Long-term prediction test procedure for most ICs, based on linear response theory

Experimentally, thermal annealing is known to be a factor which enables a number of different integrated circuits (IC's) to recover their operating characteristics after suffering radiation damage in the space radiation environment; thus, decreasing and limiting long term cumulative total-dose effects. This annealing is also known to be accelerated at elevated temperatures both during and after irradiation. Linear response theory (LRT) was applied, and a linear response function (LRF) to predict the radiation/annealing response of sensitive parameters of IC's for long term (several months or years) exposure to the space radiation environment were constructed. Compressing the annealing process from several years in orbit to just a few hours or days in the laboratory is achieved by subjecting the IC to elevated temperatures or by increasing the typical spaceflight dose rate by several orders of magnitude for simultaneous radiation/annealing only. The accomplishments are as follows: (1) the test procedure to make predictions of the radiation response was developed; (2) the calculation of the shift in the threshold potential due to the charge distribution in the oxide was written; (3) electron tunneling processes from the bulk Si to the oxide region in an MOS IC were estimated; (4) in order to connect the experimental annealing data to the theoretical model, constants of the model of the basic annealing process were established; (5) experimental data obtained at elevated temperatures were analyzed; (6) time compression and reliability of predictions for the long term region were shown; (7) a method to compress test time and to make predictions of response for the nonlinear region was proposed; and (8) nonlinearity of the LRF with respect to log(t) was calculated theoretically from a model

Ergatic dynamic control systems

Synthesis and analysis of systems containing a man in their control circuits are considered. The concepts of ergonomics and ergatic systems are defined, and tasks and problems of ergonomics are outlined. The synthesis of the structure of an astronautic ergatic organism is presented, as well as the synthesis of nonstationary ergatic systems. Problems of selecting the criteria for complex systems are considered, and the results are presented from a study of ergatic control systems with any degree of human participation

Photoinitiated azo-hydrazo tautomerizm of 1- p

A novel photochromic compound with NH-N intramolecular H-bond (1-p-toluenesulphonylazo- 2,4,6,8-tetrakis(tert-butyl)phenoxazine) and the corresponding model structures (1-oxo-2,4,6,8-tetrakis(tertbutyl) phenoxazine, 2,4,5,7-tetrakis (tert-butyl )-1-( veratroylazo ) phenoxazine, 2,4,5,7-tetrakis ( tert-butyl )-Nacetyl- 1-(p-toluenesulphonylazo)phenoxazine) have been synthesized and their spectral and photochemical properties are studied. The photochromic transformations observed are found to be conditioned by ESIPT (as a primary step) followed by E-Z isomerisation about N–N-bond

Alternative fast quantum logic gates using nonadiabatic Landau-Zener-St\"{u}ckelberg-Majorana transitions

A conventional realization of quantum logic gates and control is based on resonant Rabi oscillations of the occupation probability of the system. This approach has certain limitations and complications, like counter-rotating terms. We study an alternative paradigm for implementing quantum logic gates based on Landau-Zener-St\"{u}ckelberg-Majorana (LZSM) interferometry with non-resonant driving and the alternation of adiabatic evolution and non-adiabatic transitions. Compared to Rabi oscillations, the main differences are a non-resonant driving frequency and a small number of periods in the external driving. We explore the dynamics of a multilevel quantum system under LZSM drives and optimize the parameters for increasing single- and two-qubit gates speed. We define the parameters of the external driving required for implementing some specific gates using the adiabatic-impulse model. The LZSM approach can be applied to a large variety of multi-level quantum systems and external driving, providing a method for implementing quantum logic gates on them.Comment: 15 pages, 12 figure

Mirabegron: pharmacoeconomic aspects of the use of the drug for the treatment of overactive bladder syndrome

