Background: Efgartigimod is a human IgG1 antibody Fc-fragment that reduces IgG levels through FcRn blockade. A key efficacy indicator in the treatment of IgG autoantibody-mediated generalized myasthenia gravis (gMG) is improvement in MG-ADL score. Methods: The ADAPT phase 3 trial evaluated safety and efficacy of efgartigimod in patients with gMG, including reaching and maintaining of minimal symptom expression (MSE; defined as an MG-ADL total score of 0 or 1). Results: 167 patients (AChR-Ab+, n=129; AChR-Ab-, n=38) were randomized to receive treatment cycles of 4 weekly infusions of efgartigimod or placebo. Significantly more AChR-Ab+ efgartigimod-treated patients achieved MSE during cycle 1 compared to placebo-treated patients (40.0% [n=26/65] vs 11.1% [n=7/63; P<0.0001]). In cycle 2, 31.4% (n=16/51) of AChR-Ab+ patients in the efgartigimod cohort achieved MSE compared to none in the placebo cohort. MG-ADL score improved by ≥6 points in 56.9% of AChR-Ab+ efgartigimod-treated patients compared to 20.6% of placebo-treated patients in cycle 1. Most patients achieved MSE by week 4 of a cycle, paralleling early reduction in IgG levels, and MSE duration ranged from 1 to ≥10 weeks. Adverse events were predominantly mild to moderate. Conclusions: Efgartigimod treatment resulted in more patients with AChR-Ab+ gMG achieving both MSE and clinically meaningful MG-ADL improvements.

Background: Efgartigimod, a human IgG1 antibody Fc-fragment, reduces IgG levels through neonatal Fc receptor blockade. Patients with anti-acetylcholine receptor antibody–negative (AChR-Ab–) generalized myasthenia gravis (gMG) comprise 15%-20% of the gMG population and have limited approved treatment options. We evaluated long-term safety and efficacy of efgartigimod in AChR-Ab– patients from ADAPT/ADAPT+ (open-label extension). Methods: ADAPT evaluated safety and efficacy of efgartigimod versus placebo in AChR-Ab+ (n=129) and Ab– (n=38) patients with gMG. This integrated analysis includes 37 AChR-Ab– patients who received ≥1 dose of efgartigimod in ADAPT/ADAPT+ through October 2020 (median[range] follow-up: 453[85-721] days). Responder status was defined as ≥2-point (MG-ADL) and ≥3-point (QMG) improvement for ≥4 consecutive weeks (with first improvement 1 week after last infusion). Results: Among AChR-Ab– patients in ADAPT (cycle 1), 68.4% (13/19) efgartigimod-treated were MG-ADL responders (placebo, 63.2% [12/19]), and 52.6% (10/19) were QMG responders (placebo, 36.8% [7/19]). In the integrated ADAPT/ADAPT+ analysis (cycle 1), AChR-Ab– patients improved from baseline in MG-ADL/QMG scores, with consistent improvements across multiple subsequent cycles. No clinically meaningful differences in safety or efficacy outcomes between AChR-Ab+ and Ab– patients occurred. Conclusions: Long-term treatment (median >1 year) with efgartigimod was well tolerated and associated with clinically meaningful improvements in MG-ADL/QMG scores in AChR-Ab– patients.

Background: Efgartigimod is a human IgG1 antibody Fc-fragment that reduces total and pathogenic IgG autoantibody levels through FcRn blockade. ADAPT was a phase 3 trial evaluating efgartigimod in patients with generalized myasthenia gravis (gMG). Patients who completed ADAPT could enroll in ADAPT+ (open-label extension). Methods: Efgartigimod (10 mg/kg intravenous) was administered in cycles of 4 weekly infusions, with subsequent cycles initiated based on clinical evaluation. ADAPT+ evaluated long-term safety and tolerability of efgartigimod in patients with gMG. Efficacy was assessed utilizing MG-ADL and QMG scores. Results: Of 167 patients from ADAPT, 151 (90%) entered ADAPT+, and 145 received ≥1 cycle as of January 2022. Over 217.55 patient-years of follow-up (mean duration per patient, 548 days), incidence of adverse events did not increase with subsequent cycles. AChR-Ab+ patients with ≥1 year of follow-up across ADAPT/ADAPT+ (n=95) received a median (range) 5.0 (0.4–7.6) cycles per year. All AChR-Ab+ patients (n=111) demonstrated consistent improvements (mean change [SE], week 3 of cycle 1) in MG-ADL (-5.0 [0.33]; up to 14 cycles) and QMG (-4.7 [0.41]; up to 7 cycles) scores during each cycle. Conclusions: These ADAPT+ analyses suggest long-term efgartigimod treatment is well tolerated and efficacious. Additional final data cut analyses will be presented at CNSF 2023.

