98 research outputs found

    Incident-energy dependence of the effective temperature in heavy-ion collisions

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    We study the behaviour of the effective temperature for K+ in several energy domains. For this purpose, we apply the recently developed SPheRIO code for hydrodynamics in 3+1 dimensions, using both Landau-type compact initial conditions and spatially more spread ones. We show that initial conditions given in small volume, like Landau-type ones, are unable to reproduce the effective temperature together with other data (multiplicities and rapidity distributions). These quantities can be reproduced altogether only when using a large initial volume with an appropriate velocity distribution

    Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children

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    BACKGROUND: Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide. OBJECTIVES: To describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomised, placebo-controlled trials and regulatory comments. SEARCH METHODS: We searched trial registries, electronic databases (to 22 July 2013) and regulatory archives, and corresponded with manufacturers to identify all trials. We also requested clinical study reports. We focused on the primary data sources of manufacturers but we checked that there were no published randomised controlled trials (RCTs) from non-manufacturer sources by running electronic searches in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE (Ovid), EMBASE, Embase.com, PubMed (not MEDLINE), the Database of Reviews of Effects, the NHS Economic Evaluation Database and the Health Economic Evaluations Database. SELECTION CRITERIA: Randomised, placebo-controlled trials on adults and children with confirmed or suspected exposure to naturally occurring influenza. DATA COLLECTION AND ANALYSIS: We extracted clinical study reports and assessed risk of bias using purpose-built instruments. We analysed the effects of zanamivir and oseltamivir on time to first alleviation of symptoms, influenza outcomes, complications, hospitalisations and adverse events in the intention-to-treat (ITT) population. All trials were sponsored by the manufacturers. MAIN RESULTS: We obtained 107 clinical study reports from the European Medicines Agency (EMA), GlaxoSmithKline and Roche. We accessed comments by the US Food and Drug Administration (FDA), EMA and Japanese regulator. We included 53 trials in Stage 1 (a judgement of appropriate study design) and 46 in Stage 2 (formal analysis), including 20 oseltamivir (9623 participants) and 26 zanamivir trials (14,628 participants). Inadequate reporting put most of the zanamivir studies and half of the oseltamivir studies at a high risk of selection bias. There were inadequate measures in place to protect 11 studies of oseltamivir from performance bias due to non-identical presentation of placebo. Attrition bias was high across the oseltamivir studies and there was also evidence of selective reporting for both the zanamivir and oseltamivir studies. The placebo interventions in both sets of trials may have contained active substances. Time to first symptom alleviation. For the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval (CI) 8.4 to 25.1 hours, P 1000) and nausea whilst on treatment (RD 4.15%, 95% CI 0.86 to 9.51); NNTH = 25 (95% CI 11 to 116). AUTHORS' CONCLUSIONS: Oseltamivir and zanamivir have small, non-specific effects on reducing the time to alleviation of influenza symptoms in adults, but not in asthmatic children. Using either drug as prophylaxis reduces the risk of developing symptomatic influenza. Treatment trials with oseltamivir or zanamivir do not settle the question of whether the complications of influenza (such as pneumonia) are reduced, because of a lack of diagnostic definitions. The use of oseltamivir increases the risk of adverse effects, such as nausea, vomiting, psychiatric effects and renal events in adults and vomiting in children. The lower bioavailability may explain the lower toxicity of zanamivir compared to oseltamivir. The balance between benefits and harms should be considered when making decisions about use of both NIs for either the prophylaxis or treatment of influenza. The influenza virus-specific mechanism of action proposed by the producers does not fit the clinical evidence

    Rectal GIST Presenting as a Submucosal Calculus

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    This case report presents an incidental finding of a rectal GIST (gastrointestinal stromal tumor) presenting as a submucosal calculus, not previously reported. A 53-year-old man without a significant medical history presented with abdominal pain in the left lower quadrant, and with constipation. Upon rectal examination, a hard submucosal swelling was palpated 4 cm from the anus, at 3 o’clock, in the left rectum wall. X-ray photos, computerized tomography (CT)-scan and a magnetic resonance imaging (MRI) scan clearly showed a calculus. Excision revealed a turnip-like lesion, 3.1×2.3×1.8 cm. Analysis showed it was a rectal GIST, a rare mesenchymal tumor of the gastrointestinal tract, which expressed CD117 (or c-kit, a marker of kit-receptor tyrosine kinase) and CD34. Calcification is not a usual clinicopathological feature of GISTs [1–3], and although a number of rectal GISTs have been reported [4–9], we have found no cases so far of rectal GIST presenting as a submucosal calculus

    Study of the nucleon-induced preequilibrium reactions in terms of the Quantum Molecular Dynamics

