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- Helgeson, J.ab, et al.
(författare)
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The role of knowledge, learning and mental models in public perceptions of climate change related risks
- 2012
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Ingår i: Learning for Sustainability in Times of Accelerating Change. - The Netherlands : Wageningen Academic Publishers. - 9789086862030 ; , s. 329-346
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Climate change represents a complex set of challenges, in part because it is marked by risks that are not easily observed and identified - risks that humans have significant difficulty estimating. A large body of research has shown that the construction of human risk perception is a complex, multi-faceted process. Determining viable mitigation and adaptation strategies toward climate change risks therefore necessitates models that appropriately reflect human knowledge systems and learning processes. In learning for a sustainable future, we must look beyond traditional measures of risk variables and obtain a more comprehensive and holistic understanding of risk behaviour. In this chapter, we aim to provide such an interdisciplinary overview. Using practical examples we outline five fundamental processes that help form, shape and guide human perceptions of climate-related risks, namely: (1) cognitive; (2) subconscious; (3) affective; (4) socio-cultural and (5) individual factors. We subsequently critically review techniques for measuring risk perception, discuss (existing) public perceptions of climate change related risks and illuminate the different mechanisms by which risk perception can influence public action. A major conclusion is that eliciting effective adaptation and mitigation responses requires greater public understanding of and multi-level engagement with climate change and to this extent, we provide several recommendations for public policy.
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- Kular, L, et al.
(författare)
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DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2397-
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Tidskriftsartikel (refereegranskat)abstract
- The human leukocyte antigen (HLA) haplotype DRB1*15:01 is the major risk factor for multiple sclerosis (MS). Here, we find that DRB1*15:01 is hypomethylated and predominantly expressed in monocytes among carriers of DRB1*15:01. A differentially methylated region (DMR) encompassing HLA-DRB1 exon 2 is particularly affected and displays methylation-sensitive regulatory properties in vitro. Causal inference and Mendelian randomization provide evidence that HLA variants mediate risk for MS via changes in the HLA-DRB1 DMR that modify HLA-DRB1 expression. Meta-analysis of 14,259 cases and 171,347 controls confirms that these variants confer risk from DRB1*15:01 and also identifies a protective variant (rs9267649, p < 3.32 × 10−8, odds ratio = 0.86) after conditioning for all MS-associated variants in the region. rs9267649 is associated with increased DNA methylation at the HLA-DRB1 DMR and reduced expression of HLA-DRB1, suggesting a modulation of the DRB1*15:01 effect. Our integrative approach provides insights into the molecular mechanisms of MS susceptibility and suggests putative therapeutic strategies targeting a methylation-mediated regulation of the major risk gene.
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- Newby, D, et al.
(författare)
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Comparative effect of metformin versus sulfonylureas with dementia and Parkinson's disease risk in US patients over 50 with type 2 diabetes mellitus
- 2022
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Ingår i: BMJ open diabetes research & care. - : BMJ. - 2052-4897. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes is a risk factor for dementia and Parkinson’s disease (PD). Drug treatments for diabetes, such as metformin, could be used as novel treatments for these neurological conditions. Using electronic health records from the USA (OPTUM EHR) we aimed to assess the association of metformin with all-cause dementia, dementia subtypes and PD compared with sulfonylureas.Research design and methodsA new user comparator study design was conducted in patients ≥50 years old with diabetes who were new users of metformin or sulfonylureas between 2006 and 2018. Primary outcomes were all-cause dementia and PD. Secondary outcomes were Alzheimer’s disease (AD), vascular dementia (VD) and mild cognitive impairment (MCI). Cox proportional hazards models with inverse probability of treatment weighting (IPTW) were used to estimate the HRs. Subanalyses included stratification by age, race, renal function, and glycemic control.ResultsWe identified 96 140 and 16 451 new users of metformin and sulfonylureas, respectively. Mean age was 66.4±8.2 years (48% male, 83% Caucasian). Over the 5-year follow-up, 3207 patients developed all-cause dementia (2256 (2.3%) metformin, 951 (5.8%) sulfonylurea users) and 760 patients developed PD (625 (0.7%) metformin, 135 (0.8%) sulfonylurea users). After IPTW, HRs for all-cause dementia and PD were 0.80 (95% CI 0.73 to 0.88) and 1.00 (95% CI 0.79 to 1.28). HRs for AD, VD and MCI were 0.81 (0.70–0.94), 0.79 (0.63–1.00) and 0.91 (0.79–1.04). Stronger associations were observed in patients who were younger (<75 years old), Caucasian, and with moderate renal function.ConclusionsMetformin users compared with sulfonylurea users were associated with a lower risk of all-cause dementia, AD and VD but not with PD or MCI. Age and renal function modified risk reduction. Our findings support the hypothesis that metformin provides more neuroprotection for dementia than sulfonylureas but not for PD, but further work is required to assess causality.
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