DNA methylation age is accelerated in alcohol dependence.

Alcohol dependence (ALC) is a chronic, relapsing disorder that increases the burden of chronic disease and significantly contributes to numerous premature deaths each year. Previous research suggests that chronic, heavy alcohol consumption is associated with differential DNA methylation patterns. In addition, DNA methylation levels at certain CpG sites have been correlated with age. We used an epigenetic clock to investigate the potential role of excessive alcohol consumption in epigenetic aging. We explored this question in five independent cohorts, including DNA methylation data derived from datasets from blood (n = 129, n = 329), liver (n = 92, n = 49), and postmortem prefrontal cortex (n = 46). One blood dataset and one liver tissue dataset of individuals with ALC exhibited positive age acceleration (p < 0.0001 and p = 0.0069, respectively), whereas the other blood and liver tissue datasets both exhibited trends of positive age acceleration that were not significant (p = 0.83 and p = 0.57, respectively). Prefrontal cortex tissue exhibited a trend of negative age acceleration (p = 0.19). These results suggest that excessive alcohol consumption may be associated with epigenetic aging in a tissue-specific manner and warrants further investigation using multiple tissue samples from the same individuals

Syndemics and the PrEP Cascade: Results from a Sample of Young Latino Men Who Have Sex with Men.

Young Latino men who have sex with men (MSM) are a highly vulnerable population for HIV infection. Pre-exposure prophylaxis (PrEP) is a novel biomedical HIV prevention tool that may aid in reducing the disparity in HIV incidence among Latino MSM. However, PrEP use is disproportionally low among Latino MSM and, therefore, identifying barriers along the PrEP continuum of care (the "PrEP cascade") would provide insight into how to best deploy PrEP interventions. Syndemics theory is a prominent framework employed in HIV prevention; however, to date, no known studies have applied this theory to PrEP. Thus, the aim of the current study was to explore the association between syndemics and the PrEP cascade, including the degree to which psychosocial and structural syndemic constructs are related to the PrEP cascade. Participants were 151 young Latino MSM (M age = 24 years; SD = 3) residing in San Diego, California, who completed a battery of online self-report measures. Results indicated high levels of syndemic indicators and varying levels of engagement across the PrEP cascade. As syndemic indicators increased, the odds of engagement across the PrEP cascade were significantly lowered. Psychosocial and structural syndemic factors accounted for unique variance in the PrEP cascade. Results highlight the need for combination interventions that address both psychosocial and structural barriers to PrEP use and persistence among young Latino MSM

Online media scans: Applying systematic review techniques to assess statewide human papillomavirus vaccination activities

Background. Although the human papillomavirus (HPV) vaccine has been approved for use in adolescents in the US for over a decade, vaccination uptake remains low. Of concern, HPV vaccine coverage is below the national average in Minnesota, USA. To understand the reach of current HPV programming and research, we use an online media scan; this method may be applied to other jurisdictions to gain insight about various public health issues.Design and Methods. This online media scan describes the nature and scope of ongoing activities to increase HPV vaccination in Minnesota. The media scan included: a) structured internet searches of HPV vaccine health education/promotion activities ongoing in Minnesota since 2013, and b) searches in research databases of the published literature on HPV vaccination in Minnesota from 2013 to 2018. Results. Searches resulted in 880 online and 142 research article matches, with 40 and 36 meeting selection criteria. Results were categorized by activities focusing on race/ethnicity, sex, health providers, parents, lesbian, gay, bisexual, transgender and queer or questioning (LGBTQ) populations, geographic location, catchup vaccination, and insurance status. Most activities were statewide (52% health education/promotion and 35% research), followed by activities located in entirely urban areas (15% health education/promotion and 41% research) with only 6% of health education/promotion activities and 2% of research activities carried out in entirely rural areas.Conclusions. A range of local and statewide HPV vaccine health education/promotion and research activities were identified in Minnesota. Several efforts partnered with American Indian and Somali/Somali-American communities, but fewer activities focused on HPV vaccination among LGBTQ youth and HPV vaccination in rural areas

