Testing significance relative to a fold-change threshold is a TREAT

Motivation: Statistical methods are used to test for the differential expression of genes in microarray experiments. The most widely used methods successfully test whether the true differential expression is different from zero, but give no assurance that the differences found are large enough to be biologically meaningful

The development of service user-led recommendations for health and social care services on leaving hospital with memory loss or dementia – the SHARED study

YesBackground Health and social care services are under strain providing care in the community particularly at hospital discharge. Patient and carer experiences can inform and shape services. Objective To develop service user-led recommendations enabling smooth transition for people living with memory loss from acute hospital to community. Design Lead and co-researchers conducted semi-structured interviews with 15 pairs of carers and patients with memory loss at discharge, 6 and 12 weeks post-discharge and one semi-structured interview with health and social care professionals and Admiral Nurses. Framework analysis was guided by co-researchers. Two focus groups of study participants, facilitated by co-researchers, met to shape and finalize recommendations. Setting and participants Recruitment took place in acute hospitals in two National Health Service (NHS) Trusts in England. Patients were aged 65 and over, with memory loss, an in-patient for at least 1 week returning to the community, who had a carer consenting to be in the study. Results Poor delivery of services caused considerable stress to some study families living with memory loss. Three key recommendations included a need for a written, mutually agreed discharge plan, a named coordinator of services, and improved domiciliary care services. Discussion and conclusions Vulnerable patients with memory loss find coming out of hospital after an extended period a stressful experience. The SHARED study contributes to understanding the hospital discharge process through the eyes of the patient and carer living with memory loss and has the potential to contribute to more efficient use of resources and to improving health outcomes in communities.National Institute for Health Research. Grant Number: PB-PG-1112-2906

Influences on recruitment to randomised controlled trials in mental health settings in England: a national cross-sectional survey of researchers working for the Mental Health Research Network

Background: Recruitment to trials is complex and often protracted; selection bias may compromise generalisability. In the mental health field (as elsewhere), diverse factors have been described as hindering researcher access to potential participants and various strategies have been proposed to overcome barriers. However, the extent to which various influences identified in the literature are operational across mental health settings in England has not been systematically examined. Methods: A cross-sectional, online survey of clinical studies officers employed by the Mental Health Research Network in England to recruit to trials from National Health Service mental health services. The bespoke questionnaire invited participants to report exposure to specified influences on recruitment, the perceived impact of these on access to potential participants, and to describe additional positive or negative influences on recruitment. Analysis employed descriptive statistics, the framework approach and triangulation of data. Results: Questionnaires were returned by 98 (58%) of 170 clinical studies officers who reported diverse experience. Data demonstrated a disjunction between policy and practice. While the particulars of trial design and various marketing and dommunication strategies could influence recruitment, consensus was that the culture of NHS mental health services is not donducive to research. Since financial rewards for recruitment paid to Trusts and feedback about studies seldom reaching frontline services, clinicians were described as distanced from research. Facing continual service change and demanding clinical workloads, clinicians generally did not prioritise recruitment activities. Incentives to trial participants had variable impact on access but recruitment could be enhanced by engagement of senior investigators and integrating referral with routine practice. Comprehensive, robust feasibility studies and reciprocity between researchers and clinicians were considered crucial to successful recruitment. Conclusions: In the mental health context, researcher access to potential trial participants is multiply influenced. Gatekeeping clinicians are faced with competing priorities and resources constrain research activity. It seems that environmental adjustment predicated on equitable resource allocation is needed if clinicians in NHS mental health services are to fully support the conduct of randomised controlled trials. Whilst cultural transformation, requiring changes in assumptions and values, is complex, our findings suggest that attention to practical matters can support this and highlight issues requiring careful consideration

Teenagers’ understandings of and attitudes towards vaccines and vaccine-preventable diseases: a qualitative study

<p>Background: To examine immunisation information needs of teenagers we explored understandings of vaccination and vaccine-preventable diseases, attitudes towards immunisation and experiences of immunisation. Diseases discussed included nine for which vaccines are currently offered in the UK (human papillomavirus, meningitis, tetanus, diphtheria, polio, whooping cough, measles, mumps and rubella), and two not currently included in the routine UK schedule (hepatitis B and chickenpox).</p> <p>Methods Twelve focus groups conducted between November 2010 and March 2011 with 59 teenagers (29 girls and 30 boys) living in various parts of Scotland.</p> <p>Results Teenagers exhibited limited knowledge and experience of the diseases, excluding chickenpox. Measles, mumps and rubella were perceived as severe forms of chickenpox-like illness, and rubella was not associated with foetal damage. Boys commonly believed that human papillomavirus only affects girls, and both genders exhibited confusion about its relationship with cancer. Participants considered two key factors when assessing the threat of diseases: their prevalence in the UK, and their potential to cause fatal or long-term harm. Meningitis was seen as a threat, but primarily to babies. Participants explained their limited knowledge as a result of mass immunisation making once-common diseases rare in the UK, and acknowledged immunisation's role in reducing disease prevalence.</p> <p>Conclusions While it is welcome that fewer teenagers have experienced vaccine-preventable diseases, this presents public health advocates with the challenge of communicating benefits of immunisation when advantages are less visible. The findings are timely in view of the Joint Committee on Vaccination and Immunisation's recommendation that a booster of meningitis C vaccine should be offered to teenagers; that teenagers did not perceive meningitis C as a significant threat should be a key concern of promotional information. While teenagers’ experiences of immunisation in school were not always positive, they seemed enthusiastic at the prospect of introducing more vaccines for their age group.</p&gt

