1,720,959 research outputs found

    Opportunities for paediatricians to do research with the National Institute for Health Research

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    Research is an essential part of the healthcare system and of the NHS. It benefits present and future patients, drives continual improvement in cost-effectiveness for the NHS and provides challenging but rewarding work for healthcare professionals. Whether pursuing an academic career or recruiting patients from clinical service, all clinicians should have the opportunity to be involved in research. The National Institute for Health Research is provides support, training, infrastructure and funding for undertaking research. In this review we will look at the different opportunities available in association with the National Institute for Health Research and how clinicians can access them at different stages of their caree

    Phase I studies: the role of publicly funded academic-healthcare partnerships

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    Emanuel and colleagues’ meta-analysis found that phase I studies are very safe.1 However, the accompanying editorial mentioned that phase I studies are a “secret realm” and that “most studies are conducted outside academic medical centres at private facilities run by pharmaceutical companies or contract research organisations.”2After a major safety problem at a commercial phase I facility in 2006,3 the UK Medicines and Healthcare products Regulatory Agency (MHRA) introduced an accreditation scheme to enhance phase I safety standards in the UK. There are now four publicly funded phase I accredited clinical research facilities in the UK that have been open to non-commercial facilities since 2013. These include one university-hospital partnership (the Southampton National Institute for Health Research (NIHR) Wellcome Trust Clinical Research Facility) funded by the National Institute for Health Research. This provides an environment for early phase studies within the heart of an acute NHS hospital along with academic input from local university investigators. Phase I studies in patient populations and healthy volunteers are a crucial part of drug development. The UK Department of Health NIHR experimental medicine infrastructure has created a setting that delivers industry and publicly funded phase I trials while allowing recruitment from the entire UK population.<br/

    Neisseria lactamica controlled human infection model

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    Neisseria lactamica is a nonpathogenic commensal of the human upper respiratory tract that has been associated with protection against N. meningitidis colonization and disease. We have previously utilized the N. lactamica controlled human infection model to investigate the protective effect of N. lactamica colonization on N. meningitidis colonization, the nature of cross-reactive immune responses mounted toward N. meningitidis following N. lactamica colonization, and the microevolution of N. lactamica over a 5-month colonization period. More recently, we have assessed the possibility of utilizing genetically modified strains of N. lactamica to enable use of the commensal as a vehicle for prolonged exposure of the nasopharynx of humans to antigens of interest, expressed in carried organisms. A controlled infection with N. lactamica expressing the meningococcal antigen NadA has been executed and the results demonstrate that this strategy is effective at generating immune responses to the target antigen. Throughout this chapter, we outline in a step-by-step manner the methodologies utilized when performing controlled human infection with N. lactamica including procedures relating to: (1) the dilution of N. lactamica stock vials to derive intranasal inocula, (2) the delivery of intranasal inocula to human volunteers, (3) the determination of N. lactamica colonization status following intranasal inoculation using oropharyngeal swabbing and nasal wash sampling, (4) the microbiological procedures utilized to identify N. lactamica colonization among study volunteers, and (5) the identification of N. lactamica colonies as strain Y92-1009 using polymerase chain reaction.</p

    Controlled human infection model of Neisseria lactamica in late pregnancy investigating mother-to-infant transmission in the UK: a single-arm pilot trial

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    Background: the infant respiratory microbiome is derived largely from the mother and is associated with downstream health and disease. Manipulating maternal respiratory flora peripartum to influence the infant microbiome has not previously been investigated. Neisseria lactamica is a harmless pharyngeal commensal that correlates inversely with Neisseria meningitidis carriage and disease. Intranasal N lactamica inoculation is a safe and well characterised controlled human infection model (CHIM) in non-pregnant healthy adults. We hypothesised that N lactamica inoculation in pregnancy induces mother-to-infant N lactamica transmission postnatally. Methods: inthis single-arm trial, 21 healthy pregnant female participants aged 18 years or older were inoculated at 36–38 weeks’ gestation with 105 colony-forming units of N lactamica Y92–1009 at University Hospital Southampton Clinical Research Facility, Southampton, UK. N lactamica selective culture, genome sequencing, and serological testing were performed on maternal and infant oral, nasopharyngeal, breastmilk, and serum samples over 15 weeks postpartum. Seven female participants naturally colonised with N lactamica at baseline were followed up, but not inoculated. Oral samples were obtained from 12 cohabiting siblings younger than 5 years. The primary endpoint was infant N lactamica colonisation. This study was registered with ClinicalTrials.gov, NCT04784845, and is now complete. Findings: between Oct 25, 2021, and March 7, 2022, 31 adult female participants (median age 33·5 years [range 23·1–39·9]; 26 [84%] were White, British) were screened and enrolled, of whom seven were already colonised with N lactamica. After exclusion of three participants, 21 participants were inoculated, of whom 15 (71%) became N lactamica-colonised, and no sustained N lactamica Y92–1009 transmission to their infants was observed. Conversely, non-Y92–1009 N lactamica strain sharing was observed in four (57%) of seven uninoculated mother–sibling pairs, and Moraxella catarrhalis strain sharing in nine (38%) of 24 mother–infant pairs completing the study. Anti-N lactamica serum IgG titres increased in seven (88%) of eight N lactamica Y92–1009-colonised female participants, but none of their infants (where paired sera were available). There were no serious adverse reactions to the inoculum. Interpretation: as the world's first perinatal CHIM, this trial demonstrates that this model in pregnancy is feasible, and that N lactamica Y92–1009 can safely and efficiently colonise pregnant individuals. Lack of sustained mother-to-infant N lactamica transmission, despite evidence supporting mother-to-infant M catarrhalis and sibling-to-mother N lactamica transmission, challenges conventional perceptions of infants as passive recipients of maternal microbes, suggesting that respiratory commensal transmission is selective and microbe-specific. Funding: Medical Research Council and National Institute for Health Research Southampton Biomedical Research Centre.</p

    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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