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

The role of patient-and treatment-related factors and early functional imaging in late radiation-induced xerostomia in oropharyngeal cancer patients

The advent of quantitative imaging in personalized radiotherapy (RT) has offered the opportunity for a better understanding of individual variations in intrinsic radiosensitivity. We aimed to assess the role of magnetic resonance imaging (MRI) biomarkers, patient-related factors, and treatment-related factors in predicting xerostomia 12 months after RT (XER12 ) in patients affected by oropharyngeal squamous cell carcinoma (OSCC). Patients with locally advanced OSCC underwent diffusion-weighted imaging (DWI) and dynamic-contrast enhanced MRI at baseline; DWI was repeated at the 10th fraction of RT. The Radiation Therapy Oncology Group (RTOG) toxicity scale was used to evaluate salivary gland toxicity. Xerostomia-related questionnaires (XQs) were administered weekly during and after RT. RTOG toxicity ≥ grade 2 at XER12 was considered as endpoint to build prediction models. A Decision Tree classification learner was applied to build the prediction models following a five-fold cross-validation. Of the 89 patients enrolled, 63 were eligible for analysis. Thirty-six (57.1%) and 21 (33.3%) patients developed grade 1 and grade 2 XER12, respectively. Including only baseline variables, the model based on DCE-MRI and V65 (%) (volume of both glands receiving doses ≥ 65 Gy) had a fair accuracy (77%, 95% CI: 66.5–85.4%). The model based on V65 (%) and XQ-Intmid (integral of acute XQ scores from the start to the middle of RT) reached the best accuracy (81%, 95% CI: 71–88.7%). In conclusion, non-invasive biomarkers from DCE-MRI, in combination with dosimetric variables and self-assessed acute XQ scores during treatment may help predict grade 2 XER12 with a fair to good accuracy

Impact of chemotherapy dose-density on radiotherapy dose-intensity after breast conserving surgery

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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