Crisis Management and Communication Strategies: RUSAL’s Case

No company is immune to crisis situations, an affirmation which, despite its triviality, is undeniably true. However, from the early 2014, such statement may have become even more true to Russian corporations, as the annexation of the Crimean Peninsula gave start to rounds of economic sanctions that are still perpetrated today. Such measures, which were initiated in response to the Kremlin’s political maneuvers, have hit a number of Russian companies, and increased the degree of uncertainty in which they have to operate, as they see economic restriction’s impact not only on the business activity tangible factors—i.e., economic rewards, service, and performance—but also on intangible factors—i.e., image and reputation—as well. Crises are integral parts of all world systems, unfortunately. While they are a theoretically well-understood issue, in practice, crises are perceived as a very painful phenomenon. A crisis can be compared to riding a roller coaster. First, as we gain speed and climb up the tracks we are filled with a sense of joy and delight. These feelings are quickly replaced with anticipation, panic, and fear as the roller coaster plunges into the “abyss.

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Experimental poetics of “The adventures of the Electric Harlequin” by V.G. Shershenevich: the genre features

The article is devoted to the genre features in the insufficiently explored work "The Adventures of the Electric Harlequin" by imaginist V.G. Shershenevich. The author of the article identifies the signs of the commedia dell'arte, the tragic farce, the farcical action, the "drama for reading", the elements of poetry and drama. The author concludes syncretic nature of genre in this work

Value Foundations of Youth Education in China (1950-2000s)

The research is based on the scientific idea that the value orientations of youth are dynamic, therefore their study is relevant at any period of time, therefore it is important to study trends and their transformation in the development of the value foundations of upbringing in order to solve the most complex problems of personality upbringing. Research methods: theoretical analysis, synthesis,generalization of facts, events, phenomena; discursive analysis of the value foundations of education in different historical periods; methods of systematizing and generalizing the theory and practice of educating youth in China; survey, questionnaires, statistical methods. The main results of the study: on the basis of the periodization of this process in China, the genesis (stages) of the value foundations of youth upbringing was determined, an analysis of the leading trends, achievements and contradictions in the study period was carried out, the characteristics were substantiated and the transformation of the development of value orientations of youth at each of their stages was revealed. Thus, the historical and pedagogical analysis of the value foundations of the education of young people in China allowed us to come to the following general conclusions: the goal of education was transformed from an orientation towards strengthening the moral foundations of citizens, towards the integration of morality and knowledge/skills - towards the education of morally stable and educated people. The modern values of educating young people in China represent a dualism of values: traditions and modernization, preservation and transformation, a symbiosis of Chinese folk and international culture. Of great interest to science is the phenomenon of "stability", where for many decades in China there has been a fundamental and stable value foundations of the education of young people who do not differ from the actions of the individual, demonstrate exceptional ability to work, citizenship, reverence and respect for elders, law-abidingness, and certain moral qualities. All this requires a deeper study and the identification of effective means of their formation and development

Modern nomads: education on the way

The study is based on the scientific idea of the need to organize the education of children of the indigenous peoples of the North, Siberia and the Far East of Russia, leading a nomadic lifestyle with their parents. Globalization processes taking place in the world pose new challenges for the peoples of Russia. Accordingly, the study and analysis of the practice of education of indigenous children in the places of their natural residence and habitual economic activity in Russia becomes relevant. The authors, taking into account the historical background, present the results of a study on the study of the current state of the education system for children of indigenous small peoples of the North, Siberia and the Far East, leading a nomadic lifestyle with their parents, which has a certain specificity; identifying the main trends and scenarios for modeling nomadic education in Russia. As a result of the study, methodological recommendations were prepared for organizing the education of children leading a nomadic lifestyle with their parents

Homocystinuria due to cystathionine beta-synthase (CBS) deficiency in Russia: Molecular and clinical characterization

We present the results of the 45-year clinical observation of 27 Russian homocystinuria patients. We made a mutation analysis of the CBS gene for thirteen patients from eleven unrelated genealogies. All patients except for the two were compound heterozygotes for the mutations detected. The most frequent mutation in the cohort investigated was splice mutation IVS11-2a->c. We detected one new nonsense mutation, one new missense-mutation and three novel small deletions. We also report the clinical case of the B6-responsive patient genotyped as Ile278Thr/Cys109Arg

Аналіз сил різання при шліфуванні титанового сплаву та корозійностійкої сталі кругами з алмазу, електрокорунду та кубічного нітриду бору

The object of research is the process of circular and surface grinding of titanium alloy and corrosion-resistant steel, namely, the cutting forces arising from mechanical processing. One of the most problematic areas in work is the selection of the required grinding modes, material and grinding wheel grain size. In the course of the experiment, we used samples of VT8 titanium alloy and 12Х18N9T steel, on which the grinding process was studied with wheels made of various materials (electrocorundum, cubic boron nitride (CBN), diamond). The values of the cutting forces Py and Pz were obtained in the latitude of permissible modes, which are most often used in circular and flat grinding, and can reach maximum values, respectively, Py=27 N, Pz=15.5 N. The data were obtained at a low wheel speed from electrocorundum, about 15 m/s and grain size 8. By reducing the grain size of the wheel, we get the effect of increasing the energy consumption of the grinding process, due to the increase in the values of the cutting forces. If we compare the cutting forces arising from grinding with different wheels, then the following can be noted. Compared to electrocorundum wheels, when using CBN wheels, the cutting forces are reduced by 20–25 %, and when grinding with diamond wheels (despite the high wear of the diamond wheel), the effect of cutting forces is reduced by 25–30 %. This is due to the fact that cutting conditions are the most favorable for diamond and CBN grains, which makes it possible to use more intense cutting conditions. The results of the study allow predicting the performance of the grinding wheel, reducing the energy consumption of production, and also adjusting the processing mode of the part to obtain the necessary quality indicators of the surface layer and the geometric dimensions of the part.Объектом исследования является процесс круглого и плоского шлифования титанового сплава и коррозионностойкой стали, а именно сил резания, возникающих при механической обработке. Одним из самых проблемных мест в работе является подбор необходимых режимов шлифования, материала и зернистости шлифовального круга. В ходе эксперимента использовались образцы титанового сплава ВТ8 и стали 12Х18Н9Т, на которых исследовался процесс шлифовки кругами из различных материалов (электрокорунд, кубический нитрид бора (КНБ), алмаз). Получены величины сил резания Ру и Рz в широте допустимых режимов, которые чаще всего применяются при круглом и плоском шлифовании, и могут достигать максимальных значений, соответственно, Ру=27 Н, Рz=15,5 Н. Данные получены при небольшой скорости круга из электрокорунда, порядка 15 м/с и зернистостью 8. Уменьшая зернистость круга, получаем эффект увеличения энергетических затрат процесса шлифования, за счет роста величин сил резания. Если сравнивать силы резания, возникающие при шлифовании различными кругами, то можно отметить следующее. По сравнению с електрокорундовими кругами, при использовании кругов из КНБ силы резания уменьшаются на 20–25 %, а, шлифуя алмазными кругами (несмотря на высокий износ алмазного круга), влияние сил резания снижается на 25–30 %. Это связано с тем, что условия резания наиболее благоприятные алмазными и зернами с КНБ, что дает возможность использовать более напряженные режимы резания. Результаты исследования позволяют прогнозировать работоспособность шлифовального круга, уменьшить энергозатраты производства, а также скорректировать режим обработки детали для получения необходимых показателей качества поверхностного слоя и геометрических размеров детали.Об'єктом дослідження є процес круглого та плоского шліфування титанового сплаву та корозійностійкої сталі, а саме сил різання, що виникають при механічний обробці. Одним з найбільш проблемних місць в роботі є підбір необхідних режимів шліфування, матеріалу та зернистості шліфувального круга. В ході експерименту використовувались зразки титанового сплаву ВТ8 та сталі 12Х18Н9Т, на яких досліджувався процес шліфування кругами з різних матеріалів (електрокорунд, кубічний нітрид бору (КНБ), алмаз). Отримано величини сил різання Ру та Рz в широті допустимих режимів, які найчастіше застосовуються при круглому та плоскому шліфуванні, та можуть досягати максимальних значень, відповідно, Ру=27 Н, Рz=15,5 Н. Дані отримані при невеликій швидкості круга з електрокорунду, порядку 15 м/с та зернистістю 8. Зменшуючи зернистість круга, отримуємо ефект збільшення енергетичних витрат процесу шліфування, за рахунок зростання величин сил різання. Якщо порівнювати сили різання, що виникають при шліфуванні різними кругами, то можливо відзначити наступне. У порівнянні з електрокорундовими кругами, при використанні кругів з КНБ сили різання зменшуються на 20–25 %, а, здійснюючи шліфування алмазними кругами (незважаючи на високий знос алмазного круга), вплив сил різання знижується на 25–30 %. Це пов'язано з тим, що умови різання найбільш сприятливі алмазними та зернами з КНБ, що дає можливість використовувати більш напружені режими різання. Результати дослідження дозволяють прогнозувати працездатність шліфувального круга, зменшити енергозатрати виробництва, а також скорегувати режим обробки деталі для отримання необхідних показників якості поверхневого шару та геометричних розмірів деталі

First trimester thyroid function in pregnant women residing in Saint Petersburg (Russia): reference values and risk of gestational diabetes

