768 research outputs found

    High resolution numerical study of the Algiers 2001 flash flood: sensitivity to the upper-level potential vorticity anomaly

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    From 9 to 11 November 2001, intense cyclogenesis affected the northern coasts of Africa and more particularly the densely populated city of Algiers. During the morning of 10 November, more than 130 mm of precipitation was recorded at Bouzareah and resulted in mudslides which devastated the Bab-el-Oued district. This disaster caused more than 700 casualties and catastrophic damage. Like many other heavy rainstorms in the western Mediterranean, this event was associated with the presence of an upper-level trough materialized by a deep stratospheric intrusion and characterized by high potential vorticity values. In this study, the impact of this synoptic structure on the localization and intensity of the precipitation which affected Algiers is investigated using a potential vorticity (PV) inversion method coupled for the first time with the French non-hydrostatic MESO-NH model. A set of perturbed synoptic environments was designed by slightly modifying the extent and the intensity of the coherent potential vorticity structures in the operational ARPEGE analysis. It is shown that such modifications may have a strong impact on the fine-scale precipitation forecast in the Algiers region, thereby demonstrating the fundamental role played by the potential vorticity anomaly during this exceptional meteorological event

    Ibrutinib added to 10-day decitabine for older patients with AML and higher risk MDS

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    The treatment of older, unfit patients with acute myeloid leukemia (AML) is challenging. Based on preclinical data of Bruton tyrosine kinase expression/phosphorylation and ibrutinib cytotoxicity in AML blasts, we conducted a randomized phase 2 multicenter study to assess the tolerability and efficacy of the addition of ibrutinib to 10-day decitabine in unfit (ie, Hematopoietic Cell Transplantation Comorbidity Index ≥3) AML patients and higher risk myelodysplasia patients (HOVON135/SAKK30/15 trial). In total, 144 eligible patients were randomly (1:1) assigned to either 10-day decitabine combined with ibrutinib (560 mg; sequentially given, starting the day after the last dose of decitabine) (n = 72) or to 10-day decitabine (n = 72). The addition of ibrutinib was well tolerated, and the number of adverse events was comparable for both arms. In the decitabine plus ibrutinib arm, 41% reached complete remission/complete remission with incomplete hematologic recovery (CR/CRi), the median overall survival (OS) was 11 months, and 2-year OS was 27%; these findings compared with 50% CR/CRi, median OS of 11.5 months, and 2-year OS of 21% for the decitabine group (not significant). Extensive molecular profiling at diagnosis revealed that patients with STAG2, IDH2, and ASXL1 mutations had significantly lower CR/CRi rates, whereas patients with mutations in TP53 had significantly higher CR/CRi rates. Furthermore, multicolor flow cytometry revealed that after 3 cycles of treatment, 28 (49%) of 57 patients with available bone marrow samples had no measurable residual disease. In this limited number of cases, measurable residual disease revealed no apparent impact on event-free survival and OS. In conclusion, the addition of ibrutinib does not improve the therapeutic efficacy of decitabine. This trial was registered at the Netherlands Trial Register (NL5751 [NTR6017]) and has EudraCT number 2015-002855-85
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