Cognitive deficits as well as affective and physical symptoms are common after traumatic brain injury (TBI). However, little is known about how these deficits affect functional outcomes. The purpose of this study was to investigate the relationship between neuropsychological, affective and physical sequelae and outcomes such as social function and quality of life in patients with TBI. We studied these relationships in 57 patients with TBI over the course of 6 months post-injury. The patients completed neuropsychological assessments, including the Wechsler Adult Intelligence Scale-III, the Rivermead Behavioural Memory Test, and verbal fluency test. Affective and physical symptoms were assessed by beck depression inventory-II, Chalder fatigue scale, and Pittsburgh sleep quality index. Functional outcomes were assessed using the world health organization (WHO) disability assessment rated by others and the WHO quality of life assessment (WHO/QOL 26). The patients showed impairments in executive function assessed by verbal fluency test. The affective and physical assessments showed mild depressive mood and fatigue problem. Multiple regression analysis revealed that executive function and depressive mood were the best predictors of social function and quality of life, respectively. The findings of this study suggest that executive function and depressive mood are important factors to predict functional outcomes in patients with TBI.

In laboratory experiments, horizontal translational motion of columnar vortices formed in rotating Rayleigh–Bénard convection was investigated. Two types of measurements, vertical velocity fields and horizontal temperature fields, were conducted with water as the test fluid. Using particle image velocimetry, the vertical velocity fields determined the parameter range at which the quasi-two-dimensional columnar vortices emerged. Locally, the duration characteristics of the columns, evaluated with their vertical coherence, indicate the minimum time scale of translational motion of the vortices in the horizontal plane. Vortex tracking of the horizontal temperature fields over long observation periods (${>}10^{3}~\text{s}$) was conducted using encapsulated thermochromic liquid crystal visualization. Two cylindrical vessels with different radii showed the emergence of the centrifugal effect in $O({>}10^{2}~\text{s})$ despite the small Froude number ($Fr<0.1$). Further, in the horizontal plane the columnar vortices behaved in a random-walk-like diffusive motion. The statistically calculated mean-squared displacements indicated anomalous diffusive motion of the columns; displacement increasing with time as $t^{\unicode[STIX]{x1D6FE}}$ with $\unicode[STIX]{x1D6FE}\neq 1$. We discuss the causes of this anomaly in both the instantaneous and long-term statistical data gathered from experimental observations over different time scales. The enclosure effect from the repulsion of up-welling and down-welling vortices ensures that vortices diffuse only little, resulting in a sub-diffusive (decelerated) motion $\unicode[STIX]{x1D6FE}<1$ in $O(10^{1}~\text{s})$. With this weak centrifugal contribution, the translational motion of the columns slowly accelerates in the radial direction and thereby yields a super-diffusive (accelerated) motion $\unicode[STIX]{x1D6FE}>1$ in $O(10^{2}~\text{s})$.

The accumulation and transmission of tomato spotted wilt virus (TSWV) was examined in second instar larvae and adults of two thrips genera, Frankliniella and Thrips. The species tested were F. occidentalis (Pergande), F. intonsa (Trybom), T. tabaciLindeman, T. setosus Moulton, T. palmi Karny and T. hawaiiensis (Morgan). In a standard petunia leaf disc assay, the efficiencies of TSWV transmission by two species of Frankliniella were higher than those of any Thrips species in the adult stage. A triple antibody sandwich enzyme-linked immunosorbent assay (TAS-ELISA) showed that large amounts of the TSWV-nucleocapsid (N) protein were present in the ELISA-positive larvae of each species, with the exception of T. palmi. The ELISA titre of and the proportion of virus-infected individuals of the two Frankliniella species increased or did not significantly change from the larval to the adult stages, whereas those of the four Thrips species decreased significantly. These results show that the specificity of virus transmission by adult thrips is probably affected by the amount of viral N protein accumulation in the adults and that the accumulation pattern from the larval to the adult stages is in between the two genera tested in the present study.

