244 research outputs found

    Fexofenadine is Efficacious and Safe in Children (Aged 6-11 Years) with Seasonal Allergic Rhinitis

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    Background: This is the first prospective, randomized, doubleblind, placebo-controlled study showing statistical improvement of an H1-antihistamine in children with seasonal allergic rhinitis in all symptoms throughout the entire treatment period. Objective: This randomized, placebo-controlled, parallelgroup,double-blind study was performed to assess the efficacy and safety of fexofenadine in children with seasonal allergic rhinitis. Methods: This study was conducted at 148 centers in 15 countries. Nine hundred thirty-five children (aged 6-11 years) were randomized and treated with either fexofenadine HCl 30 mg (n = 464) or placebo (n = 471) tablets twice a day for 14 days. Individual symptoms (sneezing; rhinorrhea; itchy nose, mouth, throat, and/or ears; itchy, watery, and/or red eyes; and nasal congestion) were assessed at baseline and then daily at 7:00 AM and 7:00 PM (±1 hour) during the double-blind treatment period. Each total symptom score was the sum of all symptoms, excluding nasal congestion. The primary efficacy variable was the change from baseline in the average of the daily 12-hour evening reflective total symptom scores throughout the double-blind treatment. Safety was evaluated from adverse-event reporting, vital signs, physical examinations, and clinical laboratory data at screening and study end point

    Filaggrin mutations in relation to skin barrier and atopic dermatitis in early infancy

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    Background Loss-of-function mutations in the skin barrier gene filaggrin (FLG) increase the risk of atopic dermatitis (AD), but their role in skin barrier function, dry skin and eczema in infancy is unclear. Objectives To determine the role of FLG mutations in impaired skin barrier function, dry skin, eczema and AD at 3 months of age and throughout infancy. Methods FLG mutations were analysed in 1836 infants in the Scandinavian population-based PreventADALL study. Transepidermal water loss (TEWL), dry skin, eczema and AD were assessed at 3, 6 and 12 months of age. Results FLG mutations were observed in 166 (9%) infants. At 3 months, carrying FLG mutations was not associated with impaired skin barrier function (TEWL > 11 center dot 3 g m(-2) h(-1)) or dry skin, but was associated with eczema [odds ratio (OR) 2 center dot 89, 95% confidence interval (CI) 1 center dot 95-4 center dot 28; P < 0 center dot 001]. At 6 months, mutation carriers had significantly higher TEWL than nonmutation carriers [mean 9 center dot 68 (95% CI 8 center dot 69-10 center dot 68) vs. 8 center dot 24 (95% CI 7 center dot 97-8 center dot 15), P < 0 center dot 01], and at 3 and 6 months mutation carriers had an increased risk of dry skin on the trunk (OR 1 center dot 87, 95% CI 1 center dot 25-2 center dot 80; P = 0 center dot 002 and OR 2 center dot 44, 95% CI 1 center dot 51-3 center dot 95; P < 0 center dot 001) or extensor limb surfaces (OR 1 center dot 52, 95% CI 1 center dot 04-2 center dot 22; P = 0 center dot 028 and OR 1 center dot 74, 95% CI 1 center dot 17-2 center dot 57; P = 0 center dot 005). FLG mutations were associated with eczema and AD in infancy. Conclusions FLG mutations were not associated with impaired skin barrier function or dry skin in general at 3 months of age, but increased the risk for eczema, and for dry skin on the trunk and extensor limb surfaces at 3 and 6 months.Peer reviewe

    The academic–vocational divide in three Nordic countries : implications for social class and gender

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    In this study we examine how the academic–vocational divide is manifested today in Finland, Iceland and Sweden in the division between vocationally (VET) and academicallyoriented programmes at the upper-secondary school level. The paper is based on a critical re-analysis of results from previous studies; in it we investigate the implications of this divide for class and gender inequalities. The theoretical lens used for the synthesis is based on Bernstein®s theory of pedagogic codes. In the re-analysis we draw on previous studies of policy, curriculum and educational praxis as well as official statistics. The main conclusions are that contemporary policy and curriculum trends in all three countries are dominated by a neo-liberal discourse stressing principles such as “market relevance” and employability. This trend strengthens the academic–vocational divide, mainly through an organisation of knowledge in VET that separates it from more general and theoretical elements. This trend also seems to affect VET students’ transitions in terms of reduced access to higher education, particularly in male-dominated programmes. We also identify low expectations for VET students, manifested through choice of textbooks and tasks, organisation of teacher teams and the advice of career counsellors.Peer reviewe

    Discovery of distinct immune phenotypes using machine learning in pulmonary arterial hypertension

