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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).
Background: The physician-reported Quantitative Myasthenia Gravis (QMG) test was a key efficacy measure in REGAIN, a 26-week, phase 3, placebo-controlled study of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalized MG. Ocular and generalized weakness have shown variable responses to therapies including prednisone and intravenous immunoglobulin/plasma exchange. Using the patient-reported MG Activities of Daily Living (MG-ADL) scale during REGAIN, eculizumab showed a consistent trend toward rapid and sustained improvement across bulbar, respiratory, limb and ocular domains. We analyzed the effect of eculizumab on bulbar, respiratory, gross motor and ocular domains during REGAIN, using the QMG test. Methods: QMG domain score changes to REGAIN week 26 were determined for patients with abnormal baseline scores. Repeated-measures analyses were performed for bulbar (swallowing/speech), respiratory (forced vital capacity), gross motor (limb/axial motor items) and ocular (ocular/facial muscles) domains. Results: Eculizumab-treated patients showed improvements in all four QMG domain scores to week 26. Rapid, sustained improvements were demonstrated across all domains, with a trend toward significant differences between eculizumab and placebo (bulbar, p=0.0628; respiratory, p=0.0682; gross motor, p=0.0114; ocular, p=0.0017). The eculizumab safety profile was consistent with previous reports. Conclusions: Eculizumab demonstrated a consistent response across all QMG muscle domains. This aligns with previously reported MG-ADL findings with eculizumab. (NCT01997229).
The objective of this study was to investigate the relationship between the thickness of N radical irradiated InN template with crystallographic quality and electrical properties of InN film grown with the previously proposed method, in situ surface modification by radical beam irradiation. In this study, three InN samples were grown with this method on different thickness of irradiated templates. The crystallographic quality of InN films was analyzed by X-ray diffraction and the electrical properties were studied by Hall effect measurement. InN grown on 100 nm thick irradiated template shows lower full-width at half-maximum of X-ray rocking curves and lower carrier concentration compared to InN grown on 200 nm and 450 nm thick irradiated templates. Transmission electron microscopy revealed that threading dislocation density in the InN film decreased by an order of magnitude to ∼4.6×109cm-2. These results suggest that this method is possible for reduction of threading dislocation density in InN and the thickness of irradiated template should be minimized for higher crystallographic quality and electrical properties of the entire InN film.
We present a comprehensive review of the status and changes in glacier length (since the 1850s), area and mass (since the 1960s) along the Himalayan-Karakoram (HK) region and their climate-change context. A quantitative reliability classification of the field-based mass-balance series is developed. Glaciological mass balances agree better with remotely sensed balances when we make an objective, systematic exclusion of likely flawed mass-balance series. The Himalayan mean glaciological mass budget was similar to the global average until 2000, and likely less negative after 2000. Mass wastage in the Himalaya resulted in increasing debris cover, the growth of glacial lakes and possibly decreasing ice velocities. Geodetic measurements indicate nearly balanced mass budgets for Karakoram glaciers since the 1970s, consistent with the unchanged extent of supraglacial debris-cover. Himalayan glaciers seem to be sensitive to precipitation partly through the albedo feedback on the short-wave radiation balance. Melt contributions from HK glaciers should increase until 2050 and then decrease, though a wide range of present-day area and volume estimates propagates large uncertainties in the future runoff. This review reflects an increasing understanding of HK glaciers and highlights the remaining challenges.
Pre-weaning mortality (11.9% as estimated by M.L.C., 2000) continues to be a major economic and welfare problem in commercial indoor pig production. The main causes of mortality are crushing by the sow and low viability/starvation. Both of these causes of death may be as a result of increasing sow body size and smaller piglet body size as a result of intense genetic selection for increasing litter size. However it is unclear whether sows are consistent across parities in their level of pre-weaning mortality. Therefore this study aimed to examine individual differences in piglet mortality of sows throughout their reproductive life, investigate factors likely to affect piglet mortality, and to assess whether piglet mortality may be a candidate trait for genetic selection.
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.
Structural analyses of ice collected from the bare ice surface in the region of the Sør-Rondane Mountains were carried out. Crystal-orientation fabrics and the disposition of surface cracks were investigated to determine the stress/strain configuration in the ice sheet near the mountains. Single-maximum fabric patterns with the axis of the maximum roughly perpendicular to the flow line on the horizontal plane were observed. It was deduced from the observations that the ice exhibits a fabric pattern indicating that the ice sheet is subjected to vertical shear strain between the ice flow and the nunataks.
