Body

MORGANTOWN, W. Va.--Large-scale behavior change is a critical component when it comes to mitigating the effects of the COVID-19 pandemic. But, as one West Virginia University researcher points out, it can also be leveraged to address a separate, yet, equally important, persistent public health crisis: gun violence in our nation's schools.

As School of Public Health Professor and Chair Keith Zullig highlights in a Journal of Adolescent Health editorial, gun access is strongly correlated with unintentional and intentional injury, with many acts of violence occurring at school. According to a 2018 special report in the New England Journal of Medicine, firearms are the second leading cause of death for adolescents.

"In school shootings alone in the United States between 1996 through 2019, there have been approximately 196 students and 30 school staff killed and another 243 wounded," Zullig said. "Although the likelihood of a school shooting in any given school district remains statistically low, in the absence of strong legislation, schools have taken action by implementing active shooter drills."

Despite the fact that little research has attempted to include the perceptions of students impacted by these active shooter drills - often referred to as "lockdown drills," which involve confining students to specific areas with additional instructions in the event of an incident - the vast majority (95 percent) of American public schools had active shooter drills in place during the 2015-2016 school year.

'Uncertain ultimate benefit'

Researchers have discovered that, in many cases, active shooter drills are having an adverse effect on students.

"It's been reported that the drills youth have received caused emotional distress, where about 60 percent reported feeling unsafe, scared, helpless, or sad as a result of experiencing active shooter drills," Zullig said. "Moreover, although about 58 percent of youth reported that active shooter drills teach them what to do if such a situation presents itself, they were uncertain of their ultimate bene?t."

Part of this can be attributed to schools implementing only portions of evidence-based active shooter drill strategies.

Zullig points out that additional research is needed to better understand the critical components of effective shooter drills and how to successfully implement them, as well as how to best prepare students.

He outlines a multifaceted approach and several evidence-based tactics that can be used to complement active shooter drills, with many of them being behavior- and relationship-driven.

A safe, supportive environment

"At the individual level, monitoring patterns of behavior and responding quickly to students experiencing strain may be useful in identifying vulnerable students early and enable school personnel to connect them with appropriate services before tragic violence occurs," he said.

"Systems-level approaches are also necessary," he added. "For instance, school leaders could focus on developing a strong school climate to foster trusting and positive relationships and connectedness among faculty, staff, and students. A strong school climate, coupled with identifying facilitators and barriers to successful implementation of evidence-based strategies, could prove effective."

From the interpersonal and organizational perspective, Zullig points out that school leaders play a key role in fostering a safe and supportive learning environment because they set the tone and the expectations for behavior which, in turn, affect faculty, staff and students.

Research demonstrates that higher perceptions of academic support are not only strongly associated with higher reported grade point averages, but also with an increase in feeling safe at school and lower reported incidents of fighting and being bullied.

Social-emotional learning programs and school-based bullying interventions can also be key. Examples include increased teacher involvement and supervision and clear order and disciplinary policies that lead to stronger relationships among teachers, students, and their school.

Still work to be done

Zullig suggests there is still much work to done at the community and public policy levels, too.

"In an effort to encourage greater action from lawmakers, grass roots efforts led by capable advocacy groups must continue to point out successful examples from other industrialized nations where gun violence has been significantly reduced," he said.

He points to Japan as an example, where, in 2014, they experienced just six gun deaths compared to 33,599 in the United States - a milestone that could only be accomplished through a variety of policies, including mandatory educational training, written and shooting examinations, mental health and drug screenings, and criminal records searches.

And while not all of Japan's policies would be possible in the United States, research suggests "child access protection laws display the strongest evidence of subsequent reductions in firearm deaths when compared to right-to-carry and stand your ground laws."

"Our children are our most vulnerable national treasure," Zullig said. "Given the evidence available to us, it's clear there are steps we can take as a country to further protect them."

Researchers at the University of Illinois Urbana-Champaign have found that a combination of exercise and mindfulness training can help reduce fatigue in breast cancer survivors. The results from their preliminary trials might be useful in designing interventions for other cancer patients.

The study "Acute effects of aerobic exercise and relaxation training on fatigue in breast cancer survivors: A feasibility trial" was published in Psycho-Oncology.

"When it comes to cancer patients, hospitals treat the disease. However, treating the patients is equally important and sometimes that aspect is overlooked," said Jason Cohen, a former graduate student from Sean Mullen's Exercise, Technology, and Cognition Laboratory, which is affiliated with the Beckman Institute for Advanced Science and Technology. "We wanted to look at improving the quality of life in breast cancer survivors after chemotherapy."

After enduring rigorous cancer treatments, the survivors often experience mental and physical fatigue, anxiety, and poor sleep. Although other researchers have found that either exercise or relaxation techniques help relieve fatigue, there are very few studies that have tested them in combination. "We wanted to see if there were any added benefits," Cohen said.

The trial took place over seven days, and it included 40 women. The participants were asked to fill out questionnaires about their perceived fatigue levels. They were then divided into three groups where they were asked to either exercise or undergo mindfulness training or a combination of both.

"We found that initially all the participants had a moderate level of self-reported mental fatigue," Cohen said. "Over the course of the week, the groups that took part in a combination of exercise and mindfulness training reported a drop in fatigue levels from moderate to mild. The other groups did not show a comparable degree of improvement."

