A mathematical justification for metronomic chemotherapy in oncology

We mathematically justify metronomic chemotherapy as the best strategy to apply most cytotoxic drugs in oncology for both curative and palliative approaches, assuming the classical pharmacokinetic model together with the Emax pharmacodynamic and the Norton-Simon hypothesis.From the mathematical point of view, we will consider two mixed-integer nonlinear optimization problems, where the unknowns are the number of the doses and the quantity of each one, adjusting the administration times a posteriori.Mathematics Subject Classification: 93C15, 92C50, 90C30

The cost of not knowing enough: mixed-integer optimization with implicit Lipschitz nonlinearities

It is folklore knowledge that nonconvex mixed-integer nonlinear optimization problems can be notoriously hard to solve in practice. In this paper we go one step further and drop analytical properties that are usually taken for granted in mixed-integer nonlinear optimization. First, we only assume Lipschitz continuity of the nonlinear functions and additionally consider multivariate implicit constraint functions that cannot be solved for any parameter analytically. For this class of mixed-integer problems we propose a novel algorithm based on an approximation of the feasible set in the domain of the nonlinear function—in contrast to an approximation of the graph of the function considered in prior work. This method is shown to compute approximate global optimal solutions in finite time and we also provide a worst-case iteration bound. In some first numerical experiments we show that the “cost of not knowing enough” is rather high by comparing our approach with the open-source global solver . This reveals that a lot of work is still to be done for this highly challenging class of problems and we thus finally propose some possible directions of future research.

Generalized Benders Decomposition Method to Solve Big Mixed-Integer Nonlinear Optimization Problems with Convex Objective and Constraints Functions

The paper presents the Generalized Benders Decomposition (GBD) method, which is now one of the basic approaches to solve big mixed-integer nonlinear optimization problems. It concentrates on the basic formulation with convex objectives and constraints functions. Apart from the classical projection and representation theorems, a unified formulation of the master problem with nonlinear and linear cuts will be given. For the latter case the most effective and, at the same time, easy to implement computational algorithms will be pointed out.

Solving mixed-integer nonlinear optimization problems using simultaneous convexification: a case study for gas networks

Solving mixed-integer nonlinear optimization problems (MINLPs) to global optimality is extremely challenging. An important step for enabling their solution consists in the design of convex relaxations of the feasible set. Known solution approaches based on spatial branch-and-bound become more effective the tighter the used relaxations are. Relaxations are commonly established by convex underestimators, where each constraint function is considered separately. Instead, a considerably tighter relaxation can be found via so-called simultaneous convexification, where convex underestimators are derived for more than one constraint function at a time. In this work, we present a global solution approach for solving mixed-integer nonlinear problems that uses simultaneous convexification. We introduce a separation method that relies on determining the convex envelope of linear combinations of the constraint functions and on solving a nonsmooth convex problem. In particular, we apply the method to quadratic absolute value functions and derive their convex envelopes. The practicality of the proposed solution approach is demonstrated on several test instances from gas network optimization, where the method outperforms standard approaches that use separate convex relaxations.

Mixed-integer nonlinear optimization for district heating network expansion

We present a mixed-integer nonlinear optimization model for computing the optimal expansion of an existing tree-shaped district heating network given a number of potential new consumers. To this end, we state a stationary and nonlinear model of all hydraulic and thermal effects in the pipeline network as well as nonlinear models for consumers and the network’s depot. For the former, we consider the Euler momentum and the thermal energy equation. The thermal aspects are especially challenging. Here, we develop a novel polynomial approximation that we use in the optimization model. The expansion decisions are modeled by binary variables for which we derive additional valid inequalities that greatly help to solve the highly challenging problem. Finally, we present a case study in which we identify three major aspects that strongly influence investment decisions: the estimated average power demand of potentially new consumers, the distance between the existing network and the new consumers, and thermal losses in the network.