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Ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists (NMDAR antagonists) recently demonstrated antidepressant efficacy for the treatment of refractory depression, but effect sizes, trajectories and possible class effects are unclear.
We searched PubMed/PsycINFO/Web of Science/clinicaltrials.gov until 25 August 2015. Parallel-group or cross-over randomized controlled trials (RCTs) comparing single intravenous infusion of ketamine or a non-ketamine NMDAR antagonist v. placebo/pseudo-placebo in patients with major depressive disorder (MDD) and/or bipolar depression (BD) were included in the analyses. Hedges’ g and risk ratios and their 95% confidence intervals (CIs) were calculated using a random-effects model. The primary outcome was depressive symptom change. Secondary outcomes included response, remission, all-cause discontinuation and adverse effects.
A total of 14 RCTs (nine ketamine studies: n = 234; five non-ketamine NMDAR antagonist studies: n = 354; MDD = 554, BD = 34), lasting 10.0 ± 8.8 days, were meta-analysed. Ketamine reduced depression significantly more than placebo/pseudo-placebo beginning at 40 min, peaking at day 1 (Hedges' g = −1.00, 95% CI −1.28 to −0.73, p < 0.001), and loosing superiority by days 10–12. Non-ketamine NMDAR antagonists were superior to placebo only on days 5–8 (Hedges' g = −0.37, 95% CI −0.66 to −0.09, p = 0.01). Compared with placebo/pseudo-placebo, ketamine led to significantly greater response (40 min to day 7) and remission (80 min to days 3–5). Non-ketamine NMDAR antagonists achieved greater response at day 2 and days 3–5. All-cause discontinuation was similar between ketamine (p = 0.34) or non-ketamine NMDAR antagonists (p = 0.94) and placebo. Although some adverse effects were more common with ketamine/NMDAR antagonists than placebo, these were transient and clinically insignificant.
A single infusion of ketamine, but less so of non-ketamine NMDAR antagonists, has ultra-rapid efficacy for MDD and BD, lasting for up to 1 week. Development of easy-to-administer, repeatedly given NMDAR antagonists without risk of brain toxicity is of critical importance.
The mode of onset and the course of schizophrenia illness exhibit substantial individual variations. Previous studies have pointed out that the mode of onset affects the duration of untreated psychosis (DUP) and clinical outcomes, such as cognitive and social functioning. This study attempted to clarify the association between the DUP and clinical features, taking the different modes of onset into consideration, in a prospective longitudinal study examining patients with first-episode schizophrenia.
This study was conducted in six areas of Japan. Patients with first-episode schizophrenia were followed for over 18 months. Cognitive function, psychopathology, and social functioning were assessed at baseline and at 6, 12, and 18-month follow-up points.
We identified 168 patients and sufficient information was available to determine the DUP and the mode of onset for 156 patients (92.9%): 79 had an acute onset, and 77 had an insidious onset. The DUP was significantly associated with quality of life (QOL), social functioning, and cognitive function at most of the follow-up points in the insidious-onset group. The DUP and negative symptoms at baseline were significant predictors of cognitive function at the 18-month follow-up in the insidious-onset group.
The present results further support the hypothesis that the DUP affects QOL, social functioning, and cognitive function over the course of illness, especially in patients with an insidious onset. Effective strategies for detecting and caring for individuals with insidious onset early during the course of schizophrenia will be essential for achieving a full patient recovery.
Shiga-toxin-producing Escherichia coli (STEC) infections usually cause haemolytic uraemic syndrome (HUS) equally in male and female children. This study investigated the localization of globotriaosylceramide (Gb3) in human brain and kidney tissues removed from forensic autopsy cases in Japan. A fatal case was used as a positive control in an outbreak of diarrhoeal disease caused by STEC O157:H7 in a kindergarten in Urawa in 1990. Positive immunodetection of Gb3 was significantly more frequent in female than in male distal and collecting renal tubules. To correlate this finding with a clinical outcome, a retrospective analysis of the predictors of renal failure in the 162 patients of two outbreaks in Japan was performed: one in Tochigi in 2002 and the other in Kagawa Prefecture in 2005. This study concludes renal failure, including HUS, was significantly associated with female sex, and the odds ratio was 4·06 compared to male patients in the two outbreaks. From 2006 to 2009 in Japan, the risk factor of HUS associated with STEC infection was analysed. The number of males and females and the proportion of females who developed HUS were calculated by age and year from 2006 to 2009. In 2006, 2007 and 2009 in adults aged >20 years, adult women were significantly more at risk of developing HUS in Japan.
Highly transparent conductive Ga-doped ZnO (GZO) films are one of the promising transparent conductive oxide (TCO) films for use in electrodes of flat display panels and window layers of thin film solar cells. For the ZnO-based TCO films, the stability to damp-heat environment is a crucial issue for practical applications. We will report moisture resistant GZO codoped with indium films (GZO:In) on the basis of analysis of data obtained a damp-heat test for solar cells (85°C and 85% relative humidity for 1000 hours).
We used ZnO sintered targets with contents of 3 wt% Ga2O3 and 0.25 wt% In2O3 to grow GZO:In films in ion plating with direct current arc-discharge system. GZO:In films with different thicknesses (0.1-1 μm) were deposited on glass substrates at 200°C under the O2 flow rate of 15 sccm. As the film thickness increased from 0.1 to 1 μm, the resistivity and sheet resistance decreased from 4.3 μΩm to 2.6 μΩm and from 42.7 Ω/Sq. to 2.6 Ω/Sq., respectively. And the average optical transmittance (Tav) in the range from 0.4 to 1 μm decreased from ∼ 86% to ∼ 75%. The GZO:In film with a thickness of ∼300 nm had a low sheet resistance of 10.5 Ω/Sq. and a Tav of 82.5%. After 1000 hours damp-heat (DH) test under 85°C and 85% relative humidity, the relative change of sheet resistance is 3.4% with a Hall mobility of 26.4 cm2/V.s and a Tav of 82.7% after test. The film thicker than 300 nm has a sheet resistance lower than 10 Ω/Sq. and a relative change of resistance of ∼3% after DH test.
In order to measure precisely the polarization of Crab Nebula and Cygnus X-1, we have been developing a hard X-ray polarimeter for balloon-borne experiments called PHENEX (Polarimetry of High ENErgy X-rays). It consists of several detectors called unit counters. The unit counter has a detection efficiency of 20% and a modulation factor of 53% at 80 keV. Up to now, we have finished the installation of eight unit counters to the polarimeter, that will be launched in Spring 2009 to observe the Crab Nebula. If the polarization of this source is more than 30%, the PHENEX polarimeter will be able to measure the degree and the direction of the polarization with errors less than 10% and 10°, respectively.
X-ray astronomy has been much advanced by three observations: spectroscopy, timing, and imaging. Also in the hard X-ray region, these three observations will be realized by ASTRO-H and XEUS. However, the observation of the polarization is at the moment left out in spite of its potential usefulness. This is because of the difficulty of developing polarimeters with high sensitivity. Since the origin of the polarization is often due to nonthermal radiation processes such as synchrotron radiation, observations in the hard X-ray region are possibly more important than those in the soft X-ray region: it is expected that the degree of polarization in the hard X-ray region would be higher than that at lower energies.
Using the ion-temperature-gradient-driven drift waves as a paradigm for drift-wave anomalous transport, we explore the structure of the linear and nonlinear modes. Two phases of transport are shown to exist: (i) Bohm-like transport for parameters close to marginal stability; (ii) gyro-Bohm transport for turbulent convection cells in systems driven away from marginal stability. Nonlinear relaxation to large-scale coherent convective structures is observed in three-dimensional toroidal particle simulations.
In Southeast Asian tropical rainforests, two events, severe droughts associated with the El Niño-Southern Oscillation and general flowering, a type of community-wide mass flowering, occur at irregular, supra-annual intervals. The relationship between these two supra-annual events and patterns of insect population fluctuations has yet to be clearly elucidated. Leaf beetles (Chrysomelidae) are major herbivores and flower-visitors of canopy trees, affecting their growth and reproduction and, in turn, affected by tree phenology; but their population fluctuations in the Southeast Asian tropics have not been extensively investigated. We examined population fluctuation patterns of the 34 most dominant chrysomelid species in relation to the two supra-annual events by conducting monthly light-trapping over seven years in a lowland dipterocarp forest in Borneo. Our results showed large community variation in population fluctuation patterns and a supra-annual (between-year) variation in abundance for most of the dominant chrysomelids that was significantly larger than the annual (within-year) variation. Specifically, in response to a severe drought in 1998, chrysomelid species exhibited different population responses. These results show that population fluctuations of individual species, rather than the entire assemblage, must be analyzed to determine the effects of changes in environmental conditions on the structure of insect assemblages in the tropics, especially in regions where supra-annual environmental changes are relatively more important than seasonal changes.
