Alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking

Twin studies indicate that additive genetic effects explain most of the variance in nicotine dependence (ND), a construct emphasizing habitual heavy smoking despite adverse consequences, tolerance and withdrawal. To detect ND alleles, we assessed cigarettes per day (CPD) regularly smoked, in two European populations via whole genome association techniques. In these approximately 7500 persons, a common haplotype in the CHRNA3-CHRNA5 nicotinic receptor subunit gene cluster was associated with CPD (nominal P=6.9 x 10(-5)). In a third set of European populations (n= approximately 7500) which had been genotyped for approximately 6000 SNPs in approximately 2000 genes, an allele in the same haplotype was associated with CPD (nominal P=2.6 x 10(-6)). These results (in three independent populations of European origin, totaling approximately 15 000 individuals) suggest that a common haplotype in the CHRNA5/CHRNA3 gene cluster on chromosome 15 contains alleles, which predispose to ND

Healthcare Professionals’ Perspectives on Improving Dietary Supplement Documentation in the Electronic Medical Record: Current Challenges and Opportunities to Enhance Quality of Care and Patient Safety

Background Around half the US population uses dietary supplements (DS), and concomitant use with medications is common. Many DS include bioactive substances that can interact with medications; therefore, accurate tracking is critical for patient safety. Unfortunately, documentation of patients’ DS use is often missing or incomplete in the electronic medical record (EMR), leaving patients susceptible to potential adverse events. Novel approaches to assist healthcare professionals (HCPs) in capturing patients’ DS use are needed. Objective To assess HCPs’ perspectives on challenges and facilitators of DS documentation in the EMR and their opinions on a proposed mHealth application (app) to aid in DS capture. Methods HCPs, recruited from professional networks, largely in North Carolina, using purposive sampling, took part in semi-structured interviews. We inquired about HCPs’ experiences with DS documentation in the EMR and their opinions about our proposed mHealth app. Interviews were recorded, transcribed, and coded. Thematic analysis included deductive codes based on the interview guide, and inductive codes that emerged during transcript review. Results HCPs (N = 30) included 60% females, mean age 46 ± 10; 70% White. Pharmacists (20%), nurses (17%), and physicians (17%) were the most represented professions. Years in practice ranged from 3–35 years. Most HCPs were concerned about DS safety and potential supplement-drug interactions, and cited several barriers to accurate EMR DS documentation including time constraints, database inconsistencies, and poor patient-HCP communication about DS. HCPs’ views on our proposed mHealth app were generally positive. They expressed that our proposed mHealth app could streamline documentation processes and enhance patient-provider communication. HCPs expressed desire for a high-quality mHealth app that includes access to evidence-based DS information, integrates with the EMR, and does not increase time burdens. Conclusion HCPs believe documentation of patients’ DS use is important but not accurately captured in the EMR. Support was expressed for our proposed barcode-scanning DS mHealth app

Relationship between Maternal Clinical Factors and Mother-Reported Child Problems

Maternal depression has been associated with mothers’ elevated reports of child problems. However, it is unclear the extent to which elevations in mother ratings reflect having a depression diagnosis, having any mental illness diagnosis, or having a diagnosis vs. symptom levels. As part of a NIMH-funded, longitudinal study of mothers with serious mental illness ( N =379), we examined the relationship between mother-reported adolescent behavior problems ( N =78) and maternal depression vs. other diagnoses, as well as the effects of depression diagnosis vs. symptom levels. Mothers were recruited from the public mental health system in an urban area, and are primarily African-American and low income. We found that maternal psychiatric symptoms made a unique and significant contribution to explaining the variance in mother-reported child problems, independent of controls (e.g., teacher reports and child demographics), while maternal diagnosis did not. Implications of findings are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44321/1/10597_2005_Article_6425.pd

