A phase 3 trial of azacitidine versus a semi-intensive fludarabine and cytarabine schedule in older patients with untreated acute myeloid leukemia

PETHEMA Group.[Background] Options to treat elderly patients (≥65 years old) newly diagnosed with acute myeloid leukemia (AML) include intensive and attenuated chemotherapy, hypomethylating agents with or without venetoclax, and supportive care. This multicenter, randomized, open-label, phase 3 trial was designed to assess the efficacy and safety of a fludarabine, cytarabine, and filgrastim (FLUGA) regimen in comparison with azacitidine (AZA).[Methods] Patients (n = 283) were randomized 1:1 to FLUGA (n = 141) or AZA (n = 142). Response was evaluated after cycles 1, 3, 6, and 9. Measurable residual disease (MRD) was assessed after cycle 9. When MRD was ≥0.01%, patients continued with the treatment until relapse or progressive disease. Patients with MRD < 0.01% suspended treatment to enter the follow-up phase. [Results] The complete remission (CR) rate after 3 cycles was significantly better in the FLUGA arm (18% vs 9%; P = .04), but the CR/CR with incomplete recovery rate at 9 months was similar (33% vs 29%; P = .41). There were no significant differences between arms in early mortality at 30 or 60 days. Hematologic toxicities were more frequent with FLUGA, especially during induction. The 1-year overall survival (OS) rate and the median OS were superior with AZA versus FLUGA: 47% versus 27% and 9.8 months (95% confidence interval [CI], 5.6-14 months) versus 4.1 months (95% CI, 2.7-5.5 months; P = .005), respectively. The median event-free survival was 4.9 months (95% CI, 2.8-7 months) with AZA and 3 months (95% CI, 2.5-3.5 months) with FLUGA (P = .001). [Conclusions] FLUGA achieved more remissions after 3 cycles, but the 1-year OS rate was superior with AZA. However, long-term outcomes were disappointing in both arms (3-year OS rate, 10% vs 5%). This study supports the use of an AZA backbone for future combinations in elderly patients with AML.This study was supported by the Spanish Biomedical Research Centre in Cancer of the Carlos III Health Institute (CB16/12/00369) and by the Carlos III Health Institute/Subdirectorate General for Health Research (FIS No. PI16/01661). Celgene provided the azacitidine and financial support for this study

Effects of functional remediation on neurocognitively impaired bipolar patients: enhancement of verbal memory

Background: functional remediation is a novel intervention with demonstrated efficacy at improving functional outcome in euthymic bipolar patients. However, in a previous trial no significant changes in neurocognitive measures were detected. The objective of the present analysis was to test the efficacy of this therapy in the enhancement of neuropsychological functions in a subgroup of neurocognitively impaired bipolar patients. Method: a total of 188 out of 239 DSM-IV euthymic bipolar patients performing below two standard deviations from the mean of normative data in any neurocognitive test were included in this subanalysis. Repeated-measures analyses of variance were conducted to assess the impact of the treatment arms [functional remediation, psychoeducation, or treatment as usual (TAU)] on participants' neurocognitive and functional outcomes in the subgroup of neurocognitively impaired patients. Results: patients receiving functional remediation (n = 56) showed an improvement on delayed free recall when compared with the TAU (n = 63) and psychoeducation (n = 69) groups as shown by the group × time interaction at 6-month follow-up [F 2,158 = 3.37, degrees of freedom (df) = 2, p = 0.037]. However, Tukey post-hoc analyses revealed that functional remediation was only superior when compared with TAU (p = 0.04), but not with psychoeducation (p = 0.10). Finally, the patients in the functional remediation group also benefited from the treatment in terms of functional outcome (F 2,158 = 4.26, df = 2, p = 0.016). Conclusions: functional remediation is effective at improving verbal memory and psychosocial functioning in a sample of neurocognitively impaired bipolar patients at 6-month follow-up. Neurocognitive enhancement may be one of the active ingredients of this novel intervention, and, specifically, verbal memory appears to be the most sensitive function that improves with functional remediation

