ORCID Profile
0000-0002-6464-2286
Current Organisations
University of Ulm
,
University of Nottingham
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Publisher: Oxford University Press (OUP)
Date: 11-2003
Publisher: Wiley
Date: 19-05-2023
DOI: 10.1111/MEC.16983
Abstract: Understanding the immunogenetic basis of coronavirus (CoV) susceptibility in major pathogen reservoirs, such as bats, is central to inferring their zoonotic potential. Members of the cryptic Hipposideros bat species complex differ in CoV susceptibility, but the underlying mechanisms remain unclear. The genes of the major histocompatibility complex (MHC) are the best understood genetic basis of pathogen resistance, and differences in MHC ersity are one possible reason for asymmetrical infection patterns among closely related species. Here, we aimed to link asymmetries in observed CoV (CoV‐229E, CoV‐2B and CoV‐2Bbasal) susceptibility to immunogenetic differences amongst four Hipposideros bat species. From the 2072 bats assigned to their respective species using the mtDNA cytochrome b gene, members of the most numerous and ubiquitous species, Hipposideros caffer D , were most infected with CoV‐229E and SARS‐related CoV‐2B. Using a subset of 569 bats, we determined that much of the existent allelic and functional (i.e. supertype) MHC DRB class II ersity originated from common ancestry. One MHC supertype shared amongst all species, ST12, was consistently linked to susceptibility with CoV‐229E, which is closely related to the common cold agent HCoV‐229E, and infected bats and those carrying ST12 had a lower body condition. The same MHC supertype was connected to resistance to CoV‐2B, and bats with ST12 were less likely be co‐infected with CoV‐229E and CoV‐2B. Our work suggests a role of immunogenetics in determining CoV susceptibility in bats. We advocate for the preservation of functional genetic and species ersity in reservoirs as a means of mitigating the risk of disease spillover.
Publisher: Hindawi Limited
Date: 29-07-2021
DOI: 10.1111/JZS.12506
Publisher: Public Library of Science (PLoS)
Date: 29-06-2017
Publisher: National Institute for Health and Care Research
Date: 05-2017
DOI: 10.3310/HTA21260
Abstract: There is currently no disease-modifying treatment available to halt or delay the progression of the disease pathology in dementia. An agreed core set of the best-available and most appropriate outcomes for disease modification would facilitate the design of trials and ensure consistency across disease modification trials, as well as making results comparable and meta-analysable in future trials. To agree a set of core outcomes for disease modification trials for mild to moderate dementia with the UK dementia research community and patient and public involvement (PPI). We included disease modification trials with quantitative outcomes of efficacy from (1) references from related systematic reviews in workstream 1 (2) searches of the Cochrane Dementia and Cognitive Improvement Group study register, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Latin American and Caribbean Health Sciences Literature and PsycINFO on 11 December 2015, and clinical trial registries [International Standard Randomised Controlled Trial Number (ISRCTN) and clinicaltrials.gov] on 22 and 29 January 2016 and (3) hand-searches of reference lists of relevant systematic reviews from database searches. The project consisted of four workstreams. (1) We obtained related core outcome sets and work from co-applicants. (2) We systematically reviewed published and ongoing disease modification trials to identify the outcomes used in different domains. We extracted outcomes used in each trial, recording how many used each outcome and with how many participants. We ided outcomes into the domains measured and searched for validation data. (3) We consulted with PPI participants about recommended outcomes. (4) We presented all the synthesised information at a conference attended by the wider body of National Institute for Health Research (NIHR) dementia researchers to reach consensus on a core set of outcomes. We included 149 papers from the 22,918 papers screened, referring to 125 in idual trials. Eighty-one outcomes were used across trials, including 72 scales [31 cognitive, 12 activities of daily living (ADLs), 10 global, 16 neuropsychiatric and three quality of life] and nine biological techniques. We consulted with 18 people for PPI. The conference decided that only cognition and biological markers are core measures of disease modification. Cognition should be measured by the Mini Mental State Examination (MMSE) or the Alzheimer’s Disease Assessment Scale – Cognitive subscale (ADAS-Cog), and brain changes through structural magnetic resonance imaging (MRI) in a subset of participants. All other domains are important but not core. We recommend using the Neuropsychiatric Inventory for neuropsychiatric symptoms: the Disability Assessment for Dementia for ADLs, the Dementia Quality of Life Measure for quality of life and the Clinical Dementia Rating scale to measure dementia globally. Most of the trials included participants with Alzheimer’s disease, so recommendations may not apply to other types of dementia. We did not conduct economic analyses. The PPI consultation was limited to members of the Alzheimer’s Society Research Network. Cognitive outcomes and biological markers form the core outcome set for future disease modification trials, measured by the MMSE or ADAS-Cog, and structural MRI in a subset of participants. We envisage that the core set may be superseded in the future, particularly for other types of dementia. There is a need to develop an algorithm to compare scores on the MMSE and ADAS-Cog. The project was registered with Core Outcome Measures in Effectiveness Trials [ tudies/details/819?result=true (accessed 7 April 2016)]. The systematic review protocol is registered as PROSPERO CRD42015027346. The National Institute for Health Research Health Technology Assessment programme.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2015
End Date: 2020
Funder: Economic and Social Research Council
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