The role of schizophrenia susceptibility genes in hippocampal-dependent long-term memory in the adult rat

It was concluded that some of the schizophrenia susceptibility genes were regulated in association with hippocampal-dependent LTM processes but not schizophrenia susceptibility genes were identified to be causally involved in hippocampal-dependent LTM processes.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The role of schizophrenia susceptibility genes in hippocampal-dependent long-term memory in the adult rat

This thesis investigates whether genes that have been associated with schizophrenia have a role in hippocampal-dependent long-term memory. Schizophrenia is psychiatric disorder in which individuals experience, amongst other symptoms, cognitive difficulties including long­ term memory (LTM) impairments. The functional roles of many schizophrenia susceptibility genes remain unknown. In this study, a selection of schizophrenia susceptibility genes and their splice variants, in particular Neuregulin 1 (Nrg1), Dysbindin 1 (Dtnbpl), Disrupted-in- schizophrenia 1 (Disci) and Early growth response factor 3 (Egr3), were hypothesized to be regulated in association with the processes of LTM. The contextual fear conditioning behavioural paradigm in which a rat associates an electric footshock with a distinct context was used to investigate hippocampal-dependent LTM

Completeness of Reporting in Diet- and Nutrition-Related Randomized Controlled Trials and Systematic Reviews With Meta-Analysis:Protocol for 2 Independent Meta-Research Studies

Background: Journal articles describing randomized controlled trials (RCTs) and systematic reviews with meta-analysis of RCTs are not optimally reported and often miss crucial details. This poor reporting makes assessing these studies’ risk of bias or reproducing their results difficult. However, the reporting quality of diet- and nutrition-related RCTs and meta-analyses has not been explored. Objective: We aimed to assess the reporting completeness and identify the main reporting limitations of diet- and nutrition-related RCTs and meta-analyses of RCTs, estimate the frequency of reproducible research practices among these RCTs, and estimate the frequency of distorted presentation or spin among these meta-analyses. Methods: Two independent meta-research studies will be conducted using articles published in PubMed-indexed journals. The first will include a sample of diet- and nutrition-related RCTs; the second will include a sample of systematic reviews with meta-analysis of diet- and nutrition-related RCTs. A validated search strategy will be used to identify RCTs of nutritional interventions and an adapted strategy to identify meta-analyses in PubMed. We will search for RCTs and meta-analyses indexed in 1 calendar year and randomly select 100 RCTs (June 2021 to June 2022) and 100 meta-analyses (July 2021 to July 2022). Two reviewers will independently screen the titles and abstracts of records yielded by the searches, then read the full texts to confirm their eligibility. The general features of these published RCTs and meta-analyses will be extracted into a research electronic data capture database (REDCap; Vanderbilt University). The completeness of reporting of each RCT will be assessed using the items in the CONSORT (Consolidated Standards of Reporting Trials), its extensions, and the TIDieR (Template for Intervention Description and Replication) statements. Information about practices that promote research transparency and reproducibility, such as the publication of protocols and statistical analysis plans will be collected. There will be an assessment of the completeness of reporting of each meta-analysis using the items in the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement and collection of information about spin in the abstracts and full-texts. The results will be presented as descriptive statistics in diagrams or tables. These 2 meta-research studies are registered in the Open Science Framework. Results: The literature search for the first meta-research retrieved 20,030 records and 2182 were potentially eligible. The literature search for the second meta-research retrieved 10,918 records and 850 were potentially eligible. Among them, random samples of 100 RCTs and 100 meta-analyses were selected for data extraction. Data extraction is currently in progress, and completion is expected by the beginning of 2023. Conclusions: Our meta-research studies will summarize the main limitation on reporting completeness of nutrition- or diet-related RCTs and meta-analyses and provide comprehensive information regarding the particularities in the reporting of intervention studies in the nutrition field

Completeness of reporting in diet- and nutrition-related randomized controlled trials and systematic reviews with meta-analysis: protocol for 2 independent meta-research studies

