Search

Aims: Inadequate antidepressant response interrupts effective treatment of major depressive disorder (MDD). The BLESS study evaluates the dosage, efficacy, and safety of brexpiprazole adjunctive therapy in Japanese patients with inadequate antidepressant therapy (ADT) response. Methods: This placebo‐controlled, randomized, multicenter, parallel‐group phase 2/3 study randomized Japanese MDD patients (Hamilton Rating Scale for Depression 17‐item total score ≥ 14; historical inadequate response to 1–3 ADTs) with inadequate response to 8‐week single‐blind, prospective SSRI/SNRI treatment to 6‐week adjunctive treatment with brexpiprazole 1 mg, 2 mg, or placebo. The primary endpoint was change in Montgomery‐Åsberg Depression Rating Scale (MADRS) total score from baseline. Secondary endpoints included MADRS response, remission rate, and Clinical Global Impression‐Improvement score. Safety was comprehensively evaluated, especially regarding antipsychotic adverse events (AEs). Results: Of 1194 screened patients, 740 were randomized and 736 (1 mg, n = 248; 2 mg, n = 245; placebo, n = 243) had ≥1 baseline/post‐baseline MADRS total score. The LSM (SE) change from baseline in MADRS total score at Week 6 by MMRM analysis was −8.5 (0.47) with brexpiprazole 1 mg, −8.2 (0.47) with brexpiprazole 2 mg, and −6.7 (0.47) with placebo (placebo‐adjusted LSM difference [95% CI]: 1 mg, −1.7 [−3.0, −0.4]; P = 0.0089; 2 mg, −1.4 [−2.7, −0.1]; P = 0.0312). Secondary efficacy results supported the primary endpoint. Brexpiprazole was generally well tolerated. Conclusion: Brexpiprazole 1 mg daily was an appropriate starting dose and both 1 mg and 2 mg daily were effective and well tolerated as adjunctive therapy for Japanese MDD patients not adequately responsive to ADT. [ABSTRACT FROM AUTHOR]

A system of Navier–Stokes-type equations with two temperatures is derived, for a polyatomic gas with temperature-dependent specific heats (thermally perfect gas), from the ellipsoidal statistical (ES) model of the Boltzmann equation extended to such a gas. Subsequently, the system is applied to the problem of shock-wave structure for a gas with large bulk viscosity (or, equivalently, with slow relaxation of the internal modes), and the numerical results are compared with those based on the ordinary Navier–Stokes equations. It is shown that the latter equations fail to describe the double-layer structure of shock profiles for a gas with large bulk viscosity. [ABSTRACT FROM AUTHOR]

Objectives: To determine the long‐term safety of switching to brexpiprazole from aripiprazole or non‐aripiprazole dopamine antagonists. Methods: Post‐hoc analysis of 56‐week study of Japanese outpatients with schizophrenia switched to brexpiprazole 2 mg/day over 4‐week switching period with further titration (1–4 mg/day) allowed during the 52‐week, open‐label period. Major assessment items: total/low‐density lipoprotein (LDL)‐/high‐density lipoprotein (HDL)‐cholesterol, triglycerides, blood glucose, body weight and prolactin. Secondary evaluations were related to efficacy, treatment emergent adverse events (TEAEs), extrapyramidal symptoms, and corrected QT interval (QTc). Results: 84/186 (45.2%) patients (aripiprazole, 32.9%; non‐aripiprazole, 54.8%) discontinued treatment over 56 weeks mainly because of consent withdrawal/adverse events. From baseline to Week 56, both groups showed minimal mean changes in total/LDL‐/HDL‐cholesterol, triglycerides, and glucose levels and a slight increase in mean (SD) body weight (aripiprazole, 1.1 [4.4] kg; non‐aripiprazole, 0.4 [4.6] kg). Mean prolactin levels increased slightly in the aripiprazole group, but decreased in the non‐aripiprazole group. Symptom severity scores decreased similarly in both groups. TEAEs occurred in 161/186 (86.6%) patients (aripiprazole, 84.1% [serious, 9.8%]; non‐aripiprazole, 88.5% [serious, 14.4%]). Few changes occurred in extrapyramidal symptom scales or QTc interval. Conclusions: Switching to brexpiprazole is associated with a low long‐term risk for metabolic abnormalities (including weight gain), hyperprolactinemia, extrapyramidal symptoms and QTc changes and minimal changes in psychiatric symptoms. [ABSTRACT FROM AUTHOR]

We study the statistics of backward clusters in a gas of hard spheres at low density. A backward cluster is defined as the group of particles involved directly or indirectly in the backwards-in-time dynamics of a given tagged sphere. We derive upper and lower bounds on the average size of clusters by using the theory of the homogeneous Boltzmann equation combined with suitable hierarchical expansions. These representations are known in the easier context of Maxwellian molecules (Wild sums). We test our results with a numerical experiment based on molecular dynamics simulations. [ABSTRACT FROM AUTHOR]

