts displayed more random patterns, perhaps meeting up with different people and taking up unplanned options.

Agreeable people had more random activity patterns and were busier on weekends and weekday evenings than others.

Friendly and compassionate females made more outgoing calls than anyone else.

Conscientious, organized people didn't tend to contact the same person often in a short space of time.

Sensitive or neurotic females often checked their phones or moved with their phones regularly well into the night, past midnight. Sensitive or neurotic males did the opposite.

More inventive and curious people tended to make and receive fewer phone calls compared to others.

Study lead author and RMIT University PhD student, Nan Gao, said the potential applications from this research were exciting.

"There are applications for this technology in social media with friend recommendations, online dating matches and targeted advertising, but I think the most exciting part is what we can learn about ourselves," said Gao.

"Many of our habits and behaviours are unconscious but, when analysed, they tell us a lot about who we really are so we can understand ourselves better, resist social pressure to conform and to empathize with others. Most importantly, being who we truly are can make our experience of life richer, more exciting and more meaningful."

"In Ancient Greece there is a saying about knowing yourself as the beginning of wisdom, applications like this can really help to reveal who we are to ourselves."

The results were analysed in accordance with the Big Five personality traits, which are:

Extraversion: how energetic, sociable and talkative you are.

Openness: how curious and inventive you are.

Agreeableness: how friendly and compassionate, rather than suspicious and hostile, you are to others.

Conscientiousness: how organized, efficient and careful you are.

Neuroticism: how nervous and sensitive, rather than confident and secure, you are.

Bottom Line: The U.S. Preventive Services Task Force (USPSTF) recommends screening for hepatitis B virus (HBV) infection in pregnant women at their first prenatal visit. The USPSTF routinely makes recommendations about the effectiveness of preventive care services and this statement is a reaffirmation of its 2009 recommendation. Screening for HBV infection during pregnancy identifies infants who are at risk of acquiring this infection from their mothers before or after birth. Children infected with HBV during infancy or childhood are more likely to develop chronic infection.

(doi:10.1001/jama.2019.9365)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Note: More information about the U.S. Preventive Services Task Force, its process, and its recommendations can be found on the newsroom page of its website.

PHILADELPHIA - Brain imaging of 40 U.S. government personnel who experienced a host of neurological symptoms after possible exposure of an unknown source while serving in Cuba revealed significant differences in brain tissue and connectivity when compared to healthy individuals, according to a new report from researchers at the University of Pennsylvania's Perelman School of Medicine. The findings are published today in JAMA.

"The areas implicated in the patients' brains, namely the cerebellum as well as the visuospatial and auditory networks, align with the neurological symptoms that were observed in the patients," said lead author Ragini Verma, PhD, a professor of Radiology and head of the DiCIPHR (Diffusion and Connectomics in Precision Healthcare Research) imaging lab at Penn. "These differences persisted even when people with some history of brain injury were excluded from the analysis."

In 2016, U.S. government personnel serving in Havana, Cuba, and their family members began to report a variety of neurological symptoms, including difficulty with concentration and memory, dizziness, visual issues, and balance problems. The symptoms were linked to sudden, intensely loud noises heard in their homes and hotel rooms, which State Department officials later referred to as a "sonic attack" or "directional phenomena," though the specifics of the alleged event remain unsolved. After initial examinations, the patients were sent to Penn's Center for Brain Injury and Repair for evaluation, treatment, and rehabilitation in the summer of 2017, under the direction of center director and study co-author Douglas H. Smith, MD, the Robert A. Groff Professor of Teaching and Research in Neurosurgery.

A 2018 JAMA report published by Penn researchers documented the neurological symptoms that 21 patients who had reported exposure to the mysterious phenomena in Cuba experienced. Summing up these findings, Smith said that the symptoms were, "similar to those found in persistent concussion syndrome, yet there was no evidence of blunt head trauma."

As part of the investigation into their signs and symptoms, the patients also underwent advanced neuroimaging with multimodal magnetic resonance imaging (MRI) at Penn, prior to receiving any comprehensive rehabilitation treatment. This retrospective analysis compared the brain images of 40 potentially-exposed personnel to 48 healthy individuals who were not exposed and did not demonstrate these signs and symptoms.

The group-based analysis, published in the new 2019 JAMA study, used various computational tools to examine structural, diffusion, and functional MRI images, finding statistically significant differences in brain volume, tissue properties, and connectivity between the patients and healthy control group. There was reduced white matter volume in the affected patients, along with a pattern of differences in measures of water diffusion in the tissue. The imaging also revealed lower functional connectivity in the visuospatial and auditory subnetworks. Notably, differences in tissue volume, water diffusion, and connectivity were found in the cerebellum, the part of the brain responsible for performing voluntary tasks, such as walking and writing.