Phase-shift analysis of low-energy π±p\pi^{\pm}p elastic-scattering data

Using electromagnetic corrections previously calculated by means of a potential model, we have made a phase-shift analysis of the $\pi^\pm p$ elastic-scattering data up to a pion laboratory kinetic energy of 100 MeV. The hadronic interaction was assumed to be isospin invariant. We found that it was possible to obtain self-consistent databases by removing very few measurements. A pion-nucleon model was fitted to the elastic-scattering database obtained after the removal of the outliers. The model-parameter values showed an impressive stability when the database was subjected to different criteria for the rejection of experiments. Our result for the pseudovector $\pi N N$ coupling constant (in the standard form) is $0.0733 \pm 0.0014$. The six hadronic phase shifts up to 100 MeV are given in tabulated form. We also give the values of the s-wave scattering lengths and the p-wave scattering volumes. Big differences in the s-wave part of the interaction were observed when comparing our hadronic phase shifts with those of the current GWU solution. We demonstrate that the hadronic phase shifts obtained from the analysis of the elastic-scattering data cannot reproduce the measurements of the $\pi^- p$ charge-exchange reaction, thus corroborating past evidence that the hadronic interaction violates isospin invariance. Assuming the validity of the result obtained within the framework of chiral perturbation theory, that the mass difference between the $u$- and the $d$-quark has only a very small effect on the isospin invariance of the purely hadronic interaction, the isospin-invariance violation revealed by the data must arise from the fact that we are dealing with a hadronic interaction which still contains residual effects of electromagnetic origin.Comment: 43 pages, 6 figure

"It's making contacts" : notions of social capital and implications for widening access to medical education

Acknowledgements Our thanks to the Medical Schools Council (MSC) of the UK for funding Study A; REACH Scotland for funding Study B; and Queen Mary University of London, and to the medical school applicants and students who gave their time to be interviewed. Our thanks also to Dr Sean Zhou and Dr Sally Curtis, and Manjul Medhi, for their help with data collection for studies A and B respectively. Our thanks also to Dr Lara Varpio, Uniformed Services University of the USA, for her advice and guidance on collating data sets and her comments on the draft manuscript.Peer reviewedPublisher PD

Developing a model of mental health self-care support for children and young people through an integrated evaluation of available types of provision involving systematic review, meta-analysis and case study

Background The mental health of children and young people (CYP) is a major UK public health concern. Recent policy reviews have identified that service provision for CYP with mental health needs is not as effective, responsive, accessible or child-centred as it could be. Following on from a previous National Institute for Health Research (NIHR) study into self-care support for CYP with long-term physical health needs, this study explored self-care support’s potential in CYP’s mental health. Objectives To identify and evaluate the types of mental health self-care support used by, and available to, CYP and their parents, and to establish how such support interfaces with statutory and non-statutory service provision. Design Two inter-related systematic literature reviews (an effectiveness review with meta-analysis and a perceptions review), together with a service mapping exercise and case study. Setting Global (systematic reviews); England and Wales (mapping exercise and case study). Participants (case study) Fifty-two individuals (17 CYP, 16 family members and 19 staff) were interviewed across six sites. Main outcome measures (meta-analysis) A measure of CYP’s mental health symptomatology. Data sources (literature reviews) MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, All Evidence-Based Medicine (EBM) Reviews, Applied Social Sciences Index and Abstracts (ASSIA) and Education Resources Information Center (ERIC). Review methods Titles and abstracts of papers were screened for relevance then grouped into studies. Two independent reviewers extracted data from studies meeting the inclusion criteria. A descriptive analysis and meta-analysis were conducted for the effectiveness review; descriptive analyses were conducted for the perceptions review. These analyses were integrated to elicit a mixed-methods review. Results Sixty-five of 71 included studies were meta-analysable. These 65 studies elicited 71 comparisons which, when meta-analysed, suggested that self-care support interventions were effective at 6-month [standardised mean difference (SMD) = −0.20; 95% confidence interval (CI) −0.28 to −0.11] and 12-month (SMD = −0.12; 95% CI −0.17 to −0.06) follow-ups. However, judged against Cochrane criteria, the studies were mostly low quality. Key elements of self-care support identified in the perceptions review were the acquisition of knowledge and skills, peer support and the relationship with the self-care support agent; CYP also had different perceptions from adults about what is important in self-care support. The mapping exercise identified 27 providers of 33 self-care support services. According to the case study data, effective self-care support services are predicated on flexibility; straightforward access; non-judgemental, welcoming organisations and staff; the provision of time and attention; opportunities to learn and practise skills relevant to self-care; and systems of peer support. Conclusions Mental health self-care support interventions for CYP are modestly effective in the short to medium term. Self-care support can be conceptualised as a process which has overlap with ‘recovery’. CYP and their families want choice and flexibility in the provision of such interventions and a continued relationship with services after the nominal therapy period. Those delivering self-care support need to have specific child-centred attributes. Future work Future work should focus on under-represented conditions (e.g. psychosis, eating disorders, self-harm); the role of technology, leadership and readiness in self-care support; satisfaction in self-care support; the conceptualisation of self-care support in CYP’s mental health; and efficacy and cost-effectiveness

