Исследование устойчивости планов применения средств управления активными подвижными объектами

Рассматривается задача исследования устойчивости планов применения средств управления активными подвижными объектами (АПО) – материальными объектами, перемещающимися в пространстве и осуществляющими информационное, вещественное и энергетическое взаимодействие с объектами и пунктами управления, другими АПО. Применение АПО по назначению обычно регламентируется жесткими требованиями, поэтому любая временная задержка или неполное достижение целевого эффекта недопустимы. Причиной срыва выполнения целевой задачи может быть разработка некорректного плана применения средств управления, процесс реализации которого оказывается неустойчивым вследствие влияния случайных факторов либо целенаправленных воздействий среды и других систем. В статье рассматриваются проблемные вопросы комплексного исследования устойчивости планов применения средств управления активными подвижными объектами. Авторами предлагаются количественные и качественные методы оценивания устойчивости планов, пути и способы обеспечения требуемых уровней устойчивости. При этом задача планирования рассматривается как динамическая, предусматривающая корректировку плана за счет организационных, структурных и программно-алгоритмических мероприятий по обеспечению устойчивост

Decrease of cardiovascular risk in patients with type 2 diabetes: review of the common strategies and clinical studies

Military Medical Academy of S.M. Kirov, Saint-Petersburg, Russia Recent clinical trials about the cardiovascular safety of empagliflozin and liraglutide demonstrated a convincing lowering effect on mortality from cardiovascular causes among the patients with type 2 diabetes. These findings resulted in many questions about why this phenomenon was seen in two drugs with widely different mechanisms of functioning. It is important to note that the glucose-lowering effect was moderate, although a feature seen in both empagliflozin and liraglutide was their ability to increase insulin sensitivity. In many fundamental studies, this feature was associated with a reduction of cardiovascular risks. Insulin resistance, which has always been a pathophysiological base for the development of cardiovascular disease in patients with type 2 diabetes, is a topic for this report. Different methods to manage insulin resistance, including lifestyle changes, drug treatment and metabolic surgery, are discussed. Furthermore, the most common features of glucose-lowering drugs are analysed, including protective effects for cardiovascular outcomes in patients with type 2 diabetes presented in randomised clinical trials. Studies include the United Kingdom Prospective Diabetes Study (UKPDS), PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive), Insulin Resistance Intervention After Stroke (IRIS), Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) and the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME). The current study shows that the potential to reduce the risk of cardiovascular disease is determined not only by effective lowering of glucose but also by the ability to lower insulin resistance, which causes a paradigm shift in the management of type 2 diabetes

Прикладные аспекты оптимизации орбитальных структур спутниковых систем за счет уточнения параметров орбитального движения

Рассмотрены вопросы оптимизации баллистической структуры спутниковой системы дистанционного зондирования Земли. Подходы к баллистическому проектированию спутниковой системы, ранее разработанные специалистами различных научных школ, были ориентированы на поддержание структурной устойчивости системы за счет развертывания группировок с одинаковой геометрией и с одинаковыми наклонениями, что обеспечивало одинаковые вековые уходы элементов всех орбит. Вместе с тем существует целый комплекс задач, при котором необходимо сформировать спутниковую систему на орбитах разных высот. Для решения задачи обеспечения требуемого уровня устойчивости нового кластера орбитальных структур предлагается подход, включающий эвристическое формирование множества целевых разновысотных орбит; определение некоторой базовой околокруговой орбиты; направленный перебор возможных итерационных вариантов квазисинхронных орбит; согласование состава вектора характеристик условий движения и окончательный расчет приемлемого варианта, который гарантирует заданную точность цикла замыкания трассы. Апробация предлагаемого подхода проведена на примере определения параметров орбит, обеспечивающих равенство эффективных суток в заданном диапазоне высот. Приводится методика выбора степени учета различных физических факторов космической среды, которая позволяет достигнуть одинаковых отклонений прогнозной траектории от эталонной. Характеристики математической модели движения квазисинхронной орбиты, используемые при прогнозировании, рассчитываются из условия обеспечения устойчивости на заданном временном интервале. Для получения соответствующих оценок используются поправки к параметрам орбиты, приведенные из гринвичской системы координат. Описывается детальный алгоритм, позволяющий однозначно определить характеристики устойчивой структуры, при реализации которого осуществляется переход от решения нормальной системы уравнений к решению двух треугольных систем. Анализ предметной области показал, что предложенный подход является новым, а решаемая научная задача относится к классу обратных задач космической кибернетики

SGLT2 inhibitors and kidneys: mechanisms and main effects in diabetes mellitus patients

Type 2 diabetes mellitus (T2DM) is the cause of the development of diabetic nephropathy — a complication that determines the high degree of disability and mortality of such patients. Until recently, approaches to normalizing glucose levels did not have a significant possibility of influencing the outcome of kidney damage in diabetes. Type 2 sodium glucose cotransporter inhibitors (SGLT2) are a new class of glucose-lowering drugs that improve glycemic control due to an insulin-independent mechanism of action associated with increased urinary glucose excretion. The review provides an analysis of the results of studies on the assessment of nephroprotective actions — one of the pleiotropic actions of this drugs group. These materials show the properties of SGLT2 inhibitors to reduce the risk of developing and the progression of albuminuria, to save glomerular filtration rate, to reduce the frequency of end-stage renal disease and the need for renal replacement therapy in patients with T2DM. The article gives and analyzes the currently existing hypotheses of the mechanism of action of these glucose-lowering drugs. The risk of the most common renal complications with the use of SGLT2 inhibitors is considered. The practical aspects of the use of SGLT2 inhibitors in modern algorithms for the care of patients with T2DM are indicated, as well as the prospects for new randomized clinical trials

