Mathematical modeling and optimal control of malaria

Malaria continues to infect millions and kill hundreds of thousands of people worldwide each year, despite over a century of research and attempts to control and eliminate this infectious disease. Challenges such as the development and spread of drug resistant malaria parasites, insecticide resistance to mosquitoes, climate change, the presence of individuals with subpatent malaria infections which normally are asymptomatic and behavioral plasticity in the mosquito hinder the prospects of malaria control and elimination. In this thesis, mathematical models of malaria transmission and control that address the role of drug resistance, immunity, iron supplementation and anemia, immigration and visitation, and the presence of asymptomatic carriers in malaria transmission are developed. A within-host mathematical model of severe Plasmodium falciparum malaria is also developed. First, a deterministic mathematical model for transmission of antimalarial drug resistance parasites with superinfection is developed and analyzed. The possibility of increase in the risk of superinfection due to iron supplementation and fortification in malaria endemic areas is discussed. The model results calls upon stakeholders to weigh the pros and cons of iron supplementation to individuals living in malaria endemic regions. Second, a deterministic model of transmission of drug resistant malaria parasites, including the inflow of infective immigrants, is presented and analyzed. The optimal control theory is applied to this model to study the impact of various malaria and vector control strategies, such as screening of immigrants, treatment of drug-sensitive infections, treatment of drug-resistant infections, and the use of insecticide-treated bed nets and indoor spraying of mosquitoes. The results of the model emphasize the importance of using a combination of all four controls tools for effective malaria intervention. Next, a two-age-class mathematical model for malaria transmission with asymptomatic carriers is developed and analyzed. In development of this model, four possible control measures are analyzed: the use of long-lasting treated mosquito nets, indoor residual spraying, screening and treatment of symptomatic, and screening and treatment of asymptomatic individuals. The numerical results show that a disease-free equilibrium can be attained if all four control measures are used. A common pitfall for most epidemiological models is the absence of real data; model-based conclusions have to be drawn based on uncertain parameter values. In this thesis, an approach to study the robustness of optimal control solutions under such parameter uncertainty is presented. Numerical analysis of the optimal control problem in the presence of parameter uncertainty demonstrate the robustness of the optimal control approach that: when a comprehensive control strategy is used the main conclusions of the optimal control remain unchanged, even if inevitable variability remains in the control profiles. The results provide a promising framework for the design of cost-effective strategies for disease control with multiple interventions, even under considerable uncertainty of model parameters. Finally, a separate work modeling the within-host Plasmodium falciparum infection in humans is presented. The developed model allows re-infection of already-infected red blood cells. The model hypothesizes that in severe malaria due to parasite quest for survival and rapid multiplication, the Plasmodium falciparum can be absorbed in the already-infected red blood cells which accelerates the rupture rate and consequently cause anemia. Analysis of the model and parameter identifiability using Markov chain Monte Carlo methods is presented.

«Constrained-optimal strategy-proof assignment: beyond the groves mechanisms»

A single object must be allocated to at most one of n agents. Money transfers are possible and preferences are quasilinear. We offer an explicit description of the individually rational mechanisms which are Pareto-optimal in the class of feasible, strategy-proof, anonymous and envy-free mechanisms. These mechanisms form a one-parameter infinite family; the Vickrey mechanism is the only Groves mechanism in that family.

Optimal control theory for a unitary operation under dissipative evolution

We show that optimizing a quantum gate for an open quantum system requires the time evolution of only three states irrespective of the dimension of Hilbert space. This represents a significant reduction in computational resources compared to the complete basis of Liouville space that is commonly believed necessary for this task. The reduction is based on two observations: the target is not a general dynamical map but a unitary operation; and the time evolution of two properly chosen states is sufficient to distinguish any two unitaries. We illustrate gate optimization employing a reduced set of states for a controlled phasegate with trapped atoms as qubit carriers and a iSWAP gate with superconducting qubits.

