Sleep characteristics modify the association between genetic predisposition to obesity and anthropometric measurements in 119,679 UK Biobank participants

Background - Obesity is a multifactorial condition influenced by genetics, lifestyle and environment. Objective - To investigate whether the association between a validated genetic profile risk score for obesity (GPRS-obesity) with body mass index (BMI) and waist circumference (WC) was modified by sleep characteristics. Design - This study included cross-sectional data from 119,859 white European adults, aged 37-73 years, participating on the UK Biobank. Interactions between GPRS-obesity, and sleep characteristics (sleep duration, chronotype, day napping, and shift work) in their effects on BMI and WC were investigated. Results - The GPRS-obesity was associated with BMI (β:0.57 kg.m-2 per standard deviation (SD) increase in GPRS, [95%CI:0.55, 0.60]; P=6.3x10-207) and WC (β:1.21 cm, [1.15, 1.28]; P=4.2x10-289). There were significant interactions between GPRS-obesity and a variety of sleep characteristics in their relationship with BMI (P-interaction <0.05). In participants who slept <7 hrs or >9 hrs daily, the effect of GPRS-obesity on BMI was stronger (β:0.60 [0.54, 0.65] and 0.73 [0.49, 0.97] kg.m-2 per SD increase in GPRS, respectively) than in normal length sleepers (7-9 hours; β:0.52 [0.49, 0.55] kg.m-2 per SD). A similar pattern was observed for shiftworkers (β:0.68 [0.59, 0.77] versus 0.54 [0.51, 0.58] kg.m-2 for non-shiftworkers) and for night-shiftworkers (β:0.69 [0.56, 0.82] versus 0.55 [0.51, 0.58] kg.m-2 for non-night- shiftworkers), for those taking naps during the day (β:0.65 [0.52, 0.78] versus 0.51 [0.48, 0.55] kg.m-2 for those who never/rarely had naps) and for those with a self-reported evening chronotype (β:0.72 [0.61, 0.82] versus β:0.52 [0.47, 0.57] kg.m-2 for morning chronotype). Similar findings were obtained using WC as the outcome. Conclusions – This study shows that the association between genetic risk for obesity and phenotypic adiposity measures is exacerbated by adverse sleeping characteristics

Dietary fat and total energy intake modifies the association of genetic profile risk score on obesity: evidence from 48 170 UK Biobank participants

Background: Obesity is a multifactorial condition influenced by both genetics and lifestyle. The aim of this study was to investigate whether the association between a validated genetic profile risk score for obesity (GPRS-obesity) and body mass index (BMI) or waist circumference (WC) was modified by macronutrient intake in a large general population study. Methods: This study included cross-sectional data from 48 170 white European adults, aged 37–73 years, participating on the UK Biobank. Interactions between GPRS-obesity, and macronutrient intake (including total energy, protein, fat, carbohydrate and dietary fibre intake) and its effects on BMI and WC were investigated. Results: The 93-SNPs genetic profile risk score was associated with a higher BMI (β:0.57 kg.m−2 per standard deviation (s.d.) increase in GPRS, [95%CI:0.53–0.60]; P=1.9 × 10−183) independent of major confounding factors. There was a significant interaction between GPRS and total fat intake (P[interaction]=0.007). Among high fat intake individuals, BMI was higher by 0.60 [0.52, 0.67] kg.m−2 per s.d. increase in GPRS-obesity; the change in BMI with GPRS was lower among low fat intake individuals (β:0.50 [0.44, 0.57] kg.m-2). Significant interactions with similar patterns were observed for saturated fat intake (High β:0.66 [0.59, 0.73] versus Low β:0.49 [0.42, 0.55] kg.m-2, P-interaction=2 × 10-4), and total energy intake (High β:0.58 [0.51, 0.64] versus Low β:0.49 [0.42, 0.56] kg.m−2, P-interaction=0.019), but not for protein intake, carbohydrate intake and fiber intake (P-interaction >0.05). The findings were broadly similar using WC as the outcome. Conclusions: These data suggest that the benefits of reducing the intake of fats and total energy intake, may be more important in individuals with high genetic risk for obesity

U-Pb geochronology and paleogeography of the Valanginian–Hauterivian Neuquén Basin: Implications for Gondwana-scale source areas

