Dynamic Games of Social Distancing During an Epidemic: Analysis of Asymmetric Solutions.

Individual behaviors play an essential role in the dynamics of transmission of infectious diseases, including COVID-19. This paper studies a dynamic game model that describes the social distancing behaviors during an epidemic, assuming a continuum of players and individual infection dynamics. The evolution of the players' infection states follows a variant of the well-known SIR dynamics. We assume that the players are not sure about their infection state, and thus, they choose their actions based on their individually perceived probabilities of being susceptible, infected, or removed. The cost of each player depends both on her infection state and on the contact with others. We prove the existence of a Nash equilibrium and characterize Nash equilibria using nonlinear complementarity problems. We then exploit some monotonicity properties of the optimal policies to obtain a reduced-order characterization for Nash equilibrium and reduce its computation to the solution of a low-dimensional optimization problem. It turns out that, even in the symmetric case, where all the players have the same parameters, players may have very different behaviors. We finally present some numerical studies that illustrate this interesting phenomenon and investigate the effects of several parameters, including the players' vulnerability, the time horizon, and the maximum allowed actions, on the optimal policies and the players' costs.

Individualized growth prediction of mice skin tumors with maximum likelihood estimators.

BACKGROUND & OBJECTIVE: In this work, we focus on estimating the parameters of the Gompertz model in order to predict tumor growth. The estimation is based on measurements from mice skin tumors of de novo carcinogenesis. The main objective is to compare the Maximum Likelihood estimator with the best performance from our previous work with the Non-linear Least Squares estimator which is commonly used in the literature to estimate the growth parameters of the Gompertz model. METHODS: To describe tumor growth, we propose a stochastic model which is based on the Gompertz growth function. The principle of Maximum Likelihood is used to estimate both the growth rate and the carrying capacity of the Gompertz function, along with the characteristics of the additive Gaussian process and measurement noise. Moreover, we examine whether a Maximum A Posteriori estimator is able to utilize any available prior knowledge in order to improve the predictions. RESULTS: Experimental data from a total of 24 tumors in 8 mice (3 tumors each) were used to study the performance of the proposed methods with respect to prediction accuracy. Our results show that the Maximum Likelihood estimator is able to provide, in most cases, more accurate predictions. Moreover, the Maximum A Posteriori estimator has the potential to correct potentially non-realistic estimates for the carrying capacity at early growth stages. CONCLUSION: In most cases, the Maximum Likelihood estimator is able to provide more reliable predictions for the tumor's growth on individual test subjects. The Maximum A Posteriori estimator, it has the potential to improve the prediction when the available experimental data do not provide adequate information by utilizing prior knowledge about the unknown parameters.

Tumor growth modeling: Parameter estimation with Maximum Likelihood methods.

BACKGROUND & OBJECTIVE: In this work, we focus on estimating the parameters of the widely used Gompertz tumor growth model, based on measurements of the tumor's volume. Being able to accurately describe the dynamics of tumor growth on an individual basis is very important both for growth prediction and designing personalized, optimal therapy schemes (e.g. when using model predictive control). METHODS: Our analysis aims to compute both the growth rate and the carrying capacity of the Gompertz function, along with the characteristics of the additive Gaussian process and measurement noise of the system. Three methods based on Maximum Likelihood estimation are proposed. The first utilizes an assumption regarding the measurement noise that simplifies the problem, the second combines the Extended Kalman Filter and Maximum Likelihood estimation, and the third is a nonstandard exact form of Maximum Likelihood estimation, where numerical integration is used to approximate the likelihood of the measurements, along with a novel way to reduce the required computations. RESULTS: Synthetic data were used in order to perform extensive simulations aiming to compare the methods' effectiveness, with respect to the accuracy of the estimation. The proposed methods are able to estimate the growth dynamics, even when the noise characteristics are not estimated accurately. Another very important finding is that the methods perform best in the case that corresponds to the problem needed to be solved when dealing with experimental data. CONCLUSION: Using nonstandard, problem specific techniques can improve the estimation accuracy and best exploit the available data.

A switching control strategy for the attenuation of blood glucose disturbances.

In this computational study we consider a generalized minimal model structure for the intravenously infused insulin-blood glucose dynamics, which can represent a wide variety of diabetic patients, and augment this model structure with a glucose rate disturbance signal that captures the aggregate effects of various internal and external factors on blood glucose. Then we develop a model-based, switching controller, which attempts to balance between optimal performance, reduced computational complexity and avoidance of dangerous hypoglycaemic events. We evaluate the proposed algorithm relative to the widely studied proportional-derivative controller for the regulation of blood glucose with continuous insulin infusions. The results show that the proposed switching control strategy can regulate blood glucose much better than the proportional-derivative controller for all the different types of diabetic patients examined. This new algorithm is also shown to be remarkably robust in the event of concurrent, unknown variations in critical parameters of the adopted model.

Model Predictive Control of blood glucose in Type 1 diabetes: the Principal Dynamic Modes approach.

This computational study demonstrates the efficacy of regulating blood glucose in Type 1 diabetics with a Model Predictive Control strategy, utilizing a nonparametric / Principal Dynamic Modes model. For this purpose, a stochastic glucose disturbance signal is introduced and a simple methodology for predicting its future values is developed. The results of our simulations confirm that the proposed algorithm achieves very good performance, is computationally efficient and avoids hypoglycaemic events.