Analysis of the common genetic component of large-vessel vasculitides through a meta- Immunochip strategy

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P?=?7.54E-07; ORGCA?=?1.19, ORTAK?=?1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA?=?5.52E-04, ORGCA?=?1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus

First evidence of direct CP violation in charmless two-body decays of Bs mesons

Using a data sample corresponding to an integrated luminosity of 0.35 $\mathrm{fb}^{-1}$ collected by LHCb in 2011, we report the first evidence of CP violation in the decays of $B^0_s$ mesons to $K^\pm \pi^\mp$ pairs, $A_{CP}(B^0_s \rightarrow K \pi)=0.27 \pm 0.08\,\mathrm{(stat)} \pm 0.02\,\mathrm{(syst)}$, with a significance of 3.3$\sigma$. Furthermore, we report the first observation of CP violation in $B^0$ decays at a hadron collider, $A_{CP}(B^0 \rightarrow K\pi)=-0.088 \pm 0.011\,\mathrm{(stat)} \pm 0.008\,\mathrm{(syst)}$, with a significance exceeding 6$\sigma$.Comment: 8 pages, 2 figures, 2 tables; v2 with minor changes after journal revie

Precision measurement of CPCP violation in Bs0→J/ψK+K−B_s^0 \to J/\psi K^+K^- decays

The time-dependent $CP$ asymmetry in $B_s^0 \to J/\psi K^+K^-$ decays is measured using $pp$ collision data, corresponding to an integrated luminosity of $3.0$fb$^{-1}$, collected with the LHCb detector at centre-of-mass energies of $7$ and $8$TeV. In a sample of 96 000 $B_s^0 \to J/\psi K^+K^-$ decays, the $CP$-violating phase $\phi_s$ is measured, as well as the decay widths $\Gamma_{L}$ and $\Gamma_{H}$ of the light and heavy mass eigenstates of the $B_s^0-\bar{B}_s^0$ system. The values obtained are $\phi_s = -0.058 \pm 0.049 \pm 0.006$ rad, $\Gamma_s \equiv (\Gamma_{L}+\Gamma_{H})/2 = 0.6603 \pm 0.0027 \pm 0.0015$ps$^{-1}$, and$\Delta\Gamma_s \equiv \Gamma_{L} - \Gamma_{H} = 0.0805 \pm 0.0091 \pm 0.0032$ps$^{-1}$, where the first uncertainty is statistical and the second systematic. These are the most precise single measurements of those quantities to date. A combined analysis with $B_s^{0} \to J/\psi \pi^+\pi^-$ decays gives $\phi_s = -0.010 \pm 0.039$rad. All measurements are in agreement with the Standard Model predictions. For the first time the phase $\phi_s$ is measured independently for each polarisation state of the $K^+K^-$ system and shows no evidence for polarisation dependence.Comment: 6 figure

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Microbiological hazards associated with the use of water in the post‐harvest handling and processing operations of fresh and frozen fruits, vegetables and herbs (ffFVHs). Part 1 (outbreak data analysis, literature review and stakeholder questionnaire)

The contamination of water used in post-harvest handling and processing operations of fresh and frozen fruit, vegetables and herbs (ffFVHs) is a global concern. The most relevant microbial hazards associated with this water are: Listeria monocytogenes, Salmonella spp., human pathogenic Escherichia coli and enteric viruses, which have been linked to multiple outbreaks associated with ffFVHs in the European Union (EU). Contamination (i.e. the accumulation of microbiological hazards) of the process water during post-harvest handling and processing operations is affected by several factors including: the type and contamination of the FVHs being processed, duration of the operation and transfer of microorganisms from the product to the water and vice versa, etc. For food business operators (FBOp), it is important to maintain the microbiological quality of the process water to assure the safety of ffFVHs. Good manufacturing practices (GMP) and good hygienic practices (GHP) related to a water management plan and the implementation of a water management system are critical to maintain the microbiological quality of the process water. Identified hygienic practices include technical maintenance of infrastructure, training of staff and cooling of post-harvest process water. Intervention strategies (e.g. use of water disinfection treatments and water replenishment) have been suggested to maintain the microbiological quality of process water. Chlorine-based disinfectants and peroxyacetic acid have been reported as common water disinfection treatments. However, given current practices in the EU, evidence of their efficacy under industrial conditions is only available for chlorine-based disinfectants. The use of water disinfection treatments must be undertaken following an appropriate water management strategy including validation, operational monitoring and verification. During operational monitoring, real-time information on process parameters related to the process and product, as well as the water and water disinfection treatment(s) are necessary. More specific guidance for FBOp on the validation, operational monitoring and verification is needed

Randomized trial of two intravenous schedules of the topoisomerase I inhibitor liposomal lurtotecan in women with relapsed epithelial ovarian cancer: A trial of the National Cancer Institute of Canada Clinical Trials Group

Purpose Liposomal lurtotecan (OSI-211) is a liposomal formulation of the water-soluble topoisomerase I inhibitor lurtotecan (GI147211), which demonstrated superior levels of activity compared with topotecan in preclinical models. We studied two schedules of OSI-211 in a randomized design in relapsed ovarian cancer to identify the more promising of the two schedules for further study.Patients and Methods Eligible patients had measurable epithelial ovarian, fallopian, or primary peritoneal cancer that was recurrent after one or two prior regimens of chemotherapy. Patients were randomly assigned to receive either arm A (OSI-211 1.8 mg/m(2)/d administered by 30-minute intravenous infusion on days 1, 2, and 3 every 3 weeks) or arm B (OSI-211 2.4 mg/m(2)/d administered by 30-minute intravenous infusion on days 1 and 8 every 3 weeks). The primary outcome measure was objective response, which was confirmed by independent radiologic review, and a pick the winner statistical design was used to identify the schedule most likely to be superior.Results Eighty-one patients were randomized between October 2000 and September 2001. The hematologic toxic effects were greater on arm A than on arm B (grade 4 neutropenia, 51% v 22%, respectively), as was febrile neutropenia (26% v 2.4%, respectively). Of the 80 eligible patients, eight patients (10%) had objective responses; six responders (15.4%; 95% CI, 6% to 30%) were in arm A and two responders (4.9%,- 95% CI, 1% to 17%) were in arm B.Conclusion The OSI-211 daily for 3 days intravenous schedule met the statistical criteria to be declared the winner in terms of objective response. This schedule was also associated with more myelosuppression than the schedule of OSI-211 administered in arm B. (c) 2005 by American Society of Clinical Oncology

Lifeline

Lifeline is a composition for trombone, electronics and video graphics. The sound of the trombone is analysed in real-time and used to control and generate live video graphics created using Open GL. Using the software programme MAX, video graphics respond in real-time to the instrumentalist's sound, enabling the player to use dynamic and timbral variations in their performance to control both the visuals and the music

Measurement of relative branching fractions of B decays to psi(2S) and J/psi mesons

The relative rates of B-meson decays into J/ψ and ψ(2S) mesons are measured for the three decay modes in pp collisions recorded with the LHCb detector. The ratios of branching fractions ( B ) are measured to be where the third uncertainty is from the ratio of the ψ(2S) and J/ψ branching fractions to μ + μ −