Optimal Design and Operation of WHO-EPI Vaccine Distribution Chains

Vaccination has been proven to be the most effective method to prevent infectious diseases and in 1974 the World Health Organization (WHO) established the Expanded Programme on Immunization (EPI) to provide universal access to all important vaccines for all children, with a special focus on underserved low- and middle-income countries. However, there are still roughly 20 million infants worldwide who lack access to routine immunization services and remain at risk, and millions of additional deaths could be avoided if global vaccination coverage could improve. The broad goal of this research is to optimize the design and operation of the WHO-EPI vaccine distribution chain in these underserved low- and middle-income countries. We first present a network design problem for a general WHO-EPI vaccine distribution network by developing a mathematical model that formulates the network design problem as a mixed integer program (MIP). We then present three algorithms for typical problems that are too large to be solved using commercial MIP software. We test the algorithms using data derived from four different countries in sub-Saharan Africa and show that with our final algorithm, high-quality solutions are obtained for even the largest problems within a few minutes. We then discuss the problem of outreach to remote population centers when resources are limited and direct clinic service is unavailable. A set of these remote population centers is chosen, and over an appropriate planning period, teams of clinicians and support personnel are sent from a depot to set up mobile clinics at these locations to vaccinate people there and in the immediate surrounding area. We formulate the problem of designing outreach efforts as an MIP that is a combination of a set covering problem and a vehicle routing problem. We then incorporate uncertainty to study the robustness of the worst-case solutions and the related issue of the value of information. Finally, we study a variation of the outreach problem that combines Set Covering and the Traveling Salesmen Problem and provides an MIP formulation to solve the problem. Motivated by applications where the optimal policy needs to be updated on a regular basis and where repetitively solving this via MIP can be computationally expensive, we propose a machine learning approach to effectively deal with this problem by providing an opportunity to learn from historical optimal solutions that are derived from the MIP formulation. We also present a case study on outreach operations and provide numerical results. Our results show that while the novel machine learning based mechanism generates high quality solution repeatedly for problems that resemble instances in the training set, it does not generalize as well on a different set of optimization problems. These mixed results indicate that there are promising research opportunities to use machine learning to achieve tractability and scalability

Reducing the Size of Combinatorial Optimization Problems Using the Operator Vaccine by Fuzzy Selector with Adaptive Heuristics

Nowadays, solving optimally combinatorial problems is an open problem. Determining the best arrangement of elements proves being a very complex task that becomes critical when the problem size increases. Researchers have proposed various algorithms for solving Combinatorial Optimization Problems (COPs) that take into account the scalability; however, issues are still presented with larger COPs concerning hardware limitations such as memory and CPU speed. It has been shown that the Reduce-Optimize-Expand (ROE) method can solve COPs faster with the same resources; in this methodology, the reduction step is the most important procedure since inappropriate reductions, applied to the problem, will produce suboptimal results on the subsequent stages. In this work, an algorithm to improve the reduction step is proposed. It is based on a fuzzy inference system to classify portions of the problem and remove them, allowing COPs solving algorithms to utilize better the hardware resources by dealing with smaller problem sizes, and the use of metadata and adaptive heuristics. The Travelling Salesman Problem has been used as a case of study; instances that range from 343 to 3056 cities were used to prove that the fuzzy logic approach produces a higher percentage of successful reductions

Population-Based Optimization Algorithms for Solving the Travelling Salesman Problem

