Long-term efficacy and safety of eculizumab in Japanese patients with generalized myasthenia gravis : a subgroup analysis of the REGAIN open-label extension study

The terminal complement inhibitor eculizumab was shown to improve myasthenia gravis-related symptoms in the 26-week, phase 3, randomized, double-blind, placebo-controlled REGAIN study (NCT01997229). In this 52-week sub-analysis of the open-label extension of REGAIN (NCT02301624), eculizumab's efficacy and safety were assessed in 11 Japanese and 88 Caucasian patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis. For patients who had received placebo during REGAIN, treatment with open-label eculizumab resulted in generally similar outcomes in the Japanese and Caucasian populations. Rapid improvements were maintained for 52 weeks, assessed by change in score from open-label extension baseline to week 52 (mean [standard error]) using the following scales (in Japanese and Caucasian patients, respectively): Myasthenia Gravis Activities of Daily Living (-2.4 [1.34] and - 3.3 [0.651); Quantitative Myasthenia Gravis (-2.9 [1.98] and - 4.3 [0.79]); Myasthenia Gravis Composite (-4.5 [2.63] and - 4.9 [1.19]); and Myasthenia Gravis Quality of Life 15-item questionnaire (-8.6 [5.68) and - 6.5 [1.93]). Overall, the safety of eculizumab was consistent with its known safety profile. In this interim sub-analysis, the efficacy and safety of eculizumab in Japanese and Caucasian patients were generally similar, and consistent with the overall REGAIN population

Gyrofluid simulations of collisionless reconnection in the presence of diamagnetic effects

The effects of the ion Larmor radius on magnetic reconnection are investigated by means of numerical simulations, with a Hamiltonian gyrofluid model. In the linear regime, it is found that ion diamagnetic effects decrease the growth rate of the dominant mode. Increasing ion temperature tends to make the magnetic islands propagate in the ion diamagnetic drift direction. In the nonlinear regime, diamagnetic effects reduce the final width of the island. Unlike the electron density, the guiding center density does not tend to distribute along separatrices and at high ion temperature, the electrostatic potential exhibits the superposition of a small scale structure, related to the electron density, and a large scale structure, related to the ion guiding-center density

Gyrofluid simulations of collisionless reconnection in the presence of diamagnetic effects

The effects of the ion Larmor radius on magnetic reconnection are investigated by means of numerical simulations, with a Hamiltonian gyrofluid model. In the linear regime, it is found that ion diamagnetic effects decrease the growth rate of the dominant mode. Increasing ion temperature tends to make the magnetic islands propagate in the ion diamagnetic drift direction. In the nonlinear regime, diamagnetic effects reduce the final width of the island. Unlike the electron density, the guiding center density does not tend to distribute along separatrices and at high ion temperature, the electrostatic potential exhibits the superposition of a small scale structure, related to the electron density, and a large scale structure, related to the ion guiding-center density

Gyrofluid simulations of collisionless reconnection in the presence of diamagnetic effects

The effects of the ion Larmor radius on magnetic reconnection are investigated by means of numerical simulations, with a Hamiltonian gyrofluid model. In the linear regime, it is found that ion diamagnetic effects decrease the growth rate of the dominant mode. Increasing ion temperature tends to make the magnetic islands propagate in the ion diamagnetic drift direction. In the nonlinear regime, diamagnetic effects reduce the final width of the island. Unlike the electron density, the guiding center density does not tend to distribute along separatrices and at high ion temperature, the electrostatic potential exhibits the superposition of a small scale structure, related to the electron density, and a large scale structure, related to the ion guiding-center density

Expression of chemokine receptors on peripheral blood lymphocytes in multiple sclerosis and neuromyelitis optica