"These findings parallel the ones that my team has collected from other studies involving aerobic exercise paired with brain training," said Sean Mullen, an associate professor of kinesiology and community health. "Although each of our studies are different in aims, scope and population, our research consistently supports the idea that two health behavior interventions is better than one. Sometimes it is assumed that in merging them together, we end up watering down their unique effects. In our experience, they tend to work just as well, if not better, together."

The researchers hope to use the information from the trial as preliminary data in future grant applications. In doing so, they hope to increase sample size and trial duration to assess whether the intervention can provide a more robust improvement on quality of life. "When expanding behavioral interventions, the key is not to overwhelm participants with too much new information and to offer sufficient education, training and resources to ensure they stick with the program," Mullen said.

The researchers are continuing to explore opportunities to work with other adult populations with and without chronic disease, using a variety of intervention modalities, to determine if combined treatments are helpful.

CLEVELAND, Ohio (December 2, 2020)--Women being treated for cancer often experience menopause quite suddenly with common symptoms, such as hot flashes, amplified more than had menopause occurred naturally. A new study suggests that the intensity and volume of physical activity could mitigate some of those symptoms. Study results are published online in Menopause, the journal of The North American Menopause Society (NAMS).

Menopause symptoms may arise as the result of radiotherapy to the pelvic field, surgical removal of the ovaries, or systemic chemotherapy. When such procedures occur in premenopausal or perimenopausal women, they often result in sudden and sometimes irreversible menopause that is accompanied by more frequent and severe menopause symptoms. Various cancer-treating endocrine therapies, such as the use of tamoxifen, can also amplify symptoms, especially hot flashes.

A new study involving nearly 300 women sought to investigate the association between self-reported physical activity and menopause symptoms. In addition, the researchers evaluated whether intervention targeting lifestyle behavior could improve changes in physical activity levels and menopause symptoms.

Results suggest that menopause symptoms are less severe in women with medium to high levels of physical activity than in women with low levels of such activity. The intervention, however, was not determined to play a role in increasing physical activity in women being treated for breast, reproductive, or blood cancers. Although this is not the first study to examine the association of physical activity with menopause symptoms, it is the first to look specifically at the volume and intensity of physical activity.

Severe menopause symptoms, including poor mental well-being, are associated with a sedentary lifestyle and low physical activity, even in women experiencing natural menopause. Researchers of the current study additionally found that women being treated for breast cancer, for example, who experience worse menopause symptoms are less likely to engage in health-promoting behaviors.

On the basis of study results, researchers suggest that an increased focus on exercise training should be part of the long-term maintenance program for women after cancer treatment.

Results are published in the article "Physical activity and menopausal symptoms in women who have received menopause-inducing cancer treatments: results from the Women's Wellness After Cancer Program."

"This study highlights some of the many known benefits of exercise in women with or without cancer. Although exercise was not associated with less bothersome hot flashes, findings consistent with prior studies, it may help with other menopause symptoms, including mood and sleep disturbances," says Dr. Stephanie Faubion, NAMS medical director.

DALLAS, Dec. 2, 2020 -- Lesbian, gay and bisexual (LGB) adults who may benefit from cholesterol-lowering medicine to prevent cardiovascular disease are less likely than non-LGB adults to take them, according to new research published today in the Journal of the American Heart Association, an open access journal of the American Heart Association.

According to an American Heart Association scientific statement, LGB adults have higher cardiovascular disease risk than non-LGB adults, in part because they are more likely to smoke, drink alcohol, use drugs and be obese. There is strong evidence that cholesterol-lowering medicines called statins help prevent cardiovascular disease in adults who do not yet have cardiovascular disease but have risk factors like high cholesterol or diabetes. When prescribed for someone not yet diagnosed with heart disease, this is referred to as primary prevention for cardiovascular disease. Statins also benefit people who already have cardiovascular disease; for these adults, statins are taken for secondary prevention.

"Our study was the first to estimate the prevalence of statin use among the LGB population," said study author Yi Guo, Ph.D., M.S.P.H., assistant professor of Health Outcomes and Biomedical Informatics at the University of Florida College of Medicine in Gainesville, Fla. "We compared the rate of statin use among LGB and non-LGB individuals using Facebook-delivered online surveys and observed that the LGB respondents had significantly lower rates of statin use for primary cardiovascular disease prevention compared to the non-LGB respondents, yet that was not the case in secondary prevention."

Guo and colleagues conducted an online survey between September and December 2019 using a paid advertising Facebook campaign. Targeting adult Facebook users in the U.S. with interests in LGB keywords, such as "gay pride," the researchers developed a series of ads linking to the survey. The survey asked about sexual orientation, gender identity, statin use, health status, chronic conditions, smoking status and more.

Their analysis of 1,531 Facebook respondents ages 40 years and older revealed:

More than 12% identified as LGB.

Nearly a third of all respondents were taking statins.

Less than 21% of LGB adults were taking statins for primary prevention compared to nearly 44% of non-LGB adults.

There was no notable difference in statin use between the LGB and non-LGB groups for secondary prevention.
"There could be many reasons for the difference we observed," Guo said. "LGB individuals may not go to the doctor as often, which leads to lower chances of being recommended statins for cardiovascular disease prevention."

He adds that the LGB population may also be less aware of their cardiovascular disease risk and the protective effect of statins. "We were surprised to see such a big difference in primary prevention, with less than half of the rate as the non-LGB population. This highlights the urgent need for tailored interventions and campaigns that promote the awareness of statin use and cardiovascular health in the LGB population."

