33 research outputs found
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Applying the Non-adoption, Abandonment, Scale-up, Spread and Sustainability (NASSS) Framework to evaluate automated evidence synthesis in health behaviour change
YesAutomated tools to speed up the process of evidence synthesis are increasingly apparent within health behaviour research, however, frameworks to evaluate the development and implementation of such tools are not routinely used. This commentary explores the potential of the Non-adoption, Abandonment, Scale-up, Spread and Sustainability framework (NASSS; Greenhalgh et al., 2017) for supporting automated evidence synthesis in health behaviour change by applying it to the ongoing Human Behaviour-Change Project, which aims to revolutionise evidence synthesis within behaviour change intervention research. To increase the relevance of NASSS for health behaviour change, we recommend i) terminology changes (‘condition’ to ‘behaviour’ and ‘patient’ to ‘end user’) and ii) a that it is used prospectively so that complexities can be addressed iteratively. We draw three conclusions about i) the need to specify the organisations that will use the technology, ii) identifying what to do if interdependencies fail and iii) even though we have focused on automated evidence synthesis, NASSS would arguably be beneficial for technology developments in health behaviour change more generally, particularly for invention development (e.g. for a behaviour change app)
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A registered report survey of open research practices in psychology departments in the UK and Ireland
YesOpen research practices seek to enhance the transparency and reproducibility of research. Whilst there is evidence of increased uptake in these practices, such as study preregistration and open data, facilitated by new infrastructure and policies, little research has assessed general uptake of such practices across psychology university researchers. The current study estimates psychologists’ level of engagement in open research practices across universities in the United Kingdom and Ireland, while also assessing possible explanatory factors that may impact their engagement. Data were collected from 602 psychology researchers in the UK and Ireland on the extent to which they have implemented various practices (e.g., use of preprints, preregistration, open data, open materials). Here we present the summarised descriptive results, as well as considering differences between various categories of researcher (e.g., career stage, subdiscipline, methodology), and examining the relationship between researcher’s practices and their self-reported capability, opportunity, and motivation (COM-B) to engage in open research practices. Results show that while there is considerable variability in engagement of open research practices, differences across career stage and subdiscipline of psychology are small by comparison. We observed consistent differences according to respondent’s research methodology and based on the presence of institutional support for open research. COM-B dimensions were collectively significant predictors of engagement in open research, with automatic motivation emerging as a consistently strong predictor. We discuss these findings, outline some of the challenges experienced in this study, and offer suggestions and recommendations for future research. Estimating the prevalence of responsible research practices is important to assess sustained behaviour change in research reform, tailor educational training initiatives, and to understand potential factors that might impact engagement.Research funding: Aston University. Article funding: Open access funding provided by IReL
Characterisation of the Fibroblast Growth Factor Dependent Transcriptome in Early Development
BACKGROUND: FGF signaling has multiple roles in regulating processes in animal development, including the specification and patterning of the mesoderm. In addition, FGF signaling supports self renewal of human embryonic stem cells and is required for differentiation of murine embryonic stem cells into a number of lineages. METHODOLOGY/PRINCIPAL FINDINGS: Given the importance of FGF signaling in regulating development and stem cell behaviour, we aimed to identify the transcriptional targets of FGF signalling during early development in the vertebrate model Xenopus laevis. We analysed the effects on gene expression in embryos in which FGF signaling was inhibited by dominant negative FGF receptors. 67 genes positively regulated by FGF signaling and 16 genes negatively regulated by FGF signaling were identified. FGF target genes are expressed in distinct waves during the late blastula to early gastrula phase. Many of these genes are expressed in the early mesoderm and dorsal ectoderm. A widespread requirement for FGF in regulating genes expressed in the Spemann organizer is revealed. The FGF targets MKP1 and DUSP5 are shown to be negative regulators of FGF signaling in early Xenopus tissues. FoxD3 and Lin28, which are involved in regulating pluripotency in ES cells are shown to be down regulated when FGF signaling is blocked. CONCLUSIONS: We have undertaken a detailed analysis of FGF target genes which has generated a robust, well validated data set. We have found a widespread role for FGF signaling in regulating the expression of genes mediating the function of the Spemann organizer. In addition, we have found that the FGF targets MKP1 and DUSP5 are likely to contribute to the complex feedback loops involved in modulating responses to FGF signaling. We also find a link between FGF signaling and the expression of known regulators of pluripotency
Cdx ParaHox genes acquired distinct developmental roles after gene duplication in vertebrate evolution
BACKGROUND: The functional consequences of whole genome duplications in vertebrate evolution are not fully understood. It remains unclear, for instance, why paralogues were retained in some gene families but extensively lost in others. Cdx homeobox genes encode conserved transcription factors controlling posterior development across diverse bilaterians. These genes are part of the ParaHox gene cluster. Multiple Cdx copies were retained after genome duplication, raising questions about how functional divergence, overlap, and redundancy respectively contributed to their retention and evolutionary fate. RESULTS: We examined the degree of regulatory and functional overlap between the three vertebrate Cdx genes using single and triple morpholino knock-down in Xenopus tropicalis followed by RNA-seq. We found that one paralogue, Cdx4, has a much stronger effect on gene expression than the others, including a strong regulatory effect on FGF and Wnt genes. Functional annotation revealed distinct and overlapping roles and subtly different temporal windows of action for each gene. The data also reveal a colinear-like effect of Cdx genes on Hox genes, with repression of Hox paralogy groups 1 and 2, and activation increasing from Hox group 5 to 11. We also highlight cases in which duplicated genes regulate distinct paralogous targets revealing pathway elaboration after whole genome duplication. CONCLUSIONS: Despite shared core pathways, Cdx paralogues have acquired distinct regulatory roles during development. This implies that the degree of functional overlap between paralogues is relatively low and that gene expression pattern alone should be used with caution when investigating the functional evolution of duplicated genes. We therefore suggest that developmental programmes were extensively rewired after whole genome duplication in the early evolution of vertebrates
Genetic mechanisms of critical illness in COVID-19.