"The cerebellar findings in this neuroimaging study are notable, given that a number of the patients evaluated exhibited abnormalities in balance and the coordinated movement of the eyes, both of which are associated with cerebellar dysfunction in the brain," said study co-author Randel Swanson, DO, PhD, an assistant professor of Physical Medicine and Rehabilitation at Penn.

According to Verma, the pattern of differences found in this study do not resemble imaging-based investigations of any other pathology, like concussion and traumatic brain injury.

"These findings may represent something not seen before," Smith said.

Verma likened the brain to a highway system, comprising roads (white matter) and traffic. Structural MRI provides information about the size of the roads, while diffusion imaging gives insight into the road conditions and how they are connected. An injury to the brain could contribute to a deterioration in the condition of the roads (reflected in white matter differences), leading to an alternate traffic pattern (altered functional connectivity). Therefore, Verma said, a multimodal investigation is essential to see a more complete picture of the injury. As the brain recovers, while the traffic pattern may go back to normal, the overuse of some roads may lead to wear and tear, or compensatory changes in the brain.

"It's hard to tell where the problem started; the brain differences observed could be an immediate effect of the brain injury, or it could a compensatory effect of the recovery process," Verma said. "It's very difficult to say, especially with a retrospective, heterogeneous study, where people were included at various times after potential exposure. The important thing is that we did see differences at the group level."

A Mediterranean-style diet in pregnancy does not reduce the risk of overall adverse maternal and offspring complications, but may reduce weight gain during pregnancy and the risk of gestational diabetes, according to a new study published this week in PLOS Medicine by Shakila Thangaratinam of Queen Mary University of London, UK, and colleagues.

A Mediterranean-style diet is defined by high intake of nuts, extra virgin olive oil, fruits, vegetables, non-refined grains and legumes; moderate intake of fish; low intake of red and processed meat; and avoidance of sugary drinks, fast food, and food rich in animal fat. In the new ESTEEM study, researchers randomized 1252 pregnant women with metabolic risk factors from five inner city UK hospitals. 627 were assigned to a Mediterranean-style diet, and were given mixed nuts and olive oil, and participated in three face-to-face sessions as well as follow up phone calls to reinforce dietary goals. 625 women were assigned to a control group and received dietary advice per UK national guidelines.

Women in the intervention group consumed significantly more nuts (adjusted OR 6.8, 95% CI 4.3-10.6), more extra virgin olive oil (aOR 32.2, 95% CI 16.0-64.6), increased their consumption of fish, white meat and pulses, and decreased their consumption of red meat, butter, margarine and cream. There was no significant reduction in the odds of overall maternal or offspring outcomes with the Mediterranean-style diet. However, there was a reduction in the odds of gestational diabetes by 35% (aOR 0.65, 95% CI 0.47-0.91), and this benefit was consistently observed when ESTEEM data were combined with those of similar trials (OR 0.67, 95% CI 0.53-0.84). Women in the ESTEEM intervention group gained, on average, 6.8 kilograms in weight compared to 8.3 kilograms gained in the control group.

"Future studies should assess the effect of in utero exposure to Mediterranean-style diet, particularly to nuts and olive oil, on childhood obesity, allergy and asthma, and on mother's future risk of type 2 diabetes," the authors say.

Current concentrations of fine particulate matter pollution, which mostly meet the national ambient air quality standard, are still associated with mortality and loss of life expectancy in the US, with larger impacts in poorer counties, according to a study published July 23 in the open-access journal PLOS Medicine by an international team of researchers from the Center for Air, Climate, and Energy Solutions led by Majid Ezzati of Imperial College London, UK.

Exposure to fine particulate matter pollution (PM2.5) is hazardous to health, and reducing PM2.5 is likely to lower mortality, especially from cardiorespiratory diseases. Yet there is not only resistance to more stringent control of PM2.5, but also attempts to roll back current standards. In the new study, Ezzati and colleagues set out to directly estimate the health and longevity impacts of current PM2.5 concentrations, and the benefits of reductions from 1999 to 2015, nationally and at county level, for the entire contemporary population of the contiguous United States. To do so, they used vital registration and population data with information on sex, age, cause of death and county of residence, as well as statistical models to directly estimate mortality and life expectancy loss.