Learning To Follow Directions in Street View

Navigating and understanding the real world remains a key challenge in machine learning and inspires a great variety of research in areas such as language grounding, planning, navigation and computer vision. We propose an instruction-following task that requires all of the above, and which combines the practicality of simulated environments with the challenges of ambiguous, noisy real world data. StreetNav is built on top of Google Street View and provides visually accurate environments representing real places. Agents are given driving instructions which they must learn to interpret in order to successfully navigate in this environment. Since humans equipped with driving instructions can readily navigate in previously unseen cities, we set a high bar and test our trained agents for similar cognitive capabilities. Although deep reinforcement learning (RL) methods are frequently evaluated only on data that closely follow the training distribution, our dataset extends to multiple cities and has a clean train/test separation. This allows for thorough testing of generalisation ability. This paper presents the StreetNav environment and tasks, models that establish strong baselines, and extensive analysis of the task and the trained agents

Inducing Error Management Culture – Evidence From Experimental Team Studies

Field studies indicate that error management culture can be beneficial for organizational performance. The question of whether and how error management culture can be induced remained unanswered. We conducted two experiments with newly formed teams, in which we aimed to induce error management culture and to explore whether we would also find beneficial effects of error management culture on performance in an experimental setting. Furthermore, we tested whether culture strength moderates the relationship between error management culture and performance. In Study 1, we used two tasks that require rational problem solving. In Study 2, we used a task that requires creative problem solving. We successfully manipulated error management culture in terms of an effect on perceived error management culture within the teams. While we did not find a direct effect of error management culture on performance, Study 2 revealed an indirect effect via communication in the teams. To our surprise, culture strength did not influence the hypothesized relationship. We discuss potential theoretical and alternative explanations for our results, and provide an outlook for future studies

Real-Time Mobile Detection of Drug Use with Wearable Biosensors: A Pilot Study

While reliable detection of illicit drug use is paramount to the field of addiction, current methods involving self-report and urine drug screens have substantial limitations that hinder their utility. Wearable biosensors may fill a void by providing valuable objective data regarding the timing and contexts of drug use. This is a preliminary observational study of four emergency department patients receiving parenteral opioids and one individual using cocaine in a natural environment. A portable biosensor was placed on the inner wrist of each subject, to continuously measure electrodermal activity (EDA), skin temperature, and acceleration. Data were continuously recorded for at least 5 min prior to drug administration, during administration, and for at least 30 min afterward. Overall trends in biophysiometric parameters were assessed. Injection of opioids and cocaine use were associated with rises in EDA. Cocaine injection was also associated with a decrease in skin temperature. Opioid tolerance appeared to be associated with a blunted physiologic response as measured by the biosensor. Laterality may be an important factor, as magnitude of response varied between dominant and nondominant wrists in a single patient with bilateral wrist measurements. Changes in EDA and skin temperature are temporally associated with intravenous administration of opioids and cocaine; the intensity of response, however, may vary depending on history and extent of prior use.University of Massachusetts Medical School. Department of Emergency MedicineNational Institute on Drug AbuseNational Institutes of Health (U.S.) (Grant R01DA033769-01

Genetically engineered pigs and target-specific immunomodulation provide significant graft survival and hope for clinical cardiac xenotransplantation

