Protection and mechanism of action of a novel human respiratory syncytial virus vaccine candidate based on the extracellular domain of small hydrophobic protein

Infections with human respiratory syncytial virus (HRSV) occur globally in all age groups and can have devastating consequences in young infants. We demonstrate that a vaccine based on the extracellular domain (SHe) of the small hydrophobic (SH) protein of HRSV, reduced viral replication in challenged laboratory mice and in cotton rats. We show that this suppression of viral replication can be transferred by serum and depends on a functional IgG receptor compartment with a major contribution of FcRI and FcRIII. Using a conditional cell depletion method, we provide evidence that alveolar macrophages are involved in the protection by SHe-specific antibodies. HRSV-infected cells abundantly express SH on the cell surface and are likely the prime target of the humoral immune response elicited by SHe-based vaccination. Finally, natural infection of humans and experimental infection of mice or cotton rats does not induce a strong immune response against HRSV SHe. Using SHe as a vaccine antigen induces immune protection against HRSV by a mechanism that differs from the natural immune response and from other HRSV vaccination strategies explored to date. Hence, HRSV vaccine candidates that aim at inducing protective neutralizing antibodies or T-cell responses could be complemented with a SHe-based antigen to further improve immune protection

Exploring the equity of GP practice prescribing rates for selected coronary heart disease drugs: a multiple regression analysis with proxies of healthcare need

Background There is a small, but growing body of literature highlighting inequities in GP practice prescribing rates for many drug therapies. The aim of this paper is to further explore the equity of prescribing for five major CHD drug groups and to explain the amount of variation in GP practice prescribing rates that can be explained by a range of healthcare needs indicators (HCNIs). Methods The study involved a cross-sectional secondary analysis in four primary care trusts (PCTs 1–4) in the North West of England, including 132 GP practices. Prescribing rates (average daily quantities per registered patient aged over 35 years) and HCNIs were developed for all GP practices. Analysis was undertaken using multiple linear regression. Results Between 22–25% of the variation in prescribing rates for statins, beta-blockers and bendrofluazide was explained in the multiple regression models. Slightly more variation was explained for ACE inhibitors (31.6%) and considerably more for aspirin (51.2%). Prescribing rates were positively associated with CHD hospital diagnoses and procedures for all drug groups other than ACE inhibitors. The proportion of patients aged 55–74 years was positively related to all prescribing rates other than aspirin, where they were positively related to the proportion of patients aged >75 years. However, prescribing rates for statins and ACE inhibitors were negatively associated with the proportion of patients aged >75 years in addition to the proportion of patients from minority ethnic groups. Prescribing rates for aspirin, bendrofluazide and all CHD drugs combined were negatively associated with deprivation. Conclusion Although around 25–50% of the variation in prescribing rates was explained by HCNIs, this varied markedly between PCTs and drug groups. Prescribing rates were generally characterised by both positive and negative associations with HCNIs, suggesting possible inequities in prescribing rates on the basis of ethnicity, deprivation and the proportion of patients aged over 75 years (for statins and ACE inhibitors, but not for aspirin)

Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Nutritional evaluation of children with phenylketonuria

CONTEXT: Dietary phenylalanine (PA) restriction is the most effective form for reducing its excess in the blood and is the only efficient method for treating phenylketonuria. The diet is complex and should be adapted to combine the patients' eating habits, growth and development. It depends basically on the use of industrialized products as substitutes free of PA for proteins that are not fully supplied. OBJECTIVE: To evaluate the nutritional status of children with phenylketonuria (PKU) by anthropometric measurements and food intake. DESIGN: Cross-sectional study. SETTING: Children with PKU attending the Association of Parents and Friends of Handicapped Children (Associação de Pais e Amigos dos Excepcionais - APAE) and normal children attending at municipal day care centers in São Paulo. PARTICIPANTS: 42 children with PKU and 31 normal children aged 1 to 12 of both sexes were assessed in two groups, under and over 7 years of age. MAIN MEASUREMENTS: Weight and height measurements. RESULTS: Children with PKU ingested calories, calcium, iron, zinc, and copper below the recommended values, whereas the protein intake was within the normal range. Food intake in the group of normal children was within normality rates. The height/weight Z-score means for children with PKU were 0.47 for those under 7 years and 1.86 for 7 year-olds and over; in normal children the means were 0.97 <7 years and 1.54 ³7 years, with no statistically significant difference. The height/age Z-score means were significantly lower in the PKU children <7 years (-1.23) than in the normal controls (0.91). CONCLUSIONS: The data presented demonstrate the importance of nutritional surveillance in patients with PKU so as to support adequacy of nutrient intake and to guarantee growth within the relevant standards.CONTEXTO: A restrição dietética da fenilalanina (FAL) é a forma mais efetiva para reduzir o seu excesso no sangue e o único método efetivo de tratar a fenilcetonúria. A dieta é complexa e deve ser adaptada para combinar hábitos alimentares, crescimento e desenvolvimento dos pacientes. Depende basicamente do uso de produtos industrializados como substitutos protéicos isentos de FAL, não totalmente suplementados. OBJETIVO: Avaliar o estado nutricional das crianças fenilcetonúricas por medidas antropométricas e o consumo alimentar. TIPO DE ESTUDO: Estudo transversal LOCAL: Associação de Pais e Amigos dos Excepcionais (APAE) de São Paulo, Creche e Centro de Juventude da Prefeitura de São Paulo. PARTICIPANTES: 42 crianças fenilcetonúricas e 31 normais, na faixa etária de 1 a 12 anos, divididas em dois grupos abaixo e acima de 7 anos, de ambos os sexos. RESULTADOS: As fenilcetonúricas apresentaram porcentagem de adequação da ingestão de calorias, cálcio, ferro, zinco e cobre abaixo do recomendado. A ingestão protéica estava dentro da normalidade. O consumo alimentar no grupo de crianças normais apresentou-se dentro da faixa da normalidade. As médias de peso para estatura em escore z das fenilcetonúricas foram 0.47 < 7 anos e 1.86 ³ 7 anos; nas normais 0.97 < 7 anos e 1.54 ³ 7 anos, sem diferença estatisticamente significante. As médias de E/I apresentaram diferença estatisticamente significante entre fenilcetonúricas < 7 anos (- 1.23) e crianças normais de mesma faixa etária (0,91). CONCLUSÃO: Concluiu-se que a vigilância nutricional em crianças fenilcetonúricas é importante para manutenção dos padrões de crescimento e o adequado consumo de nutrientes.University of São PauloFederal University of São PauloUNIFESPSciEL