Background: Journal articles describing randomized controlled trials (RCTs) and systematic reviews with meta-analysis of RCTs are not optimally reported and often miss crucial details. This poor reporting makes assessing these studies’ risk of bias or reproducing their results difficult. However, the reporting quality of diet- and nutrition-related RCTs and meta-analyses has not been explored. Objective: We aimed to assess the reporting completeness and identify the main reporting limitations of diet- and nutrition-related RCTs and meta-analyses of RCTs, estimate the frequency of reproducible research practices among these RCTs, and estimate the frequency of distorted presentation or spin among these meta-analyses. Methods: Two independent meta-research studies will be conducted using articles published in PubMed-indexed journals. The first will include a sample of diet- and nutrition-related RCTs; the second will include a sample of systematic reviews with meta-analysis of diet- and nutrition-related RCTs. A validated search strategy will be used to identify RCTs of nutritional interventions and an adapted strategy to identify meta-analyses in PubMed. We will search for RCTs and meta-analyses indexed in 1 calendar year and randomly select 100 RCTs (June 2021 to June 2022) and 100 meta-analyses (July 2021 to July 2022). Two reviewers will independently screen the titles and abstracts of records yielded by the searches, then read the full texts to confirm their eligibility. The general features of these published RCTs and meta-analyses will be extracted into a research electronic data capture database (REDCap; Vanderbilt University). The completeness of reporting of each RCT will be assessed using the items in the CONSORT (Consolidated Standards of Reporting Trials), its extensions, and the TIDieR (Template for Intervention Description and Replication) statements. Information about practices that promote research transparency and reproducibility, such as the publication of protocols and statistical analysis plans will be collected. There will be an assessment of the completeness of reporting of each meta-analysis using the items in the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement and collection of information about spin in the abstracts and full-texts. The results will be presented as descriptive statistics in diagrams or tables. These 2 meta-research studies are registered in the Open Science Framework. Results: The literature search for the first meta-research retrieved 20,030 records and 2182 were potentially eligible. The literature search for the second meta-research retrieved 10,918 records and 850 were potentially eligible. Among them, random samples of 100 RCTs and 100 meta-analyses were selected for data extraction. Data extraction is currently in progress, and completion is expected by the beginning of 2023. Conclusions: Our meta-research studies will summarize the main limitation on reporting completeness of nutrition- or diet-related RCTs and meta-analyses and provide comprehensive information regarding the particularities in the reporting of intervention studies in the nutrition field. International Registered Report Identifier (IRRID): DERR1-10.2196/4353

Impact of issuing longer- versus shorter-duration prescriptions: a systematic review.

BACKGROUND: Long-term conditions place a substantial burden on primary care services, with drug therapy being a core aspect of clinical management. However, the ideal frequency for issuing repeat prescriptions for these medications is unknown. AIM: To examine the impact of longer-duration (2-4 months) versus shorter-duration (28-day) prescriptions. DESIGN AND SETTING: Systematic review of primary care studies. METHOD: Scientific and grey literature databases were searched from inception until 21 October 2015. Eligible studies were randomised controlled trials and observational studies that examined longer prescriptions (2-4 months) compared with shorter prescriptions (28 days) in patients with stable, chronic conditions being treated in primary care. Outcomes of interest were: health outcomes, adverse events, medication adherence, medication wastage, professional administration time, pharmacists' time and/or costs, patient experience, and patient out-of-pocket costs. RESULTS: From a search total of 24 876 records across all databases, 13 studies were eligible for review. Evidence of moderate quality from nine studies suggested that longer prescriptions are associated with increased medication adherence. Evidence from six studies suggested that longer prescriptions may increase medication waste, but results were not always statistically significant and were of very low quality. No eligible studies were identified that measured any of the other outcomes of interest, including health outcomes and adverse events. CONCLUSION: There is insufficient evidence relating to the overall impact of differing prescription lengths on clinical and health service outcomes, although studies do suggest medication adherence may improve with longer prescriptions. UK recommendations to provide shorter prescriptions are not substantiated by the current evidence base