ObjectivesCardiac transplantation and available mechanical alternatives are the only possible solutions for end-stage cardiac disease. Unfortunately, because of the limited supply of human organs, xenotransplantation may be the ideal method to overcome this shortage. We have recently seen significant prolongation of heterotopic cardiac xenograft survival from 3 to 12 months and beyond.MethodsHearts from genetically engineered piglets that were alpha 1-3 galactosidase transferase knockout and expressed the human complement regulatory gene, CD46 (groups A-C), and the human thrombomodulin gene (group D) were heterotropically transplanted in baboons treated with antithymocyte globulin, cobra venom factor, anti-CD20 antibody, and costimulation blockade (anti-CD154 antibody [clone 5C8]) in group A, anti-CD40 antibody (clone 3A8; 20 mg/kg) in group B, clone 2C10R4 (25 mg/kg) in group C, or clone 2C10R4 (50 mg/kg) in group D, along with conventional nonspecific immunosuppressive agents.ResultsGroup A grafts (n = 8) survived for an average of 70 days, with the longest survival of 236 days. Some animals in this group (n = 3) developed microvascular thrombosis due to platelet activation and consumption, which resulted in spontaneous hemorrhage. The median survival time was 21 days in group B (n = 3), 80 days in group C (n = 6), and more than 200 days in group D (n = 5). Three grafts in group D are still contracting well, with the longest ongoing graft survival surpassing the 1-year mark.ConclusionsGenetically engineered pig hearts (GTKOhTg.hCD46.hTBM) with modified targeted immunosuppression (anti-CD40 monoclonal antibody) achieved long-term cardiac xenograft survival. This potentially paves the way for clinical xenotransplantation if similar survival can be reproduced in an orthotopic transplantation model

Probing the excited state nature of coordination complexes with blended organic and inorganic chromophores using vibrational spectroscopy

The use of transient vibrational spectroscopy in the analysis of rhenium(I) and ruthenium(II) complexes is discussed. Particular focus is given to the use resonance Raman spectroscopy to probe initial photoexcitation and transient resonance Raman and infrared spectroscopy to observe subsequent relaxation processes. The utility of these techniques is given by discussion of examples in which the electronic complexity of the system increases from systems which are nominally pure metal-to-ligand charge-transfer through to systems which have complex interplay between intraligand and metal-to-ligand charge transfer states. The use of these later systems in dye-sensitised solar cells is also briefly discussed

Integrating Natural Language Processing and Interpretive Thematic Analyses to Gain Human-Centered Design Insights on HIV Mobile Health: Proof-of-Concept Analysis

Background: HIV mobile health (mHealth) interventions often incorporate interactive peer-to-peer features. The user-generated content (UGC) created by these features can offer valuable design insights by revealing what topics and life events are most salient for participants, which can serve as targets for subsequent interventions. However, unstructured, textual UGC can be difficult to analyze. Interpretive thematic analyses can preserve rich narratives and latent themes but are labor-intensive and therefore scale poorly. Natural language processing (NLP) methods scale more readily but often produce only coarse descriptive results. Recent calls to advance the field have emphasized the untapped potential of combined NLP and qualitative analyses toward advancing user attunement in next-generation mHealth. Objective: In this proof-of-concept analysis, we gain human-centered design insights by applying hybrid consecutive NLP-qualitative methods to UGC from an HIV mHealth forum. Methods: UGC was extracted from Thrive With Me, a web app intervention for men living with HIV that includes an unstructured peer-to-peer support forum. In Python, topics were modeled by latent Dirichlet allocation. Rule-based sentiment analysis scored interactions by emotional valence. Using a no v el ranking standard, the experientially richest and most emotionally polarized segments of UGC were condensed and then analyzed thematically in Dedoose. Design insights were then distilled from these themes. Results: The refined topic model detected K=3 topics: A: disease coping; B: social adversities; C: salutations and check-ins. Strong intratopic themes included HIV medication adherence, survivorship, and relationship challenges. Negative UGC often involved strong negative reactions to external media events. Positive UGC often focused on gratitude for survival, well-being, and fellow users’ support. Conclusions: With routinization, hybrid NLP-qualitative methods may be viable to rapidly characterize UGC in mHealth environments. Design principles point to ward opportunities to align mHealth intervention features with the organically occurring uses captured in these analyses, for example, by foregrounding inspiring personal narratives and expressions of gratitude, or de-emphasizing anger-inducing media