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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.
The authors examined the effect of tandospirone on tardive dyskinesia (TD) and parkinsonian symptoms in an open study. Tandospirone did not bring about any favourable effect on TD, but it had a good effect on the parkinsonian symptoms.
We present ALMA detection of the [O iii] 88 μm line and 850 μm dust continuum emission in a Y-dropout Lyman break galaxy, MACS0416_Y1. The [O iii] detection confirms the object with a spectroscopic redshift to be z = 8.3118±0.0003. The 850 μm continuum intensity (0.14 mJy) implies a large dust mass on the order of 4×106M⊙. The ultraviolet-to-far infrared spectral energy distribution modeling, where the [O iii] emissivity model is incorporated, suggests the presence of a young (τage ≍ 4 Myr), star-forming (SFR ≍ 60M⊙yr−1), and moderately metal-polluted (Z ≍ 0.2Z⊙) stellar component with a stellar mass of 3 × 108M⊙. An analytic dust mass evolution model with a single episode of star formation does not reproduce the metallicity and dust mass in ≍ 4 Myr, suggesting an underlying evolved stellar component as the origin of the dust mass.
Pneumococcal serotype replacement is an important issue after the introduction of pneumococcal conjugate vaccine (PCV) in children. After the introduction of 13-valent PCV, the incidence of invasive pneumococcal diseases (IPD) caused by Streptococcus pneumoniae serotype 12F (Sp12F) have increased in some countries; however, an outbreak of Sp12F has not reported in the post-13-valent PCV era. We experienced a local outbreak of Sp12F during March through May 2016 in Tsuruoka city, Japan after the introduction of 13-valent PCV in 2013. The IPD patients were two children and seven adults, three of whom died with a rapid disease progress. Although the clear transmission route was not determined, eight of the nine patients (89%) had close contact with children, which suggests that transmitted colonisation of Sp12F among children and adults might be the source of transmission. Continuous monitoring of IPDs, along with the determination of pneumococcal serotypes, is warranted in the post–13-valent PCV era. New IPD control strategies may be needed if this fatal outbreak continues to occur.
One of promising photorechargeable electrode, which has two functions of photovoltaic and electrical energy storage, is a composite film of mesoporous TiO2 and conducting polymer polyaniline. Galvanostatic charge/discharge characteristics of the TiO2-polyaniline composite were examined to reveal how fast the film was charged. The film with a specific capacity 60-120 mAh g–1 was found to be fully charged at high charging rate 20 mA cm–2 which is comparable to high performance solar cells. Such high charging rate was achieved by the compact polyaniline layer covering the large specific surface area of mesoporous TiO2 film.
A cross-sectional serological survey was conducted during January to August 2001 to determine the seroprevalence of Leptospira serovars in five species of livestock in Thailand and to identify associations between seropositivity and sex, age, species and geographical locations. Sera from 14188 livestock (9288 cattle, 1376 buffaloes, 1898 pigs, 1110 sheep, 516 goats) from 36 provinces were tested for antibodies against 24 Leptospira serovars with the microscopic agglutination test (MAT) for which the criterion for a positive result was set at a titre of ⩾1:50. A total of 1635 [11·5%, 95% confidence interval (CI) 11·0–12·0] animals were seropositive and the highest prevalence (30·4%, 95% CI 28·2–32·5) of evidence of infection was recorded in the northeast region followed by the central region (22·2%, 95% CI 20–24·6). Seroprevalences recorded for cattle, buffaloes, pigs, sheep and goats were 9·9% (95% CI 9·3–10·5), 30·5% (95% CI 28·1–32·9), 10·8% (95% CI 9·5–12·3), 4·7% (95% CI 3·6–6·1) and 7·9% (95% CI 5·8–10·5), respectively. Buffaloes were 3·1 (95% CI 2·8–3·4) times more likely than cattle to be seropositive. The most commonly detected antibodies were against L. interrogans serovars Ranarum, Sejroe, and Mini in cattle, Mini, Sejroe, and Bratislava in buffaloes, Ranarum, Pomona, and Bratislava in pigs and Mini, Shermani, and Ranarum in sheep and goats. Seroprevalences in cattle and buffaloes trended upwards with increasing age and there was no difference in the risk of seropositivity between males and females.