Background. Subclinical hypothyroidism during pregnancy and gestational diabetes mellitus (GDM) is known to be associated with maternal and child morbidity. The concept of subclinical dysfunction of the thyroid gland in pregnant women depends on the population-specific and trimester-specific reference values so fixed universal cutoff concentrations for thyroid-stimulating hormone (TSH) that were recommended earlier now are put under the question. Population-specific and trimester-specific reference values have not been defined for pregnant women residing in Saint Petersburg. The data concerning the association of maternal thyroid status with GDM development are controversial. Aims. The aim of the study was to determine the reference values of TSH and free thyroxin (fT4) in the first trimester of pregnancy in women living in St. Petersburg, and to assess the relationship between thyroid status and the risk of subsequent development of GDM. Materials and methods. The levels of TSH, fT4 and thyroid peroxidase antibodies (TPO-Ab) were analyzed in 503 pregnant women before the 14th week of gestation. The women underwent oral glucose tolerance test (OGTT) at 2428 weeks to find out those with GDM. The association between thyroid function, thyroid autoimmunity and the risk of GDM we estimated. Results. The reference values for TSH were 0.07 4.40 mU /L, and for fT4 11.7 20.3 pmol/L. The prevalence of subclinical hypothyroidism in the 503 pregnant women was 16.9% according to the diagnostic criteria of TSH 2.5 mIU / L and 3.8% using our calculated reference interval. Hypothyroxinemia was registered in 5,3% using reference values recommended by diagnostic tests manufacturer and in 2,8% according to our calculated reference interval for fT4. GDM was diagnosed in 23% of women. Logistic regression analysis showed associations of hypothyroxinemia and TPO-Ab-positivity with the increased risk of GDM that remained significant after adjustments on age and body mass index (BMI) [adjusted OR (95% CI) = 7.39 (1.2742.93) for hypothyroxinemia, p=0.026; and adjusted OR (95% CI) = 2.02 (1.014.04) for TPO-Ab-positivity, p=0.047). Conclusions. Reference intervals for first trimester TSH and fT4 have been established for pregnant women living in St. Petersburg. Hypothyroxinemia and TPO-Ab-positivity were associated with the increased risk of GDM

Difluoromethylornithine (DFMO), an Inhibitor of Polyamine Biosynthesis, and Antioxidant <i>N</i>-Acetylcysteine Potentiate Immune Response in Mice to the Recombinant Hepatitis C Virus NS5B Protein

Hepatitis C virus (HCV) is one of the main triggers of chronic liver disease. Despite tremendous progress in the HCV field, there is still no vaccine against this virus. Potential vaccines can be based on its recombinant proteins. To increase the humoral and, especially, cellular immune response to them, more effective adjuvants are needed. Here, we evaluated a panel of compounds as potential adjuvants using the HCV NS5B protein as an immunogen. These compounds included inhibitors of polyamine biosynthesis and urea cycle, the mTOR pathway, antioxidants, and cellular receptors. A pronounced stimulation of cell proliferation and interferon-γ (IFN-γ) secretion in response to concanavalin A was shown for antioxidant N-acetylcysteine (NAC), polyamine biosynthesis inhibitor 2-difluoromethylornithine (DFMO), and TLR9 agonist CpG ODN 1826 (CpG). Their usage during the immunization of mice with the recombinant NS5B protein significantly increased antibody titers, enhanced lymphocyte proliferation and IFN-γ production. NAC and CpG decreased relative Treg numbers; CpG increased the number of myeloid-derived suppressor cells (MDSCs), whereas neither NAC nor DFMO affected MDSC counts. NAC and DFMO suppressed NO and interleukin 10 (IL-10) production by splenocytes, while DFMO increased the levels of IL-12. This is the first evidence of immunomodulatory activity of NAC and DFMO during prophylactic immunization against infectious diseases

Human Mesenchymal Stem Cells Modified with the NS5A Gene of Hepatitis C Virus Induce a Cellular Immune Response Exceeding the Response to DNA Immunization with This Gene

Hepatitis C virus (HCV) is one of the basic culprits behind chronic liver disease, which may result in cirrhosis and hepatocarcinoma. In spite of the extensive research conducted, a vaccine against HCV has not been yet created. We have obtained human mesenchymal stem cells (hMSCs) and used them for expressing the HCV NS5A protein as a model vaccination platform. Sixteen hMSC lines of a different origin were transfected with the pcNS5A-GFP plasmid to obtain genetically modified MSCs (mMSCs). The highest efficiency was obtained by the transfection of dental pulp MSCs. C57BL/6 mice were immunized intravenously with mMSCs, and the immune response was compared with the response to the pcNS5A-GFP plasmid, which was injected intramuscularly. It was shown that the antigen-specific lymphocyte proliferation and the number of IFN-γ-synthesizing cells were two to three times higher after the mMSC immunization compared to the DNA immunization. In addition, mMSCs induced more CD4+ memory T cells and an increase in the CD4+/CD8+ ratio. The results suggest that the immunostimulatory effect of mMSCs is associated with the switch of MSCs to the pro-inflammatory phenotype and a decrease in the proportion of myeloid derived suppressor cells. Thus, the possibility of using human mMSCs for the creation of a vaccine against HCV has been shown for the first time