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
Bilateral renal agenesis/hypoplasia/dysplasia (BRAHD):postmortem analysis of 45 cases with breakpoint mapping of two de novo translocations
Bilateral renal agenesis/hypoplasia/dysplasia (BRAHD) is a relatively common, lethal malformation in humans. Established clinical risk factors include maternal insulin dependent diabetes mellitus and male sex of the fetus. In the majority of cases, no specific etiology can be established, although teratogenic, syndromal and single gene causes can be assigned to some cases.45 unrelated fetuses, stillbirths or infants with lethal BRAHD were ascertained through a single regional paediatric pathology service (male:female 34:11 or 3.1:1). The previously reported phenotypic overlaps with VACTERL, caudal dysgenesis, hemifacial microsomia and Müllerian defects were confirmed. A new finding is that 16/45 (35.6%; m:f 13:3 or 4.3:1) BRAHD cases had one or more extrarenal malformations indicative of a disoder of laterality determination including; incomplete lobulation of right lung (seven cases), malrotation of the gut (seven cases) and persistence of the left superior vena cava (five cases). One such case with multiple laterality defects and sirelomelia was found to have a de novo apparently balanced reciprocal translocation 46,XY,t(2;6)(p22.3;q12). Translocation breakpoint mapping was performed by interphase fluorescent in-situ hybridization (FISH) using nuclei extracted from archival tissue sections in both this case and an isolated bilateral renal agenesis case associated with a de novo 46,XY,t(1;2)(q41;p25.3). Both t(2;6) breakpoints mapped to gene-free regions with no strong evidence of cis-regulatory potential. Ten genes localized within 500 kb of the t(1;2) breakpoints. Wholemount in-situ expression analyses of the mouse orthologs of these genes in embryonic mouse kidneys showed strong expression of Esrrg, encoding a nuclear steroid hormone receptor. Immunohistochemical analysis showed that Esrrg was restricted to proximal ductal tissue within the embryonic kidney.The previously unreported association of BRAHD with laterality defects suggests that renal agenesis may share a common etiology with heterotaxy in some cases. Translocation breakpoint mapping identified ESRRG as a plausible candidate gene for BRAHD
Teaching open and reproducible scholarship: A critical review of the evidence base for current pedagogical methods and their outcomes
In recent years, the scientific community has called for improvements in the credibility, robustness and reproducibility of research, characterized by increased interest and promotion of open and transparent research practices. While progress has been positive, there is a lack of consideration about how this approach can be embedded into undergraduate and postgraduate research training. Specifically, a critical overview of the literature which investigates how integrating open and reproducible science may influence student outcomes is needed. In this paper, we provide the first critical review of literature surrounding the integration of open and reproducible scholarship into teaching and learning and its associated outcomes in students. Our review highlighted how embedding open and reproducible scholarship appears to be associated with (i) students' scientific literacies (i.e. students’ understanding of open research, consumption of science and the development of transferable skills); (ii) student engagement (i.e. motivation and engagement with learning, collaboration and engagement in open research) and (iii) students' attitudes towards science (i.e. trust in science and confidence in research findings). However, our review also identified a need for more robust and rigorous methods within pedagogical research, including more interventional and experimental evaluations of teaching practice. We discuss implications for teaching and learning scholarship
Recommended from our members
Teaching open and reproducible scholarship: a critical review of the evidence base for current pedagogical methods and their outcomes
In recent years, the scientific community has called for improvements in the credibility, robustness, and reproducibility of research, characterized by increased interest and promotion of open and transparent research practices. While progress has been positive, there is a lack of consideration about how this approach can be embedded into undergraduate and postgraduate research training. Specifically, a critical overview of the literature which investigates how integrating open and reproducible science may influence student outcomes is needed. In this paper, we provide the first critical review of literature surrounding the integration of open and reproducible scholarship into teaching and learning and its associated outcomes in students. Our review highlighted how embedding open and reproducible scholarship appears to be associated with (1) students’ scientific literacies (i.e., students’ understanding of open research, consumption of science, and the development of transferable skills); (2) student engagement (i.e., motivation and engagement with learning, collaboration, and engagement in open research), and (3) students’ attitudes towards science (i.e., trust in science and confidence in research findings). However, our review also identified a need for more robust and rigorous methods within pedagogical research, including more interventional and experimental evaluations of teaching practice. We discuss implications for teaching and learning scholarship
'Think differently and be prepared to demonstrate trust' : findings from public hearings, England, on supporting lay people in public health roles
Professional support processes are critical for the establishment and maintenance of community health worker programmes. This paper reports on three public hearings held in England, UK, that were conducted as part of a national study into approaches to develop and support lay people in public health roles. Individuals with relevant theoretical or practical expertise, including lay activists, presented evidence in public as expert witnesses. Formal presentations, questions and plenary discussions were recorded and later analysed as qualitative data. This paper presents the results and critically examines emergent issues relating to the sustainability of lay health worker programmes. Consideration is given to the diversity of contemporary practice in England. Barriers seen to affect sustainability included organizational culture and onerous bureaucratic processes. Major themes emerging from the expert evidence included recruitment and training strategies, financial support and the need for a robust infrastructure. The expert hearings, in creating a public space for deliberation, opened up discussion on the levels and type of programme support required to foster lay health worker programmes. The paper concludes that professional support needs to be accompanied by a reorientation of public services to support lay engagement in programme delivery.Peer reviewe