What factors influence successful recruitment of siblings of individuals with first episode psychosis to e-health interventions? A qualitative study.

BACKGROUND: Recruitment to clinical research studies can prove complex. This is particularly true of mental health research, given factors such as confidentiality, capacity and consent, or when attempting to recruit family members as opposed to service users themselves. AIM: This study investigated the challenges experienced and strategies employed in the recruitment of siblings of people with first episode psychosis using Early Intervention in Psychosis Services (EIPS) in England. METHODS: As part of a randomized controlled trial (RCT) of an e-health intervention for siblings, we conducted a process evaluation study whereby semistructured interview was undertaken with clinical and research staff involved in recruitment of siblings. Data were analysed thematically. RESULTS: Twelve participants from six EIPS were interviewed. Data analysis revealed seven key themes: (i) limited comprehensive family data available; (ii) data governance and consent issues; (iii) organizational factors; (iv) convoluted recruitment methods; (v) concerns about service users' opinions; (vi) fluidity in siblings' needs and expectations; and (vii) strategies to enhance recruitment. CONCLUSIONS: Recruitment challenges identified in this study concerned administrative, organizational, process and attitudinal issues. These are similar to other studies recruiting mental health service users as well as family members. Failure to recruit to target implies that studies are underpowered to detect potential statistically or clinically meaningful changes. Future studies should establish how best to enhance family inclusiveness in clinical practice and research

A Systematic Mapping Approach of 16q12.2/FTO and BMI in More Than 20,000 African Americans Narrows in on the Underlying Functional Variation: Results from the Population Architecture using Genomics and Epidemiology (PAGE) Study

Genetic variants in intron 1 of the fat mass- and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI-associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-map this region and narrow in on the functional variant. To comprehensively explore the 16q12.2/FTO locus and to search for second independent signals in the broader region, we fine-mapped a 646-kb region, encompassing the large FTO gene and the flanking gene RPGRIP1L by investigating a total of 3,756 variants (1,529 genotyped and 2,227 imputed variants) in 20,488 AAs across five studies. We observed associations between BMI and variants in the known FTO intron 1 locus: the SNP with the most significant p-value, rs56137030 (8.3×10-6) had not been highlighted in previous studies. While rs56137030was correlated at r2>0.5 with 103 SNPs in Europeans (including the GWAS index SNPs), this number was reduced to 28 SNPs in AA. Among rs56137030 and the 28 correlated SNPs, six were located within candidate intronic regulatory elements, including rs1421085, for which we predicted allele-specific binding affinity for the transcription factor CUX1, which has recently been implicated in the regulation of FTO. We did not find strong evidence for a second independent signal in the broader region. In summary, this large fine-mapping study in AA has substantially reduced the number of common alleles that are likely to be functional candidates of the known FTO locus. Importantly our study demonstrated that comprehensive fine-mapping in AA provides a powerful approach to narrow in on the functional candidate(s) underlying the initial GWAS findings in European populations

Bacterial Acquisition in Juveniles of Several Broadcast Spawning Coral Species

Coral animals harbor diverse microorganisms in their tissues, including archaea, bacteria, viruses, and zooxanthellae. The extent to which coral-bacterial associations are specific and the mechanisms for their maintenance across generations in the environment are unknown. The high diversity of bacteria in adult coral colonies has made it challenging to identify species-specific patterns. Localization of bacteria in gametes and larvae of corals presents an opportunity for determining when bacterial-coral associations are initiated and whether they are dynamic throughout early development. This study focuses on the early onset of bacterial associations in the mass spawning corals Montastraea annularis, M. franksi, M. faveolata, Acropora palmata, A. cervicornis, Diploria strigosa, and A. humilis. The presence of bacteria and timing of bacterial colonization was evaluated in gametes, swimming planulae, and newly settled polyps by fluorescence in situ hybridization (FISH) using general eubacterial probes and laser-scanning confocal microscopy. The coral species investigated in this study do not appear to transmit bacteria via their gametes, and bacteria are not detectable in or on the corals until after settlement and metamorphosis. This study suggests that mass-spawning corals do not acquire, or are not colonized by, detectable numbers of bacteria until after larval settlement and development of the juvenile polyp. This timing lays the groundwork for developing and testing new hypotheses regarding general regulatory mechanisms that control bacterial colonization and infection of corals, and how interactions among bacteria and juvenile polyps influence the structure of bacterial assemblages in corals