Predicting cell types and genetic variations contributing to disease by combining GWAS and epigenetic data

Genome-wide association studies (GWASs) identify single nucleotide polymorphisms (SNPs) that are enriched in individuals suffering from a given disease. Most disease-associated SNPs fall into non-coding regions, so that it is not straightforward to infer phenotype or function; moreover, many SNPs are in tight genetic linkage, so that a SNP identified as associated with a particular disease may not itself be causal, but rather signify the presence of a linked SNP that is functionally relevant to disease pathogenesis. Here, we present an analysis method that takes advantage of the recent rapid accumulation of epigenomics data to address these problems for some SNPs. Using asthma as a prototypic example; we show that non-coding disease-associated SNPs are enriched in genomic regions that function as regulators of transcription, such as enhancers and promoters. Identifying enhancers based on the presence of the histone modification marks such as H3K4me1 in different cell types, we show that the location of enhancers is highly cell-type specific. We use these findings to predict which SNPs are likely to be directly contributing to disease based on their presence in regulatory regions, and in which cell types their effect is expected to be detectable. Moreover, we can also predict which cell types contribute to a disease based on overlap of the disease-associated SNPs with the locations of enhancers present in a given cell type. Finally, we suggest that it will be possible to re-analyze GWAS studies with much higher power by limiting the SNPs considered to those in coding or regulatory regions of cell types relevant to a given disease

Can burglary prevention be low-carbon and effective? Investigating the environmental performance of burglary prevention measures

There has been limited study to date on the environmental impacts of crime prevention measures. We address this shortfall by estimating the carbon footprint associated with the most widely used burglary prevention measures: door locks, window locks, burglar alarms, lighting and CCTV cameras. We compare these footprints with a measure of their effectiveness, the security protection factor, allowing us to identify those measures that are both low-carbon and effective in preventing burglary. Window locks are found to be the most effective and low-carbon measure available individually. Combinations of window locks, door locks, external and indoor lightings are also shown to be effective and low-carbon. Burglar alarms and CCTV do not perform as strongly, with low security against burglary and higher carbon footprints. This information can be used to help inform more sustainable choices of burglary prevention within households as well as for crime prevention product design

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Perceptions of parents on satisfaction with care in the pediatric intensive care unit: the EMPATHIC study

Abstract: PURPOSE: To identify parental perceptions on pediatric intensive care-related satisfaction items within the framework of developing a Dutch pediatric intensive care unit (PICU) satisfaction instrument. METHODS: Prospective cohort study in tertiary PICUs at seven university medical centers in The Netherlands. PARTICIPANTS: Parents of 1,042 children discharged from a PICU. RESULTS: A 78-item questionnaire was sent to 1,042 parents and completed by 559 (54%). Seventeen satisfaction items were rated with mean scores or =1.65, and thus considered of limited value. The empirical structure of the items was in agreement with the theoretically formulated domains: Information, Care a

Matching Schur complement approximations for certain saddle-point systems

The solution of many practical problems described by mathematical models requires approximation methods that give rise to linear(ized) systems of equations, solving which will determine the desired approximation. This short contribution describes a particularly effective solution approach for a certain class of so-called saddle-point linear systems which arises in different contexts

Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of $\sqrt{s}=7\;\mathrm{TeV}$ proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Measuring subjective well-being from a multidimensional and temporal perspective: Italian adaptation of the I COPPE scale

Background: The objective of this study is to present the psychometric and cultural adaptation of the I COPPE scale to the Italian context. The original 21-item I COPPE was developed by Isaac Prilleltensky and colleagues to integrate a multidimensional and temporal perspective into the quantitative assessment of people’s subjective well-being. The scale comprises seven domains (Overall, Interpersonal, Community, Occupation, Psychological, Physical, and Economic well-being), which tap into past, present, and future self-appraisals of well-being. Methods: The Italian adapted version of the I COPPE scale underwent translation and backtranslation procedure. After a pilot study was conducted on a local sample of 683 university students, a national sample of 2432 Italian citizens responded to the final translated version of the I COPPE scale, 772 of whom re-completed the same survey after a period of four months. Respondents from both waves of the national sample were recruited partly through on-line social networks (i.e. Facebook, Twitter, and SurveyMonkey) and partly by university students who had been trained in Computer-Assisted Survey Information Collection. Results: Data were first screened for non-valid cases and tested for multivariate normality and missing data. The correlation matrix revealed highly significant correlation values, ranging from medium to high for nearly all congeneric variables of the I COPPE scale. Results from a series of nested and non-nested model comparisons supported the 7-factor correlated-traits model originally hypothesised, with factor loadings and inter-item reliability ranging from medium to high. In addition, they revealed that the I COPPE scale has strong internal reliability, with composite reliability always higher than .7, satisfactory construct validity, with average variance extracted nearly always higher than .5, and and full strict invariance across time. Conclusions: The Italian adaptation of the I COPPE scale presents appropriate psychometric properties in terms of both validity and reliability, and therefore can be applied to the Italian context. Some limitation and recommendations for future studies are discussed

A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome

Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function. We characterize MYMK-CFZS as a congenital myopathy with marked facial weakness and additional clinical and pathologic features that distinguish it from other congenital neuromuscular syndromes. We show that a heterologous cell fusion assay in vitro and allelic complementation experiments in mymk knockdown and mymk insT/insT zebrafish in vivo can differentiate between MYMK wild type, hypomorphic and null alleles. Collectively, these data establish that MYMK activity is necessary for normal muscle development and maintenance in humans, and expand the spectrum of congenital myopathies to include cell-cell fusion deficits