The Combined Effect of Polygenic Risk from FTO and ADRB2 Gene Variants, Odds of Obesity, and Post-Hipcref Diet Differences

Background: Computing polygenic risk scores (PRS) to predict the degree of risk for obesity may contribute to weight management programs strategically. Objectives: To investigate the combined effect of FTO rs9930501, rs9930506, and rs9932754 and ADRB2 rs1042713 and rs1042714 using PRS on (1) the odds of obesity and (2) post-intervention differences in dietary, anthropometric, and cardiometabolic parameters in response to high-protein calorie-restricted, high-vitamin E, high-fiber (Hipcref) diet intervention in Malaysian adults. Methods: Both a cross-sectional study (n = 178) and a randomized controlled trial (RCT) (n = 128) were conducted to test the aforementioned objectives. PRS was computed as the weighted sum of the risk alleles possessed by each individual participant. Participants were stratified into first (PRS 0–0.64), second (PRS 0.65–3.59), and third (PRS 3.60–8.18) tertiles. Results: The third tertile of PRS was associated with significantly higher odds of obesity: 2.29 (95% CI = 1.11–4.72, adjusted p = 0.025) compared to the first tertile. Indians (3.9 ± 0.3) had significantly higher PRS compared to Chinese (2.1 ± 0.4) (p = 0.010). In the RCT, a greater reduction in high-sensitivity C-reactive protein (hsCRP) levels was found in second and third tertiles after Hipcref diet intervention compared to the control diet (p interaction = 0.048). Conclusion: Higher PRS was significantly associated with increased odds of obesity. Individuals with higher PRS had a significantly greater reduction in hsCRP levels after Hipcref diet compared to the control diet

Association of ADRB2 rs1042713 with Obesity and Obesity-Related Phenotypes and Its Interaction with Dietary Fat in Modulating Glycaemic Indices in Malaysian Adults

Gene-diet interaction studies have reported that individual variations in phenotypic traits may be due to variations in individual diet. Our study aimed to evaluate (i) the association of ADRB2 rs1042713 with obesity and obesity-related metabolic parameters and (ii) the effect of dietary nutrients on these associations in Malaysian adults. ADRB2 genotyping, dietary, physical activity, anthropometric, and biochemical data were collected from 79 obese and 99 nonobese individuals. Logistic regression revealed no association between ADRB2 rs1042713 and obesity (p = 0.725). However, the carriers of G allele (AG + GG genotypes) of rs1042713 were associated with increased odds of insulin resistance, 2.83 (CI = 1.04–7.70, adjusted p = 0.042), in the dominant model, even after adjusting for potential confounders. Obese individuals carrying the G allele were associated with higher total cholesterol (p = 0.011), LDL cholesterol levels (p = 0.008), and total cholesterol/HDL cholesterol ratio (p = 0.048), compared to the noncarriers (AA), even after adjusting for potential confounders. Irrespective of obesity, the carriers of GG genotype had significantly lower fasting glucose levels with low saturated fatty acid intake (<7.3% of TE/day) (4.92 ± 0.1 mmol/L vs 5.80 ± 0.3 mmol/L, p = 0.011) and high intake of polyunsaturated fatty acid:saturated fatty acid ratio (≥0.8/day) (4.83 ± 0.1 mmol/ L vs 5.93 ± 0.4 mmol/L, p = 0.006). Moreover, the carriers of GG genotype with high polyunsaturated fatty acid intake (≥6% of TE/day) had significantly lower HOMA-IR (1.5 ± 0.3 vs 3.0 ± 0.7, p = 0.026) and fasting insulin levels (6.8 ± 1.6 µU/mL vs 11.4 ± 2.1 µU/mL, p = 0.036). *ese effects were not found in the noncarriers (AA). In conclusion, G allele carriers of ADRB2 rs1042713 were associated with increased odds of insulin resistance. Obese individuals carrying G allele were compromised with higher blood lipid levels. Although it is premature to report gene-diet interaction on the regulation of glucose and insulin levels in Malaysians, we suggest that higher quantity of PUFA-rich food sources in regular diet may benefit overweight and obese Malaysian adults metabolically. Large-scale studies are required to replicate and confirm the current findings in the Malaysian population

