On integrable system on S2S^2 with the second integral quartic in the momenta

We consider integrable system on the sphere $S^2$ with an additional integral of fourth order in the momenta. At the special values of parameters this system coincides with the Kowalevski-Goryachev-Chaplygin system.Comment: LaTeX, 6 page

Spherical model of the Stark effect in external scalar and vector fields

The Bohr-Sommerfeld quantization rule and the Gamow formula for the width of quasistationary level are generalized by taking into account the relativistic effects, spin and Lorentz structure of interaction potentials. The relativistic quasi-classical theory of ionization of the Coulomb system (V_{Coul}=-\xi/r) by radial-constant long-range scalar (S_{l.r.}=(1-\lambda)(\sigma r+V_0)) and vector (V_{l.r.}=\lambda(\sigma r+V_0)) fields is constructed. In the limiting cases the approximated analytical expressions for the position E_r and width \Gamma of below-barrier resonances are obtained. The strong dependence of the width \Gamma of below-barrier resonances on both the bound level energy and the mixing constant \lambda is detected. The simple analytical formulae for asymptotic coefficients of the Dirac radial wave functions at zero and infinity are also obtained.Comment: 25 pages, 4 figures. Submitted to Int. J. Mod. Phys.

Skyrme-Rpa Description of Dipole Giant Resonance in Heavy and Superheavy Nuclei

The E1(T=1) isovector dipole giant resonance (GDR) in heavy and super-heavy deformed nuclei is analyzed over a sample of 18 rare-earth nuclei, 4 actinides and three chains of super-heavy elements (Z=102, 114 and 120). Basis of the description is self-consistent separable RPA (SRPA) using the Skyrme force SLy6. The self-consistent model well reproduces the experimental data (energies and widths) in the rare-earth and actinide region. The trend of the resonance peak energies follows the estimates from collective models, showing a bias to the volume mode for the rare-earths isotopes and a mix of volume and surface modes for actinides and super-heavy elements. The widths of the GDR are mainly determined by the Landau fragmentation which in turn is found to be strongly influenced by deformation. A deformation splitting of the GDR can contribute about one third to the width and about 1 MeV further broadening can be associated to mechanism beyond the mean-field description (escape, coupling with complex configurations).Comment: 9 pages, 12 figures, 2 table

Planning a clinical trial programme for direct-acting antivirals for chronic viral hepatitis C

Scientific relevance. Direct-acting antivirals have significantly improved the effectiveness of treatment for hepatitis C. However, Russia and the Eurasian Economic Union lack recommendations for the clinical development of medicinal products from this pharmacotherapeutic group.Aim. The study aimed to analyse the requirements and recommendations for planning safety and efficacy clinical trials of direct-acting antivirals for chronic viral hepatitis C, outlined in the regulatory documents of the European Union and the United States.Discussion. Upon analysing the requirements and recommendations, the authors explained the reasons behind choosing the target population and the design for the efficacy and confirmatory studies. The article covers the clinical development of direct-acting antivirals in special populations, including patients with hepatitis C and HIV co-infection, a liver transplant, and prior treatment experience. According to the authors, patients who achieved a sustained virological response should be followed up for a full year after the end of treatment in order to confirm the durability of their response. A dose-finding study should first identify a suitable dose range for monotherapy and, subsequently, for combined therapy. Current treatment regimens should be optimised, and studies should be conducted to reduce treatment duration.Conclusions. The authors outlined the main approaches and a methodology for clinical trial programmes that should take into account the degree of correlation between the efficacy of direct-acting antivirals and the genotype/subtype of hepatitis C virus

Density-of-states picture and stability of ferromagnetism in the highly-correlated Hubbard model

The problem of stability of saturated and non-saturated ferromagnetism in the Hubbard model is considered in terms of the one-particle Green's functions. Approximations by Edwards and Hertz and some versions of the self-consistent approximations based on the 1/z-expansion are considered. The account of longitudinal fluctuations turns out to be essential for description of the non-saturated state. The corresponding pictures of density of states are obtained. "Kondo" density-of-states singularities owing to spin-flip processes are analyzed. The critical electron concentrations for instabilities of saturated ferromagnetism and paramagnetic state are calculated for various lattices. Drawbacks of various approximations are discussed. A comparison with the results of previous works is performed.Comment: 16 pages, 7 eps figure

Planning of clinical trial programmes for medicines for the treatment of obesity

Scientific relevance. Obesity is a significant public health problem. Currently, the Russian Federation and the other Member States of the Eurasian Economic Union (EAEU) do not have regulatory documents and recommendations for planning clinical trials (CTs) of new (original) medicines for the treatment of obesity.Aim. The study aimed to provide recommendations on the basic principles of planning and conducting CTs of medicines for the treatment of obesity.Discussion. The authors reviewed the requirements for conducting CTs of medicines for the treatment of obesity set forth by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). In addition, the authors analysed approaches to CTs providing for a reliable evaluation of the efficacy and safety of medicines for the treatment of obesity. The primary endpoint of such CTs is a statistically significant loss of at least 5% of the baseline weight after 12 months of treatment. Secondary endpoints include assessments of abdominal obesity reduction, subcutaneous and visceral fat reduction, and the medicinal product’s effect on maintaining a reduced body weight.Conclusions. In addition, CTs should investigate the effects of treatment on cardiovascular risk factors and cardiovascular morbidity/mortality. A CT protocol should define the intercurrent events that should be considered in the analysis of trial results. When investigating the safety of medicines for the treatment of obesity, studies should focus on neuropsychiatric safety, the potential for abuse/addiction and withdrawal reactions, and the development of valvulopathy and pulmonary hypertension. These recommendations may be of use to experts evaluating clinical development programmes or marketing authorisation submissions for medicines for the treatment of obesity

Development of an Approach to the Assessment of Changes to Approved Biological Products

The need to strengthen the post-approval regulation of biological products stems from their increasing role in the treatment of serious human diseases. Until recently, there were open questions on the classification of changes and supporting data necessary to confirm the comparability of a biological medicinal product before and after any changes, as well as on the procedures and deadlines for the submission and approval of variations. In October 2017 the WHO Expert Committee on Biological Standardisation developed and published the «Guidelines on procedures and data requirements for changes to approved biotherapeutic products». The WHO recommendations are primarily aimed at resolving the complexities and current problems in the global life cycle management of biotherapeutic products. Guidelines suggest approaches that ensure continued quality, efficacy, and safety of this group of products, as well as continuity in supply and access. The purpose of this paper was to analyse the WHO recommendations on post-approval changes to biotherapeutic products in order to develop harmonised approaches to the assessment of post-approval changes to biological medicinal products in the Russian Federation. The categories of quality changes, supporting data, conditions to be fulfilled, procedures and deadlines set forth in this paper can serve as a basis for further improvement of the national regulatory and methodological framework

Coherent responses of resonance atom layer to short optical pulse excitation

Coherent responses of resonance atom layer to short optical pulse excitation are numerically considered. The inhomogeneous broadening of one-photon transition, the local field effect, and the substrate dispersion are involved into analysis. For a certain intensity of incident pulses a strong coherent interaction in the form of sharp spikes of superradiation is observed in transmitted radiation. The Lorentz field correction and the substrate dispersion weaken the effect, providing additional spectral shifts. Specific features of photon echo in the form of multiple responses to a double or triple pulse excitation is discussed.Comment: only PDF,15 page