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In the treatment of psychosis, agitation and aggression in Alzheimer's disease, guidelines emphasise the need to ‘use the lowest possible dose’ of antipsychotic drugs, but provide no information on optimal dosing.
This analysis investigated the pharmacokinetic profiles of risperidone and 9-hydroxy (OH)-risperidone, and how these related to treatment-emergent extrapyramidal side-effects (EPS), using data from The Clinical Antipsychotic Trials of Intervention Effectiveness in Alzheimer's Disease study (Clinicaltrials.gov identifier: NCT00015548).
A statistical model, which described the concentration–time course of risperidone and 9-OH-risperidone, was used to predict peak, trough and average concentrations of risperidone, 9-OH-risperidone and ‘active moiety’ (combined concentrations) (n = 108 participants). Logistic regression was used to investigate the associations of pharmacokinetic biomarkers with EPS. Model-based predictions were used to simulate the dose adjustments needed to avoid EPS.
The model showed an age-related reduction in risperidone clearance (P < 0.0001), reduced renal elimination of 9-OH-risperidone (elimination half-life 27 h), and slower active moiety clearance in 22% of patients, (concentration-to-dose ratio: 20.2 (s.d. = 7.2) v. 7.6 (s.d. = 4.9) ng/mL per mg/day, Mann–Whitney U-test, P < 0.0001). Higher trough 9-OH-risperidone and active moiety concentrations (P < 0.0001) and lower Mini-Mental State Examination (MMSE) scores (P < 0.0001), were associated with EPS. Model-based predictions suggest the optimum dose ranged from 0.25 mg/day (85 years, MMSE of 5), to 1 mg/day (75 years, MMSE of 15), with alternate day dosing required for those with slower drug clearance.
Our findings argue for age- and MMSE-related dose adjustments and suggest that a single measure of the concentration-to-dose ratio could be used to identify those with slower drug clearance.
Health-related quality of life (HRQOL) is significantly affected in individuals with schizophrenia or bipolar I disorder (BD-I). The current study investigated whether symptomatic remission and resilience might differently impact HRQOL in these patients.
Fifty-two patients with schizophrenia and 60 patients suffering from BD-I from outpatient mental health services as well as 77 healthy control subjects from the general community were included into a cross-sectional study. HRQOL and resilience were assessed using the WHOQOL-BREF and the Resilience Scale. In patients, psychopathology was quantified by the Positive and Negative Syndrome Scale or the Montgomery Asberg Depression Rating Scale and the Young Mania Rating Scale, respectively.
Notably, both patient groups showed lower HRQOL and resilience compared to control subjects, non-remitted patients indicated lower HRQOL than remitted ones. The effect of remission on HRQOL was significantly larger in patients with BD-I than in those with schizophrenia but did not explain the difference in HRQOL between groups. Resilience predicted HRQOL in all three groups. When accounting for the effect of resilience among remitted patients, only the difference in HRQOL between schizophrenia patients and control subjects was significant.
These findings demonstrate the impact of symptomatic remission and resilience on HRQOL of both patients suffering from schizophrenia and BD-I and indicate that these factors are especially relevant for HRQOL of patients with BD-I.
We have developed a group of school-based universal prevention programs for children's health and adjustment. The programs are characterized by new theories such as the somatic-marker hypothesis and enjoyable methods that utilize animated stories and games. This study adopted one of the programs for the development of self-confidence.
The aim was to examine the effectiveness of the program. In addition to the direct purposes of the program, children's adjustments at school and homeroom class were evaluated as extended effects.
Participants were third grade children in six public elementary schools in Japan. The final sample included 442 children (219 boys and 223 girls). The program was implemented weekly in one regular 45-minute class over 8 weeks. Participants completed a battery of three questionnaires three times, 1 month before the start of the program (T1), 1 week before the start of the program (T2), and during 1 week after the last class of the program (T3).
Results showed that all of the main endpoints of the program significantly improved in the intervention condition (i.e., changes from T2 to T3), compared to the control condition (i.e., changes from T1 to T2). Moreover, children's adjustment at school and homeroom class increased in the intervention condition, compared to the control condition. However, implicit affect was unchanged.
