To evaluate the efficacy and safety of different doses and regimens of filgotinib, an oral Janus kinase 1 inhibitor, as add-on treatment to methotrexate (MTX) in patients with active rheumatoid ...arthritis (RA) and inadequate response to MTX.
In this 24-week phase IIb study, patients with moderate-to-severe active RA receiving a stable dose of MTX were randomised (1:1:1:1:1:1:1) to receive placebo or 50, 100 or 200 mg filgotinib, administered once daily or twice daily. Primary end point was the percentage of patients achieving a week 12 American College of Rheumatology (ACR)20 response.
Overall, 594 patients were randomised and treated. At week 12, significantly more patients receiving filgotinib 100 mg once daily or 200 mg daily (both regimens) achieved an ACR20 response versus placebo. For other key end points at week 12 (ACR50, ACR-N, Disease Activity Score based on 28 joints and C reactive protein value, Clinical Disease Activity Index, Simplified Disease Activity Index and Health Assessment Questionnaire-Disability Index), differences in favour of 100 or 200 mg filgotinib daily were seen versus placebo; responses were maintained or improved through to week 24. Rapid onset of action and dose-dependent responses were observed for most efficacy end points and were associated with an increased haemoglobin concentration. No significant differences between once-daily and twice-daily regimens were seen. Treatment-emergent adverse event rates were similar in placebo and filgotinib groups. Serious infections occurred in one and five patients in the placebo and filgotinib groups, respectively. No tuberculosis or opportunistic infections were reported.
Filgotinib as add-on to MTX improved the signs and symptoms of active RA over 24 weeks and was associated with a rapid onset of action. Filgotinib was generally well tolerated.
NCT01888874.
The group theoretical description of the periodic system of elements in the framework of the Rumer–Fet model is considered. We introduce the concept of a single quantum system, the generating core of ...which is an abstract C*-algebra. It is shown that various concrete implementations of the operator algebra depend on the structure of the generators of the fundamental symmetry group attached to the energy operator. In the case of the generators of the complex shell of a group algebra of a conformal group, the spectrum of states of a single quantum system is given in the framework of the basic representation of the Rumer–Fet group, which leads to a group-theoretic interpretation of the Mendeleev’s periodic system of elements. A mass formula is introduced that allows giving the termwise mass splitting for the main multiplet of the Rumer–Fet group. The masses of elements of the Seaborg table (eight-periodic extension of the Mendeleev table) are calculated starting from the atomic number Z=3 and going to Z=220. The continuation of the Seaborg homology between lanthanides and actinides is established with the group of superactinides. A 10-periodic extension of the periodic table is introduced in the framework of the group-theoretic approach. The multiplet structure of the extended table’s periods is considered in detail. It is shown that the period lengths of the system of elements are determined by the structure of the basic representation of the Rumer–Fet group. The theoretical masses of the elements of 10th and 11th periods are calculated starting from Z=221 and going to to Z=364. The concept of hypertwistor is introduced.
The NB-Fi protocol is a promising solution for the implementation of low power wide area networks. It was adopted in 2022 as a national standard of the Russian Federation. The NB-Fi devices transmit ...data in unlicensed spectrum and can operate in two modes: with and without carrier sense. This paper compares the power consumption of NB-Fi devices that use these modes with different carrier sense implementations. It is shown that even at low traffic intensity (more than 30 packets per second) and the presence of hidden devices in the network, the carrier sense mode allows reducing significantly the power consumption of devices in comparison with the mode without carrier sense.
A variant of the technological scheme for thick layer mining with top coal caving and pre-destruction of coal by means of advanced parallel chambers is proposed. Based on the results of numerical ...modeling, the optimum dimensions are justified for chambers, interchamber coal pillars as well as crown pillar between the chambers and immediate roof rocks. It has been proved that after the advanced chambers are made, the strength roof coal is reduced by a factor of 2 to 2.5, and therefore the conditions are created for uniform coal caving without dilution. A variant of the technology of unmanned coal mining in the chambers is proposed.
The article is devoted to the assessment of the network community as a collective subject, as a group of interconnected and interdependent persons performing joint activities. According to the main ...research hypothesis, various forms of group subjectness, which determine its readiness for joint activities, are manifested in the discourse of the network community. Discourse constitutes a network community, mediates the interaction of its participants, represents ideas about the world, values, relationships, attitudes, sets patterns of behavior. A procedure is proposed for identifying discernible traces of the subjectness of a network community at various levels (lexical, semantic, content-analytical scales, etc.). The subjective structure of the network community is described based on experts' implicit representations. The revealed components of the subjectness of network communities are compared with the characteristics of the subjectness of offline social groups. It is shown that the structure of the subjectness of network communities for some components is similar to the structure of the characteristics of the subjectness of offline social groups: the discourse of the network community represents a discussion of joint activities, group norms, and values, problems of civic identity. The specificity of network communities' subjectness is revealed, which is manifested in the positive support of communication within the community, the identification and support of distinction between "us" and "them". Two models of the relationship between discursive features and the construct "subjectness" are compared: additive-cumulative and additive. The equivalence of models is established based on the discriminativeness and the level of consistency with expert evaluation by external criteria.
Based on the results of numerical modeling of stresses and strains in rock mass, geomechanical parameters of development workings adjacent to coal face operation area are provided for multi-entry ...preparation and extraction of flat seams with production faces of variable length. The negative effects on the geomechanical situation during the transition from the longwall to shortwall mining in a fully mechanized extraction face are found.
The article gives a revision of the Semagystia monticola (Groum-Grshimaïlo, 1890) species group (Lepidoptera, Cossidae, Cossinae). The group comprises nine valid species. Detailed data on the ...distribution of all the species are provided. Four new species from Central Asia are described: S. churkini Yakovlev & Shapoval, sp. n. (Type locality: Kyrgyzstan, Moldo-Too Range, Kichine-Kindyk River), S. fomichevi Yakovlev & Shapoval, sp. n. (Type locality: Tajikistan, Eastern Pamir Mts., Zulumart Palangguzar Mt. Rg.), S. toropovi Yakovlev & Shapoval, sp. n. (Type locality: Kirgizia, Tschatkal Mt., Sary-Chelek lake), and S. uvaydo Yakovlev & Shapoval, sp. n. (Type locality: Tajikistan, Darvaz Mts., Khozratishoh Range, Khaburobot pass). The article is illustrated with imagoes of specimens from different localities and male genitalia of all new species.
Pollen morphology of seven Alyssum L. taxa growing on serpentine soils in different places in the European Mediterranean macrobioclimate territory were studied, described and compared. Cluster ...analysis was performed to show similarity between species and their populations. The shape of the pollen grains varies among the species and among the grains within the same anther. The pollen grains are 3-colpate, prolate, with long and narrow colpi reaching the poles. The ornamentation of the exine varies from micro-reticulate to reticulate between the species. Pollen sterility/fertility was also calculated. The highest percentage of sterile pollen (73.76%) was calculated for Alyssum murale subsp. murale and the lowest (9.54%) for A. bertolonii subsp. bertolonii. All species are representatives of sect. Odontarrhena (C.A. Meyer) Koch well known as Ni-hyperaccumulators. Nickel and other elements present in pollen and stamen were studied by inductively coupled plasma-mass spectrometry. The stamen parts of all species were micromorphologically analyzed by scanning electron microscopy coupled to an energy-dispersive X-ray probe. Accumulation of Ni was detected in the stamens of all studied species and rarely in the pollen grains. The distribution patterns of Ni were similar among the species examined.
Within the framework of the robotic coal mine design for deep-level coal beds with the high gas content in the seismically active areas in the southern Kuzbass, the motion path parameters for an ...effector of a robotic mining machine are evaluated. The simulation model is meant for selection of minimum energy-based optimum trajectory for the robot effector, calculation of stresses and strains in a coal bed in a variable perimeter shortwall in the course of coal extraction, determination of coordinates of a coal bed edge area with the maximum disintegration of coal, and for choice of direction of the robot effector to get in contact with the mentioned area and to break coal at the minimum energy input. It is suggested to use the model in the engineering of the robot intelligence.
The results of numerical simulation of the stress-strain state in a rock block and surrounding mass mass under multi-roadway preparation to mining are presented. The numerical solutions obtained by ...the nonlinear modeling and using the constitutive relations of the theory of elasticity are compared. The regularities of the stress distribution in the vicinity of the pillars located in the zone of the abutment pressure of are found.
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