Association between a comprehensive movement assessment and metabolically healthy overweight obese adults

Physical activity (PA) and sedentary behavior are associated with metabolic health in overweight and obese individuals. However, the role of comprehensive health-related movement guidelines on PA, recreational screen time, and sleep among Metabolically Healthy Overweight-Obese (MHO) individuals is unknown. We investigated differences in comprehensive movement assessment scores between adults classified as MHO or Non-MHO. The sample included 513 adults (46.2% male), aged 19 to 85 years, body mass index (BMI) ≥ 25, from cycle 2005–2006 of the National Health and Nutrition Examination Survey. Comprehensive movement assessment outcomes were defined as meeting modified 24-Hour Movement Guidelines criteria, with thresholds adapted for adults. 13.8% of participants were MHO (normal serum glucose, triglycerides, HDL-cholesterol, and systolic and diastolic blood pressure). Only 1.4% of MHO participants met all guidelines. MHO and Non-MHO participants had similar comprehensive movement assessment scores (MHO: 18.3% vs. Non-MHO: 10.9%; p = 0.072). MHO individuals had less continuous recreational screen time than Non-MHO individuals (1.8 ± 1.4 hrs/day vs. 2.5 ± 1.6 hrs/day; p < 0.001). Meeting the recreational screen time recommendation was the only variable associated with the MHO phenotype (OR:4.84 95%CI: 2.33–10.07). This association remained after adjusting for age, sex, ethnicity, education, and BMI (OR: 3.53 95%CI: 1.72–7.24). Our results suggest the importance of limiting recreational screen time in adults to optimize cardiometabolic risk profile in individuals living with overweight or obesity. Using movement guidelines with a screen time component to assess the risk associated with health outcomes in adults appears to provide a better assessment

Open orbifold Gromov-Witten invariants of [C^3/Z_n]: localization and mirror symmetry

We develop a mathematical framework for the computation of open orbifold Gromov-Witten invariants of [C^3/Z_n], and provide extensive checks with predictions from open string mirror symmetry. To this aim we set up a computation of open string invariants in the spirit of Katz-Liu, defining them by localization. The orbifold is viewed as an open chart of a global quotient of the resolved conifold, and the Lagrangian as the fixed locus of an appropriate anti-holomorphic involution. We consider two main applications of the formalism. After warming up with the simpler example of [C^3/Z_3], where we verify physical predictions of Bouchard, Klemm, Marino and Pasquetti, the main object of our study is the richer case of [C^3/Z_4], where two different choices are allowed for the Lagrangian. For one choice, we make numerical checks to confirm the B-model predictions; for the other, we prove a mirror theorem for orbifold disc invariants, match a large number of annulus invariants, and give mirror symmetry predictions for open string invariants of genus \leq 2.Comment: 44 pages + appendices; v2: exposition improved, misprints corrected, version to appear on Selecta Mathematica; v3: last minute mistake found and fixed for the symmetric brane setup of [C^3/Z_4]; in pres

Extended Holomorphic Anomaly in Gauge Theory

The partition function of an N=2 gauge theory in the Omega-background satisfies, for generic value of the parameter beta=-eps_1/eps_2, the, in general extended, but otherwise beta-independent, holomorphic anomaly equation of special geometry. Modularity together with the (beta-dependent) gap structure at the various singular loci in the moduli space completely fixes the holomorphic ambiguity, also when the extension is non-trivial. In some cases, the theory at the orbifold radius, corresponding to beta=2, can be identified with an "orientifold" of the theory at beta=1. The various connections give hints for embedding the structure into the topological string.Comment: 25 page

Yukawa Couplings in Heterotic Compactification

We present a practical, algebraic method for efficiently calculating the Yukawa couplings of a large class of heterotic compactifications on Calabi-Yau three-folds with non-standard embeddings. Our methodology covers all of, though is not restricted to, the recently classified positive monads over favourable complete intersection Calabi-Yau three-folds. Since the algorithm is based on manipulating polynomials it can be easily implemented on a computer. This makes the automated investigation of Yukawa couplings for large classes of smooth heterotic compactifications a viable possibility.Comment: 38 page

Typicality, Black Hole Microstates and Superconformal Field Theories

We analyze the structure of heavy multitrace BPS operators in N = 1 superconformal quiver gauge theories that arise on the worldvolume of D3-branes on an affine toric cone. We exhibit a geometric procedure for counting heavy mesonic operators with given U(1) charges. We show that for any fixed linear combination of the U(1) charges, the entropy is maximized when the charges are in certain ratios. This selects preferred directions in the charge space that can be determined with the help of a piece of string. We show that almost all heavy mesonic operators of fixed U(1) charges share a universal structure. This universality reflects the properties of the dual extremal black holes whose microstates they create. We also interpret our results in terms of typical configurations of dual giant gravitons in AdS space.Comment: 40 pages + 3 appendices, 11 figure

Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P&lt;10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P&lt;5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health

Genetic insights into resting heart rate and its role in cardiovascular disease.

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding