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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.
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.
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.
Medium scale integrated circuits with 108 CNT-TFTs have been fabricated using CNTs grown by plasma enhanced chemical vapor deposition (PECVD) which has the advantage of preferential growth of CNTs with semiconducting behavior in the FET current–voltage characteristics. High-speed operation with a switching time of 0.51 μs/gate, which is highest in the CNT-TFT integrated circuits to our knowledge, was demonstrated by a 53-stage ring oscillator. Characterization of CNT-TFTs using scanning probe microscopy has also been performed. The island-like structure in the electrical properties of the CNT network was observed even in a high-density CNT network in the subthreshold regime. This was explained by the decrease of the effective number of CNTs which contribute the electrical conduction.
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.
Proton flux and temperature dependent generation rates of radiation-induced defect clusters under 17 MeV proton irradiation have been studied by in-situ Deep Level Transient Spectroscopy (DLTS) measurement, to obtain information on clustering processes. The proton flux was ranged from 2.51×10up to 1.6×1012ions/cm2s with irradiation temperature 200 K or 300 K. Flux dependence is related to the ratio of impurity and primary defect concentrations created during irradiation. Change in temperature mainly modifies the diffusion constants of defects which determine the reaction rates. Rate equations of the defect reactions based on the Oerlein model  were solved numerically and compared to the experimental results. The numerical calculation successfully explained temperature and flux dependence except in the higher flux region.
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.
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.
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.
High-energy particles incident to a semiconductor sensitively produce electron-hole pairs and the excited current has been used for radiation detectors. Although semiconductors have advantages such as high sensitivity and fast response, a drawback is weakness in radiation damage. To improve the radiation resistance, effects of shallow-impurity doping was explored for Si. Specimens of CZ-Si doped with P or B were bombarded with 17 MeV protons. The radiation-induced current of doped Si has been evaluated, as a function of proton fluence. The signal of particle-induced conductivity showed a fairly constant response to a proton flux, up to 1015 ions/cm2. The fluence range applicable as Si sensors was extended 103-104 times as much as that of non-doped Si, instead of a lower signal-to-noise ratio. Shallow impurities passivate the deep centers of radiation-induced defects, and the radiation tolerance continues until the pre-existent carriers are exhausted. The tolerant fluence is also usable to detect the integrated fluence, by controlling the initial impurity concentration.
Deep centers related to proton-induced defects and impurities in n-Si were investigated using an in-situ DLTS system. The measurement system was installed in the beamline of NRIM cyclotron. Floating zone (FZ) or Czochralski (CZ) Si was irradiated at a flux of about 30 nA/cm2. The total dose was varied between 1.0 ∼ 7.2 × 1013 ions/cm2. Samples were irradiated at 200 K or 300 K. Their defect concentrations were determined by in-situ DLTS. Quantitative relationship between oxygen and phosphorus concentration and defect creation rates were presented. Isothermal annealing at 250 K was conducted for a CZ-Si sample and the resuflt indicated the meta-stable nature of the carbon defect complex.
The technologies utilizing Fluorinated Silicon Oxide (FSG, k=3.6) and Hydrogen Silsesquioxane (HSQ, k=3.0) have been established for 0.25-μm and 0.18-μm generation ULSIs. However, low-k materials for the next generation ULSIs, which have a dielectric constant of less than 3.0, have not become mature yet. In this paper, we review process integration issues in applying FSG and HSQ, and describe integration results and device performance using Fluorinated Amorphous Carbon (a-C:F, k=2.5) as one of the promising low-k materials for the next generation ULSIs.
Thermoelectric power generation is a promising technology for increasing the efficiency of electrical and optical electrical devices. We prepared samples by Electron Beam evaporating Zn4Sb3 and CeFe2Co2Sb12 thin films on silicon dioxide (silica) substrates. The materials were co-evaporated and then were prepared for gold over-coating. Following electron deposition we performed post ion bombardment at a constant energy of 5 MeV while varying fluence from 1×1012, 1×1013, 1×1014, 1×1015 ions/cm2, respectfully. The production of nano-clusters generated from the MeV Si ions bombardment modifies the electrical and phonon interactions in the materials. Also, we will report on the fluence dependence of the figure of merit, Seebeck Coefficient, thermal conductivity and electrical conductivity. In addition, Rutherford backscattering spectrometry (RBS) was used to analyze the elemental composition and the thickness of the deposited material.
