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Purpose of the study. Educational methodological activity plays an important role in the life of the university, on the one hand, it determines the content of the educational process and sets the direction of development, on the other hand, it requires a significant amount of time from teachers, staff and managers. Continuing changes in the system of Russian higher education are reflected in educational methodological activities. When introducing and refining higher education standards and other normative documents, the means of describing the educational process in educational and methodological documentation change. The composition of educational methodological documents and the requirements for them are changing. Such concepts as “competence”, “type of activity”, “tasks of professional activity”, “labor functions”, etc. appear and then transform. The present work aims to track the dynamics of these changes and assess the increase in the complexity of educational methodological support. Materials and Methods. To assess the dynamics of development of educational and methodological support, we will carry out a retrospective substantive analysis of educational and methodological support for each stage of its development, starting with the first generation of state educational standards. The analysis results will be visualized with the Entity-Relationship" diagrams, which allow reflecting the main entities of the scope, their attributes and relationships. Examples of entities are: competence, professional standard, educational result (different forms of skills), topic, module, etc. Such diagrams can be interpreted as metamodels of educational and methodological support. Next, we will carry out a comparative analysis of the obtained sequence of metamodels, which will allow us to understand the dynamics of their development. Results. A set of metamodels of educational and methodological activities was built. The dynamics of the growth of the number of entities and relationships by year was found. We also studied changes in entities and details. A set of metamodels of educational and methodological activities was built, including metamodels for the following stages: state educational standards of the first generation, second generation, federal state educational standards or the third generation, generation 3+, generation 3 ++. If the first two models are characterized by relative simplicity, then the standards of the third generation required the development of a significant number of new entities associated with competencies, and another increase in complexity is observed for generation 3 ++, which is associated with the introduction of professional standards. The dynamics of growth in the number of entities, attributes and especially relationships has been established. Over the past two decades, the number of entities that are used in the creation of educational and methodological support has increased from 9 to 32, and the number of connections between them from 12 to 45. Changes in individual entities and details were also studied as the metamodels of educational and methodological support developed. Conclusion. Based on the results of the analysis, describing tools for the educational and methodological support tend to become considerably more sophisticated. This is reflected in the labor costs of the formation of documents, as well as the time that must be spent by teachers and staff on studying the language of description of educational and methodological documents. Thus, there are risks of the educational and methodological support quality reducing and the risk of a gap between educational and methodological documentation and the real educational process of the university.

The paper examines the doctrinal aspects of understanding cyber terrorism as an atypical manifestation (form) of traditional terrorism updated in light of the intensive development and widespread dissemination of information and communication technologies (ICT) in the modern world. The conclusion is substantiated that cyber terrorism is a conceptually relevant concept, which is perceived either as a method of committing a terrorist act (reduced understanding), or as any crimes of a terrorist nature that are committed using information and communication technologies (broad understanding). Analysis and generalization of scientific positions allowed us to define this phenomenon of social reality as the illegal use of information and communication technologies in relation to computer information, computer systems and networks in critical segments of the state and in the private sector, which pose a risk of death, causing significant property damage or the onset of other socially dangerous consequences, with the aim of whipping up fear and tension, as well as influencing the authorities for political or other motives characteristic of the ideology of terrorism.

The article discusses the use of the Agile methodology in providing educational and methodological activities at university. The article presents the current results of the study carried out with the financial support of the Russian Foundation for Basic Research (RFBR) in the framework of the research project No. 19-013-00690 “Economics of educational and methodological activities in high school”. The article proposes the requirements that can be applied to the use of the Agile methodology in providing educational and methodological activities of the University. The possibility and expediency of using this methodology for the successful implementation of these processes has been substantiated. The principles and tools of Agile in adaptation to the educational process of the university are presented. The components of the proposed approach are considered, in particular: the basic principles of the Agile methodology and the possibility of their application in educational and methodological activities; the compatibility of Agile with the existing system of educational and methodological support; areas where Agile technologies and principles can be adapted immediately and without significant problems. The problems on the way of introducing flexible methodologies into the educational and methodological activities of the university are indicated.

Background The relationship between a daily dose of olanzapine, its serum concentration, and the genotype of young nonsmoking men treated for schizophrenia or schizophreniform disorder was investigated in day-to-day clinical practice. Pharmacogenetics was also examined for the selected patients. Methods A total of 49 participants were recruited as in-patients at the Mental Health Research Center (Moscow, Russia). Inclusion criteria were patients who had been diagnosed with schizophrenia or schizoaffective disorder (following DSM-IV guidelines) and were being treated with OLZ. A prospective, observational, open-study design was implemented. In line with the literature, patients were only included if they attained steady-state OLZ concentrations lasting for at least 8 days. A liquid chromatographic-tandem mass spectrometric method was developed for analyzing OLZ in human serum. The single cytochrome P450 polymorphisms were genotyped using an amplifier real-time polymerase chain reaction system following standard protocols. Results Evidence indicating that CYP2D6 polymorphism has a significant (P = 0.046) effect on the pharmacokinetics of olanzapine was obtained, confirming the beneficial effects of therapeutic drug monitoring (TDM) for olanzapine. Conclusions TDM should therefore be used as a standard care during olanzapine therapy. TDM is also useful in assessing adherence and may have a role in limiting olanzapine dosage geared at minimizing the risk of long-term toxicity.

Objectives. To study the N-acetylaspartate (NAA) content in the plasma of elderly patients with depression during treatment with antidepressants combined with Actovegin. Materials and methods. Nineteen patients – seven men, 12 women, age 70.5 ± 5.8 years – were treated in hospital conditions. Patients underwent clinical psychiatric evaluation using a series of psychometric scales, along with computerized tomography (CT) and biochemical assay of NAA. Patients received antidepressants (venlafaxine and fluvoxamine at therapeutic doses) and Actovegin for 28 days and were investigated before and after treatment (day 28). Results and conclusions. Decreases in blood NAA were found in pretreatment patients as compared with healthy subjects, with increases after treatment, which corresponded to a significant improvement in patients’ status both clinically and on psychometric scales. Heterogeneity was found in the cohort of patients in relation to the nature of changes in contents (increases or decreases) of NAA, which was not linked with treatment efficacy but correlated with the burden of comorbid somatic diseases, especially vascular, and some CT features (leukoaraiosis). The authors emphasize the preliminary nature of the results.

Summary. The results of treatment of 108 patients with unstable fractures of the pelvic bones and internal organs lesions were provided for the period from 2009 to 2017, 56 of them were victims of the proposed tactic, which allowed to reduce the postoperative mortality by 17,3 %, the frequency of purulent-septic complications by 14,7 %.

The ongoing shift from the industrial to the digital era dramatically affects the institutional structures, public and private communication in society, the dynamics of the search for a balance of interests, etc. Data is becoming a new driving force for economic and social development, shaping the post-capitalistic era. The authors discuss one of the most rapidly developing technological trends in the modern world—digital platforms, cloud technologies, and artificial intelligence systems in general. At the same time, the research notes that the existing legal regulation tries to “fit” the changes taking place within the existing concepts, models, legal structures, and terms. And, these models, constructions, and terms often come into conflict with newly emerging specific phenomena and the practice of their implementation. In the context of the collision of the state and society with the global challenges, there is a strong necessity to create institutions and mechanisms that provide social and legal control, algorithmization of political processes based on digital platforms, etc. It is also noted that it is reasonable to start the solution of these problems from the formulation of the concept of advanced legal modeling, the creation of a common doctrine, methodology, and standardization of the processes of developing autonomous vehicles, software, forecasting the relationship between man and machine, and so on. And only then is it possible to implement a comprehensive program of legislative changes, the development of relevant sub-sectors, and individual branches of law.

Actuality. Arterial hypertension (AH) is the main risk factor for the development of cardiovascular diseases, disability and cardiovascular mortality. Episodes of blood pressure (BP) increase during the day in patients receiving antihypertensive therapy are an unfavourable factor contributing to the development and progression of cardiac remodeling. Aim. The purpose of the research is to study the features of changes in the structural and functional state of the heart under the influence of high blood pressure at night in patients with arterial hypertension with the dynamic three-year observation. Material and methods. 47 patients with the diagnosis of AH were examined. Patients were divided into two groups, randomized by age, duration and severity of AH. Group 1 included 24 patients who as a result of ambulatory blood pressure monitoring (ABPM) on the background of combined antihypertensive therapy suffered from constantly increased BP at night. The second group combined 23 patients without the increase in BP during the night according to the ABPM with antihypertensive therapy. The examination included measurement of the office BP, ABPM, two-fold echocardiography with a three-year interval. Results. When assessing the indices of office BP in the groups, there were no significant differences, all patients achieved the target values of BP. In patients in Group 1, higher values of BP were observed during the day, according to ABPM. Echocardiography over a three year period of observation revealed a more pronounced increase in diastolic interventricular septum thickness, the thickness of the left ventricle posterior wall during diastole, sizes of left atrium in the patients of the first group, patients of the second group had a more pronounced thickness of the left ventricle posterior wall during systole. The increase in the size of the right ventricle was revealed in both groups. Conclusions. 1) In patients with the increase in blood pressure at night, the values of BP variability were higher during the day. 2) Three-year dynamic observation revealed that the increase in BP at night in patients with hypertension facilitated acceleration of cardiac remodelling and was associated with an increase in the left ventricular posterior wall, interventricular septum thickness, the size of the left atrium, and the size of the right ventricle.

One of the negative factors of civilization around the world is the significant growth of injury rate. The manifestations of the latter include suicidal acts that occur in the process of social and individual life. Sometimes people commit suicide because of having incurable diseases. Alcohol addiction contributes to suicide risk. To share with the general medical community the rare case of suicidal trauma which seemed fatal but resolved favorably, though it was not immediately verified. Only after performing a radiological examination in two projections, the subject of suicidal action was detected. We observed a case of a suicide victim: a 55-year-old patient who, being impaired by alcohol, decided to commit suicide after learning about COVID-19 mortality. One hour later he was admitted to the emergency department. After stabbing himself with a kitchen knife, a 55-year-old patient called an ambulance and was delivered in satisfactory condition to the emergency surgical department 1 hour after the injury. There were no signs of bleeding or its consequences or manifestations of vena cava compression. Hemodynamics was stable; there were no external respiration disorders. Clinical blood test was within normal range. Revision of the wound in the lower neck was performed. At a depth of 2.5 cm, something perceived as a sternal notch was located manually, which later turned out to be a foreign body. Due to the location of the injury, it was decided to hospitalize the injured patient for observation. Plain and lateral radiography was performed. Longitudinal sternotomy was chosen for access. Under the entrance wound in the neck, in the lateral mediastinum above the root of the lung, a knife was found above the diaphragm penetrating the parenchyma of the lower lobe. After removing the knife, the lung wound was sutured. The postoperative period ended successfully. Before surgery, an imaging study with at least two different views is mandatory for all chest wounds. If possible, thoracotomy should be scheduled for the daytime.

In the context of this study, the authors narrow the concept of modern information technologies to artificial intelligence technologies (to a greater extent - strong artificial intelligence) to consider the prospects, threats and risks associated with the introduction of these technologies within the framework of Legal Tech system in legal processes. So the main issue becomes the conclusion that professional legal sphere in future may possibly exist as a combination of technological and human resources. Artificial intelligence is described not a the threat to professional lawyers’ activity but a the great tool for democratization of the whole system of professional legal help and also will minimize the routine component of the work of a particular lawyer, allowing him or her to concentrate on finding non-standard solutions within his or her specialization.