Dynamic Adaptation on Non-Stationary Visual Domains

Domain adaptation aims to learn models on a supervised source domain that perform well on an unsupervised target. Prior work has examined domain adaptation in the context of stationary domain shifts, i.e. static data sets. However, with large-scale or dynamic data sources, data from a defined domain is not usually available all at once. For instance, in a streaming data scenario, dataset statistics effectively become a function of time. We introduce a framework for adaptation over non-stationary distribution shifts applicable to large-scale and streaming data scenarios. The model is adapted sequentially over incoming unsupervised streaming data batches. This enables improvements over several batches without the need for any additionally annotated data. To demonstrate the effectiveness of our proposed framework, we modify associative domain adaptation to work well on source and target data batches with unequal class distributions. We apply our method to several adaptation benchmark datasets for classification and show improved classifier accuracy not only for the currently adapted batch, but also when applied on future stream batches. Furthermore, we show the applicability of our associative learning modifications to semantic segmentation, where we achieve competitive results

Epilepsy Is a Risk Factor for Sudden Cardiac Arrest in the General Population

Background People with epilepsy are at increased risk for sudden death. The most prevalent cause of sudden death in the general population is sudden cardiac arrest (SCA) due to ventricular fibrillation (VF). SCA may contribute to the increased incidence of sudden death in people with epilepsy. We assessed whether the risk for SCA is increased in epilepsy by determining the risk for SCA among people with active epilepsy in a community-based study. Methods and Results This investigation was part of the Amsterdam Resuscitation Studies (ARREST) in the Netherlands. It was designed to assess SCA risk in the general population. All SCA cases in the study area were identified and matched to controls (by age, sex, and SCA date). A diagnosis of active epilepsy was ascertained in all cases and controls. Relative risk for SCA was estimated by calculating the adjusted odds ratios using conditional logistic regression (adjustment was made for known risk factors for SCA). We identified 1019 cases of SCA with ECG-documented VF, and matched them to 2834 controls. There were 12 people with active epilepsy among cases and 12 among controls. Epilepsy was associated with a three-fold increased risk for SCA (adjusted OR 2.9 [95%CI 1.1–8.0.], p = 0.034). The risk for SCA in epilepsy was particularly increased in young and females. Conclusion Epilepsy in the general population seems to be associated with an increased risk for SCA

On the dynamic mechanical properties of open-cell metal foams - A re-assessment of the 'simple-shock theory'

Metal foams are increasingly used for energy absorption especially in lightweight structures and to resist blast and impact loads. This requires an understanding of the dynamic response of these materials for modelling purposes. As a supplement to Tan et al., 2005a and Tan et al., 2005b, hereinafter referred to as T–L for brevity, this paper provides experimental data for the dynamic mechanical properties of open-cell Duocel® foams having a three-dimensional (3D) distribution of cells. These confirm significant enhancement of the foam’s compressive strength, accompanied by changes in their deformation pattern in certain loading régimes, particularly what has come to be described as the ‘shock’ régime by Zheng et al. (2012). This paper examines experimentally, in a similar fashion as T–L, how the structural response of the individual cell walls is affected by cell-shape anisotropy at the cell (meso)-scale and how this, in turn, alters the pattern of cell crushing and the dynamic, mechanical properties. The distinctive role of cell microinertia and ‘shock’ formation are discussed in relation to the mechanical properties measured for these 3D cylindrical specimens. For consistency the same procedures described in T–L are used. The features identified are shown to be consistent with those observed in finite-element simulations of two-dimensional (2D) honeycombs as estimated by the one-dimensional (1D) steady-shock theory summarised in T–L. The different deformation patterns that develop in the various loading régimes are categorised according to the compression rate/impact speed. Critical values of impact velocity, corresponding to the transition from one pattern to the other, are quantified and predictive formulae for the compressive uniaxial strengths in the directions of two of the principal axes of the material in each loading régime are derived and discussed. The accuracy of the predictive formula in T–L is shown to critically depend on the ‘densification strain’ of the foam specimens. This parameter and the discussion that follows could assist the formulation and validation of alternative theoretical/computational models on the dynamic deformation of such materials

RAMP2 influences glucagon receptor pharmacology via trafficking and signaling

Endogenous satiety hormones provide an attractive target for obesity drugs. Glucagon causes weight loss by reducing food intake and increasing energy expenditure. To further understand the cellular mechanisms by which glucagon and related ligands activate the glucagon receptor (GCGR), we investigated the interaction of the GCGR with receptor activity modifying protein (RAMP)2, a member of the family of receptor activity modifying proteins. We used a combination of competition binding experiments, cell surface enzyme-linked immunosorbent assay, functional assays assessing the Gαs and Gαq pathways and β-arrestin recruitment, and small interfering RNA knockdown to examine the effect of RAMP2 on the GCGR. Ligands tested were glucagon; glucagonlike peptide-1 (GLP-1); oxyntomodulin; and analog G(X), a GLP-1/glucagon coagonist developed in-house. Confocal microscopy was used to assess whether RAMP2 affects the subcellular distribution of GCGR. Here we demonstrate that coexpression of RAMP2 and the GCGR results in reduced cell surface expression of the GCGR. This was confirmed by confocal microscopy, which demonstrated that RAMP2 colocalizes with the GCGR and causes significant GCGR cellular redistribution. Furthermore, the presence of RAMP2 influences signaling through the Gαs and Gαq pathways, as well as recruitment of β-arrestin. This work suggests that RAMP2 may modify the agonist activity and trafficking of the GCGR, with potential relevance to production of new peptide analogs with selective agonist activities