Measurement of the top quark-pair production cross section with ATLAS in pp collisions at \sqrt{s}=7\TeV

A measurement of the production cross-section for top quark pairs(\ttbar) in $pp$ collisions at \sqrt{s}=7 \TeV is presented using data recorded with the ATLAS detector at the Large Hadron Collider. Events are selected in two different topologies: single lepton (electron $e$ or muon $\mu$) with large missing transverse energy and at least four jets, and dilepton ($ee$, $\mu\mu$ or $e\mu$) with large missing transverse energy and at least two jets. In a data sample of 2.9 pb-1, 37 candidate events are observed in the single-lepton topology and 9 events in the dilepton topology. The corresponding expected backgrounds from non-\ttbar Standard Model processes are estimated using data-driven methods and determined to be $12.2 \pm 3.9$ events and $2.5 \pm 0.6$ events, respectively. The kinematic properties of the selected events are consistent with SM \ttbar production. The inclusive top quark pair production cross-section is measured to be \sigmattbar=145 \pm 31 ^{+42}_{-27} pb where the first uncertainty is statistical and the second systematic. The measurement agrees with perturbative QCD calculations.Comment: 30 pages plus author list (50 pages total), 9 figures, 11 tables, CERN-PH number and final journal adde

Inclusive search for same-sign dilepton signatures in pp collisions at root s=7 TeV with the ATLAS detector

An inclusive search is presented for new physics in events with two isolated leptons (e or mu) having the same electric charge. The data are selected from events collected from p p collisions at root s = 7 TeV by the ATLAS detector and correspond to an integrated luminosity of 34 pb(-1). The spectra in dilepton invariant mass, missing transverse momentum and jet multiplicity are presented and compared to Standard Model predictions. In this event sample, no evidence is found for contributions beyond those of the Standard Model. Limits are set on the cross-section in a fiducial region for new sources of same-sign high-mass dilepton events in the ee, e mu and mu mu channels. Four models predicting same-sign dilepton signals are constrained: two descriptions of Majorana neutrinos, a cascade topology similar to supersymmetry or universal extra dimensions, and fourth generation d-type quarks. Assuming a new physics scale of 1 TeV, Majorana neutrinos produced by an effective operator V with masses below 460 GeV are excluded at 95% confidence level. A lower limit of 290 GeV is set at 95% confidence level on the mass of fourth generation d-type quarks

Measurement of inclusive two-particle angular correlations in pp collisions with the ATLAS detector at the LHC

We present a measurement of two-particle angular correlations in proton- proton collisions at s√=900 GeV and 7 TeV. The collision events were collected during 2009 and 2010 with the ATLAS detector at the Large Hadron Collider using a single-arm minimum bias trigger. Correlations are measured for charged particles produced in the kinematic range of transverse momentum p T  > 100 MeV and pseudorapidity |η| < 2.5. A complex structure in pseudorapidity and azimuth is observed at both collision energies. Results are compared to pythia 8 and herwig++ as well as to the AMBT2B, DW and Perugia 2011 tunes of pythia 6. The data are not satisfactorily described by any of these models

Measurement of D*+/- meson production in jets from pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

This paper reports a measurement of D*+/- meson production in jets from proton-proton collisions at a center-of-mass energy of sqrt(s) = 7 TeV at the CERN Large Hadron Collider. The measurement is based on a data sample recorded with the ATLAS detector with an integrated luminosity of 0.30 pb^-1 for jets with transverse momentum between 25 and 70 GeV in the pseudorapidity range |eta| < 2.5. D*+/- mesons found in jets are fully reconstructed in the decay chain: D*+ -> D0pi+, D0 -> K-pi+, and its charge conjugate. The production rate is found to be N(D*+/-)/N(jet) = 0.025 +/- 0.001(stat.) +/- 0.004(syst.) for D*+/- mesons that carry a fraction z of the jet momentum in the range 0.3 < z < 1. Monte Carlo predictions fail to describe the data at small values of z, and this is most marked at low jet transverse momentum.Comment: 10 pages plus author list (22 pages total), 5 figures, 1 table, matches published version in Physical Review

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011