Development of an inverse method for coastal risk management

Recent flooding events, like Katrina (USA, 2005) or Xynthia (France, 2010), illustrate the complexity of coastal systems and the limits of traditional flood risk analysis. Among other questions, these events raised issues such as: "how to choose flooding scenarios for risk management purposes?", "how to make a society more aware and prepared for such events?" and "which level of risk is acceptable to a population?". The present paper aims at developing an inverse approach that could seek to address these three issues. The main idea of the proposed method is the inversion of the usual risk assessment steps: starting from the maximum acceptable hazard level (defined by stakeholders as the one leading to the maximum tolerable consequences) to finally obtain the return period of this threshold. Such an "inverse" approach would allow for the identification of all the offshore forcing conditions (and their occurrence probability) inducing a threat for critical assets of the territory, such information being of great importance for coastal risk management. This paper presents the first stage in developing such a procedure. It focuses on estimation (through inversion of the flooding model) of the offshore conditions leading to the acceptable hazard level, estimation of the return period of the associated combinations, and thus of the maximum acceptable hazard level. A first application for a simplified case study (based on real data), located on the French Mediterranean coast, is presented, assuming a maximum acceptable hazard level. Even if only one part of the full inverse method has been developed, we demonstrate how the inverse method can be useful in (1) estimating the probability of exceeding the maximum inundation height for identified critical assets, (2) providing critical offshore conditions for flooding in early warning systems, and (3) raising awareness of stakeholders and eventually enhance preparedness for future flooding events by allowing them to assess risk to their territory. The next challenge is to develop a framework to properly identify the acceptable hazard level, as an input to the present inverse approach

Isolated lymph node recurrence in epithelial ovarian cancer: recurrence with better prognosis?

International audienceIntroduction The aim of this study was to compare overall survival (OS) between women with isolated lymph node recurrence (ILNR) and those with isolated peritoneal localization of recurrence (ICR), in patients managed for epithelial ovarian cancer.Methods Data from 1508 patients with ovarian cancer were collected retrospectively from1 January 2000 to 31 December 2016, from the FRANCOGYN database, pooling data from 11 centres specialized in ovary treatment. Median overall survival was determined using the Kaplan-Meier method. Univariate and multivariate analyses were performed to define prognostic factors of overall survival. Patients included had a first recurrence defined as ILNR or ICR during their follow up.Results 79 patients (5.2 %) presented with ILNR, and 247 (16.4 %) patients had isolated carcinomatosis recurrence. Complete lymphadenectomy was performed more frequently in the ILNR group vs. the ICR group (67.1 % vs. 53.4 %, p = 0.004) and the number of pelvic lymph nodes involved was higher (2.4 vs. 1.1, p = 0.008). The number of involved pelvic LN was an independent predictor of ILNR (OR = 1.231, 95 % CI [1.074–1.412], p = 0.0024). The 3-year and 5-year OS rates in the ILNR group were 85.2 % and 53.7 % respectively, compared to 68.1 % and 46.8 % in patients with ICR. There was no significant difference in terms of OS after initial diagnosis (p = 0.18). 3- year and 5-year OS rates after diagnosis of recurrence were 62.6 % and 15.6 % in the ILNR group, and 44 % and 15.7 % in patients with ICR (p = 0.21).Conclusion ILNR does not seem to be associated with a better prognosis in terms of OS

A BBS1 SVA F retrotransposon insertion is a frequent cause of Bardet-Biedl syndrome

Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinitis pigmentosa, obesity, polydactyly, cognitive impairment and renal failure. Pathogenic variants in 24 genes account for the molecular basis of >80% of cases. Toward saturated discovery of the mutational basis of the disorder, we carefully explored our cohorts and identified a hominid-specific SINE-R/VNTR/Alu type F (SVA-F) insertion in exon 13 of BBS1 in eight families. In six families, the repeat insertion was found in trans with c.1169 T > G, p.Met390Arg and in two families the insertion was found in addition to other recessive BBS loci. Whole genome sequencing, de novo assembly and SNP array analysis were performed to characterize the genomic event. This insertion is extremely rare in the general population (found in 8 alleles of 8 BBS cases but not in >10 800 control individuals from gnomAD-SV) and due to a founder effect. Its 2435 bp sequence contains hallmarks of LINE1 mediated retrotransposition. Functional studies with patient-derived cell lines confirmed that the BBS1 SVA-F is deleterious as evidenced by a significant depletion of both mRNA and protein levels. Such findings highlight the importance of dedicated bioinformatics pipelines to identify all types of variation