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Abstract Background Recent large-scale sequencing efforts have shed light on the genetic contribution to the etiology of congenital heart defects (CHD); however, the relative impact of genetics on clinical outcomes remains less understood. Outcomes analyses using genetics are complicated by the intrinsic severity of the CHD lesion and interactions with conditionally dependent clinical variables. Methods Bayesian Networks were applied to describe the intertwined relationships between clinical variables, demography, and genetics in a cohort of children with single ventricle CHD. Results As isolated variables, a damaging genetic variant in a gene related to abnormal heart morphology and prolonged ventilator support following stage I palliative surgery increase the probability of having a low Mental Developmental Index (MDI) score at 14 months of age by 1.9- and 5.8-fold, respectively. However, in combination, these variables act synergistically to further increase the probability of a low MDI score by 10-fold. The absence of a damaging variant in a known syndromic CHD gene and a shorter post-operative ventilator support increase the probability of a normal MDI score 1.7- and 2.4-fold, respectively, but in combination increase the probability of a good outcome by 59-fold. Conclusions Our analyses suggest a modest genetic contribution to neurodevelopmental outcomes as isolated variables, similar to known clinical predictors. By contrast, genetic, demographic, and clinical variables interact synergistically to markedly impact clinical outcomes. These findings underscore the importance of capturing and quantifying the impact of damaging genomic variants in the context of multiple, conditionally dependent variables, such as pre- and post-operative factors, and demography.

В статье изучается возможность использования альтернативного подхода к прогнозированию статистических показателей эпидемии вируса нового типа. Представлен систематический обзор моделей прогнозирования эпидемий новых инфекций в зарубежной и российской научной литературе. Анализируется точность модели SIR при прогнозировании весенней волны эпидемии COVID-19 в России. В качестве альтернативного подхода к моделированию эпидемии предлагается использование вместо традиционной модели SIR новой дискретной стохастической модели распространения эпидемии CIR, основанной на балансе показателей эпидемии в текущий и прошлые моменты времени. Новая модель описывает динамику общего количества заболевших (С), общего количества выздоровевших и умерших (R) и числа активных случаев (I). Параметрами системы являются процентный прирост величины C(t) и характеристика динамического баланса эпидемиологического процесса, впервые введенная в этой статье. Сформулирован принцип динамического баланса эпидемиологического процесса, предполагающий наличие у любого процесса свойства близости значений общего количества заболевших в прошлые периоды и значений общего количества выздоровевших и умерших в текущий момент времени. Для вычисления значений характеристики динамического баланса используется задача целочисленного программирования. Продемонстрировано, что в общем случае динамическая характеристика эпидемиологического процесса не является постоянной величиной. Эпидемиологический процесс, динамическая характеристика которого не является постоянной величиной, называется нестационарным. Для построения среднесрочных прогнозов показателей эпидемиологического процесса на промежутках стационарности эпидемиологического процесса разработан специальный алгоритм. Исследован вопрос об использовании этого алгоритма на промежутках стационарности и нестационарности. Приведены примеры применения модели CIR для построения прогнозов рассматриваемых показателей эпидемии в России в мае-июне 2020 года.

The consideration of infectious diseases from a mathematical point of view can reveal possible options for epidemic control and fighting the spread of infection. However, predicting and modeling the spread of a new, previously unexplored virus is still difficult. The present paper examines the possibility of using a new approach to predicting the statistical indicators of the epidemic of a new type of virus based on the example of COVID-19. The important result of the study is the description of the principle of dynamic balance of epidemiological processes, which has not been previously used by other researchers for epidemic modeling. The new approach is also based on solving the problem of predicting the future dynamics of precisely random values of model parameters, which is used for defining the future values of the total number of: cases (C); recovered and dead (R); and active cases (I). Intelligent heuristic algorithms are proposed for calculating the future trajectories of stochastic parameters, which are called the percentage increase in the total number of confirmed cases of the disease and the dynamic characteristics of epidemiological processes. Examples are given of the application of the proposed approach for making forecasts of the considered indicators of the COVID-19 epidemic, in Russia and European countries, during the first wave of the epidemic.

In this work multiple depot vehicle routing problem is considered in case of variable travel times between nodes on a metropolis network. This variant of the classic multiple depot vehicle routing problem is motivated by the fact that in urban contexts variable traffic conditions play an essential role and can not be ignored in order to perform a realistic optimization. Time-travel matrices corresponding to each period of planning horizon were formed by solving the traffic assignment problem in conjunction with shortest path problem. Routing problem instances include from 20 to 100 customers randomly chosen from a road network of Saint-Petersburg. The results demonstrate that taking into account traffic flow information can reduce route time by 8-37% depending on number of customers in the problem instance.

Because of the lack of reliable information on the spread parameters of COVID-19, there is an increasing demand for new approaches to efficiently predict the dynamics of new virus spread under uncertainty. The study presented in this paper is based on the Case-Based Reasoning method used in statistical analysis, forecasting and decision making in the field of public health and epidemiology. A new mathematical Case-Based Rate Reasoning model (CBRR) has been built for the short-term forecasting of coronavirus spread dynamics under uncertainty. The model allows for predicting future values of the increase in the percentage of new cases for a period of 2–3 weeks. Information on the dynamics of the total number of infected people in previous periods in Italy, Spain, France, and the United Kingdom was used. Simulation results confirmed the possibility of using the proposed approach for constructing short-term forecasts of coronavirus spread dynamics. The main finding of this study is that using the proposed approach for Russia showed that the deviation of the predicted total number of confirmed cases from the actual one was within 0.3%. For the USA, the deviation was 0.23%.

IDP-core is a new cooperative solution for dynamic and differential games. A novel approach of constructing solutions for dynamic and differential games was employed in which the time consistency property was used as the main axiom property for the cooperative solution. Another new and important approach used for constructing IDP-core is the IDP dominance, which allows to select undominated imputation distribution procedures and construct the cooperative solution or imputation set. This approach shows the potential of using the time consistency property as the main axiom for solutions in various fields such as Social Choice and Mechanism Design. The overall procedure for defining the cooperative solution is also new since IDP-core was constructed using imputation distribution procedures but not by using imputations directly.