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    The preequilibrium (nucleon-in, nucleon-out) angular distributions of 27^{27}Al, 58^{58}Ni and 90^{90}Zr have been analyzed in the energy region from 90 to 200 MeV in terms of the Quantum Moleculear Dynamics (QMD) theory. First, we show that the present approach can reproduce the measured (p,xp') and (p,xn) angular distributions leading to continuous final states without adjusing any parameters. Second, we show the results of the detailed study of the preequilibrium reaction processes; the step-wise contribution to the angular distribution, comparison with the quantum-mechanical Feshbach-Kerman-Koonin theory, the effects of momentum distribution and surface refraction/reflection to the quasifree scattering. Finally, the present method was used to assess the importance of multiple preequilibrium particle emission as a function of projectile energy up to 1 GeV.Comment: 22pages, Revex is used, 10 Postscript figures are available by request from [email protected]

    Climate scenarios for Switzerland CH2018 - approach and implications

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    To make sound decisions in the face of climate change, government agencies, policymakers and private stakeholders require suitable climate information on local to regional scales. In Switzerland, the development of climate change scenarios is strongly linked to the climate adaptation strategy of the Confederation. The current climate scenarios for Switzerland CH2018 - released in form of six user-oriented products - were the result of an intensive collaboration between academia and administration under the umbrella of the National Centre for Climate Services (NCCS), accounting for user needs and stakeholder dialogues from the beginning. A rigorous scientific concept ensured consistency throughout the various analysis steps of the EURO-CORDEX projections and a common procedure on how to extract robust results and deal with associated uncertainties. The main results show that Switzerland?s climate will face dry summers, heavy precipitation, more hot days and snow-scarce winters. Approximately half of these changes could be alleviated by mid-century through strong global mitigation efforts. A comprehensive communication concept ensured that the results were rolled out and distilled in specific user-oriented communication measures to increase their uptake and to make them actionable. A narrative approach with four fictitious persons was used to communicate the key messages to the general public. Three years after the release, the climate scenarios have proven to be an indispensable information basis for users in climate adaptation and for downstream applications. Potential for extensions and updates has been identified since then and will shape the concept and planning of the next scenario generation in Switzerland

    Association between mental health conditions and rehospitalization, mortality, and functional outcomes in patients with stroke following inpatient rehabilitation

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    <p>Abstract</p> <p>Background</p> <p>Limited evidence exists regarding the association of pre-existing mental health conditions in patients with stroke and stroke outcomes such as rehospitalization, mortality, and function. We examined the association between mental health conditions and rehospitalization, mortality, and functional outcomes in patients with stroke following inpatient rehabilitation.</p> <p>Methods</p> <p>Our observational study used the 2001 VA Integrated Stroke Outcomes database of 2162 patients with stroke who underwent rehabilitation at a Veterans Affairs Medical Center.</p> <p>Separate models were fit to our outcome measures that included 6-month rehospitalization or death, 6-month mortality post-discharge, and functional outcomes post inpatient rehabilitation as a function of number and type of mental health conditions. The models controlled for patient socio-demographics, length of stay, functional status, and rehabilitation setting.</p> <p>Results</p> <p>Patients had an average age of 68 years. Patients with stroke and two or more mental health conditions were more likely to be readmitted or die compared to patients with no conditions (OR: 1.44, p = 0.04). Depression and anxiety were associated with a greater likelihood of rehospitalization or death (OR: 1.33, p = 0.04; OR:1.47, p = 0.03). Patients with anxiety were more likely to die at six months (OR: 2.49, p = 0.001).</p> <p>Conclusions</p> <p>Patients with stroke with pre-existing mental health conditions may need additional psychotherapy interventions, which may potentially improve stroke outcomes post-hospitalization.</p

    MS4a4B, a CD20 Homologue in T Cells, Inhibits T Cell Propagation by Modulation of Cell Cycle

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    MS4a4B, a CD20 homologue in T cells, is a novel member of the MS4A gene family in mice. The MS4A family includes CD20, FcεRIβ, HTm4 and at least 26 novel members that are characterized by their structural features: with four membrane-spanning domains, two extracellular domains and two cytoplasmic regions. CD20, FcεRIβ and HTm4 have been found to function in B cells, mast cells and hematopoietic cells respectively. However, little is known about the function of MS4a4B in T cell regulation. We demonstrate here that MS4a4B negatively regulates mouse T cell proliferation. MS4a4B is highly expressed in primary T cells, natural killer cells (NK) and some T cell lines. But its expression in all malignant T cells, including thymoma and T hybridoma tested, was silenced. Interestingly, its expression was regulated during T cell activation. Viral vector-driven overexpression of MS4a4B in primary T cells and EL4 thymoma cells reduced cell proliferation. In contrast, knockdown of MS4a4B accelerated T cell proliferation. Cell cycle analysis showed that MS4a4B regulated T cell proliferation by inhibiting entry of the cells into S-G2/M phase. MS4a4B-mediated inhibition of cell cycle was correlated with upregulation of Cdk inhibitory proteins and decreased levels of Cdk2 activity, subsequently leading to inhibition of cell cycle progression. Our data indicate that MS4a4B negatively regulates T cell proliferation. MS4a4B, therefore, may serve as a modulator in the negative-feedback regulatory loop of activated T cell

