Military Combat and Risk of Coronary Heart Disease and Ischemic Stroke in Aging Men: The Atherosclerosis Risk in Communities (ARIC) Study

To assess the long-term association of military combat stress with coronary heart disease (CHD) and ischemic stroke (IS)

The impact of water on slip system activity in olivine and the formation of bimodal crystallographic preferred orientations

Crystallographic preferred orientations (CPOs) in olivine are widely used to infer the mechanisms, conditions, and kinematics of deformation of mantle rocks. Recent experiments on water-saturated olivine were the first to produce a complex CPO characterised by bimodal orientation distributions of both [100] and [001] axes and inferred to form by combined activity of (001)[100], (100)[001], and (010)[100] slip. This result potentially provides a new microstructural indicator of deformation in the presence of elevated concentrations of intracrystalline hydrous point defects and has implications for the interpretation of seismic anisotropy. Here, we document a previously unexplained natural example of this CPO type in a xenolith from Lesotho and demonstrate that it too may be explained by elevated concentrations of hydrous point defects. We test and confirm the hypothesis that combined (001)[100], (100)[001], and (010)[100] slip were responsible for formation of this CPO by (1) using high-angular resolution electron backscatter diffraction to precisely characterise the dislocation types present in both the experimental and natural samples and (2) employing visco-plastic self-consistent simulations of CPO evolution to assess the ability of these slip systems to generate the observed CPO. Finally, we utilise calculations based on effective-medium theory to predict the anisotropy of seismic wave velocities arising from the CPO of the xenolith. Maxima in S-wave velocities and anisotropy are parallel to both the shear direction and shear plane normal, whereas maxima in P-wave velocities are oblique to both, adding complexity to interpretation of deformation kinematics from seismic anisotropy.D. Wallis, L.N. Hansen, and A.J. Wilkinson acknowledge support from the Natural Environment Research Council Grant NE/M000966/1. M. Tasaka acknowledges support through a JSPS Research Fellowship for Young Scientists (26-4879) and the Japan Society for the Promotion of Science (16K17832). D.L. Kohlstedt acknowledges support through NASA Grant NNX15AL53G. K.M. Kumamoto acknowledges support through NSF Division of Earth Science grants 1255620 and 1625032

Military combat and burden of subclinical atherosclerosis in middle aged men: The ARIC Study

Studies of the cardiovascular consequences of combat stress are few and inconclusive

Medication, reperfusion therapy and survival in a community-based setting of hospitalised myocardial infarction

To examine the survival benefit of multiple medical therapies in a large, community-based population of validated myocardial infarction (MI) events

Codesigning a Measure of Person-Centred Coordinated Care to Capture the Experience of the Patient: The Development of the P3CEQ

Background: Person-centred coordinated care (P3C) is a priority for stakeholders (ie, patients, carers, professionals, policy makers). As a part of the development of an evaluation framework for P3C, we set out to identify patient-reported experience measures (PREMs) suitable for routine measurement and feedback during the development of services. Methods: A rapid review of the literature was undertaken to identity existing PREMs suitable for the probing person-centred and/or coordinated care. Of 74 measures identified, 7 met our inclusion criteria. We critically examined these against core domains and subdomains of P3C. Measures were then presented to stakeholders in codesign workshops to explore acceptability, utility, and their strengths/weaknesses. Results: The Long-Term Condition 6 questionnaire was preferred for its short length, utility, and tone. However, it lacked key questions in each core domain, and in response to requests from our codesign group, new questions were added to cover consideration as a whole person, coordination, care plans, carer involvement, and a single coordinator. Cognitive interviews, on-going codesign, and mapping to core P3C domains resulted in the refinement of the questionnaire to 11 items with 1 trigger question. The 11-item modified version was renamed the P3C Experiences Questionnaire. Conclusions: Due to a dearth of brief measures available to capture people’s experience of P3C for routine practice, an existing measure was modified using an iterative process of adaption and validation through codesign workshops. Next steps include psychometric validation and modification for people with dementia and learning difficulties.</p

Disease-driven Reduction in Human Mobility Influences Human-Mosquito Contacts and Dengue Transmission Dynamics

Heterogeneous exposure to mosquitoes determines an individual’s contribution to vector-borne pathogen transmission. Particularly for dengue virus (DENV), there is a major difficulty in quantifying human-vector contacts due to the unknown coupled effect of key heterogeneities. To test the hypothesis that the reduction of human out-of-home mobility due to dengue illness will significantly influence population-level dynamics and the structure of DENV transmission chains, we extended an existing modeling framework to include social structure, disease-driven mobility reductions, and heterogeneous transmissibility from different infectious groups. Compared to a baseline model, naïve to human pre-symptomatic infectiousness and disease-driven mobility changes, a model including both parameters predicted an increase of 37% in the probability of a DENV outbreak occurring; a model including mobility change alone predicted a 15.5% increase compared to the baseline model. At the individual level, models including mobility change led to a reduction of the importance of out-of-home onward transmission (R, the fraction of secondary cases predicted to be generated by an individual) by symptomatic individuals (up to -62%) at the expense of an increase in the relevance of their home (up to +40%). An individual’s positive contribution to R could be predicted by a GAM including a non-linear interaction between an individual’s biting suitability and the number of mosquitoes in their home (\u3e10 mosquitoes and 0.6 individual attractiveness significantly increased R). We conclude that the complex fabric of social relationships and differential behavioral response to dengue illness cause the fraction of symptomatic DENV infections to concentrate transmission in specific locations, whereas asymptomatic carriers (including individuals in their pre-symptomatic period) move the virus throughout the landscape. Our findings point to the difficulty of focusing vector control interventions reactively on the home of symptomatic individuals, as this approach will fail to contain virus propagation by visitors to their house and asymptomatic carriers

