Multilevel governance of coastal flood risk reduction : a public finance perspective

Authors acknowledge funding from the European Union's Horizon 2020 research and innovation program under Grant 642018 (GREEN‐WIN project) and funding from the project INSeaPTION as part of ERA4CS, an ERA‐NET initiated by JPI Climate, and funded by BMBF (DE), MINECO (ES), NWO (NL), and ANR (FR) with co-funding by the European Union (Grant 690462).Coastal flood risk reduction (CFRR) presents a significant public funding challenge, due to its high upfront costs and long-term benefits, and this challenge will increase with future sea-level rise. The funding challenge necessarily involves multiple levels of government, due to the regional nature of CFRR public goods involved. Yet there has been little research comparing such multilevel arrangements across countries, and in particular exploring the performance of public funding arrangements for providing coastal flood risk reduction. We address this gap, applying fiscal federalism to develop a multilevel governance analysis of public decision-making and fiscal authorities for CFRR in the Netherlands, Germany, the UK and Australia. For each country, we locate key decision-making and fiscal authorities in multilevel governance arrangements, and analyse their alignment with the benefits of CFRR measures (spillovers). We find diverse coastal flood risk governance arrangements ranging from highly centralised (NL), mixed arrangements, involving regional centralisation (Germany) or partial devolvement (UK), to full decentralisation (AUS). Further, we find that in accordance with fiscal federalism, multilevel coastal flood risk governance arrangements are generally reflective of the distribution of the benefits across different levels of government, with some exceptions (Germany and UK). Finally, exploring the outlook of current arrangements under sea-level rise, we find that major fiscal redistributions may be put under pressure by rising costs likely under SLR and future coastal development. This is particularly the case for those systems which operate under hazard-based, as opposed to risk-based, coastal protection policies. Further, we find that both fully and moderately decentralised arrangements may require greater central support for alternative measures, such as retreat, in light of growing financial burdens on local governments.PostprintPeer reviewe

OCS Reduction According to the Presence of Nasal Polyps or Atopic Status in the PONENTE Study

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Participatory Design of Multi-Use Platforms at Sea

European oceans are subject to rapid development. New activities such as aquaculture and ocean energy have gained importance. This triggers interest in “multi-use platforms at sea” (MUPS), i.e., areas at sea in which different activities are combined. MUPS are complex features with regards to technology, governance, and financial, socioeconomic, and environmental aspects. To identify realistic and sustainable solutions and designs for MUPS, the MERMAID project applied a participatory design process (PDP) involving a range of stakeholders representing companies, authorities, researchers, and NGOs. This paper evaluates if and how the participatory design process contributed to the design of multi-use platforms. It is based on interviews with the managers of the case study sites and a questionnaire administered to all stakeholders participating in the PDP workshops. Analyzing the four case studies, we conclude that the participatory design process has had a valuable contribution to the development of the four different designs of MUPS, even though the preconditions for carrying out a participatory design process differed between sites. In all four cases, the process has been beneficial in generating new and shared knowledge. It brought new design issues to the table and increased knowledge and understanding among the different stakeholders

Adrenal Insufficiency is Not a Barrier to OCS Elimination in the PONENTE Study

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Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Systematic meta-analyses, field synopsis and global assessment of the evidence of genetic association studies in colorectal cancer

Objective: To provide an understanding of the role of common genetic variations in colorectal cancer (CRC) risk, we report an updated field synopsis and comprehensive assessment of evidence to catalogue all genetic markers for CRC (CRCgene2). Design: We included 869 publications after parallel literature review and extracted data for 1063 polymorphisms in 303 different genes. Meta-Analyses were performed for 308 single nucleotide polymorphisms (SNPs) in 158 different genes with at least three independent studies available for analysis. Scottish, Canadian and Spanish data from genome-wide association studies (GWASs) were incorporated for the meta-Analyses of 132 SNPs. To assess and classify the credibility of the associations, we applied the Venice criteria and Bayesian False-Discovery Probability (BFDP). Genetic associations classified as â € positive' and â € less-credible positive' were further validated in three large GWAS consortia conducted in populations of European origin. Results: We initially identified 18 independent variants at 16 loci that were classified as â € positive' polymorphisms for their highly credible associations with CRC risk and 59 variants at 49 loci that were classified as â € less-credible positive' SNPs; 72.2% of the â € positive' SNPs were successfully replicated in three large GWASs and the ones that were not replicated were downgraded to â € less-credible' positive (reducing the â € positive' variants to 14 at 11 loci). For the remaining 231 variants, which were previously reported, our meta-Analyses found no evidence to support their associations with CRC risk. Conclusion: The CRCgene2 database provides an updated list of genetic variants related to CRC risk by using harmonised methods to assess their credibility.</p

Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn’s disease: long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresource

Objective: Thiopurines are widely used as maintenance therapy in inflammatory bowel disease (IBD) but the evidence base for their use is sparse and their role increasingly questioned. Using the largest series reported to date, we assessed the long-term effectiveness of thiopurines in ulcerative colitis (UC) and Crohn’s disease (CD), including their impact on need for surgery. Design: Outcomes were assessed in 11 928 patients (4968 UC, 6960 CD) in the UK IBD BioResource initiated on thiopurine monotherapy with the intention of maintaining medically induced remission. Effectiveness was assessed retrospectively using patient-level data and a definition that required avoidance of escalation to biological therapy or surgery while on thiopurines. Analyses included overall effectiveness, time-to-event analysis for treatment escalation and comparison of surgery rates in patients tolerant or intolerant of thiopurines. Results: Using 68 132 patient-years of exposure, thiopurine monotherapy appeared effective for the duration of treatment in 2617/4968 (52.7%) patients with UC compared with 2378/6960 (34.2%) patients with CD (p<0.0001). This difference was corroborated in a multivariable analysis: after adjusting for variables including treatment era, thiopurine monotherapy was less effective in CD than UC (OR 0.47, 95% CI 0.43 to 0.51, p<0.0001). Thiopurine intolerance was associated with increased risk of surgery in UC (HR 2.44, p<0.0001); with a more modest impact on need for surgery in CD (HR=1.23, p=0.0015). Conclusion: Thiopurine monotherapy is an effective long-term treatment for UC but significantly less effective in CD