巴黎第十一大学

Many papers refer in a revised way to the two-step scenario of the Messinian Crisis conceived by Clauzon et al. (1996). The present paper recalls the basis for the two-step scenario and discrepancies with the later modified version, completed by new data supported by extensive micropaleontological analyses. Our interpretation of the Sicilian Eraclea Minoa section as belonging to a peripheral basin is the centre of the debate. We show the great amplitude of fluvial erosion during the peak of the crisis, which for the Rhône River, exceeded 400 km upstream of the present shoreline. Based on dinoflagellate cysts, we also recall the reasons for supporting the occurrence of three successive Lago Mare episodes of two different origins. The first and third episodes constitute phases of high sea-level exchanges between the Mediterranean and the Paratethys respectively just before the onset of paroxysm and after it. The second episode is due to overflowing Paratethyan waters from the Aegean Basin just before the end of paroxysm. Similarly, the demonstration of the marine reflooding of the Mediterranean Basin prior to the Zanclean is repeated. We emphasize dissimilarity between basins, focussing in particular on those, isolated or perched ones, which were continuously filled by waters during the desiccation phase: western part of the Alboran Sea and southeastern part of the Levantine Basin (marine waters), Apennine Foredeep (fresh waters), and Aegean Basin (brackish waters). The Apennine Foredeep cannot be the reference for the entire Mediterranean with respect to its evolution during the crisis. During the crisis, water exchanges between the Aegean Basin and the Eastern Paratethys (Dacic Basin, Black Sea) were impossible through the Marmara region because of the development of two opposed fluvial networks. Such exchanges existed thanks to a gateway that was probably located within the Balkans. Investigations around the Levantine Basin point to areas submitted to fluvial erosion during the crisis paroxysm and nearby areas, which might have received marine waters from the Red Sea. Much information is still to be discovered and that more progress is still needed in order to fully decipher this outstanding event.

Polyphenols represent the largest and most diverse class of dietary antioxidants. Epidemiological evidence linking specific (poly)phenol classes, such as flavonoids and lignans, to breast cancer (BC) risk remains limited and largely inconclusive in prospective studies. The aim of this study is to examine the association between the intake of total (poly)phenols-and its classes and subclasses-and BC risk-overall and by subtypes (estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2))-in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The EPIC cohort includes 257,960 adult women from seven European countries. During a mean follow-up of 14 years, there were 10,722 incident overall BC cases. Associations were computed using Cox regression models adjusted for potential confounders. No significant associations were found between total (poly)phenol intake and overall BC risk (HRQ5 vs. Q1 = 1.02; 95% CI: 0.95-1.11). In addition, null associations were mostly found between classes and subclasses of (poly)phenols and BC subtypes. After stratifying by menopausal status, no significant associations were observed. In conclusion, this study found no evidence of associations between the intake of any class or subclass of (poly)phenols and BC risk in the European population.

Background Early Scientific Advice (ESA) is an independent, non-binding process that gives patient-centred scientific guidance to manufacturers in the pre-market stage of product development. Unlike advisory boards, ESA provides objective advice from Health Technology Assessment (HTA) bodies or regulatory authorities, aiming to support the development of healthcare technologies in line with regulatory and health policy goals. This study examines global ESA practices and suggests a framework for implementing ESA in Saudi Arabia. Methods A literature review was conducted to examine established ESA systems, focusing on processes, workflows, timings, challenges, and lessons learned. Additionally, a roundtable discussion with experts from regulatory bodies, healthcare providers, and industry was held to identify the key pillars of the Saudi ESA framework. Several related topics were covered, including governance, patient involvement, types of products, review timing, the distinction between ESA and advisory boards, horizon scanning, and the use of ESA for technical quality assessments. Results The roundtable discussion revealed that the ESA framework in Saudi Arabia should focus on pharmaceuticals as well as medical devices. The panel proposed considering ESA before drug registration in late-stage clinical development and for phase 2 and 3 trials of drugs for diseases with local relevance (e.g., rare diseases). For medical devices, the ESA process should occur post-marketing authorization. It was agreed that the ESA process should be governed by the HTA body. Experts also recommended patient involvement during ESA review using targeted questionnaires to ensure a comprehensive review. Conclusion ESA in Saudi Arabia can enhance stakeholder engagement in the approval and reimbursement processes for pharmaceuticals, diagnostics, and medical devices. Implementing ESA within Saudi Arabia's advanced healthcare system is essential to support manufacturers, optimize outcomes, and improve access to these interventions.

OBJECTIVES:To characterize the longitudinal evolution of B-cell biomarkers in patients with primary Sjögren's disease (SjD) and analyse their association with the clinical disease course. METHODS:We analysed data from the French multicentre prospective ASSESS cohort. Patients fulfilling AECG criteria with ≥2 visits including both immunological assessments and ClinESSDAI scores over a 5 years follow-up were included. Baseline B-cell biomarkers included immunoglobulin levels, monoclonal component, cryoglobulinaemia, complement fractions, RF and β2-microglobulin. Disease activity was assessed using ClinESSDAI score. Associations between the number of abnormal B-cell markers and disease activity were analysed using ANOVA and Kruskal-Wallis tests. Changes in IgG were evaluated according to the biological domain of the STAR index, defined as a relative decrease ≥10%. RESULTS:Among the 395 ASSESS participants, 362 met inclusion criteria. Mean follow-up was 56.4 months (±10.6), with a mean of 5.3 visits per patient (±0.5). B-cell biomarkers remained stable in 80.5%. According to STAR criteria, 43.1% were classified as biological responders to the biological domain of STAR based on IgG decrease, occurring mostly within the first year, without correlation with changes in ClinESSDAI or ESSPRI. Although baseline ClinESSDAI did not differ by the number of B-cell abnormalities (P = 0.096), patients with multiple B-cell activity markers-particularly ≥5-had an increased risk of persistent or worsening disease (OR 4.6, 95% CI 1.2-17.8; P = 0.002). CONCLUSION:B-cell biomarkers profile in SjD is largely stable over time. However, a high baseline 'B-cell burden' identifies patients at risk of poorer outcomes, supporting their use for stratification and monitoring.