Solving the Top-percentile traffic routing problem by Approximate Dynamic Programming

Internet Service Providers (ISPs) have the ability to route their traffic over different network providers. This study investigates the optimal routing strategy under multihoming in the case where network providers charge ISPs according to top-percentile pricing (i.e. based on the ?th highest volume of traffic shipped). We call this problem the Top-percentile Traffic Routing Problem (TpTRP). The TpTRP is a multistage stochastic optimization problem. Routing decision for every time period should be made before knowing the amount of traffic that is to be sent. The stochastic nature of the problem forms the critical difficulty of this study. Solution approaches based on Stochastic Integer Programming or Stochastic Dynamic Programming (SDP) suffer from the curse of dimensionality, which restricts their applicability. To overcome this, we suggest to use Approximate Dynamic Programming, which exploits the structure of the problem to construct continuous approximations of the value functions in SDP. Thus, the curse of dimensionality is largely avoided

Optimization-Based Islanding of Power Networks Using Piecewise Linear AC Power Flow

In this paper, a flexible optimization-based framework for intentional islanding is presented. The decision is made of which transmission lines to switch in order to split the network while minimizing disruption, the amount of load shed, or grouping coherent generators. The approach uses a piecewise linear model of AC power flow, which allows the voltage and reactive power to be considered directly when designing the islands. Demonstrations on standard test networks show that solution of the problem provides islands that are balanced in real and reactive power, satisfy AC power flow laws, and have a healthy voltage profile

Local solutions of the optimal power flow problem

The existence of locally optimal solutions to the AC optimal power flow problem (OPF) has been a question of interest for decades. This paper presents examples of local optima on a variety of test networks including modified versions of common networks. We show that local optima can occur because the feasible region is disconnected and/or because of nonlinearities in the constraints. Standard local optimization techniques are shown to converge to these local optima. The voltage bounds of all the examples in this paper are between ±5% and ±10% off-nominal. The examples with local optima are available in an online archive (http://www.maths.ed.ac.uk/optenergy/LocalOpt/) and can be used to test local or global optimization techniques for OPF. Finally we use our test examples to illustrate the behavior of a recent semi-definite programming approach that aims to find the global solution of OPF

MILP formulation for controlled islanding of power networks

This paper presents a flexible optimization approach to the problem of intentionally forming islands in a power network. A mixed integer linear programming (MILP) formulation is given for the problem of deciding simultaneously on the boundaries of the islands and adjustments to generators, so as to minimize the expected load shed while ensuring no system constraints are violated. The solution of this problem is, within each island, balanced in load and generation and satisfies steady-state DC power flow equations and operating limits. Numerical tests on test networks up to 300 buses show the method is computationally efficient. A subsequent AC optimal load shedding optimization on the islanded network model provides a solution that satisfies AC power flow. Time-domain simulations using second-order models of system dynamics show that if penalties were included in the MILP to discourage disconnecting lines and generators with large flows or outputs, the actions of network splitting and load shedding did not lead to a loss of stability

Top-percentile traffic routing problem by dynamic programming

Multi-homing is a technology used by Internet Service Provider (ISP) to connect to the Internet via different network providers. To make full use of the underlying networks with minimum cost, an optimal routing strategy is required by ISPs. This study investigates the optimal routing strategy in case where network providers charge ISPs according to top-percentile pricing. We call this problem the Top-percentile Traffic Routing Problem (TpTRP). The TpTRP is a multistage stochastic optimisation problem in which routing decision should be made before knowing the amount of traffic that is to be routed in the following time period. The stochastic nature of the problem forms the critical difficulty of this study. In this paper several approaches are investigated in modelling and solving the problem. We begin by modelling the TpTRP as a multi-stage stochastic programming problem, which is hard to solve due to the integer variables introduced by top-percentile pricing. Several simplifications of the original TpTRP are then explored in the second part of this work. Some of these allow analytical solutions which lead to bounds on the achievable optimal solution. We also establish bounds by investigation several "naive" routing policies. In the end, we explore the solution of the TpTRP as a stochastic dynamic programming problem by a discretization of the state space. This SDP model gives us achievable routing policies on medium size instances of TpTRP, which of course improve the naive routing policies. With a classification of the SDP decision table, a crude routing policy for realistic size instances can be developed from the smaller size SDP model. © 2011 Springer Science+Business Media, LLC

Treatment approach in patients with hyperbilirubinemia secondary to liver metastases in gastrointestinal malignancies: a case series and review of literature

BACKGROUND: Treatment of patients with severe liver dysfunction including hyperbilirubinemia secondary to liver metastases of gastrointestinal (GI) cancer is challenging. Regimen of oxaliplatin and fluoropyrimidine (FP)/folinic acid (FA) ± a monoclonal antibody (moAb), represents a feasible option considering the pharmacokinetics. Clinical data on the respective dosage and tolerability are limited and no recommendations are available. METHODS: Consecutive patients with severe hyperbilirubinemia [>2 × upper limit of the normal range (ULN) and >2.4 mg/dl] due to liver metastases of GI cancer without options for drainage receiving oxaliplatin, FP/FA ± moAb were analyzed. To collect further data a review of the literature was performed. RESULTS: A total of 12 patients were identified between 2011 and 2015. At treatment start, median bilirubin level was 6.1 mg/dl (>5 × ULN, range 2.7-13.6). The majority of patients (n = 11) received dose-reduced regimen with oxaliplatin (60-76%) and FP/FA (0-77%), rapidly escalating to full dose regimen. During treatment, bilirubin levels dropped more than 50% within 8 weeks or normalized within 12 weeks in 6 patients (responders). Median overall survival was 5.75 months (range 1.0-16.0 months) but was significantly prolonged in responders compared to nonresponders [9.7 and 3.0 months, p = 0.026 (two-sided test); 95% confidence interval (CI): 1.10-10.22]. In addition, case reports or series comprising a further 26 patients could be identified. Based on the obtained data a treatment algorithm was developed. CONCLUSION: Treatment with oxaliplatin, FP/FA ± moAb is feasible and may derive relevant benefits in patients with severe liver dysfunction caused by GI cancer liver metastases without further options of drainage

