Inactivation defects caused by myotonia-associated mutations in the sodium channel III-IV linker.

Missense mutations in the skeletal muscle Na+ channel alpha subunit occur in several heritable forms of myotonia and periodic paralysis. Distinct phenotypes arise from mutations at two sites within the III-IV cytoplasmic loop: myotonia without weakness due to substitutions at glycine 1306, and myotonia plus weakness caused by a mutation at threonine 1313. Heterologous expression in HEK cells showed that substitutions at either site disrupted inactivation, as reflected by slower inactivation rates, shifts in steady-state inactivation, and larger persistent Na+ currents. For T1313M, however, the changes were an order of magnitude larger than any of three substitutions at G1306, and recovery from inactivation was hastened as well. Model simulations demonstrate that these functional difference have distinct phenotypic consequences. In particular, a large persistent Na+ current predisposes to paralysis due to depolarization-induced block of action potential generation

Incidence and recurrence of boils and abscesses within the first year: a cohort study in UK primary care

Background Boils and abscesses are common in primary care but the burden of recurrent infection is unknown. Aim To investigate the incidence of and risk factors for recurrence of boil or abscess for individuals consulting primary care. Design and setting Cohort study using electronic health records from primary care in the UK. Method The Health Improvement Network (THIN) database was used to identify patients who had consulted their GP for a boil or abscess. Poisson regression was used to examine the relationship between age, sex, social deprivation, and consultation and to calculate the incidence of, and risk factors for, repeat consultation for a boil or abscess. Results Overall, 164 461 individuals were identified who consulted their GP for a boil or abscess between 1995 and 2010. The incidence of first consultation for a boil or abscess was 512 (95% CI = 509 to 515) per 100 000 person-years in females and 387 (95% CI = 385 to 390) per 100 000 person-years in males. First consultations were most frequent in younger age groups (16–34 years) and those with the greatest levels of social deprivation. The rate of repeat consultation for a new infection during follow up was 107.5 (95% confidence interval [CI] = 105.6 to 109.4) per 1000 person-years. Obesity (relative risk [RR] 1.3, 95% CI = 1.2 to 1.3), diabetes (RR 1.3, 95% CI = 1.2 to 1.3), smoking (RR 1.3, 95% CI = 1.2 to 1.4), age <30 years (RR 1.2, 95% CI = 1.2 to 1.3), and prior antibiotic use (RR 1.4, 95% CI = 1.3–1.4) were all associated with repeat consultation for a boil or abscess. Conclusion Ten percent of patients with a boil or abscess develop a repeat boil or abscess within 12 months. Obesity, diabetes, young age, smoking, and prescription of an antibiotic in the 6 months before initial presentation were independently associated with recurrent infection, and may represent options for prevention

Common Genetic Variants Explain the Majority of the Correlation Between Height and Intelligence : The Generation Scotland Study

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Temperature and oxygen dependent metabolite utilization by Salmonella enterica Serovars Derby and Mbandaka

Salmonella enterica is a zoonotic pathogen of clinical and veterinary significance, with over 2500 serovars. In previous work we compared two serovars displaying host associations inferred from isolation statistics. Here, to validate genome sequence data and to expand on the role of environmental metabolite constitution in host range determination we use a phenotypic microarray approach to assess the ability of these serovars to metabolise ~500 substrates at 25°C with oxygen (aerobic conditions) to represent the ex vivo environment and at 37°C with and without oxygen (aerobic/anaerobic conditions) to represent the in vivo environment. A total of 26 substrates elicited a significant difference in the rate of metabolism of which only one, D-galactonic acid-g-lactone, could be explained by the presence (S. Mbandaka) or the absence (S. Derby) of metabolic genes. We find that S. Mbandaka respires more efficiently at ambient temperatures and under aerobic conditions on 18 substrates including: glucosominic acid, saccharic acid, trehalose, fumaric acid, maltotriose, N-acetyl-D-glucosamine, N-acetyl-beta-D-mannosamine, fucose, L-serine and dihydroxy-acetone; whereas S. Derby is more metabolically competent anaerobically at 37°C for dipeptides, glutamine-glutamine, alanine-lysine, asparagine-glutamine and nitrogen sources glycine and nitrite. We conclude that the specific phenotype cannot be reliably predicted from the presence of metabolic genes directly relating to the metabolic pathways under study