Even though reductions in PM2.5 since 1999 have lowered mortality in the great majority of counties, PM2.5 pollution in excess of the lowest observed concentration (2.8 μg/m3) was responsible for an estimated 15,612 deaths (95% credible interval 13,248-17,945) in females and for 14,757 deaths (95% credible interval 12,617-16,919) in males. These deaths would lower national life expectancy by an estimated 0.15 years (95% credible interval 0.13-0.17) for women and 0.13 years (95% credible interval 0.11-0.15) for men. The life expectancy loss due to PM2.5 was largest around Los Angeles and in some southern states, such as Arkansas, Oklahoma and Alabama. At any PM2.5 concentration, life expectancy loss was, on average, larger in counties with lower income than in wealthier counties. According to the authors, further lowering PM2.5 pollution is likely to benefit the health of the entire US population, and lower health inequalities.

Identifying with someone is an exercise that makes us understand them deeply, empathize with them, and helps us overcome mistrust and prejudice. And this occurs even when that someone is a robot. These interpersonal dynamics were confirmed by an experimental study that was published days ago in Scientific Reports. The study is the result of scientific collaboration between Italian and French scientists.

One of its authors, Francesco Pavani, professor of Psychology at the Center for Mind/Brain Sciences (CIMeC) and at the Department of Psychology and Cognitive Science of the University of Trento, commented: "We have demonstrated that by 'beaming' a participant into a robot we can change his or her attitude towards the robot".

Pavani explained how this was achieved: "By 'beaming', we mean that we gave the participants the illusion that they were looking through the robot's eyes, moving its head as if it were their head, look in the mirror and see themselves as a robot".

This, as a result, made human participants identify with robots and feel them closer: "Unlike exercises in which the participants couldn't t move the robot's head or do that in a coordinated manner with other body movements, in our study the experience of walking in the shoes of a robot led the participants to adopt a friendlier attitude, to perceive them as socially closer".

The study contributes to improving the relationship with technology and helps people overcome their fear of robots. Pavani underlined: "These aspects are very important, because one of the problems of robotics today is how to make robots more acceptable to humans. I am thinking about automated assistive devices, in particular, which will be used more and more to help people in their daily life, for example in the case of individuals with reduced mobility. In our study we demonstrate that experiencing how it feels to be inside a robot makes it easier to accept them and communicate with them".

A new paper that challenges widely held ideas about autism has attracted comments from more than 30 scholars across the disciplines of psychology, anthropology, education, and neuroscience.

The authors maintain that many of the behaviors common to autism--including low eye contact, repetitive movements, and the verbatim repetition of words and phrases--are misinterpreted as a lack of interest in social engagement. On the contrary, they say, many people with autism express a deep longing for social connection.

Coauthors Nameera Akhtar, professor of psychology at the University of California, Santa Cruz, and Vikram Jaswal, associate professor of psychology at the University of Virginia, put forth the provocative ideas in their paper, "Being vs. Appearing Socially Uninterested: Challenging Assumptions about Social Motivation in Autism." The article appears in Behavioral and Brain Sciences, which publishes in an innovative format known as "open peer commentary." The journal specializes in "particularly significant and controversial pieces of work," which the editors publish with commentaries on each article from specialists within and across disciplines, as well as the authors' response to the input. Free online access to the paper is available here.

Akhtar and Jaswal welcomed the engagement from scholars, nearly all of whom endorsed their approach, which drew heavily on "testimonies" from people with autism.

"This work began with questions about the widespread assumptions people make about how much--or how little--autistic people want to interact with others," said Akhtar. "We explored those questions by turning to what people with autism say about themselves."

According to some autistic people, low eye contact can help them focus their attention, thereby actually enhancing social engagement, said Akhtar. Similarly, repeating phrases--even though the meaning may not be immediately obvious to others--may also be a behavior designed to connect with others. Repetitive movements may simply be comforting, she noted.

"When you ask autistic people about these behaviors, their answers shed new light on the range of desire autistics have for social connection, and they express frustration that their behavior is misinterpreted," said Akhtar. "The familiar stereotypes about social aversion do autistic people a great injustice."

