The transgressive that: making the world uncanny.

In this article, we examine how the demonstrative that may be used to notice an event in the world in such a way as to suggest it has highly unusual or transgressive properties and in so doing invite others to align with that implicit claim. Drawing on Freud's notion of the uncanny, we examine instances of the transgressive that in circumstances in which participants at least entertain the possibility that they are experiencing anomalous or paranormal objects and entities. The analysis outlines the basic features of the transgressive that and examines how it may be the vehicle for a range of delicate interpersonal activities. Throughout the article, we try to show the broader relevance of the analytic argument by reference to data from more mundane interactional settings and to other forms of discourse, including fiction, commentary and interview narrative

Systematic review of health-related work outcome measures and quality criteria-based evaluations of their psychometric properties

Objective To examine the state of psychometric validation in the health-related work outcome literature. Data Sources We searched PubMed, PubMed Central, CINAHL, Embase (plus Embase Classic), and PsycINFO from inception to January 2016 using the following search terms: stroke, multiple sclerosis, epilepsy, spinal cord injury, brain injury, musculoskeletal disease, work, absenteeism, presenteeism, occupation, employment, job, outcome measure, assessment, work capacity evaluation, scale, and questionnaire. Study Selection From the 22,676 retrieved abstracts, 597 outcome measures were identified. Inclusion was based on content analysis. There were 95 health-related work outcome measures retained; of these, 2 were treated as outliers and therefore are discussed separately. All 6 authors individually organized the 93 remaining scales based on their content. Data Extraction A follow-up search using the same sources, and time period, with the name of the outcome measures and the terms psychometric, reliability, validity, and responsiveness, identified 263 unique classical test theory psychometric property datasets for the 93 tools. An assessment criterion for psychometric properties was applied to each article, and where consensus was not achieved, the rating delivered by most of the assessors was reported. Data Synthesis Of the articles reported, 18 reporting psychometric data were not accessible and therefore could not be assessed. There were 39 that scored 80%. The 3 outcome measures associated with the highest scoring datasets were the Sheehan Disability Scale, the Fear Avoidance Beliefs Questionnaire, and the assessment of the Subjective Handicap of Epilepsy. Finally, only 2 psychometric validation datasets reported the complete set of baseline psychometric properties. Conclusions This systematic review highlights the current limitations of the health-related work outcome measure literature, including the limited number of robust tools available

The functions of the A1A2A3 domains in von Willebrand factor include multimerin 1 binding.

Multimerin 1 (MMRN1) is a massive, homopolymeric protein that is stored in platelets and endothelial cells for activation-induced release. In vitro, MMRN1 binds to the outer surfaces of activated platelets and endothelial cells, the extracellular matrix (including collagen) and von Willebrand factor (VWF) to support platelet adhesive functions. VWF associates with MMRN1 at high shear, not static conditions, suggesting that shear exposes cryptic sites within VWF that support MMRN1 binding. Modified ELISA and surface plasmon resonance were used to study the structural features of VWF that support MMRN1 binding, and determine the affinities for VWF-MMRN1 binding. High shear microfluidic platelet adhesion assays determined the functional consequences for VWF-MMRN1 binding. VWF binding to MMRN1 was enhanced by shear exposure and ristocetin, and required VWF A1A2A3 region, specifically the A1 and A3 domains. VWF A1A2A3 bound to MMRN1 with a physiologically relevant binding affinity (KD: 2.0 ± 0.4 nM), whereas the individual VWF A1 (KD: 39.3 ± 7.7 nM) and A3 domains (KD: 229 ± 114 nM) bound to MMRN1 with lower affinities. VWF A1A2A3 was also sufficient to support the adhesion of resting platelets to MMRN1 at high shear, by a mechanism dependent on VWF-GPIbα binding. Our study provides new information on the molecular basis of MMRN1 binding to VWF, and its role in supporting platelet adhesion at high shear. We propose that at sites of vessel injury, MMRN1 that is released following activation of platelets and endothelial cells, binds to VWF A1A2A3 region to support platelet adhesion at arterial shear rates.This study was supported by the Heart and Stroke Foundation (CPMH), the Canadian Institutes of Health Research (CPMH), the British Heart Foundation (RWF), The Wellcome Trust (RWF), and the National Institutes of Health (JES).This is the author accepted manuscript. The final version is available from Schattauer Publishers via http://dx.doi.org/10.1160/TH15-09-070

Histologic and phenotypic factors and MC1R status associated with BRAF(V600E), BRAF(V600K), and NRAS mutations in a community-based sample of 414 cutaneous melanomas