Burden of Illness in UK Subjects with Reported Respiratory Infections Vaccinated or Unvaccinated against Influenza: A Retrospective Observational Study

<div><p>Objective</p><p>Detailed data are lacking on influenza burden in the United Kingdom (UK). The objective of this study was to estimate the disease burden associated with influenza-like illness (ILI) in the United Kingdom stratified by age, risk and influenza vaccination status.</p><p>Methods</p><p>This retrospective, cross-sectional, exploratory, observational study used linked data from the General Practice Research Database and the Hospital Episode Statistics databases to estimate resource use and cost associated with ILI in the UK.</p><p>Results</p><p>Data were included from 156,193 patients with ≥1 general practitioner visit with ILI. There were 21,518 high-risk patients, of whom 12,514 (58.2%) were vaccinated and 9,004 (41.8%) were not vaccinated, and 134,675 low-risk patients, of whom 17,482 (13.0%) were vaccinated and 117,193 (87.0%) were not vaccinated. High-risk vaccinated patients were older (p<0.001) and had more risk conditions (p<0.001). High-risk (odds ratio [OR] 2.16) or vaccinated (OR 1.19) patients had a higher probability of >1 general practitioner visit compared with low-risk and unvaccinated patients. Patients who were high-risk and vaccinated had a reduced risk of >1 general practitioner visit (OR 0.82; p<0.001). High-risk individuals who were also vaccinated had a lower probability of ILI-related hospitalisation than individuals who were high-risk or vaccinated alone (OR 0.59). In people aged ≥65 years, the mortality rate was lower in vaccinated than unvaccinated individuals (OR 0.75). The cost of ILI-related GP visits and hospital admissions in the UK over the study period in low-risk vaccinated patients was £27,391,142 and £141,932,471, respectively. In low-risk unvaccinated patients the corresponding values were £168,318,709 and £112,534,130, respectively.</p><p>Conclusions</p><p>Although vaccination rates in target groups have increased, many people are still not receiving influenza vaccination, and the burden of ILI in the United Kingdom remains substantial. Improving influenza vaccination uptake may have the potential to reduce this burden.</p></div

Minimum length effects in black hole physics

We review the main consequences of the possible existence of a minimum measurable length, of the order of the Planck scale, on quantum effects occurring in black hole physics. In particular, we focus on the ensuing minimum mass for black holes and how modified dispersion relations affect the Hawking decay, both in four space-time dimensions and in models with extra spatial dimensions. In the latter case, we briefly discuss possible phenomenological signatures.Comment: 29 pages, 12 figures. To be published in "Quantum Aspects of Black Holes", ed. X. Calmet (Springer, 2014

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

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Search for squarks and gluinos with the ATLAS detector in final states with jets and missing transverse momentum using √s=8 TeV proton-proton collision data

A search for squarks and gluinos in final states containing high-p T jets, missing transverse momentum and no electrons or muons is presented. The data were recorded in 2012 by the ATLAS experiment in s√=8 TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 20.3 fb−1. Results are interpreted in a variety of simplified and specific supersymmetry-breaking models assuming that R-parity is conserved and that the lightest neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 1330 GeV for a simplified model incorporating only a gluino and the lightest neutralino. For a simplified model involving the strong production of first- and second-generation squarks, squark masses below 850 GeV (440 GeV) are excluded for a massless lightest neutralino, assuming mass degenerate (single light-flavour) squarks. In mSUGRA/CMSSM models with tan β = 30, A 0 = −2m 0 and μ > 0, squarks and gluinos of equal mass are excluded for masses below 1700 GeV. Additional limits are set for non-universal Higgs mass models with gaugino mediation and for simplified models involving the pair production of gluinos, each decaying to a top squark and a top quark, with the top squark decaying to a charm quark and a neutralino. These limits extend the region of supersymmetric parameter space excluded by previous searches with the ATLAS detector