Microscopic simulation of xenon-based optical TPCs in the presence of molecular additives

[EN] We introduce a simulation framework for the transport of high and low energy electrons in xenon-based optical time projection chambers (OTPCs). The simulation relies on elementary cross sections (electron-atom and electron-molecule) and incorporates, in order to compute the gas scintillation, the reaction/quenching rates (atom-atom and atom-molecule) of the first 41 excited states of xenon and the relevant associated excimers, together with their radiative cascade. The results compare positively with observations made in pure xenon and its mixtures with CO2 and CF4 in a range of pressures from 0.1 to 10 bar. This work sheds some light on the elementary processes responsible for the primary and secondary xenon-scintillation mechanisms in the presence of additives, that are of interest to the OTPC technology.DGD is supported by the Ramon y Cajal program (Spain) under contract number RYC-2015-18820. The authors want to acknowledge the RD51 collaboration for encouragement and support during the elaboration of this work, and in particular discussions with F. Resnati, A. Milov, V. Peskov, M. Suzuki and A. F. Borghesani. The NEXT Collaboration acknowledges support from the following agencies and institutions: the European Research Council (ERC) under the Advanced Grant 339787-NEXT; the Ministerio de Economia y Competitividad of Spain under grants FIS2014-53371-C04 and the Severo Ochoa Program SEV-2014-0398; the GVA of Spain under grant PROM-ETEO/2016/120; the Portuguese FCT and FEDER through the program COMPETE, project PTDC/FIS-NUC/2525/2014 and UID/FIS/04559/2013; the U.S. Department of Energy under contracts number DE-AC02-07CH11359 (Fermi National Accelerator Laboratory) and DE-FG02-13ER42020 (Texas A& and the University of Texas at Arlington.Azevedo, C.; Gonzalez-Diaz, D.; Biagi, SF.; Oliveira, CAB.; Henriques, CAO.; Escada, J.; Monrabal, F.... (2018). Microscopic simulation of xenon-based optical TPCs in the presence of molecular additives. Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment. 877:157-172. https://doi.org/10.1016/j.nima.2017.08.049S15717287

Optimizing the dynamics of a two-cell DC–DC buck converter by time delayed feedback control

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Power adaptor device for domestic DC microgrids based on commercial MPPT inverters

This paper presents a power adaptor device, referred to as smart panel device, allowing the connection of additional energy sources and storage elements to a domestic photovoltaic (PV) grid-connected system. The adaptor output port is designed to behave as a power source/sink, thus enabling its hot-swap parallel connection to renewable power sources without modifying their maximum power point (MPP). Moreover, the adaptor device features a power characteristic with a single controllable MPP and allows the control of the injected power within the operating range of the dc–ac grid-connected inverter. The work presents the design principles of such device by describing the operation of a sliding- mode controlled quadratic-boost converter. The proper operation of the device is experimentally verified for several scenarios in a small PV-based microgrid system including a fuel-cell stack, a 1-kW three-phase wind turbine, a battery charger–discharger, and commercial grid-connected PV invertersPeer ReviewedPostprint (published version

Power adaptor device for domestic DC microgrids based on commercial MPPT inverters

This paper presents a power adaptor device, referred to as smart panel device, allowing the connection of additional energy sources and storage elements to a domestic photovoltaic (PV) grid-connected system. The adaptor output port is designed to behave as a power source/sink, thus enabling its hot-swap parallel connection to renewable power sources without modifying their maximum power point (MPP). Moreover, the adaptor device features a power characteristic with a single controllable MPP and allows the control of the injected power within the operating range of the dc–ac grid-connected inverter. The work presents the design principles of such device by describing the operation of a sliding- mode controlled quadratic-boost converter. The proper operation of the device is experimentally verified for several scenarios in a small PV-based microgrid system including a fuel-cell stack, a 1-kW three-phase wind turbine, a battery charger–discharger, and commercial grid-connected PV invertersPeer Reviewe