Investigating the Three-Dimensional Microstructural Characteristics of Lithium-Sulfur Electrodes with X-Ray Micro-Tomography

The Li-S battery has the potential to replace Li-ion batteries in high capacity and high gravimetric energy density applications, but certain technical challenges result in diminished cycle life and have hindered its commercialization. Lab-scale X-ray micro-tomography was performed on an elemental sulfur electrode and a miniaturized in-situ tomography Li-S cell, and the 3D visualization achieved with this technique provides a wealth of information, improving understanding of the evolution of morphological and microstructural parameters of the different phases. As X-ray imaging is inherently non-destructive, it enables these parameters to be observed in-situ as a function of cycle life and state of charge. The inherently anisotropic nature of active material dissolution, recrystallization and other degradation processes within the electrode necessitates a three-dimensional approach to enable their visualization and quantification, and X-ray tomography is a useful tool in informing the development of more optimal electrode designs

Body Fat Percentage and the Long-term Risk of Fractures. The EPIC-Norfolk Prospective Population Cohort Study

Background: This cohort study aimed to determine the association between body fat percentage (BF%), incident fractures and calcaneal broadband ultrasound attenuation (BUA). Methods: Participants were drawn from the EPIC-Norfolk Prospective Population Cohort Study (median follow-up = 16.4 years). Cox models analysed the relationship between BF% and incident fractures (all and hip). Linear and restricted cubic spline (RCS) regressions modelled the relationship between BF% and BUA. Results: 14,129 participants (56.2 % women) were included. There were 1283 and 537 incident all and hip fractures respectively. The participants had a mean (standard deviation) age of 61.5 (9.0) years for women and 62.9 (9.0) years for men. Amongst men, BF% was not associated with incident all fractures. While BF% 23 % was associated with increased risk of hip fractures by up to 50 % (hazard ratio (95 % confidence interval) = 1.49 (1.06–2.12)). In women, BF% 35 % was not associated with this outcome. Higher BF% was associated with lower risk of incident hip fractures in women. Higher BF% was associated with higher BUA amongst women. Higher BF% up to ~23 % was associated with higher BUA amongst men. Conclusions: Higher BF% is associated with lower risk of fractures in women. While there was no association between BF% and all fractures in men, increasing BF% >23 % was associated with higher risk of hip fractures in men. This appears to be independent of estimated bone mineral density. Fracture prevention efforts need to consider wider physical, clinical, and environmental factors

The Detection of Monoclinic Zirconia and Non-Uniform 3D Crystallographic Strain in a Re-Oxidized Ni-YSZ Solid Oxide Fuel Cell Anode

The solid oxide fuel cell (SOFC) anode is often composed of nickel (Ni) and yttria-stabilized zirconia (YSZ). The yttria is added in small quantities (e.g., 8 mol %) to maintain the crystallographic structure throughout the operating temperatures (e.g., room-temperature to >800 °C). The YSZ skeleton provides a constraining structural support that inhibits degradation mechanisms such as Ni agglomeration and thermal expansion miss-match between the anode and electrolyte layers. Within this structure, the Ni is deposited in the oxide form and then reduced during start-up; however, exposure to oxygen (e.g., during gasket failure) readily re-oxidizes the Ni back to NiO, impeding electrochemical performance and introducing complex structural stresses. In this work, we correlate lab-based X-ray computed tomography using zone plate focusing optics, with X-ray synchrotron diffraction computed tomography to explore the crystal structure of a partially re-oxidized Ni/NiO-YSZ electrode. These state-of-the-art techniques expose several novel findings: non-isotropic YSZ lattice distributions; the presence of monoclinic zirconia around the oxidation boundary; and metallic strain complications in the presence of variable yttria content. This work provides evidence that the reduction–oxidation processes may destabilize the YSZ structure, producing monoclinic zirconia and microscopic YSZ strain, which has implications upon the electrode’s mechanical integrity and thus lifetime of the SOFC