Dynamic vehicle routing with time windows in theory and practice

The vehicle routing problem is a classical combinatorial optimization problem. This work is about a variant of the vehicle routing problem with dynamically changing orders and time windows. In real-world applications often the demands change during operation time. New orders occur and others are canceled. In this case new schedules need to be generated on-the-fly. Online optimization algorithms for dynamical vehicle routing address this problem but so far they do not consider time windows. Moreover, to match the scenarios found in real-world problems adaptations of benchmarks are required. In this paper, a practical problem is modeled based on the procedure of daily routing of a delivery company. New orders by customers are introduced dynamically during the working day and need to be integrated into the schedule. A multiple ant colony algorithm combined with powerful local search procedures is proposed to solve the dynamic vehicle routing problem with time windows. The performance is tested on a new benchmark based on simulations of a working day. The problems are taken from Solomon’s benchmarks but a certain percentage of the orders are only revealed to the algorithm during operation time. Different versions of the MACS algorithm are tested and a high performing variant is identified. Finally, the algorithm is tested in situ: In a field study, the algorithm schedules a fleet of cars for a surveillance company. We compare the performance of the algorithm to that of the procedure used by the company and we summarize insights gained from the implementation of the real-world study. The results show that the multiple ant colony algorithm can get a much better solution on the academic benchmark problem and also can be integrated in a real-world environment

Intake of nitrate and nitrite and the risk of gastric cancer: a prospective cohort study.

The association between the intake of nitrate or nitrite and gastric cancer risk was investigated in a prospective cohort study started in 1986 in the Netherlands, of 120,852 men and women aged 55-69 years. At baseline, data on dietary intake, smoking habits and other covariates were collected by means of a self-administered questionnaire. For data analysis, a case-cohort approach was used, in which the person-years at risk were estimated from a randomly selected subcohort (1688 men and 1812 women). After 6.3 years of follow-up, 282 microscopically confirmed incident cases of stomach cancer were detected: 219 men and 63 women. We did not find a higher risk of gastric cancer among people with a higher nitrate intake from food [rate ratio (RR) highest/lowest quintile = 0.80, 95% CI 0.47-1.37, trend-P = 0.18], a higher nitrate intake from drinking water (RR highest/lowest quintile = 0.88, 95% CI 0.59-1.32, trend-P = 0.39) or a higher intake of nitrite (RR highest/lowest quintile = 1.44, 95% CI 0.95-2.18, trend-P = 0.24). Rate ratios for gastric cancer were also computed for each tertile of nitrate intake from foods within tertiles of vitamin C intake and intake of beta-carotene, but no consistent pattern was found. Therefore, our study does not support a positive association between the intake of nitrate or nitrite and gastric cancer risk

Non-Cross Resistant Sequential Single Agent Chemotherapy in First-Line Advanced Non-Small Cell Lung Cancer Patients: Results of a Phase II Study

Background. sequential chemotherapy can maintain dose intensity and preclude cumulative toxicity by increasing drug diversity. Purpose. to investigate the toxicity and efficacy of the sequential regimen of gemcitabine followed by paclitaxel in first line advanced stage non-small cell lung cancer (NSCLC) patients with good performance status (PS). Patients and methods. gemcitabine 1250 mg/m2 was administered on day 1 and 8 of course 1 and 2; Paclitaxel 150 mg/m2 on day 1 and 8 of course 3 and 4. Primary endpoint was response rate (RR), secondary endpoints toxicity and time to progression (TTP). Results. Of the 21 patients (median age 56, range 38–80 years; 62% males, 38% females) 10% (2/21) had stage IIIB, 90% (19/21) stage IV, 15% PS 0, 85% PS 1. 20% of patients had a partial response, 30% stable disease, 50% progressive disease. Median TTP was 12 weeks (range 6–52 weeks), median overall survival (OS) 8 months (range 1–27 months), 1-year survival was 33%. One patient had grade 3 hematological toxicity, 2 patients a grade 3 peripheral neuropathy. Conclusions. sequential administration of gemcitabine followed by paclitaxel in first line treatment of advanced NSCLC had a favourable toxicity profile, a median TTP and OS comparable with other sequential trials and might, therefore, be a treatment option for NSCLC patients with high ERCC1 expression

Personalized decision‑making for aneurysm treatment of aneurysmal subarachnoid hemorrhage:development and validation of a clinical prediction tool