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    RATIONALE: Accumulating evidence implicates inflammation in pulmonary arterial hypertension (PAH) and therapies targeting immunity are under investigation, though it remains unknown if distinct immune phenotypes exist. OBJECTIVE: Identify PAH immune phenotypes based on unsupervised analysis of blood proteomic profiles. METHODS AND RESULTS: In a prospective observational study of Group 1 PAH patients evaluated at Stanford University (discovery cohort, n=281) and University of Sheffield (validation cohort, n=104) between 2008-2014, we measured a circulating proteomic panel of 48 cytokines, chemokines, and factors using multiplex immunoassay. Unsupervised machine learning (consensus clustering) was applied in both cohorts independently to classify patients into proteomic immune clusters, without guidance from clinical features. To identify central proteins in each cluster, we performed partial correlation network analysis. Clinical characteristics and outcomes were subsequently compared across clusters. Four PAH clusters with distinct proteomic immune profiles were identified in the discovery cohort. Cluster 2 (n=109) had low cytokine levels similar to controls. Other clusters had unique sets of upregulated proteins central to immune networks- cluster 1 (n=58)(TRAIL, CCL5, CCL7, CCL4, MIF), cluster 3 (n=77)(IL-12, IL-17, IL-10, IL-7, VEGF), and cluster 4 (n=37)(IL-8, IL-4, PDGF-ÎČ, IL-6, CCL11). Demographics, PAH etiologies, comorbidities, and medications were similar across clusters. Non-invasive and hemodynamic surrogates of clinical risk identified cluster 1 as high-risk and cluster 3 as low-risk groups. Five-year transplant-free survival rates were unfavorable for cluster 1 (47.6%, CI 35.4-64.1%) and favorable for cluster 3 (82.4%, CI 72.0-94.3%)(across-cluster p<0.001). Findings were replicated in the validation cohort, where machine learning classified four immune clusters with comparable proteomic, clinical, and prognostic features. CONCLUSIONS: Blood cytokine profiles distinguish PAH immune phenotypes with differing clinical risk that are independent of World Health Organization Group 1 subtypes. These phenotypes could inform mechanistic studies of disease pathobiology and provide a framework to examine patient responses to emerging therapies targeting immunity

    Allergen-specific immunotherapy provides immediate, long-term and preventive clinical effects in children and adults: the effects of immunotherapy can be categorised by level of benefit -the centenary of allergen specific subcutaneous immunotherapy

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    Allergen Specific Immunotherapy (SIT) for respiratory allergic diseases is able to significantly improve symptoms as well as reduce the need for symptomatic medication, but SIT also has the capacity for long-term clinical effects and plays a protective role against the development of further allergies and symptoms. The treatment acts on basic immunological mechanisms, and has the potential to change the pathological allergic immune response. In this paper we discuss some of the most important achievements in the documentation of the benefits of immunotherapy, over the last 2 decades, which have marked a period of extensive research on the clinical effects and immunological background of the mechanisms involved. The outcome of immunotherapy is described as different levels of benefit from early reduction in symptoms over progressive clinical effects during treatment to long-term effects after discontinuation of the treatment and prevention of asthma. The efficacy of SIT increases the longer it is continued and immunological changes lead to potential long-term benefits. SIT alone and not the symptomatic treatment nor other avoidance measures has so far been documented as the therapy with long-term or preventive potential. The allergic condition is driven by a subset of T-helper lymphocytes (Th2), which are characterised by the production of cytokines like IL-4, and IL-5. Immunological changes following SIT lead to potential curative effects. One mechanism whereby immunotherapy suppresses the allergic response is through increased production of IgG4 antibodies. Induction of specific IgG4 is able to influence the allergic response in different ways and is related to immunological effector mechanisms, also responsible for the reduced late phase hyperreactivity and ongoing allergic inflammation. SIT is the only treatment which interferes with the basic pathophysiological mechanisms of the allergic disease, thereby creating the potential for changes in the long-term prognosis of respiratory allergy. SIT should not only be recognised as first-line therapeutic treatment for allergic rhinoconjunctivitis but also as secondary preventive treatment for respiratory allergic diseases

    The importance of Real-Life research in Respiratory Medicine: Manifesto of the Respiratory Effectiveness Group:Endorsed by the International Primary Care Respiratory Group and the World Allergy Organization

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    Stochastic Inversion of P-to-S Converted Waves for Mantle Composition and Thermal Structure: Methodology and Application

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    We present a new methodology for inverting P‐to‐S receiver function (RF) waveforms directly for mantle temperature and composition. This is achieved by interfacing the geophysical inversion with self‐consistent mineral phase equilibria calculations from which rock mineralogy and its elastic properties are predicted as a function of pressure, temperature, and bulk composition. This approach anchors temperatures, composition, seismic properties, and discontinuities that are in mineral physics data, while permitting the simultaneous use of geophysical inverse methods to optimize models of seismic properties to match RF waveforms. Resultant estimates of transition zone (TZ) topography and volumetric seismic velocities are independent of tomographic models usually required for correcting for upper mantle structure. We considered two end‐member compositional models: the equilibrated equilibrium assemblage (EA) and the disequilibrated mechanical mixture (MM) models. Thermal variations were found to influence arrival times of computed RF waveforms, whereas compositional variations affected amplitudes of waves converted at the TZ discontinuities. The robustness of the inversion strategy was tested by performing a set of synthetic inversions in which crustal structure was assumed both fixed and variable. These tests indicate that unaccounted‐for crustal structure strongly affects the retrieval of mantle properties, calling for a two‐step strategy presented herein to simultaneously recover both crustal and mantle parameters. As a proof of concept, the methodology is applied to data from two stations located in the Siberian and East European continental platforms.This work was supported by a grant from the Swiss National Science Foundation (SNF project 200021_159907). B. T. was funded by a DĂ©lĂ©gation CNRS and CongĂ© pour Recherches et Conversion ThĂ©matique from the UniversitĂ© de Lyon to visit the Research School of Earth Sciences (RSES), The Australian National University (ANU). B. T. has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement 79382
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