"Health care providers should address their own biases and understand the complexities of LGB patients, making sure to provide guideline-directed recommendations in a culturally competent way," said study co-author Jiang Bian, Ph.D., associate professor of Health Outcomes and Biomedical Informatics at the University of Florida College of Medicine.

"What we have found is very much in line with the American Heart Association's statement for LBGTQ adults," Bian said. "First, more research is needed to better understand the cardiovascular disease health risks and outcomes in the LGB population. Second, educational programs are needed to educate health professionals on these unique health risks and outcomes in the LGB population and the appropriate way to communicate with LGB people."

Among the study's limitations are that using Facebook as a source may not accurately represent the LGB population as a whole, and the health information was self-reported. "However, since no studies have reported the prevalence of statin use in the sexual- and gender-minority population, our study provides important initial data and validates the need for additional research," Guo said. "We need detailed studies to help us understand LGB statin use with clinical data from the real-word, such as those in electronic health records (EHRs) or administrative claims."

Bottom Line: Among patients with lung cancer from Latin America, genomic and ancestry analyses revealed that Native American ancestry was associated with increased mutations in the EGFR gene, independent of smoking status.

Journal in Which the Study was Published: Cancer Discovery, a journal of the American Association for Cancer Research

Author: Matthew Meyerson, MD, PhD, director of the Center for Cancer Genomics at Dana-Farber Cancer Institute in Boston; professor of genetics and medicine at Dana-Farber Cancer Institute and Harvard Medical School; and an Institute Member of the Broad Institute of MIT and Harvard in Cambridge, Massachusetts

Background: "Lung cancer is the leading cause of cancer mortality, both in the United States and globally, and understanding inherited risk factors for this disease may help us to identify populations that would benefit from increased screening efforts," said Meyerson.

"Previous work has demonstrated that EGFR-mutant lung cancer is more common among populations from East Asia compared with populations from North America or Europe, about 50 percent versus 10 percent of lung cancer cases, respectively," said Meyerson. "But it is not clear whether the ethnic difference in EGFR-mutant lung cancer is due to environmental or genetic factors," he added.

How the Study was Conducted & Results: Meyerson and colleagues analyzed samples from 1,153 patients with lung cancer from Latin America. Of them, 601 were from Mexico and 552 were from Colombia, and 499 patients self-reported as non-smokers. Through genomic analysis of tumor samples, the researchers identified somatic mutations in EGFR, KRAS, and other target genes.

Using a new method developed by Jian Carrot-Zhang, PhD, and Alexander Gusev, PhD, the researchers also performed ancestry analyses from tumor samples in this admixed population. Global ancestry analysis was performed to measure proportions of African, European, and Native American ancestry across the genome. Additionally, local ancestry analysis was performed, which evaluates genetic ancestry at a particular chromosomal location. Because local ancestry only evaluates a small portion of the genome, there is less potential for observed associations to be confounded by environmental exposures or socioeconomic status, which may be seen in global ancestry analyses, Meyerson explained.

Using the genomic and ancestry data, the researchers assessed the associations of somatic mutations in target genes and global ancestry groups within a single admixed population. After adjusting for a variety of factors, including self-reported smoking status and sample-specific tumor mutational burden, the researchers found that global Native American ancestry was positively correlated with mutations in the EGFR gene. Further, the researchers found that Native American ancestry was predominantly associated with oncogenic mutations in the EGFR gene, but not with non-oncogenic mutations.

Meyerson and colleagues then stratified patients by their self-reported smoking status and evaluated the association between global ancestry and mutations in target genes. In both never smokers and smokers, global Native American ancestry was associated with mutations in the EGFR gene, suggesting that the genomic differences associated with Native American ancestry are independent of smoking status.

"Smoking increases the risk for KRAS-mutant lung cancers, while patients with lung cancer who are non-smokers more often develop EGFR-mutant lung cancer," Meyerson said. "However, we show in our study that EGFR-mutant lung cancer is also elevated among smokers with Native American ancestry."

The researchers next developed a local Native American ancestry risk score to evaluate the association of ancestry with EGFR mutation frequency across multiple distinct sites in the genome. They found that the correlation between ancestry and increased mutation frequency in the EGFR gene was stronger at the local genome level than the global genome level. "These results suggest that germline genetics-in addition to environmental factors or socioeconomic status-may have an influence on the risk of EGFR-mutant lung cancer among those with Native American ancestry," Meyerson said.

The study was jointly led by Meyerson; by Gusev, an assistant professor of medicine at Dana-Farber and Harvard Medical School; by Andres F. Cardona, MD, of the Clinica del Country/Foundation for Clinical and Applied Cancer Research (FICMAC) in Bogota, Colombia; and by Oscar Arrieta, MD, head of Thoracic Oncology at the Instituto Nacional de Cancerologia in Mexico City. Carrot-Zhang, a postdoctoral research fellow at Dana-Farber Cancer Institute and Broad Institute, and first author of the study, developed computational methods with Gusev and performed the bulk of the computational analyses.

Author's Comments: "Many lung cancers are now treatable with targeted therapy or immunotherapy," Meyerson continued. "It is very important for patients with lung cancer to undergo somatic genetic testing to determine which treatments are most likely to be effective for their particular cancer."

Study Limitations: Limitations of the study include a small sample size, which Meyerson noted precluded the identification of the specific gene or site in the germline that is associated with increased somatic EGFR mutations among those with Native American ancestry. Further, the researchers only tested known hotspot mutations and protein truncating mutations in lung cancer driver genes, and future work is needed to comprehensively characterize lung cancer genomes from Latin American patients, Meyerson said.