The exclusive induction of extinction is gated by BDNF

We have previously reported that the reconsolidation and extinction of hippocampal-dependent contextual fear memory can be initiated by a single context conditioned stimulus (CS) presentation of either short or long duration, and that both processes require protein synthesis in this brain region. Furthermore, reconsolidation depends on Zif268 activity in this region. Here we show that by infusing a recombinant brain-derived neurotrophic factor (rBDNF) directly into the brain of rats, that high levels of mature BDNF in the hippocampus at retrieval constrain the extinction of the fear memory after prolonged memory recall. We also show after a short CS exposure that reconsolidation was impaired using antisense oligonucleotides targeting Zif268, and that, similarly, reductions in conditioned behavior were observed after prolonged CS presentation when extinction is constrained by high levels of BDNF. This is direct evidence that in the mammalian brain extinction proceeds exclusively after prolonged CS exposure. In addition, that BDNF activity in the hippocampus contributes to a molecular switch for the extinction of hippocampal-dependent memory

The impact of the National Institute for Health Research Health Technology Assessment programme, 2003–13: a multimethod evaluation

Background: The National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme supports research tailored to the needs of NHS decision-makers, patients and clinicians. This study reviewed the impact of the programme, from 2003 to 2013, on health, clinical practice, health policy, the economy and academia. It also considered how HTA could maintain and increase its impact. Methods: Interviews (n = 20): senior stakeholders from academia, policy-making organisations and the HTA programme. Bibliometric analysis: citation analysis of publications arising from HTA programme-funded research. Researchfish survey: electronic survey of all HTA grant holders. Payback case studies (n = 12): in-depth case studies of HTA programme-funded research. Results: We make the following observations about the impact, and routes to impact, of the HTA programme: it has had an impact on patients, primarily through changes in guidelines, but also directly (e.g. changing clinical practice); it has had an impact on UK health policy, through providing high-quality scientific evidence – its close relationships with the National Institute for Health and Care Excellence (NICE) and the National Screening Committee (NSC) contributed to the observed impact on health policy, although in some instances other organisations may better facilitate impact; HTA research is used outside the UK by other HTA organisations and systematic reviewers – the programme has an impact on HTA practice internationally as a leader in HTA research methods and the funding of HTA research; the work of the programme is of high academic quality – the Health Technology Assessment journal ensures that the vast majority of HTA programme-funded research is published in full, while the HTA programme still encourages publication in other peer-reviewed journals; academics agree that the programme has played an important role in building and retaining HTA research capacity in the UK; the HTA programme has played a role in increasing the focus on effectiveness and cost-effectiveness in medicine – it has also contributed to increasingly positive attitudes towards HTA research both within the research community and the NHS; and the HTA focuses resources on research that is of value to patients and the UK NHS, which would not otherwise be funded (e.g. where there is no commercial incentive to undertake research). The programme should consider the following to maintain and increase its impact: providing targeted support for dissemination, focusing resources when important results are unlikely to be implemented by other stakeholders, particularly when findings challenge vested interests; maintaining close relationships with NICE and the NSC, but also considering other potential users of HTA research; maintaining flexibility and good relationships with researchers, giving particular consideration to the Technology Assessment Report (TAR) programme and the potential for learning between TAR centres; maintaining the academic quality of the work and the focus on NHS need; considering funding research on the short-term costs of the implementation of new health technologies; improving the monitoring and evaluation of whether or not patient and public involvement influences research; improve the transparency of the priority-setting process; and continuing to monitor the impact and value of the programme to inform its future scientific and administrative development. Funding: The NIHR HTA programme

Mapping The Global Mental Health Research Funding System

This study, carried out by RAND Europe, maps the global funding of mental health research between 2009 and 2014. It builds from the bottom up a picture of who the major funders are, what kinds of research they support and how their strategies relate to one another. It uses the funding acknowledgements on journal papers as a starting point for this. The project also looks to the future, considering some of the areas of focus, challenges and opportunities which may shape the field in the coming few years. The main report is accompanied by a set of 32 'deep dive' case studies of individual research funders, a set of six cross-cutting themes that emerged from the analysis and methodological appendices. The project was supported in Canada by the Graham Boeckh Foundation, Alberta Innovates Health Solutions and the Canadian Institutes of Health Research; in the UK by the National Institute for Health Research, the Wellcome Trust and MQ: Transforming Mental Health Through Research; and in Australia by the Movember Foundation