Culture

Women who experience domestic violence and abuse (DVA) are more than twice as likely to seek emergency contraception as other women, according to a study by National Institute for Health Research (NIHR)-funded researchers at the University of Bristol and Queen Mary University of London, suggesting that requests for emergency contraception could be an important sign of abuse.

In the study, published in the British Journal of General Practice today [Tuesday 4 December], the researchers analysed medical records of over 200,000 women of reproductive age registered with a GP and found that those who had a record of DVA were 2.06 times more likely to have a consultation for emergency contraception compared to other women, rising to 2.8 times for women aged 25-39.

The researchers also found some evidence that abused women are more likely to seek emergency contraception repeatedly.

DVA is a major public health problem, with devastating consequences for the women who experience it and great financial cost to the NHS. It is known to have a significant impact on women's reproductive health, including an increased risk of unintended pregnancy and abortion, as abusive and controlling partners coerce women to have unprotected sex or rape them.

Although emergency hormonal contraceptive, also known as the morning-after pill, is available from pharmacies, women can also get it from their GP. Up to a third of all emergency contraceptives are prescribed by GPs.

The researchers are calling for this new evidence to be included in existing DVA training programmes for GPs and sexual health practitioners, and for the training to be extended to community pharmacists, to help them identify and refer women who have experienced DVA on to specialist support services. Such programmes are recommended by the National Institute for Health and Care Excellence (NICE) and the World Health Organization (WHO) as part of a multi-sector response to DVA.

Joni Jackson, Research Associate from the NIHR Collaboration for Leadership in Applied Health Research West (NIHR CLAHRC West) and co-lead author of the study, said: "We found a strong positive association between exposure to domestic violence and abuse and requests for emergency contraception. Our findings are in line with evidence from studies in other countries suggesting that women experiencing DVA use more emergency contraception than other women. GPs, pharmacists and sexual health practitioners are at the frontline responding to these requests, with community pharmacists dispensing 50 per cent of all emergency contraceptive pills. This presents an important opportunity to identify women experiencing DVA, signpost them to appropriate support services, and potentially save lives."

Dr Natalia Lewis, from the Centre for Academic Primary Care at the University of Bristol and co-lead author, added: "The negative impact of domestic violence and abuse on health results in higher use of healthcare services by abused women compared to the general population. This means that healthcare services are an important point of contact for DVA victims and survivors. We have already seen improvements in GPs' ability to identify and refer women experiencing DVA through the success of the IRIS (Identification and Referral to Improve Safety) programme. IRIS has recently been adapted for sexual and reproductive health services. Our findings support the case for adapting the IRIS intervention to the community pharmacy setting, although more research is needed to explore if and how this could be done."

DALLAS, December 3, 2018 --Full marathons may significantly raise concentrations of several biomarkers of strain on the heart, according to new research in Circulation, Journal of the American Heart Association.

Investigators in Spain compared levels of cardiac biomarkers, including - troponin I and troponin T- in 21 groups of 3 runners each after each individually ran an endurance race of three different lengths - a full marathon, a half marathon and a 10K race. All of the 63 subjects were amateur runners. They also measured levels of biomarkers for cardiac tissue stress.

Although there was little difference in 10-year risk for cardiovascular events between the runners (average about 3 percent), the strain on the heart muscle, as measured by the biomarker levels, was much greater after a full marathon.

The incidence of cardiac arrests in marathoners is only about 1 in 50,000 runners who compete in races, but a high proportion of all exercise-induced cardiac events occur during marathons, especially in men 35 years of age and older.

The number of subjects in the study was not large enough to accurately assess differences in 10-year cardiovascular risk, but the researchers are planning to examine this in a larger group of runners, said lead investigator Juan Del Coso, Ph.D., director of the exercise physiology laboratory at Camilo José Cela University, in Madrid, Spain.

"We typically assume that marathon runners are healthy individuals, without risk factors that might predispose them to a cardiac event during or after a race. But with the growing popularity of long-endurance races, the exponential increase in the number of participants, and the lack of appropriate training in some cohorts of amateur runners, our findings suggest that running shorter endurance races might reduce the strain imposed on the myocardium during running competition," Del Coso said.

Leading scientists call for action to increase global soil carbon, in advance of the annual climate summit of the United Nations Framework Convention on Climate Change (UNFCCC) in Katowice, Poland (COP24) and World Soil Day (5 Dec).

The amount of carbon in soil is over twice the amount of carbon found in trees and other biomass.

But one-third of the world's soils are already degraded, limiting agricultural production and adding almost 500 gigatons of carbon dioxide to the atmosphere, an amount equivalent to the carbon sequestered by 216 billion hectares of U.S. forest.

Modalities for climate action in agriculture will be addressed 3 December at the first workshop of the Koronivia Joint Work on Agriculture, a breakthrough initiative of the 2017 UNFCCC climate negotiations.

In a commentary piece, Put More Carbon in Soils to Meet Paris Climate Pledges, published today by the journal Nature, climate change and agricultural scientists who serve on the science and technical committee of the organization 4 per 1000 describe a path for recuperating soil carbon stocks to mitigate climate change and boost soil fertility. The scientists suggest that the KJWA formally commit to increasing global soil organic carbon stocks through coordination and activities related to eight steps.

The eight steps are:

1. Stop carbon loss - Protect peatlands through enforcement of regulations against burning and drainage.
2. Promote carbon uptake - Identify and promote best practices for storing carbon in ways suitable to local conditions, including through incorporating crop residues, cover crops, agroforestry, contour farming, terracing, nitrogen-fixing plants, and irrigation.
3. Monitor, report and verify impacts - Track and evaluate interventions with science-based harmonized protocols and standards.
4. Deploy technology - Use high-tech opportunities for faster, cheaper and more accurate monitoring of soil carbon changes.
5. Test strategies - Determine what works in local conditions by using models and a network of field sites.
6. Involve communities - Employ citizen science to collect data and create an open online platform for sharing.
7. Coordinate policies - Integrate soil carbon with national climate commitments to the Paris Agreement and other policies on soil and climate.
8. Provide support - Ensure technical assistance, incentives to farmers, monitoring systems, and carbon taxes to promote widespread implementation.

A joint forum for coordinated action and funding to close research gaps is needed, the scientists argue. The eight steps also inform the KJWA's next workshop (June 2019), which will address soil carbon.

