INTEGRATIVES AS A FORM OF PERSONNEL TRAINING IN THE CONTEXT OF IMPLEMENTATION OF A NATIONAL PROJECT “LABOR PRODUCTIVITY AND EMPLOYMENT SUPPORT”

The issue of choice of the form of conducting classes within the framework of personnel training at industrial enterprises participating in the implementation of the national project “Labor productivity and employment support” has been studied. In the process of staff training, it is necessary to ensure an interdisciplinary approach to the formation of educational programs and take into account significant restrictions on the time and cost of training, which are provided within the framework of this national project. In such conditions, the most appropriate form of conducting classes with employees of enterprises participating in the national project becomes integratives, which are the union of several academic disciplines using action learning technologies. In the course of the study, a comprehensive model of personnel training using integratives was established, tested at the enterprises participating in the national project “Labor Productivity and Employment Support” in the Perm Territory and also the problems that arise during integrative classes and ways to solve them have been defined. The results of the study can be used to draw up programs and training plans for personnel of enterprises implementing the national project “Labor Productivity and Employment Support” in the regions of the Russian Federation

Bempedoic Acid: Safety and Efficiacy of a New Lipid-Lowering Agent

Scientific relevance. Lowering low-density lipoprotein cholesterol (LDL-C) levels with statins is a generally accepted standard treatment for dyslipidaemia. However, adverse reactions and intolerance to statins have motivated the search for lipid-modifying agents with alternative mechanisms of action. Bempedoic acid is one of these alternative agents.Aim. The study aimed to review published data on the mechanism of action, pharmacokinetics, pharmacodynamics, safety and efficacy of bempedoic acid used as a lipid-lowering agent.Discussion. Similar to statins, bempedoic acid inhibits cholesterol synthesis from acetyl-CoA. Statins and bempedoic acid differ in their mechanisms of action mainly because the conversion of bempedoic acid into its active metabolite takes place only in the liver. As a result, bempedoic acid does not cause adverse drug reactions in muscles. The main safety and efficacy data on bempedoic acid were obtained in phase III CLEAR trials. Compared to placebo, bempedoic acid reduced LDL-C levels by an additional 18% in combination with maximum tolerated doses of statins and by 25% in monotherapy in patients with statin intolerance. In the CLEAR Outcomes trial, long-term treatment with bempedoic acid reduced the risk of major adverse cardiovascular events in patients with statin intolerance (n=13970) by 13%. A slight increase in gout attack frequency was observed, primarily in patients with pre-existing hyperuricaemia.Conclusions. Therefore, bempedoic acid is a safe and effective treatment option for patients with dyslipidaemia at high risk of atherosclerotic cardiovascular disease. It can be used either in combination with statins or, in the case of statin intolerance, as monotherapy and with ezetimibe

The preventive destruction of a hazardous asteroid

One means of countering a hazardous asteroid is discussed: destruction of the object using a nuclear charge. Explosion of such an asteroid shortly before its predicted collision would have catastrophic consequences, with numerous highly radioactive fragments falling onto the Earth. The possibility of exploding the asteroid several years before its impact is also considered. Such an approach is made feasible because the vast majority of hazardous objects pass by the Earth several times before colliding with it. Computations show that, in the 10 years following the explosion, only a negligible number of fragments fall onto the Earth, whose radioactivity has substantially reduced during this time. In most cases, none of these fragments collides with the Earth. Thus, this proposed method for eliminating a threat from space is reasonable in at least two cases: when it is not possible to undergo a soft removal of the object from the collisional path, and to destroy objects that are continually returning to near-Earth space and require multiple removals from hazardous orbits

ASSESSMENT OF REFRACTORY GOLD-BEARING ORES BASED OF INTERPRETATION OF THERMAL ANALYSIS DATA

The article presents the results of a study on the possibility to assess refractory gold-bearing ores using thermal analysis data. It studies the flotation concentrates obtained during the enrichment of double refractory sulfide gold-bearing ores. This type of ore is complicated by the fine impregnation of gold in sulphide minerals and the presence of sorption-active scattered carbonaceous matter, which is in close association with sulphides. The results of thermogravimetric and mass spectrometric studies of refractory gold-bearing ores are presented. The obtained fragments for kerogen CH (m/z = 15), C2H (m/z = 29) and C3H (m/z = 43) indicate the presence of various types of carbonaceous matter in the studied samples. It is justified that the degree of sorption activity of carbonaceous matter depends on the presence of kerogen and bitumen in the ore. High sorption activity of scattered carbonaceous material significantly affects the processing technology of ores and concentrates, both flotation and pyro- and hydrometallurgical methods. Thermogravimetric and mass spectroscopic analyzes can be used to determine the degree of preg-robbing of refractory gold-bearing ores. The obtained results predetermine the direction of creating new methods and technologies in the field of decarburization of refractory gold-bearing ores in the integrated development of solid minerals in the mining regions of Russia

Using Shewhart charts to monitor quality characteristics of preventive vaccines for tuberculosis

