International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations

The guinea pig ileum lacks the direct, high-potency, M2-muscarinic, contractile mechanism characteristic of the mouse ileum

We explored whether the M2 muscarinic receptor in the guinea pig ileum elicits a highly potent, direct-contractile response, like that from the M3 muscarinic receptor knockout mouse. First, we characterized the irreversible receptor-blocking activity of 4-DAMP mustard in ileum from muscarinic receptor knockout mice to verify its M3 selectivity. Then, we used 4-DAMP mustard to inactivate M3 responses in the guinea pig ileum to attempt to reveal direct, M2 receptor-mediated contractions. The muscarinic agonist, oxotremorine-M, elicited potent contractions in ileum from wild-type, M2 receptor knockout, and M3 receptor knockout mice characterized by negative log EC50 (pEC50) values ± SEM of 6.75 ± 0.03, 6.26 ± 0.05, and 6.99 ± 0.08, respectively. The corresponding Emax values in wild-type and M2 receptor knockout mice were approximately the same, but that in the M3 receptor knockout mouse was only 36% of wild type. Following 4-DAMP mustard treatment, the concentration–response curve of oxotremorine-M in wild-type ileum resembled that of the M3 knockout mouse in terms of its pEC50, Emax, and inhibition by selective muscarinic antagonists. Thus, 4-DAMP mustard treatment appears to inactivate M3 responses selectively and renders the muscarinic contractile behavior of the wild-type ileum similar to that of the M3 knockout mouse. Following 4-DAMP mustard treatment, the contractile response of the guinea pig ileum to oxotremorine-M exhibited low potency and a competitive-antagonism profile consistent with an M3 response. The guinea pig ileum, therefore, lacks a direct, highly potent, M2-contractile component but may have a direct, lower potency M2 component

BARD : a structured technique for group elicitation of Bayesian networks to support analytic reasoning

In many complex, real-world situations, problem solving and decision making require effective reasoning about causation and uncertainty. However, human reasoning in these cases is prone to confusion and error. Bayesian networks (BNs) are an artificial intelligence technology that models uncertain situations, supporting better probabilistic and causal reasoning and decision making. However, to date, BN methodologies and software require (but do not include) substantial upfront training, do not provide much guidance on either the model building process or on using the model for reasoning and reporting, and provide no support for building BNs collaboratively. Here, we contribute a detailed description and motivation for our new methodology and application, Bayesian ARgumentation via Delphi (BARD). BARD utilizes BNs and addresses these shortcomings by integrating (1) short, high-quality e-courses, tips, and help on demand; (2) a stepwise, iterative, and incremental BN construction process; (3) report templates and an automated explanation tool; and (4) a multiuser web-based software platform and Delphi-style social processes. The result is an end-to-end online platform, with associated online training, for groups without prior BN expertise to understand and analyze a problem, build a model of its underlying probabilistic causal structure, validate and reason with the causal model, and (optionally) use it to produce a written analytic report. Initial experiments demonstrate that, for suitable problems, BARD aids in reasoning and reporting. Comparing their effect sizes also suggests BARD's BN-building and collaboration combine beneficially and cumulatively

Periodontal disease and atherosclerotic vascular disease: Does the evidence support an independent association?: A scientific statement from the American heart association

A link between oral health and cardiovascular disease has been proposed for more than a century. Recently, concern about possible links between periodontal disease (PD) and atherosclerotic vascular disease (ASVD) has intensified and is driving an active field of investigation into possible association and causality. The 2 disorders share several common risk factors, including cigarette smoking, age, and diabetes mellitus. Patients and providers are increasingly presented with claims that PD treatment strategies offer ASVD protection; these claims are often endorsed by professional and industrial stakeholders. The focus of this review is to assess whether available data support an independent association between ASVD and PD and whether PD treatment might modify ASVD risks or outcomes. It also presents mechanistic details of both PD and ASVD relevant to this topic. The correlation of PD with ASVD outcomes and surrogate markers is discussed, as well as the correlation of response to PD therapy with ASVD event rates. Methodological issues that complicate studies of this association are outlined, with an emphasis on the terms and metrics that would be applicable in future studies. Observational studies to date support an association between PD and ASVD independent of known confounders. They do not, however, support a causative relationship. Although periodontal interventions result in a reduction in systemic inflammation and endothelial dysfunction in short-term studies, there is no evidence that they prevent ASVD or modify its outcomes

