A fully saturated, free-surface ground water flow model and a variably saturated model are applied to the solution of the free-surface ground water flow problem in order to determine the influence of ...the unsaturated flow component on the accuracy of the saturated flow solution and the water balance for homogeneous systems. The significance of the seepage face that must exist to provide a transition between a phreatic surface and a downstream surface water body is also evaluated. A series of simple generic cross-sectional test cases are used as the basis for the numerical investigations. The fully saturated and variably saturated models used in this study are two-dimensional Galerkin finite-element models that incorporate exit seepage face options. The fully saturated solution is found to be almost identical to the variably saturated solution below the water table, the only significant difference being that the variably saturated model predicts a slightly lower water table due to horizontal flow components in the capillary fringe. This difference is negligible for large-scale systems, showing that for homogeneous systems, unsaturated flow can be neglected and steady-state flow including seepage face discharge can be realistically simulated by a fully saturated free-surface model. For aquifer-scale systems where discretization limitations may prevent the explicit representation of seepage faces, the seepage face can be omitted because of its negligible influence on the overall water balance at the larger scale.
Recent phase III studies in hormone refractory prostate cancer (HRPC) showed an improvement in terms of overall survival (OS), objective response (OR) and biochemical response (BR); however, ...chemotherapy is usually accompanied by negative side effects that determines poor quality of life (QoL) and only marginally improves individual clinical response (ICR) in terms of pain relief and performance status.
Ellagic acid is a polyphenol that is found in many species of flowering plants. It is an antioxidant that determines apoptosis, down regulation of IGF-II, activates p21 (waf1/Cip1), mediates the cumulative effect on G1/S transition phase and prevents destruction of p-53 gene by cancer cells.
The aim of this study was to assess the effects of ellagic acid support therapy on toxicity, OR, ICR and BR in HRPC patients treated with estramustine phosphate and vinorelbine.
Patients with HRPC were randomly distributed in two study groups: a control group (group A) who underwent chemotherapy with vinorelbine and estramustine phosphate, and an experimental group (group B) where chemotherapy regimen was associated with ellagic acid.
The mean number of chemotherapy cycles/patient was 4 (range 3–8 cycles) and 6.5 (range 5–11) in group A and B patients, respectively. A reduction in systemic toxicity, statistically significant for neutropenia, associated with better results in term of OR rate, ICR, and BR were observed in group B compared with group A. On the contrary no significant difference in OS and PFS was detected between groups.
our study suggests that the use of ellagic acid as support therapy reduces chemotherapy induced toxicity, in particular neutropenia, in HRCP patients; however, further studies are required to confirm our results.
Moving immune checkpoint inhibitors (ICI) in first-line setting in advanced NSCLC, new treatment strategies are needed for patients who progress on treatment with ICI. Tedopi® (OSE-2101) is a ...neoepitope vaccine restricted to HLA-A2 positive patients (∼45% of NSCLC) targeting five tumor-associated antigens expressed in lung cancer cells: ACE, HER2, MAGE2, MAGE3 and P53. In a phase II trial (Barve et al. JCO 2008), Tedopi® showed a median overall survival (OS) of 17.3 months with a manageable safety profile in pre-treated advanced NSCLC patients. ATALANTE-1 (NCT02654587) is a randomized, open-label, phase III study comparing the efficacy of Tedopi® with standard treatment (SoC) in HLA-A2 positive patients with advanced NSCLC after progression on ICI.
Patients with advanced NSCLC (EGFR and ALK negative), progressive disease to platinum-based chemotherapy with sequential or concurrent ICI, HLA-A2 positivity (blood test), ECOG PS 0-1, treated and asymptomatic brain metastases allowed, are randomized 2:1 to receive 1ml Tedopi® subcutaneously Q3W for 6 cycles, then Q8W for the remainder of the year and finally Q12W, or SoC treatment (docetaxel 75mg/m2 Q3W or pemetrexed 500mg/m2 Q3W). In both arms, treatment continues until progression, intolerable toxicity or consent withdrawal. Stratification criteria are histology, best response to first-line, line rank of ICI. Tumor assessment is performed every 6 weeks (RECIST 1.1). Primary endpoint is OS; Secondary endpoints are: Progression Free Survival, Objective Response Rate , Disease Control Rate , Duration of response, Quality of Life and safety. This is a superiority study with a hazard ratio of 0.7, two-sided alpha 5% and power 80%, after 278 events are observed. An independent analysis (1y-OS rate) is planned in the first 84 patients treated with Tedopi®. Last study review by the Data Monitoring Committee in June 18 suggested that the study continues as planned. Translational research will evaluate pharmacodynamic markers of efficacy baseline and after treatment initiation in this population of NSCLC patients who progressed after ICI treatment.
NCT02654587.
OSE Immunotherapeutics, Paris, France.
OSE Immunotherapeutics, Paris, France.
V. Gabarre: Full / Part-time employment, employee: OSE immunotheapeuticds. J. Remon Masip: Travel / Accommodation / Expenses: OSE immunotheapeuticds. All other authors have declared no conflicts of interest.
This paper reports the high-temperature dynamic behaviour of a 3.3kV-rated Silicon Carbide (SiC) Power MOSFETs with high-k gate stack. Several devices have been tested under nominal and SOA bias ...conditions during standard inductive load switching test (ILS). Moreover, devices' ruggedness has been tested by means of short-circuit (SC) pulses with bus voltage of 1.8kV. Lastly, the tests have shown stable threshold voltage when operating with Si-standard gate voltage swing of ±15V.
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