The research is devoted to the legal and deontoloigical challenges the society faces in the time of global recognition of artificial intelligence technologies. The authors suggest that adapting current statutory and legal models to, and “adjustment” of legal and technical tools for entirely different relations is poorly effective. The shift from the instrumentalization of the law and “resemblance” mechanism require the formation of the relevant legal policy, development of a special concept of the front-running legal development of society and legal modelling of fundamentally new relations. The main difficulty of the legal and demonological regulation of the process of development and implementation of artificial intelligence systems and robotized technologies is due to the antonymic nature of the latter, since they act as the product and the object of human life activity.

Increases the complexity of educational documentation leads to the need for adequate assessment of the complexity of a particular discipline and the complexity of the teacher labor. Required to consider and create tools to quantify their work. Analysis tool is selected and neural network Kohonen self-organizing maps. The study was developed by the original soft-ware product is invariant to the number of estimated parameters, providing high-quality original data clustering and visualization of the results. The approach has been tested in the working programs of disciplines implemented for areas of “Information systems and technology” and “Applied Computer Science”. Data for the analysis were taken over the past three years.

The importance of finding predictors or biomarkers of neuropsychiatric pathology, as well as methods of its prevention, treatment and early diagnosis is beyond question. The level of neopterin in body fluids is one of the possible biomarkers. Increased levels of neopterin in biological fluids (e.g., serum, cerebrospinal fluid or urine) are closely associated with various diseases associated with cellular immune response. The data presented in the review indicate the relevance of the study of neopterin concentrations in body fluids in patients with mental illness for the development of diagnostic and prognostic tests or as a pharmacodynamic marker of drug action.Важность поиска предикторов или маркеров развития неврологической и психической патологии, а также методов ее профилактики, лечения и ранней диагностики не вызывает сомнений. Одним из возможных биомаркеров является уровень неоптерина в биологических жидкостях организма. Повышенное содержание неоптерина в биологических жидкостях (например, в сыворотке, цереброспинальной жидкости или моче) было установлено при разных заболеваниях, в патогенезе которых определенную роль играют клеточные иммунные реакции. В ряде работ была показана высокая диагностическая и прогностическая значимость показателей уровня неоптерина. Данные, представленные в обзоре, свидетельствуют об актуальности исследования концентраций неоптерина в биологических жидкостях организма у пациентов с психическими заболеваниями для разработки диагностических и прогностических тестов или в качестве фармакодинамического маркера действия лекарственных веществ.

The article deals with the educational and methodological aspects of higher education digitalization. The current digitalization of the economy and education opens up new opportunities for universities, but also entails competition from other forms of education, in particular, mass online courses (MOOCs). A comparative analysis of the educational and methodological works’ peculiarities in the context of traditional teaching and use of MOOCs is carried out in the article. For both options, models of the teaching and learning cycle, including the development of learning and teaching support materials, its implementation in the educational setting, analysis and modification are built. By a comparative analysis of the traditional model and the MOOC model, it is shown that the significant advantages of MOOCs are the following: acceleration of the teaching and learning cycle; possibility of improving learning and teaching support materials based on the analysis of educational data; shifting the focus of analysis from teaching and learning documentation to its immediate use in the educational setting. Effective implementation of new forms of education in the universities is possible only with the reconsideration of traditional approaches to teaching and methodological work.

Various methods are considered for the production of useful electric and thermal energy based the use of a steam–hydrogen mixture with parameters corresponding to the parameters upon the exit of hydrothermal oxidation of aluminum from an experimental reactor developed earlier at the Joint Institute for High Temperatures of the Russian Academy of Sciences. The appropriate types of basic power-generating equipment that operate on hydrogen are chosen. The main thermodynamic parameters of the schemes of thermal power plants are analyzed, and their thermodynamic efficiency is determined.

First results of the analysis of GPS measurement data obtained from 18 sites of two local networks in the vicinity of Ulaanbaatar (Mongolia) for the period 2010–2015 have been presented. Horizontal velocity vectors are consistent with each other in the ITRF2014 system and with the velocities of the IGS permanent station ULAB. The sites move in the E–SE direction at a rate of 25–30 mm/yr, with the displacement azimuth averaging 105°. With respect to Eurasia, the vectors for most of the sites are slighly turned to the south, but they are still of SE orientation with the azimuth range of 130°–150° and magnitude values of 2–4 mm/yr. Relative horizontal velocities tend to decrease towards southeast that determines a zonal distribution of different type of relative strain patterns. The western part of the Ulaanbaatar network is characterized by the W–E oriented extension with the elongation rate ε1 = 12–16 × 10–8 yr–1. The shortening NW–SE trending strain with calculated value ε2 = 22.4 × 10–8 yr–1 characterizes the network’s eastern part. The highest values of the maximum shear strains (εmax = 10–14 × 10–8 yr–1) form an extended area in the center of the testing ground, which is elongated in the northeastern direction, conformably with the strike of the major geologic structures. The strain distribution pattern of the Emeelt network located within the eponymous seismogenic structures is characterized by the crustal elongation (5 × 10–6 yr–1) trending SE–NW and less pronounced shortening in the SW–SE directions. The axial part of the fault crossing the network in the NW direction exhibits maximum deformations.

The paper describes the development of a software product, based on the architecture of the neural network, which allows to handle record telephone conversations and identify their emotional color. The approaches to the training of the neural network. Based on neural network developed a software product that allows you to assess the emotional state of the negotiators when contacting the emergency services to the quality of more than 60%, which was successfully tested. Carried out the integration of the software with other informational systems specified services.

The authors analyzed noninfectious complications (dislocation of endoprosthesis head, periprosthesis fractures) in 8 patients out of 40 with hip arthroplasty. There were estimated clinical, biomechanical results and quality of life of the patients. An application of the external fixator-orthezes should be recommended in order to prevent complications of hip replacement. The wearing of brace is considered to be reasonable after revision interventions.

