HSD3B1 genotype identifies glucocorticoid responsiveness in severe asthma

Asthma resistance to glucocorticoid treatment is a major health problem with unclear etiology. Glucocorticoids inhibit adrenal androgen production. However, androgens have potential benefits in asthma. HSD3B1 encodes for 3β-hydroxysteroid dehydrogenase-1 (3β-HSD1), which catalyzes peripheral conversion from adrenal dehydroepiandrosterone (DHEA) to potent androgens and has a germline missense-encoding polymorphism. The adrenal restrictive HSD3B1(1245A) allele limits conversion, whereas the adrenal permissive HSD3B1(1245C) allele increases DHEA metabolism to potent androgens. In the Severe Asthma Research Program (SARP) III cohort, we determined the association between DHEA-sulfate and percentage predicted forced expiratory volume in 1 s (FEV1PP). HSD3B1(1245) genotypes were assessed, and association between adrenal restrictive and adrenal permissive alleles and FEV1PP in patients with (GC) and without (noGC) daily oral glucocorticoid treatment was determined (n = 318). Validation was performed in a second cohort (SARP I&II; n = 184). DHEA-sulfate is associated with FEV1PP and is suppressed with GC treatment. GC patients homozygous for the adrenal restrictive genotype have lower FEV1PP compared with noGC patients (54.3% vs. 75.1%; P < 0.001). In patients with the homozygous adrenal permissive genotype, there was no FEV1PP difference in GC vs. noGC patients (73.4% vs. 78.9%; P = 0.39). Results were independently confirmed: FEV1PP for homozygous adrenal restrictive genotype in GC vs. noGC is 49.8 vs. 63.4 (P < 0.001), and for homozygous adrenal permissive genotype, it is 66.7 vs. 67.7 (P = 0.92). The adrenal restrictive HSD3B1(1245) genotype is associated with GC resistance. This effect appears to be driven by GC suppression of 3β-HSD1 substrate. Our results suggest opportunities for prediction of GC resistance and pharmacologic intervention

Integrating quantitative and qualitative data and findings when undertaking randomised controlled trials

It is common to undertake qualitative research alongside randomised controlled trials (RCTs) when evaluating complex interventions. Researchers tend to analyse these datasets one by one and then consider their findings separately within the discussion section of the final report, rarely integrating quantitative and qualitative data or findings, and missing opportunities to combine data in order to add rigour, enabling thorough and more complete analysis, provide credibility to results, and generate further important insights about the intervention under evaluation. This paper reports on a 2 day expert meeting funded by the United Kingdom Medical Research Council Hubs for Trials Methodology Research with the aims to identify current strengths and weaknesses in the integration of quantitative and qualitative methods in clinical trials, establish the next steps required to provide the trials community with guidance on the integration of mixed methods in RCTs and set-up a network of individuals, groups and organisations willing to collaborate on related methodological activity. We summarise integration techniques and go beyond previous publications by highlighting the potential value of integration using three examples that are specific to RCTs. We suggest that applying mixed methods integration techniques to data or findings from studies involving both RCTs and qualitative research can yield insights that might be useful for understanding variation in outcomes, the mechanism by which interventions have an impact, and identifying ways of tailoring therapy to patient preference and type. Given a general lack of examples and knowledge of these techniques, researchers and funders will need future guidance on how to undertake and appraise them

Trivial and normative? Online fieldwork within YouTube’s beauty community

In this article, I discuss methodological understandings around qualitative research and online ethnographic practice to bring forward a reflexive account on the particularities of doing fieldwork on YouTube. I draw from a multiyear ethnographic examination of YouTube’s beauty community that sought to understand online popularity framed by local norms and practices and shed light into the local significance of knowledge, expertise, and self-development. I argue for an epistemological perspective that acknowledges the diversity of viable, conceivable fieldwork experiences while distancing from prescriptive modes of argumentation. I propose seeing fieldwork in and through its richness and predicaments, persistently naturalistic while interpretive. I approach online popularity, fandom, and even YouTube itself from a perspective that tolerates ambivalence, contradictions, and embraces the complexity of social worlds and human interaction

Review: V Plano Clark & J Creswell (Eds) Mixed methods reader

Mixed methods has been described as the third major methodological movement, one that is perhaps just reaching "adolescence." Plano Clark and Creswell’s The Mixed Methods Reader is timely, as there is a hugely increasing wave of interest in mixed methodologies, but the authors have also, perhaps, struggled to find appropriate readings for some areas of practice from a literature that is still developing and evolving. The Reader complements an overview text on mixed methods published a year earlier by the same authors (Creswell & Plano Clark, 2007), although in my opinion, the Reader provides a more useful overview of mixed methods than does the text. It is designed for graduate students and practicing researchers. In the first page of the general introduction, the authors note that mixed methods has a broad appeal both internationally and across disciplines with the consequence that the literature is spread across a wide range of publication outlets. Their goal, then, was to bring together a selection of readings that covered the major areas of discussion in the field. The authors claim to have reflected international, and disciplinary diversity in their selections, yet, in the 14 methodological selections, just one comes from the United Kingdom and one from Canada—the remainder are from the United States, and primarily from authors working in education or educational psychology. The nine example studies are also dominated by American authors. The book is presented in two sections: Part 1 provides a methodological overview, with 14 chapters, whereas Part 2 presents nine "exemplar" studies. The overall design of the book is excellent and it has been meticulously prepared (a characteristic of all John Creswell’s books). Each reading is prefaced by an editors’ introduction; stimulating discussion questions are provided for each methodological reading and for the set of research studies, and related references that extend the topic are also provided for each methodological reading. Readings are presented in their original form, including variations in styles of presentation and referencing (and original rather than current author locations)

Qualitative data analysis with NVivo

xxiii, 349 pages : illustrations ; 24 c