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- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 2. |
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| 3. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 4. |
- Rycroft-Malone, J., et al.
(författare)
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A realist process evaluation within the Facilitating Implementation of Research Evidence (FIRE) cluster randomised controlled international trial: An exemplar
- 2018
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Ingår i: Implementation Science. - : Springer Science and Business Media LLC. - 1748-5908. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Facilitation is a promising implementation intervention, which requires theory-informed evaluation. This paper presents an exemplar of a multi-country realist process evaluation that was embedded in the first international randomised controlled trial evaluating two types of facilitation for implementing urinary continence care recommendations. We aimed to uncover what worked (and did not work), for whom, how, why and in what circumstances during the process of implementing the facilitation interventions in practice. Methods: This realist process evaluation included theory formulation, theory testing and refining. Data were collected in 24 care home sites across four European countries. Data were collected over four time points using multiple qualitative methods: observation (372h), interviews with staff (n=357), residents (n=152), next of kin (n=109) and other stakeholders (n=128), supplemented by facilitator activity logs. A combined inductive and deductive data analysis process focused on realist theory refinement and testing. Results: The content and approach of the two facilitation programmes prompted variable opportunities to align and realign support with the needs and expectations of facilitators and homes. This influenced their level of confidence in fulfilling the facilitator role and ability to deliver the intervention as planned. The success of intervention implementation was largely dependent on whether sites prioritised their involvement in both the study and the facilitation programme. In contexts where the study was prioritised (including release of resources) and where managers and staff support was sustained, this prompted collective engagement (as an attitude and action). Internal facilitators' (IF) personal characteristics and abilities, including personal and formal authority, in combination with a supportive environment prompted by managers triggered the potential for learning over time. Learning over time resulted in a sense of confidence and personal growth, and enactment of the facilitation role, which resulted in practice changes. Conclusion: The scale and multi-country nature of this study provided a novel context to conduct one of the few trial embedded realist-informed process evaluations. In addition to providing an explanatory account of implementation processes, a conceptual platform for future facilitation research is presented. Finally, a realist-informed process evaluation framework is outlined, which could inform future research of this nature. © 2018 The Author(s).
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| 5. |
- Seers, K., et al.
(författare)
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Facilitating Implementation of Research Evidence (FIRE): An international cluster randomised controlled trial to evaluate two models of facilitation informed by the Promoting Action on Research Implementation in Health Services (PARIHS) framework
- 2018
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Ingår i: Implementation Science. - : Springer Science and Business Media LLC. - 1748-5908. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Health care practice needs to be underpinned by high quality research evidence, so that the best possible care can be delivered. However, evidence from research is not always utilised in practice. This study used the Promoting Action on Research Implementation in Health Services (PARIHS) framework as its theoretical underpinning to test whether two different approaches to facilitating implementation could affect the use of research evidence in practice. Methods: A pragmatic clustered randomised controlled trial with embedded process and economic evaluation was used. The study took place in four European countries across 24 long-term nursing care sites, for people aged 60years or more with documented urinary incontinence. In each country, sites were randomly allocated to standard dissemination, or one of two different types of facilitation. The primary outcome was the documented percentage compliance with the continence recommendations, assessed at baseline, then at 6, 12, 18, and 24months after the intervention. Data were analysed using STATA15, multi-level mixed-effects linear regression models were fitted to scores for compliance with the continence recommendations, adjusting for clustering. Results: Quantitative data were obtained from reviews of 2313 records. There were no significant differences in the primary outcome (documented compliance with continence recommendations) between study arms and all study arms improved over time. Conclusions: This was the first cross European randomised controlled trial with embedded process evaluation that sought to test different methods of facilitation. There were no statistically significant differences in compliance with continence recommendations between the groups. It was not possible to identify whether different types and "doses" of facilitation were influential within very diverse contextual conditions. The process evaluation (Rycroft-Malone et al., Implementation Science. doi: 10.1186/s13012-018-0811-0) revealed the models of facilitation used were limited in their ability to overcome the influence of contextual factors. © 2018 The Author(s).
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