Funding & Disclosures: This study was supported by a Translational Research Award from the Stuart Scott Memorial Fund of the V Foundation and by the National Cancer Institute. Meyerson is an American Cancer Society Research Professor.

Meyerson is the scientific advisory board chair of OrigiMed and an inventor of patents licensed to LabCorp for the diagnosis of mutations to the EGFR gene, with pending patent applications on EGFR inhibitors. Meyerson receives research funding from Bayer, Janssen, Novo Ventures, and Ono Pharmaceutical Co.

The chip, developed at Imperial College London and known as TriSilix, is a 'micro laboratory' which performs a miniature version of the polymerase chain reaction (PCR) on the spot. PCR is the gold-standard test for detecting viruses and bacteria in biological samples such as bodily fluids, faeces, or environmental samples.

Although PCR is usually performed in a laboratory, which means test results aren't immediately available, this new lab-on-a-chip can process and present results in a matter of minutes.

The chip is made from silicon, the same material that is used to make electronic chips. Silicon itself is cheap, however, it is expensive to process into chips which requires massive, 'extremely clean' factories otherwise known as cleanrooms. To make the new lab-on-chip, the researchers developed a series of methods to produce the chips in a standard laboratory, cutting the costs and time they take to fabricate, potentially allowing them to be produced anywhere in the world.

Lead researcher Dr Firat Guder of Imperial's Department of Bioengineering said: "Rather than sending swabs to the lab or going to a clinic, the lab could come to you on a fingernail-sized chip. You would use the test much like how people with diabetes use blood sugar tests, by providing a sample and waiting for results - except this time it's for infectious diseases."

The paper is published today in Nature Communications.

The researchers have so far used TriSilix to diagnose a bacterial infection mainly present in animals as well as a synthetic version of the genetic material from SARS-CoV-2, the virus behind COVID-19.

The researchers say the system could in future be mounted onto handheld blood sugar test-style devices. This would let people test themselves and receive results at home for colds, flu, recurrent infections like those of the urinary tract (UTIs), and COVID-19.

Table-top devices for testing of infections like COVID-19 already exist, but these tests can be time-consuming and costly since the patient must go to a clinic, have a sample taken by a healthcare worker and go home or stay in clinic to wait. People leaving their homes when not feeling well increases the risk of spread of a pathogen to others.

If validated on human samples, this new test could provide results outside a clinic, at home or on-the-go within minutes.

The researchers also say a highly portable test could accelerate diagnosis of infections and reduce costs by eliminating transportation of samples. Such tests could be performed by citizens in the absence of highly trained medical professionals - hence, if they need to self-isolate, they can start immediately without potentially infecting others.

Making testing more accessible and cheaper is especially important for people in rural areas of low-income countries, where clinics can be far away and expensive to travel to. If made available to patients, it could also be used to diagnose and monitor infections like UTIs, which often recur despite antibiotics.

First author Dr Estefania Nunez-Bajo, also of the Department of Bioengineering, said: "Monitoring infections at home could even help patients, with the help of their doctor, to personalise and tailor their antibiotic use to help reduce the growing problem of antibiotic resistance."

Each lab-on-a-chip contains a DNA sensor, temperature detector and heater to automate the testing process. A typical smartphone battery could power up to 35 tests on a single charge.

Next, the researchers plan to validate their chip with clinical samples, automate the preparation of samples and advance their handheld electronics. They are looking for partners and funders to help accelerate the translation of the technology deliver testing at resource limited settings at homes, farms or remote locations in the developing world.

The release previously located at this link was posted in error and can now be found here:

https://eurekalert.org/emb_releases/2020-12/nch-bri113020.php.

MIAMI -- Exposure to ethnic discrimination on social media is associated with higher symptoms of depression and anxiety among young Hispanic males, according to a study by researchers at Florida International University's Robert Stempel College of Public Health & Social Work.

"Surprisingly, there is a lot of research about cyberbullying and social media but there really wasn't a thorough study that looked at how exposure to ethnic discrimination on social media impacts mental health," said Miguel Ángel Cano, lead author and principal investigator of the study and associate professor in the Department of Epidemiology at Stempel College.

Ethnic discrimination and hate speech on social media have been in the spotlight during recent national discussions and demonstrations over racial and ethnic injustice, leading to boycotts of social media platforms by advertisers. A 2018 Pew Research Center survey found that 73 percent of Hispanics reported using Facebook, which has the most users in the U.S.

The study--published in the Journal of Clinical Psychology-- was based on surveys of 200 young Hispanic adults, ages 18-25. Half of the participants were from Miami-Dade County, Florida and half from Maricopa County, Arizona. Researchers found that, upon exposure to social media posts such as photos, memes or videos that include ethnic discrimination, users felt higher levels of depression and anxiety.

"When participants were exposed to ethnic discrimination on social media directly, or vicariously on a friend's social media page, it was found to have adverse effects on mental health," Cano said. "A viral video or meme may not always be directed at you, but when you see someone publicly discuss your social or ethnic group in a negative or derogatory way, it, unfortunately, can have a negative impact on mental health."

The men in the study, however, were more adversely affected than the women by increased exposure to ethnic discrimination on social media, reporting higher levels of depression and anxiety, even though both men and women had about the same amount of exposure to that type of material on social media.