Duration of adjuvant chemotherapy for stage III colon cancer

BACKGROUND Since 2004, a regimen of 6 months of treatment with oxaliplatin plus a fluoropyrimidine has been standard adjuvant therapy in patients with stage III colon cancer. However, since oxaliplatin is associated with cumulative neurotoxicity, a shorter duration of therapy could spare toxic effects and health expenditures. METHODS We performed a prospective, preplanned, pooled analysis of six randomized, phase 3 trials that were conducted concurrently to evaluate the noninferiority of adjuvant therapy with either FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) administered for 3 months, as compared with 6 months. The primary end point was the rate of disease-free survival at 3 years. Noninferiority of 3 months versus 6 months of therapy could be claimed if the upper limit of the two-sided 95% confidence interval of the hazard ratio did not exceed 1.12. RESULTS After 3263 events of disease recurrence or death had been reported in 12,834 patients, the noninferiority of 3 months of treatment versus 6 months was not confirmed in the overall study population (hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15). Noninferiority of the shorter regimen was seen for CAPOX (hazard ratio, 0.95; 95% CI, 0.85 to 1.06) but not for FOLFOX (hazard ratio, 1.16; 95% CI, 1.06 to 1.26). In an exploratory analysis of the combined regimens, among the patients with T1, T2, or T3 and N1 cancers, 3 months of therapy was noninferior to 6 months, with a 3-year rate of disease-free survival of 83.1% and 83.3%, respectively (hazard ratio, 1.01; 95% CI, 0.90 to 1.12). Among patients with cancers that were classified as T4, N2, or both, the disease-free survival rate for a 6-month duration of therapy was superior to that for a 3-month duration (64.4% vs. 62.7%) for the combined treatments (hazard ratio, 1.12; 95% CI, 1.03 to 1.23; P=0.01 for superiority). CONCLUSIONS Among patients with stage III colon cancer receiving adjuvant therapy with FOLFOX or CAPOX, noninferiority of 3 months of therapy, as compared with 6 months, was not confirmed in the overall population. However, in patients treated with CAPOX, 3 months of therapy was as effective as 6 months, particularly in the lower-risk subgroup. (Funded by the National Cancer Institute and others.

The diagnosis and management of gastric cancer: expert discussion and recommendations from the 12th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2010

Well-recognized experts in the field of gastric cancer discussed during the 12th European Society Medical Oncology (ESMO)/World Congress Gastrointestinal Cancer (WCGIC) in Barcelona many important and controversial topics on the diagnosis and management of patients with gastric cancer. This article summarizes the recommendations and expert opinion on gastric cancer. It discusses and reflects on the regional differences in the incidence and care of gastric cancer, the definition of gastro-esophageal junction and its implication for treatment strategies and presents the latest recommendations in the staging and treatment of primary and metastatic gastric cancer. Recognition is given to the need for larger and well-designed clinical trials to answer many open question

Proteomic profile of KSR1-regulated signalling in response to genotoxic agents in breast cancer

Kinase suppressor of Ras 1 (KSR1) has been implicated in tumorigenesis in multiple cancers, including skin, pancreatic and lung carcinomas. However, our recent study revealed a role of KSR1 as a tumour suppressor in breast cancer, the expression of which is potentially correlated with chemotherapy response. Here, we aimed to further elucidate the KSR1-regulated signalling in response to genotoxic agents in breast cancer. Stable isotope labelling by amino acids in cell culture (SILAC) coupled to high-resolution mass spectrometry (MS) was implemented to globally characterise cellular protein levels induced by KSR1 in the presence of doxorubicin or etoposide. The acquired proteomic signature was compared and GO-STRING analysis was subsequently performed to illustrate the activated functional signalling networks. Furthermore, the clinical associations of KSR1 with identified targets and their relevance in chemotherapy response were examined in breast cancer patients. We reveal a comprehensive repertoire of thousands of proteins identified in each dataset and compare the unique proteomic profiles as well as functional connections modulated by KSR1 after doxorubicin (Doxo-KSR1) or etoposide (Etop-KSR1) stimulus. From the up-regulated top hits, several proteins, including STAT1, ISG15 and TAP1 are also found to be positively associated with KSR1 expression in patient samples. Moreover, high KSR1 expression, as well as high abundance of these proteins, is correlated with better survival in breast cancer patients who underwent chemotherapy. In aggregate, our data exemplify a broad functional network conferred by KSR1 with genotoxic agents and highlight its implication in predicting chemotherapy response in breast cancer