The following excerpts are among the published "testimonies" from autistics that Akhtar and Jaswal cited in their paper:

* "You might have been told that people with autism do not want social or romantic relationships, but this is a myth. While it is true that many of us struggle to create or maintain them, this does not mean that we do not want them." --from An Adult with an Autism Diagnosis

* "I can't believe that anyone born as a human being really wants to be left all on their own... The truth is, we'd love to be with other people. But because things never, ever go right, we end up getting used to being alone ... Whenever I overhear someone remark how much I prefer being on my own, it makes me feel desperately lonely." --from The Reason I Jump

* "Once I meet people or when I know I will meet people who know me only through my writings, my anxiety level is so high, I can act in very strange ways. I can look very childish and silly and I am very self-conscious about this. I can also seem uninterested, but this is only a self-preservation mask. I find it hard to communicate even if I have a lot of things I want to say." --from Loud hands: Autistic People, Speaking

Other scholars were generally enthusiastic about Akhtar and Jaswal's approach, and there was widespread agreement that autistic testimony is an essential and surprisingly underused resource to understand social motivation in autism. There was some concern about minimizing important differences in autistic cognition and social motivation, which the authors clarified was not their intention. Many commenters called for a more systematic study of autistic perspectives regarding social engagement, which the authors endorsed.

Akhtar and Jaswal particularly appreciated input from a number of autistic scholars who commented on their work. Leaders of the disability rights movement say, "Nothing about us without us," which Jaswal said makes it particularly gratifying to hear from autistic people at this stage of the research.

"If we want to reduce the social isolation experienced by many autistics, the next step is for both autistic and non-autistic people to learn more about each other's social goals and social signals," said Jaswal. "That's the path to greater understanding and greater inclusion."

A study led by The University of Texas at Austin has found that the majority of faults underlying the Fort Worth Basin are as sensitive to changes in stress that could cause them to slip as those that have generated earthquakes in recent years.

Researchers with UT's Bureau of Economic Geology, Stanford University and Southern Methodist University have created a comprehensive map of more than 250 faults totaling more than 1,800 miles in combined length, some of which extend under highly populated areas in the Dallas-Fort Worth region. The study, published July 23 in the Bulletin of the Seismological Society of America, found that the faults are relatively stable if left undisturbed, but that wastewater injection, a practice common during oil and gas operations, significantly increases the potential of the faults to slip if not managed properly.

"That means the whole system of faults is sensitive," said lead author Peter Hennings, a bureau research scientist and the principal investigator at the Center for Integrated Seismicity Research (CISR).

The Fort Worth Basin saw a major increase in seismic activity from 2008 to 2015 as oil and gas operations increased, but a significant reduction in earthquakes the last four years as injection has slowed. Hennings said that people should be aware that the nature of the fault system means that many areas are susceptible to potentially hosting earthquakes, and that an upturn in oil and gas production that results in increased deep wastewater disposal could also bring an upturn in quakes if not properly managed.

SMU professor and study co-author Heather DeShon pointed out that the strongest earthquakes in the area have been magnitude 4, which is much less powerful than the major earthquakes that hit California earlier this month, but said that the region needs to prepare for the hazard.

"This study provides key information to allow the public, cities, state, the federal government and industry to understand potential hazards and to design effective public policies, regulations and mitigation strategies," she said.

SMU compiled the earthquake history of the region - a step that identified the need for an updated fault map in the first place. Stanford provided a map of the tectonic stress in the region and the analysis methods used to determine fault sensitivity. UT developed the new fault map and lead the overall effort. The research also benefited from data provided by petroleum industry partners.

The team also created maps that show the sensitivity of the faults. One shows that the faults in their natural geologic condition are relatively stable and not expected to slip if left undisturbed. Another map shows the impact of general pressure to the subsurface caused by wastewater disposal and reveals that it significantly increases the likelihood for faults to slip.

"Industrial activities can increase the probability of triggering earthquakes before they would happen naturally, but there are steps we can take to reduce that probability," said co-author Jens-Erik Lund Snee, a doctoral student at Stanford University.

Stanford professor and co-author Mark Zoback added that although this research focused on the Dallas-Fort Worth region, it creates a roadmap for those interested in investigating earthquake potential in other places.

"The methodology could be used in other areas where induced seismicity is of concern but development activities are just beginning, making it possible to identify potentially problematic faults before induced seismicity occurs," Zoback said. "So it creates a framework for making decisions in the future."

CISR and the TexNet Seismological Network, managed by the bureau at the UT Jackson School of Geosciences, played a key role in the research. TexNet is a collection of seismometers across Texas that was authorized and funded by the Texas Legislature and Gov. Greg Abbott. It has been tracking seismic activity across the state since January 2017.

The study found that the Fort Worth Basin is full of faults, many of which are small in size, yet susceptible to slipping. Most are less than 6 miles long - a fact that underscores the importance in studying the area in detail using high-resolution data.

