Diffusion and jump-length distribution in liquid and amorphous Cu33_{33}Zr67_{67}

Using molecular dynamics simulation, we calculate the distribution of atomic jum ps in Cu$_{33}$Zr$_{67}$ in the liquid and glassy states. In both states the distribution of jump lengths can be described by a temperature independent exponential of the length and an effective activation energy plus a contribution of elastic displacements at short distances. Upon cooling the contribution of shorter jumps dominates. No indication of an enhanced probability to jump over a nearest neighbor distance was found. We find a smooth transition from flow in the liquid to jumps in the g lass. The correlation factor of the diffusion constant decreases with decreasing temperature, causing a drop of diffusion below the Arrhenius value, despite an apparent Arrhenius law for the jump probability

Methylation of MTHFR Moderates the Effect of Smoking on Genomewide Methylation Among Middle Age African Americans

Differential methylation at MTHFR (mMTHFR) has been examined previously as a moderator of changes in methylation among nascent smokers, but the effects of mMTHFR on genomewide patterns of methylation among established smokers in middle age are unknown. In the current investigation we examined a sample of 180 African American middle-aged smokers and non-smokers to test for patterns indicative of three different potential mechanisms of impact on epigenetic remodeling in response to long-term smoking. We found that mMTHFR moderated the association between smoking and changes in methylation for more than 25% of the 909 loci previously identified as being associated with smoking at a genomewide level of significance in middle-aged African Americans. Observed patterns of effect indicated amplification of both hyper and hypo methylating responses to smoking among those with lower mMTHFR. Moderating effects were robust to controls for sex, age, diet, and cell-type variation. Implications for potential mechanisms conferring effects are discussed. Of particular potential practical importance was a strong effect of mMTHFR on hypomethylation at GPR15 in response to smoking, indicative of the differential impact of MTHFR activity on changes in a specific cell population linked to inflammatory disease in smokers

Education and older adults at the University of the Third Age

This article reports a critical analysis of older adult education in Malta. In educational gerontology, a critical perspective demands the exposure of how relations of power and inequality, in their myriad forms, combinations, and complexities, are manifest in late-life learning initiatives. Fieldwork conducted at the University of the Third Age (UTA) in Malta uncovered the political nature of elder-learning, especially with respect to three intersecting lines of inequality - namely, positive aging, elitism, and gender. A cautionary note is, therefore, warranted at the dominant positive interpretations of UTAs since late-life learning, as any other education activity, is not politically neutral.peer-reviewe

Impact of child sex abuse on adult psychopathology: A genetically and epigenetically informed investigation

Genetic, environmental, and epigenetic influences and their transactions were examined in a sample of 155 women from the Iowa adoptee sample who had been removed from their biological parents shortly after birth and assessed when participants were an average of 41.10 years old. We observed an interactive effect of child sex abuse (CSA) and biological parent psychopathology (i.e., genetic load) on substance abuse as well as a main effect of CSA on substance abuse in adulthood. We also observed main effects of CSA and genetic load on depression and on antisocial characteristics. As predicted, CSA, but not genetic load or later substance abuse, was associated with epigenetic change. In addition, the interaction between genetic load and CSA predicted epigenetic change, indicating a potential genetic basis for a differential impact of CSA on epigenetic change. Finally, epigenetic change partially mediated the effect of CSA on antisocial characteristics. The results suggest the relevance of genetic and epigenetic processes for future theorizing regarding marital and family precursors of several forms of adult psychopathology. Implications for preventive intervention are discussed

Establishing a generalized polyepigenetic biomarker for tobacco smoking

Large-scale epigenome-wide association meta-analyses have identified multiple 'signatures'' of smoking. Drawing on these findings, we describe the construction of a polyepigenetic DNA methylation score that indexes smoking behavior and that can be utilized for multiple purposes in population health research. To validate the score, we use data from two birth cohort studies: The Dunedin Longitudinal Study, followed to age-38 years, and the Environmental Risk Study, followed to age-18 years. Longitudinal data show that changes in DNA methylation accumulate with increased exposure to tobacco smoking and attenuate with quitting. Data from twins discordant for smoking behavior show that smoking influences DNA methylation independently of genetic and environmental risk factors. Physiological data show that changes in DNA methylation track smoking-related changes in lung function and gum health over time. Moreover, DNA methylation changes predict corresponding changes in gene expression in pathways related to inflammation, immune response, and cellular trafficking. Finally, we present prospective data about the link between adverse childhood experiences (ACEs) and epigenetic modifications; these findings document the importance of controlling for smoking-related DNA methylation changes when studying biological embedding of stress in life-course research. We introduce the polyepigenetic DNA methylation score as a tool both for discovery and theory-guided research in epigenetic epidemiology.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.The Dunedin Longitudinal Study is funded by the New Zealand Health Research Council, the New Zealand Ministry of Business, Innovation, and Employment, the National Institute on Aging (AG032282), and the Medical Research Council (MR/P005918/1). The E-Risk Study is funded by the Medical Research Council (G1002190) and the National Institute of Child Health and Human Development (HD077482). Additional support was provided by a Distinguished Investigator Award from the American Asthma Foundation to Dr. Mill, and by the Jacobs Foundation and the Avielle Foundation. Dr. Arseneault is the Mental Health Leadership Fellow for the U.K. Economic and Social Research Council. Dr. Belsky is a Jacobs Foundation Fellow. This work used a high-performance computing facility partially supported by grant 2016-IDG-1013 (“HARDAC + : Reproducible HPC for Next-generation Genomics”) from the North Carolina Biotechnology Center. Illumina DNA methylation data are accessible from the Gene Expression Omnibus (accession code: GSE105018).pre-print, post-print, publisher's PD