Sedimentary basins located at the margins of continents act as the final base level for continental-scale catchments that are sometimes located thousands of kilometers away from the basin, and this condition of exceptionally long sediment transfer zones is probably reinforced in supercontinents, such as Gondwana. One of the most prominent marine basins in southwestern Gondwana during the Jurassic and Early Cretaceous was the Neuquén Basin (west-central Argentina), but its role as a sediment repository of far-flung source areas has not been extensively considered. This contribution provides the first detailed detrital-zircon U-Pb geochronology of the Valanginian–Hauterivian Pilmatué Member of the Agrio Formation, which is combined with sedimentology and paleogeographic reconstructions of the unit within the Neuquén Basin for a better understanding of the fluvial delivery systems. Our detrital-zircon signatures suggest that Triassic–Permian zircon populations were probably sourced from the adjacent western sector of the North Patagonian Massif, whereas Early Jurassic, Cambrian, Ordovician, and Proterozoic grains were most likely derived from farther east, in the eastern sector of the North Patagonian Massif, as well as presently remote terranes such as the Saldania Belt in southern Africa. We thus propose a Valanginian–Hauterivian longitudinal delivery system that, starting in the mid-continent region of southwestern Gondwana and by effective sorting, was bringing fine-grained or finer caliber sand to the Neuquén Basin shoreline. This delivery system was probably active (though not necessarily continuously) from Early Jurassic to Early Cretaceous until finally coming to an end during the opening of the South Atlantic Ocean in the latest Early Cretaceous.Fil: Schwarz, Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Finzel, E.S.. University of Iowa; Estados UnidosFil: Veiga, Gonzalo Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Rapela, Carlos Washington. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Echevarria, C.. No especifíca;Fil: Spalletti, Luis Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; Argentin

Alzheimer disease genetic risk factor APOE e4, and cognitive abilities in 111,739 UK Biobank participants

Background: the apolipoprotein (APOE) e4 locus is a genetic risk factor for dementia. Carriers of the e4 allele may be more vulnerable to conditions that are independent risk factors for cognitive decline, such as cardiometabolic diseases. Objective: we tested whether any association with APOE e4 status on cognitive ability was larger in older ages or in those with cardiometabolic diseases. Subjects: UK Biobank includes over 500,000 middle- and older aged adults who have undergone detailed medical and cognitive phenotypic assessment. Around 150,000 currently have genetic data. We examined 111,739 participants with complete genetic and cognitive data. Methods: baseline cognitive data relating to information processing speed, memory and reasoning were used. We tested for interactions with age and with the presence versus absence of type 2 diabetes (T2D), coronary artery disease (CAD) and hypertension. Results: in several instances, APOE e4 dosage interacted with older age and disease presence to affect cognitive scores. When adjusted for potentially confounding variables, there was no APOE e4 effect on the outcome variables. Conclusions: future research in large independent cohorts should continue to investigate this important question, which has potential implications for aetiology related to dementia and cognitive impairment

Human pluripotent stem cell expansion in vertical-wheel bioreactors

Human induced pluripotent stem cells (hiPSC) have been regarded as an enormous breakthrough for medicine, since they can be derived from patients and be used to generate virtually all types of cells in the human body. One of the great bottlenecks in the usage of these cells for regenerative medicine or drug discovery applications is their expansion to relevant quantities. The Vertical-Wheel Bioreactors (PBS Biotech) present a novel scalable bioreactor configuration, whose agitation mechanism allows for homogeneous mixing conditions inside the single-use vessel, while conveying less shear stress to the cells when compared to traditional alternatives. These characteristics are advantageous for hiPSC expansion and thus, in this work, hiPSC were expanded in the Vertical-Wheel Bioreactor using different strategies, namely culturing the cells 1) on microcarriers and 2) as floating aggregates. In the first approach, cells were cultured under xeno-free conditions, using the Essential 8 medium together with microcarriers and coatings devoid of any animal-derived products [1]. The culture conditions were optimized in terms of initial cell/microcarrier ratio, inoculation method and agitation rate, in the PBS 0.1 vessel (working volume: 80 mL). The cells were successfully expanded, maintaining a normal karyotype, up to a 6.7-fold increase in cell number, after 6 days. These optimized culture conditions were successfully repeated in a larger vessel, the PBS 0.5 (300 mL working volume) demonstrating the scalability of the Vertical-Wheel system. In the second approach, hiPSC were expanded as floating aggregates, a methodology which does not require a separation step at the end of culture, to remove microcarriers, facilitating the downstream processing and Good Manufacturing Practice-compliance of the process. Cells were cultured in the PBS 0.1 (working volume: 60 mL), using mTeSR1, a serum-free medium and were monitored throughout culture regarding growth kinetics, aggregate size distribution and expression of pluripotency markers. The Vertical-Wheel Bioreactors were shown to efficiently keep the cell aggregates in suspension, under lower linear agitation speeds than an equivalent volume spinner flask (7 cm/s vs. 13 cm/s). Following 7 days of culture, cells were expanded up to a 5.2 ± 0.6-fold increase in cell number. The hiPSC aggregates increased in size over time, from an average diameter of 135 ± 61 µm to 397 ± 119 µm after 7 days. Pluripotency was maintained throughout time, as assessed by sustained high (\u3e 80%) expression of pluripotency markers OCT4, SOX2 and TRA-1-60, and low (\u3c 10%) expression of early differentiation marker SSEA-1. The results were validated using a second hiPSC line. This study revealed that the Vertical-Wheel Bioreactor allows hiPSC growth either on microcarriers and as aggregates and suggested it to have advantages versus other configurations. These results make the Vertical-Wheel Bioreactor a promising platform for hiPSC expansion and, prospectively, differentiation approaches, contributing for the generation of bona fide cells for various biomedical applications, namely drug screening, disease modelling, and, ultimately, for Regenerative Medicine. [1] Rodrigues CAV, Silva TP, Nogueira DES, Fernandes TG, Hashimura Y, Wesselschmidt R, Diogo MM, Lee B, Cabral JMS (2018), “Scalable Culture Of Human Induced Pluripotent Cells On Microcarriers Under Xeno‐Free Conditions Using Single‐Use Vertical‐Wheel™ Bioreactors”, Journal of Chemical Technology and Biotechnology, DOI: 10.1002/jctb.573