Why alternative teenagers self-harm: exploring the link between non-suicidal self-injury, attempted suicide and adolescent identity

Background: The term ‘self-harm’ encompasses both attempted suicide and non-suicidal self-injury (NSSI). Specific adolescent subpopulations such as ethnic or sexual minorities, and more controversially, those who identify as ‘Alternative’ (Goth, Emo) have been proposed as being more likely to self-harm, while other groups such as ‘Jocks’ are linked with protective coping behaviours (for example exercise). NSSI has autonomic (it reduces negative emotions) and social (it communicates distress or facilitates group ‘bonding’) functions. This study explores the links between such aspects of self-harm, primarily NSSI, and youth subculture.&lt;p&gt;&lt;/p&gt; Methods: An anonymous survey was carried out of 452 15 year old German school students. Measures included: identification with different youth cultures, i.e. Alternative (Goth, Emo, Punk), Nerd (academic) or Jock (athletic); social background, e.g. socioeconomic status; and experience of victimisation. Self-harm (suicide and NSSI) was assessed using Self-harm Behavior Questionnaire and the Functional Assessment of Self-Mutilation (FASM).&lt;p&gt;&lt;/p&gt; Results: An “Alternative” identity was directly (r ≈ 0.3) and a “Jock” identity inversely (r ≈ -0.1) correlated with self-harm. “Alternative” teenagers self-injured more frequently (NSSI 45.5% vs. 18.8%), repeatedly self-injured, and were 4–8 times more likely to attempt suicide (even after adjusting for social background) than their non-Alternative peers. They were also more likely to self-injure for autonomic, communicative and social reasons than other adolescents.&lt;p&gt;&lt;/p&gt; Conclusions: About half of ‘Alternative’ adolescents’ self-injure, primarily to regulate emotions and communicate distress. However, a minority self-injure to reinforce their group identity, i.e. ‘To feel more a part of a group’

CD4 + T cells recognize conserved influenza A epitopes through shared patterns of V-Gene usage and complementary biochemical features

T cell recognition of peptides presented by human leukocyte antigens (HLAs) is mediated by the highly variable T cell receptor (TCR). Despite this built-in TCR variability, individuals can mount immune responses against viral epitopes by using identical or highly related TCRs expressed on CD8+ T cells. Characterization of these TCRs has extended our understanding of the molecular mechanisms that govern the recognition of peptide-HLA. However, few examples exist for CD4+ T cells. Here, we investigate CD4+ T cell responses to the internal proteins of the influenza A virus that correlate with protective immunity. We identify five internal epitopes that are commonly recognized by CD4+ T cells in five HLA-DR1+ subjects and show conservation across viral strains and zoonotic reservoirs. TCR repertoire analysis demonstrates several shared gene usage biases underpinned by complementary biochemical features evident in a structural comparison. These epitopes are attractive targets for vaccination and other T cell therapies

Fibroblast Growth Factor Receptor Signaling Dramatically Accelerates Tumorigenesis and Enhances Oncoprotein Translation in the Mouse Mammary Tumor Virus-Wnt-1 Mouse Model of Breast Cancer

Fibroblast growth factor (FGF) cooperates with the Wnt/β-catenin pathway to promote mammary tumorigenesis. To investigate the mechanisms involved in FGF/Wnt cooperation, we genetically engineered a model of inducible FGF receptor (iFGFR) signaling in the context of the well-established mouse mammary tumor virus–Wnt-1 transgenic mouse. In the bigenic mice, iFGFR1 activation dramatically enhanced mammary tumorigenesis. Expression microarray analysis did not show transcriptional enhancement of Wnt/β-catenin target genes but instead showed a translational gene signature that also correlated with elevated FGFR1 and FGFR2 in human breast cancer data sets. Additionally, iFGFR1 activation enhanced recruitment of RNA to polysomes, resulting in a marked increase in protein expression of several different Wnt/β-catenin target genes. FGF pathway activation stimulated extracellular signal-regulated kinase and the phosphorylation of key translation regulators both in vivo in the mouse model and in vitro in a human breast cancer cell line. Our results suggest that cooperation of the FGF and Wnt pathways in mammary tumorigenesis is based on the activation of protein translational pathways that result in, but are not limited to, increased expression of Wnt/β-catenin target genes (at the level of protein translation). Further, they reveal protein translation initiation factors as potential therapeutic targets for human breast cancers with alterations in FGF signaling