The representative recent works of us, Optical Single Crystals Group, NIMS, Japan, are reviewed. Our group has been working on the development of novel single crystals for electro-optical applications based on the Czochralski technique. Here, 3 kinds of topics are reviewed. 1st one is transparent conductive β- single crystals as semiconductor, which has quite large bandgap, 4.8 eV, for LED and power device applications. 2nd one is a new concept of phospher material, single-crystal phospher, based on Y3AI5O12 single crystal. These single-crystal phosphers are promising for highly efficient, resin-free, high brightness white LEDs/LDs. 3rd one is superior magneto-optical single crystals for optical isolators. {Tb3}[Sc2-xLux](Al3)Oi2 single crystals for near infrared to visible region, and CeF3/PrF3 single crystals for UV region are realized. [ABSTRACT FROM AUTHOR]

A constitutive model for marine sediments containing natural gas hydrate is essential for the simulation of the geomechanical response to gas extraction from a gas-hydrate reservoir. In this study, the triaxial compressive properties of artificial methane-hydrate-bearing sediment samples reported in an earlier work were analyzed to examine the applicability of a nonlinear elastic constitutive model based on the Duncan-Chang model. The presented model considered the dependences of the mechanical properties on methane hydrate saturation and effective confining pressure. Some parameters were decided depending on the type of sand forming a specimen. The behaviors of lateral strain versus axial strain were also formulated as a function of effective confining pressure. The constitutive model presented in this study will provide a basis for an elastic analysis of the geomechanical behaviors of the gas-hydrate reservoir in the future study, although it is currently available to a limited extent. [ABSTRACT FROM AUTHOR]

The behavior of a slightly rarefied monatomic gas between two parallel plates whose temperature grows slowly and linearly in time is investigated on the basis of the kinetic theory of gases. This problem is shown to be equivalent to a boundary-value problem of the steady linearized Boltzmann equation describing a rarefied gas subject to constant volumetric heating. The latter has been recently studied by Radtke, Hadjiconstantinou, Takata, and Aoki (RHTA) as a means of extracting the second-order temperature jump coefficient. This correspondence between the two problems gives a natural interpretation to the volumetric heating source and explains why the second-order temperature jump observed by RHTA is not covered by the general theory of slip flow for steady problems. A systematic asymptotic analysis of the time-dependent problem for small Knudsen numbers is carried out and the complete fluid-dynamic description, as well as the related half-space problems that determine the structure of the Knudsen layer and the coefficients of temperature jump, are obtained. Finally, a numerical solution is presented for both the Bhatnagar-Gross-Krook model and hard-sphere molecules. The jump coefficient is also calculated by the use of a symmetry relation; excellent agreement is found with the result of the numerical computation. The asymptotic solution and associated second-order jump coefficient obtained in the present paper agree well with the results by RHTA that are obtained by a low variance stochastic method. [ABSTRACT FROM AUTHOR]

A rarefied gas flow thermally induced around a heated (or cooled) flat plate, contained in a vessel, is considered in two different situations: (i) both sides of the plate are simultaneously and uniformly heated (or cooled); and (ii) only one side of the plate is uniformly heated. The former is known as the thermal edge flow and the latter, typically observed in the Crookes radiometer, may be called the radiometric flow. The steady behaviour of the gas induced in the container is investigated on the basis of the Bhatnagar–Gross–Krook (BGK) model of the Boltzmann equation and the diffuse reflection boundary condition by means of an accurate finite-difference method. The flow features are clarified for a wide range of the Knudsen number, with a particular emphasis placed on the structural similarity between the two flows. The limiting behaviour of the flow as the Knudsen number tends to zero (and thus the system approaches the continuum limit) is investigated for both flows. The detailed structure of the normal stress on the plate as well as the cause of the radiometric force (the force acting on the plate from the hotter to the colder side) is also clarified for the present infinitely thin plate. [ABSTRACT FROM PUBLISHER]

Objective: The causal agents of gastric cancer could include fungus toxins. Sterigmatocystin (ST), a fungus toxin, is a risk factor of gastric cancer. We investigated the effects of ST on the stomach tissues of Mongolian gerbils. Methods: Seventy-five-week-old male Mongolian gerbils received ST ad libitum at a concentration of 0 ppb (non-treated, n = 11), 100 ppb ( n = 7), or 1,000 ppb ( n = 13) dissolved in drinking water for a period of 24 weeks. After administration, we tested the histopathological changes and immunostaining for proliferating cell nuclear antigen (PCNA), p53, and MDM2 expression. Results: We investigated the histopathological changes and determined the incidence of histopathological changes in animals with various gastric diseases after ST administration at a dose of 0 ppb (non-treated control), 100, or 1,000 ppb as follows: firstly, indices for gastritis were 18.2, 100, and 100%, those for erosion events were 9.1, 100, and 92.3%, and those for polyps were 0, 71.4, and 61.5%, respectively. These incidences in the ST-administered groups (100 or 1,000 ppb) showed significant increases compared with those in the non-treated control group. And, lastly, indices for intestinal metaplasia were 0, 100, and 15.4%, respectively. Furthermore, immunostaining for PCNA, p53, and MDM2 expression showed significantly greater rates in the ST-administered groups (100 or 1,000 ppb) than in the non-treated control group. Conclusion: The histopathological and immunohistopathological findings of this study indicate that ST exerts a marked influence on gastric mucus and gland cells, showing dominant gastritis, erosion events, polyps, and intestinal metaplasia in these animals. [ABSTRACT FROM AUTHOR]