Coupling of Cyclic Voltammetry and Electrochemical Impedance Spectroscopy for Probing the Thermodynamics of Facilitated Ion Transfer Reactions Exhibiting Chemical Kinetic Hindrances

Mathematical models under conditions of cyclic staircase voltammetry and electrochemical impedance spectroscopy (EIS), which consider the kinetic effects due to the complexation reaction by the facilitated transfer of metal ions at polarized interfaces, are presented. Criteria for qualitative recognition of these kinetic effects from the features of simulated cyclic voltammograms are given. In case of the existence of these effects, only the EIS can bring access to the thermodynamics and kinetics of the complexation chemical reaction. Analytical equations for estimating the thermodynamic parameters by such systems under EIS conditions are evaluated. The theoretical results are compared with the experimental results of the facilitated Cu2+ transfer at the polarized water-1,2-dichlorethane interface, assisted by two phenanthroline-containing macrocycles. In the experimental case where kinetic effects due to the complexation step exist, we show how elegantly EIS can be used as a tool for estimation of the complexation constant of Cu2+ and 5-oxo-2,8-dithia [9],(2,9)-1,10-phenanthrolinophane (PhenOS2)

In vivo variability in quantitative coronary ultrasound and tissue characterization measurements with mechanical and phased-array catheters

Background: Both mechanical and phased-array catheters are used in clinical trials to assess quantitative parameters. Only limited evaluation of the in vivo agreement of volumetrical measurements between such systems has been performed, despite the fact that such information is essential for the conduction of atherosclerosis regression trials. Methods and results: We prospectively evaluated the agreement in morphometric measurements and intravascular ultrasound (IVUS)-based plaque characterization between a 40 MHz rotating transducer (3.2 F Atlantis, Boston Scientific Corp.) and a 20 MHz phased-array catheter (2.9 F Eagle Eye, Volcano Therapeutics, Rancho Cordova, California) in 16 patients. Lumen (7.3 ± 2.0 mm2 vs. 6.7 ± 1.8 mm2, p = 0.001) and vessel (11.8 ± 3.3 mm2 vs. 11.0 ± 2.9 mm2, p = 0.02) cross-sectional areas (CSA) were significantly greater with the 20 MHz system. Plaque CSA measurements showed no significant difference between systems (4.4 ± 2.3 mm2 vs. 4.4 ± 2.1). The relative differences were less than 10% for the three variables. On IVUS-based tissue characterization (13 patients), calculated percentage hypoechogenic volume was significantly higher for the 20 MHz system (96.7 ± 2.38 vs. 88.4 ± 5.53, p < 0.0001). Conclusions: Quantitative IVUS analyses display significant catheter type-dependent variability. It is unclear whether the variability reflects overestimation of measurements with the phased-array or underestimation with the mechanical system. Although plaque burden measurements did not differ significantly between systems, it appears prudent to recommend the use of a single system for progression/ regression studies

Experimental and numerical validation of guided wave phased arrays integrated within standard data acquisition systems for structural health monitoring

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143695/1/stc2171_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143695/2/stc2171.pd

Theory of the Diamagnetism Above the Critical Temperature for Cuprates

Recently experiments on high critical temperature superconductors has shown that the doping levels and the superconducting gap are usually not uniform properties but strongly dependent on their positions inside a given sample. Local superconducting regions develop at the pseudogap temperature ($T^*$) and upon cooling, grow continuously. As one of the consequences a large diamagnetic signal above the critical temperature ($T_c$) has been measured by different groups. Here we apply a critical-state model for the magnetic response to the local superconducting domains between $T^*$ and $T_c$ and show that the resulting diamagnetic signal is in agreement with the experimental results.Comment: published versio