214 research outputs found

    Aus dem Asklepieion von Kos

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    Holographic dilepton production in a thermalizing plasma

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    We determine the out-of-equilibrium production rate of dileptons at rest in strongly coupled N=4 Super Yang-Mills plasma using the AdS/CFT correspondence. Thermalization is achieved via the gravitational collapse of a thin shell of matter in AdS_5 space and the subsequent formation of a black hole, which we describe in a quasistatic approximation. Prior to thermalization, the dilepton spectral function is observed to oscillate as a function of frequency, but the amplitude of the oscillations decreases when thermal equilibrium is approached. At the same time, we follow the flow of the quasinormal spectrum of the corresponding U(1) vector field towards its equilibrium limit.Comment: 21 pages, 7 figures. v2: Version accepted for publication in JHEP; minor modifications, added reference

    Determining the interviewer effect on CQ Index outcomes: a multilevel approach

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    <p>Abstract</p> <p>Background</p> <p>The CQ Index for the elderly, a quality-of-care questionnaire administered by conducting interviews, is used to assess clients' experiences in Dutch nursing homes and homes for the elderly. This article describes whether inter-interviewer differences influence the perceived quality of healthcare services reported by residents, the size of this interviewer effect and the influence of the interviewer characteristics on CQ Index dimensions for public reporting.</p> <p>Methods</p> <p>Data from 4345 questionnaires was used. Correlations were calculated, reliability analyses were performed, and a multilevel analysis was used to calculate the degree of correlation between two interviewers within one health care institution. Five models were constructed and the Intra Class Correlation (ICC) was calculated. Healthcare institutions were given 1-5 stars on every quality dimensions (1 = worst and 5 = best), adjusted for resident and interviewer characteristics. The effect of these characteristics on the assignment of the stars was investigated.</p> <p>Results</p> <p>In a multilevel approach, the ICC showed a significant amount of variance on five quality dimensions. Of the interviewer characteristics, only previous interviewing experience, the reason of interviewing and general knowledge of health care had a significant effect on the quality dimensions. Adjusting for interviewer characteristics did not affect the overall star assignment to the institutions regarding 7 of 12 quality dimensions. For the other five dimensions (Shared decision-making, Meals, Professional competency, Autonomy, and Availability of personnel) a minor effect was found.</p> <p>Conclusions</p> <p>We have shown that training, the use of experienced interviewers, written instructions, supervision and educational meetings do not automatically prevent interviewer effects. While the results of this study can be used to improve the quality of services provided by these institutions, several CQ index dimensions should be interpreted with caution for external purposes (accountability and transparency).</p

    Proteolytic processing of QSOX1A ensures efficient secretion of a potent disulfide catalyst

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    QSOX1 (quiescin sulfhydryl oxidase 1) efficiently catalyses the insertion of disulfide bonds into a wide range of proteins. The enzyme is mechanistically well characterized, but its subcellular location and the identity of its protein substrates remain ill-defined. The function of QSOX1 is likely to involve disulfide formation in proteins entering the secretory pathway or outside the cell. In the present study, we show that this enzyme is efficiently secreted from mammalian cells despite the presence of a transmembrane domain. We identify internal cleavage sites and demonstrate that the protein is processed within the Golgi apparatus to yield soluble enzyme. As a consequence of this efficient processing, QSOX1 is probably functional outside the cell. Also, QSOX1 forms a dimer upon cleavage of the C-terminal domain. The processing of QSOX1 suggests a novel level of regulation of secretion of this potent disulfide catalyst and producer of hydrogen peroxide

    Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID)

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    Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting. Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm). Conclusions: Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies

    Pharyngeal electrical stimulation for neurogenic dysphagia following stroke, traumatic brain injury or other causes: Main results from the PHADER cohort study

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    BackgroundNeurogenic dysphagia is common and has no definitive treatment. We assessed whether pharyngeal electrical stimulation (PES) is associated with reduced dysphagia.MethodsThe PHAryngeal electrical stimulation for treatment of neurogenic Dysphagia European Registry (PHADER) was a prospective single-arm observational cohort study. Participants were recruited with neurogenic dysphagia (comprising five groups – stroke not needing ventilation; stroke needing ventilation; ventilation acquired; traumatic brain injury; other neurological causes). PES was administered once daily for three days. The primary outcome was the validated dysphagia severity rating scale (DSRS, score best-worst 0–12) at 3 months.FindingsOf 255 enrolled patients from 14 centres in Austria, Germany and UK, 10 failed screening. At baseline, mean (standard deviation) or median [interquartile range]: age 68 (14) years, male 71%, DSRS 11·4 (1·7), time from onset to treatment 32 [44] days; age, time and DSRS differed between diagnostic groups. Insertion of PES catheters was successfully inserted in 239/245 (98%) participants, and was typically easy taking 11·8 min. 9 participants withdrew before the end of treatment. DSRS improved significantly in all dysphagia groups, difference in means (95% confidence intervals, CI) from 0 to 3 months: stroke (n = 79) –6·7 (–7·8, –5·5), ventilated stroke (n = 98) –6·5 (–7·6, –5·5); ventilation acquired (n = 35) –6·6 (–8·4, –4·8); traumatic brain injury (n = 24) -4·5 (–6·6, –2·4). The results for DSRS were mirrored for instrumentally assessed penetration aspiration scale scores. DSRS improved in both supratentorial and infratentorial stroke, with no difference between them (p = 0·32). In previously ventilated participants with tracheotomy, DSRS improved more in participants who could be decannulated (n = 66) –7·5 (–8·6, –6·5) versus not decannulated (n = 33) –2·1 (–3·2, –1·0) (

    Assessment of the performance of CORDEX Regional Climate Models in Simulating Eastern Africa Rainfall

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    This study evaluates the ability of 10 regional climate models (RCMs) from the Coordinated Regional Climate Downscaling Experiment (CORDEX) in simulating the characteristics of rainfall patterns over eastern Africa. The seasonal climatology, annual rainfall cycles, and interannual variability of RCM output have been assessed over three homogeneous subregions against a number of observational datasets. The ability of the RCMs in simulating large-scale global climate forcing signals is further assessed by compositing the El Niño–Southern Oscillation (ENSO) and Indian Ocean dipole (IOD) events. It is found that most RCMs reasonably simulate the main features of the rainfall climatology over the three subregions and also reproduce the majority of the documented regional responses to ENSO and IOD forcings. At the same time the analysis shows significant biases in individual models depending on subregion and season; however, the ensemble mean has better agreement with observation than individual models. In general, the analysis herein demonstrates that the multimodel ensemble mean simulates eastern Africa rainfall adequately and can therefore be used for the assessment of future climate projections for the region

    Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

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    The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

    Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

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    Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe
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