Predictive simulations of NBI ion power load to the ICRH antenna in Wendelstein 7-X

In Wendelstein 7-X (W7-X), a new ion cyclotron resonance heating (ICRH) antenna will be commissioned during the operational campaign OP2.1. The antenna will have to sustain power loads not only from thermal plasma and radiation but also fast ions. Predictive simulations of fast-ion power loads to the antenna components are therefore important to establish safe operational limits. In this work, the fast-ion power loads from the W7-X neutral beam injection (NBI) system to the ICRH antenna was simulated using the ASCOT suite of codes. Five reference magnetic configurations and five antenna positions were considered to provide an overview of power load behavior under various operating conditions. The NBI power load was found to have an exponential dependence on the antenna insertion depth. Differences between magnetic configurations were significant, with the antenna limiter power load varying between 380 W and 100 kW depending on the configuration. Qualitative differences in power load patterns between configurations were also observed, with the low mirror and low iota configurations exhibiting higher loads to the sensitive antenna straps. The local fast-ion power flux to the antenna limiter was also considered and found to exceed the 2.0 MW m−2 steady-state safety limit only in specific cases. The NBI system might thus pose a safety concern to the ICRH antenna during concurrent NBI-ICRH operation, but additional heat propagation simulations of antenna components are needed to establish more realistic operational time limits

Prediction of sudden cardiac death with automated high-throughput analysis of heterogeneity in standard resting 12-lead electrocardiograms

BACKGROUND Heterogeneity of depolarization and repolarization underlies the development of lethal arrhythmias. OBJECTIVE We investigated whether quantification of spatial depolarization and repolarization heterogeneity identifies individuals at risk for sudden cardiac death (SCD). METHODS Spatial R-, J-, and T-wave heterogeneity (RWH, JWH, and TWH, respectively) was analyzed using automated second central moment analysis of standard digital 12-lead electrocardiograms in 5618 adults (2588, 46% men; mean +/- SEM age 50.9 +/- 0.2 years), who took part in the epidemiological Health 2000 Survey as representative of the entire Finnish adult population. RESULTS During the follow-up period of 7.7 +/- 0.2 years, a total of 72 SCDs occurred (1.3%), with an average yearly incidence rate of 0.17% per year. Increased RWH, JWH, and TWH in left precordial leads (V-4-V-6) were univariately associated with SCD (P = 102 mu V) was associated with a 1.7-fold adjusted relative risk for SCD (95% confidence interval [CI] 1.0-2.9; P = .048) and increased JWH (>= 123 mu V) with a 2.0-fold adjusted relative risk for SCD (95% CI 1.2-3.3; P = .006). When both TWH and JWH were above the threshold, the adjusted relative risk for SCD was 2.9-fold (95% CI 1.5-5.7; P = .002). When RWH (>= 470 mu V), JWH, and TWH were all above the threshold, the adjusted relative risk for SCD was 3.2-fold (95% CI 1.4-7.1; P = .009). CONCLUSION Second central moment analysis of standard resting 12-lead electrocardiographic morphology provides an ultrarapid means for the automated measurement of spatial RWH, JWH, and TWH, enabling analysis of high subject volumes and screening for SCD risk in the general population.Peer reviewe

Genome-wide association study of nocturnal blood pressure dipping in hypertensive patients

Background: Reduced nocturnal fall (non-dipping) of blood pressure (BP) is a predictor of cardiovascular target organ damage. No genome-wide association studies (GWAS) on BP dipping have been previously reported.Methods: To study genetic variation affecting BP dipping, we conducted a GWAS in Genetics of Drug Responsiveness in Essential Hypertension (GENRES) cohort (n = 204) using the mean night-to-day BP ratio from up to four ambulatory BP recordings conducted on placebo. Associations with P< 1 x 10(-5) were further tested in two independent cohorts: Haemodynamics in Primary and Secondary Hypertension (DYNAMIC) (n = 183) and Dietary, Lifestyle and Genetic determinants of Obesity and Metabolic Syndrome (DILGOM) (n = 180). We also tested the genome-wide significant single nucleotide polymorphism (SNP) for association with left ventricular hypertrophy in GENRES.Results: In GENRES GWAS, rs4905794 near BCL11B achieved genome-wide significance (beta = - 4.8%, P = 9.6 x 10(-9) for systolic and beta = - 4.3%, P = 2.2 x 10(-6) for diastolic night-to-day BP ratio). Seven additional SNPs in five loci had P values < 1 x 10(-5). The association of rs4905794 did not significantly replicate, even though in DYNAMIC the effect was in the same direction (beta = - 0.8%, P = 0.4 for systolic and beta = - 1.6%, P = 0.13 for diastolic night-to-day BP ratio). In GENRES, the associations remained significant even during administration of four different antihypertensive drugs. In separate analysis in GENRES, rs4905794 was associated with echocardiographic left ventricular mass (beta = -7.6 g/m(2), P = 0.02).Conclusions: rs4905794 near BCL11B showed evidence for association with nocturnal BP dipping. It also associated with left ventricular mass in GENRES. Combined with earlier data, our results provide support to the idea that BCL11B could play a role in cardiovascular pathophysiology