<p>Abstract</p> <p>Background</p> <p>The role of different chemokine receptors in the pathogenesis of multiple sclerosis (MS) has been extensively investigated; however, little is known about the difference in the role of chemokine receptors between the pathogenesis of neuromyelitis optica (NMO) and MS. Therefore, we examined the expression of chemokine receptors on peripheral blood lymphocytes (PBL) in MS and NMO.</p> <p>Methods</p> <p>We used flow cytometry to analyse lymphocyte subsets in 12 patients with relapsing NMO, 24 with relapsing-remitting MS during relapse, 3 with NMO and 5 with MS during remission.</p> <p>Results</p> <p>Compared with healthy controls (HC), the percentage of lymphocytes in white blood cells was significantly lower in NMO and MS patients. The percentage of T cells expressing CD4⁺CD25⁺and CD4⁺CD45RO⁺was higher, while that of CD4⁺CC chemokine receptor (CCR)3⁺(T helper 2, Th2) was significantly lower in MS patients than in HC. The ratios of CD4⁺CXC chemokine receptors (CXCR)3⁺/CD4⁺CCR3⁺(Th1/Th2) and CD8⁺CXCR3⁺/CD8⁺CCR4⁺(T cytotoxic 1, Tc1/Tc2) were higher in MS patients than in HC. The percentage of CD8⁺CXCR3⁺T cell (Tc1) and CD4⁺CXCR3⁺T cell (Th1) decreased significantly during remission in MS patients (<it>P <</it>0.05). No significant differences were identified in the expression of the chemokine receptors on PBL in NMO patients compared with MS patients and HC.</p> <p>Conclusions</p> <p>Th1 dominance of chemokine receptors on blood T cells and the correlation between CXCR3⁺T cell (Th1 and Tc1) and disease activity in MS patients were confirmed by analysing chemokines receptors on PBL. In contrast, deviation in the Th1/Th2 balance was not observed in NMO patients.</p

Compact objects and the swampland

Recently, two simple criteria were proposed to assess if vacua emerging from an effective scalar field theory are part of the string “landscape” or “swampland”. The former are the vacua that emerge from string compactifications; the latter are not obtained by any such compactification and hence may not survive in a UV completed theory of gravity. So far, these criteria have been applied to inflationary and dark energy models. Here we consider them in the context of solitonic compact objects made up of scalar fields: boson stars. Analysing several models (static, rotating, with and without self-interactions), we find that, in this context, the criteria are not independent. Furthermore, we find the universal behaviour that in the region wherein the boson stars are expected to be perturbatively stable, the compact objects may be part of the landscape. By contrast, in the region where they may be faithful black hole mimickers, in the sense they possess a light ring, the criteria fail (are obeyed) for static (rotating) ultracompact boson stars, which should thus be part of the swampland (landscape). We also consider hairy black holes interpolating between these boson stars and the Kerr solution and establish the part of the domain of existence where the swampland criteria are violated. In interpreting these results one should bear in mind, however, that the swampland criteria are not quantitatively strict.publishe

Natural extension of choice functions

International Conference on Information Processing and Management of Uncertainty in Knowledge-Based Systems, IPMU (17 th, 2018, Cádiz, Spain

Radiosensitivity of pimonidazole-unlabelled intratumour quiescent cell population to γ-rays, accelerated carbon ion beams and boron neutron capture reaction.

[Objectives] To detect the radiosensitivity of intratumour quiescent (Q) cells unlabelled with pimonidazole to accelerated carbon ion beams and the boron neutron capture reaction (BNCR). [Methods] EL4 tumour-bearing C57BL/J mice received 5-bromo-2′-deoxyuridine (BrdU) continuously to label all intratumour proliferating (P) cells. After the administration of pimonidazole, tumours were irradiated with γ-rays, accelerated carbon ion beams or reactor neutron beams with the prior administration of a [10]B-carrier. Responses of intratumour Q and total (P+Q) cell populations were assessed based on frequencies of micronucleation and apoptosis using immunofluorescence staining for BrdU. The response of pimonidazole-unlabelled tumour cells was assessed by means of apoptosis frequency using immunofluorescence staining for pimonidazole. [Results] Following γ-ray irradiation, the pimonidazole-unlabelled tumour cell fraction showed significantly enhanced radiosensitivity compared with the whole tumour cell fraction, more remarkably in the Q than total cell populations. However, a significantly greater decrease in radiosensitivity in the pimonidazole-unlabelled cell fraction, evaluated using a delayed assay or a decrease in radiation dose rate, was more clearly observed among the Q than total cells. These changes in radiosensitivity were suppressed following carbon ion beam and neutron beam-only irradiaton. In the BNCR, the use of a[10]B-carrier, especially L-para-boronophenylalanine-[10]B, enhanced the sensitivity of the pimonidazole-unlabelled cells more clearly in the Q than total cells. [Conclusion] The radiosensitivity of the pimonidazole-unlabelled cell fraction depends on the quality of radiation delivered and characteristics of the [10]B-carrier used in the BNCR