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- Levis, Mark, et al.
(författare)
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Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse
- 2011
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 117:12, s. 3294-3301
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Tidskriftsartikel (refereegranskat)abstract
- In a randomized trial of therapy for FMS-like tyrosine kinase-3 (FLT3) mutant acute myeloid leukemia in first relapse, 224 patients received chemotherapy alone or followed by 80 mg of the FLT3 inhibitor lestaurtinib twice daily. Endpoints included complete remission or complete remission with incomplete platelet recovery (CR/CRp), overall survival, safety, and tolerability. Correlative studies included pharmacokinetics and analysis of in vivo FLT3 inhibition. There were 29 patients with CR/CRp in the lestaurtinib arm and 23 in the control arm (26% vs 21%; P = .35), and no difference in overall survival between the 2 arms. There was evidence of toxicity in the lestaurtinib-treated patients, particularly those with plasma levels in excess of 20 mu M. In the lestaurtinib arm, FLT3 inhibition was highly correlated with remission rate, but target inhibition on day 15 was achieved in only 58% of patients receiving lestaurtinib. Given that such a small proportion of patients on this trial achieved sustained FLT3 inhibition in vivo, any conclusions regarding the efficacy of combining FLT3 inhibition with chemotherapy are limited. Overall, lestaurtinib treatment after chemotherapy did not increase response rates or prolong survival of patients with FLT3 mutant acute myeloid leukemia in first relapse. This study is registered at www.clinicaltrials.gov as #NCT00079482. (Blood. 2011;117(12): 3294-3301)
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- Brönnimann, Stefan, et al.
(författare)
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Unlocking Pre-1850 Instrumental Meteorological Records : A Global Inventory
- 2019
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 100:12, s. ES389-ES413
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Tidskriftsartikel (refereegranskat)abstract
- Instrumental meteorological measurements from periods prior to the start of national weather services are designated early instrumental data. They have played an important role in climate research as they allow daily to decadal variability and changes of temperature, pressure, and precipitation, including extremes, to be addressed. Early instrumental data can also help place twenty-first century climatic changes into a historical context such as defining preindustrial climate and its variability. Until recently, the focus was on long, high-quality series, while the large number of shorter series (which together also cover long periods) received little to no attention. The shift in climate and climate impact research from mean climate characteristics toward weather variability and extremes, as well as the success of historical reanalyses that make use of short series, generates a need for locating and exploring further early instrumental measurements. However, information on early instrumental series has never been electronically compiled on a global scale. Here we attempt a worldwide compilation of metadata on early instrumental meteorological records prior to 1850 (1890 for Africa and the Arctic). Our global inventory comprises information on several thousand records, about half of which have not yet been digitized (not even as monthly means), and only approximately 20% of which have made it to global repositories. The inventory will help to prioritize data rescue efforts and can be used to analyze the potential feasibility of historical weather data products. The inventory will be maintained as a living document and is a first, critical, step toward the systematic rescue and reevaluation of these highly valuable early records. Additions to the inventory are welcome.
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