Poor growth, social inequalities and coronary risk.

Data from 5 epidemiological studies, spanning an age range from childhood to late adult life, are used to investigate associations between components of height, used as markers of growth at different phases, and arterial stiffness, subclinical atherosclerosis and cardiovascular risk. The roles of prenatal growth and life course socioeconomic position are considered. In the 1946 Birth Cohort, shorter leg, but not trunk length, was associated with greater pulse pressure, a measure of arterial stiffness, in adult men and women. Longitudinal analyses suggested that these effects were due to a steeper rise of blood pressure with age, independent of potential confounders and mediators considered. In the Whitehall II Study, shorter leg and trunk length were both associated with adverse levels of several cardiovascular risk factors and also lower distensibility and greater stiffness of the carotid arteries in men. In a cross-sectional examination of Filipino-American women, coronary disease was most strongly associated with leg length, while diabetes prevalence was not associated with measures of growth, but highest in women who were socioeconomically disadvantaged in childhood and adulthood. Higher blood pressure levels were observed in children with shorter leg length, relative to total body height, of a contemporary US birth cohort at age 3 years. The contribution of prenatal growth was considered in all studies where birthweight was available and found to be limited. Finally, results from the first Whitehall Study suggested that associations between stature and cardiovascular mortality may differ by socioeconomic position. These findings lend some support to the hypothesis that factors limiting leg growth are associated with arterial stiffness, subclinical atherosclerosis and cardiovascular risk these associations may originate in childhood and be amplified with age. The specificity of leg length as a marker of early influences on growth that alter cardiovascular risk is questioned

A Systematic Review of Biomarkers and Risk of Incident Type 2 Diabetes: An Overview of Epidemiological, Prediction and Aetiological Research Literature

$\textbf{BACKGROUND}$ Blood-based or urinary biomarkers may play a role in quantifying the future risk of type 2 diabetes (T2D) and in understanding possible aetiological pathways to disease. However, no systematic review has been conducted that has identified and provided an overview of available biomarkers for incident T2D. We aimed to systematically review the associations of biomarkers with risk of developing T2D and to highlight evidence gaps in the existing literature regarding the predictive and aetiological value of these biomarkers and to direct future research in this field. $\textbf{METHODS AND FINDINGS}$ We systematically searched PubMed MEDLINE (January 2000 until March 2015) and Embase (until January 2016) databases for observational studies of biomarkers and incident T2D according to the 2009 PRISMA guidelines. We also searched availability of meta-analyses, Mendelian randomisation and prediction research for the identified biomarkers. We reviewed 3910 titles (705 abstracts) and 164 full papers and included 139 papers from 69 cohort studies that described the prospective relationships between 167 blood-based or urinary biomarkers and incident T2D. Only 35 biomarkers were reported in large scale studies with more than 1000 T2D cases, and thus the evidence for association was inconclusive for the majority of biomarkers. Fourteen biomarkers have been investigated using Mendelian randomisation approaches. Only for one biomarker was there strong observational evidence of association and evidence from genetic association studies that was compatible with an underlying causal association. In additional search for T2D prediction, we found only half of biomarkers were examined with formal evidence of predictive value for a minority of these biomarkers. Most biomarkers did not enhance the strength of prediction, but the strongest evidence for prediction was for biomarkers that quantify measures of glycaemia. $\textbf{CONCLUSIONS}$ This study presents an extensive review of the current state of the literature to inform the strategy for future interrogation of existing and newly described biomarkers for T2D. Many biomarkers have been reported to be associated with the risk of developing T2D. The evidence of their value in adding to understanding of causal pathways to disease is very limited so far. The utility of most biomarkers remains largely unknown in clinical prediction. Future research should focus on providing good genetic instruments across consortia for possible biomarkers in Mendelian randomisation, prioritising biomarkers for measurement in large-scale cohort studies and examining predictive utility of biomarkers for a given context.This study was supported by the Medical Research Council UK (grant reference no. MC_UU_12015/1), http://gtr.rcuk.ac.uk/projects?ref=MC_UU_12015/1; Netherlands Organization for Scientific Research (NWO project number 825.13.004), http://www.nwo.nl/en/research-and-results/research-projects/i/85/10585.html; Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no. 115372, resources of which are composed of financial contributions from the European Union's Seventh Framework Programme (FP7/2007-2013), http://www.emif.eu/about. GSK provided support in the form of salaries for DW, DJN, AS. Pfizer provided support in the form of salary to JMB

Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

OBJECTIVE Glycated hemoglobin (HbA1c), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA1c. We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA1c levels. RESEARCH DESIGN AND METHODS We studied associations with HbA1c in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA1c loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening. RESULTS Ten loci reached genome-wide significant association with HbA1c, including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 × 10−26), HFE (rs1800562/P = 2.6 × 10−20), TMPRSS6 (rs855791/P = 2.7 × 10−14), ANK1 (rs4737009/P = 6.1 × 10−12), SPTA1 (rs2779116/P = 2.8 × 10−9) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 × 10−9), and four known HbA1c loci: HK1 (rs16926246/P = 3.1 × 10−54), MTNR1B (rs1387153/P = 4.0 × 10−11), GCK (rs1799884/P = 1.5 × 10−20) and G6PC2/ABCB11 (rs552976/P = 8.2 × 10−18). We show that associations with HbA1c are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (% HbA1c) difference between the extreme 10% tails of the risk score, and would reclassify ∼2% of a general white population screened for diabetes with HbA1c. CONCLUSIONS GWAS identified 10 genetic loci reproducibly associated with HbA1c. Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA1c levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA1c

Changing Winds: National Politics And Its Role In Funding For Rural Development In Alaska

Thesis (M.A.) University of Alaska Fairbanks, 2010The combination of the election of Senator Mark Begich in 2008, an increased emphasis on transparency, and a growing movement away from congressionally-directed spending (earmarks) and toward competitively-awarded and formula-based funding has the potential to drastically reduce federal funding for rural development in Alaska. Alaska's basic needs for infrastructure remain equivalent to those of some of the least developed nations of the world. Rural development projects in Alaska, however, fight an uphill battle for federal funding because rural populations are low in numbers and remote, costs of rural development in Alaska far exceed similar projects in the "lower 48," and changes in the U.S. Congress have drastically reduced Alaskans' ability to circumvent formula-based and competitively-awarded funding avenues. This thesis is an analysis of recent changes that affect rural development funding in Alaska, and it hypothesizes how rural development funding for Alaska may continue to change

Measurement of the Spin-Dependence of the pbar-p Interaction at the AD-Ring

We propose to use an internal polarized hydrogen storage cell gas target in the AD ring to determine for the first time the two total spin-dependent pbar-p cross sections sigma_1 and sigma_2 at antiproton beam energies in the range from 50 to 450 MeV. The data obtained are of interest by themselves for the general theory of pbar-p interactions since they will provide a first experimental constraint of the spin-spin dependence of the nucleon-antinucleon potential in the energy range of interest. In addition, measurements of the polarization buildup of stored antiprotons are required to define the optimum parameters of a future, dedicated Antiproton Polarizer Ring (APR), intended to feed a double-polarized asymmetric pbar-p collider with polarized antiprotons. Such a machine has recently been proposed by the PAX collaboration for the new Facility for Antiproton and Ion Research (FAIR) at GSI in Darmstadt, Germany. The availability of an intense stored beam of polarized antiprotons will provide access to a wealth of single- and double-spin observables, thereby opening a new window on QCD spin physics.Comment: 51 pages, 23 figures, proposal submitted to the SPS committee of CER

Chemical shifts and cluster structure

The 2p core-level electron binding energies of size-selected silicon cluster ions have been determined from soft x-ray photoionization efficiency curves. Local chemical shifts and global charging energy contributions to the 2p binding energy can be separated, because core-level and valence-band electron binding energies exhibit the same inverse radius dependence. The experimental 2p binding energy distributions show characteristic size-specific patterns that are well reproduced by the corresponding electronic density of states obtained from density functional theory modeling. These results demonstrate that 2p binding energies in silicon clusters are dominated by initial state effects, i.e., by the interaction with the local valence electron density, and can thus be used to corroborate structural assignments

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Commentary and Worked Examples to EN 1993-1-10 "Material Toughness and Through Thickness Properties" and Other Toughness Oriented Rules in EN 1993

This commentary gives explanations and worked examples to the design rules in Eurocode 3 that are influenced by the strength and toughness properties of the structural steels used. It is a commentary and background document to EN 1993-1-10 "Material toughness and through thickness properties" and its extension in EN 1993-1-12 "Design rules for high-strength steels", where toughness properties are explicitly addressed. It however provides also background to other parts of EN 1993, e.g. to EN 1993-1-1 "Design of steel structures - Basic rules and rules for buildings", where the design rules are related only to strength properties as the yield strength and the tensile strength without explicitly mentioning the role of toughness that is hidden behind the resistance formulae. Finally it gives some comments to chapter 6 of EN 1998-1: "Design of structures for earthquake resistance - Part 1: General rules, seismic actions and rules for buildings".JRC.G.5-European laboratory for structural assessmen