PDE8 Regulates Rapid Teff Cell Adhesion and Proliferation Independent of ICER

BACKGROUND: Abolishing the inhibitory signal of intracellular cAMP by phosphodiesterases (PDEs) is a prerequisite for effector T (Teff) cell function. While PDE4 plays a prominent role, its control of cAMP levels in Teff cells is not exclusive. T cell activation has been shown to induce PDE8, a PDE isoform with 40- to 100-fold greater affinity for cAMP than PDE4. Thus, we postulated that PDE8 is an important regulator of Teff cell functions. METHODOLOGY/PRINCIPAL FINDINGS: We found that Teff cells express PDE8 in vivo. Inhibition of PDE8 by the PDE inhibitor dipyridamole (DP) activates cAMP signaling and suppresses two major integrins involved in Teff cell adhesion. Accordingly, DP as well as the novel PDE8-selective inhibitor PF-4957325-00 suppress firm attachment of Teff cells to endothelial cells. Analysis of downstream signaling shows that DP suppresses proliferation and cytokine expression of Teff cells from Crem-/- mice lacking the inducible cAMP early repressor (ICER). Importantly, endothelial cells also express PDE8. DP treatment decreases vascular adhesion molecule and chemokine expression, while upregulating the tight junction molecule claudin-5. In vivo, DP reduces CXCL12 gene expression as determined by in situ probing of the mouse microvasculature by cell-selective laser-capture microdissection. CONCLUSION/SIGNIFICANCE: Collectively, our data identify PDE8 as a novel target for suppression of Teff cell functions, including adhesion to endothelial cells

Drinking to ease the burden: a cross-sectional study on trauma, alcohol abuse and psychopathology in a post-conflict context

Ertl V, Saile R, Neuner F, Catani C. Drinking to ease the burden: a cross-sectional study on trauma, alcohol abuse and psychopathology in a post-conflict context. BMC Psychiatry. 2016;16(1): 202.Background It is likely that alcohol use and abuse increase during and after violent conflicts. The most prominent explanation of this phenomenon has been referred to as self-medication hypothesis. It predicts that psychotropic substances are consumed to deal with conflict-related psychic strains and trauma. In northern Uganda, a region that has been affected by a devastating civil war and is characterized by high levels of alcohol abuse we examined the associations between war-trauma, childhood maltreatment and problems related to alcohol use. Deducing from the self-medication hypothesis we assumed alcohol consumption moderates the relationship between trauma-exposure and psychopathology. Methods A cross-sectional epidemiological survey targeting war-affected families in post-conflict northern Uganda included data of male (n = 304) and female (n = 365) guardians. We used standardized questionnaires in an interview format to collect data on the guardians’ socio-demography, trauma-exposure, alcohol consumption and symptoms of alcohol abuse, PTSD and depression. Results Symptoms of current alcohol use disorders were present in 46 % of the male and 1 % of the female respondents. A multiple regression model revealed the unique contributions of emotional abuse in the families of origin and trauma experienced outside the family-context in the prediction of men’s alcohol-related symptoms. We found that alcohol consumption moderated the dose-effect relationship between trauma-exposure and symptoms of depression and PTSD. Significant interactions indicated that men who reported more alcohol-related problems experienced less increase in symptoms of PTSD and depression with increasing trauma-exposure. Conclusions The gradual attenuation of the dose-effect the more alcohol-related problems were reported is consistent with the self-medication hypothesis. Hence, the functionality of alcohol consumption has to be considered when designing and implementing addiction treatment in post-conflict contexts

Community Violence and Youth: Affect, Behavior, Substance Use, and Academics

Community violence is recognized as a major public health problem (WHO, World Report on Violence and Health,2002) that Americans increasingly understand has adverse implications beyond inner-cities. However, the majority of research on chronic community violence exposure focuses on ethnic minority, impoverished, and/or crime-ridden communities while treatment and prevention focuses on the perpetrators of the violence, not on the youth who are its direct or indirect victims. School-based treatment and preventive interventions are needed for children at elevated risk for exposure to community violence. In preparation, a longitudinal, community epidemiological study, The Multiple Opportunities to Reach Excellence (MORE) Project, is being fielded to address some of the methodological weaknesses presented in previous studies. This study was designed to better understand the impact of children’s chronic exposure to community violence on their emotional, behavioral, substance use, and academic functioning with an overarching goal to identify malleable risk and protective factors which can be targeted in preventive and intervention programs. This paper describes the MORE Project, its conceptual underpinnings, goals, and methodology, as well as implications for treatment and preventive interventions and future research