An outbreak of psittacosis related to a bird park occurred in Matsue City, Shimane Prefecture, Japan, during winter 2001. Seventeen cases of psittacosis (12 visitors, three staff, and two student interns) were confirmed. A cohort study was conducted among the park staff and students to determine the risk factors for the development of acute serologically confirmed psittacosis (SCP) infection. Being ‘bird staff’ had an increased risk of SCP infection (RR 3·96, 95% CI 1·48–10·58). Entering the staff building, where ill birds were maintained without proper isolation, was also associated with an increased risk of SCP infection (RR 3·61, 95% CI 1·03–12·6). Isolation of ill birds and quarantine measures were found to be insufficient. Dehumidifiers and a high-pressure water spray under a closed ventilation environment may have raised the concentration of Chlamydophila psittaci in the hothouses. Bird park staff and visitors should be educated about psittacosis.
By using a particle code including atomic and relaxation processes, we investigated the ionization dynamics of a carbon film irradiated by an intense laser pulse. We found two types of ionization dynamics, namely, a fast time scale convective propagation of the ionization front with C4+ triggered by induced plasma waves, and a slow front with C5+ and C6+ triggered by heated electrons due to non-local thermal conduction. Thus, ionization dynamics in solids are found to evolve through multiple stages.
A comprehensive particle based integrated code including atomic and relaxation processes has been developed. By using the code, we have investigated the lightning process of compressed neon gas that in a uniformly applied electric field. After a long time interval, streamers are slowly developed from a tiny ionization spot that is initially set. Then a complicated branching is suddenly and also explosively triggered, leading to fine net-like structures or sprites. Electromagnetic radiations are emitted from the sprite and show a low-power wave number spectrum, suggesting that the sprite exhibits a fractal nature.
The dynamics of secondary fluctuations with poloidal long wavelength and low frequency in electron-temperature-gradient (ETG) turbulence saturation is considered in sheared slab geometry. A simplified modeling analysis shows that this kind of large-scale structure including streamers may saturate primary ETG instability through poloidal mode coupling. Spectral analyses in three-dimensional ETG simulations clearly exhibit the secondary excitation and the probable relevancy to ETG saturation. The result may implicate a lower fluctuation level in ETG turbulence.
We have succeeded in the fabrication of low-resistivity p-type ZnS with blue -Ag emission by triple-codoping using Ag, a Zn-substituting species, In, a Zn-substituting species, and N, a S-substituting species. For the realization of blue-Ag emission at 436 nm, we use In species as co-activators with Ag activators. For the control of conduction type to obtain p-type ZnS thin films, we introduce N species as acceptors into ZnS codoped with the Ag and In. On the basis of the analysis of the experimental data and calculated results, we proposed a model for ZnS:(Ag, In, and N), in which some of the In species act as coactivators with Ag activators and other In species act as reactive codopants with N acceptors.
We investigated the aluminum wiring reliability of fluorinated amorphous carbon (a-C:F) interlayer dielectrics (ILD) using electromigration tests at the wafer level under accelerated stress conditions with current density ranging from 25–32 MA/cm2 and a the substrate temperature of 300 K. The a-C:F film is one of the low-k organic materials with a dielectric constant of 2.5. The thermal conductivity of the a-C:F film (0.108 W/m·K) is about one order lower than that of SiO2 (1.2 W/m.K). We found that joule heating effect is enhanced by the lower thermal conductivity of a-C:F and that the wiring lifetime for a-C:F ILD is about one order lower than that for SiO2 ILD under high current stress. However, when the wiring lifetime is plotted as a function of the wiring temperature, the wiring lifetimes for both a-C:F ILD and SiO2 ILD became almost the same. The degradation of the wiring lifetime for a-C:F ILD is explained by the increase of the wiring temperature which is caused from joule heating. Moreover, the activation energy of the electromigration for a-C:F ILD has the same value as that of SiO2 LD at a temperature.
