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

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

paediatric respiratory disease past present and future

Paediatric respiratory disease has changed in the past 20 yrs; we could fill a whole issue of the journal paying tribute to our famous forebears. We are posing new challenges to our colleagues in the field of adult respiratory disease. They have to learn to deal with conditions that 20 yrs ago were rare in the adult chest clinic, such as cystic fibrosis (CF) and the long-term consequences of premature birth and congenital malformations of the respiratory tract. Furthermore, studies in childhood are challenging pathophysiological concepts throughout life. The many great prospective birth cohort studies have shed light on the different patterns of wheezing, their risk factors and their evolution through childhood. Who would have thought it was good to be born in a barn! It is becoming increasingly clear that even for "adult" diseases, such as chronic obstructive pulmonary disease (COPD), antenatal and early life events are at least as important as smoking in adulthood 1. CF has become a disease also of adults 2. Although many factors have contributed, the main reason has been the development of expert special CF centres, a model increasingly adopted by adult teams. This can serve as a model for other diseases; how a well-structured multidisciplinary approach to treatment can translate into benefits for patients. Perhaps numerically the most important achievement is in the field of public health. The benefit of the decrease in invasive bacterial infections, due to vaccination programmes for infants, is among the most important achievements of the past. Other areas of change include the survival of ever smaller preterm neonates. These children are reaching adult life with impaired lung function and abnormal computed tomography scans. What will happen to their ageing lungs? Interstitial lung disease (ILD) is becoming increasingly well understood, with new genetic entities, such as

Seafloor seismic monitoring of an active submarine volcano : local seismicity at Vailulu'u Seamount, Samoa

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 5 (2004): Q06007, doi:10.1029/2004GC000702.We deployed five ocean bottom hydrophones (OBHs) for a 1-year seismic monitoring study of Vailulu'u Seamount, the youngest and easternmost volcano in the Samoan Archipelago. Four instruments were placed on the summit crater rim at 600–700 m water depth, and one was placed inside the crater at 1000 m water depth. An analysis of the first 45 days of records shows a very large number of seismic events, 211 of them local. These events define a steady background activity of about four seismic events per day, increasing to about 10 events per day during a week of heightened seismic activity, which peaked at 40 events during 1 day. We identified 107 earthquakes, whose arrivals could be picked on all five stations and that are likely located within the seamount, based on their similar waveforms. Two linear trends are defined by 21 of these events. These are extremely well correlated and located, first downward then upward on a steeply inclined plane that is close to the axial plane of the southeast rift as it emerges from the main summit of Vailulu'u. These events resemble volcanotectonic earthquakes from subaerial volcanoes in displaying very coherent seismic waveforms and by showing systematic, narrowly defined progressions in hypocenter locations. We propose that these events reflect brittle rock failure due to magma redistribution in or near a central magma reservoir.The bulk of this work was funded by NSF-OCE, in grants to HS and SRH and the OBSIP facility at Scripps

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

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

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-β, 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

Optimization and geophysical inverse problems

A fundamental part of geophysics is to make inferences about the interior of the earth on the basis of data collected at or near the surface of the earth. In almost all cases these measured data are only indirectly related to the properties of the earth that are of interest, so an inverse problem must be solved in order to obtain estimates of the physical properties within the earth. In February of 1999 the U.S. Department of Energy sponsored a workshop that was intended to examine the methods currently being used to solve geophysical inverse problems and to consider what new approaches should be explored in the future. The interdisciplinary area between inverse problems in geophysics and optimization methods in mathematics was specifically targeted as one where an interchange of ideas was likely to be fruitful. Thus about half of the participants were actively involved in solving geophysical inverse problems and about half were actively involved in research on general optimization methods. This report presents some of the topics that were explored at the workshop and the conclusions that were reached. In general, the objective of a geophysical inverse problem is to find an earth model, described by a set of physical parameters, that is consistent with the observational data. It is usually assumed that the forward problem, that of calculating simulated data for an earth model, is well enough understood so that reasonably accurate synthetic data can be generated for an arbitrary model. The inverse problem is then posed as an optimization problem, where the function to be optimized is variously called the objective function, misfit function, or fitness function. The objective function is typically some measure of the difference between observational data and synthetic data calculated for a trial model. However, because of incomplete and inaccurate data, the objective function often incorporates some additional form of regularization, such as a measure of smoothness or distance from a prior model. Various other constraints may also be imposed upon the process. Inverse problems are not restricted to geophysics, but can be found in a wide variety of disciplines where inferences must be made on the basis of indirect measurements. For instance, most imaging problems, whether in the field of medicine or non-destructive evaluation, require the solution of an inverse problem. In this report, however, the examples used for illustration are taken exclusively from the field of geophysics. The generalization of these examples to other disciplines should be straightforward, as all are based on standard second-order partial differential equations of physics. In fact, sometimes the non-geophysical inverse problems are significantly easier to treat (as in medical imaging) because the limitations on data collection, and in particular on multiple views, are not so severe as they generally are in geophysics. This report begins with an introduction to geophysical inverse problems by briefly describing four canonical problems that are typical of those commonly encountered in geophysics. Next the connection with optimization methods is made by presenting a general formulation of geophysical inverse problems. This leads into the main subject of this report, a discussion of methods for solving such problems with an emphasis upon newer approaches that have not yet become prominent in geophysics. A separate section is devoted to a subject that is not encountered in all optimization problems but is particularly important in geophysics, the need for a careful appraisal of the results in terms of their resolution and uncertainty. The impact on geophysical inverse problems of continuously improving computational resources is then discussed. The main results are then brought together in a final summary and conclusions section