Mild orotic aciduria in UMPS heterozygotes: a metabolic finding without clinical consequences

BACKGROUND: Elevated urinary excretion of orotic acid is associated with treatable disorders of the urea cycle and pyrimidine metabolism. Establishing the correct and timely diagnosis in a patient with orotic aciduria is key to effective treatment. Uridine monophosphate synthase is involved in de novo pyrimidine synthesis. Uridine monophosphate synthase deficiency (or hereditary orotic aciduria), due to biallelic mutations in UMPS, is a rare condition presenting with megaloblastic anemia in the first months of life. If not treated with the pyrimidine precursor uridine, neutropenia, failure to thrive, growth retardation, developmental delay, and intellectual disability may ensue. METHODS AND RESULTS: We identified mild and isolated orotic aciduria in 11 unrelated individuals with diverse clinical signs and symptoms, the most common denominator being intellectual disability/developmental delay. Of note, none had blood count abnormalities, relevant hyperammonemia or altered plasma amino acid profile. All individuals were found to have heterozygous alterations in UMPS. Four of these variants were predicted to be null alleles with complete loss of function. The remaining variants were missense changes and predicted to be damaging to the normal encoded protein. Interestingly, family screening revealed heterozygous UMPS variants in combination with mild orotic aciduria in 19 clinically asymptomatic family members. CONCLUSIONS: We therefore conclude that heterozygous UMPS-mutations can lead to mild and isolated orotic aciduria without clinical consequence. Partial UMPS-deficiency should be included in the differential diagnosis of mild orotic aciduria. The discovery of heterozygotes manifesting clinical symptoms such as hypotonia and developmental delay are likely due to ascertainment bias

X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag

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

Modelling home care organisations from an operations management perspective

Home Care (HC) service consists of providing care to patients in their homes. During the last decade, the HC service industry experienced significant growth in many European countries. This growth stems from several factors, such as governmental pressure to reduce healthcare costs, demographic changes related to population ageing, social changes, an increase in the number of patients that suffer from chronic illnesses, and the development of new home-based services and technologies. This study proposes a framework that will enable HC service providers to better understand HC operations and their management. The study identifies the main processes and decisions that relate to the field of HC operations management. Hence, an IDEF0 (Integrated Definition for Function Modelling) activity-based model describes the most relevant clinical, logistical and organisational processes associated with HC operations. A hierarchical framework for operations management decisions is also proposed. This analysis is derived from data that was collected by nine HC service providers, which are located in France and Italy, and focuses on the manner in which operations are run, as well as associated constraints, inputs and outputs. The most challenging research areas in the field of HC operations management are also discussed

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

Planck 2015 results: XV. gravitational lensing

We present the most significant measurement of the cosmic microwave background (CMB) lensing potential to date (at a level of 40 sigma), using temperature and polarization data from the Planck 2015 full-mission release. Using a polarization-only estimator we detect lensing at a significance of 5 sigma. We cross-check the accuracy of our measurement using the wide frequency coverage and complementarity of the temperature and polarization measurements. Public products based on this measurement include an estimate of the lensing potential over approximately 70% of the sky, an estimate of the lensing potential power spectrum in bandpowers for the multipole range 40<L<400 and an associated likelihood for cosmological parameter constraints. We find good agreement between our measurement of the lensing potential power spectrum and that found in the best-fitting LCDM model based on the Planck temperature and polarization power spectra. Using the lensing likelihood alone we obtain a percent-level measurement of the parameter combination σ 8 Ω 0.25 m =0.591±0.021 . We combine our determination of the lensing potential with the E-mode polarization also measured by Planck to generate an estimate of the lensing B-mode. We show that this lensing B-mode estimate is correlated with the B-modes observed directly by Planck at the expected level and with a statistical significance of 10 sigma, confirming Planck's sensitivity to this known sky signal. We also correlate our lensing potential estimate with the large-scale temperature anisotropies, detecting a cross-correlation at the 3 sigma level, as expected due to dark energy in the concordance LCDM model

Search for supersymmetry in events with four or more leptons in √s =13 TeV pp collisions with ATLAS

Results from a search for supersymmetry in events with four or more charged leptons (electrons, muons and taus) are presented. The analysis uses a data sample corresponding to 36.1 fb −1 of proton-proton collisions delivered by the Large Hadron Collider at s √ =13 TeV and recorded by the ATLAS detector. Four-lepton signal regions with up to two hadronically decaying taus are designed to target a range of supersymmetric scenarios that can be either enriched in or depleted of events involving the production and decay of a Z boson. Data yields are consistent with Standard Model expectations and results are used to set upper limits on the event yields from processes beyond the Standard Model. Exclusion limits are set at the 95% confidence level in simplified models of General Gauge Mediated supersymmetry, where higgsino masses are excluded up to 295 GeV. In R -parity-violating simplified models with decays of the lightest supersymmetric particle to charged leptons, lower limits of 1.46 TeV, 1.06 TeV, and 2.25 TeV are placed on wino, slepton and gluino masses, respectively

Measurements of integrated and differential cross sections for isolated photon pair production in pp collisions at √s=8 TeV with the ATLAS detector

A measurement of the production cross section for two isolated photons in proton-proton collisions at a center-of-mass energy of √s=8 TeV is presented. The results are based on an integrated luminosity of 20.2 fb−1 recorded by the ATLAS detector at the Large Hadron Collider. The measurement considers photons with pseudorapidities satisfying |ηγ|40GeV and EγT,2>30 GeV for the two leading photons ordered in transverse energy produced in the interaction. The background due to hadronic jets and electrons is subtracted using data-driven techniques. The fiducial cross sections are corrected for detector effects and measured differentially as a function of six kinematic observables. The measured cross section integrated within the fiducial volume is 16.8 ± 0.8  pb . The data are compared to fixed-order QCD calculations at next-to-leading-order and next-to-next-to-leading-order accuracy as well as next-to-leading-order computations including resummation of initial-state gluon radiation at next-to-next-to-leading logarithm or matched to a parton shower, with relative uncertainties varying from 5% to 20%