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This study aims at assessing the deformation processes affecting an area NW of the city of Ravenna (northern Italy), caused by groundwater withdrawal activities. In-situ data, geologic and structural maps, piezometric measurements, underground water withdrawal volumes, and satellite C-band SAR data were used to jointly exploit two different techniques: 1) fluid-dynamic and geomechanical modelling (by RSE S.p.A), and 2) Differential Synthetic Aperture Radar Interferometry (DInSAR) analysis (by CNR - IREA). The results of the comparative analysis presented in this work brought new evidence about the contribution of groundwater withdrawal to the total subsidence affecting the area during the 2000-2017 time interval. In particular, they show an increase of the subsidence from year 2000 to 2010 and a decrease from year 2010 to 2017. These results are generally in line with groundwater withdrawal data that report a reduction of the extracted water volumes during the considered temporal interval. Meantime, they show a delay effect in the subsidence process, partially recovered during the 2010-2017 thanks to a stabilisation of the extracted groundwater volumes. The presented results shade new light on the groundwater withdrawal contribution to the subsidence of the analysed zone, although further investigations are foreseen to better clarify the ongoing scenario.

The SPOT Project (potentially triggerable offshore seismicity and tsunamis) is aimed at helping Italian authorities to comply with the application of the Safety of Offshore Oil and Gas Operations European Directive (2013/30/EU) and the ensuing Italian codes. An extensive reconstruction of offshore geological structures is being implemented in order to assess the existence of potentially seismogenic faults in the surroundings of offshore oil and gas platforms, as a propaedeutic step for the assessment of potentially triggered seismicity connected with operations on such platforms. The descriptive parameters of the identified faults will be used to estimate their natural earthquake rates. The impact of these natural earthquakes along the coasts will then be modeled in terms of expected ground shaking and tsunamis. In turn, these models will be used to estimate potential human and economic losses in a multi-hazard approach to risk assessment. Wherever the combined earthquake and tsunami modeling indicates a relevant impact along the coasts, a more detailed analysis will be carried out, also involving the operators of the related platforms, to perform specific models which also take into account production data. The project has been conceived and funded by the Italian Ministry of Economic Development, with the technical support of the National Department of Civil Protection. The involved research institutes are the Institute of Marine Sciences of the National Research Council (ISMAR), the National Institute of Geophysics and Volcanology (INGV), the European Centre for Training and Research in Earthquake Engineering (EUCENTRE), and the Laboratories University Network of Seismic Engineering (ReLUIS).

Hydrocarbon seepage is overlooked in the marine environment, mostly due to lack of marine exploration data, especially over the continental shelf and upper slope, where data may be available but not at adequate resolution. Shallow marine environments, such as the north and the central Adriatic Sea, are ideal for the formation of hydrocarbons, because organic matter sinks to the sea bottom where undergoes rapid burial and anaerobic degradation. On the other hand, deeply-trapped hydrocarbons tend to migrate to shallower sedimentary horizons, they may pierce the seabed, giving rise to peculiar seafloor morphology, and, under particular conditions, fluids escape the seabed to form gas plumes in the water column. The latter can be accurately detected by modern multibeam sonar systems as 3D density anomalies, which sometimes can reach high at the sea surface. This contribution is about the geophysical and geochemical investigation of two seepage sites on the shelf of the Adriatic Sea. The study areas are represented by: an oil spill off Civitanova Marche, at water depth of 10 m; scattered biogenic seeps offshore Mt. Conero, at water depth of 84 m. Dissolved benthic fluxes of nutrients, metals and DIC have been measured by in situ deployment of a benthic chamber equipped with an automatic water sampler and a multi-parameter probe. Geochemical analysis was performed to identify the presence of and characterize hydrocarbons in the water samples and provide insights into the origins of the organic matter. Concentration of Polycyclic Aromatic Hydrocarbons and major and trace elements was analyzed to provide an estimate of hydrocarbon contamination in the surrounding sediment. We conducted these research activities under the umbrella of a technical agreement between ISMARCNR and the Italian Ministry of Economic Development, Directorate General for Safety - National Mining Office for Hydrocarbons and Georesources, within the Clypea Innovation Network, which seeks to increase the safety, also in terms of environmental protection, of offshore oil & gas exploration and exploitation, using innovative approaches. This study aims at: i) establishing a cost-effective and relocatable geochemical and geophysical monitoring system for natural hydrocarbon seepage to mitigate the adverse effects of hydrocarbon spill and discharge, especially if located near the coast or nearby human activities; ii) delivering a better understanding of the characteristics and origins of the petroleum system, adding a valuable layer of information to more conventional offshore exploration data; iii) to unravel the relationship of fluid seepage with geohazards, notably softsediment deformation, and sea level changes as triggering mechanism.

Hydrocarbon seepage is overlooked in the marine environment, mostly due to the lack of high-resolution exploration data. This contribution is about the geophysical and geochemical investigation of two seepage sites on the shelf of the Adriatic Sea: an oil spill off Civitanova Marche, at water depth of 10 m; scattered biogenic seeps offshore Mt. Conero, at water depth of 84 m. The accurate detection of gas plumes was achieved with a multibeam system acquisition of the water column reflectivity. Dissolved benthic fluxes of nutrients, metals and DIC were measured by in situ deployment of a benthic chamber, which was used also for the first time as water samples collector for hydrocarbons gas characterization. In addition, concentration of Polycyclic Aromatic Hydrocarbons and major and trace elements was analyzed to provide an estimate of hydrocarbon contamination in the surrounding sediment.

