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

Measurement of stratospheric and mesospheric winds with a submillimeter wave limb sounder: results from JEM/SMILES and simulation study for SMILES-2

Satellite missions for measuring winds in the troposphere and thermosphere will be launched in a near future. There is no plan to observe winds in the altitude range between 30-90 km, though middle atmospheric winds are recognized as an essential parameter in various atmospheric research areas. Sub-millimetre limb sounders have the capability to fill this altitude gap. In this paper, we summarize the wind retrievals obtained from the Japanese Superconducting Submillimeter Wave Limb Emission Sounder (SMILES) which operated from the International Space Station between September 2009 and April 2010. The results illustrate the potential of such instruments to measure winds. They also show the need of improving the wind representation in the models in the Tropics, and globally in the mesosphere. A wind measurement sensitivity study has been conducted for its successor, SMILES-2, which is being studied in Japan. If it is realized, sub-millimeter and terahertz molecular lines suitable to determine line-of-sight winds will be measured. It is shown that with the current instrument definition, line-of-sight winds can be observed from 20 km up to more than 160 km. Winds can be retrieved with a precision better than 5 m s(-1) and a vertical resolution of 2-3 km between 35-90 km. Above 90 km, the precision is better than 10 m s(-1) with a vertical resolution of 3-5 km. Measurements can be performed day and night with a similar sensitivity. Requirements on observation parameters such as the antenna size, the satellite altitude are discussed. An alternative setting for the spectral bands is examined. The new setting is compatible with the general scientific objectives of the mission and the instrument design. It allows to improve the wind measurement sensitivity between 35 to 90 km by a factor 2. It is also shown that retrievals can be performed with a vertical resolution of 1 km and a precision of 5-10 m s(-1) between 50 and 90 km. RAGAM A, 1953, PHYSICAL REVIEW, V92, P144

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

Sulfatide and its synthetic analogues recognition by Moraxella catarrhalis

Moraxella catarrhalis is one of the major pathogens of respiratory and middle ear infections. Attachment of this bacterium to the surface of human pharyngeal epithelial cells is the first step in the pathogenesis of infections. This study revealed that sulfatide might act as a binding molecule for the attachment of M. catarrhalis to human pharyngeal epithelial cells. Furthermore, six different synthetic sulfatides were found to inhibit the attachment of M. catarrhalis significantly at an optimum concentration of 10 μg/ml. Synthetic sulfatides may have the potential to be used as a therapy to prevent M. catarrhalis infections

Brane World Effective Action at Low Energies and AdS/CFT Correspondence

A low energy iteration scheme to study nonlinear gravity in the brane world is developed. As a result, we obtain the brane world effective action at low energies. The relation between the geometrical approach and the approach using the AdS/CFT correspondence is also clarified. In particular, we find generalized dark radiation as homogeneous solutions in our iteration scheme. Moreover, the precise correspondence between the bulk geometry and the brane effective action is established, which gives a holographic view of the brane world.Comment: Revtex4, 12 pages, references added. Version accepted for publicaton in Phys. Rev.

Environmental Mortality and Long-Run Growth

There is emerging evidence that environmental degradation increases human mortality. This paper provides a long-run consumer optimization model in which mortality is endogenous to emissions generated by production. Emissions are assumed to follow the EKC path, first rising and then falling along with ouput. In the optimum, some deaths are accepted as an exchange for consumption. The model is estimated for the European outdoor air pollution data, showing that Europe has reached the downward sloping sement of the EKC. Economic growth will thus decrease rather than increase air pollution and the associted deaths in most countries in Europe

Mathematical utility theory and the representability of demand by continuous homogeneous functions

The resort to utility-theoretical issues will permit us to propose a constructive procedure for deriving a homogeneous of degree one continuous function that gives raise to a primitive demand function under suitably mild conditions. This constitutes the first self-contained and elementary proof of a necessary and sufficient condition for an integrability problem to have a solution by continuous (subjective utility) functions.info:eu-repo/semantics/publishedVersio