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Driver’s stress affects decision-making and the probability of risk occurrence, and it is therefore a key factor in road safety. This suggests the need for continuous stress monitoring. This work aims at validating a stress neurophysiological measure—a Neurometric—for out-of-the-lab use obtained from lightweight EEG relying on two wet sensors, in real-time, and without calibration. The Neurometric was tested during a multitasking experiment and validated with a realistic driving simulator. Twenty subjects participated in the experiment, and the resulting stress Neurometric was compared with the Random Forest (RF) model, calibrated by using EEG features and both intra-subject and cross-task approaches. The Neurometric was also compared with a measure based on skin conductance level (SCL), representing one of the physiological parameters investigated in the literature mostly correlated with stress variations. We found that during both multitasking and realistic driving experiments, the Neurometric was able to discriminate between low and high levels of stress with an average Area Under Curve (AUC) value higher than 0.9. Furthermore, the stress Neurometric showed higher AUC and stability than both the SCL measure and the RF calibrated with a cross-task approach. In conclusion, the Neurometric proposed in this work proved to be suitable for out-of-the-lab monitoring of stress levels.

BACKGROUND: There is no established treatment regimen for recurrent GBM. GBMs have activation of multiple signaling pathways in the tumor microenvironment, including the receptor tyrosine kinases, VEGFR, FGFR, and PDGFR. Regorafenib (REG), an oral multikinase inhibitor, inhibits these angiogenic kinases and the mutant oncogenic kinases KIT, RET, and B‐RAF. MATERIAL AND METHODS: We present, after the first analysis, the updated results of REGOMA trial. The primary aim of this trial was to assess REG activity in prolonging overall survival (OS) in PTS with relapsed GBM after surgery and Stupp regimen (α = 0.2, 1-sided; β = 0.2). Secondary objectives were PFS, disease control rate (DCR), safety, quality of life (QoL); exploratory objectives included analysis of metabolic tissue biomarkers as possible predictors of response. PTS with histologically confirmed GBM, ECOG PS 0‐1, documented disease progression were randomized 1:1 to receive REG 160 mg/day (3 weeks on, 1 week off) or lomustine (LOM) 110 mg/m2 (every 6 weeks) until disease progression or unacceptable toxicity. Tumor response was evaluated by brain MRI every 8 weeks according to the RANO criteria. RESULTS: 119 PTS were randomized (n = 59 REG; n = 60 LOM) and stratified for surgery at recurrence; baseline characteristics, including MGMT methylation status, were balanced. Median age was 57.3 yrs; 27 PTS (22.7%) had surgery at recurrence, 22% and 23.3% in REG and LOM arm. At the time of analysis (cut-off date: Dec 31, 2017), median follow up was 15.4 months(m), 99 PTS had died. Median OS was 7.4m (95% CI 5.8–12.0) for REG and 5.6m (95% CI 4.7–7.3) for LOM (HR = 0.50, 80%CI 0.38–0.65; p = 0.0007; 1-sided Log-rank test); 12m-OS rates were 38.9% and 15.0% for REG and LOM. 6m-PFS rates were 16.9% and 8.3% (HR = 0.65; 95% CI 0.45‐0.95; p = 0.0223) for REG and LOM, DCR was 44.8% and 21.1% (p = 0.009) for REG and LOM. Grade ≥3 adverse events were reported in 56% and 40% for REG andLOM, no treatment-related deaths were reported. CONCLUSION: In this multicenter, randomized study, REG significantly improved OS, PFS and DCR in recurrent GBM PTS. REG treatment was feasible and well tolerated. QoL and biomarker analyses are ongoing. A phase 3 study will be planned

Introduction. Sorafenib, an oral multikinase inhibitor, is the only targeted agent approved for the treatment of patients with hepatocellular carcinoma (HCC) after demonstration to increase overall survival compared to placebo in two randomized phase III study. GIDEON (Global Investigation of therapeutic DEcisions in HCC and Of its treatment with sorafeNib) is the largest, global, non-interventional, prospective study of patients with uHCC (n>3200) treated with sorafenib in real-life clinical practice conditions. Here we report the final analysis of safety and efficacy in the Italian cohort of patients. Methods. Patients with unresectable HCC who are candidates for systemic therapy, and for whom a decision has been made to treat with sorafenib, are eligible for inclusion. Patients demographics disease characteristics and treatment history were recorded at baseline visit. Sorafenib dose, concomitant medications, performance status, liver function, adverse events and efficacy (survival and response rate) were collected throughout the study. Results. In the Italian cohort of the GIDEON study 278 patients were included in 36 centers. The global rate of adverse events was 81%. Drug-related events accounted for 67%, mostly of grade 1 and 2, and only 8% were classified as serious. The most common were diarrhea (24%), fatigue (23%), dermatological (14%), rash/exfoliation (10%), hypertension (9%), hemorrage/bleeding of gastrointestinal tract (6%). Overall survival was 14.4 months and time to progression 6.2 months. Objective responses were observed in 14 patients (5%) with 3 complete responses (1%). Stable diseases of at least 6 weeks were observed in 113 patients (41%) with a 30% of disease control rate. Discussion. The safety profile of sorafenib in terms of rate and type of adverse events is similar to that emerged in the global international GIDEON study as well as in the pivotal registration studies.