Poly(tetrafluoroethylene) (PTFE) microstructure with high aspect ratio (> 200) and without solid debris along the edge was fabricated with high etch rate by using FIB. Gasification of PTFE by FIB is responsible for the high aspect ratio, the high etch rate, and the no solid debris. Roughness of etched surface of the PTFE increases with fluence, although edge of the etched area has good profiles. The etch mechanism seems to be complicated.
The conducting carbon nanowires embedded in fullerene matrix are synthesized by high energy heavy ion irradiation of thin fullerene film. We report the control growth of carbon nanowires, their electrical and field emission properties. The typical diameter of the conducting tracks is observed to be about 40 to 100 nm. The conductivity of the conducting zone is about seven orders of magnitude higher than that of the fullerene matrix. Conducting atomic force microscopy evidences the conducting nano wires. All the nanowires are parallel to each other and are perpendicular to the substrate. The density (spacing), growth direction and length of these carbon nanowires simply can be changed by ion fluence, angle of irradiation and the film thickness, respectively. The field emission measurements on these nanowires reveal that the threshold voltage is about ( ~13 V/mm), whereas the as deposited fullerene films shows a break down at ( ~ 51 V/mm). The present approach of making controlled conducting carbon nanowires is quite promising, as it takes few seconds of ion irradiation and no catalyst is required.
Pulsed low-energy (200 eV) ion-beam-induced nucleation during Ge deposition on thin SiO2 film was used to form dense homogeneous arrays of Ge nanocrystals. The ion-beam action is shown to stimulate the nucleation of Ge nanocrystals when being applied after thin Ge layer deposition. Temperature and flux variation was used to optimize the nanocrystal size and array density required for memory device. Kinetic Monte Carlo simulation shows that ion impacts open an additional channel of atom displacement from a nanocrystal onto SiO2 surface. This results both in decrease of the average nanocrystal size and in increase of nanocrystal density.
Fabrication of Nanodots on semiconductor surfaces has immense importance due to their application in memory and optoelectronic devices. Ion irradiation methods display an easy and cost effective route for developing self assembled structures. We have studied the formation of Nano-dots on InP(111) surfaces by 3keV Ar ion irradiation. The distribution of nano Dots on InP surfaces has been investigated by Scanning Probe Microscopy (SPM). A 5 min irradiation of InP surface with Ar ions leads to the appearance of dots on the surface. The density of dots is, however very small. These dots have been obtained at room temperature, in the absence of sample rotation, with an angle of 15 degree between the ion axis and the sample normal. After an irradiation of 10 min a large density of dots appear on InP surface and display a narrow distribution of size and height. The dots at this stage have an average diameter of 25nm and a height of 4nm. With increased irradiation time the average size and the height of the dots increase and their distribution also become broader. This scenario, however, changes after a 40 min irradiation where large rectangular shaped dots of about 100 nm diameters and 40 nm height are observed. Surprisingly, for larger irradiation times a reduction in the size and heights is observed. The studies suggest “Critical Time” tc at t= 40 min such that the dot structures grow with time below tc but diminish in size beyond it.
We have used MeV ion beams to fabricate nanopores in Poly(tetrafluorethylene-co-perfluoro-(propyl vinyl ether)) (PFA) fluoropolymer membranes. We have developed an in house system to produce nanopores. Using MeV ion beams we developed a method to produce pores from nanometers to one-micron diameter. A thin film of the PFA polymer was mounted to cover a window to a gas filled chamber and then exposed to a uniformly scanned MeV ion beam masked to define the exposed area. The gas leak rate through the fabricated pores was monitored by an in situ RGA system both during and after each bombardment to correlate the leakage with the total area of the pores produced. In this project we used MeV light and heavy ions to best define the pore diameter through each hole and the pore entrance and exit dimensions in the membranes.
In order to investigate the interactions of methanol cluster ion beams with solid surfaces, Si substrates and SiO2 films were irradiated at different acceleration voltages. The sputtered depth increased with increase of the acceleration voltage. When the acceleration voltage was 9 kV, the sputtered depths of Si and SiO2 at a dose of 1×1016ions/cm2 were 1497.1 nm and 147.8 nm, respectively. The selectivity between Si and SiO2 surfaces arose from the volatility of the reaction products. Furthermore, the sputtering yield for the Si surface was approximately seven hundreds times larger than that by Ar monomer ion beams. This suggested that chemical sputtering was predominant for the methanol cluster ion irradiation. In addition, the etching and cleaning process by the methanol cluster ion irradiation was performed on the Si surfaces contaminated with a small amount of metal particles such as Au and Al. Thus, methanol cluster ion beams have unique characteristics such as surface etching and cleaning with high sputtering yield and smooth surface.