"Most of the faults that have slipped are too small to have been previously recognized; they're very difficult to find," Hennings said. "We certainly haven't identified all of the faults in the region, but this new work is a big improvement compared to what was previously available."

The new maps are important tools in understanding the seismic hazard underling the Dallas-Fort Worth area, the most populated area in Texas. However, Hennings said that they provide just a general overview. He said that the team is working on a more in-depth analysis of individual faults that will give a more nuanced view of the unique factors influencing seismic hazard.

"In 2020, we will be publishing an updated version of the fault map as well as a comprehensive model that indicates the degree of pressurization that each of the earthquake faults has experienced from wastewater disposal," he said. "Combined with this current work, the future research will give industry and our regulators powerful tools to use in managing the hazard and reducing risk."

A new study led by researchers at the Johns Hopkins Bloomberg School of Public Health found that cigarette smoking boosts the risk of peripheral artery disease, and this elevated risk can persist up to 30 years after smoking cessation. The study also found that the link between smoking and peripheral artery disease was even stronger than that for coronary heart disease and stroke.

The study found that compared with never-smokers, those who smoked for more than 40 pack-years had roughly 4 times more risk for peripheral artery disease, versus 2.1 times and 1.8 times more risk for coronary heart disease and stroke, respectively. A pack-year is a parameter of smoking: 10 pack-years can mean 1 pack per day for 10 years or 2 packs per day for 5 years or some other combination.

Similarly, participants who reported currently smoking more than a pack per day had a relative increased risk--5.4 times more for peripheral artery disease versus 2.4 for coronary heart disease and 1.9 for stroke--compared to those who had never smoked.

The study, published July 22 in the Journal of the American College of Cardiology, is the first comprehensive comparison, in a large population moving through time, of the smoking-elevated risks of peripheral artery disease, coronary heart disease, and stroke. The analysis was based on a sample of 13,355 Atherosclerosis Risk in Communities (ARIC) cohort participants, including 3,323 current smokers and 4,185 former smokers, who were tracked for a median period of 26 years.

Peripheral artery disease features the atherosclerotic buildup of cholesterol-laden deposits in arteries serving the legs. The reduction of blood flow leads to limb pain, poor wound healing, and other signs and symptoms. The U.S. Centers for Disease Control and Prevention estimates that about 8.5 million people in the U.S. have peripheral artery disease, including more than 10 percent of people older than 69, though most cases go undiagnosed and there is relatively little public awareness of the disorder.

"Our results underscore the importance of both smoking prevention for nonsmokers and early smoking cessation for smokers. The study also suggests that campaigns about smoking's health risks should emphasize the elevated risk of peripheral artery disease, not just coronary heart disease and stroke," says senior author Kunihiro Matsushita, MD, PhD, associate professor in the Department of Epidemiology at the Bloomberg School.

The study was an offshoot of the ARIC study, which began in the late 1980s with funding from the National Heart, Lung, and Blood Institute. The ARIC study initially enrolled cohorts totaling 15,792 participants aged 45-64 years from four U.S. communities, and over three decades has included periodic follow-ups to record their health, as well as potential health risk factors such as smoking and diet. The main goal of the ARIC cohort study was to identify and quantify risk factors--such as smoking--for coronary heart disease, heart attacks, and stroke. But Matsushita and colleagues in the new study were able to use the large ARIC dataset to examine the links between smoking and peripheral artery disease.

The effect of smoking on peripheral artery disease risk was not just stronger; it was also longer-lasting. Only after 30 years of smoking cessation did the peripheral artery disease risk for former smokers return to the baseline level seen in never-smokers. By comparison, coronary heart disease risk took about 20 years to return to baseline after smoking cessation.

The good news from the analysis is that quitting smoking appeared to bring a meaningful drop in peripheral artery disease risk fairly quickly. "We observed a lower risk for peripheral artery disease, coronary heart disease, and stroke within five years of smoking cessation," says Ning Ding, MBBS, ScM, a data analyst at the Bloomberg School and first author of the study. Smoking cessation for 5 to 9 years was linked to a much greater drop in peripheral artery disease risk, 57 percent, compared to 30-40 percent for coronary heart disease and stroke.

Overall, the results suggest that public health campaigns against smoking should include reference to the elevated peripheral artery disease risk and should emphasize how long it takes to eliminate that risk.

"Smoking almost always starts in adolescence or early adulthood, and it's very important that young people understand how long the elevated health risk persists even after they've quit," Matsushita says.

The ARIC study is ongoing and may continue for another decade or two. To date, ARIC researchers have published more than 2,000 peer-reviewed papers on the project's findings.