Scientific relevance. The quality of medicinal products, particularly vaccines, is contingent on the stability of the manufacturing process at all stages, which can be evaluated using Shewhart charts for data obtained by monitoring the quality attributes of interest.Aim. This study evaluated the stability of the quality and manufacturing processes of the BCG and BCG-M tuberculosis vaccines using Shewhart charts.Materials and methods. This study focused on samples of the BCG tuberculosis vaccine and the BCG-M tuberculosis vaccine, a less reactogenic alternative for primary immunisation. Both vaccines were released to the market in 2019–2022. The quality of samples was assessed for stability based on their potency and total bacterial count, which are the key parameters for immunogenicity evaluation. These quality parameters were compared using test results submitted by the manufacturer and obtained at the testing centre. The authors plotted individuals charts (X-charts) and moving range charts (R-charts) in accordance with national standards GOST R 50779.42-99 and GOST R ISO 7870-2-2015.Results. The quality of the BCG and BCG-M vaccines remained stable during the entire follow-up period (2019–2022). For some periods, the retrospective analysis of R- and X-charts revealed characteristic trends meeting special cause criteria. The Pearson correlation coefficient (r) between the data submitted by the manufacturer and the data obtained at the testing centre ranged from 0.2 to 0.8.Conclusions. The Shewhart charts demonstrated that the quality parameters of the BCG and BCG-M tuberculosis vaccines tested in 2019–2022 were stable. These vaccines had stable manufacturing processes, as shown by the R- and X-charts. However, the warning signs indicated that additional measures should be taken to standardise the manufacturing processes. The findings suggest that Shewhart charts may be recommended for monitoring the production and quality of tuberculosis vaccines

Specific Aspects of Tuberculin Products Standardisation

According to the existing international practice, reference materials, which are used to assess specific activity of purified tuberculin products, are meant to be used for several decades and are therefore characterised by high stability. For instance, PPD-S tuberculin produced in the USA in 1944 has been used ever since as the international reference standard of purified tuberculin and is stored as lyophilisate in ampoules (PPDT) containing 5000 IU each. The Russian PPD-L-2 industry reference standard is made from material produced by the Leningrad Research Institute of Vaccines and Sera in 1973. It has been used for many years to control production batches of PPD-L purified tuberculin because of its high stability that is regularly confirmed in large-scale studies using various experimental models in accordance with the requirements of the World Health Organisation. The aim of the study was to evaluate the long-term stability of the substance of industry reference standard of purified tuberculin (PPD-L-2 IRS) by determining its specific activity relative to the international standard of purified tuberculin, and determine the feasibility of using this substance for the preparation of lyophilised reference product samples. Materials and methods: PPD-L-2 IRS specific activity was determined relative to the PPDT international standard in accordance with the procedure specified in the monograph FS.3.3.1.0023.15 of the State Pharmacopoeia of Russian Federation (14 edition) using guinea pigs vaccinated with various BCG substrains or sensitized by virulent mycobacteria («live» or «inactivated») in accordance with the recommendations of the WHO (WHO TRS 45, 1987). Results: the analysis of the obtained data showed that there were 3–4-fold differences in PPD-L-2 IRS relative potency depending on the BCG substrain used for guinea pigs vaccination (animal sensitization model). This effect of the titration model manifested itself when comparing specific activity of tuberculins obtained by various methods of tuberculoprotein precipitation (PPD-L-2 and PPDT), i.e. different in antigen composition. The specific activity of the previously established dose of PPD-L-2 IRS was shown to be equivalent to the international reference standard in animals sensitized with mycobacteria tuberculosis. Conclusions: the results of PPD-L-2 IRS specific activity assessment obtained in this study are consistent with the data obtained during development and certification of this reference material in the 1980s and confirm the long-term stability of the intermediate powder product of the Russian reference standard of purified tuberculin. At the same time, the production of a freeze-dried form of the IRS, in addition to being economically feasible, would rule out some potential errors that are inevitable during annual preparation and control of the reference standard dilutions, and would make it possible to spare the substance which would improve prospects for the future long-term use of PPD-L as an industry reference standard

Stability of the Industrial Reference Standard of Tuberculosis Vaccine (BCG)