"Taking steps to increase global soil carbon requires multi-stakeholder collaboration at the science-policy interface. 4p1000 initiative, which has 281 partners from 39 countries, is showing how such collaboration can be used to address sustainable development goals in an integrated way," said Cornelia Rumpel, lead author of the commentary and Research Director of the National Research Center at France's Institute of Ecology and Environmental Sciences.

Co-author Farshad Amiraslani, Remote Sensing Specialist and Deputy Dean of Academic Affairs, Faculty of Geography, University of Tehran, is concerned with how lack of coordination among stakeholders and no comprehensive database is hindering the impact of land restoration efforts. We need to apply satellite imagery to capture changes occurring at large scales more frequently and cost-effectively, he said.

"We are amassing a rich body of knowledge on how to increase soil carbon stocks," said Claire Chenu, a Professor of Soil Sciences at AgroParisTech. "But further research is needed. For example, we know root systems make an important contribution to soil carbon stocks, but we are still researching how specific crops with deep roots, vs. cover crops, vs. agroforestry systems differentially contribute to increasing soil carbon. We need more data on the effects of agricultural practices in different ecosystems."

"Challenges to achieving large-scale carbon sequestration include nutrient limits, inadequate farmer incentives and lack of organic matter in some places, but even impacts at lesser scales will benefit the climate and food security," said co-author Lini Wollenberg, Low Emissions Development Leader for the CGIAR Research Program on Climate Change, Agriculture and Food Security (CCAFS) and Research Professor at the University of Vermont's Gund Institute for Environment.

"The potential benefits are too large to ignore," Wollenberg said.

BLOOMINGTON, Ind. - In a new study, Indiana University scientists found toxic flame retardants in newly manufactured children's car seats, sparking concerns about children's health. Of the 18 children's car seats tested, 15 contained new or traditional hazardous flame retardant chemicals.

"New replacement flame retardants, often marketed as safer alternatives, are lurking in children's products without rigorous safety testing and may pose risks for children's health," said Marta Venier, associate scientist at IU's School of Public and Environmental Affairs and principal investigator on the study. "The abundance of emerging flame retardant chemicals in children's car seats and the key role these products play as potential sources of chemical exposure is a cause for concern."

The research was conducted in conjunction with the Ecology Center, an independent nonprofit organization in Ann Arbor, Michigan. The car seats tested in this study were purchased by the Ecology Center and shipped to Indiana University for analyses. All of the car seats were newly manufactured between January 2017 and February 2018 and were made in China, Canada, or the United States. In total, the researchers tested 36 different fabric and foam samples from 18 car seats.

For the first time, two cyclic phosphonate esters (PMMMPs) were measured at high levels in North America, suggesting their use as a replacement flame retardant for compounds that are known to be harmful. PMMMPs were found in 34 of the 36 car seat sampled at levels much higher than those of traditional flame retardants. Little is known about their health effects. Two other emerging flame retardants (tris(2,4-di-t-butylphenyl) phosphate (TDTBPP) and resorcinol bis(diphenyl phosphate) (RDP)) were also measured in baby products for the first time.

Polybrominated diphenyl ethers (PBDEs) were observed in 75 percent of the samples tested, despite being phased out of use in the United States in 2013 over health concerns. However, PBDEs were detected at such low levels that it is unlikely they were added intentionally. They may have been impurities or found in parts containing recycled materials. Conversely, decabromodiphenyl ethane (DBDPE) was detected in four samples at high levels, suggesting that it was intentionally used. DBDPE is a brominated flame retardant known to cause oxidative stress, hormone disruption and thyroid problems.

Unlike other baby products, children's car seats are required to meet the flammability standards for car interiors outlined in the Federal Motor Vehicle Safety Standard 302, which was created in 1971 by the National Highway Traffic Safety Administration. Flame retardants are routinely used as a cost-effective way to meet this standard. However, flame retardants have been linked to a variety of negative health effects, including hormone disruption, impaired brain development, liver damage and cancer. Children are more susceptible to these effects than adults because of their smaller size and their tendency to put their hands and objects in their mouths.

Children can be exposed to flame retardants in car seats by breathing in chemicals that leach into the air out of fabrics and foam. This is especially problematic for children during the summer months, when heat increases the rate at which flame retardants enter the poorly ventilated, semi-closed car environment. Children can also be exposed to flame retardants by ingesting the dust which accumulates inside the vehicle, through skin contact or by chewing on their car seats.

"We found that car seat manufacturers are intentionally moving away from certain toxic chemicals compounds that they know to be harmful, which is good news," said Yan Wu, a postdoctoral researcher at Indiana University and the lead author of the study. "However, we know very little about the replacement chemicals they're using. Car seats are vital for protecting children during a vehicle crash, but more research is needed to ensure that those seats are chemically safe as well."

A follow-up analysis of patients enrolled in a Phase I/II multi-center trial for diffuse large B-cell lymphoma (DLBCL) reported 51 percent of patients receiving an anti-CD19 chimeric antigen receptor (CAR T) called axi-cel were still alive two years post-treatment. Axi-cel was approved by the U.S. Food and Drug Administration for treatment of DLBCL in October 2017 and by the European Commission in August 2018.

The study, co-led by Sattva Neelapu, M.D., professor of Lymphoma & Myeloma at The University of Texas MD Anderson Cancer Center, reported its findings in the Dec. 2 online issue of The Lancet Oncology and during a presentation at the 60th American Society of Hematology Annual Meeting & Exposition in San Diego.

"This two-year assessment demonstrates that axi-cel can induce durable remissions in a substantial proportion of patients with an acceptable long-term safety profile," said Neelapu. "There also is evidence of gradual B-cell recovery in most patients with refractory large B-cell lymphoma who otherwise have limited treatment options."

With a median follow-up of 27.1 months for 101 patients enrolled in Phase II, the study found that 83 percent of patients achieved a reduction in cancer activity tied to treatment, known as an objective response; 58 percent had no detectable cancer or a complete response, and 39 percent reported ongoing responses. Median overall survival was not reached, and no axi-cel related adverse effects were reported after the 12-month period.

The results mirrored findings of a previously reported median follow up of 15.4 months at which time objective response rate was 82 percent, complete response rate was 58 percent, with 42 percent of patients reporting ongoing responses.

In addition, exploratory analyses were performed to assess CAR T-cell persistence and B-cell recovery in patients with ongoing remission, and at 24 months, persisting CAR gene-marked cells were observed in 66 percent of patients with evaluable biomarker samples. Peripheral blood B-cells were measurable in 75 percent of patients.