The Potential Observation Network Design with Mesoscale Ensemble Sensitivities in Complex Terrain

Observation network design requires some framework for sensitivity studies. The goal is to place observations where they will reduce forecast error the most. We use uncertainty estimates from our best forecast models as an indicator of forecast error. The first step is then to find initial-state perturbations that reduce forecast uncertainty by minimizing a user-dependent norm. Adjoint models have helped meet this challenge for decades. More recently, ensemble sensitivities have emerged as a powerful alternative to adjoint models. Under the conditions of Gaussian statistics and an infinite ensemble, lagged covariances from an ensemble can be used equivalently to an adjoint model to give the least-squares minimization of a given cost function. One practical advantage is that costly development and maintenance of tangent linear and adjoint models are avoided. Ensemble sensitivities have been shown to be an effective alternative to adjoint models. They have been used successfully to diagnose predictors of forecast error in synoptic storms, extratropical transition and developing hurricanes. Because they rely on lagged covariances from a finite-sized ensemble, they are subject to sampling error and spurious covariances. However, their efficacy for high-resolution forecasts in mountainous environments has not been thoroughly explored. We present results from experiments designed to establish the potential for ensemble sensitivity computations with a high resolution mesoscale model (grid spacing 4 km) in complex terrain. Using the Weather Research and Forecast (WRF) model and the Data Assimilation Research Testbed (DART) we compute sensitivities with cost functions defined to emphasize parameters affecting fog forecasting in the boundary layer. High sensitivities are interpreted as indicating low predictability for forecasting in the mountains. Results from convergence studies reveal the ensemble sizes needed to robustly estimate the sensitivities. We comment on the implications of results for observation placement and on the expected impact of model inadequacy.http://archive.org/details/thepotentialobse109456774Captain, United States Air Forc

The potential utility of high-resolution ensemble sensitivity analysis for observation placement during weak flow in complex terrain

The article of record as published may be found at http://dx.doi.org/10.1175/WAF-D-14-00066.1Expansion in the availability of relocatable near-surface atmospheric observing sensors introduces the question of where placement maximizes gain in forecast accuracy. As one possible method of addressing observation placement, the performance of ensemble sensitivity analysis (ESA) is examined for high-resolution (Dx 5 4 km) predictions in complex terrain and during weak flow. ESA can be inaccurate when the underlying assumptions of linear dynamics (and Gaussian statistics) are violated, or when the sensitivity cannot be robustly sampled. A case study of a fog event at Salt Lake City International Airport (KSLC) in Utah provides a useful basis for examining these issues, with the additional influence of complex terrain. A realistic upper-air observing network is used in perfect-model ensemble data assimilation experiments, providing the statistics for ESA. Results show that water vapor mixing ratios over KSLC are sensitive to potential temperature on the first model layer tens of kilometers away, 6 h prior to verification and prior to the onset of fog. Potential temperatures indicate inversion strength in the Salt Lake basin; the ESA predicts southerly flow and strengthened inversions will increase water vapor over KSLC. Linearity tests show that the nonlinear response is about twice the expected response. Experiments with smaller ensembles show that qualitatively similar conclusions about the sensitivity pattern can be reached with ensembles as small as 48 members, but smaller ensembles do not produce accurate sensitivity estimates. Taken together, the results motivate a closer look at the fundamental characteristics of ESA when dynamics (and therefore correlations) are weak.This research was funded in part by the Office of Naval Research under the Mountain Terrain Atmospheric Modeling and Observations (MATERHORN) program