Simulating CH_4 and CO_2 over South and East Asia using the zoomed chemistry transport model LMDz-INCA

The increasing availability of atmospheric measurements of greenhouse gases (GHGs) from surface stations can improve the retrieval of their fluxes at higher spatial and temporal resolutions by inversions, provided that transport models are able to properly represent the variability of concentrations observed at different stations. South and East Asia (SEA; the study area in this paper including the regions of South Asia and East Asia) is a region with large and very uncertain emissions of carbon dioxide (CO_2) and methane (CH_4), the most potent anthropogenic GHGs. Monitoring networks have expanded greatly during the past decade in this region, which should contribute to reducing uncertainties in estimates of regional GHG budgets. In this study, we simulate concentrations of CH_4 and CO_2 using zoomed versions (abbreviated as ZAs) of the global chemistry transport model LMDz-INCA, which have fine horizontal resolutions of  ∼ 0.66° in longitude and  ∼ 0.51° in latitude over SEA and coarser resolutions elsewhere. The concentrations of CH_4 and CO_2 simulated from ZAs are compared to those from the same model but with standard model grids of 2.50° in longitude and 1.27° in latitude (abbreviated as STs), both prescribed with the same natural and anthropogenic fluxes. Model performance is evaluated for each model version at multi-annual, seasonal, synoptic and diurnal scales, against a unique observation dataset including 39 global and regional stations over SEA and around the world. Results show that ZAs improve the overall representation of CH_4 annual gradients between stations in SEA, with reduction of RMSE by 16–20% compared to STs. The model improvement mainly results from reduction in representation error at finer horizontal resolutions and thus better characterization of the CH_4 concentration gradients related to scattered distributed emission sources. However, the performance of ZAs at a specific station as compared to STs is more sensitive to errors in meteorological forcings and surface fluxes, especially when short-term variabilities or stations close to source regions are examined. This highlights the importance of accurate a priori CH_4 surface fluxes in high-resolution transport modeling and inverse studies, particularly regarding locations and magnitudes of emission hotspots. Model performance for CO_2 suggests that the CO_2 surface fluxes have not been prescribed with sufficient accuracy and resolution, especially the spatiotemporally varying carbon exchange between land surface and atmosphere. In addition, the representation of the CH_4 and CO_2 short-term variabilities is also limited by model's ability to simulate boundary layer mixing and mesoscale transport in complex terrains, emphasizing the need to improve sub-grid physical parameterizations in addition to refinement of model resolutions

Simulating CH_4 and CO_2 over South and East Asia using the zoomed chemistry transport model LMDz-INCA

The increasing availability of atmospheric measurements of greenhouse gases (GHGs) from surface stations can improve the retrieval of their fluxes at higher spatial and temporal resolutions by inversions, provided that transport models are able to properly represent the variability of concentrations observed at different stations. South and East Asia (SEA; the study area in this paper including the regions of South Asia and East Asia) is a region with large and very uncertain emissions of carbon dioxide (CO_2) and methane (CH_4), the most potent anthropogenic GHGs. Monitoring networks have expanded greatly during the past decade in this region, which should contribute to reducing uncertainties in estimates of regional GHG budgets. In this study, we simulate concentrations of CH_4 and CO_2 using zoomed versions (abbreviated as ZAs) of the global chemistry transport model LMDz-INCA, which have fine horizontal resolutions of  ∼ 0.66° in longitude and  ∼ 0.51° in latitude over SEA and coarser resolutions elsewhere. The concentrations of CH_4 and CO_2 simulated from ZAs are compared to those from the same model but with standard model grids of 2.50° in longitude and 1.27° in latitude (abbreviated as STs), both prescribed with the same natural and anthropogenic fluxes. Model performance is evaluated for each model version at multi-annual, seasonal, synoptic and diurnal scales, against a unique observation dataset including 39 global and regional stations over SEA and around the world. Results show that ZAs improve the overall representation of CH_4 annual gradients between stations in SEA, with reduction of RMSE by 16–20% compared to STs. The model improvement mainly results from reduction in representation error at finer horizontal resolutions and thus better characterization of the CH_4 concentration gradients related to scattered distributed emission sources. However, the performance of ZAs at a specific station as compared to STs is more sensitive to errors in meteorological forcings and surface fluxes, especially when short-term variabilities or stations close to source regions are examined. This highlights the importance of accurate a priori CH_4 surface fluxes in high-resolution transport modeling and inverse studies, particularly regarding locations and magnitudes of emission hotspots. Model performance for CO_2 suggests that the CO_2 surface fluxes have not been prescribed with sufficient accuracy and resolution, especially the spatiotemporally varying carbon exchange between land surface and atmosphere. In addition, the representation of the CH_4 and CO_2 short-term variabilities is also limited by model's ability to simulate boundary layer mixing and mesoscale transport in complex terrains, emphasizing the need to improve sub-grid physical parameterizations in addition to refinement of model resolutions

Bosutinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia: final results from the BFORE trial

