A reduced integer programming model for the ferry scheduling problem

We present an integer programming model for the ferry scheduling problem, improving existing models in various ways. In particular, our model has reduced size in terms of the number of variables and constraints compared to existing models by a factor of approximately O(n), where n being the number of ports. The model also handles efficiently load/unload time constraints, crew scheduling and passenger transfers. Experiments using real world data produced high quality solutions in 12 hours using CPLEX 12.4 with a performance guarantee of within 15% of optimality, on average. This establishes that using a general purpose integer programming solver is a viable alternative in solving the ferry scheduling problem of moderate size.Comment: To appear in Public Transpor

Intravesical Treatments of Bladder Cancer: Review

For bladder cancer, intravesical chemo/immunotherapy is widely used as adjuvant therapies after surgical transurethal resection, while systemic therapy is typically reserved for higher stage, muscle-invading, or metastatic diseases. The goal of intravesical therapy is to eradicate existing or residual tumors through direct cytoablation or immunostimulation. The unique properties of the urinary bladder render it a fertile ground for evaluating additional novel experimental approaches to regional therapy, including iontophoresis/electrophoresis, local hyperthermia, co-administration of permeation enhancers, bioadhesive carriers, magnetic-targeted particles and gene therapy. Furthermore, due to its unique anatomical properties, the drug concentration-time profiles in various layers of bladder tissues during and after intravesical therapy can be described by mathematical models comprised of drug disposition and transport kinetic parameters. The drug delivery data, in turn, can be combined with the effective drug exposure to infer treatment efficacy and thereby assists the selection of optimal regimens. To our knowledge, intravesical therapy of bladder cancer represents the first example where computational pharmacological approach was used to design, and successfully predicted the outcome of, a randomized phase III trial (using mitomycin C). This review summarizes the pharmacological principles and the current status of intravesical therapy, and the application of computation to optimize the drug delivery to target sites and the treatment efficacy

Approximate Local Search in Combinatorial Optimization

Local search algorithms for combinatorial optimization problems are in general of pseudopolynomial running time and polynomial-time algorithms are often not known for finding locally optimal solutions for NP-hard optimization problems. We introduce the concept of epsilon-local optimality and show that an epsilon-local optimum can be identified in time polynomial in the problem size and 1/epsilon whenever the corresponding neighborhood can be searched in polynomial time, for epsilon > 0. If the neighborhood can be searched in polynomial time for a delta-local optimum, we present an algorithm that produces a (delta+epsilon)-local optimum in time polynomial in the problem size and 1/epsilon. As a consequence, a combinatorial optimization problem has a fully polynomial-time approximation scheme if and only if it has a fully polynomial-time augmentation sche

Management of bacillus Calmette-Guerin (BCG) refractory superficial bladder cancer: results with intravesical BCG and Interferon combination therapy

BCG is the most efficacious intravesical treatment for superficial bladder cancer. However, 30%-40% of tumors are refractory. BCG failure is an indication for cystectomy but several salvage intravesical (IVe) strategies have been proposed. Early results with reduced dose BCG in combination with IFN-a in patients are currently the most promising. We have adopted this approach and now report our preliminary results. This is the first report of this salvage therapy from Canada, the birthplace of IVe BCG therapy for superficial bladder cancer. The "O'Donnell protocol" of reduced dose IVe BCG plus IFN-a was followed in 12 patients with BCG refractory superficial transitional cell carcinoma. A retrospective review of the efficacy and toxicity of the treatment was conducted. One year from induction therapy with salvage BCG/IFN-a, 6 of the 12 (50%) of patients were tumor free. Of the six recurrences, 3(50%) did not respond to the IVe therapy and had residual/recurrent tumor at the first follow-up visit. Risk factors for treatment failure were identified. The combinative therapy was well tolerated with minimal toxicity compared to previous full dose BCG. Our 12 month data with reduced dose IVe BCG plus IFN-a salvage therapy for BCG refractory superficial TCC confirm previous reports of >50% complete response rates. We need longer follow up in a larger patient population to determine the durability of this promising therapy in patients who would otherwise undergo radical cystectomy

Approximate Local Search in Combinatorial Optimization

Local search algorithms for combinatorial optimization problems are in general of pseudopolynomial running time and polynomial-time algorithms are often not known for finding locally optimal solutions for NP-hard optimization problems. We introduce the concept of epsilon-local optimality and show that an epsilon-local optimum can be identified in time polynomial in the problem size and 1/epsilon whenever the corresponding neighborhood can be searched in polynomial time, for epsilon > 0. If the neighborhood can be searched in polynomial time for a delta-local optimum, we present an algorithm that produces a (delta+epsilon)-local optimum in time polynomial in the problem size and 1/epsilon. As a consequence, a combinatorial optimization problem has a fully polynomial-time approximation scheme if and only if it has a fully polynomial-time augmentation schemLocal Search, Neighborhood Search, Approximation Algorithms, Computational Complexity, Combinatorial Optimization, 0/1-Integer Programming,