Regional Social Infrastructure Management in the System of Tools Used for Improving the Quality of Life for Regional Population

This paper analyzes the processes in the social sphere and the performance of operating the social infrastructure to improve the population’s quality of life in the Russian regions. Particular attention has been paid to the role of organizational and administrative components, which include the regulation of social infrastructure institutions, planning, and programming that affect the performance of infrastructure facilities utilization. The goal of this study was to evaluate the effectiveness of social infrastructure management through the congruence of immediate results (dynamics of indicators for social services) and final results (parameters of the population’s quality of life). The working hypothesis of the study was a breach of infrasystemic principle in the infrastructural support for improving the population’s quality of life in the constituent entities of the Russian Federation because of the insufficient effectiveness of public administration. The work on this paper involved using a set of methodological approaches, such as structured, factorial, systemic, and evolutionary approaches, to substantiate the conceptual framework, prepare the method-based approaches, and determine the impact made by the changes in the parameters of social infrastructure facilities on provided services and shifts in the indicators of the population’s quality of life. The paper proposes a method-based approach to quantifying the effectiveness of organizational and administrative components by using the diagnostics of sufficiency in the implementation of infrasystemic principle for the operation of social infrastructure based on elasticity coefficients. The proposed approach and analytical data obtained in the areas, such as health care, education, trade, housing utilities, culture sport, allowed ranking the regions of the Ural Federal District and identifying the areas of insufficient effectiveness in the organizational and administrative mechanism used for improving the population’s quality of life as the basis for developing practical recommendations for the executive branch of constituent entities of the Russian Federation and adjustment of socioeconomic policies

The FOXE1 locus is a major genetic determinant for radiation-related thyroid carcinoma in Chernobyl.

Papillary thyroid cancer (PTC) among individuals exposed to radioactive iodine in their childhood or adolescence is a major internationally recognized health consequence of the Chernobyl accident. To identify genetic determinants affecting individual susceptibility to radiation-related PTC, we conducted a genome-wide association study employing Belarusian patients with PTC aged 0-18 years at the time of accident and age-matched Belarusian control subjects. Two series of genome scans were performed using independent sample sets, and association with radiation-related PTC was evaluated. Meta-analysis by the Mantel-Haenszel method combining the two studies identified four SNPs at chromosome 9q22.33 showing significant associations with the disease (Mantel-Haenszel P: mhp = 1.7 x 10(-9) to 4.9 x 10(-9)). The association was further reinforced by a validation analysis using one of these SNP markers, rs965513, with a new set of samples (overall mhp = 4.8 x 10(-12), OR = 1.65, 95% CI: 1.43-1.91). Rs965513 is located 57-kb upstream to FOXE1, a thyroid-specific transcription factor with pivotal roles in thyroid morphogenesis and was recently reported as the strongest genetic risk marker of sporadic PTC in European populations. Of interest, no association was obtained between radiation-related PTC and rs944289 (mhp = 0.17) at 14p13.3 which showed the second strongest association with sporadic PTC in Europeans. These results show that the complex pathway underlying the pathogenesis may be partly shared by the two etiological forms of PTC, but their genetic components do not completely overlap each other, suggesting the presence of other unknown etiology-specific genetic determinants in radiation-related PTC