Nanoparticles of Cu were fabricated by negative-ion implantation, leading to spontaneous formation at high beam fluxes. Negative ions, alleviating surface charging, exhibit significant merits in carrying out low-energy implantation at high dose rates. The kinetic processes were studied by measuring dose-rate dependence of colloid formation and resultant optical properties. Negative-Cu ions of 60 keV were implanted into silica glasses at high-current densities, up to 260 μA/cm2, fixing the total dose at 3.0 × 1016 ions/cm2. Spherical nanocrystals of Cu atoms formed within a narrow region, near the projectile range of Cu ions. Simultaneously, much smaller particles spread out beyond a depleted zone, deeper than the projectile range. The nanocrystal growth and optical properties were greatly dependent on the dose rate and the specimen boundary condition. The growth process is explained by a droplet-model based on surface tension and radiation-induced diffusion. Beam-surface interactions also play an important role in the mass transport from the beam flux to the interior solid.
Radiation damage of amorphous Si (a- Si) under 17 MeV- proton bombardment has been studied, measuring particle- induced conductivity(PIC) and photoconductivity(PC). The in- situ measurements have been conducted to focus on the structural flexibility and the metastable nature, inherent in the amorphous structure. While the PC (with weak illumination) has a fast response and reversible nature, the PIC has a long time- constant ∼60 s, followed by a persistent conductivity for more than ∼103 s. Both the PIC and the PC remain fairly stable against further irradiation, comparing to crystalline Si (c-Si), but they decay in the higher fluence region. A large part of the decayed PC recovers after annealing at 450 K. The results of a- Si are compared with those of c- Si. It is suggested that, in the lower fluence region, a-Si is more resistant against proton irradiation than c- Si, relaxing the atomic displacements, and the excited conductivities gradually decay with accumulation of the dangling bonds.
High- current implantation of Cu- ions into silica glasses has been demonstrated using mAclass negative ion beams at 60 keV. Negative ion implantation has an advantage to alleviate specimen charging for insulating substrates and has attained high dose rates, up to 260 μA/cm2. Spherical Cu colloids form in the silica glasses without additional thermal annealing. Optical absorption and reflection of the implanted specimens vary with the current density, even at a fixed dose level. A beam- induced surface plasma may affect the high current implantation.
Deep level transient spectroscopy (DLTS) has been conducted to reveal electronic states of deep centers in n-Si, under 17 MeV-proton irradiation. The DLTS device was installed into the beam line of the cyclotron. The in-situ experiment was concentrated on, to study the dynamical defect evolution and the effect of irradiation temperature on the deep centers. DLTS signals of four deep levels E0-E3 were observed when n-Si was irradiated at 300 K. Three of the four peaks were identified as V-O, V-V2− and P-V centers, in comparison with the past data of electron irradiation. The other unknown level (EO) was located at 0.16 eV below the conduction band, and 0.02 eV lower than the V-O level. The E0 peak showed a characteristic behavior dependent on the irradiation temperature. The EQ did not emerge when irradiated at 200 K, but appeared after being annealed at 300 K following the 200 K irradiation. The evolution of these levels was consecutively investigated with accumulating the proton fluence and with annealing after the irradiation.
Control of charge carrier collection by high-energy boron-implanted layers has been investigated to clarify the validity of buried well structures against soft errors in dynamic random-access memories (DRAMs) by ion-induced-current measurements using high-energy proton microprobes. A finely focused 1.3 MeV proton beam has been used to irradiate normal to n+p diodes with buried layers fabricated by B+ implantation at 160 — 1000 keV and to doses of 1 × 1012 — 1 × 101 ions/cm2, and reverse-biased at 1 to 5 V. The measured current was induced by carriers generated by ion microprobes. The collection of charge carriers induced by microprobe irradiation could be reduced by a buried layer formed by boron implantation. It was found that the rate of charge collection depended not on the depth but on the implantation dose of the buried layer. The carrier collection efficiency of the n+p diode with twin wells (i.e., a retrograde well) was two thirds of that with a conventional well.