Genealogy and clinical course of catecholaminergic polymorphic ventricular tachycardia caused by the ryanodine receptor type 2 P2328S mutation

Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe inherited arrhythmic disease associated with a risk of syncope and sudden cardiac death (SCD).Aims We aimed at identifying RYR2 P2328S founder mutation carriers and describing the clinical course associated with the mutation.Methods The study population was drawn from the Finnish Inherited Cardiac Disorder Research Registry, and from the present genealogical study. Kaplan-Meier graphs, log-rank test and Cox regression model were used to evaluate the clinical course.Results Genealogical study revealed a common ancestor couple living in the late 17(th) century. A total of 1837 living descendants were tested for RYR2 P2328S mutation unveiling 62 mutation carriers aged mean 3923 years old. No arrhythmic deaths were documented among genotyped subjects, but 11 SCDs were detected in non-genotyped family members since 1970. Three genotyped patients (5%) suffered an aborted cardiac arrest (ACA), and 15 (25%) had a syncope triggered by exercise or stress. Rate of cardiac events was higher among patients who in exercise stress test showed a maximum rate of premature ventricular contractions >30/min (68% vs 17%, p<0.01; hazard ratio = 7.1, p = 0.02), in comparison to patients without the respective finding. A cardioverter-defibrillator (ICD) was implanted to 13 (22%) patients, with an appropriate ICD shock in four (31%) subjects. All ICD shocks, one ACA, and one syncope occurred during -blocker medication.Conclusions Previously undiagnosed CPVT patients may be identified by well-conducted genealogical studies. The RYR2 P2328S mutation causes a potentially severe phenotype, but its expression is variable, thus calling for additional studies on modifying factors

Employment status and differences in the one-year coverage of physician visits: different needs or unequal access to services?

BACKGROUND: The dichotomy employed vs. unemployed is still a relevant, but rather crude measure of status in current labour markets. Also, studies concerning the association of employment status with health have to specify the type of the employment as well as the characteristics of the unemployment. This study aims to reveal differences and potential inequalities in physician visits among seven groups in the core-periphery structures of the labour markets. METHODS: A total of 16 000 Finns responded to a postal survey in 2003. Their visits to physicians in public primary health care, occupational health care, private health services, hospital outpatient clinics and dental care services during previous year were measured as indicators of service utilisation. Participants were classified as employees having a permanent or fixed-term and full-time or part-time contract and as those experiencing short-term, prolonged or long-term unemployment. Differences in the one-year coverage of physician visits between these groups of employees were analysed using logistic regression analyses where differences in the need for services were controlled for by including demographics and self-rated health assessments in the models. RESULTS: Permanently employed respondents had visited a physician most often, and the need-adjusted regression models showed significantly lower odds ratios for a visit among fixed-term employees (OR 0.65, 95% CI 0.53–0.81) and in particular among the long-term unemployed (OR 0.21, 95% CI 0.14–0.31). A stratified analysis according to health care sector showed the lowest odds ratios in occupational health care and private physicians (ORs between 0.05 and 0.73) and also low odds ratios for dentists (ORs between 0.45 and 0.91), whereas visits to public primary health care were more common among non-permanent employees and the unemployed (ORs between 1.46 and 2.39). CONCLUSION: The use of physician services varies according to labour market status, being relatively low among the non-permanently employed and the unemployed. This underuse is emphasised when clinical need is taken into account. The main reasons for the variance evidently lie in the structures of the Finnish health service system. The result may indicate non-optimal health care of the population on the periphery of the labour market, but it may also reflect the importance of employment status as a context for need and the decision to visit a physician

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Ageism and sexuality

Sexuality remains important throughout a person’s life, but sexual behavior does not receive the same levels of acceptance at all ages. Older people are challenged by ageist attitudes and perceptions that hinder their sexual expression. They are stereotyped as non-sexual beings who should not, cannot, and do not want to have sexual relationships. Expressing sexuality or engaging in sexual activity in later life is considered by many in society as immoral or perverted. False expectations for older people also stem from ideals of beauty, centralization of the biomedical perspective on sexuality of older adults, and the association of sex with reproduction. Unfortunately, older people internalize many ageist attitudes towards sexuality in later life and become less interested in sex and less sexually active. The following chapter explores attitudes towards sexuality in later life among the media, young people, older people themselves, and care providers. In order to enable older people to express their sexuality and sexual identity freely and fully, awareness of ageist perceptions must be raised and defeated