L'Estellon (Baronnies, France), une "Pierre de Rosette" pour la biostratigraphie de l'Urgonien

Des associations d'organismes habituellement caractéristiques de faibles tranches d'eau (des orbitolinidés et des algues, en particulier) ont été identifiées dans des faciès relativement profonds de la "fosse vocontienne" (SE de la France), où ces éléments ont été transportés gravitairement et précocement resédimentés. Dans un tel contexte paléoenvironnemental, ces associations benthiques peuvent être directement calibrées sur les zones d'ammonites. D'après ces nouvelles observations, entre autres résultats, la première apparition de Palorbitolina lenticularis ainsi que celles de quatre représentants du genre Orbitolinopsis, soi-disant typiques de l'Aptien inférieur, sont datées du Barrémien inférieur. De fait la plupart des espèces d'orbitolinidés connues dans le Barrémien supérieur sont déjà présentes au Barrémien inférieur à L'Estellon. Concernant les plates-formes urgoniennes, les schémas de corrélations couramment utilisés, qui s'appuient sur des distributions biaisées (tronquées) d'orbitolinidés -- et par conséquent les conclusions et hypothèses qui en sont dérivées --, nécessitent au moins des révisions en profondeur, sinon un rejet définitif.Shallow-water assemblages of transported ("freshly reworked") bioclasts (mainly orbitolinids and dasycladales) are observed in the deeper facies of the "Vocontian Trough" (SE France). There these benthic assemblages can be directly correlated with ammonite zones. These new finds give an Early Barremian age to the earliest record of Palorbitolina lenticularis as well as those of four so-called "typical Early Aptian" representatives of the genus Orbitolinopsis. Actually most orbitolinid species recorded from the Late Barremian interval are now found present in Lower Barremian strata at L'Estellon. Some currently used correlation schemes for the Urgonian platforms, that are based on partial stratigraphic distribution ranges for the orbitolinids, --and consequently derived conclusions and hypotheses- - require at least in-depth revisions when they are not definitively refuted.The study of the ammonite fauna in the L'Estellon section (Drôme department, SE France) allows us to date episodes with gravitational deposition in this area of the "Vocontian Trough". They span most of the Barremian Stage, from the Nicklesi Zone up to the Giraudi Zone. We did not identify any Bedoulian redeposits, the "Bedoulian ridge" auct. being latest Barremian in age

Visceral adiposity and left ventricular mass and function in patients with aortic stenosis : the PROGRESSA study

Background : Recent studies have reported that obesity, metabolic syndrome, and diabetes are associated with left ventricular (LV) hypertrophy (LVH) and dysfunction in patients with aortic stenosis (AS). The purpose of this study was to examine the association between amount and distribution of body fat and LVH and systolic dysfunction in AS patients. Methods : One hundred twenty-four patients with AS were prospectively recruited in the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) study and underwent Doppler echocardiography and computed tomography scan. Presence and severity of LVH was assessed according to LV mass indexed for height2.7 and LV dysfunction according to global longitudinal strain (GLS). Computed tomography was used to quantify abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue, and total adipose tissue (TAT). Results : Body mass index (BMI) correlated strongly with TAT (r = 0.85), moderately with VAT (r = 0.70), and SAT (r = 0.69), and weakly with the proportion of VAT (VAT/TAT ratio: r = 0.19). In univariate analysis, greater BMI, TAT, VAT, SAT, and VAT/TAT were associated with increased LV mass index and greater VAT and VAT/TAT ratio were associated with reduced GLS. Multivariate analysis revealed that larger BMI (P < 0.0001) and greater VAT/TAT ratio (P = 0.01) were independently associated with higher prevalence of LVH, and only the VAT/TAT ratio (P = 0.03) was independently associated with reduced GLS. Conclusions : The results of this study suggest that total and visceral adiposity are independently associated with LVH in patients with AS. Furthermore, impairment of LV systolic function does not appear to be influenced by total obesity but is rather related to excess visceral adiposity. These findings provide impetus for elaboration of interventional studies aiming at visceral adiposity in the AS population.De récentes études ont rapporté que l’obésité, le syndrome métabolique et le diabète étaient associés à l’hypertrophie (HVG) et à la dysfonction ventriculaire gauche des patients souffrant d’une sténose aortique (SA). Le but de cette étude était d’examiner le lien entre la quantité et la répartition de la graisse corporelle, l’HVG et la dysfonction systolique chez les patients souffrant d’une SA. Méthodes : Cent vingt-quatre patients souffrant d’une SA ont été recrutés de manière prospective dans l’étude PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis), et ont subi une échocardiographie Doppler et une tomodensitométrie. La présence et la sévérité de l’HVG ont été évaluées au moyen de la masse VG indexée par la taille2.7 et la dysfonction systolique du VG par la déformation longitudinale globale du VG (DLG). La tomodensitométrie a été utilisée pour quantifier le tissu adipeux abdominal viscéral (TAV) et sous-cutané (TAS), et le tissu adipeux total (TAT). Résultats : L’indice de masse corporelle (IMC) corrélait fortement avec le TAT (r = 0,85), modérément avec le TAV (r = 0,70) et le TAS (r = 0,69), et faiblement avec la proportion de TAV (rapport TAV/TAT : r = 0,19). En analyse multivariée, des IMC, TAT, TAV, TAS et VAT/TAT plus élevés étaient associés à une augmentation de la masse VG indexée et un TAV et un rapport TAV/TAT plus élevés étaient associés à la réduction de la DLG. L’analyse multivariée a révélé qu’un IMC plus élevé (P < 0,0001) et un rapport TAV/TAT plus élevé (P = 0,01) étaient indépendamment associés à une HVG plus importante, et seul un rapport TAV/TAT était indépendamment associé à une réduction de la DLG. Conclusions : Les résultats de cette étude montrent que l’adiposité totale et l'adiposité viscérale sont indépendamment associées à une HVG chez les patients souffrant d’une SA. De plus, la détérioration de la fonction systolique VG ne semble pas être influencée par l’obésité totale, mais est plutôt liée à une adiposité viscérale excessive. Ces résultats incitent à l’élaboration d’études interventionnelles visant l’adiposité viscérale dans la population souffrant de SA

The origins and spread of domestic horses from the Western Eurasian steppes

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: All collapsed and paired-end sequence data for samples sequenced in this study are available in compressed fastq format through the European Nucleotide Archive under accession number PRJEB44430, together with rescaled and trimmed bam sequence alignments against both the nuclear and mitochondrial horse reference genomes. Previously published ancient data used in this study are available under accession numbers PRJEB7537, PRJEB10098, PRJEB10854, PRJEB22390 and PRJEB31613, and detailed in Supplementary Table 1. The genomes of ten modern horses, publicly available, were also accessed as indicated in their corresponding original publications57,61,85-87.NOTE: see the published version available via the DOI in this record for the full list of authorsDomestication of horses fundamentally transformed long-range mobility and warfare. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling at Botai, Central Asia around 3500 BC. Other longstanding candidate regions for horse domestication, such as Iberia and Anatolia, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 BC, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 BC driving the spread of Indo-European languages. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium BC Sintashta culture

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049