Fiducial Lower Confidence Limit of Reliability for a Power Distribution System

Reliability performance, especially the lower confidence limit of reliability, plays an important role in system risk and safety assessment. A good estimator of the lower confidence limit of system reliability can help engineers to make the right decisions. Based on the lifetime of the key component in a typical satellite intelligent power distribution system, the generalized fiducial method is adopted to estimate the lower confidence limit of the system reliability in this paper. First, the generalized pivotal quantity and the lower confidence limit of reliability for the key component are derived for the lifetimes of the exponential-type and Weibull-type components. Simulations show that the sample median is more appropriate than the sample mean when the lower confidence limit of reliability is estimated. Moreover, the lower confidence limit of reliability is obtained for the typical satellite intelligent power distribution system through the pseudo-lifetime data of the metallic oxide semiconductor field effect transistor. The lower confidence limit of reliability for this power distribution system at 15 years is 0.998, which meets the factory’s reliability requirement. Finally, through the comparison, a hot standby subsystem can be substituted with a cold standby subsystem to increase the lower confidence limit of the system reliability.

Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315I mutation

Chronic myeloid leukemia (CML) patients with the BCR-ABL T315I mutation do not benefit from therapy with currently approved tyrosine kinase inhibitors. Omacetaxine mepesuccinate is a protein synthesis inhibitor that has demonstrated activity in cells harboring the T315I mutation. This phase 2 trial assessed the efficacy of omacetaxine in CML patients with T315I and tyrosine kinase inhibitor failure. Patients received subcutaneous omacetaxine 1.25 mg/m2 twice daily, days 1-14, every 28 days until hematologic response or a maximum of 6 cycles, and then days 1-7 every 28 days as maintenance. Results for patients treated in chronic phase are reported here. Patients (n = 62) received a median of 7 (range, 1-41) cycles. Complete hematologic response was achieved in 48 patients (77%; 95% lower confidence limit, 65%); median response duration was 9.1 months. Fourteen patients (23%; 95% lower confidence limit, 13%) achieved major cytogenetic response, including complete cytogenetic response in 10 (16%). Median progression free-survival was 7.7 months. Grade 3/4 hematologic toxicity included thrombocytopenia (76%), neutropenia (44%), and anemia (39%) and was typically manageable by dose reduction. Nonhematologic adverse events were mostly grade 1/2 and included infection (42%), diarrhea (40%), and nausea (34%). Omacetaxine may provide a safe and effective treatment for CML patients with T315I mutation. This study is registered at www.clinicaltrials.gov as NCT00375219.