Feasibility and acceptability of e-PROMs data capture and feedback among patients receiving haemodialysis in the Symptom monitoring WIth Feedback Trial (SWIFT) pilot: protocol for a qualitative study in Australia

INTRODUCTION: People receiving haemodialysis experience a high symptom burden and impaired quality of life. The use of patient-reported outcome measures (PROMs) is increasing in nephrology care, however their acceptability, utility and impacts are not well understood. METHODS AND ANALYSIS: We describe a protocol for a qualitative study to evaluate the feasibility and acceptability of electronic-PROMs (e-PROMs) data capture and feedback in haemodialysis following the pilot Symptom monitoring WIth Feedback Trial (SWIFT). SWIFT involves linkage of e-PROMs data, including symptoms and health-related quality of life, to the Australia and New Zealand Dialysis and Transplant Registry with feedback to patients' treating nephrologists and nurse unit managers. Focus groups and semistructured interviews will be conducted with nephrologists (n=15), dialysis nurses (n=24) and patients receiving haemodialysis (n=24) from six dialysis units in Australia. Question topics will include the technical and clinical feasibility and acceptability of e-PROMs reporting and feedback (including the barriers and enablers to uptake) and perceived impact on patient care and outcomes. Transcripts will be analysed thematically and guided by Normalisation Process Theory. ETHICS AND DISSEMINATION: Ethics approval was obtained from the relevant hospital Human Research Ethics Committees (HREC/18/CALHN/481; HREC/MML/54599). The findings from the SWIFT pilot and qualitative evaluation will inform the implementation of the SWIFT main trial, and more broadly, the use of e-PROMs in clinical settings and registries. TRIAL REGISTRATION NUMBER: ANZCTRN12618001976279.Emily Duncanson, Paul N Bennett, Andrea Viecelli, Kathryn Dansie, William Handke, Allison Ton

The Importance of Consistent Global Forest Aboveground Biomass Product Validation

Several upcoming satellite missions have core science requirements to produce data for accurate forest aboveground biomass mapping. Largely because of these mission datasets, the number of available biomass products is expected to greatly increase over the coming decade. Despite the recognized importance of biomass mapping for a wide range of science, policy and management applications, there remains no community accepted standard for satellite-based biomass map validation. The Committee on Earth Observing Satellites (CEOS) is developing a protocol to fill this need in advance of the next generation of biomass-relevant satellites, and this paper presents a review of biomass validation practices from a CEOS perspective. We outline the wide range of anticipated user requirements for product accuracy assessment and provide recommendations for the validation of biomass products. These recommendations include the collection of new, high-quality in situ data and the use of airborne lidar biomass maps as tools toward transparent multi-resolution validation. Adoption of community-vetted validation standards and practices will facilitate the uptake of the next generation of biomass products

Security (studies) and the limits of critique: why we should think through struggle

This paper addresses the political and epistemological stakes of knowledge production in post-structuralist Critical Security Studies. It opens a research agenda in which struggles against dominant regimes of power/knowledge are entry-points for analysis. Despite attempts to gain distance from the word ‘security’, through interrogation of wider practices and schemes of knowledge in which security practices are embedded, post-structuralist CSS too quickly reads security logics as determinative of modern/liberal forms of power and rule. At play is an unacknowledged ontological investment in ‘security’, structured by disciplinary commitments and policy discourse putatively critiqued. Through previous ethnographic research, we highlight how struggles over dispossession and oppression call the very frame of security into question, exposing violences inadmissible within that frame. Through the lens of security, the violence of wider strategies of containing and normalizing politics are rendered invisible, or a neutral backdrop against which security practices take place. Building on recent debates on critical security methods, we set out an agenda where struggle provokes an alternative mode of onto political investment in critical examination of power and order

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children.

Bacteremia (bacterial bloodstream infection) is a major cause of illness and death in sub-Saharan Africa but little is known about the role of human genetics in susceptibility. We conducted a genome-wide association study of bacteremia susceptibility in more than 5,000 Kenyan children as part of the Wellcome Trust Case Control Consortium 2 (WTCCC2). Both the blood-culture-proven bacteremia case subjects and healthy infants as controls were recruited from Kilifi, on the east coast of Kenya. Streptococcus pneumoniae is the most common cause of bacteremia in Kilifi and was thus the focus of this study. We identified an association between polymorphisms in a long intergenic non-coding RNA (lincRNA) gene (AC011288.2) and pneumococcal bacteremia and replicated the results in the same population (p combined = 1.69 × 10(-9); OR = 2.47, 95% CI = 1.84-3.31). The susceptibility allele is African specific, derived rather than ancestral, and occurs at low frequency (2.7% in control subjects and 6.4% in case subjects). Our further studies showed AC011288.2 expression only in neutrophils, a cell type that is known to play a major role in pneumococcal clearance. Identification of this novel association will further focus research on the role of lincRNAs in human infectious disease.Wellcome Trust (Grant ID: 084716/Z/08/Z)This is the final version of the article. It first appeared from Cell Press/Elsevier via http://dx.doi.org/10.1016/j.ajhg.2016.03.02

MiR-137-derived polygenic risk: effects on cognitive performance in patients with schizophrenia and controls

Variants at microRNA-137 (MIR137), one of the most strongly associated schizophrenia risk loci identified to date, have been associated with poorer cognitive performance. As microRNA-137 is known to regulate the expression of ~1900 other genes, including several that are independently associated with schizophrenia, we tested whether this gene set was also associated with variation in cognitive performance. Our analysis was based on an empirically derived list of genes whose expression was altered by manipulation of MIR137 expression. This list was cross-referenced with genome-wide schizophrenia association data to construct individual polygenic scores. We then tested, in a sample of 808 patients and 192 controls, whether these risk scores were associated with altered performance on cognitive functions known to be affected in schizophrenia. A subgroup of healthy participants also underwent functional imaging during memory (n=108) and face processing tasks (n=83). Increased polygenic risk within the empirically derived miR-137 regulated gene score was associated with significantly lower performance on intelligence quotient, working memory and episodic memory. These effects were observed most clearly at a polygenic threshold of P=0.05, although significant results were observed at all three thresholds analyzed. This association was found independently for the gene set as a whole, excluding the schizophrenia-associated MIR137 SNP itself. Analysis of the spatial working memory fMRI task further suggested that increased risk score (thresholded at P=10−5) was significantly associated with increased activation of the right inferior occipital gyrus. In conclusion, these data are consistent with emerging evidence that MIR137 associated risk for schizophrenia may relate to its broader downstream genetic effects

A genome-wide association study of anorexia nervosa.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field