According to the International Continence Society (ICS), symptoms of overactive bladder (OAB) are present in 17 % of the adult population of Europe. The prevalence of overactive bladder in Russia is unknown but is considered comparable to that in European countries. According to Russian guidelines, patients with OAB could be treated with antimuscarinics or beta 3-agonists. The results of a meta-analysis by Wang J et al. (2018) showed comparable efficacy and safety of mirabegron and solifenacin. At the same time, according to Chapple CR et al. (2017) and Yeowell G et al. (2018) the use of mirabegron is associated with greater adherence to therapy and longer average drug use before the need to change therapy compared to antimuscarinics. From an economic point of view, greater adherence to drug therapy is associated with lower costs per patient with OAB per year and mirabegron have demonstrated to be cost-eff ective in comparison to solifenacin. The results of the analysis of the structure and volume of providing various types of medical care to patients with OAB in the Moscow region demonstrate the need to expand approaches to providing drug care to this group of patients. Currently, the majority of costs related to patients with OAB are associated with surgical treatment, which indicates the opportunity to expand the possibilities of drug therapy, including within the framework of preferential drug provision

Клинико-экономическая оценка применения генно-инженерных биологических препаратов и таргетных синтетических препаратов при анкилозирующем спондилите в условиях системы здравоохранения Российской Федерации

Objective: clinical and economic evaluation of the use of biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), Janus kinase inhibitors (iJAK), for the treatment of ankylosing spondylitis (AS).Patients and methods. Among comparison technologies for further analysis were included: adalimumab (ADA), golimumab (GLM), ixekizumab (IXE), secukinumab (SEC), tofacitinib (TOFA), certolizumab pegol (CZP), upadacitinib (UPA), etanercept (ETC). The efficacy and safety of the bDMARDs and tsDMARDs included in the study were evaluated based on the results of a systematic search and analysis of data on the comparative clinical efficacy and safety of their use. Any phase III randomized controlled trials of drugs used to treat active AS in adults (age ≥18) were considered as an investigational treatment versus placebo or versus another active drug. Analysis of the economic consequences of the use of bDMARDs and tsDMARDs for AS treatment was carried out only taking into account drug therapy. For the clinical and economic evaluation of the use of bDMARDs and tsDMARDs, the cost minimization indicator was calculated. As a criterion for clinical and economic efficiency and for the analysis of the impact on the budget, the cost per responder (CpR) indicator was estimated, which was calculated based on the cost of treating AS by the time the response was achieved according to the ASAS20/40 criteria and BASDAI50.Results and discussion. The results of the meta-analysis indicated a greater effectiveness of bDMARDs and iJAK compared with placebo in terms of the frequency of achieving ASAS 20/40, BASDAI 50 criteria. From an economic point of view, compared with the reference (minimum) value (ETC biosimilar, Erelzi®), the difference in the treatment cost of 1 patient with AS during the year varied widely (from +4.22 to +40.29%) and depended on the selected therapy option. At the same time, UPA 15 mg was characterized by the lowest cost of a course of treatment in the first year among original drugs. Among the original drugs, the lowest CpR values before reaching the ASAS20 criterion were in ADA (380,986.58 rubles), ETC (426,868.81 rubles), GLM (559,619.28 rubles) and UPA 15 mg (582,003.89 rub.), according to the ASAS40 criterion – for ADA (534,518.49 rubles.), ETC (726,347.45 rubles) and UPA 15 mg (557,753.73 rubles), according to the BASDAI50 criterion – for ADA (488,911.11 rubles), ETC (636,386.99 rubles) and UPA 15 mg (640,204.28 rubles).Conclusion. The study confirmed the clinical and economic feasibility of using various options for treatment of AS in real practice, including bDMARDs and iJAK. At the same time, the use of original drugs is not always associated with significant costs per 1 patient who responded to treatment. The creation of full-fledged patient registries will make it possible to introduce a system for monitoring clinical outcomes depending on the chosen treatment strategy, as well as smooth out the assumptions and limitations that are used in the study of the clinical and economic aspects of medical technologies, which will save resources and increase the availability of drugs for patients with rheumatic diseases.