This study suggests that the program is effective for enhancing self-confidence, along with adjustments at school and in class. Future research that examines the sustainability of the effectiveness of the program is planned.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Dog treats might be contaminated with Salmonella. In Canada and the USA, outbreaks of human salmonellosis related to exposure to animal-derived dog treats were reported. Consequently, surveillance data on Salmonella contamination of dog treats have been gathered in many countries, but not in Japan. In the current study, we investigated whether dog treats in Japan were contaminated with Salmonella. Overall, 303 dog treats (of which 255 were domestically produced) were randomly collected and the presence of Salmonella investigated. Seven samples were positive for Salmonella enterica subsp. enterica. Among these isolates, three were identified as serovar 4,5,12:i:–; two were serovar Rissen; and two were serovar Thompson. All serovar 4,5,12:i:– and Thompson isolates were resistant to one or more drugs. Two serovar Rissen isolates were fully susceptible to all tested antimicrobial agents. All Salmonella isolates were susceptible to cefotaxime, ciprofloxacin and nalidixic acid. The gene blaTEM was detected in two serovar 4,5,12:i:– isolates. The blaCTX−M and blaCMY genes were not detected in any isolates. This study demonstrated that dog treats in Japan could constitute a potential source of dog and human Salmonella infections, including multidrug-resistant Salmonella isolates.
The present study investigated the dry matter yield (DMY) and arbuscular mycorrhizal (AM) colonization (internal hyphae, arbuscules, and vesicles) of two genotypes of zoysia grass (Zoysia japonica strain Aso and cv. Asagake) at three rates (10, 20 and 40 g N/m2/year) of application of digested slurry (DS) or mineral fertilizer. Soil chemical properties (available phosphorus concentration, pH and electrical conductivity (EC)) were also measured as factors associated with AM colonization. The fertilizer type (DS v. mineral fertilizer) had an effect on DMY depending on the plant genotypes but had little or no effect on AM colonization, and soil chemical properties, indicating that DS can be used as a substitute for mineral fertilizer; however, it is necessary to apply it taking into account the ratio of inorganic nitrogen (N). However, heavy DS application decreased colonization by internal hyphae. Furthermore, even at the lowest rate, the continuous application of DS decreased colonization by arbuscules and vesicles in both genotypes, which were associated with decreasing soil pH and increasing EC. The results suggest that zoysia grass should be fertilized with DS at a rate of <10 g N/m2/year in order to achieve a continuous association with AM fungi, although this range of N application is sub-optimal for zoysia grass production.
Water-quality markets that allow point-nonpoint trades assume that nonpoint best management practices (BMPs) achieve the targeted reductions as soon as they are implemented. However, changes in water quality in response to BMPs occur over time—from a few months to decades. We simulate emission allocations using static and dynamic-optimization models to determine whether a simple static allocation can produce results comparable economically and environmentally to complex multi-period designs for nitrogen emissions to Chesapeake Bay. We find that static rules provide relatively large cost savings compared to dynamic rules but result in a delay in achievement of water-quality targets.
In the previous work, it is reported that the Spin-Seebeck effect (SSE), which refer to the generation of a spin current from a temperature gradient, can be enhanced by Fe interface treatment. Here, we investigated the Fe thickness (dFe) dependency of spin-Seebeck voltage (VSSE) and mixing conductance (gr) in Pt/Fe/Bi:YIG/SGGG system. As a result, magnitude of VSSE had a peak at dFe ≓ 1 ML (monolayer , ≓ 0.3 mm), and also increase of gr was saturated at this point. It suggests that VSSE increase with increasing gr when dFe is smaller than 1.0 ML. For the case in which dFe is larger than 1.0ML, however, VSSE decreases due to a spin current decay in Fe layer with a constant gr. These experimental results are consistent with previous theoretical works.