Serotonin tranporter methylation and response to cognitive behaviour therapy in children with anxiety disorders

Anxiety disorders that are the most commonly occurring psychiatric disorders in childhood, are associated with a range of social and educational impairments and often continue into adulthood. Cognitive behaviour therapy (CBT) is an effective treatment option for the majority of cases, although up to 35-45% of children do not achieve remission. Recent research suggests that some genetic variants may be associated with a more beneficial response to psychological therapy. Epigenetic mechanisms such as DNA methylation work at the interface between genetic and environmental influences. Furthermore, epigenetic alterations at the serotonin transporter (SERT) promoter region have been associated with environmental influences such as stressful life experiences. In this study, we measured DNA methylation upstream of SERT in 116 children with an anxiety disorder, before and after receiving CBT. Change during treatment in percentage DNA methylation was significantly different in treatment responders vs nonresponders. This effect was driven by one CpG site in particular, at which responders increased in methylation, whereas nonresponders showed a decrease in DNA methylation. This is the first study to demonstrate differences in SERT methylation change in association with response to a purely psychological therapy. These findings confirm that biological changes occur alongside changes in symptomatology following a psychological therapy such as CBT

A mixed‐methods analysis of younger adults\u27 perceptions of asthma, self‐management, and preventive care: This isn\u27t helping me none

Background: Young adults (ages 18‐44) have increased emergency department use for asthma and poor adherence to medications. The objective of this mixed‐methods study was to understand experiences with and approaches to managing asthma, of which little is known in this age group. Methods: Surveys (Asthma Control Questionnaire, Asthma Quality of Life Questionnaire) and 1:1 semi‐structured interviews were used to explore experiences with asthma, symptoms, self‐management behaviors, and relationship to asthma control and quality of life. Qualitative data were analyzed using content analysis techniques. Descriptive statistics and bivariate correlations were used to examine distributive characteristics and associations between variables. Results: Forty urban adults participated (mean age 32.7 ± 6.2, 1σ). Coughing was reported nearly 46% more often than wheezing, with 42.5% (17/40) coughing until the point of vomiting most days. Most participants delayed using medication for symptoms due to misperceptions about inhalers. Higher symptom frequency and worse asthma control were associated with greater use of non‐pharmacologic symptom management strategies (r=0.645, p\u3c0.001; r=0.360, p=0.022, respectively). Five themes were identified regarding young adults experiences with asthma: (1) having asthma means being limited and missing out on life; (2) healthcare for asthma is burdensome and other things are more important; (3) there is not enough personal benefit in medical interactions to make preventive care worthwhile; (4) there is insufficient support and education about asthma for adults; and (5) people normalize chronic symptoms over time and find ways of coping that fit with their lifestyle. Conclusions & Clinical Relevance: Young adults may tolerate symptoms without using quick‐relief medication or seeking preventive care. Increasing engagement with preventive services will require decreasing perceived burdens and increasing the personal benefits of care. Evaluating for non‐pharmacologic approaches to managing symptoms and asthma‐related coughing may identify uncontrolled asthma. Enhanced training for clinicians in patient‐centric asthma care may be needed

Going Mobile with Primary Care: Smartphone-Telemedicine for Asthma Management in Young Urban Adults (TEAMS)

Background: The majority of adults with persistent asthma have chronically uncontrolled disease and interventions to improve outcomes are needed. We evaluated the efficacy, feasi- bility, and acceptability of a multi-component smartphone-telemedicine program (TEAMS) to deliver asthma care remotely, support provider adherence to asthma management guide- lines, and improve patient outcomes. Methods: TEAMS utilized: (1) remote symptom monitoring, (2) nurse-led smartphone-tele- medicine with self-management training for patients, and (3) Electronic medical record- based clinical decision support software. Adults aged 18-44 (N=33) and primary care providers (N=4) were recruited from a safety-net practice in Upstate New York. Asthma con- trol, quality of life, and FEV1 were measured at 0, 3 and 6 months. Acceptability was assessed via survey and end-of-study interviews. Paired t-test and mixed effects modeling were used to evaluate the effect of the intervention on asthma outcomes. Results: At baseline, 80% of participants had uncontrolled asthma. By 6-months, 80% classi- fied as well-controlled. Improvements in control and quality of life were large (d=1.955, d=1.579). FEV%pred increased 4.2% (d=1.687) with the greatest gain in males, smokers, and lower educational status. Provider adherence to national guidelines increased from 43.3% to 86.7% (CI = 22.11-64.55) and patient adherence to medication increased from 45.58% to 85.29% (CI = 14.79-64.62). Acceptability was 95.7%; In follow up interviews, 29/30 patients and all providers indicated TEAMS worked better than usual care, supported effective self- management, and reduced symptoms over time, which led to greater self-efficacy and motivation to manage asthma. Discussion: Based on these findings, we conclude that smartphone telemedicine could substantially improve clinical asthma management, adherence to guidelines, and patient outcomes