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.
It has been indicated that low-luminosity active galactic nuclei (LLAGNs) are accelerating high-energy cosmic-ray (CR) protons in their radiatively inefficient accretion flows (RIAFs). If this is the case, Sagittarius A* (Sgr A*) should also be generating CR protons, because Sgr A* is a LLAGN. Based on this scenario, we calculate a production rate of CR protons in Sgr A* and their diffusion in the central molecular zone (CMZ) around Sgr A*. The CR protons diffusing in the CMZ create gamma-rays through pp interaction. We show that the gamma-ray luminosity and spectrum are consistent with observations if Sgr A* was active in the past.
Superwind galaxies at high-redshift are now considered to be the important clue for understanding the interaction and evolution of both galaxies and intergalactic matter. In order to improve our knowledge of superwind galaxies at high redshift, a large sample of superwind candidates is needed. During the course of our new search for Lyman alpha emitters at z = 5.7, we have found a candidate superwind galaxy, LAE J1044-0130, at z = 5.69. The emission-line profile of this object is asymmetric, showing excess red-wing emission and the observed broad line width (= 340 km/s). In this poster, we report detailed observed properties of LAE J1044-0130 as an example of a superwind galaxy.
We performed first-principles calculations to obtain the phonon deformation potential (PDP) constants of wurtzite ZnO. The results are in good agreement with available experimental data except for a few PDP constants. We also found that the phonon frequencies of the A1 and B2 modes have relatively stronger nonlinear characteristics than the other modes.
This paper investigated the silicon substrate orientation dependence on the electrical properties of high-κ HfN gate insulator formed by electron-cyclotron-resonance (ECR) plasma sputtering. The effect of N2/4.9%H2 forming-gas annealing (FGA) was studied. By using N2/4.9%H2 FGA at 500°C for 20 min, the interfacial layer (IL) formation was not formed and led to the zero-interface layer (ZIL). The EOTs of 0.47 and 0.51 nm with leakage current of 1.1 and 1.4 A/cm2 (@VFB -1 V) were obtained on p-Si(100) and p-Si(110), respectively. The density of interface states (Dit) with the order of 1011 cm-2eV-1 was obtained on both p-Si(100) and p-Si(110). This suggests that the direct deposition of HfN film with ZIL prevented the degradation of electrical characteristics on the p-Si(100) and p-Si(110) substrate in comparison to the case of oxide-based hafnium gate insulator.
Changes in critical current properties depending on growth temperature (Ts) were clarified for Ba-Nb-O-doped YBa2Cu3Oy (Y123) films deposited by YAG- and excimer-PLD. Due to the introduction of Ba-Nb-O-nanorods, a vortex-Bose-glass-like behavior emerged as irreversibility lines and in-field critical current densities (Jcs) were improved. Crossover magnetic fields (Bcr) and in-field Jcs increased with the increase in Ts for the Y123 films with nanorods. These Ts-dependent critical current properties were attributable to the changes in morphology of the nanorods with Ts and were independent of laser source in PLD apparatuses. For the fabrication of RE123 coated conductors containing nanorods, optimization of Ts with taking both materials of RE123 matrix and nanorod into account is necessary to achieve higher in-field Jc.
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.
Hydrogenation properties of some amorphous Zr-Ni-Ti-V based alloys were investigated. Pressure-composition(P-C) isotherms and hydrogen storage capacities at room temperatures were measured and effects of elemental substitution of the components with Pd or Mn were studied. The alloy electrodes were prepared by using amorphous (Zr-Ni-Ti-V)-(Pd,Mn) alloys prepared by the melt spinning method. The amorphous alloys in the electrode kept their amorphous structures during cycles of charge and discharge. The electrochemical hydrogen storage capacities were strongly affected by the substitution amounts of Pd or Mn. Even a small amount of substitution, changed the equilibrium dissociation pressures of the alloy. In the present study, the rechargeable capacity was optimized up to H/M=0.5 for the alloy electrode with the composition of (Zr45Ni30Ti25)-3at%Pd. The slope in the P-C isotherm suggested that the maximum H/M of the alloy would exceed 1.0 at higher hydrogen pressure than 1.0 MPa, however, the wide distribution of hydrogen site energy in the amorphous hydride resulted in extremely large slope in P-C isotherms, and consequently restricted the rechargeable capacities of the electrodes.