In order to evaluate the role of the RAD51 G135C genetic polymorphism on the risk of gastric cancer induced by Helicobacter pylori infection, we determined allele frequency and genotype distribution of this polymorphism in Bhutan – a population documented with high prevalence of gastric cancer and extremely high prevalence of H. pylori infection. The status of RAD51 G135C was examined by restriction fragment length polymorphism analysis of PCR amplified fragments and sequencing. Histological scores were evaluated according to the updated Sydney system. G135C carriers showed significantly higher scores for intestinal metaplasia in the antrum than G135G carriers [mean (median) 0·33 (0) vs. 0·08 (0), P = 0·008]. Higher scores for intestinal metaplasia of G135C carriers compared to those of G135G carriers were also observed in H. pylori-positive patients [0·3 (0) vs. 0·1 (0), P = 0·002] and H. pylori-positive patients with gastritis [0·4 (0) vs. 0·1 (0), P = 0·002] but were not found in H. pylori-negative patients. Our findings revealed that a combination of H. pylori infection and RAD51 G135C genotype of the host showed an increasing score for intestinal metaplasia. Therefore, RAD51 G135C might be the important predictor for gastric cancer of H. pylori-infected patients.
In this paper, we discuss the characteristics of the InGaP/GaAs heterojunction phototransistors (HPTs) before and after the electrical stress at room temperature and assess the effectiveness of the emitter-ledge passivation. Although an electrical stress given to the phototransistors by keeping a collector current density of 37 A/cm2 for 1 hour at room temperature was too small to affect the room-temperature common-emitter current gain and photocurrent of both HPTs with and without the emitter-ledge passivation, they showed a significant decrease at 420 K due to the room-temperature electrical stress. Nevertheless, the room-temperature common-emitter current gain and photocurrent of the HPT with the emitter-ledge passivation were still higher than those of the HPT without the emitter-ledge passivation. The effectiveness of the emitter-ledge passivation against the electrical stress was more significant than that on the current gain in the dark. In addition to the electrical stress experiment, for a potential application of the InGaP/GaAs HPTs in space, we will irradiate the HPTs with 1-MeV electrons at the Japan Atomic Energy Agency. Both current gain and photocurrent decreased significantly after the electron irradiation. In contrast to the electrical stress, the damage due to the high-energy electron irradiation is a bulk-related phenomenon, and the emitter-ledge passivation does not seem to suppress the degradation.
We propose some chemical processing procedures for fabricating thin films in Hf-Zr-O system by a unique film deposition technique using supercritical carbon dioxide fluid (scCO2), i.e., supercritical fluid deposition (SCFD), which would be an prospective approach for fabricating metal-oxide films for integrated circuits because of its unique characteristics; e.g., extraction ability, transportation capability, and reaction equilibrium etc., are quite favorable for the film deposition from metal-complex precursors.
The SCFD was accomplished in a closed batch-type reaction apparatus, consisting of two steps; (a) material deposition and (b) subsequent post-treatment under scCO2 atmosphere. Thin films of amorphous Hf-Zr-O were deposited on platinized silicon [(111)Pt/TiO2/(100)Si] substrates by SCFD using metal-complex precursors M[OCH(CH3)]2(C9H11O2)2 (M = Hf or Zr) at reaction temperature of 100 – 300 °C, significantly lower than those for MOCVD. These films possessed dielectric permittivity’s of approximately 20 – 25, comparable to those from conventional processes, although they still included residue of organic species that prompt the dielectric degradation under lower-frequency bias application.
The prevalence of Helicobacter pylori infection in Indonesia is controversial. We examined the H. pylori infection rate in 78 patients in a hospital in Surabaya using five different tests, including culture, histology, immunohistochemistry, rapid urease test, and urine antibody test. Furthermore, we analysed virulence factors in H. pylori strains from Indonesia. The H. pylori infection rate was only 11·5% in all patients studied, and 2·3% of Javanese patients and 18·0% of Chinese patients were infected (P = 0·01). Although severe gastritis was not observed, activity and inflammation were significantly higher in patients positive for H. pylori than in patients negative for H. pylori. Among genotypes identified from five isolated strains, cagA was found in four; two were vacA s1m1. All cagA-positive strains were oipA ‘on’ and iceA1 positive. We confirmed both a low H. pylori infection rate and a low prevalence of precancerous lesions in dyspeptic patients in a Surabaya hospital, which may contribute to the low incidence of gastric cancer in Indonesia.