'Real-world' outcomes support ZUMA-1 findings

A subsequent "real-world" assessment of 274 patients who received axi-cel, post FDA-approval of the therapy revealed similar results to the overall ZUMA-1 study. The real-world retrospective study included 17 centers that contributed data independent from the manufacturer-funded trial.

Findings from the study, led by Loretta Nastoupil, M.D., assistant professor of Lymphoma & Myeloma, were presented Dec. 1 at the ASH Annual Meeting & Exposition. By day 90, the real-world assessment reported 81 percent of patients had an objective response and 57 percent had a complete response.

"Although limited by a relatively short follow up, 90-day responses in the real-world setting are comparable to the best responses observed in the pivotal ZUMA-1 clinical trial," said Nastoupil. "Importantly, safety appears comparable to the ZUMA-1 trial despite nearly half of patients failing to meet ZUMA-1 eligibility criteria."

People with epilepsy living in high crime neighborhoods in Chicago had three times as many seizures as those living in neighborhoods with lower crime rates according to new research from the University of Illinois at Chicago presented at the American Epilepsy Society 2018 conference in New Orleans.

Epilepsy is a chronic neurological disorder characterized by abnormal brain activity and seizures that affects more than 65 million people worldwide. About one-third have difficulty controlling their seizures even with medication. Seizures can interfere with work, relationships, and the ability to live independently. Previous research has shown that living in neighborhoods with high rates of crime have significantly higher levels of the stress hormone, cortisol. Stress is also a factor that is commonly reported to trigger seizures in people with epilepsy.

The UIC study included 63 adults with epilepsy living within the city limits of Chicago who were participating in a larger study testing the efficacy of a tablet-based educational tool that provides tailored information about epilepsy. That study, called PAUSE, involves patients at the University of Illinois Hospital's epilepsy clinic and in the Chicagoland community and is facilitated by the Epilepsy Foundation of Greater Chicago.

The researchers determined the levels of crime in neighborhoods of the 63 participants by mapping their zip codes to specific neighborhoods and then cross-referencing those neighborhoods with local crime rates available through the City of Chicago Police data portal. Participants self-reported the number of seizures they had in the past month and in the past three months.

"We found that people living with epilepsy who live in high-crime neighborhoods experienced significantly more seizures," said Jessica Levy, a research coordinator in the UIC department of neurology and rehabilitation who presented the findings. "On average, people in high-crime neighborhoods had three seizures versus one for people living in low-crime neighborhoods when we looked back over the last 30 days. Over the course of 90 days, people in high-crime neighborhoods had seven seizures on average compared to three for those living in low-crime neighborhoods, so the link between crime and seizure activity is significant."

The researchers found no overall association between neighborhood crime status and the duration of epilepsy or between crime status and poverty.

Having more seizures can significantly lower quality of life. Seizures that result in falls can cause bruising or even broken bones. There can also be a stigma associated with having a seizure in public.

"Understanding the impact of violence and crime as potential triggers for seizures underscores the need for further research that might allow clinicians to make better-informed recommendations for self-management education and stress management skills," said Dr. Dilip Pandey, associate professor of neurology and rehabilitation at UIC and an investigator on the study.

Sunday, Dec. 2, 2018, SAN DIEGO: At the American Society of Hematology (ASH) Annual Meeting, Cleveland Clinic medical hematologist and oncologist Aziz Nazha, M.D., will present results of a personalized prediction model that surpassed current prediction models for Myelodysplastic Syndromes (MDS).

Dr. Nazha and colleagues report the model outperformed current prognostic scoring systems, such as the Revised International Prognostic Scoring System (IPSS-R), in predicting an MDS patient's risk of mortality and transformation to acute myeloid leukemia (AML), a more aggressive type of bone marrow cancer. "A Personalized Prediction Model to Risk Stratify Patients with MDS" will be presented Monday, Dec.3, at 2:45 p.m. in Grand Hall A at ASH.

Patients with MDS have survival outcomes that can range from months to decades. Although several prognostic scoring systems have been developed to risk stratify MDS patients, survival varies even within distinct categories, which may lead to over- or under-treatment. Researchers hypothesized that discrepancies may be due to analytic approaches or lack of incorporation of molecular data.

"Determining prognosis in oncology is one of the most important parts of our job. All oncology patients want to know how long they are going to live," said Dr. Nazha. "Too often we find a significant gap between what we predicted, based on existing prediction models, and what actually happened to our patients."

The new model designed by Dr. Nazha and team incorporates individual patient genomic and clinical data using a machine-learning algorithm to better predict survival probabilities and outcomes. Patients' clinical and mutational variables are entered into a web application that runs the personalized prediction model and provides overall survival and AML transformation probabilities at different time points that are specific for a patient. Patient data used to test the model came from Cleveland Clinic and Munich Leukemia Laboratory and was validated in a separate collection of patient data from Moffitt Cancer Center.

In a comparison using medical records, the new model predicted a patient's likelihood of surviving for a given period of time 74 percent of the time, compared to IPSS-R accuracy of 67 percent. The model accurately predicted a patient's risk of AML 80 percent of the time, compared to IPSS-R accuracy of 73 percent.

Dr. Nazha's next step is to build a website where clinicians can input a patient's clinical and genetic characteristics and get back the patient's probability of surviving at different time points such as six months, 12 months, and 18 months.

"Understanding a patient's prognosis allows us to more appropriately develop a treatment plan and counsel patients," Dr. Nazha said. "We are optimistic an improved prediction will lead to more personalized care."

Dr. Nazha also presented "A Personalized Prediction Model for Outcomes after Allogeneic Hematopoietic Stem Cell Transplant in Patients with MDS: On Behalf of the CIBMTR Chronic Leukemia Committee" at ASH on Saturday, Dec. 1.

In this study, Dr. Nazha and colleagues developed a personalized prediction model for outcomes after allogeneic hematopoietic cell transplant (HCT) in patients with MDS. In allogeneic HCT a person receives blood-forming stem cells from a genetically similar donor. HCT remains the only potentially curative option for MDS, and previous research has shown genetic alterations have an impact on outcomes after HCT in MDS.