    A Genetically Encoded Tag for Correlated Light and Electron Microscopy of Intact Cells, Tissues, and Organisms

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    Electron microscopy (EM) achieves the highest spatial resolution in protein localization, but specific protein EM labeling has lacked generally applicable genetically encoded tags for in situ visualization in cells and tissues. Here we introduce “miniSOG” (for mini Singlet Oxygen Generator), a fluorescent flavoprotein engineered from Arabidopsis phototropin 2. MiniSOG contains 106 amino acids, less than half the size of Green Fluorescent Protein. Illumination of miniSOG generates sufficient singlet oxygen to locally catalyze the polymerization of diaminobenzidine into an osmiophilic reaction product resolvable by EM. MiniSOG fusions to many well-characterized proteins localize correctly in mammalian cells, intact nematodes, and rodents, enabling correlated fluorescence and EM from large volumes of tissue after strong aldehyde fixation, without the need for exogenous ligands, probes, or destructive permeabilizing detergents. MiniSOG permits high quality ultrastructural preservation and 3-dimensional protein localization via electron tomography or serial section block face scanning electron microscopy. EM shows that miniSOG-tagged SynCAM1 is presynaptic in cultured cortical neurons, whereas miniSOG-tagged SynCAM2 is postsynaptic in culture and in intact mice. Thus SynCAM1 and SynCAM2 could be heterophilic partners. MiniSOG may do for EM what Green Fluorescent Protein did for fluorescence microscopy

    Growth effects of exclusive breastfeeding promotion by peer counsellors in sub-Saharan Africa: the cluster-randomised PROMISE EBF trial

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    Background: In this multi-country cluster-randomized behavioural intervention trial promoting exclusive breastfeeding (EBF) in Africa, we compared growth of infants up to 6 months of age living in communities where peer counsellors promoted EBF with growth in those infants living in control communities. Methods: A total of 82 clusters in Burkina Faso, Uganda and South Africa were randomised to either the intervention or the control arm. Feeding data and anthropometric measurements were collected at visits scheduled 3, 6, 12 and 24 weeks post-partum. We calculated weight-for-length (WLZ), length-for-age (LAZ) and weight-for-age (WAZ) z-scores. Country specific adjusted Least Squares Means with 95% confidence intervals (CI) based on a longitudinal analysis are reported. Prevalence ratios (PR) for the association between peer counselling for EBF and wasting (WLZ < −2), stunting (LAZ < −2) and underweight (WAZ < −2) were calculated at each data collection point. Results: The study included a total of 2,579 children. Adjusting for socio-economic status, the mean WLZ at 24 weeks were in Burkina Faso −0.20 (95% CI −0.39 to −0.01) and in Uganda −0.23 (95% CI −0.43 to −0.03) lower in the intervention than in the control arm. In South Africa the mean WLZ at 24 weeks was 0.23 (95% CI 0.03 to 0.43) greater in the intervention than in the control arm. Differences in LAZ between the study arms were small and not statistically significant. In Uganda, infants in the intervention arm were more likely to be wasted compared to those in the control arm at 24 weeks (PR 2.36; 95% CI 1.11 to 5.00). Differences in wasting in South Africa and Burkina Faso and stunting and underweight in all three countries were small and not significantly different. Conclusions: There were small differences in mean anthropometric indicators between the intervention and control arms in the study, but in Uganda and Burkina Faso, a tendency to slightly lower ponderal growth (weight-for-length z-scores) was found in the intervention arms. Trial registration number: ClinicalTrials.gov: NCT0039715

    Whole-body tissue stabilization and selective extractions via tissue-hydrogel hybrids for high-resolution intact circuit mapping and phenotyping

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    To facilitate fine-scale phenotyping of whole specimens, we describe here a set of tissue fixation-embedding, detergent-clearing and staining protocols that can be used to transform excised organs and whole organisms into optically transparent samples within 1–2 weeks without compromising their cellular architecture or endogenous fluorescence. PACT (passive CLARITY technique) and PARS (perfusion-assisted agent release in situ) use tissue-hydrogel hybrids to stabilize tissue biomolecules during selective lipid extraction, resulting in enhanced clearing efficiency and sample integrity. Furthermore, the macromolecule permeability of PACT- and PARS-processed tissue hybrids supports the diffusion of immunolabels throughout intact tissue, whereas RIMS (refractive index matching solution) grants high-resolution imaging at depth by further reducing light scattering in cleared and uncleared samples alike. These methods are adaptable to difficult-to-image tissues, such as bone (PACT-deCAL), and to magnified single-cell visualization (ePACT). Together, these protocols and solutions enable phenotyping of subcellular components and tracing cellular connectivity in intact biological networks
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