Developing a decision aid to guide public sector health policy decisions: A study protocol

<p>Abstract</p> <p>Background</p> <p>Decision aids have been developed in a number of health disciplines to support evidence-informed decision making, including patient decision aids and clinical practice guidelines. However, policy contexts differ from clinical contexts in terms of complexity and uncertainty, requiring different approaches for identifying, interpreting, and applying many different types of evidence to support decisions. With few studies in the literature offering decision guidance specifically to health policymakers, the present study aims to facilitate the structured and systematic incorporation of research evidence and, where there is currently very little guidance, values and other non-research-based evidence, into the policy making process. The resulting decision aid is intended to help public sector health policy decision makers who are tasked with making evidence-informed decisions on behalf of populations. The intent is not to develop a decision aid that will yield uniform recommendations across jurisdictions, but rather to facilitate more transparent policy decisions that reflect a balanced consideration of all relevant factors.</p> <p>Methods/design</p> <p>The study comprises three phases: a modified meta-narrative review, the use of focus groups, and the application of a Delphi method. The modified meta-narrative review will inform the initial development of the decision aid by identifying as many policy decision factors as possible and other features of methodological guidance deemed to be desirable in the literatures of all relevant disciplines. The first of two focus groups will then seek to marry these findings with focus group members' own experience and expertise in public sector population-based health policy making and screening decisions. The second focus group will examine issues surrounding the application of the decision aid and act as a sounding board for initial feedback and refinement of the draft decision aid. Finally, the Delphi method will be used to further inform and refine the decision aid with a larger audience of potential end-users.</p> <p>Discussion</p> <p>The product of this research will be a working version of a decision aid to support policy makers in population-based health policy decisions. The decision aid will address the need for more structured and systematic ways of incorporating various evidentiary sources where applicable.</p

Personal recovery suits us all: A study in patients with non-affective psychosis, unaffected siblings and healthy controls

Personal recovery transcends illness and is a unifying human experience. Core elements in personal recovery are hope, meaning, and rebuilding oneself. Here we aim to investigate whether factors associated with personal recovery in patients with non-affective psychosis, unaffected siblings and healthy controls are similar. We investigated the association between personal recovery and resilience, social support, socio-demographic and illness-related variables in 580 patients, 630 siblings, and 351 healthy controls who participated in the Genetic Risk and Outcome of Psychosis (GROUP) study. Bi-variate associations between personal recovery and individual variables were assessed and multiple linear regression analyses were performed to estimate the proportion of variance in personal recovery that could be accounted for by the predictors and to investigate which predictors independently added to the model. Positive self was significantly and independently associated with personal recovery in all three groups. Pro-active action taking also seems to be important. Social functioning significantly contributed to explained variance in patients and siblings. Regarding illness-related factors, depressive symptoms had impact on personal recovery in both patients and siblings, whereas positive symptoms only did in siblings. The findings imply that not only personal recovery itself, but also some associated factors are universally human and suit us all. This means that patients and non-patients share supportive factors of personal recovery which may help to reach mutual understanding. Recovery-oriented practices and mental health services might be more effective when focusing also on improving self-image, functional coping styles and generating social interaction, next to the reduction of affective symptoms

Gains in QTL Detection Using an Ultra-High Density SNP Map Based on Population Sequencing Relative to Traditional RFLP/SSR Markers

Huge efforts have been invested in the last two decades to dissect the genetic bases of complex traits including yields of many crop plants, through quantitative trait locus (QTL) analyses. However, almost all the studies were based on linkage maps constructed using low-throughput molecular markers, e.g. restriction fragment length polymorphisms (RFLPs) and simple sequence repeats (SSRs), thus are mostly of low density and not able to provide precise and complete information about the numbers and locations of the genes or QTLs controlling the traits. In this study, we constructed an ultra-high density genetic map based on high quality single nucleotide polymorphisms (SNPs) from low-coverage sequences of a recombinant inbred line (RIL) population of rice, generated using new sequencing technology. The quality of the map was assessed by validating the positions of several cloned genes including GS3 and GW5/qSW5, two major QTLs for grain length and grain width respectively, and OsC1, a qualitative trait locus for pigmentation. In all the cases the loci could be precisely resolved to the bins where the genes are located, indicating high quality and accuracy of the map. The SNP map was used to perform QTL analysis for yield and three yield-component traits, number of tillers per plant, number of grains per panicle and grain weight, using data from field trials conducted over years, in comparison to QTL mapping based on RFLPs/SSRs. The SNP map detected more QTLs especially for grain weight, with precise map locations, demonstrating advantages in detecting power and resolution relative to the RFLP/SSR map. Thus this study provided an example for ultra-high density map construction using sequencing technology. Moreover, the results obtained are helpful for understanding the genetic bases of the yield traits and for fine mapping and cloning of QTLs

