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Background: Chronic intravenous immunoglobulin (IVIg) is used to treat refractory myasthenia gravis (MG). This subgroup analysis evaluated response to eculizumab in patients receiving chronic IVIg before entry to REGAIN, a phase 3, randomized, double-blind, placebo-controlled study of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalized MG. Methods: IVIg was only permitted during REGAIN as rescue therapy; previously treated patients underwent a 4-week washout before randomization. Patients included in this analysis had received chronic IVIg ≥4 times in 1 year, with ≥1 dose within 6 months before REGAIN entry. Exacerbations and MG status changes were assessed. Results: Eighteen patients were evaluated; four experienced exacerbations (eculizumab-treated, 1/9; placebo-treated, 3/9). Clinically relevant improvements were larger with eculizumab than placebo, respectively (mean change, standard deviation [SD]: MG Activities of Daily Living score [MG-ADL], -5.3 [4.0] vs -2.1 [2.8]; Quantitative MG score [QMG], -4.1 [6.1] vs -1.3 [3.5]). More patients receiving eculizumab (7/9) had clinically meaningful responses (MG-ADL ≥3 and/or QMG ≥5 points) than those receiving placebo (3/9). Eculizumab safety was consistent with previous reports. Interim data from the open-label extension of REGAIN will be presented. Conclusions: In patients previously receiving chronic IVIg, eculizumab showed a trend toward meaningful clinical improvements and fewer exacerbations compared with placebo. (NCT01997229, NCT02301624).
Background: Patients with anti-acetylcholine receptor antibody-positive (AChR+) generalized myasthenia gravis (MG) unresponsive to conventional treatment experience greater disease burden than responsive patients. This is partly due to exacerbations, which may result in significant healthcare resource utilization. Eculizumab is well tolerated and gives clinically meaningful benefits in these patients. We evaluated the effect of long-term eculizumab treatment on exacerbations, hospitalizations and rescue therapy in the REGAIN study and its open-label extension. Methods: Exacerbations were defined as clinical worsening/deterioration, MG crises or rescue therapy usage; pre-study exacerbations/hospitalizations were defined from patient records. Event rates adjusted for patient-years were calculated for all patients in the pre-study year, patients receiving placebo during REGAIN, and patients receiving eculizumab during REGAIN and its open-label extension (median exposure, 27.5 months [range, 22 days–42.8 months]); rates were compared using a Poisson regression model. Results: Eculizumab treatment reduced exacerbations by 65% (p=0.0057), hospitalizations by 71% (p=0.0316) and rescue therapy use by 66% (p=0.0072) versus placebo. Eculizumab treatment reduced exacerbations by 74% and hospitalizations by 83% (both p<0.0001) versus the pre-study year. Conclusions: Long-term eculizumab treatment reduces disease burden and healthcare resource utilization, demonstrating continuing improvements in clinical endpoints that lead to additional meaningful outcomes for patients with AChR+ generalized MG. (NCT01997229, NCT02301624).
An X-ray transmission method has been developed to obtain a continuous profile of bulk densities of ice cores. Intensities of X-rays transmitted through an ice-core sample were continuously measured by an X-ray detector during translation of the sample across the X-ray beam. A thick section of an ice core with a constant thickness was prepared by band-sawing followed by microtome planing. The X-ray intensity profile obtained was converted to a density profile using a calibration curve for X-ray absorption vs ice thickness. Using this method, spatial resolution of the density profile was down to 1 mm. X-ray radiographs were also taken on a two-dimensional detector imaging plate, in order to observe layer structures of the ice cores.
The method was applied to Dome Fuji (Antarctica) ice cores from the surface to 110 m depth. From the density profile obtained we calculated the power spectrum of the density variation by the discrete Fourier transform, and obtained several peaks at different frequencies. The center period in the spectrum was close to the annual accumulation thickness at the drill site.