"Men may be more affected by ethnic discrimination in social media because it is likely that they are exposed to more egregious forms of racist/discriminatory content that specifically depicts men," Cano said. "Consequently, this may have a stronger or longer-lasting impact, and it may also threaten their concept of masculinity and threaten their perceived social status and power."

Previous studies have shown that young adults experience higher symptoms of depression and anxiety when compared to adolescents and other adult age groups. When considering the high usage of social media among this age group, especially Hispanics, social media discrimination may be a factor that compounds the risk of developing poor mental health, Cano said.

The researchers determined that more studies on the topic were needed to develop culturally appropriate, evidence-based interventions for adolescents and young adults.

The role of a protein in detecting the common cold virus and kickstarting an immune response to fight infection has been uncovered by a team of scientists from Nanyang Technological University, Singapore (NTU Singapore), the Agency for Science, Technology and Research (A*STAR) and the National University of Singapore.

In a study published in one of the world's leading scientific journals Science on 22 October 2020, they showed that the protein NLRP1, found on the skin and in the airways, is a sensor that detects the human rhinovirus (HRV). When NLRP1 breaches the respiratory tract, it triggers an immune response leading to inflammation in the lungs and causes symptoms of the common cold.

HRV is a major cause of the common cold and acute respiratory disease in children and adults, which in severe cases, leads to bronchiolitis and pneumonia.

The research team said that discovering NLRP1's purpose could lead to new treatments for the symptoms of the common cold, which affects millions of people annually. They plan to work with clinicians to develop drugs that 'turn off' or block NLRP1, to lessen the severity of symptoms for HRV-related diseases. However, the team noted that blocking the protein in human lung cells did not increase the viral load, which refers to the amount of virus in an infected person's blood.

"Now that we know that NLRP1 is the "on switch" for inflammation after it detects the common cold virus, the next step is to figure out how to block its activation and to minimise the inflammatory response it triggers," said Assistant Professor Franklin Zhong from NTU's Lee Kong Chian School of Medicine and A*STAR's Skin Research Institute of Singapore (SRIS).

Asst Prof Zhong is the corresponding author of the study, along with Professor Bruno Reversade from A*STAR's Genome Institute of Singapore and Institute of Molecular and Cellular Biology and first author, Dr Kim S Robinson, Research Fellow at SRIS, A*STAR.

Asst Prof Zhong said that their new insights into immune system functions could help scientists to develop more effective treatments for other inflammatory diseases of the human airway.

"This work represents a significant advance in our understanding of how our immune system uses special proteins to sense and defend against viral pathogens. This knowledge will be useful in the design of treatments for viral diseases including influenza and Covid-19," he said.

NLRP1 has been known to scientists for years but its exact purpose was unknown. It is a member of a class called 'Nod-like Receptor' proteins that are sensors in the immune system that trigger the human body's response against invading pathogens.

When the team began their study in 2017, they hypothesised that NLRP1 serves as a sensor for viruses, because it is highly abundant in the human skin and lungs - surfaces that are commonly exposed to viral pathogens.

The team screened NLRP1 against several viruses to see if any would trigger the protein. After months of trials, they observed that an enzyme made by HRV called 3Cpro activated NLRP1 in human airway cells.

They saw that the 3Cpro enzyme cut into NLRP1 at a specific point, triggering a form of inflammatory 'cell death', which is an important process in rapidly clearing pathogens like HRV during an infection (see video).

Prof Reversade, who is also Professor of Genetics at Koç University in Istanbul, Turkey, said that pinpointing NLRP1's purpose marked a key step in understanding how our bodies react to HRV infections.

"There is immediate value from this finding, as we can better understand why an HRV infection could lead to complications in individuals with weaker immune systems, such as young children, the elderly, and those with asthma," said Prof Reversade.

He added that the value from this research could extend to other diseases caused by viruses of the same family.

"Targeting NLRP1 in patients is likely to provide therapeutic benefits in a number of human diseases. Our findings on the immune response to this class of viruses also bear relevance to Coxsackieviruses which are responsible for hand, foot, and mouth disease (HFMD) in young children."

Obese women have an increased risk of hip fracture earlier than others, already well before the age of 70, a new study from the University of Eastern Finland shows. The study followed 12,715 women for a period of 25 years. The new findings from the Osteoporosis Risk Factor and Prevention (OSTPRE) study were published in Osteoporosis International.

Launched at the University of Eastern Finland in 1989, the OSTPRE study is a population-based cohort study that recruited all women born in Kuopio Province, Eastern Finland, between 1932 and 1941. In the 25-year follow-up, the researchers analysed the association of body mass index (BMI) at the age of 58 with the risk of early hip fracture up until the age of 70. They also analysed the association of body mass index at the age of 70 with the risk of hip fracture later in life, up until the age of 83. The risk of hip fracture was examined in groups of normal-weight, overweight and obese women. Data on hip fractures, mechanisms of injury, and mortality were obtained from national health registers.

Normal weight was defined as a BMI of 25 or less, overweight as a BMI of 25-29.9, and obesity as a BMI of 30 or over (kg/m2). At baseline, 39.6 per cent of the women were normal-weight, 40 per cent were overweight, and 19.9 per cent were obese. A small fraction of the women (n=59, 0.5%) had a BMI below the normal range, i.e. less than 18.5 kg/m2. Ageing was associated with some increase in the BMI: at 70 years of age, 33.4% of the women were normal-weight, 40.9% were overweight, and 25.7% were obese.

