‘Missing out’: Reflections on the positioning of ethnographic research within an evaluative framing

Contemporary approaches to evaluating ‘complex’ social and health interventions are opening up spaces for methodologies attuned to examining contextual complexities, such as ethnography. Yet the alignment of the two agendas – evaluative and ethnographic – is not necessarily comfortable in practice. I reflect on experiences of conducting ethnographic research alongside a public health evaluation of a community-based initiative in the UK, using the lens of ‘missing out’ to examine intersections between my own ethnographic concerns and those of the communities under study. I examine potential opportunities posed by the discomfort of ‘missing out’, particularly for identifying the processes and spaces of inclusion and exclusion that contributed both to my ethnographic experiences and to the realities of the communities engaging with the initiative. This reveals productive possibilities for a focus on ‘missing out’ as a form of relating for evaluations of the impacts of such initiatives on health and social inequalities

Evidence for spatially-responsive neurons in the rostral thalamus

Damage involving the anterior thalamic and adjacent rostral thalamic nuclei may result in a severe anterograde amnesia, similar to the amnesia resulting from damage to the hippocampal formation. Little is known, however, about the information represented in these nuclei. To redress this deficit, we recorded units in three rostral thalamic nuclei in freely-moving rats (the parataenial nucleus, the anteromedial nucleus and nucleus reuniens). We found units in these nuclei possessing previously unsuspected spatial properties. The various cell types show clear similarities to place cells, head direction cells, and perimeter/border cells described in hippocampal and parahippocampal regions. Based on their connectivity, it had been predicted that the anterior thalamic nuclei process information with high spatial and temporal resolution while the midline nuclei have more diffuse roles in attention and arousal. Our current findings strongly support the first prediction but directly challenge or substantially moderate the second prediction. The rostral thalamic spatial cells described here may reflect direct hippocampal/parahippocampal inputs, a striking finding of itself, given the relative lack of place cells in other sites receiving direct hippocampal formation inputs. Alternatively, they may provide elemental thalamic spatial inputs to assist hippocampal spatial computations. Finally, they could represent a parallel spatial system in the brain

Identification of an allosteric binding site on the human glycine transporter, GlyT2, for bioactive lipid analgesics

© Mostyn et al. The treatment of chronic pain is poorly managed by current analgesics, and there is a need for new classes of drugs. We recently developed a series of bioactive lipids that inhibit the human glycine transporter GlyT2 (SLC6A5) and provide analgesia in animal models of pain. Here, we have used functional analysis of mutant transporters combined with molecular dynamics simulations of lipid-transporter interactions to understand how these bioactive lipids interact with GlyT2. This study identifies a novel extracellular allosteric modulator site formed by a crevice between transmembrane domains 5, 7, and 8, and extracellular loop 4 of GlyT2. Knowledge of this site could be exploited further in the development of drugs to treat pain, and to identify other allosteric modulators of the SLC6 family of transporters

First-year compliance with the Nevada Clean Indoor Air Act

Objectives: We quantitatively evaluated compliance with the Nevada Clean Indoor Air Act (NCIAA) by different types of businesses in Nevada and determined whether compliance affected indoor concentrations of benzene and 3-ethenyl pyridine (3-EP), markers of tobacco smoke. Methods: Managers of 181 businesses in Washoe County, Nevada, were interviewed about business characteristics and practices and policies related to smoking. During unannounced visits, compliance data and air samples (n=66) were collected from interviewed businesses and from an additional sample (n = 56) of businesses without knowledge of the study. Results: Overall compliance, as defined by the NCIAA, was low (28.2%). Benzene concentrations were higher in casino restaurants than in other businesses, although most complied with the requirements of the ban. Neither benzene nor 3-EP concentrations differed significantly between compliant and non-compliant businesses. Conclusions: The finding that casino restaurants had poorer air quality despite their compliance with the NCIAA suggests that compliance alone may not be sufficient to reduce exposure to secondhand smoke, particularly in buildings with both nonsmoking and smoking areas

Improving ranking for systematic reviews using query adaptation

Identifying relevant studies for inclusion in systematic reviews requires significant effort from human experts who manually screen large numbers of studies. The problem is made more difficult by the growing volume of medical literature and Information Retrieval techniques have proved to be useful to reduce workload. Reviewers are often interested in particular types of evidence such as Diagnostic Test Accuracy studies. This paper explores the use of query adaption to identify particular types of evidence and thereby reduce the workload placed on reviewers. A simple retrieval system that ranks studies using TF.IDF weighted cosine similarity was implemented. The Log-Likelihood, ChiSquared and Odds-Ratio lexical statistics and relevance feedback were used to generate sets of terms that indicate evidence relevant to Diagnostic Test Accuracy reviews. Experiments using a set of 80 systematic reviews from the CLEF2017 and CLEF2018 eHealth tasks demonstrate that the approach improves retrieval performance

A genome-wide association study to identify genetic markers associated with endometrial cancer grade

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Mutation p.R356Q in the Collybistin Phosphoinositide Binding Site Is Associated With Mild Intellectual Disability

The recruitment of inhibitory GABAA receptors to neuronal synapses requires a complex interplay between receptors, neuroligins, the scaffolding protein gephyrin and the GDP-GTP exchange factor collybistin (CB). Collybistin is regulated by protein-protein interactions at the N-terminal SH3 domain, which can bind neuroligins 2/4 and the GABAAR α2 subunit. Collybistin also harbors a RhoGEF domain which mediates interactions with gephyrin and catalyzes GDP-GTP exchange on Cdc42. Lastly, collybistin has a pleckstrin homology (PH) domain, which binds phosphoinositides, such as phosphatidylinositol 3-phosphate (PI3P/PtdIns3P) and phosphatidylinositol 4-monophosphate (PI4P/PtdIns4P). PI3P located in early/sorting endosomes has recently been shown to regulate the postsynaptic clustering of gephyrin and GABAA receptors and consequently the strength of inhibitory synapses in cultured hippocampal neurons. This process is disrupted by mutations in the collybistin gene (ARHGEF9), which cause X-linked intellectual disability (XLID) by a variety of mechanisms converging on disrupted gephyrin and GABAA receptor clustering at central synapses. Here we report a novel missense mutation (chrX:62875607C>T, p.R356Q) in ARHGEF9 that affects one of the two paired arginine residues in the PH domain that were predicted to be vital for binding phosphoinositides. Functional assays revealed that recombinant collybistin CB3SH3-R356Q was deficient in PI3P binding and was not able to translocate EGFP-gephyrin to submembrane microaggregates in an in vitro clustering assay. Expression of the PI3P-binding mutants CB3SH3-R356Q and CB3SH3-R356N/R357N in cultured hippocampal neurones revealed that the mutant proteins did not accumulate at inhibitory synapses, but instead resulted in a clear decrease in the overall number of synaptic gephyrin clusters compared to controls. Molecular dynamics simulations suggest that the p.R356Q substitution influences PI3P binding by altering the range of structural conformations adopted by collybistin. Taken together, these results suggest that the p.R356Q mutation in ARHGEF9 is the underlying cause of XLID in the probands, disrupting gephyrin clustering at inhibitory GABAergic synapses via loss of collybistin PH domain phosphoinositide binding

Systematic Reviews in Educational Research: Methodology, Perspectives and Application

This chapter explores the processes of reviewing literature as a research method. The logic of the family of research approaches called systematic review is analysed and the variation in techniques used in the different approaches explored using examples from existing reviews. The key distinctions between aggregative and configurative approaches are illustrated and the chapter signposts further reading on key issues in the systematic review process