Multiple effects of bariatric surgery on human biochemical status

Beneficial effect of bariatric surgery is expressed not only in reducing body weight, but also in improving the functioning of the body as a whole. On the one hand, numerous studies devoted to the investigations of specific mechanisms of the influence of bariatric surgery on the general condition of an organism testify to the enormous interest of scientists in this problem. On the other hand, the range of changes is so vast that it covers almost all physiological and biochemical processes. The most noticeable response to bariatric surgery is from the digestive (including the composition of the microbiota), immune (reducing the level of systemic and local inflammation), cardiovascular (reducing the risks of atherosclerosis and other diseases) systems. Partial or complete compensation of type 2 diabetes mellitus and metabolic syndrome also occurs. Among the variety of data, there is insufficient research on only standard biomarkers: leptin, C-reactive protein, interleukin 6, etc. A detailed study of the profiles of both circulating biomarkers and local ones is necessary. At the same time, it is obligate to continue to accumulate evidence on the positive effect of bariatric surgery, since this type of surgical intervention has come into practice relatively recently. Unfortunately, at the present time in Russia bariatric surgery is not an affordable and popular treatment for morbid obesity (MO). Nevertheless, it is extremely important to change the current situation, since bariatric treatment is an optimal and effective solution to socially significant diseases such as MO or type 2 diabetes mellitus

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Empagliflozin as a new management strategy on outcomes in patients with type 2 diabetes mellitus

Patients with type 2 diabetes mellitus have an increased risk of cardiovascular (CV) complications. Although hyperglycaemia contributes to the pathogenesis of atherosclerosis and heart failure in these patients, glucose-lowering strategies did not have a significant effect on reducing CV risk, particularly in patients with a long duration of type 2 diabetes mellitus and prevalent CV disease (CVD). Sodium-glucose linked transporter-2 (SGLT2) inhibitors are a new class of anti-hyperglycaemic medications that increase glycaemic control via insulin-dependent mechanism of action associated with increased urinary glucose excretion. In this review, we present an analysis of the Empa-Reg Outcomes investigation, focussed on assessing the CV safety of empagliflozin, an inhibitor of SGLT2. We discuss the impressive results of trials that provide evidence on the cardiac and renal properties of empagliflozin. We present and analyse the current hypothesis on the mechanism of action of glucose-lowering medication, which has such a severe and complex impact on outcomes in patients with type 2 diabetes at high CV risk

Possibilities of metabolic surgery for the treatment of type 2 diabetes mellitus in patients with grade 1 alimentary obesity

Many studies have demonstrated the high effectiveness of bariatric surgery in patients with grade 23 obesity and type 2 diabetes mellitus. Currently, surgery is one of the most effective ways to decrease body mass, to maintain long-term weight loss and to manage type 2 diabetes mellitus. Particular interest has been generated by the strong influence of bariatric surgical interventions on the disruption of carbohydrate metabolism in patients who undergo surgery. This change leads to an improvement in the course of type 2 diabetes mellitus as well as its full remission. This review presents information on the mechanisms that are needed to improve glycaemic control in patients with obesity even after bariatric surgery. This review also contains a comparative analysis of how various surgical interventions influence the course of diabetes, the reasons for postbariatric glycaemia and predictors of the effectiveness of bariatric surgeries in terms of metabolic control in patients with type 2 diabetes mellitus. Until recently, the primary focus of the studies by bariatric surgeons was on patients with grade 23 obesity and type 2 diabetes mellitus. However, in this review, special attention is given to the patients with a body mass index that ranges from 30 to 35 kg/m. Gained experience of the bariatric surgeons leads to high effectiveness with respect to the influence on the course of diabetes in patients with grade 1 obesity, which allows us to significantly expand the range of patients who should be recommended for this surgery. In addition, some information concerning surgical and metabolic complications of bariatric surgical intervention is provided, which allows us to seriously consider this treatment

Atherosclerosis, Cardiovascular Disorders and COVID-19: Comorbid Pathogenesis

The article describes how atherosclerosis and coronavirus disease 19 (COVID-19) may affect each other. The features of this comorbid pathogenesis at various levels (vascular, cellular and molecular) are considered. A bidirectional influence of these conditions is described: the presence of cardiovascular diseases affects different individuals’ susceptibility to viral infection. In turn, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can have a negative effect on the endothelium and cardiomyocytes, causing blood clotting, secretion of pro-inflammatory cytokines, and thus exacerbating the development of atherosclerosis. In addition to the established entry into cells via angiotensin-converting enzyme 2 (ACE2), other mechanisms of SARS-CoV-2 entry are currently under investigation, for example, through CD147. Pathogenesis of comorbidity can be determined by the influence of the virus on various links which are meaningful for atherogenesis: generation of oxidized forms of low-density lipoproteins (LDL), launch of a cytokine storm, damage to the endothelial glycocalyx, and mitochondrial injury. The transformation of a stable plaque into an unstable one plays an important role in the pathogenesis of atherosclerosis complications and can be triggered by COVID-19. The impact of SARS-CoV-2 on large vessels such as the aorta is more complex than previously thought considering its impact on vasa vasorum. Current information on the mutual influence of the medicines used in the treatment of atherosclerosis and acute COVID-19 is briefly summarized

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)