The near-Earth environment can be considered a unique place where different space radiation fields exist and can play a significant role in the estimation of radiation risks both for robotic and manned space missions. One cannot exclude the cumulative effect for particular spacecraft orbits the result of simultaneous impact of the different radiation fields. Among the types of space radiation, we consider: trapped radiation at low Earth orbits (LEO): solar energetic particles (SEP) penetration in the magnetosphere, including ground level enhancement events (GLE); and variations of galactic cosmic rays (GCR) during the different extreme levels of geomagnetic and solar activity. Results of empirical modeling of these different radiation fields and some results of measurements of their physical parameters (energy spectra, space and time variations) for different solar (extreme solar maxima and solar minima) and geomagnetic (the major magnetic storms) conditions are analyzed. The models are based on quantitative relationships between the particle fluxes, taking into account the solar activity (sunspot numbers). Examples of using these models to estimate changes of radiation hazards in interplanetary space for the possible case of solar activity reduction during the nearest solar cycles 25 and 26 are analyzed.

BACKGROUND Haloperidol is used for the treatment of alcohol use disorders in patients with signs of alcohol-related psychosis. Haloperidol therapy poses a high risk of adverse drug reactions (ADR). Contradictory data, which include the effects of genetic polymorphisms in genes encoding the elements of haloperidol biotransformation system on haloperidol metabolism rate and plasma drug concentration ratio, are described in patients with different genotypes. The primary objective of this study was to investigate the effects of CYP2D6 and CYP3A5 genetic polymorphisms on haloperidol equilibrium concentration in patients with alcohol use disorder. METHODS The study included 69 male patients with alcohol use disorder. Genotyping was performed using the allele-specific real-time PCR. CYP2D6 and CYP3A were phenotyped with HPLC-MS using the concentration of endogenous substrate of the enzyme and its urinary metabolites [6-hydroxy-1,2,3,4-tetrahydro-β-carboline(6-HO-THBC) to pinoline ratio for CYP2D6 and 6-β-hydroxycortisol to cortisol ratio for CYP3A]. The equilibrium plasma concentration was determined using LC-MS-MS. RESULTS Results indicated that both C/D indexes and equilibrium concentration levels depend on CYP2D6 genetic polymorphism, but only in patients receiving haloperidol intramuscular injections [0.26 (0.09; 0.48) vs. 0.54 (0.44; 0.74), p=0.037]. CONCLUSIONS The study demonstrates that CYP2D6 genetic polymorphism (1846G>A) can affect haloperidol concentration levels in patients with alcohol use disorder.

There are plenty of evidencessupporting the contribution of genetic variability to the mechanisms that responsible for both therapeutic and adverse effects of antipsychotic medications. We report a case that is an example of using cytochrome P450 pharmacogenetics and therapeutic drug monitoring in an attempt to guide schizophrenia treatment. This example illustrates the potential of applying the principles of predictive, preventive, and personalized medicine to the therapy of psychotic disorders.

Results of long-term experimental studies and modelling of faulting are briefly reviewed, and research methods and the-state-of-art issues are described. The article presents the main results of faulting modelling with the use of non-transparent elasto-viscous plastic and optically active models. An area of active dynamic influence of fault (AADIF) is the term introduced to characterise a fault as a 3D geological body. It is shown that AADIF's width (М) is determined by thickness of the layer wherein a fault occurs (Н), its viscosity (η) and strain rate (V). Multiple correlation equations are proposed to show relationships between AADIF's width (М), H, η and V for faults of various morphological and genetic types. The irregularity of AADIF in time and space is characterised in view of staged formation of the internal fault structure of such areas and geometric and dynamic parameters of AADIF which are changeable along the fault strike. The authors pioneered in application of the open system conception to find explanations of regularities of structure formation in AADIFs. It is shown that faulting is a synergistic process of continuous changes of structural levels of strain, which differ in manifestation of specific self-similar fractures of various scales. Such levels are changeable due to self-organization processes of fracture systems. Fracture dissipative structures (FDS) is the term introduced to describe systems of fractures that are subject to self-organization. It is proposed to consider informational entropy and fractal dimensions in order to reveal FDS in AADIF. Studied are relationships between structure formation in AADIF and accompanying processes, such as acoustic emission and terrain development above zones wherein faulting takes place. Optically active elastic models were designed to simulate the stress-and-strain state of AADIF of main standard types of fault jointing zones and their analogues in nature, and modelling results are reported in the article. A good correlation is revealed between the available seismological, structural geological and geodetic data.

Objectives: This article provides a look from the inside at present-day higher education – its current state and the latest issues and reforms in it, as seen by college professors with extensive work experience. The authors view education as an element in the society’s education – individual’ system. Methods/Statistical Analysis: The authors rely on their own professional experience to prove that at present society and authorities are not doing much in the way of creating the necessary and sufficient conditions for colleges to function effectively. Hence, the lack (and ineffectiveness) of reform in education. Colleges do not have access to resources they need in order to achieve their goals and meet the objectives set by society. Findings: Models for the reformation and development of higher education vary drastically depending on which element’s interests and needs are put at the top of the list: society, the individual, or education (e.g., institutions of higher learning) as a social institute and a particular type of relations. Most of the latest proposals on improving the quality and effectiveness of education tend to be geared towards the interests and objectives of society as a whole. It is to a lesser degree that these proposals are directed towards the interests of the individual (learner). The interests of education as a particular institute are not being considered at all. Having said that, the development of any system requires that the conditions necessary for the existence and development of each of the system’s elements be met. Application/Improvements: The authors propose a special approach to defining a set of goals and objectives in higher education, which they term a problem-objective approach. The idea is simple: overcoming the major issues most law schools tend to face during the process of an educational activity must become a proximal and current objective in legal education.

