GlobVolcano Project Overview

The GlobVolcano project is part of the ESA DUE programme. The project aims at demonstrating EO-based services to support the Volcanological Observatories and other mandate users (e.g. Civil Protection authorities, scientific communities of volcanoes) in their monitoring activities. During the project a worldwide selection of user organizations will cooperate with the GlobVolcano team in order to harmonize user’s requirements and to evaluate the EO-based services . The “Osservatorio Vesuviano” of Naples (INGV-Italy) coordinates the communications between the project and the User Community. IPGP of Paris is responsible for the scientific coordination and the validation activities. The project activities are split in two phases. During the first phase (completed in June 2008) the service infrastructure and interface to the users have been developed. Prototype EO-based information products have been generated and validated. Service provision on pre-operational basis will take place during the second phase

lba22negative hyper selection of ras wild type wt metastatic colorectal cancer mcrc patients randomized to first line folfox plus panitumumab pan followed by maintenance therapy with either 5fu lv plus pan or single agent pan translational analyses of the valentino study

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o 016first line folfox plus panitumumab followed by 5 fu lv plus panitumumab or single agent panitumumab as maintenance therapy in patients with ras wild type metastatic colorectal cancer mcrc the valentino study

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Volcanic SO2 by UV-TIR satellite retrievals: validation by using ground-based network at Mt. Etna

Mt. Etna volcano in Italy is one of the most active degassing volcanoes worldwide, emitting a mean of 1.7 Mt/year of Sulphur Dioxide (SO2) in quiescent periods. In this work, SO2 measurements retrieved by Moderate Resolution Imaging Spectroradiometer (MODIS), hyper-spectral Infrared Atmospheric Sounding Interferometer (IASI) and the second Global Ozone Monitoring Experiment (GOME-2) data are compared with the ground-based data from the FLux Automatic MEasurement monitoring network (FLAME). Among the eighteen lava fountain episodes occurring at Mt. Etna in 2011, the 10 April paroxysmal event has been selected as a case-study for the simultaneous observation of the SO2 cloud by satellite and ground-based sensors. For each data-set two retrieval techniques were adopted and the measurements of SO2 mass and flux with their respective uncertainty were obtained. With respect to the FLAME SO2 mass of 4.5 Gg, MODIS, IASI and GOME-2 differ by about 10%, 15% and 30%, respectively. The SO2 flux correlation coefficient between MODIS and FLAME is 0.84. All the retrievals within the respective errors are in agreement with the ground-based measurements supporting the validity of these space measurements

Maintenance Therapy with Panitumumab Alone vs Panitumumab Plus Fluorouracil-Leucovorin in Patients with RAS Wild-Type Metastatic Colorectal Cancer: A Phase 2 Randomized Clinical Trial