Optimal management of natural resources. Accounting for heterogeneity

Dynamic optimization methods have become increasingly important over the last years in economics. Within the dynamic optimization techniques employed, optimal control has emerged as the most powerful tool for the theoretical economic analysis. However, there is the need to advance further and take account that many dynamic economic processes are, in addition, dependent on some other parameter different than time. One can think of relaxing the assumption of a representative (homogeneous) agent in macro- and micro-economic applications allowing for heterogeneity among the agents. For instance, the optimal adaptation and diffusion of a new technology over time, may depend on the age of the person that adopted the new technology. Therefore, the economic models must take account of heterogeneity conditions within the dynamic framework. This thesis intends to accomplish two goals. The first goal is to analyze and revise existing environmental policies that focus on defining the optimal management of natural resources over time, by taking account of the heterogeneity of environmental conditions. Thus, the thesis makes a policy orientated contribution in the field of environmental policy by defining the necessary changes to transform an environmental policy based on the assumption of homogeneity into an environmental policy which takes account of heterogeneity. As a result the newly defined environmental policy will be more efficient and likely also politically more acceptable since it is tailored more specifically to the heterogeneous environmental conditions. Additionally to its policy orientated contribution, this thesis aims making a methodological contribution by applying a new optimization technique for solving problems where the control variables depend on two or more arguments --- the so-called two-stage solution approach ---, and by applying a numerical method --- the Escalator Boxcar Train Method --- for solving distributed optimal control problems, i.e., problems where the state variables, in addition to the control variables, depend on two or more arguments. Chapter 2 presents a theoretical framework to determine optimal resource allocation over time for the production of a good by heterogeneous producers, who generate a stock externalit and derives government policies to modify the behavior of competitive producers in order to achieve optimality. Chapter 3 illustrates the method in a more specific context, and integrates the aspects of quality and time, presenting a theoretical model that allows to determine the socially optimal outcome over time and space for the problem of waterlogging in irrigated agricultural production. Chapter 4 of this thesis concentrates on forestry resources and analyses the optimal selective-logging regime of a size-distributed forest.

The geometry of optimal control solutions on some six dimensional lie groups

This paper examines optimal solutions of control systems with drift defined on the orthonormal frame bundle of particular Riemannian manifolds of constant curvature. The manifolds considered here are the space forms Euclidean space E-3, the spheres S-3 and the hyperboloids H-3 with the corresponding frame bundles equal to the Euclidean group of motions SE(3), the rotation group SO(4) and the Lorentz group SO(1,3). The optimal controls of these systems are solved explicitly in terms of elliptic functions. In this paper, a geometric interpretation of the extremal solutions is given with particular emphasis to a singularity in the explicit solutions. Using a reduced form of the Casimir functions the geometry of these solutions are illustrated.

Application of constrained predictive control on a 3D crane system

This paper describes the SIMULINK implementation of a constrained predictive control algorithm based on quadratic programming and linear state space models, and its application to a laboratory-scale 3D crane system. The algorithm is compatible with Real Time. Windows Target and, in the case of the crane system, it can be executed with a sampling period of 0.01 s and a prediction horizon of up to 300 samples, using a linear state space model with 3 inputs, 5 outputs and 13 states.

Genetic algorithms for optimal control of beer fermentation

This paper uses genetic algorithms to optimise the mathematical model of a beer fermentation process that operates in batch mode. The optimisation is based in adjusting the temperature profile of the mixture during a fixed period of time in order to reach the required ethanol levels but considering certain operational and quality restrictions.

Model predictive control using dynamic integrated system optimisation and parameter estimation (DISOPE)

DISOPE is a technique for solving optimal control problems where there are differences in structure and parameter values between reality and the model employed in the computations. The model reality differences can also allow for deliberate simplification of model characteristics and performance indices in order to facilitate the solution of the optimal control problem. The technique was developed originally in continuous time and later extended to discrete time. The main property of the procedure is that by iterating on appropriately modified model based problems the correct optimal solution is achieved in spite of the model-reality differences. Algorithms have been developed in both continuous and discrete time for a general nonlinear optimal control problem with terminal weighting, bounded controls and terminal constraints. The aim of this paper is to show how the DISOPE technique can aid receding horizon optimal control computation in nonlinear model predictive control.