We investigated electronic structure of one-dimensional biradical molecular chain which is constructed by exploiting the covalency between organic molecules of a diphenyl derivative of s-indacenodiphenalene (Ph2-IDPL). To control the crystallinity, we used gas deposition method. Ultraviolet photoelectron spectroscopy (UPS) revealed developed band structure with wide dispersion of the one-dimensional biradical molecular chain.
A discharge-emission spectrometer and a cavity ringdown spectrometer have been developed to aid in the solution to the diffuse interstellar band (DIB) problem. A hollow cathode was used to generate molecular ions in a discharge because it has been suggested that molecular ions are probable DIB candidates. The discharge was produced by a pulsed voltage of 1300–1500 V. A wide wavelength range of optical emission from the discharge was examined by a HORIBA Jobin Yvon iHR320 monochromator. The dispersed discharge emission was detected by a photomultiplier and was recorded via a lock-in amplifier. The 2B3u–X2B2g electronic transition of the butatriene cation H2CCCCH2+ was observed in the discharge emission of 2-butyne H3CCCCH3. The frequency of the electronic transition was measured to be 20381 cm−1, and a comparison study was made with known DIB spectra.
The resolution of the discharge-emission spectrometer is insufficient to make precise comparisons between laboratory frequencies and astronomically observed DIB spectra. We therefore developed the cavity ringdown spectrometer using the same hollow cathode. The high sensitivity of this spectrometer was confirmed by the observation of the forbidden band of O2.
Solar flares are thought to be caused by reconnection of magnetic fields and their associated electric currents in the solar corona. The currents have to be there to provide available energy over and above the current-free minimum energy state, but what generates them has been little discussed. This paper investigates the idea that twisting motions in the turbulent convection zone below may provide a natural source for the currents and explain some of their properties. The twists generate upward-propagating Alfvén waves with a Poynting flux of the right order of magnitude to power a flare. Depending on the depth it takes place, the twisting event that initiates a particular flare may occur hours, days or even months before the flare itself.
In this paper, we give arguments that there are two types of coronal mass ejection (CME).The first type of CME discussed here is the ‘loop-type’, whose occurrence is related to an arcade flare somewhere between the footpoints. It was found that there were pre-event magnetic connections between the flare location and the locations of the footpoints of a CME of this type, and that these connections disappeared after the event. This suggests that the footpoints of loop-type CMEs are special prescribed points, and this was verified by the observation that the footpoints do not move in this type of CME.
The other type of CME is the ‘bubble-type’, which is associated with the flare blast from explosive flares. We confirmed the association of this type of CME with the so-called EIT (Extreme Ultra-violet Imaging Telescope) waves, but the velocity of expansion of the bubble is twice or more greater than that of the EIT waves depending on events. Although EIT waves were widely considered to be Moreton waves viewed by SoHO/EIT in the solar activity minimum period, recent simultaneous observations of both have revealed that the EIT wave is something different from the Moreton wave, and propagates separately with a velocity less than half that of a Moreton wave.We therefore propose a new overall picture: the bubble-type CMEs are the flare-produced MHD blast waves themselves, whose skirt is identified as a Moreton wave. EIT waves may be interpreted as follows: the slow-mode gas motions from the source cause secondary longwavelength fast-mode waves which are trapped in the “waveguide” in the low corona. The secondary long-wavelength wave in the fast-mode, which is trapped in the low corona, has a slower propagation velocity due to the nature of the waves trapped in a “waveguide”. This trapped wave induces slow-mode motions of the gas through a mode-coupling process in the high chromosphere, where the propagation velocities of the fastand slow-mode waves match.
Three-dimensional MHD simulations for these two types of CME are in progress, and are previewed in this paper.