Дискретна модель системи міокард–коронарні судини

Background. The numerical heat transfer model for a system of myocardium coronary vessels is considered.Objective. The goal is to develop a discrete model for the physical system of myocardium and coronary vessels that would make it possible to explore the process of hypo- and hyperthermia with cardiopulmonary bypass.Methods. To solve the differential equation of heat conduction in the MSC Sinda thermal system the network method (TNM – Thermal Network Method) is used, in which system of heat equations is presented in the form of cellular-centered nodes and resistances between the nodes using the finite difference method. In constructing the model of myocardial in the MSC Sinda system the thermal contact between three-dimensional bodies is implemented – the myocardium, coronary arteries, a liquid cooling of heart.Results. Implementation of the model of heat exchange in the MSC Sinda system for infarction cooling process gives on the final process step in establishing the heat balance the temperature difference at the boundary between the myocardium and coronary vessels not more than 0,5 °C. However, in the areas of the myocardium that are removed from the coronary vessels the temperature difference exceeds 1,0 °C. The use of additional cooling for hearts allows for the cooling of myocardium with using of ice surface, that provides the unevenness reduction of the heart temperature during its cooling with cardiopulmonary bypass. This result allows exploring the dynamics of the process of hypo- and hyperthermia with cardiopulmonary bypass.Conclusions. The discrete 3D-model of heat transfer in the layer structure of the myocardium and coronary vessels allows us to investigate the process of hypo- and hyperthermia with cardiopulmonary bypass. The simulation results also make it possible to perform the analysis of the temperature distribution on the surface of the myocardium provided free convection of heat between the layers. Проблематика. Рассматривается реализация численной модели теплообмена для системы миокард–коронарные сосуды.Цель исследования. Разработка дискретной модели физической системы миокарда и коронарных сосудов, которая позволила бы исследовать процесс гипо- и гипертермии в условиях искусственного кровообращения.Методика реализации. Для решения дифференциального уравнения теплопроводности в системе MSC Sinda использован метод тепловой сети (TNM), в котором система уравнений теплопроводности представлена с помощью конечноразностного метода в виде клеточно-ориентированных узлов и сопротивлений между узлами. При построении модели миокарда в системе MSC Sinda реализован тепловой контакт между трехмерными телами – миокардом, коронарными артериями, жидкостью для охлаждения сердца.Результаты исследования. Реализация модели теплообмена в системе MSC Sinda для процесса охлаждения миокарда дает на конечной стадии процесса, при установлении теплового баланса, разность температур на границе между миокардом и коронарными сосудами температур не более 0,5 °C. При этом в областях миокарда, которые удалены от коронарных сосудов разность температур превышает 1,0 °C. Использование дополнительного охлаждения для сердца предусматривает охлаждение миокарда с использованием поверхности льда, что обеспечивает снижение неравномерности распределения температуры сердца при его охлаждении искусственным кровообращением. Этот результат позволяет исследовать динамику процесса гипо- и гипертермии в условиях искусственного кровообращения.Выводы. Дискретная 3D-модель теплопередачи для системы слой миокарда-коронарные сосуды позволяет исследовать процесс гипо- и гипертермии в условиях искусственного кровообращения. Результаты моделирования также дают возможность провести анализ распределения температуры на поверхности миокарда при свободной конвекции тепла между слоями.Проблематика. Розглядається реалізація числової моделі теплообміну для системи міокард–коронарні судини.Мета дослідження. Розробка дискретної моделі фізичної системи міокарда та коронарних судин, яка б дала змогу досліджувати процес гіпо- та гіпертермії в умовах штучного кровообігу.Методика реалізації. Для розв’язання диференціального рівняння теплопровідності в системі MSC Sinda використано метод теплової мережі (TNM), у якому система рівнянь теплопровідності представлена за допомогою скінченнорізницевого методу у вигляді клітино-орієнтованих вузлів і опорів між вузлами. При побудові моделі міокарда в системі MSC Sinda реалізований тепловий контакт між тривимірними тілами – міокардом, коронарними артеріями, рідиною для охолодження серця.Результати дослідження. Реалізація моделі теплообміну в системі MSC Sinda для процесу охолодження міокарда дає на кінцевій стадії процесу, при встановленні теплового балансу, різницю температур на межі між міокардом і коронарними судинами температур не більше 0,5 °C. При цьому в областях міокарда, які віддалені від коронарних судин, різниця температур перевищує 1,0 °C. Використання додаткового охолодження для серця передбачає охолодження міокарда з використанням поверхні льоду, що забезпечує зниження нерівномірності розподілу температури серця при його охолодженні штучним кровообігом. Цей результат дає змогу досліджувати динаміку процесу гіпо- та гіпертермії в умовах штучного кровообігу.Висновки. Дискретна 3D-модель теплопередачі для системи шар міокарда–коронарні судини дає змогу досліджувати процес гіпо- та гіпертермії в умовах штучного кровообігу. Результати моделювання також дають можливість провести аналіз розподілу температури на поверхні міокарда за умови вільної конвекції тепла між шарами

Effectiveness and safety of empegfilgrastim (Extimia®) in patients with solid tumors receiving cytotoxic therapy: final results of the DEFENDOR study

Aim. To evaluate the effectiveness and safety of Extimia® (empegfilgrastim, JSC "BIOCAD") in reducing the frequency, duration of neutropenia, the incidence of febrile neutropenia (FN) and infections caused by FN in patients with solid tumors receiving myelosuppressive therapy. Materials and methods. The paper presents the final results of a multicenter prospective observational post-marketing study of the safety and effectiveness of Extimia® (empegfilgrastim) in patients with solid tumors receiving cytotoxic therapy. For the primary prevention of FN, all patients received empegfilgrastim at 7.5 mg subcutaneously once per course of chemotherapy (CT) 24 hours after the end of CT administration. The primary endpoint included an assessment of the relative dose-intensity (RDI) of the CT courses administered. The endpoints of interest included the assessment of the RDI of CT courses by nosology and CT regimen, the frequency of dose-limiting neutropenia, and the incidence of all adverse events (AEs) in patients who received at least one dose of the study medication, including serious AEs. Results. From February 2021 to December 2022, 3218 patients with various malignancies were included in 41 study centers of the Russian Fede- ration. Of these, 3217 (99.97%) patients received at least one dose of the study drug, and 2663 (82.8%) patients were included in the RDI evaluation population according to the study protocol. The mean age in this group was 56.9 (18–84) years. RDI ≥85% was achieved in 2,415 (90.7%) patients. The mean RDI was 96.2%, with a median of 100%. FN risk factors were present in 1216 (45.7%) patients, with age ≥65 years being the most common risk factor at 761/2663 (28.6%). It should be noted that in patients younger than 65 years, the RDI was 91.5%, and in elderly patients (≥65 years) 88.7%. Dose-limiting neutropenia was reported in 19 (0.7%) patients. There were 74 cases of grade 3–4 AEs (according to CTCAE v.5) in 59 (1.8%) patients. The most common were neutropenia, anemia, and diarrhea in 19 (0.7%), 7 (0.2%), and 6 (0.2%) patients, respectively. Serious AEs were reported in 17 patients (0.5%). Conclusion. Primary prophylaxis of FN with long-acting granulocyte colony-stimulating factor empegfilgrastim effectively maintains RDI in various nosological and therapeutic groups of patients with different CT regimens in real-world clinical practice