Introduction The antipsychotic action of haloperidol is due to the blockade of D2 receptors in the mesolimbic dopamine pathway, while the adverse drug reactions are associated with striatal D2 receptors blockade. Contradictory data concerning the effects of genetic polymorphisms of genes encoding these receptors and associated structures (catechol-O-Methyltransferase, glycine transporter and gene encoding the density of D2 receptors on the neuronal membrane) [1,2], and also genes encoding the elements of haloperidol biotransformation system on haloperidol metabolism rate as well as plasma drug concentration ratio is described in patients with different genotypes [3,4]. Aims To evaluate the correlation between DRD2, SLC6A3 (DAT) and COMT genetic polymorphisms and to investigate their effect on the development of adverse drug reactions in patients with alcohol use disorder who received haloperidol. The second objective of this study was to investigate the effects of CYP2D6 and CYP3A5 genetic polymorphisms on haloperidol equilibrium concentration in patients with alcohol use disorder. Methods The study included 114 male patients (average age 38.12±9.08; median age 39; LQ 34; UQ 48). Bio-Rad CFX Manager™ software (USA) and "SNP-Screen" sets of "Syntol" (Russia) were used to determine polymorphisms rs4680, rs1800497, rs1124493, rs2242592, rs2298826, and rs2863170. In every “SNP-Screen” set, two allele-specific hybridizations were used, which allowed to determine two alleles of studied polymorphism separately on two fluorescence channels. Genotyping was performed using the allele-specific real-time PCR. CYP2D6 and CYP3A were phenotyped with high-performance liquid chromatography-mass spectrometry using concentration of endogenous substrate of the enzyme and its urinary metabolites (6-hydroxy-1,2,3,4-tetrahydro-beta-carboline(6-HO-THBC) to pinoline ratio [5] for CYP2D6 and 6-beta-hydroxycortisol to cortisol ratio for CYP3A). The equilibrium plasma concentration was determined using LC-MS-MS. Statistical analysis of the results was performed with non-parametric methods using the ”Statsoft Statistica v. 10.0“ (Dell Statistica, Tulsa, OK, USA). The normality of samples distribution was evaluated using W-Shapiro-Wilk test and taken into account when choosing a method. The differences were considered as statistically significant at р Results Results of this study detected a statistically significant difference in the adverse drug reactions intensity in patients receiving haloperidol with genotypes 9/10 and 10/10 of polymorphic marker SLC6A3 rs28363170. In patients receiving haloperidol in tablets the increases in the UKU score of 10.99 ± 2.12 (10/10) vs 13.14 ± 2.08 (9/10) (p Conclusions Polymorphism of the SCL6A3 gene can affect the safety of haloperidol, and that should be taken into account during the choice of drug and its dosage regimen. Also our study demonstrates that CYP2D6 genetic polymorphism (1846G>A) can affect haloperidol concentration levels in patients with alcohol use disorder.

To conduct a routine therapeutic drug monitoring (TDM) and analyze its results for the optimization of pharmacotherapy.Fifty-six inpatients (in total 68 samples) with various forms of schizophrenia were enrolled. High performance liquid chromatography with mass-spectrometric detection was used for quantitative determination of risperidone and 9-hydroxyrisperidone in the serum.Concentrations of risperidone and 9-hydroxyrisperidone were correlated with drug dose. Total concentrations in the blood at doses from 2 to 8 mg per day were distributed as follows: 44.1% were in the therapeutic, 29.4% in sub-therapeutic (20 ng/mL) and 26.5% in conditionally toxic range (60 ng/mL).Concentrations of risperidone and 9-hydroxyrisperidone did not follow the normal distribution. The results showed that monitoring of the total concentration of risperidone and its metabolite 9-hydroxyrisperidone was an effective tool for testing and quality control for the purpose of individualization of pharmacotherapy.Цель исследования. Проведение терапевтического лекарственного мониторинга рисперидона (РИC) и анализ его показателей в аспекте оптимизации проводимой фармакотерапии. Материал и методы. Обследовали 56 пациентов (всего 68 образцов крови) с различными формами шизофрении, проходивших лечение в условиях стационара. Для количественного определения РИC и его активного метаболита - 9-оксирисперидона (9-ОН-РИC) в крови применяли метод высокоэффективной жидкостной хроматографии с масс-спектрометрическим детектированием. Результаты. Установлена зависимость между концентрацией РИC и 9-ОН-РИC и дозой препарата. Полученные данные об их суммарной концентрации в крови при использовании доз от 2 до 8 мг в сутки распределились следующим образом: 44,1% исследованных образцов находились в пределах терапевтического диапазона, 29,4% - субтерапевтического (20 нг/мл) и 26,5% - условно-токсического (60 нг/мл). Заключение. Приведенное распределение концентрации РИC и 9-ОН-РИC не подчиняется нормальному закону распределения. Полученные данные в целом показывают, что мониторинг суммарной концентрации РИC и его метаболита является необходимым условием индивидуализации фармакотерапии и интерпретации результатов ее эффективности.

Aim.To assess the effectiveness of a complex programme of primary cardiovascular prevention, including statin therapy (Liptonorm), among men from an occupational sample who have high coronary risk levels.Material and methods.The occupational sample included male train drivers and train driver assistants, aged 40–55 yeas. The primary prevention programme included the assessment of the risk factors (RFs) and SCORE risk levels; the development of an individual prevention plan; the Workplace Health School, with Self-Control Diary distribution; and the 6-month administration of Liptonorm (mean dose 14,7±5,1 mg/d) in the high-risk group.Results.In 2010–2011, 224 men participated in the primary prevention programme. The high-risk group, as assessed by the SCORE scale, comprised 14,3%. The results of preventive measures, including the 6-month Liptonorm therapy, are presented for the high-risk group. In particular, 29,4% of the men stopped smoking. The daily number of cigarettes smoked at workplace decreased by 5,1. Consumption of >2 drinks per day, overweight, and abdominal obesity prevalence decreased by 12,5%. The prevalence of insufficient rest time and night sleep Conclusion.The workplace administration of the complex preventive programme, including statin administration, facilitates modification of behavioural RFs, achievement of target blood lipid levels, and total coronary risk reduction.