Цель исследования – клинико-экономическая оценка применения генно-инженерных биологических препаратов (ГИБП) и таргетных синтетических базисных противовоспалительных препаратов (тсБПВП) – ингибиторов Янус-киназ (иJAK) – для лечения анкилозирующего спондилита (АС).Пациенты и методы. К технологиям сравнения для дальнейшего анализа были отнесены: адалимумаб (АДА), голимумаб (ГЛМ), иксекизумаб (ИКСЕ), секукинумаб (СЕК), тофацитиниб (ТОФА), цертолизумаба пэгол (ЦЗП), упадацитиниб (УПА), этанерцепт (ЭТЦ). Эффективность и безопасность ГИБП и тсБПВП, включенных в исследование, оценивались по результатам систематического поиска и анализа данных о сравнительной клинической эффективности и безопасности их применения. Рассматривались любые рандомизированные контролируемые исследования III фазы препаратов, которые используются для терапии активного АС у взрослых (возраст ≥18) в качестве исследуемого лечения по сравнению с плацебо или с другим активным препаратом. Анализ экономических последствий применения ГИБП и тсБПВП для лечения АС проведен только с учетом медикаментозной терапии. Для клинико-экономической оценки применения ГИБП и тсБПВП был рассчитан показатель минимизации затрат. В качестве критерия клинико-экономической эффективности и для анализа влияния на бюджет оценивался показатель стоимости на 1 пациента, ответившего на терапию (cost per responder, СpR), который был рассчитан исходя из затрат на лечение АС к моменту достижения ответа по критериям ASAS20/40 и BASDAI50.Результаты и обсуждение. Результаты метаанализа свидетельствовали о большей эффективности ГИБП и иJAK по сравнению с плацебо по частоте достижения критериев ASAS20/40, BASDAI50. С экономической точки зрения по сравнению с референсным (минимальным) значением (биосимиляр ЭТЦ, Эрелзи®) разница в затратах на лечение 1 пациента с АС в течение года варьировалась в широких пределах (от +4,22 до +40,29%) и зависела от выбранной терапии. В то же время среди оригинальных лекарственных препаратов (ЛП) наименьшей стоимостью курса лечения в 1-й год в расчете на 1 пациента характеризовался УПА 15 мг. Среди оригинальных ЛП наименьшие показатели СpR до достижения критерия ASAS20 были у АДА (380 986,58 руб.), ЭТЦ (426 868,81 руб.), ГЛМ (559 619,28 руб.) и УПА 15 мг (582 003,89 руб.), по критерию ASAS40 – у АДА (534 518,49 руб.), ЭТЦ (726 347,45 руб.) и УПА 15 мг (557 753,73 руб.), по критерию BASDAI50 – также у АДА (488 911,11 руб.), ЭТЦ (636 386,99 руб.) и УПА 15 мг (640 204,28 руб.).Заключение. Проведенное исследование подтвердило клинико-экономическую целесообразность использования в реальной практике различных вариантов лечения АС, включающих ГИБП и иJAK. При этом применение оригинальных препаратов не всегда сопряжено со значительными затратами в расчете на 1 ответившего на лечение пациента. Создание полноценных регистров пациентов позволит внедрить систему мониторинга клинических исходов в зависимости от выбранной стратегии лечения, а также сгладить допущения и ограничения, которые используются при изучении клинико-экономических аспектов медицинских технологий, что будет способствовать экономии ресурсов и повышению доступности лекарственной помощи для пациентов с ревматическими заболеваниями

Применение метода многокритериального анализа принятия решений (MCDA) для разработки инструмента оценки уровня терапевтической ценности (инновационности) оригинальных лекарственных препаратов

Among the most important aspects of the health policy are the methods for pricing of medicines, especially of innovative medicines. In many countries, the “therapeutic value” of a medicine is commonly used as a major criterion in negotiations on medicine prices. The existing tools for assessing the therapeutic value of medicines are not used in the Russian Federation. Here we propose a method for estimating the therapeutic value of innovative medicines based on the multi-criterial analysis.Одним из наиболее актуальных вопросов в области политики здравоохранения являются методы ценового регулирования лекарственных препаратов (ЛП) и, в первую очередь, инновационных ЛП. Во многих странах в качестве аргумента для обоснования цен на ЛП используется оценка уровня терапевтической ценности ЛП. Поскольку ни один из существующих инструментов оценки терапевтической ценности ЛП не может быть использован в условиях РФ, нами были предложены подходы и разработан набор критериев для оценки терапевтической ценности инновационных ЛП на основе методологии многокритериального анализа