A simple Mediterranean-style diet in pregnancy does not reduce the overall risk of adverse maternal and offspring complications, but has the potential to reduce weight gain in pregnancy and the risk of gestational diabetes, according to a clinical trial led by Queen Mary University of London and the University of Warwick.

The results, published in the journal PLOS Medicine and funded by Barts Charity, show that having a Mediterranean-style diet (including 30g of mixed nuts per day and extra virgin olive oil) led to a 35 per cent lower risk of developing diabetes in pregnancy, and on average 1.25 Kg less weight gain in pregnancy, compared to those who received routine antenatal care.

The study suggests a Mediterranean-style diet could be an effective intervention for women who enter pregnancy with pre-existing obesity, chronic hypertension or raised lipid levels.

Professor Shakila Thangaratinam from Queen Mary University of London said: "This is the first study to show that pregnant women at high risk of complications may benefit from a Mediterranean-style diet to reduce their weight gain and risk of gestational diabetes.

"Implementing this diet seems to be effective and acceptable to women. Current national dietary guidelines do not include the key components of the Mediterranean-style diet in their recommendations. Women who are at risk of gestational diabetes should be encouraged to take action early on in pregnancy, by consuming more nuts, olive oil, fruit and unrefined grains, while reducing their intake of animal fats and sugar."

Dr Bassel Wattar from the University of Warwick and Queen Mary University of London said: "Although a Mediterranean-style diet has been shown to reduce the risk of type 2 diabetes and cardiovascular complications in the general population, until now we did not know the effect of such a diet in high-risk pregnant women, and whether it could be culturally adapted for an ethnically diverse population.

"Now we know that pregnant women from an inner city, high-risk, multi-ethnic population are able to adapt their diet to a Mediterranean-style, and that this can bring them important benefits including a reduction in weight gain and a lower risk of developing gestational diabetes."

One in four mothers enter pregnancy with pre-existing obesity, chronic hypertension or raised lipid levels. These can lead to pregnancy complications, including gestational diabetes (when high blood sugar develops during pregnancy) and pre-eclampsia - the onset of high blood pressure in pregnancy which can sometimes develop into more serious conditions affecting multiple organs. These mothers and their babies are also at long-term risk of diabetes and cardiovascular complications.

A Mediterranean-style diet, rich in unsaturated fatty acids, reduces the incidence of cardiovascular diseases in the non-pregnant population. In pregnancy, such a diet has the potential to improve maternal and offspring outcomes, but has not been widely evaluated until now.

The ESTEEM study involved 1,252 women at five UK maternity units (four in London, including hospitals at Barts Health NHS Trust and St George's University Hospitals NHS Foundation Trust, and one in Birmingham).

Multi-ethnic inner-city pregnant women with metabolic risk factors, including obesity and chronic hypertension, were randomised to either receive routine antenatal care or a Mediterranean-style diet in addition to their antenatal care. The diet included a high intake of nuts, extra virgin olive oil, fruit, vegetables, non-refined grains and legumes; moderate to high consumption of fish, small-moderate intake of poultry and dairy products; and low intake of red meat and processed meat; and avoidance of sugary drinks, fast food, and food rich in animal fat.

Despite the improvements in gestational diabetes and pregnancy weight gain, there was no improvement in other important pregnancy complications such as high blood pressure, pre-eclampsia, stillbirth, small for gestational age foetus, or admission to a neonatal care unit.

The participants in the Mediterranean-style diet group reported better overall quality of life than those in the control group and reduced bloatedness in pregnancy, but there was no effect on other symptoms such as nausea, vomiting or indigestion.

When the data from the study was combined with published data from a Spanish study involving 874 pregnant women on a Mediterranean diet, the team observed a similarly large reduction in gestational diabetes (a 33 per cent reduction), but no effect on other outcomes.

Fiona Miller Smith, Chief Executive at Barts Charity said: "With the growing problems of diabetes and obesity in pregnant women, we're so proud to support this study which looks at preventing these risks. We're happy that our funding of the Barts Research Centre for Women's Health is being used to improve the health of East London mothers, and in turn helping future generations."

To promote their intake in pregnancy, participants on the Mediterranean-style diet were provided with complementary mixed nuts (30g/day of walnuts, hazelnuts, and almonds) and extra virgin olive oil (0?5 litre/week) as the main source of cooking fat. Participants also received individualised dietary advice at 18, 20 and 28 weeks' gestation.