Incidence of Schizophrenia and Other Psychoses in England, 1950–2009: A Systematic Review and Meta-Analyses

Background We conducted a systematic review of incidence rates in England over a sixty-year period to determine the extent to which rates varied along accepted (age, sex) and less-accepted epidemiological gradients (ethnicity, migration and place of birth and upbringing, time). Objectives To determine variation in incidence of several psychotic disorders as above. Data Sources Published and grey literature searches (MEDLINE, PSycINFO, EMBASE, CINAHL, ASSIA, HMIC), and identification of unpublished data through bibliographic searches and author communication. Study Eligibility Criteria Published 1950–2009; conducted wholly or partially in England; original data on incidence of non-organic adult-onset psychosis or one or more factor(s) pertaining to incidence. Participants People, 16–64 years, with first -onset psychosis, including non-affective psychoses, schizophrenia, bipolar disorder, psychotic depression and substance-induced psychosis. Study Appraisal and Synthesis Methods Title, abstract and full-text review by two independent raters to identify suitable citations. Data were extracted to a standardized extraction form. Descriptive appraisals of variation in rates, including tables and forest plots, and where suitable, random-effects meta-analyses and meta-regressions to test specific hypotheses; rate heterogeneity was assessed by the I2-statistic. Results 83 citations met inclusion. Pooled incidence of all psychoses (N = 9) was 31.7 per 100,000 person-years (95%CI: 24.6–40.9), 23.2 (95%CI: 18.3–29.5) for non-affective psychoses (N = 8), 15.2 (95%CI: 11.9–19.5) for schizophrenia (N = 15) and 12.4 (95%CI: 9.0–17.1) for affective psychoses (N = 7). This masked rate heterogeneity (I2: 0.54–0.97), possibly explained by socio-environmental factors; our review confirmed (via meta-regression) the typical age-sex interaction in psychosis risk, including secondary peak onset in women after 45 years. Rates of most disorders were elevated in several ethnic minority groups compared with the white (British) population. For example, for schizophrenia: black Caribbean (pooled RR: 5.6; 95%CI: 3.4–9.2; N = 5), black African (pooled RR: 4.7; 95%CI: 3.3–6.8; N = 5) and South Asian groups in England (pooled RR: 2.4; 95%CI: 1.3–4.5; N = 3). We found no evidence to support an overall change in the incidence of psychotic disorder over time, though diagnostic shifts (away from schizophrenia) were reported. Limitations Incidence studies were predominantly cross-sectional, limiting causal inference. Heterogeneity, while evidencing important variation, suggested pooled estimates require interpretation alongside our descriptive systematic results. Conclusions and Implications of Key Findings Incidence of psychotic disorders varied markedly by age, sex, place and migration status/ethnicity. Stable incidence over time, together with a robust socio-environmental epidemiology, provides a platform for developing prediction models for health service planning

eIF4A2 drives repression of translation at initiation by Ccr4-Not through purine-rich motifs in the 5'UTR

Background: Regulation of the mRNA life cycle is central to gene expression control and determination of cell fate. miRNAs represent a critical mRNA regulatory mechanism, but despite decades of research, their mode of action is still not fully understood. Results: Here, we show that eIF4A2 is a major effector of the repressive miRNA pathway functioning via the Ccr4-Not complex. We demonstrate that while DDX6 interacts with Ccr4-Not, its effects in the mechanism are not as pronounced. Through its interaction with the Ccr4-Not complex, eIF4A2 represses mRNAs at translation initiation. We show evidence that native eIF4A2 has similar RNA selectivity to chemically inhibited eIF4A1. eIF4A2 exerts its repressive effect by binding purine-rich motifs which are enriched in the 5′UTR of target mRNAs directly upstream of the AUG start codon. Conclusions: Our data support a model whereby purine motifs towards the 3′ end of the 5′UTR are associated with increased ribosome occupancy and possible uORF activation upon eIF4A2 binding

Unraveling infectious structures, strain variants and species barriers for the yeast prion [PSI+]

Prions are proteins that can access multiple conformations, at least one of which is beta-sheet rich, infectious and self-perpetuating in nature. These infectious proteins show several remarkable biological activities, including the ability to form multiple infectious prion conformations, also known as strains or variants, encoding unique biological phenotypes, and to establish and overcome prion species (transmission) barriers. In this Perspective, we highlight recent studies of the yeast prion [PSI+], using various biochemical and structural methods, that have begun to illuminate the molecular mechanisms by which self-perpetuating prions encipher such biological activities. We also discuss several aspects of prion conformational change and structure that remain either unknown or controversial, and we propose approaches to accelerate the understanding of these enigmatic, infectious conformers