Radiocarbon analysis of the carbonaceous aerosol allows an apportionment of fossil and non-fossil sources of airborne particulate matter (PM). A chemical separation of total carbon (TC) into its subtractions organic carbon (OC) and elemental carbon (EC) refines this powerful technique, as OC and EC originate from different sources and undergo different processes in the atmosphere. Although 14C analysis of TC, EC, and OC has recently gained increasing attention, interlaboratory quality assurance measures have largely been missing, especially for the isolation of EC and OC. In this work, we present results from an intercomparison of 9 laboratories for 14C analysis of carbonaceous aerosol samples on quartz fiber filters. Two ambient PM samples and 1 reference material (RM 8785) were provided with representative filter blanks. All laboratories performed 14C determinations of TC and a subset of isolated EC and OC for isotopic measurement. In general, 14C measurements of TC and OC agreed acceptably well between the laboratories, i.e. for TC within 0.015–0.025 F14C for the ambient filters and within 0.041 F14C for RM 8785. Due to inhomogeneous filter loading, RM 8785 demonstrated only limited applicability as a reference material for 14C analysis of carbonaceous aerosols. 14C analysis of EC revealed a large deviation between the laboratories of 28–79% as a consequence of different separation techniques. This result indicates a need for further discussion on optimal methods of EC isolation for 14C analysis and a second stage of this intercomparison.
We observed significant reduction of thermal conductivity in semiconducting composite films of Si and molybdenum (Mo)-silicide nanocrystals (NCs). These films were synthesized by phase separation due to annealing at 700 -1000°C from sputtered amorphous Mo–Si alloy. Transmission electron microscope images showed that the NCs were grown to diameters of∼10 nm in the films by annealing at 800°C. Raman scattering spectra showed lower shift of peak positions of Si transverse optical (TO) phonon due to the confinement effect and the tensile stress. The electrical resistivity of the films was 0.17- 9 Ωm at room temperature and showed a semiconducting temperature dependence at 20-400 K. Thermal conductivity of the film was reduced to 4.4 W/mK by enhancement of phonon scattering at NC interfaces, suggesting that the composite film is promising as a high-efficiency Si-based thermoelectric material.
We have developed our original DFT (density-functional theory) calculation code “RSDFT” using real-space schemes. The code is FFT-free, leading to high-performance computing in massively-parallel supercomputers. The code allows us to deal with systems including huge numbers of atoms from first-principles. We have applied our schemes to clarify atomic and electronic structures of two relevant nano-scale systems: twisted bilayer graphene and silicene on Ag substrate.
We synthesized amorphous semiconductor films composed of Mo-encapsulating Si clusters (MoSin : n∼10) on solid substrates. The MoSi10 films had Si networks similar to hydrogenated amorphous Si and an optical gap of 1.5 eV. Electron spin resonance signals were not observed in the films indicating that dangling bonds of Si were terminated by Mo atoms. We fabricated thin-film-transistors using the MoSi10 film as a channel material. The electric field effect of the film was clearly observed. This suggests that the density of mid-gap states in the film is low enough for the field effect to occur.
We have demonstrated the dimerization of single-crystalline Ag nanocubes with reasonably high yields through stepwise integration by following three steps: the preparation of a single layer of densely packed Ag nanocubes on a substrate by modified convective assembly, the selective functionalization of the upper face of the Ag nanocubes with a hydrophobic DT-SAM using the μCP approach, and the spontaneous dimerization in a mixture of ethanol and water driven by enhanced anisotropic hydrophobic interparticle interactions. Face-selective functionalization using hydrophobic DT-SAM gave the nanocubes directionality with respect to their anisotropic interparticle interactions under an external hydrophilic environment. We conclude that the driving force that reduced the surface area of the hydrophobic faces is sufficient large to form an ordered assembly of nanosized building blocks in an aqueous solution. Both experimental and theoretical studies revealed that the 50-nm-diameter Ag nanocubes dimers with a ca. 3.3 nm gap at their junction exhibited two plasmon peaks centered at 446 nm and 600 nm, which contributed to transverse and longitudinal plasmon resonances, respectively. Elctromagnetic calculations based on the FDTD method clearly showed that a greater enhancement of the local field occurred, with an average amplitude of the electric field of 1.0×1015, at the fractal space between the aggregated Ag nanocubes when the dimer was illuminated under longitudinally polarized light.