The objective of this work was to study effects of alpha-lipoic acid (α-LA), 3-oxypyridine and succinic acid derivatives (emo­xipine, reamberine, and mexidole) on the metabolic status, conditioned reflex learning, and motivated behaviour in rats with alloxan-induced diabetes receiving basal insulin therapy. The data obtained were compared with effects of the above antioxidants (AO) on insulin sensitivity and results of glucose tolerance test in intact animals. It was shown that administration of AO during two weeks corrected disturbances of carbohydrate and lipid metabolism, normalized the behaviour and learning in terms of the conditioned reflex in diabetic rats. These effects depended on the influence of antioxidative compounds on insulin sensitivity and tolerance of glucose loading. The best correction of diabetic manifestations was achieved using course doses of a-LA that maximally enhanced insulin sensitivity and of mexidole that markedly improved glucose tolerance. It is concluded that significant elevation of blood lipoperoxide levels in rats with alloxan-induced diabetes following administration of AO agents for 14 days gives no evidence of the direct relationship between their efficiency and antioxidative action.

In recent years, as a result of performance of intensive in-tube flaw detection, the integrity and reliable operation of trunk pipelines have been achieved. However, because of an unpredictable development of such tube flaws as stress corrosion, the probability of occurrence of emergencies in pipelines substantially increases. An analysis of the stressed state in pipelines exposed to their main load—the operating pressure—and various types of additional forces is presented. As a result, it is shown that the obtained direction, value, and location of the effective maximum stresses in the tube wall fully correspond to the pattern of statistical formation of stress-corrosion flaws in pipelines. It can be concluded from the data of this study that the standardized tube-strength margin is insufficient; during tube operation, this circumstance may lead to the formation of stresses at the level of the metal yield stress and initiation and growth of stress-corrosion cracks.

The testing technique for examining the state and safe operational life of pipelines containing corrosion and stress-corrosion flaws is considered. This technique is currently used to examine the state of pipelines of OAO Gazprom. This technique is based on the processing and analysis of the database on the in-tube inspection of gas pipelines. The results of analysis provide estimation of safe operational lifetimes.

N-acetylaspartate (NAA) is an amino acid abundant in the brain and claimed the role of a biomarker of neuropsychiatric disorders. The basic ways of NAA concentration measurement in the brain are magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MRI) and chromatography. The review examined the relationship between NAA concentrations in different parts of the brain and biological liquids and neuropsychiatric disorders.N-ацетиласпартат (NAA) - аминокислота, содержащаяся в большом количестве в головном мозге и претендующая на роль биомаркера психических и неврологических нарушений. Основными методами определения концентрации NAA в мозге являются магнитно-резонансная спектроскопия (МРС) и магнитно-резонансная томография (МРТ), а также - хроматографические методы. В обзоре рассмотрена связь между концентрацией NAA в различных отделах мозга и биологических жидкостях с определенными психическими и неврологическими заболеваниями.

One of the ways for an improvement of the nuclear microprobe spatial resolution is using of more perfect probe-forming systems. The spatial resolution that a microprobe can provide mostly depends on the beam emittance and the spherical aberrations of its focusing system. The systematic investigations of parametric multiplets of magnetic quadrupole lenses were carried out trying to find out the optimal parameters for obtaining the minimum spot size of the beam on the target. The systems consisting of three, four, five, and six magnetic quadrupole lenses were considered. The value of acceptance density of a probe-forming system was used as a criterion of various systems comparison. The obtained results can be used to construct a focusing system of a nuclear microprobe.

Durante el gran evento de rayos gamma del 29 de septiembre de 1989 se observaron líneas de rayos gamma de una región alrededor de 25 grados del sitio de la ráfaga. El mecanismo que parece más plausible para explicar la aceleración de partículas responsables de los rayos gamma es un choque producido por una eyección de masa coronal (EMC). Sin embargo, no existe a la fecha una explicación de aceptación general. Por otro lado, en junio de 1991, se observaron por lo menos tres eventos de rayos gamma de larga duración. De igual manera, ninguno de los modelos que se han propuesto para explicar estos eventos es convincente. En este trabajo analizamos los datos de plasma y partículas a la órbita de la Tierra para estos dos tipos de eventos y discutimos la posibilidad de que algunas de las perturbaciones en el medio interplanetario se originaron en la cromosfera fuera de regiones activas.

The physical-technical aspects and technological background of the large scale electrical power generation with magneto-hydrodynamics (MHD) method of the conversion of the high temperature gas flow energy has been developed within the intensive R&D work, undertaken in 60-80 of the last century by the leading industrial countries. In the USSR one of the most successful program was the state R&D program of MHD generators using the fossil fuel combustion products for the base load applications. In particular, this program has resulted in the development of the auxiliary equipment for the novel power plants to be working in the cycles called later as steamgas turbine cycles where the MHD generator is replaced with gas turbine. The main efforts were conducted in the Institute of High Temperature of the Russian Academy of Sciences where the series of the experimental complex MHD facilities including the pilot power plant U-25 have constructed and successfully tested. The main results include the peak electrical power generation at 20MW, the nominal operation up to 1 hour at the 10 MW electrical output, and long duration operation up to 10 days continuously. The rather successful USSR program was R&D program of the pulse MHD generators working on the adapted solid state rocket fuel. The main problem of MHD electrical power generation technique with fossil fuel combustion products as a working media is to provide the acceptable level of electrical conductivity of the working media. Under typical operation conditions of the open cycle MHD generator on fossil fuel combustion products seeded with low potential ionization alkali metals the conductivity doesn’t exceed ` 10 MOh/m. The power density is proportional to the products of the electrical conductivityσ, the flow velocity square u and the magnetic induction square B

Defect centres induced by UV laser excitation in the germanosilicate core of optical fibre preforms both with and without Ce addition were studied by the optical absorption spectroscopy and ESR. Selective ionization of Ce3+ ions showed the paramagnetic Ge(1) centre to be formed by trapping an electron and Ge(2) to be a hole centre. Two kinds of Ge E' centres thermally annealed at different temperatures were observed. Results of gamma-ray-induced attenuation measurements of optical fibres drawn from the preforms are presented and analysed.