A deep ice core drilled to 2503 m depth at Dome Fuji, Antarctica, contains 25 visible tephra layers during the past 340 ka. The thickness of tephra layers is in the range 1-24 mm. The thickness and duration at deposition, determined by a simple ice-flow model, suggests that a violent volcanic eruption caused ash to fall onto the Antarctic ice sheet for ~5 years and to form a ~100 mm thick tephra layer at 117 ka BE Two tephra layers at depths of 573 and 2202 m probably originated from volcanoes in the South Sandwich Islands, Southern Ocean, given the size of tephra shards, >20μm in diameter, and their major chemical composition. Only eight of the 25 tephra layers can also be recognized in the Vostok (Antarctica) ice core, but all correspond to the Vostok tephras if we consider cloudy bands to be volcanic.
The Japanese Antarctic Research Expedition (JARE) has set up automatic weather stations at six sites on a 1000 km long traverse route between Syowa station (21 ma.s.l..) and Dome Fuji station (3810 ma.s.l.) since 1993. Large temperature rises in winter were observed several times in this area. There were two patterns of time delay of the temperature rises. One was that the temperature rise at Mizuho station preceded that at other stations, and the other was that the temperature rise at Dome Fuji station preceded the others. The former occurred when a disturbance came from the coast between east Enderby Land and the Amery Ice Shelf and strong winds destroyed the stable inversion layer. The latter occurred when the low-pressure center was near the coast of west Wilkes Land. in this case, temperature rise was caused by adveclion of warm air. The atmospheric pressure at Dome Fuji station and Relay Point oscillated with a period of 0.5 year and amplitude of about 15hPa. The pressure was higher in July and December, and was accompanied by a temperature rise. Fluctuations of hourly air temperature at Dome Fuji station were approximately twice as large as fluctuations at the other sites. The lapse rale of the annual mean temperature increased with elevation, while the monthly lapse rate was largest in April.
Documenting past changes in the East Antarctic surface mass balance is important to improve ice core chronologies and to constrain the ice-sheet contribution to global mean sea-level change. Here we reconstruct past changes in the ratio of surface mass balance (SMB ratio) between the EPICA Dome C (EDC) and Dome Fuji (DF) East Antarctica ice core sites, based on a precise volcanic synchronization of the two ice cores and on corrections for the vertical thinning of layers. During the past 216 000 a, this SMB ratio, denoted SMBEDC/SMBDF, varied between 0.7 and 1.1, being small during cold periods and large during warm periods. Our results therefore reveal larger amplitudes of changes in SMB at EDC compared with DF, consistent with previous results showing larger amplitudes of changes in water stable isotopes and estimated surface temperature at EDC compared with DF. Within the last glacial inception (Marine Isotope Stages, MIS-5c and MIS-5d), the SMB ratio deviates by up to 0.2 from what is expected based on differences in water stable isotope records. Moreover, the SMB ratio is constant throughout the late parts of the current and last interglacial periods, despite contrasting isotopic trends.
The aim of this study was to evaluate the dosimetric aspects of whole brain radiotherapy (WBRT) using an irregular surface compensator (ISC) in contrast to conventional radiotherapy techniques.
Treatment plans were devised for 20 patients. The Eclipse treatment planning system (Varian Medical Systems) was used for dose calculation. For the ISC, a fluence editor application was used to extend the range of optimal fluence. The treatment plan with the ISC was compared with the conventional technique in terms of doses in the planning target volume (PTV), dose homogeneity index (DHI), three-dimensional (3D) maximum dose, eye and lens doses and monitor unit (MU) counts required for treatment.
Compared with conventional WBRT, the ISC significantly reduced the DHI, 3D maximum dose and volumes receiving 105% of the prescription dose, in addition to reducing both eye and lens doses (p<0·05 for all comparisons). In contrast, MU counts were higher for the ISC technique than for conventional WBRT (828 versus 328, p<0·01).
The ISC technique for WBRT considerably improved the dose homogeneity in the PTV. As patients who receive WBRT have improved survival, the long-term side effects of radiotherapy are highly important.
We report a recent result of the FUGIN project, a Galactic plane CO survey using the Nobeyama 45-m Telescope and the FOREST receiver. In the third galactic quadrant, 42 square degrees are observed and 4752 molecular clouds are detected. Among them, 12 clouds are located at R (distance from the Galactic center) > 16 kpc. Molecular clouds at R < 16 kpc trace the Local, Perseus, and Outer arms.