The effect of constant temperature on development, reproduction and population growth of Thrips hawaiiensis (Morgan) reared on a diet of pollen and honey solution was studied. Although hatchability and survival rates from egg hatch to adult were higher than 79% between 15 and 25°C, they were lower than 55% at 10 and 30°C. Developmental rates increased linearly as rearing temperature increased. It was estimated that 153.8 degree-days, above a lower threshold temperature of 10.4°C, were required to complete development from egg to adult oviposition. According to these figures, between 11 and 18 generations of T. hawaiiensis could have developed annually under outdoor conditions in western Japan, between 1990 and 1999. Mean adult longevity decreased with increasing temperature, from a maximum of 102.7 days at 15°C to a minimum of 27.8 days at 25°C. The mean fecundity on pollen and honey solution was highest at 20°C with 536.9 eggs per female. The highest intrinsic rate of natural increase (rm) 0.208 was observed at 25°C.

We surveyed T serotypes and emm genotypes of Streptococcus pyogenes isolates from streptococcal toxic shock-like syndrome (TSLS) patients. T1 (emm1) remained dominant through 1992 to 2000, but the dominant T3 (emm3.1) strains from 1992 to 1995 disappeared during 1996–2000. Strains of several emm genotypes emerged during 1996–2000, indicating alterations in the prevalent strains causing TSLS.

There is still a controversy on the mass of the Galaxy in the deep halo, some advocate a conservative view that the rotation velocity ultimately decays in accordance with the Keplerian law at the distance of 50 kpc, while others have come to consider that the rotation curve of the Milky Way, essentially stays flat or is still increasing at the distance of the Magellanic Clouds and the Magellanic Stream.

The influence of hydrogenation on OFF current of TFTs with a bottom gate staggered structure has been investigated. The hydrogenation is done by exposing the surface of the a-Si:H channel layer to H2 plasma. The hydrogenation decreases the OFF current by more than one order of magnitude. The decrease in the OFF current is attributed to the increase in the density of states at the interface between the a-Si:H channel layer and the SiN passivating layer.

Phosphorous doped hydrogenated amorphous silicon films were deposited by microwave electron cyclotron resonance (ECR) plasma CVD at a substrate temperature of 100°C. Electrical, optical and hydrogen-incorporation properties of the films have been investigated. By optimizing the deposition condition, the dark conductivity of 3×10−4S/cm is realized without subsequent annealing. Relations between the film properties and ECR plasma properties have been studied by means of optical emission spectroscopy (OES) and quadrupole mass spectroscopy (QMS).

A number of orbits are obtained for the Large and Small Magellanic Clouds (LMC and SMC) revolving around a model Galaxy with a massive halo. It is suggested that the SMC approached the LMC as close as 3 to 7 kpc about 200 million years ago, if these clouds have been in a binary state for the past 1010 years, and the Magellanic Stream (MS) is due to the gravitational interaction among the triple system of the Galaxy, LMC, and SMC.

A brief survey is made of recent 21-cm and optical observations of the Magellanic Stream(MS). The space orientation of the Magellanic Clouds is touched upon in relation to modelling the MS. After summarizing a variety of models for the MS, we show that if our Galaxy is massive with a huge dark halo, a tidal model is most suitable for reproducing its characteristic structure and high-negative radial velocity. Past orbits of the Large and the Small Magellanic Cloud (LMC and SMC) are determined uniquely for the last 2×109 yr, if we postulate that the LMC and SMC are bound together for 1010 yr: Highly-noncircular motion of the SMC around the LMC could give a clue to understand some peculiar features associated with the Magellanic Clouds.

There are serious discrepancies among some of the recent neutron star cooling calculations by various groups. We have been investigating the possible source of these discrepancies. In this paper, we report our findings. We also report the preliminary result of our most recent cooling calculations without assuming an isothermal stellar evolution code. In this work, we used the currently existing best energy transport theories, as well as general relativity, both in thermodynamics and hydrodynamics.

Most of the neutron star cooling calculations with the only exception of Malone's (1974) have assumed an isothermal stellar core. Here we report on a neutron star cooling calculation which makes full use of the stellar evolution code and the recent thermal conductivity calculations by Flowers and Itoh (1976, 1979).

The advantages and disadvantages of both pulsed and cw scanned laser processing for Si devices are discussed. In particular, adaptions of laser processes for MOSFETs and bipolar structures are described from the viewpoint of active layer annealing. Moreover, MOSFETs fabricated in laser induced grown Si films on Si substrates having SiO2 patterns by bridging epitaxy, are discussed, as a function of sample structures, film formation conditions and laser irradiation conditions.