This paper reports the results of a study aimed at analyzing the existing seismic monitoring infrastructures of underground activities for energy production. The study was carried out by the Italian National Institute of Oceanography and Applied Geophysics (OGS), in collaboration with the Italian National Research Council - Institute for Electromagnetic Detection of the Environment (CNRIREA), in the framework of the partnership established by the Ministry of Economic Development, Directorate General for Safety of Mining and Energy Activities - National Mining Office for Hydrocarbons and Georesources (MiSE DGS-UNMIG), with Italian Universities and Research Institutions within the so-called "Network for Offshore Safety". Firstly, a survey was carried out by sending a questionnaire to companies to gather information about the infrastructures and procedures for monitoring seismicity, ground deformation and pore pressure, respectively, implemented within the hydrocarbon exploitation fields for either production or re-injection or gas-storage currently present in Italy. Then, the data obtained by the survey were analyzed with reference to the requirements of the "Italian Guidelines for monitoring the seismicity, underground deformation and pore pressure" (ILG) (Dialuce et al., 2014), in order to establish the possible needs for upgrading and, subsequently, assessing the relative costs. This paper reports the evaluation of the technical part, i.e. that concerning the upgrade of the monitoring systems

Purpose: ABL kinase domain mutations have been implicated in the resistance to the BCR-ABL inhibitor imatinib mesylate of Philadelphia-positive (Ph+) leukemia patients. Experimental Design: Using denaturing high-performance liquid chromatography and sequencing, we screened for ABL kinase domain mutations in 370 Ph+ patients with evidence of hematologic or cytogenetic resistance to imatinib. Results: Mutations were found in 127 of 297 (43%) evaluable patients. Mutations were found in 27% of chronic-phase patients (14% treated with imatinib frontline; 31% treated with imatinib post-IFN failure), 52% of accelerated-phase patients, 75% of myeloid blast crisis patients, and 83% of lymphoid blast crisis/Ph+ acute lymphoblastic leukemia (ALL) patients. Mutations were associated in 30% of patients with primary resistance (44% hematologic and 28% cytogenetic) and in 57% of patients with acquired resistance (23% patients who lost cytogenetic response; 55% patients who lost hematologic response; and 87% patients who progressed to accelerated phase/blast crisis). P-loop and T315I mutations were particularly frequent in advanced-phase chronic myeloid leukemia and Ph+ ALL patients, and often accompanied progression from chronic phase to accelerated phase/blast crisis. Conclusions: We conclude that (a) amino acid substitutions at seven residues (M244V, G250E, Y253F/H, E255K/V, T315I, M351T, and F359V) account for 85% of all resistance-associated mutations; (b) the search for mutations is important both in case of imatinib failure and in case of loss of response at the hematologic or cytogenetic level; (c) advanced-phase chronic myeloid leukemia and Ph+ ALL patients have a higher likelihood of developing imatinib-resistant mutations; and (d) the presence of either P-loop or T315I mutations in imatinib-treated patients should warn the clinician to reconsider the therapeutic strategy.

For almost 10 years imatinib has been the therapeutic standard of chronic myeloid leukemia. The introduction of other tyrosine kinase inhibitors (TKIs) raised a debate on treatment optimization. The debate is still heated: some studies have protocol restrictions or limited follow-up; in other studies, some relevant data are missing. The aim of this report is to provide a comprehensive, long-term, intention-to-treat, analysis of 559 newly diagnosed, chronic-phase, patients treated frontline with imatinib. With a minimum follow-up of 66 months, 65% of patients were still on imatinib, 19% were on alternative treatment, 12% died and 4% were lost to follow-up. The prognostic value of BCR-ABL1 ratio at 3 months (⩽10% in 81% of patients) was confirmed. The prognostic value of complete cytogenetic response and major molecular response at 1 year was confirmed. The 6-year overall survival was 89%, but as 50% of deaths occurred in remission, the 6-year cumulative incidence of leukemia-related death was 5%. The long-term outcome of first-line imatinib was excellent, also because of second-line treatment with other TKIs, but all responses and outcomes were inferior in high-risk patients, suggesting that to optimize treatment results, a specific risk-adapted treatment is needed for such patients.

Our progress in understanding pathological disease mechanisms has led to the identification of biomarkers that have had a considerable impact on clinical practice. It is hoped that the move from generalized to stratified approaches, with the grouping of patients into clinical/therapeutic subgroups according to specific biomarkers, will lead to increasingly more effective clinical treatments in the near future. This success depends on the identification of biomarkers that reflect disease evolution and can be used to predict disease state and therapy response, or represent themselves a target for treatment. Biomarkers can be identified by studying relationships between serum, tissue, or tumor microenvironment parameters and clinical or therapeutic parameters at onset and during the progression of the disease, using systems biology. Given that multiple pathways, such as those responsible for redox and immune regulation, are deregulated or altered in tumors, the future of tumor therapy could lie in the simultaneous targeting of these pathways using extracellular and intracellular targets and biomarkers. With this aim in mind, we evaluated the role of thioredoxin 1, a key redox regulator, and CD30, a cell membrane receptor, in immune regulation. Our results lead us to suggest that the combined use of these biomarkers provides more detailed information concerning the multiple pathways affected in disease and hence the possibility of more effective treatment.