This field of investigation is of special interest, firstly, because the ionizing radiation is almost completely absorbed in the irradiation material, so that the radiation has a high energy efficiency; secondly, because the radiation has a high penetrating power; thirdly, because it can be continuously controlled when processing materials. Furthermore, the radiation does not contaminate the products, it is ecologically clean, and the radiation sources are more readily available with high power levels at the present time than are other non-traditional energy forms [5-7].

We compared the effects of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) on exploratory behavior and conditioning in C57B1 and outbred animals. Two intraperitoneal injections of MPTP suppressed the orienting and exploratory behavior in C57B1 (reductions of both horizontal and vertical motor activity), but not in outbred mice, and impaired conditioning. The data indicate the dopaminergic nature of learning disturbances and suggest that the MPTP model may hold a lot of promise for the search for new drugs for the treatment of cognitive disorders in Parkinsonism.

To study a relationship between plasma levels of antipsychotics (AP) and severity of side-effects (SE) during the treatment of inpatients with exacerbation of schizophrenia.The study included 39 patients treated with risperidone, haloperidol, zuclopenthixol, clozapine, aripiprazole or olanzapine as monotherapy or in combination of two AP. Blood sampling to measure the AP plasma level was performed twice (at 7-10 and 26-30 day from start of treatment), the levels of prolactin and glucose were determined once (at 26-30 day from start of treatment). Patients were assessed by psychometric scales PANSS and NSA and the side-effects scale UKU.The increased concentration of AP was noted in 33% of the patients. The high concentration of AP was significantly associated with akathisia and hyperkinesia (by UKU scale), NSA retardation factor and hyperprolactinemia. Patients with severe hyperprolactinemia were twice as likely to have a clinically significant depression. Increased blood glucose levels were observed in 18% of the patients, there was no significant association with AP plasma levels. Mental SE were most prominent, with a drift towards the neurological SE in the group with higher AP plasma levels. Chlorpromazine equivalent didn't significantly differ in the groups with normal, high and low AP concentrations.Elevated AP plasma levels, which were associated with some clinically significant SE and some negative symptoms, were found in most patients. In this regard, therapeutic drug monitoring is a promising method for the individualization of schizophrenia exacerbation treatment in routine clinical practice.Цель работы - изучение связи концентрации антипсихотических препаратов (АП) и выраженности побочных эффектов (ПЭ) при лечении обострения шизофрении в условиях стационара. Материал и методы. В исследование были включены 39 пациентов обоего пола, поступивших в психиатрический стационар в связи с обострением шизофрении, получающие лечение АП (рисперидон, галоперидол, зуклопентиксол, клозапин, арипипразол или оланзапин) в виде монотерапии или комбинации из 2 АП, где второй использовался для седации или коррекции инсомнии. Дважды проводился забор крови для определения концентрации АП (на 7-10-й и на 26-30-й дни от начала лечения), однократно - для определения уровней пролактина и глюкозы (на 26-30-й дни от начала лечения). Пациенты оценивались по психометрическим шкалам PANSS и NSA (на 2-5-й и 26-30-й дни от начала лечения) и по шкале побочных эффектов UKU (на 26-30-й дни от начала лечения). Результаты. Повышенная концентрация АП отмечалась у 33% пациентов. Статистически достоверно связанными с повышенной концентрацией АП в нашем исследовании оказались акатизия и гиперкинезия (по шкале UKU), фактор заторможенности по шкале NSA и гиперпролактинемия. В свою очередь у пациентов с выраженной гиперпролактинемией (уровень пролактина выше 90 нг/мл) в два раза чаще (28% против 14%) возникала клинически значимая депрессия (оценка по пункту PANSSG6 'депрессия' 4 балла и выше). Повышение уровня глюкозы крови отмечалось у 18% пациентов, достоверной связи с концентрацией АП в плазме крови отмечено не было. В структуре ПЭ преобладали психические ПЭ, с тенденцией к смещению в сторону неврологических в группе с повышенной концентрацией АП. Хлорпромазиновый эквивалент статистически достоверно не различался в группах нормальной, повышенной и пониженной концентрации АП. Заключение. У значительной части пациентов был обнаружен повышенный уровень АП в плазме крови, который был связан как с некоторыми клинически значимыми ПЭ, так и с частью негативных симптомов. В связи с этим терапевтический лекарственный мониторинг является перспективным методом персонализации терапии пациентов с обострением шизофрении в повседневной клинической практике.

Increasing needs and interests of the humankind in space exploration and monitoring require to study very seriously the effects of space environment on spacecraft and, in this context, to improve significantly the Space Weather predictions (see Chapters 7–8). It does not admit of doubt that physical conditions in space are determined originally by the current level of solar activity. This level depends on time and reveals the variations in the course of 11-year solar activity cycle. The main constituents of the physical conditions in space are solar wind and interplanetary magnetic fiield (IMF) that govern charged particle motion at large time and spatial scales. Also, such a dynamic phenomenon as shock waves in solar wind plasma cause very significant changes of electromagnetic situation in the interplanetary space. In the nearest environment of the Earth a main factor in the particle behaviour is the geomagnetic field with its spatial and temporal variations.