Purpose: Lonidamine (LND) can enhance the activity of anthracyclines in patients with metastatic breast cancer. A multicenter, prospective, randomized trial was designed to determine whether the association of LND with high-dose epirubicin plus cyclophosphamide (EC) could improve disease-free survival (DFS) in patients with early breast cancer (BC) compared with EC alone. Granulocyte colony-stimulating factor (G-CSF) was added to maintain the EC dose-intensity. Patients and Methods: From October 1991 to April 1994, 506 patients with stage I/II BC were randomly assigned to four groups: (A) epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 administered intravenously on day 1 every 21 days for four cycles (124 patients); (B) EC plus LND 450 mg/d administered orally (125 patients); (C) EC plus G-CSF administered subcutaneously (129 patients); (D) EC plus LND plus G-CSF (128 patients). Results: Median follow-up was 55 months. Five-year DFS rate was similar for LND (B+D groups; 69.6%) versus non-LND arms (A+C groups; 70.3%) and G-CSF (C+D groups; 67.2%) versus non–G-CSF arms (A+B groups; 72.9%). Five-year overall survival (OS) was comparable in LND (79.1%) versus non-LND arms (81.3%) and in G-CSF (80.6%) versus non–G-CSF arms (79.6%). DFS and OS distributions in LND and G-CSF arms did not change according to tumor size, node, receptor, and menopausal status. G-CSF dramatically reduced hematologic toxicity without having a significant impact on dose-intensity (98.1% v 95.5% for C+D and A+B groups, respectively). Conclusion: EC is active and well tolerated in patients with early breast cancer. The addition of LND or G-CSF does not improve DFS or OS.

In humans, two main metabolic enzymes synthesize hydrogen sulfide (H2S): cystathionine γ lyase (CSE) and cystathionine β synthase (CBS). A third enzyme, 3-mercaptopyruvate sulfurtransferase (3-MST), synthesizes H2S in the presence of the substrate 3-mercaptopyruvate (3-MP). The immunohistochemistry analysis performed on human melanoma samples demonstrated that CSE expression was highest in primary tumors, decreased in the metastatic lesions and was almost silent in non-lymph node metastases. The primary role played by CSE was confirmed by the finding that the overexpression of CSE induced spontaneous apoptosis of human melanoma cells. The same effect was achieved using different H2S donors, the most active of which was diallyl trisulfide (DATS). The main pro-apoptotic mechanisms involved were suppression of nuclear factor-κB activity and inhibition of AKT and extracellular signal-regulated kinase pathways. A proof of concept was obtained in vivo using a murine melanoma model. In fact, either l-cysteine, the CSE substrate, or DATS inhibited tumor growth in mice. In conclusion, we have determined that the l-cysteine/CSE/H2S pathway is involved in melanoma progression. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Purpose To study the prognostic value for overall survival of baseline assessment of functional status, comorbidity, and quality of life (QoL) in elderly patients with advanced non—small-cell lung cancer treated with chemotherapy. Patients and Methods Data from 566 patients enrolled onto the phase III randomized Multicenter Italian Lung Cancer in the Elderly Study (MILES) study were analyzed. Functional status was measured as activities of daily living (ADL) and instrumental ADL (IADL). The presence of comorbidity was assessed with a checklist of 33 items; items 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 (EORTC QLQ-C30) were used to estimate QoL. ADL was dichotomized as none versus one or more dependency. For IADL and QoL, three categories were defined using first and third quartiles as cut points. Comorbidity was summarized using the Charlson scale. Analysis was performed by Cox model, and stratified by treatment arm. Results Better values of baseline QoL (P = .0003) and IADL (P = .04) were significantly associated with better prognosis, whereas ADL (P = .44) and Charlson score (P = .66) had no prognostic value. Performance status 2 (P = .006) and a higher number of metastatic sites (P = .02) also predicted shorter overall survival. Conclusions Pretreatment global QoL and IADL scores, but not ADL and comorbidity, have significant prognostic value for survival of elderly patients with advanced non—small-cell lung cancer who were treated with chemotherapy. Using these scores in clinical practice might improve prognostic prediction for treatment planning.

The theatre-auditorium under investigation following the highly reflective characteristics of materials used in it (marble, painted wood, smooth plaster, etc), architectural and structural features of the Protocol and its intended use (very multifunctional: Auditorium, theatre, cinema, musicals, conference room) from the analysis of the statement of fact made by the acoustic simulation software Ramsete and supported by data obtained through a campaign of acoustic measurements of the state of fact made on the spot by a Fonomet Svantek model SVAN 957, appears to be acoustically inadequate. After the completion of the 3D model according to the specifications necessary software used forecast in order to be recognized by him, have made three simulations, acoustic simulation of the state of and acoustic simulation of two design solutions. Improved noise characteristics found in the first design solution, compared to the state in fact consists therefore in lowering Reverberation Time that you turn most desirable value, while the Indicators of Clarity, the Baricentric Time, the Lateral Efficiency, Ratio of Low Tmedia BR and defined the Speech Intelligibility improved significantly. Improved noise characteristics found instead in the second design solution, as compared to first design solution, is finally mostly in a more uniform distribution of Leq and in lowering Reverberation Time that you turn the optimum values. Indicators of Clarity, and the Lateral Efficiency improve further but at the expense of a value slightly worse than the BR. Slightly vary the remaining indices., {"references":["A. Farina,\"Propagation of sound and noise prediction in a work\nEnvironment\",","http://svantek.com/","http://www.autodesk.it","Paolo Galaverna, Angelo Farina \"Ramsete - Manual\", Genesis Software\nand Acoustic Consultancy","Renato Spagnolo \"Handbook of Applied Acoustics\", Ed Utet Library."]}