The diet was made culturally sensitive by providing cooking advice through a bespoke recipe book (see Notes to Editors), which incorporated elements of the Mediterranean diet into the local cuisine, developed with local community teams.

The work was carried out at Barts Research Centre for Women's Health, based at Queen Mary University of London, funded by Barts Charity.

The study has limitations including its reliance on participant feedback for measuring adherence to the intervention, without use of objective biomarkers to measure nutritional intake. The team also only obtained information on dietary intake in about 40 per cent of participants in both groups, which limits the interpretation of dietary intake data.

For the average person, getting a cut or scrape on the foot may not be cause for immediate concern. However, for people with type 2 diabetes, these wounds can be life-threatening. According to a 2016 study, one-third of the cost of type 2 diabetes treatment is related to non-healing foot wounds and ulcers, which are the leading cause of amputation in the United States.

"This is a major clinical problem," says Katherine Gallagher, M.D., vascular surgeon and an Associate Professor in Michigan Medicine's Departments of Surgery and Microbiology/Immunology. "Most people don't realize that if someone has a major amputation due to a non-healing wound, they have only a 50 percent survival rate at three years, which is actually worse than most cancers."

In a new paper in the journal Immunity, Gallagher, first authors Andrew Kimball, M.D. and Frank Davis, M.D., and their colleagues describe for the first time an enzyme that seems to be critical for normal healing--and, in diabetes, appears to be missing. The discovery also hints at a possible treatment.

Steps to healing

It all starts with the immune system and cells called macrophages. During normal healing, an injury triggers the immune system to release monocytes in the blood which travel to the site of damaged tissue and become macrophages. At first, these macrophages create an inflammatory response to engulf and eliminate any bacteria or other pathogens. These same macrophages then change into a non-inflammatory repair mode to generate new tissue and promote healing. With diabetes, this conversion never takes place and inflammation persists.

Gallagher's team suspected that something environmental triggers epigenetic changes that prevents the macrophages from completing their job. "Type 2 diabetes typically develops over 20 to 30 years, and while genetics certainly play a role, we speculated that behaviors such as smoking or a long-term unhealthy diet were causing permanent epigenetic changes in the cells," she says. Epigenetics refers to changes in gene expression that do not come from changes from the underlying DNA sequence.

Using mice and human tissues, they discovered for the first time that an epigenetic enzyme called Setdb2 regulates the conversion of macrophages from an inflammatory type to a repair type. In diabetic mice, Setdb2 did not increase at the critical time and their wounds remained inflamed.

Potential treatment

Gallagher's team also found that Setdb2 appears to be a player in the metabolism of uric acid, known to be elevated in people with diabetes. People with high blood concentrations of uric acid can develop gout, which can cause painful inflamed joints. Gallagher and her team found that in normal healing, Setdb2 turns off xanthine oxidase, the enzyme that produces uric acid. In doing so, Setdb2 turns off inflammation.

To see whether blocking uric acid could help wound healing, the team administered allopurinol, a common drug used to treat gout and kidney stones, locally to wound sites in their diabetic mouse models.

"The drug seemed to improve healing," says Gallagher. "Our data looks very promising for using this as a local therapy."
Applying allopurinol directly to the wounds, she adds, could help avoid some of the toxic systemic side effects associated with the drug. The team hopes to eventually bring their findings to clinical trials, look for other inflammatory genes that may be targets, and explore ways of increasing Setdb2 for cell-based therapy.

The lab of Yongchao Ma, PhD, from Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago, discovered how the genetic defect in fragile X syndrome - a type of autism - delays production of neurons (nerve cells) at a critical time in the embryo's brain development. In a study published in Cell Reports, Dr. Ma and colleagues describe a previously unknown regulatory mechanism controlling how stem cells differentiate into neurons. They identified early disruptions in this process in fragile X syndrome, the most common inherited intellectual disability in children.

"During embryonic brain development, the right neurons have to be produced at the right time and in the right numbers," says Dr. Ma, senior author and researcher at Lurie Children's, as well as Associate Professor of Pediatrics, Neurology and Physiology at Northwestern University Feinberg School of Medicine. "We focused on what happens in the stem cells that leads to slower production of neurons that are responsible for brain functions including learning and memory. Our discoveries shed light on the earliest stages of disease development and offer novel targets for potential treatments."

Other studies in fragile X development have focused on the interactions between mature neurons. Dr. Ma's study is the first to offer a new understanding of the disease at a stem cell level.

Fragile X syndrome occurs in approximately 1 in 4,000 males and 1 in 8,000 females. It is caused by mutation in the gene called FMR1 that encodes a protein called FMRP. The genetic defect leads to reduced FMRP protein. Previously the function of FMRP protein during early brain development was not known.