Key PointsQuestionIs maintenance therapy with single-agent panitumumab noninferior to panitumumab plus fluorouracil and leucovorin after a 4-month induction treatment with panitumumab plus FOLFOX-4 in patients with previously untreated RAS wild-type metastatic colorectal cancer? FindingsIn this open-label, phase 2 randomized clinical trial of 229 patients, maintenance therapy with single-agent panitumumab alone was inferior to panitumumab plus fluorouracil-leucovorin in terms of 10-month progression-free survival (49.0% vs 59.9%). MeaningThe continuation of single-agent anti-epidermal growth factor receptor treatment in the maintenance setting will likely achieve inferior progression-free survival compared with the continuation of chemotherapy plus an anti-epidermal growth factor receptor agent in a phase 3 confirmation trial. This open-label, phase 2 randomized clinical trial assesses whether maintenance therapy with single-agent panitumumab was noninferior to panitumumab plus combined fluorouracil and leucovorin calcium among patients with RAS wild-type metastatic colorectal cancer. ImportanceFew studies are available on the role of maintenance strategies after induction treatment regimens based on anti-epidermal growth factor receptors, and the optimal regimen for an anti-epidermal growth factor receptors-based maintenance treatment in patients with RAS wild-type metastatic colorectal cancer is still to be defined. ObjectiveTo determine whether maintenance therapy with single-agent panitumumab was noninferior to panitumumab plus fluorouracil and leucovorin after a 4-month induction treatment regimen. Design, Setting, and ParticipantsThis open-label, randomized phase 2 noninferiority trial was conducted from July 7, 2015, through October 27, 2017, at multiple Italian centers. Patients with RAS wild-type, unresectable metastatic colorectal adenocarcinoma who had not received previous treatment for metastatic disease were eligible. Induction therapy consisted of panitumumab plus FOLFOX-4 (panitumumab, 6 mg/kg, oxaliplatin, 85 mg/m(2) at day 1, leucovorin calcium, 200 mg/m(2), and fluorouracil, 400-mg/m(2) bolus, followed by 600-mg/m(2) continuous 24-hour infusion at days 1 and 2, every 2 weeks). Cutoff date for analyses was July 30, 2018. InterventionsPatients were randomized (1:1) to first-line panitumumab plus FOLFOX-4 for 8 cycles followed by maintenance therapy with panitumumab plus fluorouracil-leucovorin (arm A) or panitumumab (arm B) until progressive disease, unacceptable toxic effects, or consent withdrawal. The minimization method was used to stratify randomization by previous adjuvant treatment and number of metastatic sites. Main Outcomes and MeasuresThe prespecified primary end point was 10-month progression-free survival (PFS) analyzed on an intention-to-treat basis with a noninferiority margin of 1.515 for the upper limit of the 1-sided 90% CI of the hazard ratio (HR) of arm B vs A. ResultsOverall, 229 patients (153 male [66.8%]; median age, 64 years [interquartile range (IQR), 56-70 years]) were randomly assigned to arm A (n=117) or arm B (n=112). At a median follow-up of 18.0 months (IQR, 13.1-23.3 months]), a total of 169 disease progression or death events occurred. Arm B was inferior (upper limit of 1-sided 90% CI of the HR,1.857). Ten-month PFS was 59.9% (95% CI, 51.5%-69.8%) in arm A vs 49.0% (95% CI, 40.5%-59.4%) in arm B (HR,1.51; 95% CI, 1.11-2.07; P=.01). During maintenance, arm A had a higher incidence of grade 3 or greater treatment-related adverse events (36 [42.4%] vs 16 [20.3%]) and panitumumab-related adverse events (27 [31.8%] vs 13 [16.4%]), compared with arm B. Conclusions and RelevanceIn patients with RAS wild-type metastatic colorectal cancer, maintenance therapy with single-agent panitumumab was inferior in terms of PFS compared with panitumumab plus fluorouracil-leucovorin, which slightly increased the treatment toxic effects. Trial RegistrationClinicalTrials.gov identifier: NCT0247604

Stimulation of synaptic activity promotes TFEB-mediated clearance of pathological MAPT/Tau in cellular and mouse models of tauopathies

Synapses represent an important target of Alzheimer disease (AD), and alterations of their excitability are among the earliest changes associated with AD development. Synaptic activation has been shown to be protective in models of AD, and deep brain stimulation (DBS), a surgical strategy that modulates neuronal activity to treat neurological and psychiatric disorders, produced positive effects in AD patients. However, the molecular mechanisms underlying the protective role(s) of brain stimulation are still elusive. We have previously demonstrated that induction of synaptic activity exerts protection in mouse models of AD and frontotemporal dementia (FTD) by enhancing the macroautophagy/autophagy flux and lysosomal degradation of pathological MAPT/Tau. We now provide evidence that TFEB (transcription factor EB), a master regulator of lysosomal biogenesis and autophagy, is a key mediator of this cellular response. In cultured primary neurons from FTD-transgenic mice, synaptic stimulation inhibits MTORC1 signaling, thus promoting nuclear translocation of TFEB, which, in turn, induces clearance of MAPT/Tau oligomers. Conversely, synaptic activation fails to promote clearance of toxic MAPT/Tau in neurons expressing constitutively active RRAG GTPases, which sequester TFEB in the cytosol, or upon TFEB depletion. Activation of TFEB is also confirmed in vivo in DBS-stimulated AD mice. We also demonstrate that DBS reduces pathological MAPT/Tau and promotes neuroprotection in Parkinson disease patients with tauopathy. Altogether our findings indicate that stimulation of synaptic activity promotes TFEB-mediated clearance of pathological MAPT/Tau. This mechanism, underlying the protective effect of DBS, provides encouraging support for the use of synaptic stimulation as a therapeutic treatment against tauopathies.This work was supported by the ELKARTEK [KK-2020/00034]; Spanish Ministry of Science and Innovation [PID2019-109724RB-I00]; CIBERNED [CB06/0005/0076]; T.V. is supported by AIRC, IG 2017 #20661, and Italian Ministery of University and Research grant [PRIN2020CLZ5XWTV]