This analysis from the multicenter, open-label, phase 3 BFORE trial reports efficacy and safety of bosutinib in patients with newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) after five years' follow-up. Patients were randomized to 400-mg once-daily bosutinib (n = 268) or imatinib (n = 268; three untreated). At study completion, 59.7% of bosutinib- and 58.1% of imatinib-treated patients remained on study treatment. Median duration of treatment and time on study was 55 months in both groups. Cumulative major molecular response (MMR) rate by 5 years was higher with bosutinib versus imatinib (73.9% vs. 64.6%; odds ratio, 1.57 [95% CI, 1.08-2.28]), as were cumulative MR4 (58.2% vs. 48.1%; 1.50 [1.07-2.12]) and MR4.5 (47.4% vs. 36.6%; 1.57 [1.11-2.22]) rates. Superior MR with bosutinib versus imatinib was consistent across Sokal risk groups, with greatest benefit seen in patients with high risk. Treatment-emergent adverse events (TEAEs) were consistent with 12-month data. After 5 years of follow-up there was an increase in the incidence of cardiac, effusion, renal, and vascular TEAEs in bosutinib- and imatinib-treated patients, but overall, no new safety signals were identified. These final results support 400-mg once-daily bosutinib as standard-of-care in patients with newly diagnosed CP CML.This trial was registered at www.clinicaltrials.gov as #NCT02130557

Indications et modalités de prescription du cyclophosphamide en bolus (Endoxan®) en médecine interne à propos d'une série de 22 cas

CAEN-BU Médecine pharmacie (141182102) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

Le développement d'un anticorps monoclonal dans la prévention de l'allo-immunisation fœto-maternelle anti-RhD

CAEN-BU Médecine pharmacie (141182102) / SudocSudocFranceF

Giroctocogene fitelparvovec gene therapy for severe hemophilia A: 104-week analysis of the Phase 1/2 Alta study

•Giroctocogene fitelparvovec is the first gene therapy for hemophilia A that uses a recombinant AAV serotype 6-based vector.•Giroctocogene fitelparvovec was generally well tolerated with appropriate clinical management and showed efficacy at the highest dose. Patients with hemophilia A require exogenous factor VIII (FVIII) or non-factor hemostatic agents to prevent spontaneous bleeding events. Adeno-associated virus (AAV) vector–based gene therapy is under clinical investigation to enable endogenous FVIII production. Giroctocogene fitelparvovec is a recombinant AAV serotype 6 vector containing the coding sequence for the B-domain–deleted human F8 gene. In the ongoing phase 1/2, dose-ranging Alta study, 4 sequential cohorts of male participants with severe hemophilia A received a single intravenous dose of giroctocogene fitelparvovec. The primary end points are safety and changes in circulating FVIII activity. Interim results up to 214 weeks after treatment for all participants are presented. Eleven participants were dosed. Increases in alanine and aspartate aminotransferases were the most common treatment-related adverse events (AEs), which resolved with corticosteroid administration. Two treatment-related serious AEs (hypotension and pyrexia) were reported in one participant within 6 hours of infusion and resolved within 24 hours post-infusion. At the highest dose level (3 × 1013 vg/kg; n = 5), the mean circulating FVIII activity level at week 52 was 42.6% (range, 7.8%-122.3%) and at week 104 was 25.4% (range, 0.9%–71.6%) based on a chromogenic assay. No liver masses, thrombotic events, or inhibitors were detected in any participant. These interim 104-week data suggest that giroctocogene fitelparvovec is generally well tolerated with appropriate clinical management and has the potential to provide clinically meaningful FVIII activity levels, as indicated by the low rate of bleeding events in the highest-dose cohort. (ClinicalTrials.gov Identifier: NCT03061201

Cézeaux-Aulnat-Opme-Puy De Dôme: a multi-site for the long-term survey of the tropospheric composition and climate change

International audienceFor the last 25 years, CO-PDD (Cézeaux-Aulnat-Opme-puy de Dôme) has evolved to become a full instrumented platform for atmospheric research. It has received credentials as a national observing platform in France and is internationally recognized as a global station in the GAW (Global Atmosphere Watch) network. It is a reference site of European and national research infrastructures ACTRIS (Aerosol Cloud and Trace gases Research Infrastructure) and ICOS (Integrated Carbon Observing System). The site located on top of the puy de Dôme mountain (1465 m a.s.l.) is completed by additional sites located at lower altitudes and adding the vertical dimension to the atmospheric observations: Opme (660 m a.s.l.), Cézeaux (410 m), and Aulnat (330 m). The integration of different sites offers a unique combination of in situ and remote sensing measurements capturing and documenting the variability of particulate and gaseous atmospheric composition, but also the optical, biochemical, and physical properties of aerosol particles, clouds, and precipitations. Given its location far away from any major emission sources, its altitude, and the mountain orography, the puy de Dôme station is ideally located to sample different air masses in the boundary layer or in the free troposphere depending on time of day and seasons. It is also an ideal place to study cloud properties with frequent presence of clouds at the top in fall and winter. As a result of the natural conditions prevailing at the site and of the very exhaustive instrumental deployment, scientific studies at the puy de Dôme strongly contribute to improving knowledge in atmospheric sciences, including the characterization of trends and variability, the understanding of complex and interconnected processes (microphysical, chemical, biological, chemical and dynamical), and the provision of reference information for climate/chemistry models. In this context, CO-PDD is a pilot site to conduct instrumental development inside its wind tunnel for testing liquid and ice cloud probes in natural conditions, or in situ systems to collect aerosol and cloud. This paper reviews 25 years (1995–2020) of atmospheric observation at the station and related scientific research contributing to atmospheric and climate science