Background: In patients with aneurysmal subarachnoid hemorrhage suitable for endovascular coiling and neurosurgical clip-reconstruction, the aneurysm treatment decision-making process could be improved by considering heterogeneity of treatment effect and durability of treatment. We aimed to develop and validate a tool to predict individualized treatment benefit of endovascular coiling compared to neurosurgical clip-reconstruction. Methods: We used randomized data (International Subarachnoid Aneurysm Trial, n = 2143) to develop models to predict 2-month functional outcome and to predict time-to-rebleed-or-retreatment. We modeled for heterogeneity of treatment effect by adding interaction terms of treatment with prespecified predictors and with baseline risk of the outcome. We predicted outcome with both treatments and calculated absolute treatment benefit. We described the patient characteristics of patients with ≥ 5% point difference in the predicted probability of favorable functional outcome (modified Rankin Score 0–2) and of no rebleed or retreatment within 10 years. Model performance was expressed with the c-statistic and calibration plots. We performed bootstrapping and leave-one-cluster-out cross-validation and pooled cluster-specific c-statistics with random effects meta-analysis. Results: The pooled c-statistics were 0.72 (95% CI: 0.69–0.75) for the prediction of 2-month favorable functional outcome and 0.67 (95% CI: 0.63–0.71) for prediction of no rebleed or retreatment within 10 years. We found no significant interaction between predictors and treatment. The average predicted benefit in favorable functional outcome was 6% (95% CI: 3–10%) in favor of coiling, but 11% (95% CI: 9–13%) for no rebleed or retreatment in favor of clip-reconstruction. 134 patients (6%), young and in favorable clinical condition, had negligible functional outcome benefit of coiling but had a ≥ 5% point benefit of clip-reconstruction in terms of durability of treatment. Conclusions: We show that young patients in favorable clinical condition and without extensive vasospasm have a negligible benefit in functional outcome of endovascular coiling – compared to neurosurgical clip-reconstruction – while at the same time having a substantially lower probability of retreatment or rebleeding from neurosurgical clip-reconstruction – compared to endovascular coiling. The SHARP prediction tool (https://sharpmodels.shinyapps.io/sharpmodels/) could support and incentivize a multidisciplinary discussion about aneurysm treatment decision-making by providing individualized treatment benefit estimates.</p

Personalized decision‑making for aneurysm treatment of aneurysmal subarachnoid hemorrhage:development and validation of a clinical prediction tool

Background: In patients with aneurysmal subarachnoid hemorrhage suitable for endovascular coiling and neurosurgical clip-reconstruction, the aneurysm treatment decision-making process could be improved by considering heterogeneity of treatment effect and durability of treatment. We aimed to develop and validate a tool to predict individualized treatment benefit of endovascular coiling compared to neurosurgical clip-reconstruction. Methods: We used randomized data (International Subarachnoid Aneurysm Trial, n = 2143) to develop models to predict 2-month functional outcome and to predict time-to-rebleed-or-retreatment. We modeled for heterogeneity of treatment effect by adding interaction terms of treatment with prespecified predictors and with baseline risk of the outcome. We predicted outcome with both treatments and calculated absolute treatment benefit. We described the patient characteristics of patients with ≥ 5% point difference in the predicted probability of favorable functional outcome (modified Rankin Score 0–2) and of no rebleed or retreatment within 10 years. Model performance was expressed with the c-statistic and calibration plots. We performed bootstrapping and leave-one-cluster-out cross-validation and pooled cluster-specific c-statistics with random effects meta-analysis. Results: The pooled c-statistics were 0.72 (95% CI: 0.69–0.75) for the prediction of 2-month favorable functional outcome and 0.67 (95% CI: 0.63–0.71) for prediction of no rebleed or retreatment within 10 years. We found no significant interaction between predictors and treatment. The average predicted benefit in favorable functional outcome was 6% (95% CI: 3–10%) in favor of coiling, but 11% (95% CI: 9–13%) for no rebleed or retreatment in favor of clip-reconstruction. 134 patients (6%), young and in favorable clinical condition, had negligible functional outcome benefit of coiling but had a ≥ 5% point benefit of clip-reconstruction in terms of durability of treatment. Conclusions: We show that young patients in favorable clinical condition and without extensive vasospasm have a negligible benefit in functional outcome of endovascular coiling – compared to neurosurgical clip-reconstruction – while at the same time having a substantially lower probability of retreatment or rebleeding from neurosurgical clip-reconstruction – compared to endovascular coiling. The SHARP prediction tool (https://sharpmodels.shinyapps.io/sharpmodels/) could support and incentivize a multidisciplinary discussion about aneurysm treatment decision-making by providing individualized treatment benefit estimates.</p

Optical Detection of Preneoplastic Lesions of the Central Airways

Current routine diagnosis of premalignant lesions of the central airways is hampered due to a limited sensitivity (white light bronchoscopy) and resolution (computer tomography (CT), positron emission tomography (PET)) of currently used techniques. To improve the detection of these subtle mucosal abnormalities, novel optical imaging bronchoscopic techniques have been developed over the past decade. In this review we highlight the technological developments in the field of endoscopic imaging, and describe their advantages and disadvantages in clinical use

A randomized phase II study comparing two schedules of the 21-day regimen of gemcitabine and carboplatin in advanced non-small cell lung cancer

Purpose: Carboplatin area under the curve (AUC) 5 ml/min on day 1 with gemcitabine 1,250 mg/m2on day 1 and day 8 is a widely used regimen in advanced non-small cell lung cancer. Grade 3-4 thrombocytopenia and neutropenia are frequent. The aim of this study is to investigate whether toxicity of gemcitabine/carboplatin could be reduced by administering carboplatin on day 8 instead of