Investigators used data from MDS patients enrolled in the Center for International Blood and Marrow Transplant Research Registry and built a web application where patients' genomic and clinical data are computed to predict survival probability after HCT at 6,12 and 24 months. The application identified several clinical and molecular variables that impacted overall survival and the hazard of relapse. This information may aid physicians and patients in their decision prior to HCT.

"Because of the risks of transplant-related mortality and relapse, identifying patients who may or may not benefit from HCT is clinically important," said Dr. Nazha. "Understanding survival probability at different points in time may aid physicians and patients in their approach, prior to HCT."

CINCINNATI - A daily hydroxyurea pill may finally bring some relief for young children living with the painful and deadly blood disease sickle cell anemia (SCA) in resource-challenged sub-Saharan Africa, where the disease is prevalent and health care availability is suboptimal.

This is what a large multinational clinical trial called REACH discovered when it tested daily hydroxyurea treatment in 606 children between the ages of 1 and 10 years old. The children took a pill each day for six months, followed by increases in the daily dosages based on their health status and weight. Initial doses varied between 15-20 mg/kg a day.

The treatment improved their health by controlling SCA symptoms and, in an expected finding, giving them some protection from malaria that is also prevalent in the region, according to the study's lead physicians at Cincinnati Children's Hospital Medical Center and Centre Hospitalier Monkole in Kinshasa, in the Democratic Republic of the Congo.

Study results are published today online by The New England Journal of Medicine in conjunction with being presented at the American Society of Hematology's annual meeting in San Diego.

The clinical trial determined that hydroxyurea therapy is feasible to use and safe for children in sub-Saharan Africa. Compared to pre-treatment levels, hydroxyurea use was linked to reduced rates of sickle cell pain by an average of 55 percent, infections by 38 percent, malaria by 51 percent, transfusions by 67 percent, and death by 70 percent.

"Hydroxyurea was safe and offered many benefits to these young patients, including improved anemia, fewer sickle cell pain events, less malaria, and better survival," said Russell Ware, MD, PhD, the study's senior investigator and a physician-scientist at the Cincinnati Children's Cancer and Blood Diseases Institute.

Also leading the clinical trial was Leon Tshilolo, MD, PhD, at the Centre Hospitalier Monkole. Investigators named the study REACH, an acronym for Realizing Effectiveness Across Continents with Hydroxyurea. According to Tshilolo, the clinical trial lived up to its name.

"The study shows the importance of research partnerships between the US and Africa to improve clinical care," he said. "Even in an African setting hydroxyurea is feasible to use, accepted by patients and families, well-tolerated, and safe for children with sickle cell anemia. Almost all of the children had clinical improvements, and the older patients were well enough to attend school."

SCA's Heavy Burden

Caused by a genetic mutation and most prevalent in people of African ancestry, SCA is a painful disease where blood cells turn sickle-shaped and become stuck in the vascular system where they block blood flow. This can damage vital organs and cause death. Hydroxyurea works by significantly increasing both hemoglobin and fetal hemoglobin in the blood, which helps reduce sickling, anemia and other impacts on patients.

Available therapies to treat SCA effectively are limited, although numerous studies in recent years--almost all in developed countries--show that hydroxyurea is a safe and effective drug for managing the disease and improving quality of life.

SCA affects more than 90,000 people in the United States and millions of people worldwide, with 75 percent of the disease's burden in sub-Saharan Africa. Other nations with high incidence rates are India, nations in the Caribbean, Central America, and South America.

Because of the lack of detailed medical records, the best available estimates are that 50 to 90 percent of infants with SCA born in sub-Saharan Africa die before the age of 5, according to a 2017 paper published by Cincinnati Children's researchers that included Ware. The paper also reported that efforts to help people in the region with SCA have been stagnant because most affected people lack access to basic diagnostics and clinical care.

Institutions like Cincinnati Children's are working with ASH and the National Heart, Lung, and Blood Institute (part of NIH) to invest in research and clinical programs and address the global burden of SCA in limited-resource settings, especially sub-Saharan Africa.

The Phase 1-2 multi-center open-label REACH clinical trial treated children in four sub-Saharan countries: the Democratic Republic of Congo, Uganda, Kenya and Angola. Researchers plan to follow children in the study long-term to get additional data about growth and development and to look for any possible effects on organ function and fertility.

Breast cancer survivors who used a smartphone app created at Houston Methodist consistently lost weight, largely due to daily, real-time interactions with their health care team via the mobile app. Few clinically-tested mobile apps exist today with clear measurable goals to support continued care of cancer survivors and patients.

There is increasing evidence that reducing obesity also reduces the risk of cancer recurrence and the frequency of hospital readmission. A meta-analysis of 82 studies evaluating the relationship between body weight and breast cancer in more than 213,000 women found a 35 percent increase in breast cancer mortality.

A Nov. 30 paper in JCO Clinical Cancer Informatics focused on the benefits of using the Methodist Hospital Cancer Health Application specifically designed for breast cancer survivors to interact with their clinical dietitian and reinforce healthier lifestyle choices, especially between appointments.

Of the 33 breast cancer survivors enrolled, 25 women actively used the app over a four-week period. During this pilot study, 56 percent of enrolled patients lost an average of 3.5 pounds. Also, the more the study participants used the app, the more likely they were to lose weight.

"Some breast cancer medications slow down metabolism, but one of the biggest hurdles for a survivor is finding the support needed to maintain a healthy lifestyle," said Tejal A. Patel, M.D., co-senior author and breast medical oncologist at Houston Methodist Cancer Center. "We tell our patients that losing weight reduces the risk of cancer recurrence, but don't usually provide them with structured tools to achieve and maintain this weight loss. The mobile application provides a link to the physician's office so that real-time changes can be made."

Unlike popular consumer health apps, the Houston Methodist app incorporated a clinical dietitian who actively communicated with patients and provided direct feedback and guidance. For example, if a breast cancer survivor logged her daily meals, the nutritionist reviewed it and made comments and suggestions in real time.

Studies show that fewer than 35 percent of all breast cancer survivors follow recommended levels of physical activity. Stephen T.C. Wong, Ph.D., P.E., chair and professor of the Department of Systems Medicine and Bioengineering at Houston Methodist Research Institute, and his informatics development team helped create the mobile application as a way for Houston Methodist health care providers to actively support their patients after treatment and to provide continued care beyond hospital walls.

