Orai1 deficiency leads to heart failure and skeletal myopathy in zebrafish.

Mutations in the store-operated Ca²⁺ entry pore protein ORAI1 have been reported to cause myopathies in human patients but the mechanism involved is not known. Cardiomyocytes express ORAI1 but its role in heart function is also unknown. Using reverse genetics in zebrafish, we demonstrated that inactivation of the highly conserved zebrafish orthologue of ORAI1 resulted in severe heart failure, reduced ventricular systolic function, bradycardia and skeletal muscle weakness. Electron microscopy of Orai1-deficient myocytes revealed progressive skeletal muscle instability with loss of myofiber integrity and ultrastructural abnormalities of the z-disc in both skeletal and cardiac muscle. Isolated Orai1-deficient cardiomyocytes showed loss of the calcineurin-associated protein calsarcin from the z-discs. Furthermore, we found mechanosignal transduction was affected in Orai1-depleted hearts, indicating an essential role for ORAI1 in establishing the cardiac signaling transduction machinery at the z-disc. Our findings identify ORAI1 as an important regulator of cardiac and skeletal muscle function and provide evidence linking ORAI1-mediated calcium signaling to sarcomere integrity and cardiomyocyte function

Using the Theory of Planned Behavior to Anticipate DIY E-juice Mixing among Young Adult International E-cigarette Users

Background: Trends in young adult use of electronic nicotine delivery systems (ENDS) and experimentation with do-it-yourself (DIY) e-juice mixing are growing around the world. Theoretical frameworks for examining secondary behaviors (i.e., mixing) embedded within a primary behavior (i.e., vaping) are limited, leading to challenges in scholarly understanding of behavioral performance. This study explored the theoretically driven factors surrounding ENDS users’ decision to mix DIY e-juice through a multiple behavior test of the theory of planned behavior (TPB).Methods: An international sample of young adult participants aged 18-19 (n=203) was recruited from Prolific for an online cross sectional survey. Path modeling tested four theoretically driven models to explore behavioral performance of mixing. Findings: The data supported TPB expectations and revealed new paths for secondary behavior. Primary perceptions of attitudes, norms, and intention were predictive of the same secondary perceptions. In addition, for both primary and secondary behaviors, perceived norms were a function of perceived attitudes. For the secondary behavior, normative influence was experienced indirectly through perceived attitudes. Conclusion: DIY e-juice mixing is a product of perceived attitudes and behavioral control surrounding mixing as well as perceived attitudes, norms, and intention surrounding general ENDS use. While unregulated DIY experimentation increases among youth, these findings provide a lens for public health efforts seeking to reach and reduce use. Understanding DIY e-juice behaviors isessential to anticipate stockpiling behaviors and negative outcomes from amateur experimentation

Prevalence of menopausal symptoms among mid-life women: findings from electronic medical records

BACKGROUND: To assess the prevalence of menopausal symptoms among women prescribed hormone therapy (HT) using electronic medical record data from a regional healthcare organization. METHODS: Retrospective data from the Reliant Medical Group from 1/1/2006-12/31/2011 were assessed for 102 randomly-selected patients. Study eligibility criteria included: females aged 45 to 65; prescribed oral or transdermal HT; no history of breast cancer, venous thromboembolism, stroke, gynecological cancer, or hysterectomy; continuously enrolled in the health plan for 1 year before and after the first observed HT prescription. Prevalence of menopause-related symptoms was analyzed descriptively at both the patient and visit levels. RESULTS: Mean age of patients was 54 years. The most common menopausal symptoms were: hot flushes (40%), night sweats (17%), insomnia (16%), vaginal dryness (13%), mood disorders (12%), and weight gain (12%). Among the 102 patients, 163 individual visits listing menopausal symptoms were identified, of which hot flushes (71 visits) were the most common symptom identified. CONCLUSION: Our findings provide recent data on the types of menopausal symptoms experienced by mid-life women prescribed HT. Electronic medical records may be a rich source of data for future studies of menopausal symptoms in this population

Custom Integrated Circuits

Contains reports on three research projects.U.S. Air Force (Contract F49620-81-C-0054)National Science Foundation (Grant ECS81-18160

Work-Related Mental Health and Job Performance: Can Mindfulness Help?