[Extract] Population based optimization algorithms are the techniques which are in the set of the nature based optimization algorithms. The creatures and natural systems which are working and developing in nature are one of the interesting and valuable sources of inspiration for designing and inventing new systems and algorithms in different fields of science and technology. Evolutionary Computation (Eiben& Smith, 2003), Neural Networks (Haykin, 99), Time Adaptive Self-Organizing Maps (Shah-Hosseini, 2006), Ant Systems (Dorigo & Stutzle, 2004), Particle Swarm Optimization (Eberhart & Kennedy, 1995), Simulated Annealing (Kirkpatrik, 1984), Bee Colony Optimization (Teodorovic et al., 2006) and DNA Computing (Adleman, 1994) are among the problem solving techniques inspired from observing nature. In this chapter population based optimization algorithms have been introduced. Some of these algorithms were mentioned above. Other algorithms are Intelligent Water Drops (IWD) algorithm (Shah-Hosseini, 2007), Artificial Immune Systems (AIS) (Dasgupta, 1999) and Electromagnetism-like Mechanisms (EM) (Birbil & Fang, 2003). In this chapter, every section briefly introduces one of these population based optimization algorithms and applies them for solving the TSP. Also, we try to note the important points of each algorithm and every point we contribute to these algorithms has been stated. Section nine shows experimental results based on the algorithms introduced in previous sections which are implemented to solve different problems of the TSP using well-known datasets

Research Strategies in Science-based Start-ups - Effects on performance in Danish and Swedish biotechnology

Although biotech start-ups fail or succeed based on their research few attempts have been made to examine if and how they strategize in this core of their activity. Popular views on Dedicated Biotech Firms (DBFs) see the inherent uncertainty of research as defying notions of strategizing, directing instead the attention to the quality of their science, or the roles of boards, management, and collaborative networks etc. Using a unique comprehensive dataset on Danish and Swedish biotech start-ups in drug discovery this paper analyzes their research strategies. Adopting a Simonean point of departure we develop a contingency view on complex problem solving which structures the argument into three steps: 1) Characterising the problem architectures addressed by different types of DBFs; 2) Testing and confirming that DBFs form requisite research strategies, by which we refer to problem solving approaches developed as congruent responses to problem architectures; 3) Testing and confirming that financial valuation of firms is driven by achievements conforming to requisite research strategies. These strategies, in turn, require careful combination of multiple dimensions of research. Findings demonstrate that Shonhoovens classical argument that “strategy matters” is valid not only for the larger high-tech firms covered by her study, but also for small research-based start-ups operating at the very well springs of knowledge where science directly interacts with technologies. Even though a lot more research is needed along these lines, these findings offer new implications for the understanding, management, and financing of these firms.

Quantitative analyses in basic, translational and clinical biomedical research: metabolism, vaccine design and preterm delivery prediction

2 t.There is nothing more important than preserving life, and the thesis here presented is framed in the field of quantitative biomedicine (or systems biomedicine), which has as objective the application of physico-mathematical techniques in biomedical research in order to enhance the understanding of life's basis and its pathologies, and, ultimately, to defend human health. In this thesis, we have applied physico-mathematical methods in the three fundamental levels of Biomedical Research: basic, translational and clinical. At a basic level, since all pathologies have their basis in the cell, we have performed two studies to deepen in the understanding of the cellular metabolic functionality. In the first work, we have quantitatively analyzed for the first time calcium-dependent chloride currents inside the cell, which has revealed the existence of a dynamical structure characterized by highly organized data sequences, non-trivial long-term correlation that last in average 7.66 seconds, and "crossover" effect with transitions between persistent and anti-persistent behaviors. In the second investigation, by the use of delay differential equations, we have modeled the adenylate energy system, which is the principal source of cellular energy. This study has shown that the cellular energy charge is determined by an oscillatory non-stationary invariant function, bounded from 0.7 to 0.95. At a translational level, we have developed a new method for vaccine design that, besides obtaining high coverages, is capable of giving protection against viruses with high mutability rates such as HIV, HCV or Influenza. Finally, at a clinical level, first we have proven that the classic quantitative measure of uterine contractions (Montevideo Units) is incapable of predicting preterm labor immediacy. Then, by applying autoregressive techniques, we have designed a novel tool for premature delivery forecasting, based only in 30 minutes of uterine dynamics. Altogether, these investigations have originated four scientific publications, and as far as we know, our work is the first European thesis which integrates in the same framework the application of mathematical knowledge to biomedical fields in the three main stages of Biomedical Research: basic, translational and clinical