"We are a mobile society, so digital innovations like smartphone health care apps must be made in a way that empower our patients and deliver patient-centric care," said Wong, co-senior author on the paper. "More than 90 percent of the study patients found our app easy to navigate, and they wanted to use it daily for real-time feedback and support. The app helped breast cancer patients change daily behaviors and successfully meet their personal goals."

Houston Methodist dietician Renee Stubbins said the mobile health app allowed her to interact with more patients in one day than she normally would in person, something she believes can be adapted by other registered dietitians and health care providers. Not only did she provide recommendations for diet and exercise, but she also motivated the study participants to provide virtual support to each other.

"Maintaining a healthy weight is difficult enough for the average person, let alone for those who've survived breast cancer, so being able to empower and support these women made a difference," said Stubbins, one of the paper's co-first authors.

The app is currently accessible to study patients, but the goal is to widely offer this mobile application on the App Store and Google Play. Houston Methodist will broaden the use of this app in multi-center studies and focus on long-term behavioral changes to reduce health issues most common in cancer survivors. One study will include active breast cancer patients undergoing chemotherapy or other treatment. A second study will include all cancer survivors and monitor exercise, wellness and diet over a 12-week period.

A study recently published in Translational Psychiatry, a Nature journal, has shown how using cultured cells from patients with psychotic disorders, such as schizophrenia, to investigate abnormalities in nerve connections in the brain could lead to new treatments. Strong correlations were observed between the findings in the cells in culture--grown outside the body in a controlled environment--and findings from brain imaging performed on the very same human participants.

"The findings are important, because if the health of cells in culture reflects the health of the same cells in a human brain, we may be able to create a better model for studying psychotic disorders," said the study's senior author, Bruce M. Cohen, MD, PhD, director of McLean Hospital's Program for Neuropsychiatric Research (PNPR). Cohen said such a model could give researchers a greater capacity to find genetic and biochemical targets in the brain. Using these targets, he said, "could enable us to develop novel and more effective interventions for psychotic disorders."

For their work, Cohen and his colleagues, including first author Donna L. McPhie, PhD, director of the Cellular Neuropsychiatry Laboratory in the PNPR, drew on studies showing that altered pathways of brain development can be found across most cases of schizophrenia and that inaccurate connections and "leaks" in signaling between nerve cells are a feature of many psychotic disorders. A substance called myelin, produced by cells called oligodendrocytes, serves as a kind of insulation to prevent these leaks. In studies at McLean Hospital by co-author Dost Öngür, MD, PhD, chief of the Psychotic Disorders Division at McLean, and his colleagues, myelin was measured and found to be reduced in the brain in patients with schizophrenias.

Based on this prior research, Cohen and his colleagues drew on a repository of cell lines they had obtained from patients with psychiatric disorders. These samples were reprogrammed from skin cells into brain-like cells in the laboratory. The reprogrammed cell lines, taken from both ill and healthy patients, produced nerve cells and support cells called glia, including oligodendrocytes, in laboratory cultures. Investigations into these cells revealed significant abnormalities in the development of oligodendrocytes grown from subjects with psychotic disorders.

The research also revealed a strong correlation between the number of oligodendrocytes in culture and the amount of myelin made by these cells in the brains of the same subjects who provided the cells. This finding, Cohen explained, "means that we can now study the causes of the abnormality of myelin that we have observed in living brain tissue in a laboratory setting."

For Cohen and his colleagues, the prospect of using lab cultures to examine differences in the brains of individuals with psychotic illnesses is "an exciting development." For example, Cohen said, researchers have observed that not all genes and proteins necessary to make oligodendrocytes are affected in these cells, and they can now begin to identify exactly what genes and proteins are different in these cells. It would be impossible, he said, to do these detailed studies in living brain tissue.

Such studies, the researchers believe, could lead to better treatment approaches for individuals with psychotic conditions. "Using in vitro cell cultures to study these abnormalities could help us identify specific genetic and biochemical targets that might be addressed by novel drug treatments, cell transplantation, or other interventions," Cohen said.

Heart attacks reoccurred more frequently in younger patients with several modifiable risk factors, including smoking and high blood pressure. Researchers on the new study, presented at the American College of Cardiology Asia Conference 2018 in Shanghai, suggested secondary preventive programs for younger patients should target modifiable risk factors.

"When treating younger patients with a history of heart attack, clinicians should emphasize better control of high blood pressure, high cholesterol and diabetes," said Joanne Karen Recacho-Turingan, MD, a Cardiology Fellow at The Medical City in Manila, Philippines. "Other modifiable risk factors to highlight in patient history and address with these patients include smoking habits and obesity."

Researchers analyzed 133 young patients admitted at The Medical City for a heart attack between 2013 and 2016. During the study period 22 patients had a reoccurrence. All patients who experienced a second heart attack were male with an average age of 40.9 years. Patients who did not experience a reoccurrence were 90.1 percent male and 9.9 percent female with an average age of 39.6 years.

Risk factors such as smoking, high blood pressure, family history of heart disease and chronic kidney disease were more prevalent among the patients who experienced a reoccurrence. In these patients, chest pain was the most common presenting symptom at 81.8 percent while 90.9 percent had unstable vital signs at the time of admission.

"Heart attack in young patients can cause disability and even death at the prime of life," Recacho-Turingan said. "There are often serious consequences for these patients, their families and the health system, which can lead to an increased economic burden. We must make sure to work with these patients on their modifiable risk factors to reduce their risk not just for a second heart attack, but hopefully, even preventing the first."

Previous studies have defined young heart attack patients as less than 45 years old while some used a less than 40-year old cut-off. Prior research has found these patients have a high prevalence of smoking, family history and high cholesterol.

MANHATTAN, KANSAS -- Along with a warming climate and intensified human activities, recent water storage in global landlocked basins has undergone a widespread decline. A new study reveals this decline has aggravated local water stress and caused potential sea level rise.

The study, "Recent Global Decline in Endorheic Basin Water Storage," was carried out by a team of scientists from six countries and appears in the current issue of Nature Geoscience.

"Water resources are extremely limited in the continental hinterlands where streamflow does not reach the ocean. Scientifically, these regions are called endorheic basins," said Jida Wang, a Kansas State University geographer and the study's lead author.

"Over the past few decades, we have seen increasing evidence of perturbations to the endorheic water balance," said Wang, an assistant professor of geography. "This includes, for example, the desiccating Aral Sea, the depleting Arabian aquifer and the retreating Eurasian glaciers. This evidence motivated us to ask: Is the total water storage across the global endorheic system, about one-fifth of the continental surface, undergoing a net decline?"

