1,721,127 research outputs found
Application of a challenge model to assess the protective efficacy of oral typhoid vaccines in humans
Full text linkHuman infection by Salmonella Typhi has been occurring for the last 50,000 years and still accounts for ∼ 22million new cases each year worldwide. Through faeco-oral transmission, this human-restricted infection disproportionately affects the most impoverished sections of endemic communities where adequate sanitation infrastructure and effective vaccination approaches are lacking. Development of new control measures to accurately measure the burden of disease and to prevent infection with new vaccine candidates are hindered by an incomplete understanding of host-pathogen interactions and of what constitutes a protective human response after exposure. In this thesis I describe the practical application of a recently developed human challenge model of typhoid infection in assessing new control measures, including the evaluation of the oral single-dose vaccine candidate, M01ZH09. In performing a large, double-blind, placebo-controlled study, I was able to measure the direct protective efficacy (PE) of vaccination with either M01ZH09 or 3-dose Ty21a by performing human challenge with 104CFU Salmonella Typhi, Quailes strain, 28-days later. Using clinical and microbiological definitions to confirm typhoid diagnosis during a 14-day period after ingestion, I found insignificant levels of protection afforded by a single dose of M01ZH09 (12.9%), and a low PE after Ty21a vaccination (35%), demonstrating the stringency of the model and the endpoints used. Many additional insights into pathogen dynamics and host responses were found highlighting several important characteristics of oral vaccination. M01ZH09 was highly immunogenic, and both active vaccines significantly reduced bacterial burden (bacteraemia and stool shedding) while having no effect on symptomatic severity of infection in those diagnosed. M01ZH09 receipt resulted in a significantly longer incubation period, suggesting underlying protective responses were being generated. Further findings included the first objective demonstration of primary bacteraemia occurring after typhoid exposure, and frequent asymptomatic infection or stool shedding in those exposed but remaining well. Overall, these data also demonstrated significant protective effects against challenge by anti-Vi antibody status and age at baseline. Taking these factors into account, M01ZH09 and Ty21a vaccination did convey an overall protective advantage against developing typhoid infection, each reducing the risk of diagnosis by ~two-fold during the challenge period
Brief communication. Loss of heterozygosity in sporadic primary cutaneous melanoma
No full textDifficulties in obtaining clinical samples from primary melanomas have meant that most genetic analyses of melanoma have concentrated on cell lines and metastases. Because the Breslow thickness of the primary tumour is the single best prognostic indicator, it is important to identify genetic abnormalities in primary melanomas and relate these changes to the thickness of the lesion. We have investigated 47 sporadic melanomas, of which 41 were primary lesions, for loss of heterozygosity (LOH) on several chromosomal arms, including areas where genes involved in familial melanoma and other relevant hereditary syndromes map, and where LOH has previously been reported in cell lines or metastatic lesions. LOH was identified at 66 (18%) of 358 informative loci in primary melanomas, and there was a significant relationship between the overall frequency of LOH and Breslow thickness (P < 0.0005). Loss of chromosome arm 9p was most frequent, occurring in 15 (47%) of 32 informative primary tumours, and was observed in 3 of 11 informative lesions ? 1.5 mm in depth. LOH on chromosome arms 3p, 6q, 10q, 11q, and 17p was also relatively frequent, with loss of 3p and 10q heterozygosity in lesions ? 1.5 mm in depth, while LOH on 6q, 11q, and 17p was only detected in more invasive tumours. The results suggest that loss of these chromosome regions are important in sporadic cutaneous melanoma, and are consistent with chromosome arm 9p loss occurring before loss of other chromosome arms
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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