The industrial reference standard of tuberculosis (BCG) vaccine (IRS), certified and registered by the Federal State Budgetary Institution “Scientific Centre for Expert Evaluation of Medicinal Products” of the Ministry of Health of the Russian Federation (OSO 42-28-420), is used as a reference product in quality control of tuberculosis vaccines BCG and BCG-M. The IRS is a useful means of quality control of these products, as the stability of its proper ties helps to minimise errors during quality evaluation. The shelf life of the BCG vaccine IRS is not more than 2 years if stored at 2–8 °C. It is likely that a vaccine batch could be used as the IRS for a longer period of time. The literature data suggest that the shelf life of a BCG vaccine can be prolonged if it is stored at low temperatures. However, due to significant phenotypic and genotypic differences between BCG sub-strains, the extrapolation of these data to the vaccine produced from the Russian Mycobacterium bovis BCG-I sub-strain requires appropriate testing. The aim of the study was to analyse the possibility of increasing the shelf life of the tuberculosis vaccine IRS by changing the storage temperature. Materials and methods: the effect of low temperatures on the stability of OSO 42-28-420 was studied in commercial batches of tuberculosis vaccine which met all the quality requirements for candidate IRSs. Samples from 6 IRS batches produced from 2014 through 2019 were stored at –(20 ± 1) °С. The stability of their quality characteristics, namely “Specific activity (viability)”, “Total bacterial count”, and “Dispersibility”, was monitored according to the recommendations of the World Health Organization. The obtained data were evaluated relative to the baseline data obtained during certification of each batch. Results: it was demonstrated that there was more than 95 percent probability that the tested parameters would not differ from the initial data if OSO 42-28-420 samples were stored at a low temperature for 5 years. Conclusions: the results obtained support the prolongation of the OSO 42-28-420 shelf life up to 4 years under the recommended storage conditions at –(20 ± 1) °С

A Modern View of Anomalies in the Metal Groups of the Periodic System of D.I.Mendeleev

The article is devoted to the 150th anniversary of the Periodic Table of Chemical Elements by D.I.Mendeleev. The fundamental law of nature, discovered by D.I.Mendeleev has anomalies and paradoxes associated with certain groups of metals. When studying the physical and chemical properties of complex metal compounds, many discrepancies can be found, namely, the location of elements in groups, which primarily relate to metals with different valences. By studying the approaches and methods for predicting the arrangement of chemical elements, it can be established that D.I.Mendeleev eliminated many differences for some metals during the formation of the Periodic system of chemical elements. D.I.Mendeleev developed a principle that excludes such errors when finding and discovering new elements. Analytical studies conducted by a Russian scientist helped to calculate the atomic masses and describe the properties of three elements not known at that time – «eka-boron», «eka-silicon», «eka-aluminum», the existence of which was proved and confirmed by subsequent discoveries of scandium, germanium, boron, and gallium. The paper provides a significant assessment of the forecasting of metals in various groups of the periodic system. Changes in the properties of some metals significantly influenced their location in the table of D.I.Mendeleev

Вакцинопрофилактика туберкулеза

BCG vaccine for tuberculosis was developed nearly 100 years ago and still remains the only medicine for specific immunological prevention of tuberculosis. Despite the fact it has been actively used for a long time in more than 100 countries, the results of vaccination are very contradictory. The protective effect of BCG vaccination is assessed from 0 to 80%, while the efficacy of BCG vaccination in children, especially in infants, is generally recognized. BCG helps to reduce tenfold the number of tuberculous meningitis and disseminated tuberculosis in children. However BCG neither protects the population from mycobacteria infections nor the adults from pulmonary tuberculosis, although it prevents extrapulmonary tuberculosis. For the last 20 years new tuberculosis vaccines have been intensive developed, their efficacy is believed to exceed the efficacy of BCG vaccine, with the minimized adverse reactions. Nevertheless out of more than 200 tuberculosis vaccine candidates only few were allowed for clinical trials. In the upcoming years the humanity can not count upon a medicine that could replace BCG. Therefore the research efforts should be focused on improving BCG vaccine in order to enhance its protective effect and to reduce adverse effects.Созданная почти 100 лет назад вакцина туберкулезная БЦЖ остается до настоящего времени единственным препаратом для специфической иммунологической профилактики туберкулеза. Несмотря на массовое использование в течение длительного времени в более чем в 100 странах мира, данные о результатах вакцинации остаются очень противоречивыми. Защитный эффект вакцин БЦЖ оценивают от 0 до 80%, при этом эффективность вакцинации БЦЖ детей, особенно раннего возраста, общепризнанна. Применение этого препарата способствует снижению в десятки раз числа туберкулезных менингитов и диссеминированных форм туберкулеза у детей. Однако БЦЖ не защищает население от инфицирования микобактериями, а взрослых от туберкулеза легких, хотя предотвращает внелегочные формы туберкулеза. В последние 20 лет ведутся интенсивные разработки новых туберкулезных вакцин, эффективность которых, как полагают, превысят вакцину БЦЖ, при минимальных побочных реакциях на их введение. Однако из 200 с лишним кандидатов туберкулезных вакцин до клинических исследований дошли единицы. В ближайшие годы человечество не может рассчитывать на препарат, который мог бы заменить вакцину БЦЖ. Поэтому усилия исследователей должны быть направлены на усовершенствование вакцины БЦЖ с целью повышения ее защитного эффекта и снижения побочного действия

New advances in Raman study of polyvinylchloride structure

In this work we investigated Raman spectra of a number of industrial grades of polyvinylchloride powder and films, prepared from solutions in tetrahydrofuran and acetophenone. The number and spectral characteristics of the Raman lines in the spectral regions of the C-Cl stretching vibrations and in the region of the C-H and CH2 stretching vibrations were evaluated