Cutaneous melanomas arise through causal pathways involving interplay between exposure to UV radiation and host factors, resulting in characteristic patterns of driver mutations in BRAF, NRAS, and other genes. To gain clearer insights into the factors contributing to somatic mutation genotypes in melanoma, we collected clinical and epidemiologic data, performed skin examinations, and collected saliva and tumor samples from a community-based series of 414 patients aged 18 to 79, newly diagnosed with cutaneous melanoma. We assessed constitutional DNA for nine common polymorphisms in melanocortin-1 receptor gene (MC1R). Tumor DNA was assessed for somatic mutations in 25 different genes. We observed mutually exclusive mutations in BRAF (26%), BRAF (8%), BRAF (5%), and NRAS (9%). Compared to patients with BRAF wild-type melanomas, those with BRAF mutants were significantly younger, had more nevi but fewer actinic keratoses, were more likely to report a family history of melanoma, and had tumors that were more likely to harbor neval remnants. BRAF mutations were also associated with high nevus counts. Both BRAF and NRAS mutants were associated with older age but not with high sun exposure. We also found no association between MC1R status and any somatic mutations in this community sample of cutaneous melanomas, contrary to earlier reports

Engineering behaviour and mechanical - empirical relationships for a problematic New Zealand tropical residual soil

Unlike sedimentary clays, many residual soils do not exhibit clear mechanical-empirical relationships to assist in their engineering characterisation. In contrast, this paper discusses one residual clay in which such relationships may be determined, and examines whether the effects of structure in this clay may be assessed using a framework previously developed for sedimentary clays. The Northland Allochthon residual clay of New Zealand is a problematic soil of the fersiallitic type, prone to slope instability. Atterberg limit tests on soils from five field sites in the same geological unit show considerable variation, but that they are mechanically related. Triaxial tests were performed on reconstituted and intact soil specimens from one field site. Normalization of the strength envelope using the equivalent stress on the intrinsic compression line suggests that soil structure, destroyed in reconstituted specimens, plays a role in the shear strength of this soil in its intact state. Overconsolidated behaviour, in the absence of geological preloading, suggests the existence of a pseudo-preconsolidation pressure associated with weathering processes. The results show that the saturated mechanical behaviour of this residual soil is in line with that of sedimentary clays and that mechanical-empirical relationships developed for such clays may be applied in this case

Understanding Lived Experiences of Stigma for People Living with HIV: A Community Based Participatory Research Study

The goal of this project was to better understand the experiences and impacts of HIV stigma and discrimination on people living with HIV and to co-create knowledge that has the potential to challenge existing stigma within the healthcare, social services, and public policy sectors in the province of Alberta, Canada. We employed community-based participatory research and a mixed methods design (survey methods and qualitative interviews) to address these questions. An online survey was completed by 148 people living with HIV and semi-structured interviews were conducted with an additional 20 participants. The research findings have been conceptualized within a social ecological model. The four main categories that emerged from the data included personal level factors attributed to HIV stigma, interpersonal factors related to HIV stigma, community factors related to HIV stigma, and HIV stigma in systems and institutions. Within each ecological domain we highlight the strengths and coping strategies people living with HIV identified in the study. Results will be of interest to health researchers and HIV service providers

Antibiotic prescribing in UK out-of-hours primary care services: a realist-informed scoping review of training and guidelines for healthcare professionals

Background: Antibiotic overuse has contributed to antimicrobial resistance, which is a global public health problem. In the UK, despite the fall in rates of antibiotic prescription since 2013, prescribing levels remain high in comparison with other European countries. Prescribing in out-of-hours (OOH) care provides unique challenges for prudent prescribing, for which professionals may not be prepared. Aim: To explore the guidance available to professionals on prescribing antibiotics for common infections in OOH primary care within the UK, with a focus on training resources, guidelines, and clinical recommendations. Design & setting: A realist-informed scoping review of peer-reviewed articles and grey literature. Method: The review focused on antibiotic prescribing OOH (for example, clinical guidelines and training videos). General prescribing guidance was searched whenever OOH-focused resources were unavailable. Electronic databases and websites of national agencies and professional societies were searched following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Findings were organised according to realist review components, that is, mechanisms, contexts, and outcomes. Results: In total, 46 clinical guidelines and eight training resources were identified. Clinical guidelines targeted adults and children, and included recommendations on prescription strategy, spectrum of the antibiotic prescribed, communication with patients, treatment duration, and decision-making processes. No clinical guidelines or training resources focusing specifically on OOH were found. Conclusion: The results highlight a lack of knowledge about whether existing resources address the challenges faced by OOH antibiotic prescribers. Further research is needed to explore the training needs of OOH health professionals, and whether further OOH-focused resources need to be developed given the rates of antibiotic prescribing in this setting