Still not receiving the support they deserve ... final evaluation report for the Stella Project Young Women's Initiative

AVA’s Stella Project has been working to improve services for adult women affected by overlapping Domestic Violence (DV) and Problematic Substance Use (PSU) for over ten years. Through provision of training and development work with practitioners, the organisation received frequent requests to advise agencies about how these matters affected younger women. Although this was an issue that was increasingly identified by practitioners, the UK evidence base on how to effectively support such young women was weak. In 2010, AVA successfully sought funding from the John Paul Getty Jnr Charitable Trust for a research and development project to address this gap in the evidence base. Following an open invitation to tender, AVA commissioned Forensic Psychological Services at Middlesex University to conduct the research phase of the project and to evaluate the Stella Project’s intervention with agencies working with young women affected by DV and Sexual Violence (SV) and PSU. The project’s scope allowed the Stella Project to support two London boroughs in developing their responses to these young women. AVA invited all London boroughs to submit an Expression of Interest to be involved. From 14 interested boroughs, AVA selected the London Borough of Enfield (LBE) and the Royal Borough of Kensington and Chelsea (RBKC), primarily because they are different demographically but also based on their strategic commitment to the project and the existence of relevant agencies to participate in the project. In both boroughs, the Domestic Violence Co-ordinator and the Drug and Alcohol Action Team Manager nominated four relevant agencies to participate in the project. Within each borough, agencies were selected to represent both the Violence Against Women and Girls (VAWG) and substance misuse sectors, and to cover the full age range of young women whose needs the project would address (14 to 25 years). In both boroughs, this resulted in representation from the Independent Domestic Violence Advocacy services, the young people’s substance misuse services and the Drug Intervention Programmes (DIPs), and in Enfield, the Youth Offending Service

Role of DNA-detection-based tools for monitoring the soil-transmitted helminth treatment response in drug-efficacy trials.

More than 1 billion people have been reported to be infected with at least one soil-transmitted helminth (STH) worldwide, according to the last published report of the World Health Organization (WHO) [1]. WHO guidelines for STH control mainly encompass periodic administration of benzimidazoles (albendazole or mebendazole) to at-risk people of the endemic areas [1]. However, extended use of benzimidazoles could entail a great selection pressure for parasitic-resistant strains. In veterinary medicine, anthelmintic resistance in gastrointestinal nematodes has been developed in response to their excessive use, and it is currently considered a serious threat to livestock health and welfare [2, 3]. In humans, the estimated efficacy of albendazole and mebendazole against Trichuris trichiura has been observed to significantly decrease over time [4]. This observed decrement in drug efficacy could be due to the development of anthelmintic resistance (among other reasons such as drug quality and administration, the increasing of drug-efficacy studies, improvements in sensitivity of diagnostic tools after treatment, etc) after years of mass drug-administration campaigns, which is one of the major concerns in STH control [5]. Monitoring anthelmintic efficacy trials have been traditionally done by microscopic approaches, although it is well known that microscopy's sensitivity may be insufficient in this context [6, 7]. We think that DNA-detection-based tools represent an accurate alternative to parasitological methods, and they should be evaluated and validated not only for monitoring worm burden before and after treatment but also for detecting genetic markers related to anthelmintic resistance

Discovery of novel heart rate-associated loci using the Exome Chip

Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses. Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods. We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants. Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies

Are Americans Feeling Less Healthy? The Puzzle of Trends in Self-rated Health

Although self-rated health is proposed for use in public health monitoring, previous reports on US levels and trends in self-rated health have shown ambiguous results. This study presents a comprehensive comparative analysis of responses to a common self-rated health question in 4 national surveys from 1971 to 2007: the National Health and Nutrition Examination Survey, Behavioral Risk Factor Surveillance System, National Health Interview Survey, and Current Population Survey. In addition to variation in the levels of self-rated health across surveys, striking discrepancies in time trends were observed. Whereas data from the Behavioral Risk Factor Surveillance System demonstrate that Americans were increasingly likely to report “fair” or “poor” health over the last decade, those from the Current Population Survey indicate the opposite trend. Subgroup analyses revealed that the greatest inconsistencies were among young respondents, Hispanics, and those without a high school education. Trends in “fair” or “poor” ratings were more inconsistent than trends in “excellent” ratings. The observed discrepancies elude simple explanations but suggest that self-rated health may be unsuitable for monitoring changes in population health over time. Analyses of socioeconomic disparities that use self-rated health may be particularly vulnerable to comparability problems, as inconsistencies are most pronounced among the lowest education group. More work is urgently needed on robust and comparable approaches to tracking population health

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Can we define a level of protection for allergic consumers that everyone can accept?