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.
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.
In order to realize the magnetic refrigeration system, it is necessary to develop a 100 W class refrigerator with COP > 7.5. This requires us to find new magnetic refrigerant materials, of which cooling capacity is 2.5 times higher than that of Gd. In this paper, first we discuss the cooling capacity of magnetic refrigerant materials to achieve COP = 7.5. Then, we compare the experimental results of MnAsSb, MnFe(PGe) and La(FeCoSi)13 compounds with the calculated cooling capacity. It is suggested that a composite layer material of MnFe(PGe) would show excellent cooling capacity in the temperature span of 20 K.
An advanced FSG film of k=3.4 was developed, which exhibited excellent resistance for moisture absorption. Physical and chemical properties of this advanced FSG film were compared by typical FSG films deposited in both high density plasma (HDP) and PE-CVD reactors, for the same k value.
The advanced FSG film appears to be superior to the HDP-FSG film by a wide margin in the following tests. The moisture absorption rate by TDS (after 4 days of air exposure) is about 5 times lower, the hardness was 1.8 times more, and the hygroscopicity (after 1 hr. boiling) was 2.6 times lower.
We conclude that these differences are mainly due to the unique film structure of the advanced FSG film.
Hydrogenated amorphous silicon germanium (a—SiGe:H) films were deposited by photo—chemical vapor deposition (Photo—CVD) of SiH4 and GeH4 with mercury sensitizer. Their band gap was controlled from 0.9 eV to 1.9 eV by changing the gas ratio of SiH4 and GeH4. High quality opto—electrical properties have been obtained for thea—SiGe:H films by Photo—CVD. Hydrogen termination and microstructure of a-SiGe:H were investigated by infrared absorption and transmission electron microscopy. Ana—Si:H solar cell and an a—Si:H/a—SiGe:H stacked solar cell were made, each of which has conversion efficiency 5.3% and 5.1%, respectively.
Using alloys whose initial microstructures are composed of Ni3Si(L12), Ni3Si(L12)+Ni3Ti(D024) and Ni3Si(L12)+Ni3Nb(D0a), aging phenomenon and the associated high-temperature tensile property were investigated. It was shown by micro hardness measurement that age hardening behavior due to the precipitation of the Ni3Ti(D024) phase occurs in all alloys at temperatures above 823K. It was however shown by tensile test that the precipitated Ni3Ti(D024) phase is not so much effective in improving the mechanical properties of alloys whose initial microstructures are composed of Ni3Si(L12)+Ni3Nb(D0a) or Ni3Si(L12)+Ni3Ti (D024). In alloys whose initial microstructures are composed of Ni3Si(L12)+Ni3Nb (D0a), a good combination of tensile strength and tensile elongation was found over a wide of test temperature whether or not they contain the precipitated Ni3Ti(D024) phase.
The electron irradiation induced crystalline to amorphous (C-A) transition was investigated in the Cu-Ti alloy system. As the transition is found to be dose dependent, the energy accumulated during the irradiation must make the crystal lattice unstable with respect to the amorphous state. In this paper, two possibilities for this energy accumulation, chemical disordering and the accumulation of point defects, is examined using the intermetallic compound CuTi2. Also, the effect of deviations from stoichiometry on the C-A transition is investigated in the compound CuTi. The Bragg-Williams long-rang order parameter, S, was found to decrease with electron dose. The rate of this decrease decreased with increasing temperature. At a critical temperature, the maximum obtainable degree of chemical disordering critically decreased. This critical temperature coincided with the critical temperature for the C-A transition, favoring the chemical disordering as the primary driving force. In CuTi, the C-A transition was hindered when there existed a Cu-rich deviation from stoichiometry.
Deposition technique of a-SiGe:H and its application to a stacked solar sell were investigated. Properties of a-SiGe:H were improved by a glow discharge method with a negatively biased substrate, and a mercury sensitized photo CVD under lower pressure. An a-SiGe:H single junction solar cell was improved by slight boron doping to an i layer and insertion of a buffer layer into a p/i interface. A conversion efficiency of more than 10 % was obtained by a triple stacked solar cell on a alass substrate.