Work-related mental health issues such as work-related stress and addiction to work impose a significant health and economic burden to the employee, the employing organization, and the country of work more generally. Interventions that can be empirically shown to improve levels of work-related mental health – especially those with the potential to concurrently improve employee levels of work performance – are of particular interest to occupational stakeholders. One such broad-application interventional approach currently of interest to occupational stakeholders in this respect is mindfulness-based interventions (MBIs). Following a brief explication of the mindfulness construct, this paper critically discusses current research directions in the utilization of mindfulness in workplace settings and assesses its suitability for operationalization as an organization-level work-related mental health intervention. By effecting a perceptual-shift in the mode of responding and relating to sensory and cognitive-affective stimuli, employees that undergo mindfulness training may be able to transfer the locus of control for stress from external work conditions to internal metacognitive and attentional resources. Therefore, MBIs may constitute cost-effective organization-level interventions due to not actually requiring any modifications to human resource management systems and practises. Based on preliminary empirical findings and on the outcomes of MBI studies with clinical populations, it is concluded that MBIs appear to be viable interventional options for organizations wishing to improve the mental health of their employees

Custom Integrated Circuits

Contains reports on four research projects.U.S. Air Force - Office of Scientific Research (Contract F49620-81-C-0054)U.S. Air Force - Office of Scientific Research (Contract F49620-84-C-0004)National Science Foundation (Grant ECS81-18160)National Science Foundation (Grant ECS83-10941

Implementation of a flexible and modular multiphase framework for the analysis of surface-tension-driven flows based on a LS-VOF approach

The mathematical modelling and numerical simulation of multi-phase flows are both a demanding and highly complex exercise. In typical problems with industrial relevance, the fluids are often in non-isothermal conditions and interfacial phenomena are a relevant part of the problem. A number of effects due to the presence of temperature differences must be adequately taken into account to make the results of numerical simulations consistent and realistic. Moreover, in general, gradients of surface tension at the interface separating two liquids are a source of numerical issues that can delay (and even prevent completely in some circumstances) the convergence of the solution algorithm. Here, we propose a fundamental and concerted approach for the simulation of the typical dynamics resulting from the presence of a dispersed phase in an external matrix in nonisothermal conditions based on the modular computer-aided design, modelling, and simulations capabilities of the OpenFOAM environment. The resulting framework is tested against the migration of a droplet induced by thermocapillary effects in the absence of gravity. The simulations are fully three-dimensional and based on an adaptive mesh refinement (AMR) strategy. We describe in detail the countermeasures taken to circumvent the problematic issues associated with the simulation of this kind of flows

Political Regimes and Sovereign Credit Risk in Europe, 1750-1913

This article uses a new panel data set to perform a statistical analysis of political regimes and sovereign credit risk in Europe from 1750 to 1913. Old Regime polities typically suffered from fiscal fragmentation and absolutist rule. By the start of World War I, however, many such countries had centralized institutions and limited government. Panel regressions indicate that centralized and?or limited regimes were associated with significant improvements in credit risk relative to fragmented and absolutist ones. Structural break tests also reveal close relationships between major turning points in yield series and political transformations

Measurement of red blood cell eicosapentaenoic acid (EPA) levels in a randomised trial of EPA in patients with colorectal cancer liver metastases

We investigated red blood cell (RBC) PUFA profiles, and the predictive value of RBC EPA content for tumour EPA exposure and clinical outcomes, in the EMT study, a randomised trial of EPA in patients awaiting colorectal cancer (CRC) liver metastasis surgery (Cockbain et al., 2014). There was a significant increase in RBC EPA in the EPA group (n=43; median intervention 30 days; mean absolute 1.26 [±0.14]% increase; P<0.001), but not in the placebo arm (n=45). EPA incorporation varied widely in EPA users and was not explained by treatment duration or compliance. There was little evidence of ‘contamination’ in the placebo group. The EPA level predicted tumour EPA content (r=0.36; P=0.03). Participants with post-treatment EPA ≥1.22% (n=49) had improved OS compared with EPA <1.22% (n=29; HR 0.42[95%CI 0.16–0.95]). RBC EPA content should be evaluated as a biomarker of tumour exposure and clinical outcomes in future EPA trials in CRC patients

An exploratory study of the association between online gaming addiction and enjoyment motivations for playing massively multiplayer online role-playing games

Massively multiplayer online role-playing games (MMORPGs) are a popular form of entertainment used by millions of gamers worldwide. Potential problems relating to MMORPG play have emerged, particularly in relation to being addicted to playing in such virtual environments. In the present study, factors relating to online gaming addiction and motivations for playing in MMORPGs were examined to establish whether they were associated with addiction. A sample comprised 1167 gamers who were surveyed about their gaming motivations. Latent Class Analysis revealed seven classes of motivations for playing MMORPGs, which comprised: (1) novelty; (2) highly social and discovery-orientated; (3) aggressive, anti-social and non-curious; (4) highly social, competitive; (5) low intensity enjoyment; (6) discovery-orientated; and (7) social classes. Five classes of gaming addiction-related experiences were extracted including: (1) high risk of addiction, (2) time-affected, (3) intermediate risk of addiction, (4) emotional control, and (5) low risk of addiction classes. Gender was a significant predictor of intermediate risk of addiction and emotional control class membership. Membership of the high risk of addiction class was significantly predicted by belonging to a highly social and competitive class, a novelty class, or an aggressive, anti-social, and non-curious class. Implications of these findings for assessment and treatment of MMORPG addiction are discussed