Using gravity observations from NASA/German Aerospace Center's Gravity Recovery and Climate Experiment, or GRACE, satellites, Wang and his colleagues quantified a net water loss in global endorheic basins of approximately 100 billion tons of water per year since the start of the current millennium. This means a water mass equivalent to five Great Salt Lakes or three Lake Meads is gone every year from the arid endorheic regions.

Surprisingly, this amount of endorheic water loss is double the rate of concurrent water changes across the remaining landmass except Greenland and Antarctica, Wang said. Opposite to endorheic basins, the remaining regions are exorheic, meaning streamflow originating from these basins drains to the ocean. Exorheic basins account for most of the continental surface and are home to many of the world's greatest rivers, such as the Nile, Amazon, Yangtze and Mississippi.

Wang noted that the signature of water storage changes in exorheic basins resembles some prominent oscillations of the climate system, such as El Niño and La Niña in multiyear cycles. However, the water loss in endorheic basins appears less responsive to such short-term natural variability. This contrast may suggest a profound impact of longer-term climate conditions and direct human water management, such as river diversion, damming and groundwater withdrawal, on the water balance in the dry hinterlands.

This endorheic water loss has dual ramifications, according to the researchers. Not only does it aggravate water stress in the arid endorheic regions, but it could also contribute to a significant factor of global environmental concern: sea level rise. Sea level rise is a result of two main causes: thermal expansion of sea water as a result of increased global temperature, and additional water mass to the ocean.

"The hydrosphere is mass conserved," said Chunqiao Song, researcher with the Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, and a co-lead author of the study. "When water storage in endorheic basins is in deficit, the reduced water mass doesn't disappear. It was reallocated chiefly through vapor flux to the exorheic system. Once this water is no longer landlocked, it has the potential to affect the sea level budget."

Despite an observation period of 14 years, the endorheic water loss equals an additional sea level rise of 4 millimeters, the study found. The researchers said this impact is nontrivial. It accounts for approximately 10 percent of the observed sea level rise during the same period; compares to nearly half of the concurrent loss in mountain glaciers, excluding Greenland and Antarctica; and matches the entire contribution of global groundwater consumption.

"We are not saying the recent endorheic water loss has completely ended up in the ocean," said Yoshihide Wada, deputy director of the water program at the International Institute for Applied Systems Analysis in Austria and a co-author of the study. "Instead, we are showing a perspective of how substantial the recent endorheic water loss has been. If it persists, such as beyond the decadal timescale, the water surplus added to the exorheic system may signify an important source of sea level rise."

By synergizing multi-mission satellite observations and hydrological modeling, Wang and his colleagues attributed this global endorheic water loss to comparable contributions from the surface -- such as lakes, reservoirs and glaciers -- as well as soil moisture and aquifers.

"Such comparable losses are, however, an aggregation of distinct regional variations," Wang said. "In endorheic Central Eurasia, for instance, about half of the water loss came from the surface, particularly large terminal lakes such as the Aral Sea, the Caspian Sea and Lake Urmia, and retreating glaciers in High Mountain Asia."

While glacial retreat was a response to warming temperature, water losses in the terminal lakes were a combined result of meteorological droughts and long-term water diversions from the feeding rivers.

The net water loss in endorheic Sahara and Arabia, on the other hand, was dominated by unsustainable groundwater withdrawal, according to the researchers. In endorheic North America, including the Great Basin of the U.S., a drought-induced soil moisture loss was likely responsible for most of the regional water loss. Despite a lesser extent, the surface water loss in the Great Salt Lake and the Salton Sea was at a substantial rate of 300 million tons per year, which was partially induced by mineral mining and diversion-based irrigation.

"The water losses from the world's endorheic basins are yet another example of how climate change is further drying the already dry arid and semi-arid regions of the globe. Meanwhile, human activities such as groundwater depletion are significantly accelerating this drying," said Jay Famiglietti, director of the Global Institute of Water Security, Canada 150 research chair in hydrology and remote sensing at the University of Saskatchewan, Canada and co-author of the study.

Wang said the team wants to convey three takeaway messages from their research.

"First, water storage in the endorheic system, albeit limited in total mass, can dominate the water storage trend in the entire land surface during at least decadal timescales," Wang said. "Second, the recent endorheic water loss is less sensitive to natural variability of the climate system, suggesting a possible response to longer-term climate conditions and human water management.

"Third, such a water loss in the endorheic system has dual ramifications, both to regional water sustainability and to global sea level rise," he said. "These messages highlight the underrated importance of endorheic basins in the water cycle and the need for an improved understanding of water storage changes in the global hinterlands."

The English idiom "highbrow," derived from a physical description of a skull barely able to contain the brain inside of it, comes from a long-held belief in the existence of a link between brain size and intelligence.

For more than 200 years, scientists have looked for such an association. Begun using rough measures, such as estimated skull volume or head circumference, the investigation became more sophisticated in the last few decades when MRIs offered a highly accurate accounting of brain volume.

Yet the connection has remained hazy and fraught, with many studies failing to account for confounding variables, such as height and socioeconomic status. The published studies are also subject to "publication bias," the tendency to publish only more noteworthy findings.

A new study, the largest of its kind, led by Gideon Nave of the University of Pennsylvania's Wharton School and Philipp Koellinger of Vrije Universiteit Amsterdam, has clarified the connection. Using MRI-derived information about brain size in connection with cognitive performance test results and educational-attainment measures obtained from more than 13,600 people, the researchers found that, as previous studies have suggested, a positive relationship does exist between brain volume and performance on cognitive tests. But that finding comes with important caveats.

"The effect is there," says Nave, an assistant professor of marketing at Wharton. "On average, a person with a larger brain will tend to perform better on tests of cognition than one with a smaller brain. But size is only a small part of the picture, explaining about 2 percent of the variability in test performance. For educational attainment the effect was even smaller: an additional 'cup' (100 square centimeters) of brain would increase an average person's years of schooling by less than five months." Koellinger says "this implies that factors other than this one single factor that has received so much attention across the years account for 98 percent of the other variation in cognitive test performance."

"Yet, the effect is strong enough that all future studies that will try to unravel the relationships between more fine-grained measures of brain anatomy and cognitive health should control for total brain volume. Thus, we see our study as a small, but important, contribution to better understanding differences in cognitive health."

