Efficacy and safety of blonanserin transdermal patch in patients with schizophrenia: A 6-week randomized, double-blind, placebo-controlled, multicenter study

© 2019 The Authors Background: Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia. This study determined the efficacy, safety and pharmacokinetics of a blonanserin transdermal patch in patients with acutely exacerbated schizophrenia. Methods: This double-blind, multicenter, phase 3 study consisted of a 1-week observation period during which patients were treated with two patches of placebo, followed by a 6-week double-blind period where patients were randomized (1:1:1) to receive once-daily blonanserin 40 mg, blonanserin 80 mg, or placebo patches. The primary endpoint was the change from baseline in the total Positive and Negative Symptom Scale (PANSS) score. Safety assessments included treatment-emergent adverse events (TEAEs). Results: Between December 2014 and October 2018, patients were recruited and randomly assigned to blonanserin 40 mg (n = 196), blonanserin 80 mg (n = 194), or placebo (n = 190); of these, 77.2% completed the study. Compared with placebo, blonanserin significantly improved PANSS total scores at 6 weeks (least square mean [LSM] difference vs placebo: −5.6 with blonanserin 40 mg; 95% confidence interval [CI] −9.6, −1.6; adjusted p = 0.007, and − 10.4 with blonanserin 80 mg; 95% CI −14.4, −6.4; adjusted p \u3c 0.001). Blonanserin was well tolerated; the most common TEAEs reported were application-site erythema and pruritus, akathisia, tremor, and insomnia. Conclusions: Blonanserin transdermal patch improved the symptoms of acute schizophrenia with acceptable tolerability

ヨウリョクタイガタ フェレドキシン ノ コウゾウ カイセキ 2.8Å ブンカイノウ

Remarkable progress in the physical parameters of net-current free plasmas has been made in the Large Helical Device (LHD) since the last Fusion Energy Conference in Chengdu, 2006 (O.Motojima et al., Nucl. Fusion 47 (2007) S668). The beta value reached 5 % and a high beta state beyond 4.5% from the diamagnetic measurement has been maintained for longer than 100 times the energy confinement time. The density and temperature regimes also have been extended. The central density has exceeded 1.0 x 10^21 m^-3 due to the formation of an Internal Diffusion Barrier (IDB). The ion temperature has reached 6.8 keV at the density of 2 x 10^19m^-3, which is associated with the suppression of ion heat conduction loss. Although these parameters have been obtained in separated discharges, each fusion-reactor relevant parameter has elucidated the potential of net-current free heliotron plasmas. Diversified studies in recent LHD experiments are reviewed in this paper

Practical Formal Verification for Model Based Development of Cyber-Physical Systems

The application of cyber-physical systems (CPSs) in safety-critical applications requires rigorous verification of their functional correctness and safety-relevant properties. We propose a practical verification framework which enables to fill the gaps between model-based development and the formal verification process seamlessly connecting them. The verification framework consists of (a) a model transformation method, which automatically transforms the plant models of CPSs including differential algebraic equations (DAE) to equivalent models without DAE to reduce verification complexity induced by DAE solver execution, and (b) a model simplification method, which automatically simplifies bond-graph models by replacing complex bond-graph components with simpler components for further verification overhead reductions. We successfully applied the proposed verification framework for safety verification of an automotive brake control system. The results of the study demonstrate that the automated model transformations of the CPS models yield significant verification complexity reductions without impairing the ability to detect unsafe behavior of the brake control system in a formal verification based on symbolic execution. © 2016 IEEE

A retrospective study of predictive factors for effective aripiprazole augmentation of antidepressant therapy in treatment-resistant depression

Hiroko Sugawara,1,2 Kaoru Sakamoto,1 Tsuyoto Harada,3 Satoru Shimizu,4 Jun Ishigooka1 1Department of Psychiatry, Tokyo Women’s Medical University, 2Support Center for Women Health Care Professionals and Researchers, Tokyo Women’s Medical University, Shinjuku-ku, 3Department of Psychiatry, Tokyo Women’s Medical University Medical Center East, Arakawa-ku, 4Department of Research, Medical Research Institute, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan Background: Several studies have evaluated the efficacy and tolerability of aripiprazole for augmentation of antidepressant therapy for treatment-resistant depression (TRD). Here, we investigated the efficacy of aripiprazole augmentation for TRD including both major depressive disorder and bipolar disorder and the clinical predictors of treatment efficacy in a Japanese population.  Methods: Eighty-five depressed Japanese patients who underwent aripiprazole augmentation therapy after failing to respond satisfactorily to antidepressant monotherapy were included in the study. Treatment responses were evaluated based on Clinical Global Impression Improvement scores assessed 8 weeks after initiation of aripiprazole administration. We compared demographic and diagnostic variables, psychiatric medication variables, and clinical variables between remission and nonremission groups.  Results: The aripiprazole augmentation remission rate was 36.5%. Multiple logistic regression analysis indicated that aripiprazole augmentation was significantly more effective for bipolar depression than for major depressive disorder, and both absence of comorbid anxiety disorders and current episode duration >3 months were significantly associated with the efficacy of aripiprazole augmentation.  Conclusion: Polarity of depression, comorbidity of anxiety disorders, and current episode duration may predict the efficacy of aripiprazole augmentation for TRD including both major depressive disorder and bipolar disorder. Among them, comorbidity of anxiety disorders was significantly related to the efficacy for TRD including only major depressive disorder. Additional studies are needed to examine the association between the efficacy of aripiprazole augmentation and bipolarity, and these findings should be validated further in a prospective study. Keywords: TRD, aripiprazole, predictor, bipolar depression, anxiety disorder&nbsp

Practical use of formal verification for safety critical cyber-physical systems:A case study

Cyber-Physical Systems (CPS) linking computing to physical systems are often used to monitor and controlsafety-critical processes, i.e. processes that bear the potential to cause significant damage or loss in the case of failures. While safety-critical systems have been extensively studied in both the discrete (computing) and analog (control) domains, the developed techniques apply to either one domain or the other. As cyber-physical systems span both domains, the focus on an individual domain leaves a gap on the systemlevel, where complex interactions between the domains can lead to failures that cannot be analyzed by considering only the physical orthe digital part of the integrated CPS. We discuss such a complex failure condition in a real-world brakecontrol system, and demonstrate its detection using a formalverification approach specifically targeting CPS. © 2014 IEEE

Safety verification utilizing model-based development for safety critical cyber-physical systems

The application of cyber-physical systems (CPSs) in safety-critical application domain requires rigorous verification of their functional correctness and safety-relevant properties. We propose a practical verification process which enables to conduct safety verification of safety critical CPSs. The verification process consists of (a) a system model construction method, which generates a system model by combining software described in C and plant model code reused from model-based development, (b) a model transformation method, which transforms the plant models including differential algebraic equations (DAE) to approximate models without DAE to reduce verification complexity induced by DAE solver execution, (c) a model simplification framework, which enables the simplification of bond-graph plant models using domain-knowledge-based replacement of complex model components for further verification overhead reductions, and (d) a formal verification based on symbolic execution. We implemented the proposed methods and framework, and successfully applied the proposed verification process for safety verification of automotive brake control systems. The results of the study demonstrate that the verification detects a complex failure condition in a real-world brake control system from the generated system model and that the automated model transformations of the CPS models yield significant verification complexity reductions without impairing the ability to detect unsafe behavior. © 2017 Information Processing Society of Japan