Monitor of All-sky X-ray Image (MAXI) on board International Space Station is capable of
observing gamma-ray bursts (GRBs) and sending notices of GRBs or other transient events,
using real time connection to the ground. MAXI observed 32 GRBs or short X-ray transients
as of the end of September 2012. Among them, eleven events were simultaneously detected by
other satellites. The observed rate of the MAXI GRBs is about one event per month. This
rate is comparable to a past observation with larger effective area and larger field of
view. The fact indicates that MAXI has better sensitivity to observe GRBs because of low
background. The distribution of the spectral hardness of MAXI GRBs is similar to the
results of a past instrument, which is sensitive to similar energy range.
We report the case of a patient with extensive pneumocephalus extending into the lateral ventricles from a brain abscess arising from a cholesteatoma-induced defect in the skull base.
A 70-year-old man with cholesteatoma presented with right-sided otalgia, otorrhoea and progressive headaches. Computed tomography showed a tegmental defect (approximately 2 × 2 cm) at the right mastoid antrum. A T1-weighted, gadolinium-enhanced magnetic resonance imaging scan showed pneumocephalus in both lateral ventricles, which was directly connected to the mastoid cavity via a brain abscess and a bone defect in the skull base. Radical mastoidectomy was performed to remove the cholesteatoma. The roof of the mastoid cavity was covered extensively with fascia and a pedicled temporalis muscle flap. One week post-operatively, computed tomography and magnetic resonance imaging showed no pneumocephalus.
Pneumocephalus arising from a cholesteatoma-induced brain abscess and extending into the lateral ventricles is an important entity, with an atypical appearance on computed tomography and magnetic resonance imaging.
It is difficult to get a real scale image of the solar system through lecture. A scale model is a classical and one of good solutions (e.g. Handa et al.2003, Handa et al.2008). Through this model, people living in or visiting to the city can physically understand the scale of the solar system. This scale gives 1 cm for Earth's diameter and 115 m for 1 AU. However, some gadget is required to make it attractive for public citizens.
The current trends in stimulated Brillouin scattering and optical phase conjugation are overviewed. This report is formed by the selected papers presented in the “Fifth International Workshop on stimulated Brillouin scattering and phase conjugation 2010” in Japan. The nonlinear properties of phase conjugation based on stimulated Brillouin scattering and photo-refraction can compensate phase distortions in the high power laser systems, and they will also open up potentially novel laser technologies, e.g., phase stabilization, beam combination, pulse compression, ultrafast pulse shaping, and arbitrary waveform generation.
Epitaxial Fe-Te-Se thin films were deposited by pulsed laser deposition at 250 ~ 600 °C on SrTiO3 (100, STO), MgO (100), LaAlO3 (100, LAO) and CaF2 (100) single crystal substrates. Best superconducting film was grown on CaF2: Tconset = 20.0 K and Tc0 = 16.18 K with Tdep = 300 °C, 45000 pulses, 3 Hz. The critical current density Jc at 4.2 K was 0.41×106A/cm2 at 0 T and 0.23×106 A/cm2 at 9 T. Angular dependence of Jc showed broad c-axis correlated peak when B ≥ 3 T.