Nave and Koellinger's collaborators on the work, which is published in the journal Psychological Science, included Joseph Kable, Baird Term Professor in Penn's Department of Psychology; Wi Hoon Jung, a former postdoctoral researcher in Kable's lab; and Richard Karlsson Linnér, a postdoc in Koellinger's lab.

From the outset, the researchers sought to minimize the effects of bias and confounding factors in their research. They pre-registered the study, meaning they published their methods and committed to publishing ahead of time so they couldn't simply bury the results if the findings appeared to be insignificant. Their analyses also systematically controlled for sex, age, height, socioeconomic status, and population structure, measured using the participant's genetics. Height is correlated with higher better cognitive performance, for example, but also with bigger brain size, so their study attempted to zero in on the contribution of brain size by itself.

Earlier studies had consistently identified a correlation between brain size and cognitive performance, but the relationship seemed to grow weaker as studies included more participants, so Nave, Koellinger, and colleagues hoped to pursue the question with a sample size that dwarfed previous efforts.

The study relied on a recently amassed dataset, the UK Biobank, a repository of information from more than half-a-million people across the United Kingdom. The Biobank includes participants' health and genetic information as well as brain scan images of a subset of roughly 20,000 people, a number that is growing by the month.

"This gives us something that never existed before," Koellinger says. "This sample size is gigantic--70 percent larger than all prior studies on this subject put together--and allows us to test the correlation between brain size and cognitive performance with greater reliability."

Measuring cognitive performance is a difficult task, and the researchers note that even the evaluation used in this study has weaknesses. Participants took a short questionnaire that tests logic and reasoning ability but not acquired knowledge, yielding a relatively "noisy" measure of general cognitive performance.

Using a model that incorporated a variety of variables, the team looked to see which were predictive of better cognitive performance and educational attainment. Even controlling for other factors, like height, socioeconomic status, and genetic ancestry, total brain volume was positively correlated with both.

The findings are somewhat intuitive. "It's a simplified analogy, but think of a computer," Nave says. "If you have more transistors, you can compute faster and transmit more information. It may be the same in the brain. If you have more neurons, this may allow you to have a better memory, or complete more tasks in parallel.

"However, things could be much more complex in reality. For example, consider the possibility that a bigger brain, which is highly heritable, is associated with being a better parent. In this case, the association between a bigger brain and test performance may simply reflect the influence of parenting on cognition. We won't be able to get to the bottom of this without more research."

One of the notable findings of the analysis related to differences between male and females. "Just like with height, there is a pretty substantial difference between males and females in brain volume, but this doesn't translate into a difference in cognitive performance," Nave says.

A more nuanced look at the brain scans may explain this result. Other studies have reported that in females, the cerebral cortex, the outer layer of the front part of the brain, tends to be thicker than in males.

"This might account for the fact that, despite having relatively smaller brains on average, there is no effective difference in cognitive performance between males and females," Nave says. "And of course, many other things could be going on."

The authors underscore that the overarching correlation between brain volume and "braininess" was a weak one; no one should be measuring job candidates' head sizes during the hiring process, Nave jokes. Indeed, what stands out from the analysis is how little brain volume seems to explain. Factors such as parenting style, education, nutrition, stress, and others are likely major contributors that were not specifically tested in the study.

"Previous estimates of the relationship between brain size and cognitive abilities were uncertain enough that true relationship could have been practically very important, or, alternatively, not much different from zero," says Kable. "Our study allows the field to be much more confident about the size of this effect and its relative importance moving forward."

In follow-up work, the researchers plan to zoom in to determine whether certain regions of the brain, or connectivity between them, play an outsize role in contributing to cognition.

They're also hopeful that a deeper understanding of the biological underpinnings of cognitive performance can help shine a light on environmental factors that contribute, some of which can be influenced by individual actions or government policies.

"Suppose you have necessary biology to become a fantastic golf or tennis player, but you never have the opportunity to play, so you never realize your potential," Nave says.

Adds Koellinger: "We're hopeful that, if we can understand the biological factors that are linked to cognitive performance, it will allow us to identify the environmental circumstances under which people can best manifest their potential and remain cognitively health. We've just started to scratch the surface of the iceberg here."

African-American children often are reported by parents and teachers to display behaviors of ADHD at a higher rate than children from other racial and ethnic groups. For the first time, researchers have found that African-American mothers in a study rated boys as displaying more frequent ADHD symptoms than Caucasian mothers did, regardless of child race. The findings mean that racial differences found in prior studies may be more due to maternal race than child race, said researcher George DuPaul of Lehigh University.

The findings are reported in this month's Journal of Attention Disorders, in a special print issue on Parenting Youth with ADHD.

"The primary takeaway is that common psychological assessment measures like parent behavior questionnaires are influenced by race; these assessments are not happening in a cultural vacuum," said DuPaul, a professor of school psychology who co-authored the paper, "Impact of Maternal and Child Race on Maternal Ratings of ADHD Symptoms in Black and White Boys," led by Ph.D. candidate Charles Barrett, now a school psychologist. "Hopefully these findings will alert professionals conducting evaluations that race (particularly parental race) makes a difference in how children's behavior is viewed."

Although the study focused on assessing ADHD symptoms in African-American and Caucasian boys, the findings have significant implications for the manner in which school psychologists and other professionals understand children's behavior for a host of suspected disabilities, said Barrett, who is lead school psychologist with Loudon County Public Schools in northern Virginia. "Most notably, our research underscores the importance of evaluators critically examining how factors that are beyond child behavior can influence diagnostic outcomes," Barrett said.

Results shed new light on ADHD diagnosis

For the study, African-American and Caucasian mothers watched a brief video of either an African-American or Caucasian boy displaying behaviors associated with Attention Deficit Hyperactivity Disorder (ADHD), such as inattention, hyperactivity and impulsivity. Mothers then completed a brief rating of the frequency of ADHD symptoms.

Mothers were randomly assigned to view either a Caucasian or African-American boy, making up four groups: African-American mothers viewing an African-American boy; African-American mothers viewing a Caucasian boy; Caucasian mothers viewing an African-American boy; and Caucasian mothers viewing a Caucasian boy. Children followed a script so that their behaviors were virtually identical.

Researchers found significant differences in ADHD symptom ratings as a function of maternal race, but not based on child race or the interaction between maternal and child race.

