A game-theoretic approach for reliability evaluation of public transportation transfers with stochastic features

A game-theoretic approach based on the framework of transferable-utility cooperative games is developed to assess the reliability of transfer nodes in public transportation networks in the case of stochastic transfer times. A cooperative game is defined, whose model takes into account the public transportation system, the travel times, the transfers and the associated stochastic transfer times, and the users’ demand. The transfer stops are modeled as the players of such a game, and the Shapley value – a solution concept in cooperative game theory – is used to identify their centrality and relative importance. Theoretical properties of the model are analyzed. A two-level Monte Carlo approximation of the vector of Shapley values associated with the nodes is introduced, which is efficient and able to take into account the stochastic features of the transportation network. The performance of the algorithm is investigated, together with that of its distributed computing variation. The usefulness of the proposed approach for planners and policy makers is shown with a simple example and on a case study from the public transportation network of Auckland, New Zealand

Treatment of HER2+ metastatic salivary ductal carcinoma in a pregnant woman: a case report

Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with a high mortality and poor response to treatment in the advanced setting. Human epidermal growth factor 2 (HER2) can be amplified in a fraction of SDC. We describe the case of HER2+ metastatic SDC of the submandibular gland in a young pregnant woman treated by multimodal treatment (chemotherapy, radiotherapy and targeted therapy). During pregnancy, a 27-year-old woman developed SDC of the left submandibular gland with lung and bone metastases. Given the HER2 overexpression, she was treated with trastuzumab, paclitaxel and cisplatin. Since the tumor had arisen during pregnancy, triptorelin was administered after delivery. A complete remission was observed, and after eight cycles of chemotherapy, radiotherapy was started in association with trastuzumab and triptorelin. A prolonged disease control and complete visceral remission were observed. Multimodal therapy based on patient's tumor characteristics showed good clinical efficacy in the treatment of metastatic SDC

The system to fill with oil the empty Break Out Boxes (BOBs) of the KM3NeT Detection Units

The KM3NeT collaboration aims to construct the largest underwater neutrino telescope in the Mediterranean sea. The detector is located in two sites, one in front of Toulon at 2500m sea depth and one SE Capo Passero in Sicily at 3500m depth. On both sites, one or two blocks of 115 Detection Units (DU) are connected to shore , each Du being composed by a Vertical Electro-Optical Cable (VEOC) connecting 18 Digital Optical Modules (DOMs). In this report we describe the integration of the DU carried out in our INFN laboratory in Genova, in particular one important phase of the process where some components in the VEOC have to be carefully filled with oil before connection to the DOMs

Advanced Glycation End-Products and Hyperglycemia Increase Angiopoietin-2 Production by Impairing Angiopoietin-1-Tie-2 System

The angiopoietin-Tie-2 system plays a crucial role in the maintenance of endothelial integrity. Hyperglycemia and advanced glycation end-products (AGEs) are involved in endothelial cell dysfunction responsible of the pathogenesis of microvascular complications of diabetes. Here, we investigated whether glycated serum (GS) or hyperglycemia (HG) affect the angiopoietin-Tie-2 system in the microvascular endothelial cells HMEC-1. We found that culture for 5 days in the presence of AGEs and HG (alone or in combination) decreased cell proliferation, increased reactive oxygen species (ROS) production, and reduced ratio between the oxidized and the reduced form of glutathione. Since angiopoietin-1 (Ang-1) signaling regulates angiopoietin-2 (Ang-2) expression through inactivation of the forkhead transcription factor FoxO1, we investigated intracellular signaling of Ang-1 and expression of Ang-2. HG and AGEs reduced phosphorylation of Akt and abrogated phosphorylation of FoxO1 induced by Ang-1 without affecting neither Tie-2 expression nor its activation. Furthermore, AGEs and/or HG induced nuclear translocation of FoxO1 and increased Ang-2 production. In conclusion, we demonstrated that both hyperglycemia and AGEs affect the angiopoietin-Tie-2 system by impairing Ang-1/Tie-2 signaling and by increasing Ang-2 expression. These results suggest that therapeutic strategies useful in preventing or delaying the onset of diabetic vascular complications should be aimed to preserve Ang-1 signaling

Induction chemotherapy followed by alternating chemo-radiotherapy in stage IV undifferentiated nasopharyngeal carcinoma

In locally advanced undifferentiated nasopharyngeal carcinoma (UNPC), concomitant chemo-radiotherapy is the only strategy that gave better results over radiation alone in a phase III trial. Adding effective chemotherapy to a concomitant chemo-radiotherapy programme may be a way to improve the results further. 30 patients with previously untreated T4 and/or N2–3 undifferentiated nasopharyngeal carcinoma were consecutively enrolled and initially treated with 3 courses of epidoxorubicin, 90 mg/m2, day 1 and cisplatin, 40 mg/m2, days 1 and 2, every 3 weeks. After a radiological and clinical response assessment patients underwent 3 courses of cisplatin, 20 mg/m2/day, days 1–4 and fluorouracil, 200 mg/m2/day, days 1–4, i.v. bolus, (weeks 1, 4, 7) alternated to 3 courses of radiation (week 2–3, 5–6, 8–9–10), with a single daily fractionation, up to 70 Gy. WHO histology was type 2 in 30% and type 3 in 70% of the patients. 57% had T4 and 77% N2–3 disease. All the patients are evaluable for toxicity and response. All but one received 3 courses of induction chemotherapy. Toxicity was mild to moderate in any case. At the end of the induction phase 10% of CRs, 83.3% of PRs and 6.7% of SD were recorded. All the patients but one had the planned number of chemotherapy courses in the alternating phase and all received the planned radiation dose. One patient out of 3 developed grade III–IV mucositis. Haematological toxicity was generally mild to moderate. At the final response evaluation 86.7% of CRs and 13.3% of PRs were observed. At a median follow-up of 31 months, 13.3% of patients had a loco-regional progression and 20% developed distant metastases. The 3-year actuarial progression-free survival and overall survival rates were 64% and 83%. Induction chemotherapy followed by alternating chemo-radiotherapy is feasible and patients' compliance optimal. This approach showed a very promising activity on locally advanced UNPC and merits to be investigated in phase III studies. © 2000 Cancer Research Campaign http://www.bjcancer.co