For the gate last approach of a high K metal gate scheme used in advanced CMOS technology, various materials were tested as wetting layers to allow Aluminum (Al) gap fill at gate widths of10 to 45 nanometers. In this study, Titanium (Ti) and Cobalt (Co) were investigated as a wetting layer for Al gap fill. It was discovered that Al-Ti and Al-Co alloys were formed during high temperature Al deposition. Alloys were characterized using XRD. Alloy’s impacts on line resistivity and subsequent Al Chemical Mechanical Polish (Al CMP) were also investigated. In addition, a model was established to predict the alloy type and alloy mole% with respect to feature size. The predicted Al mole% by this model correlated very well with 1) line resistivity trend and 2) morphologies. The model also predicted that due to Al lower electro-chemical potential than Ti, Co or its alloys, galvanic corrosion could take place depending on the chemical environment in the Al CMP slurry. Different slurry or cleaning chemical may reduce or increase the risk of galvanic corrosion. The knowledge gained with the help of the model provides clear directions on selection criteria for wetting layers, optimization for deposition processes and Al CMP consumable design to meet the challenges.
We have examined the intrinsic surface physical property of a CrO2 thin film by means of surface sensitive photoemission spectroscopy. Epitaxial thin film of CrO2(100) has been grown on TiO2(100) by a closed chemical vapor deposition method using a Cr8O21 precursor. Low-energy electron diffraction (LEED) observations find that epitaxial growth of rutile-phase CrO2 occurs to the top monolayer of the film. Surface sensitive x-ray photoemission spectroscopy (XPS) measurements show a finite intensity in the region of the Fermi energy. The result evidences that the physical nature of near topmost layer of CrO2 thin film is metallic. Progress of understanding of the surface physical property of CrO2 thin film helps not only perform a reliable photoemission study to understand the physics of ferromagnetic metal in CrO2, but also develop the CrO2-based devices using a half-metallic nature for spintronics applications.
As a novel biomimetic polymer gel, we have been studying polymer gels with an autonomous self-oscillating function, since firstly reported in 1996. For developing the polymer gels, we utilized oscillating chemical reaction, called the Belousov-Zhabotinsky (BZ) reaction, which is recognized as a chemical model for understanding several autonomous phenomena in biological systems. The self-oscillating polymer gel is composed of a poly(N-isopropylacrylamide) network in which the metal catalyst for the BZ reaction is covalently immobilized. Under the coexistence of the reactants, the polymer undergoes spontaneous swelling-deswelling changes (in the case of gel) or cyclic soluble-insoluble changes (in the case of an uncrosslinked polymer) without any on-off switching of external stimuli. Several kinds of functional material systems utilizing self-oscillating polymers and gels such as biomimetic actuators, mass transport surface, etc. are expected. Here recent progress on self-oscillating polymers and gels and the design of functional material systems are summarized.
High reliability, low power consumption and high speed laser diodes are required for optical interconnect. We developed 1060nm VCSELs with InGaAs/GaAs strained quantum wells, oxide-confined and double intra-cavity structures for that purpose. As for the power consumption, low power dissipation of 0.14 mW/Gbps at 10 Gbps operation has been achieved. Clear eye openings up to 20 Gbps were confirmed at a low bias current of 5 mA. In the reliability test, accelerated aging tests were performed up to 5,000 hours at 6 mA in three different temperatures, 70 oC, 90 oC and 120 oC. The total number of the VCSELs was 4,898 pcs (approximately 5,000). No failure was observed. Under the normal operating condition of 40 oC and 6 mA, the total device-hours was 7.75×107 hours assuming Ea = 0.35 eV according to Telcordia GR-468-CORE. The random failure rate of 30 FIT with the confidence level (C.L.) of 90 % and 12 FIT with the C.L. of 60 % were estimated. To estimate the wear-out lifetime and the number of FITs, high stressed aging tests with 170 oC and 6 mA were performed. With the acceleration factor of Ea = 0.7 eV in the wear-out failure, the median lifetime was 3,000 hours which was equivalent to 300 years in 40 oC ambient. The FIT numbers due to the wear-out were estimated as 0.3 FIT for 10 years. Compared with the random failure rate of 30 FIT, the wear-out failure rates are considered to be negligible. In the extremely long term aging test with 90 oC and 6 mA, no wear-out trend has been observed in both threshold current and optical power up to 20,000 hours operation. These results indicate that 1060 nm VCSEL is promising light source used in optical interconnect for high performance computers and data centers.