Based on past studies showing that African-American children, particularly boys, consistently receive higher scores on common ADHD assessment measures than Caucasian children do, the researchers expected child race to be the driving factor in accounting for differences in ratings of ADHD symptoms. Instead, "only small, nonstatistically significant effects for child race were found and the interaction between child and maternal race was also associated with small, nonstatistically significant effects," they said. "Differences in ADHD symptom ratings were influenced almost entirely by maternal race."

Accurate ADHD diagnosis is vital to treatment

Affecting 3 percent to 10 percent of the child population, ADHD is a chronic, neurodevelopmental disorder associated with significant academic and/or social impairment, according to the American Psychiatric Association. Thus, it is critical to identify children with ADHD in a reliable, valid fashion so that treatment resources, such as behavioral therapy, medication and behavioral parent training, are allocated to those in greatest need.

Current best practice in ADHD diagnosis involves multiple assessment methods and respondents to document symptoms and impairment across home and school settings, including observations by parents and teachers.

While several studies have found that adults rate the severity of ADHD symptoms higher in African-American children than in Caucasian children, studies have also consistently found significantly lower diagnostic and treatment rates for ADHD in the African-American population. "Given the apparent disparities in diagnosis and treatment of ADHD, it is critical to more systematically examine racial differences in assessment outcomes," the researchers said.

While other studies have used similar designs to look at differences in assessment of ADHD symptoms across countries, this is the first to look at racial differences in the United States, DuPaul said.

Participants in the study were 131 mothers recruited in suburban and urban locations in the Northeast, Mid-Atlantic, Southeastern and Midwest regions of the U.S. About half of participants were Caucasian and half African-American, with both racial groups primarily from middle class socio-economic status.

Mental health professionals and others who work with children with ADHD are most likely to benefit from these findings, researchers said, but it is also important that parents, teachers and the general public are aware of the influence of race on the ADHD evaluation process.

As a school-based practitioner, Barrett and his colleagues often focus on children's behavior, when child behavior is not the only variable to consider, Barrett said. "As the ultimate goal of assessment is not necessarily to uncover what is different about the child, willingness to explore and examine other variables leads to an equally important question of assessment: why child behavior is perceived differently by different people," he said.

The study results are consistent with prior findings that assessment measures used to identify ADHD may produce quantitatively different results for African-American and Caucasian children who have similar treatment needs, meaning that clinicians should not rely on a single method or respondent when screening or assessing for ADHD.

"Given consistent evidence of health disparities across racial groups with respect to ADHD, it is important to understand and address variables related to racial differences and to develop assessment measures that will provide equivalent data and lead to accurate diagnostic decisions across racial and ethnice subgroups," the researchers said.

BIRMINGHAM, Ala. - Preclinical experiments by University of Alabama at Birmingham researchers suggest the cancer drugs vorinostat, belinostat and panobinostat might be repurposed to treat infections caused by human papillomaviruses, or HPVs.

HPV infections caused an estimated 266,000 deaths from cervical cancer worldwide in 2012, according to the World Health Organization. Routine screening by Pap smears or HPV DNA tests has reduced death rates in developed countries compared to less developed regions of the globe. Still, an estimated 12,200 United States women are diagnosed with cervical cancer each year.

Highly efficacious vaccines against HPV infection exist -- including the recently approved Gardasil 9, which immunizes against nine genotypes of HPV known to cause cervical, vulvar, vaginal and anal cancers, and genital warts. But the vaccine needs to be given before a person becomes sexually active, since it has no therapeutic efficacy against existing HPV infections.

"Safe, effective and inexpensive therapeutic agents are urgently needed," said N. Sanjib Banerjee, Ph.D., assistant professor of Biochemistry and Molecular Genetics at UAB and lead author of the vorinostat study.

Epithelium of anogenital sites -- the cervix, penis and anus -- or epithelium of the mouth and throat are sites of HPV infection. But HPVs cannot be propagated in conventional cell culture, hampering the investigation into their pathogenic effects. The laboratory of Louise Chow, Ph.D., and Thomas Broker, Ph.D., in the UAB Department Biochemistry and Molecular Genetics has investigated HPV-host interactions for decades. They discovered that the productive program of HPV depends on differentiation of the epithelium into a full-thickness, squamous epithelium. Furthermore, HPV reactivates host DNA replication in these differentiated cells, such that the replication proteins and substrates become available to support viral DNA amplification.

The Chow and Broker lab re-produced a fully differentiated human squamous epithelium by culturing primary human keratinocytes at an air-media interphase for two to three weeks, a growth they call raft culture. In 2009, their lab developed a breakthrough model for a raft culture of HPV-18-infected primary human keratinocytes, allowing a robust amplification of HPV-18 DNA and production of infective viral progeny. This productive raft culture is an ideal model for preclinical investigation of potential anti-HPV agents.

Banerjee and colleagues hypothesized that inhibitors of histone deacetylases, or HDACs, would inhibit HPV DNA amplification because of their known mechanism of disrupting chromosomal DNA replication. Chromosomal replication requires HDAC alterations of histone proteins, the proteins that act like spools that wind DNA to help package and condense chromosomes and the viral genome. Vorinostat inhibits many HDACs, so it might interrupt not only chromosomal replication but also viral DNA replication.

Using the HPV-18 model raft cultures, the researchers found that vorinostat effectively inhibited HPV-18 DNA amplification and virus production. Importantly, vorinostat also induced the programmed cell death called apoptosis in a fraction of the differentiated cells. Cell death could be attributable to DNA breakage when chromosomal DNA replication was interrupted. Similar results were obtained with two additional HDAC inhibitors, belinostat and panobinostat. In contrast, the differentiated cells of uninfected raft cultures, which do not replicate their DNA, were thus largely spared in the presence of the inhibitors.

The UAB team also examined how vorinostat affected levels and functions of viral oncoproteins, and they described the mechanisms that led to programmed cell death in HPV-18-infected cultures. "On the basis of these detailed studies," Banerjee said, "we suggest that HDAC inhibitors are promising compounds for treating benign HPV infections, abrogating progeny production and hence interrupting infectious transmission."

The UAB team also reported that vorinostat caused extensive cell death in raft cultures of dysplastic and cancer cell lines harboring HPV-16. HPV-16 and HPV-18 are the most prevalent, high-risk HPVs responsible for causing anogenital and oropharyngeal cancers. "But further investigation would be required to verify that these agents could also be useful in treating HPV associated dysplasias and cancers," Banerjee said.