Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

SRNL PHASE 1 ASSESSMENT OF THE WAC/DQO AND UNIT OPERATIONS FOR THE WTP WASTE QUALIFICATION PROGRAM

The Hanford Tank Waste Treatment and Immobilization Plant (WTP) is currently transitioning its emphasis from a design and construction phase toward start-up and commissioning. With this transition, the WTP Project has initiated more detailed assessments of the requirements related to actual processing of the Hanford Site tank waste. One particular area of interest is the waste qualification program to be implemented to support the WTP. Given the successful implementation of similar waste qualification efforts at the Savannah River Site (SRS), based on critical technical support and guidance from the Savannah River National Laboratory (SRNL), WTP requested the utilization of subject matter experts from SRNL to support a technology exchange to perform a review of the WTP waste qualification program, discuss the general qualification approach at SRS, and to identify critical lessons learned through the support of DWPF's sludge batch qualification efforts. As part of Phase 1, SRNL subject matter experts in critical technical and/or process areas reviewed specific WTP waste qualification information. The Phase 1 review was a collaborative, interactive, and iterative process between the two organizations. WTP provided specific analytical procedures, descriptions of equipment, and general documentation as baseline review material. SRNL subject matter experts reviewed the information and, as appropriate, requested follow-up information or clarification to specific areas of interest. This process resulted in multiple teleconferences with key technical contacts from both organizations resolving technical issues that lead to the results presented in this report. This report provides the results of SRNL's Phase 1 review of the WAC-DQO waste acceptance criteria and processability parameters, and the specific unit operations which are required to support WTP waste qualification efforts. The review resulted in SRNL providing concurrence, alternative methods, or gap identification for the proposed WTP analytical methods or approaches. For the unit operations, the SRNL subject matter experts reviewed WTP concepts compared to what is used at SRS and provided thoughts on the outlined tasks with respect to waste qualification. Also documented in this report are recommendations and an outline on what would be required for the next phase to further mature the WTP waste qualification program

Non-physical consequences of the Muffin-tin-type intra-molecular potential

We demonstrate using a simple model that in the frame of muffin-tin - like potential non-physical peculiarities appear in molecular photoionization cross-sections that are a consequence of jumps in the potential and its first derivative at some radius. The magnitude of non-physical effects is of the same order as the physical oscillations in the cross-section of a two-atomic molecule. The role of the size of these jumps is illustrated by choosing three values of it. The results obtained are connected to the studied previously effect of non-analytical behavior as a function of r the potential V(r)acting upon a particle on its photoionization cross-section. In reality, such potential has to be analytic in magnitude and first derivative function in distance. Introduction of non-analytic features in model potential leads to non-physical features in the corresponding cross-section - oscillations, additional maxima etc.Comment: 11 pages, 5 figure

Cross-Sectional Associations of Reallocating Time Between Sedentary and Active Behaviours on Cardiometabolic Risk Factors in Young People: An International Children's Accelerometry Database (ICAD) Analysis.

INTRODUCTION: Sedentary time and time spent in various intensity-specific physical activity are co-dependent, and increasing time spent in one behaviour requires decreased time in another. OBJECTIVE: The aim of the present study was to examine the theoretical associations with reallocating time between categories of intensities and cardiometabolic risk factors in a large and heterogeneous sample of children and adolescents. METHODS: We analysed pooled data from 13 studies comprising 18,200 children and adolescents aged 4-18 years from the International Children's Accelerometry Database (ICAD). Waist-mounted accelerometers measured sedentary time, light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA). Cardiometabolic risk factors included waist circumference (WC), systolic blood pressure (SBP), fasting high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), triglycerides, insulin, and glucose. Associations of reallocating time between the various intensity categories with cardiometabolic risk factors were explored using isotemporal substitution modelling. RESULTS: Replacing 10 min of sedentary time with 10 min of MVPA showed favourable associations with WC, SBP, LDL-C, insulin, triglycerides, and glucose; the greatest magnitude was observed for insulin (reduction of 2-4%), WC (reduction of 0.5-1%), and triglycerides (1-2%). In addition, replacing 10 min of sedentary time with an equal amount of LPA showed beneficial associations with WC, although only in adolescents. CONCLUSIONS: Replacing sedentary time and/or LPA with MVPA in children and adolescents is favourably associated with most markers of cardiometabolic risk. Efforts aimed at replacing sedentary time with active behaviours, particularly those of at least moderate intensity, appear to be an effective strategy to reduce cardiometabolic risk in young people

Birth weight, cardiometabolic risk factors and effect modification of physical activity in children and adolescents: pooled data from 12 international studies

Abstract: Objectives: Low and high birth weight is associated with higher levels of cardiometabolic risk factors and adiposity in children and adolescents, and increases the risk of cardiovascular diseases, obesity, and early mortality later in life. Moderate-to-vigorous physical activity (MVPA) is associated with lower cardiometabolic risk factors and may mitigate the detrimental consequences of high or low birth weight. Thus, we examined whether MVPA modified the associations between birth weight and cardiometabolic risk factors in children and adolescents. Methods: We used pooled individual data from 12 cohort- or cross-sectional studies including 9,100 children and adolescents. Birth weight was measured at birth or maternally reported retrospectively. Device-measured physical activity (PA) and cardiometabolic risk factors were measured in childhood or adolescence. We tested for associations between birth weight, MVPA, and cardiometabolic risk factors using multilevel linear regression, including study as a random factor. We tested for interaction between birth weight and MVPA by introducing the interaction term in the models (birth weight x MVPA). Results: Most of the associations between birth weight (kg) and cardiometabolic risk factors were not modified by MVPA (min/day), except between birth weight and waist circumference (cm) in children (p = 0.005) and HDL-cholesterol (mmol/l) in adolescents (p = 0.040). Sensitivity analyses suggested that some of the associations were modified by VPA, i.e., the associations between birth weight and diastolic blood pressure (mmHg) in children (p = 0.009) and LDL- cholesterol (mmol/l) (p = 0.009) and triglycerides (mmol/l) in adolescents (p = 0.028). Conclusion: MVPA appears not to consistently modify the associations between low birth weight and cardiometabolic risk. In contrast, MVPA may mitigate the association between higher birth weight and higher waist circumference in children. MVPA is consistently associated with a lower cardiometabolic risk across the birth weight spectrum. Optimal prenatal growth and subsequent PA are both important in relation to cardiometabolic health in children and adolescents