Dr. Ma and colleagues discovered that within a stem cell, the FMRP protein plays a key role as a "reader" of a chemical tag (called m6A) on the RNA. This tag carries instructions on how to process the RNA. By reading these instructions, FMRP protein exports the RNAs from the nucleus to the cytoplasm of cells where the m6A-tagged RNAs will become proteins that control stem cell differentiation into neurons.

"We show how the reduced amount of FMRP protein in neural stem cell results in decreased nuclear export of m6A-tagged RNAs and ultimately, slower production of the neurons that are essential for healthy brain development," says first author Brittany Edens, graduate student in the Northwestern University Interdepartmental Neuroscience Program who works in Dr. Ma's lab. "Our findings also expand understanding of how the flow of genetic information form DNA to RNA to protein is regulated, which is a central question in biology."

"Currently we are exploring how to stimulate FMRP protein activity in the stem cell, in order to correct the timing of neuron production and ensure that the correct amount and types of neurons are available to the developing brain," says Dr. Ma. "There may be potential for gene therapy for fragile X syndrome."

Mammal brains -- including those of humans -- store and recall impressive amounts of information based on our good and bad decisions and interactions in an ever-changing world. Now, in a series of new experiments with mice, scientists at Johns Hopkins Medicine report they have added to evidence that such "decision-based" memories are stored in very particular parts of the brain.

"Figuring out where and how long animal brains store information about past choices can help us more broadly understand models of decision-making," says Jeremiah Cohen, Ph.D., assistant professor of neuroscience at the Johns Hopkins University School of Medicine. Eventually, he says, such models could lead to better treatments for addiction and other disorders marked by flawed or disordered decision-making.

A description of the studies was published July 4 in the journal Neuron.

For the experiments, Cohen and his colleagues at Johns Hopkins used various odors to train 36 mice to choose between two tubes that deliver water when licked and which were randomly controlled by a computer to turn the "faucets" on or off. When one tube was turned on, the other was turned off, and then, they'd switch. The experiment was designed to mimic how mice forage for water in the wild and learn where to return for the liquid.

The mice didn't know, with certainty, whether they would receive water when they made a particular choice, says Cohen. To find the water reward, they had to remember their recent choices and outcomes, he explains.

As expected, Cohen says, the mice more often explored and licked from water tubes that were turned on more frequently, maximizing the amount of water they received. Occasionally, they also explored water tubes that were turned off, licking them once in a while. When a tube with plentiful water was turned off, the mice switched to the other tube that was newly turned on, says Cohen. The scientists also found that the mice waited to make their water tube choices for up to half a minute.

Cohen says previous studies over the past decade have suggested that decision-based memories are stored in the prefrontal cortex -- the seat of complex behavior, personality and learning.

To figure out where in their brains the mice stored the water memories, a member of Cohen's team, Bilal Bari, attached microelectrodes to the brains to measure the firing rate of so-called "action potentials" crossing the membranes of more than 3,000 neurons in the prefrontal cortex.

According to Cohen, the firing rate of the neurons' action potentials in a mouse represents the internal cognitive estimate of the choice between the two water tube options -- basically, the mouse thinking about which tube to lick.

A baseline action potential rate in prefrontal cortex neurons is about two to 10 spikes per second. But when the mice were believed to be thinking about one tube choice versus the other, the scientists found action potential rates of an average of about 20 spikes per second in nearly 80% (2,401 of 3,073) of prefrontal cortex neurons.

They also found that the longer the mice took to decide between the two tubes, the action potential rate in prefrontal cortex neurons started to slow down. After 15 seconds without licking a tube, action potential rates were down to half their peak rate. "It's possible that the mouse is forgetting how valuable the particular environment is," says Cohen.

"These data give us a window into how neurons are storing these decision-based memories," says Cohen. "Not only can we see the changes in action potential firing rates, but we can quantify them too."

The researchers also measured where in the mouse brains the prefrontal cortex neurons extended to other parts of the brain, signaling structures elsewhere. They found increased electrical signaling to the dorsomedial striatum, a structure inside the basal ganglia, a region in the middle of the brain linked to movement.

Cohen says his team plans further study on where and how neurons connect from the prefrontal cortex to other parts of the brain that control movement. This information would likely shed light on how fast animals including humans learn from their experiences in the world. "We need to learn quickly in a volatile world, and figuring out more of how brains do that will offer insight into how such learning can be adjusted," Cohen says.