| 1. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 2. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 3. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 4. |
- Stassen, Willem, et al.
(författare)
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A Prehospital Randomised Controlled Trial in South Africa : Challenges and Lessons Learnt
- 2019
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Ingår i: African Journal of Emergency Medicine. - : Elsevier. - 2211-419X. ; 9:3, s. 145-149
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of cardiovascular disease and STEMI is on the rise in sub-Saharan Africa. Timely treatment is essential to reduce mortality. Internationally, prehospital 12 lead ECG telemetry has been proposed to reduce time to reperfusion. Its value in South Africa has not been established. The aim of this study was to determine the effect of prehospital 12 lead ECG telemetry on the PCI-times of STEMI patients in South Africa. A multicentre randomised controlled trial was attempted among adult patients with prehospital 12 lead ECG evidence of STEMI. Due to poor enrolment and small sample sizes, meaningful analyses could not be made. The challenges and lessons learnt from this attempt at Africa's first prehospital RCT are discussed. Challenges associated with conducting this RCT related to the healthcare landscape, resources, training of paramedics, rollout and randomisation, technology, consent and research culture. High quality evidence to guide prehospital emergency care practice is lacking both in Africa and the rest of the world. This is likely due to the difficulties with performing prehospital clinical trials. Every trial will be unique to the test intervention and setting of each study, but by considering some of the challenges and lessons learnt in the attempt at this trial, future studies might experience less difficulty. This may lead to a stronger evidence-base for prehospital emergency care.
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| 5. |
- Stassen, Willem, et al.
(författare)
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Barriers and facilitators to implementing coronary care networks in South Africa : a qualitative study
- 2020
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Ingår i: African Health Sciences. - : NISC - National Inquiry Services Centre. - 1680-6905 .- 1729-0503. ; 20:1, s. 338-350
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Tidskriftsartikel (refereegranskat)abstract
- Background: ST-elevation myocardial infarction (STEMI) is on the rise in sub-Saharan Africa. South Africa consistently fails to deliver timely reperfusion to these patients, possibly due to under-developed coronary care networks (CCN).Objectives: To determine the current perceived state of CCNs, to determine the barriers to optimising CCNs and to suggest facilitators to optimising CCNs within the South African context.Methods: A qualitative descriptive approach was employed, by performing two structured in-depth and two focus group interviews (n=4 and 5, respectively), inviting a purposely heterogeneous sample of 11 paramedics (n=4), doctors (n=5), and nurses (n=2) working within different settings in South African CCNs. Recorded interviews were transcribed verbatim and subjected to content analysis.Results: Participants described an under-resourced, unprioritised and fragmented CCN with significant variation in performance. Barriers to CCN optimisation resided in recognition and diagnosis of STEMI, transport and treatment decisions, and delays. Participants suggested that thrombolysing all STEMI patients could facilitate earlier reperfusion and that pre-hospital thrombolysis should be considered. Participants highlighted the need for regionalised STEMI guidelines, and the need for further research.Conclusion: Numerous barriers were highlighted. Healthcare policy-makers should prioritise the development of CCNs that is underpinned by evidence and that is contextualised to each specific region within the South African health care system.
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