Substantial progress has been made in characterising the risk associated with exposure to allergens in food. However, absence of agreement on what risk is tolerable has made it difficult to set quantitative limits to manage that risk and protect allergic consumers effectively. This paper reviews scientific progress in the area and the diverse status of allergen management approaches and lack of common standards across different jurisdictions, including within the EU. This lack of regulation largely explains why allergic consumers find Precautionary Allergen Labelling confusing and cannot rely on it. We reviewed approaches to setting quantitative limits for a broad range of food safety hazards to identify the reasoning leading to their adoption. This revealed a diversity of approaches from pragmatic to risk-based, but we could not find clear evidence of the process leading to the decision on risk acceptability. We propose a framework built around the criteria suggested by Murphy and Gardoni (2008) for approaches to defining tolerable risks. Applying these criteria to food allergy, we concluded that sufficient knowledge exists to implement the framework, including sufficient expertise across the whole range of stakeholders to allow opinions to be heard and respected, and a consensus to be achieved

Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis

Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluate loss of function, we observed a strong in vivo erythropoietic effect for RBPMS but not for GTF2E2, supporting the statistical fine-mapping at this locus and demonstrating that RBPMS is a regulator of erythropoiesis. Our findings show the utility of trans-ethnic GWASs for discovery and characterization of genetic loci influencing hematologic traits

Performance evaluation of Baermann techniques: The quest for developing a microscopy reference standard for the diagnosis of Strongyloides stercoralis.

BackgroundSoil-transmitted helminths (STH) are common in low and middle income countries where there is lack of access to clean water and sanitation. Effective diagnosis and treatment are essential for the control of STH infections. However, among STH parasites, Strongyloides stercoralis is the most neglected species, both in diagnostics and control strategies. Diagnostic methods cover different approaches, each with different sensitivities and specificities, such as serology, molecular techniques and microscopy based techniques. Of the later, the Baermann technique is the most commonly used procedure. In the literature, several ways have been described to perform the Baermann method, which illustrates the overall lack of a '(gold) reference standard' method for the diagnosis of S. stercoralis infection. In this study we have evaluated the performance of three Baermann techniques in order to improve the reference standard for the microscopic diagnosis of S. stercoralis infection thereby facilitating individual case detection, mapping of the disease and proper evaluation of treatment responses.Methods/principal findingsA community based cross sectional study was conducted at Zenzelima, Bahir Dar Zuria Ethiopia. A total of 437 stool samples were collected and analyzed by the following procedures: conventional Baermann (CB), modified Baermann (MB), and modified Baermann with charcoal pre-incubation (MBCI). The diagnostic sensitivity and Negative Predictive Value (NPV) of each technique was calculated using the combination of all the three techniques as a composite reference standard. Our result indicated that larvae of S. stercoralis were detected in 151 (34.6%) stool samples. The prevalence of S. stercoralis infection based on the three diagnostic methods was 9.6%, 8.0%, and 31.3% by CB, MB, and MBCI respectively. The sensitivity and NPV for CB, MB, and MBCI were 26.7% and 70.8%, 22.1% and 69.6%, and 87.0% and 93.2%, respectively. The MBCI showed significant difference (P- value = Conclusion/significanceOur results suggest the superior performance of MBCI. It is relatively easy to implement, simple to perform and comparatively cheaper. The CB is by far the commonly used method in routine diagnostic although this technique significantly underestimates the true burden of the disease and thereby contributing to the exclusion of S. stercoralis from the control strategies. Therefore, MBCI is recommended as a routine microscopy-based diagnostic test for S. stercoralis infection, particularly in settings where molecular procedures are not available