Links Between Communication and Relationship Satisfaction Among Patients With Cancer and Their Spouses: Results of a Fourteen-Day Smartphone-Based Ecological Momentary Assessment Study

Cancer treatment poses significant challenges not just for those diagnosed with the disease but also for their intimate partners. Evidence suggests that couples' communication plays a major role in the adjustment of both individuals and in the quality of their relationship. Most descriptive studies linking communication to adjustment have relied on traditional questionnaire methodologies and cross-sectional designs, limiting external validity and discernment of temporal patterns. Using the systemic-transactional model of dyadic coping as a framework, we examined intra- and inter-personal associations between communication (both enacted and perceived) and relationship satisfaction (RS) among patients with stage II–IV breast or colorectal cancer and their spouses (N = 107 couples). Participants (mean age = 51, 64.5% female patients, and 37.4% female spouses) independently completed twice-daily ecological momentary assessments (EMA) via smartphone for 14 consecutive days. Items assessed RS and communication (expression of feelings, holding back from expression, support and criticism of partner, and parallel ratings of partner behavior). Linear mixed models employing an Actor Partner Interdependence Model were used to examine concurrent, time-lagged, and cross-lagged associations between communication and RS. Expressing one's feelings was unassociated with RS. Holding back from doing so, in contrast, was associated with lower RS for both patients and spouses in concurrent models. These effects were both intrapersonal and interpersonal, meaning that when individuals held back from expressing their feelings, they reported lower RS and so too did their partner. Giving and receiving support were associated with one's own higher RS for both patients and spouses in concurrent models, and for patients in lagged models. Conversely, criticizing one's partner and feeling criticized were maladaptive, associated with lower RS (own and in some cases, partner's). Cross-lagged analyses (evening RS to next-day afternoon communication) yielded virtually no effects, suggesting that communication may have a stronger influence on short-term RS than the reverse. Findings underscore the importance of responsive communication, more so than expression per se, in explaining both concurrent and later relationship adjustment. In addition, a focus on holding back from expressing feelings may enhance the understanding of RS for couples coping with cancer

Couple Communication in Cancer: Protocol for a Multi-Method Examination

Cancer and its treatment pose challenges that affect not only patients but also their significant others, including intimate partners. Accumulating evidence suggests that couples’ ability to communicate effectively plays a major role in the psychological adjustment of both individuals and the quality of their relationship. Two key conceptual models have been proposed to account for how couple communication impacts psychological and relationship adjustment: the social-cognitive processing (SCP) model and the relationship intimacy (RI) model. These models posit different mechanisms and outcomes, and thus have different implications for intervention. The purpose of this project is to test and compare the utility of these models using comprehensive and methodologically rigorous methods. Aims are: (1) to examine the overall fit of the SCP and RI models in explaining patient and partner psychological and relationship adjustment as they occur on a day-to-day basis and over the course of 1 year; (2) to examine the fit of the models for different subgroups (males vs. females, and patients vs. partners); and (3) to examine the utility of various methods of assessing communication by examining the degree to which baseline indices from different measurement strategies predict self-reported adjustment at 1-year follow up. The study employs a longitudinal, multi-method approach to examining communication processes including: standard self-report questionnaires assessing process and outcome variables collected quarterly over the course of 1 year; smartphone-based ecological momentary assessments to sample participant reports in real time; and laboratory-based couple conversations from which we derive observational measures of communicative behavior and affective expression, as well as vocal indices of emotional arousal. Participants are patients with stage II-IV breast, colon, rectal, or lung cancer and their spouses/partners, recruited from two NCI-designated comprehensive cancer centers. Results will be published in scientific journals, presented at scientific conferences, and conveyed to a larger audience through infographics and social media outlets. Findings will inform theory, measurement, and the design and implementation of efficacious interventions aimed at optimizing both patient and partner well-being