As expected, the risk of hip fracture increased with age in all of the groups; however, the risk of early hip fracture increased faster in obese women, and slower in overweight women, than in others. In obese women, the probability of hip fracture was at 1% already at the age of 66.7, while in overweight women the 1% probability was reached 5.1 years later, at the age of 71.8. Obese women had a 2% probability of hip fracture 2.1 years earlier than overweight women, and a 4% probability 1.3 years earlier. The differences between the groups became smaller with ageing.

In obese women, hip fracture related mortality in five years after the incident was approximately 1.5 times higher than in others.

After around 75 years of age, the risk of hip fracture increased fastest in slender women whose BMI was at the lower end of normal weight. Women at the borderline between normal weight and overweight had the smallest risk all the way until old age.

The study also included a DXA bone density measurement of the hip and a related follow-up of a sub-sample of 3,136 women. At baseline, obese women had on average the highest bone density, but their bone loss was significantly faster than in others. Indeed, obese women in the lowest bone density tertile at baseline had a particularly high risk of hip fracture.

Some earlier studies have suggested that obesity could also be a factor that protects against hip fracture. However, the contradictory findings on the association of BMI with hip fracture seem to be dependent on which age group is being studied. Typically, follow-up times have been significantly shorter than those in the OSTPRE study.

"Based on this study, the risk of early hip fracture occurring before the age of 70 is clearly highest in obese women - and especially in obese women who have a below-average bone density. Later, after around 75 years of age, the risk increases fastest in slender women. Ageing women at the borderline between normal weight and overweight seem to have the lowest risk," Senior Researcher Toni Rikkonen from the University of Eastern Finland says.

The last decade has been marked by a series of remarkable discoveries identifying how the universe is composed. It is understood that the mysterious substance dark matter makes up 85% of the matter in the universe. Observable matter in the universe consists of ionized particles. Thus, a profound understanding of ionized matter and its interaction with light could lead to a deeper understanding of the relationships at play that formed the universe. While ionized matter, or plasma, is relatively easy to generate in the lab, studying it is extremely challenging as methods that can capture ionization states and density are virtually non-existant.

In a new paper published in Light Science & Application, a team of scientists, led by Professor Michael Zuerch from the University of California Berkeley, Department of Chemistry, and co-workers have succeeded in directly observing the formation and interaction of highly ionized krypton plasma using femtosecond coherent ultraviolet light and a novel four-dimensional model.

In their work, the researchers employ a laser-plasma amplifier, that uses eight-fold ionized krypton ions as laser medium. Then they launch a coherent extreme ultraviolet probe pulse into this plasma that picks up signatures of the plasma conditions as it propagates through the laser-generated plasma column.

"Using an extreme ultraviolet probe pulse with a wavelength short enough so that the plasma becomes transparent to interrogate the formed plasma is key," explains Zuerch.

This extreme ultraviolet probe pulse is then analyzed by diffracting it off a well-characterized nanoscale target. This method, known as coherent diffraction imaging, allows for measurement of the properties of the probe pulse carrying information about the plasma with very high resolution.

"Surprisingly, we found a non-trivial spatial modulation pattern that is unexpected in a waveguide geometry. Using an adapted ab initio theory modelling the plasma-light interaction in four dimensions across multiple scales we can find excellent agreement with our experimental data. This has allowed us to ascribe the observed signal to a strongly nonlinear behavior in laser-plasma interaction generating the highly-ionized krypton plasma," elaborates Zuerch.

The experimental approach, that can be easily adopted to other relevant scenarios, validates the advanced ab initio models used to simulate the laser-plasma interaction and more generally the formation of highly-ionized plasma. An important ramification of the findings shows that you cannot create arbitrarily ionized plasmas using optical techniques. The developed model will allow for predicting achievable conditions accurately and gives hope that very defined plasma conditions can be created by appropriate laser beam shaping.

Zuerch summarized the outlook of the work, "Beyond a more profound understanding of laser-plasma interactions, our findings have impacts, for example, on the upscaling of plasma-based X-ray light sources or plasma-based fusion experiments."

Meningococcus group B, the most prevalent strain of meningococcal infection, is prevented with 79 per cent effectiveness in children and young adults inoculated with the 4CMenB vaccine, also known as Bexsero, according to a new collaborative study from researchers in Portugal and the UK and led by the University of Bristol which evaluated the vaccine's performance in a real-world setting. The findings are published today [1 December] in the Journal of the American Medical Association (JAMA).

In 2015, the UK was the first country in the world to offer the 4CMenB vaccine free after recommendations from the Joint Committee on Vaccination and Immunisation (JCVI) that it should be included in the childhood immunisation schedule. Following the vaccine's UK roll-out, reductions in meningococcus group B disease cases have been observed in vaccine-eligible age groups but until now, no studies have conclusively demonstrated its effectiveness over time in the real-world using comparison of vaccination rates among cases with closely matched controls.

In this case-control study, a team led by Adam Finn, Professor of Paediatrics and Director of the Bristol Children's Vaccine Centre at Bristol Medical School, assessed the 4CMenB vaccine's effectiveness by analysing the immunisation and medical records of 117 children and young people across 31 paediatric hospitals in Portugal who had the disease between 2014 and 2019. In Portugal, medical records are linked electronically to immunisation records and contain the details of all vaccinations including those that are not in the country's national immunisation programme and only available through private clinics as was the 4CMenB vaccine over this period.

