Messinian erosional and salinity crises: View from the Provence Basin (Gulf of Lions, Western Mediterranean)

International audienceThough the late Miocene “Messinian Salinity Crisis” has been intensely researched along the circum-Mediterranean basins, few studies have focused on the central part of the Mediterranean Basin and, especially, the pre-salt deposits. To improve our knowledge of the Messinian events, it is imperative to better understand this domain. In this study, we provide a more complete understanding of this central domain in the Provence Basin. We were able to recognize: a) thick marine detrital series (up to 1000 m) derived from the Messinian subaerial erosion which is partly prolongated in the distal part by b) a thick unit of deep marine deposits (up to 800 m) prior to the evaporites; c) a thick presumed alternation of detritals and evaporites (1500 m) below the mobile halite; and d) a two-step transgression at the end of the Messinian. Spatially, we document the eroded shelf to the deep basin (and from the western to the eastern parts of the Gulf of Lions), and temporally, we extend the interpretations from the early deposition of detritic sediments to the final sea-level rise. The results provide a new basis for discussion not only for the development of the Messinian Salinity Crisis but also for the reconstruction of the subsidence history of the Provence Basin

Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1

Altres ajuts: This study was sponsored by Janssen.Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52-96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF

Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52–96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF

Formation and deformation of hyperextended rift systems: Insights from rift domain mapping in the Bay of Biscay-Pyrenees

International audienceThe Bay of Biscay and the Pyrenees correspond to a Lower Cretaceous rift system including both oceanic and hyperextended rift domains. The transition from preserved oceanic and rift domains in the West to their complete inversion in the East enables us to study the progressive reactivation of a hyperextended rift system. We use seismic interpretation, gravity inversion, and field mapping to identify and map former rift domains and their subsequent reactivation. We propose a new map and sections across the system illustrating the progressive integration of the rift domains into the orogen. This study aims to provide insights on the formation of hyperextended rift systems and discuss their role during reactivation. Two spatially and temporally distinct rift systems can be distinguished: the Bay of Biscay-Parentis and the Pyrenean-Basque-Cantabrian rifts. While the offshore Bay of Biscay represent a former mature oceanic domain, the fossil remnants of hyperextended domains preserved onshore in the Pyrenean-Cantabrian orogen record distributed extensional deformation partitioned between strongly segmented rift basins. Reactivation initiated in the exhumed mantle domain before it affected the hyperthinned domain. Both domains accommodated most of the shortening. The final architecture of the orogen is acquired once the conjugate necking domains became involved in collisional processes. The complex 3-D architecture of the initial rift system may partly explain the heterogeneous reactivation of the overall system. These results have important implications for the formation and reactivation of hyperextended rift systems and for the restoration of the Bay of Biscay and Pyrenean domain