The effect on melanoma risk of genes previously associated with telomere length.

Telomere length has been associated with risk of many cancers, but results are inconsistent. Seven single nucleotide polymorphisms (SNPs) previously associated with mean leukocyte telomere length were either genotyped or well-imputed in 11108 case patients and 13933 control patients from Europe, Israel, the United States and Australia, four of the seven SNPs reached a P value under .05 (two-sided). A genetic score that predicts telomere length, derived from these seven SNPs, is strongly associated (P = 8.92x10(-9), two-sided) with melanoma risk. This demonstrates that the previously observed association between longer telomere length and increased melanoma risk is not attributable to confounding via shared environmental effects (such as ultraviolet exposure) or reverse causality. We provide the first proof that multiple germline genetic determinants of telomere length influence cancer risk.This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/jnci/dju26

Phase Stability Effects on Hydrogen Embrittlement Resistance in Martensite–Reverted Austenite Steels

Earlier studies have shown that interlath austenite in martensitic steels can enhance hydrogen embrittlement (HE) resistance. However, the improvements were limited due to microcrack nucleation and growth. A novel microstructural design approach is investigated, based on enhancing austenite stability to reduce crack nucleation and growth. Our findings from mechanical tests, X-ray diffraction, and scanning electron microscopy reveal that this strategy is successful. However, the improvements are limited due to intrinsic microstructural heterogeneity effects

Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Stressful life events and identity development in early and mid-adolescence

Introduction: In the past, stressful life events have been consistently linked to developmental outcomes such as well-being and psychopathological problems. Theory on identity postulates that stressful life events may also predict a regression in identity development. While some support for this link has been found in adult populations, it is important to examine this in adolescence, a time marked by identity development as well as stressful transitions and experiences. Methods: In the present study, we examined whether having to repeat a grade and death of a family member or friend were related to regressive change in educational and relational identity in a sample of 840 Dutch adolescents (49% female, Mage W1 = 12.4) drawn from a large ongoing longitudinal study. We also investigated whether the impact of the events was moderated by neuroticism, and parental and peer support. All analyses were controlled for age, educational level, and sex. Results: Results of latent difference score models indicated that experiencing an event did not predict regressions in identity. Congruence between the domain of the event and identity (i.e., educational or relational) did not affect the strength of the effects. Neuroticism and parental and peer support did not significantly moderate this link. However, social support was related to relational and educational identity. Conclusions: The link between stressful events and identity may not be as straightforward as would be expected based on identity theory, as our results did not show evidence for a link between these events and change in identity for all adolescents

Search for physics beyond the standard model via a polarization-asymmetry correlation experiment on In-107

We report on a new precision measurement of the longitudinal polarization of positrons emitted by polarized 107In nuclei. If interpreted in the framework of the manifest left-right symmetric model, preliminary results yield a lower limit of 303 GeV/c2 for the mass of a possible, predominantly right-handed W gauge boson

Towards building active knowledge systems with conceptual graphs

Abstract. This paper outlines a vision for using conceptual graphs to build active knowledge systems that have the capability to solve practical and complex problems. A key ingredient in an active knowledge system is its ability to interact (not just interface) with the real world. Basic features of such systems go beyond logic to include support for data mining, intelligent agents, temporal actors, active sensors, a system for knowledge interchange and finally, support for knowledge-in-the-large.