Ninety-eight children with lab-confirmed invasive meningococcal disease were included of whom 69 had group B and were old enough to have been fully immunised. Only seven per cent of this group had received the right number of vaccine doses as compared to 23 per cent of control children who did not have the disease - an observed effectiveness of nearly 80 per cent. Similar results were obtained when all strains of meningococcus were included in the analysis, raising the possibility that the vaccine may provide broader protection than against group B alone.

Of 11 children with meningococcal infection who had received at least one dose of the 4CMenB vaccine, all survived, and none were left with related disabilities. In contrast, among the remaining 87 cases who were unvaccinated, seven died and 16 suffered long term injuries, suggesting that the vaccinated cases may have been partially protected.

Professor Finn said: "Although rare, meningococcus group B infection can become life-threatening within hours and can cause long-term disabilities. Young children in particular are more at risk and may die or be seriously harmed even with top quality hospital treatment. This important new study confirms that 4CMenB offers children a very high level of protection against suffering severe outcomes from this potentially deadly infection."

CLEVELAND, Ohio (Nov. 30, 2020)--With a large percentage of women in the workplace aged between 40 and 59 years, the challenge of women managing menopause symptoms while at work is commonplace. A new study examined the relationship between the number of menopause symptoms and the job performance of working women. Study results are published online in Menopause, the journal of The North American Menopause Society (NAMS).

Menopause symptoms can affect women physically, psychologically, and sexually. A new study suggests they can also affect a woman's job performance. This study coming out of Japan included nearly 600 working women aged 45 to 65 years. Nearly 61% of these women were postmenopausal.

Researchers in the study found that a higher number of menopause symptoms were correlated with a lower work performance. More important, they found that working in an appropriate environment (one without high levels of stress) and maintaining a healthy lifestyle helped to reduce menopause symptoms. Conversely, they confirmed that women with numerous menopause symptoms were more likely to report a lack of exercise, chronic disease, and job-related stress.

Such results provide critical insights for employers. For instance, employers could consider taking a proactive role by creating more productive working environments for postmenopausal women suffering with hot flashes by lowering room temperatures and adapting dress codes to allow for lighter-weight, shorter-sleeved clothing. Employers could also offer stress management classes that would help all employees, including women struggling with mood changes as a result of fluctuating levels of estrogen. The researchers point out, however, that because women are reluctant to discuss their menopause symptoms with their supervisors, employers may be less likely to attempt to make modifications in the workplace.

Although this is not the only study to evaluate the effect of various menopause symptoms, such as hot flashes, on job performance, it is the first to specifically consider the number of menopause symptoms and how they affect productivity.

Results are published in the article "Relationship between number of menopause symptoms and work performance in Japanese working women."

"This study highlights a link between menopause symptom burden and lower work performance. Notably, women in this study who had more menopause-related symptoms also tended to be caregivers and to have chronic diseases. Although workplace modifications are one potential tactic to address this issue, appropriate treatment of menopause-related symptoms and counseling regarding caregiver stress may lead to improved overall health as well as improved work performance," says Dr. Stephanie Faubion, NAMS medical director.

New insight on how a parasite can resist current therapies has been published today in the open-access eLife journal.

The study in cultures of human cells infected with Trypanosoma cruzi (T. cruzi), the parasite that causes Chagas disease, suggests that its metabolic state influences the effectiveness of azole drugs that inhibit its growth. These findings could be useful for the development of more effective antimicrobial treatments.

Chagas disease, also known as American trypanosomiasis, can cause a sudden, brief (acute) illness, or it may be a long-lasting (chronic) condition. Around six to seven million people worldwide are estimated to be infected with the T. cruzi pathogen that causes the disease, according to the World Health Organization. Symptoms can range from mild to severe, but do not often appear until the chronic stage of disease.

"The goal for the treatment of Chagas and other infectious diseases is to eliminate the pathogen from the infected host," explains first author Peter Dumoulin, Postdoctoral Fellow at senior author Barbara Burleigh's lab, Harvard T. H. Chan School of Public Health, Boston, US. "There are a few ways in which pathogens can survive antimicrobial treatment. One of the less explored options is the impact of their metabolic and environmental diversity (or heterogeneity) on the effectiveness of a given treatment, and we wanted to find out if these factors play a role in T. cruzi's drug resistance."

There is an intracellular stage in the T. cruzi life-cycle where they become amastigotes - replicative forms of the parasite that persist in the infected host. The team's work revealed that the sensitivity of amastigotes to azole drugs increases significantly in the presence of certain concentrations of the amino acid glutamine, independent of the parasite's growth rate.

Further metabolic labelling and inhibitor studies showed that T. cruzi's glutamine metabolism leads to the enhanced production of steroid alcohols (sterols), along with an accompanying accumulation of non-standard sterols and toxicity to the parasite in the presence of azoles. These findings suggest that metabolic heterogeneity in the parasite-host interaction may contribute to the failure of some drugs to achieve sterile cure, demonstrating a novel link between metabolism and drug efficacy.

"Our work provides further evidence that the metabolic state of a microorganism is important for determining its susceptibility to antimicrobials, and lays the groundwork for further studies," concludes Burleigh, Professor of Immunology and Infectious Diseases at Harvard Chan School. "Gaining a better understanding of metabolism in T. cruzi and other parasites, and why current drug candidates can fail to treat infection, could lead to more effective therapies for Chagas disease and other infections."