In this Chapter we try to give more extended description of various aspects of the radiation hazard (risk) in space. It was only within the last few years the scientists have developed the models that provide accurate quantitative information on the radiation exposure due to cosmic radiation in the Earth’s environment and deep space. Typical parameters of radiation impact, terms and concepts used in practical cosmonautics (aeronautics) are: a) absorbed dose, absorbed dose rate, quality of radiation, factor of radiation quality, dose equivalent, mean tissue dose equivalent, uniform (non-uniform) radiation exposure, acute radiation exposure, reference radiation exposure, acute dose, chronic dose, effective dose, total dose effect, integral (cumulative) dose, tolerance (permissible) dose, dose limit (maximum permissible dose, MPD), lethal (fatal) dose, linear energy transfer (LET) rate, and dosage units; b) man-made space object (vehicle, device), light-weight and low-cost device, space hardware, performance, reliability, and serviceability of space (on-board) systems; single event effects (SEE), single event upset (SEU) of integral microcircuits, latch-up (hang-up of the electronic systems); c) manned mission, manned space flight, manned spacecraft, extravehicular activity (EAV), radiation protection, mass shielding, and storm shelter; forecast and assessment of radiation risk, prediction a few days ahead, different advance of forecast, and lead time.

As one can see from above consideration, the studies of terrestrial radiation environment is important from many reasons. In particular, the fluxes of solar energetic particles (SEPs) are needed for many space studies, such as study of the Sun itself, interplanetary medium and radiation exposure of lunar samples, and applications, such as radiation damage for to humans and experiments in space. Also, radiation protection problems for the space station and approaches to their mitigation are of great practical significance (e.g., Simonsen et al., 1991, Parnell et al., 1998).

The effect of original domestic derivatives of 3-oxypiridine and succinic acid (emoxipine, reamberin and mexidol) on the resistance to acute brain ischemia was studied in an experimental mouse models.We used 260 adult outbred mice. The drugs were introduced intraperitoneally 30 min before the modeling of acute brain ischemia. Each drug was used in 3 three doses: 1/2 of the calculated equivalent of mean treatment dose (EMTD), EMTD and double EMTD. A strangulation model with the assessment of mouse mortality latency and decapitation model with the assessment of agonal respiration (gasping) were used. The efficacy of the drugs was determined by comparison against alpha-lipoic acid that was used as a reference substance in previous studies of antihypoxic activity of emoxipine, reamberin and mexidol.It was established that the derivatives of 3-oxipiridine and succinic acid protected against subtotal ischemia of rostral brain segments (of cerebral hemispheres) as evidenced by the increase in longevity. Emoxipine demonstrated the maximal effect thereby surpassing reamberin and mexidol in the intensity of antiischemic activity. Antiischemic effect of alpha-lipoic acid was comparable to emoxipine. In the model of total brain ischemia, the derivatives of 3-oxipiridine and succinic acid caused the opposite (proischemic) action on the bulbar respiratory center as evidenced by the reduction in duration of gasping. Alpha-lipoic acid did not affect the duration of gasping.Цель исследования. Сравнительный анализ влияния оригинальных отечественных производных 3-оксипиридина и янтарной кислоты (эмоксипин, реамберин и мексидол) на устойчивость к острой ишемии головного мозга в эксперименте на мышах. Материал и методы. Исследование было проведено на 260 половозрелых беспородных мышах обоего пола. Изученные лекарственные средства вводили однократно внутрибрюшинно за 30 мин до моделирования острой церебральной ишемии. Каждое лекарственное средство применяли в трех дозах: 1/2 от расчетного эквивалента средней терапевтической дозы (ЭСТД), ЭСТД и удвоенный ЭСТД. Для моделирования острой ишемии головного мозга на мышах использовали странгуляционную модель с оценкой латентности гибели мышей и декапитационную модель с оценкой длительности агонального дыхания (гаспинга). Эффективность изученных препаратов была сопоставлена с результатами применения α-липоевой кислоты (α-ЛК), которая ранее использовалась в качестве препарата сравнения при изучении антигипоксической активности эмоксипина, реамберина и мексидола. Результаты и заключение. Было установлено, что производные 3-оксипиридина и янтарной кислоты оказывают протекторное действие при субтотальной ишемии ростральных отделов головного мозга (большие полушария) по критерию увеличения продолжительности жизни. Наибольшую эффективность продемонстрировал эмоксипин, превосходивший реамберин и мексидол по выраженности антиишемического действия. α-ЛК вызывала антиишемический эффект, сопоставимый с действием эмоксипина. При моделировании тотальной ишемии головного мозга производные 3-оксипиридина и янтарной кислоты оказывали противоположное (проишемическое) действие на бульбарный дыхательный центр по критерию уменьшения длительности гаспинга. α-ЛК не влияла на продолжительность гаспинга.

Single-mode fibers with chromatic dispersion varying along the length (VD SMF) are a promising medium for nonlinear fiber optics. In a theoretical paper1 VD SMFs were proposed for communication lines to compensate for the soliton pulse broadening caused by the influence of optical losses. We were, we believe, the first to produce fibers of this kind and to use them for the adiabatic compression of femtosecond solitons2 and for the generation of 0.2-THz soliton trains.3 This paper examines optical properties of VD SMF.

A single-mode fiber waveguide with zero chromatic dispersion at the wavelength of 1.55 μm was made. This fiber had a refractive index profile which was nearly triangular. The optical losses at 1.55 μm were below 0.3 dB/km.

A comparison was made of the calculated and measured radiative losses suffered by the fundamental and first higher modes in real waveguide structures with a depressed cladding. It was found that in determination of the operating range of single-mode waveguides with a depressed cladding it is essential to allow not only for the increase in the losses due to leaking of the fundamental HE11 mode at long wavelengths, but also for the shift of the cutoff wavelength of the first higher HE21 mode for shorter wavelengths.