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    Epithelial permeability in asthma

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    Our knowledge and understanding of asthma have evolved over time, leading to new and improved treatments for this disease. Despite existing treatments however, there remains to date a significant proportion of asthmatics who remain poorly controlled, with unmet needs. Most existing treatments are based on the Th2-driven inflammation model of asthma, however there is increasing recognition of the importance of the epithelium in asthma pathogenesis. It has been proposed that the asthmatic epithelium is chronically damaged and unable to repair, with increased permeability as a result. Existing treatments do not address the epithelial damage directly, however there are now available recombinant growth factors that have been shown to have beneficial effects on epithelial healing. Our hypothesis was that modification of the epithelium, in effect boosting its repair using recombinant human keratinocyte growth factor (rhKGF), would lead to improvement in clinical parameters.This was explored in several fashions. Firstly a randomised, double-blind, placebo-controlled clinical trial was performed using 20 poorly controlled, moderate asthmatics, with the active treatment group receiving parenteral rhKGF. Assessments before and after drug administration included objective, clinically relevant, measures of asthma such as airway hyperresponsiveness (AHR) measurements, spirometric measures, exhaled nitric oxide measurements and peak flow recording. Subjective, patient-centred assessments were also made using questionnaires to assess asthma control and quality of life, and bronchoscopy was performed to obtain samples to measure biological effects of the drug. KGF treatment resulted in a significantly greater improvement in the primary outcome of mannitol AHR, together with greater improvements in quality of life in the active treatment group compared to placebo. Other features (such as methacholine AHR, asthma control questionnaire scores, spirometric values, exhaled nitric oxide and peak flow variability) did not differ significantly between the groups, although this may be due to a greater than expected placebo response. Biological outcomes also did not differ significantly between the groups, although this may have been due to the sampling time-point used.Concurrently to the clinical trial above, in vitro experiments were performed on cell cultures of epithelial cells from asthmatic and healthy donors, to verify and further explore the effects of KGF on an asthmatic epithelium. Specifically mechanical wounds were inflicted on the cultures, with assessment of the repair process using wound imaging, measurement of trans-epithelial electrical resistance (TER) and permeability to FITC-labelled dextran, in the presence and absence of KGF. As a subset of these experiments, some cultures were exposed to mechanical compression using air pressure, as a mimic for bronchoconstriction, to see if KGF was effective in these circumstances. Results confirm a biological effect for KGF on wound repair in the asthmatic epithelium, which can also partially overcome the deleterious effect of compression on wound healing. An intrinsic difference in wound healing between asthmatic and healthy cohorts, as previously reported, was not apparent.Lastly the potential of nuclear medicine imaging, to assess epithelial permeability, was explored, for its potential use in future studies of asthma treatments addressing the epithelium directly. Unfortunately this was halted after a pilot study suggested potential methodological flaws – the results and conclusions from this pilot study are presented here, with suggestions for future studies in this area

    Buckwheat allergy: a potential problem in 21st century Britain

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    Buckwheat is commonly consumed in many parts of the world and has recently become more available in the UK. Buckwheat allergy is well recognised in parts of mainland Europe and Asia, typically associated with consumption of specific regional foods. No adult cases of buckwheat allergy in the UK have been reported in the literature. The authors present two cases of buckwheat allergy that presented to our UK allergy service recently. A 57-year-old man presented with anaphylaxis after eating home-baked bread prepared using buckwheat flour bought in France. In the second case, a 63-year-old lady presented with bronchospasm and urticaria after consuming health-food muesli. Sensitisation was confirmed in both cases by positive skin prick testing and specific IgE to buckwheat. Given the growing popularity of foods that may contain buckwheat, including ethnic and health-food ranges, buckwheat allergy is likely to become increasingly common in the UK

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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