CHARLOTTESVILLE, VA (DECEMBER 1, 2020). Researchers from multiple institutions in North America have developed a fully automated, deep-learning (DL), artificial-intelligence clinical tool that can measure the volume of cerebral ventricles on magnetic resonance images (MRIs) in children within about 25 minutes. The ability to track ventricular volume over time in a clinical setting will prove invaluable in the treatment of children and adults with hydrocephalus. Details on the development of the tool and its validation are reported today in a new article, "Artificial intelligence for automatic cerebral ventricle segmentation and volume calculation: a clinical tool for the evaluation of pediatric hydrocephalus," by Jennifer L. Quon, MD, and colleagues, in the Journal of Neurosurgery: Pediatrics .

Hydrocephalus is a pathological condition caused by an excessive amount of cerebrospinal fluid (CSF) in chambers of the brain known as ventricles. The condition results from an imbalance between the production and absorption of CSF. Hydrocephalus is called "communicating" when CSF can pass from one ventricle to another and "obstructive" when passage from one ventricle to another is blocked. The prevalence of pediatric hydrocephalus is approximately six in 10,000 live births. It has been called "the most common surgically correctable neurological problem in infants, children, and adolescents."

Diagnosis of hydrocephalus is based on clinical signs and symptoms as well as on findings of enlarged ventricles on neuroimaging studies. Placement of a shunt (an internal draining system that drains excess CSF away from the brain) is the most common surgical procedure performed to reduce hydrocephalus. Following surgery, patients must be monitored periodically to ensure that the shunt continues to work properly. Changes in ventricular volume can guide clinical decision-making. However, to date, accurate assessments of ventricular volume can be time consuming or require research-level automated tools that are not easily adapted to the patient's clinical visit.

The authors of this study sought to develop an automated deep-learning (DL)-based model that could be used to evaluate changes in the volume of brain ventricles over time in children with hydrocephalus during their clinic visits. Deep learning is an advanced form of artificial intelligence that mimics the workings of the human brain; it is capable of processing large quantities of data and creating patterns used in decision making. The authors' goal was to create a DL tool that would work efficiently in multiple institutions with various clinical MRI machines from different manufacturers.

To develop and validate the model, the authors selected sets of T2-weighted MRIs from a group of 200 pediatric patients (22 years of age or younger) who had presented with acute obstructive hydrocephalus. T2-weighted MRIs have wide clinical use but are not usually used to determine ventricular volume. The patients in this group had been treated at one of four institutions: Lucile Packard Children's Hospital Stanford; Seattle Children's Hospital; The Hospital for Sick Children; and Dayton Children's Hospital. For a control group, the authors selected 200 sets of T2-weighted MRIs from 199 neurologically intact pediatric patients. Three-dimensional T1-weighted MRIs, which had been obtained in all controls and a subset of patients with hydrocephalus, were also reviewed. Three-dimensional T1-weighted MRIs are commonly used for volumetric analysis but are not readily available in the clinic.

The 400 sets of T2-weighted MRIs were separated for use in various steps of the study: training (266 MRI sets) and optimization (67 MRI sets) of the DL model, and a held-out test (67 MRI sets) for final evaluation of the model's performance. In a separate study, the authors also studied the generalizability of the DL model and its clinical usefulness using T2-weighted MRIs that were prospectively obtained in nine patients at Utah Primary Children's Hospital.

The DL model was designed to produce automatic ventricle segmentation (delineation of ventricle borders on imaging) and volume calculation. To examine the efficiency of the model, the authors compared these two processes to the gold standard of manual segmentation and volume calculation and to the use of FreeSurfer research software. The authors used the Dice similarity coefficient (0 to 1) to assess segmentation accuracy and linear regression to assess volume calculation.

According to the authors, when compared to manual segmentation, "model segmentation performed with an overall Dice score of 0.901 (0.946 in hydrocephalus, 0.856 in controls)." These numbers show great accuracy, with even better accuracy evident when used in patients with hydrocephalus. When used to assess segmentation accuracy in the patients at Utah Primary Children's Hospital, the Dice score was 0.926.

The authors found a strong correlation between ventricular volume calculations made using the DL model and the manually determined frontal-occipital horn ratio (r2 = 0.92) and Evans' index, a frontal horn ratio (r2 = 0.79). These calculations were made using T2-weighted MRIs.

The DL model was more accurate and much faster than FreeSurfer software, which "took 8.2 to 207.3 hours (median 20.3 hours) for ventricle segmentation and volume output, compared with 1.48 seconds per patient scan for the DL model."

This work is still preliminary. Evidence provided using the DL model still requires correlation with patients' symptoms, and more work needs to be done to evaluate the DL model when used with other types of hydrocephalus. Nevertheless, the authors conclude, "With near-immediate volumetric output and reliable performance across institutional scanner types, this model can be adapted to the real-time clinical evaluation of hydrocephalus and improve clinician workflow."

When asked about the findings of the study, Drs. Edwards and Yeom responded, "It has been more than 100 years since Dandy developed ventriculography to visualize the ventricular system. Our goal was to develop a rapid, reliable program using AI [artificial intelligence] Technology that is fast, accurate, and deployable across multiple imaging platforms. Having definitive ventricular volumes will remove the labor and inaccuracy in measuring and comparing ventricular size over time and should allow more accurate decisions in managing patients with hydrocephalus and other CSF volume pathologies. Our goal moving forward is to validate our technique clinically in order to move this technique into routine clinical and research use. Our hope is that this technology will provide more accurate and reliable information to allow clinicians to make better management decisions in patients with hydrocephalus and thereby improve patient care and outcomes."