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Post-orogenic back-arc magmatism is accompanied by hydrothermal ore deposits and mineralizations derived from mantle and crustal sources. We investigate Zannone Island (ZI), back-arc Tyrrhenian basin, Italy, to define the source(s) of mineralizing hydrothermal fluids and their relationships with the regional petrological-tectonic setting. On ZI, early Miocene thrusting was overprinted by late Miocene post-orogenic extension and related hydrothermal alteration. Since active submarine hydrothermal outflow is reported close to the island, Zannone provides an ideal site to determine the P-T-X evolution of the long-lived hydrothermal system. We combined field work with microstructural analyses on syn-tectonic quartz veins and carbonate mineralizations, X-ray diffraction analysis, microthermometry and element mapping of fluid inclusions (FIs), C, O, and clumped isotopes, and analyses of noble gases (He-Ne-Ar) and CO2 content in FIs. Our results document the evolution of a fluid system of magmatic origin with increasing mixing of meteoric fluids. Magmatic fluids were responsible for quartz veins precipitation at ∼125 to 150 MPa and ∼300°C–350°C. With the onset of extensional faulting, magmatic fluids progressively interacted with carbonate rocks and mixed with meteoric fluids, leading to (a) host rock alteration with associated carbonate and minor ore mineral precipitation, (b) progressive fluid neutralization, (c) cooling of the hydrothermal system (from ∼320°C to ∼86°C), and (d) embrittlement and fracturing of the host rocks. Both quartz and carbonate mineralizations show noble gases values lower than those from the adjacent active volcanic areas and submarine hydrothermal systems, indicating that the fossil-to-active hydrothermal history is associated with the emplacement of multiple magmatic intrusions.

The mutations of NPM1 and FLT3-ITD represent the most frequent genetic aberration in acute myeloid leukemia. Indeed, the presence of an NPM1 mutation reduces the negative prognostic impact of FLT3-ITD in patients treated with conventional “3+7” induction. However, little information is available on their prognostic role with intensified regimens. Here, we investigated the efficacy of a fludarabine, high-dose cytarabine and idarubicin induction (FLAI) in 149 consecutive fit AML patients (median age 52) carrying the NPM1 and/or FLT3-ITD mutation, treated from 2008 to 2018. One-hundred-and-twenty-nine patients achieved CR (86.6%). After a median follow up of 68 months, 3-year overall survival was 58.6%. Multivariate analysis disclosed that both NPM1mut (p < 0.05) and ELN 2017 risk score (p < 0.05) were significant predictors of survival. NPM1-mutated patients had a favorable outcome, with no significant differences between patients with or without concomitant FLT3-ITD (p = 0.372), irrespective of FLT3-ITD allelic burden. Moreover, in landmark analysis, performing allogeneic transplantation (HSCT) in first CR proved to be beneficial only in ELN 2017 high-risk patients. Our data indicate that FLAI exerts a strong anti-leukemic effect in younger AML patients with NPM1mut and question the role of HSCT in 1st CR in NPM1mut patients with concomitant FLT3-ITD.

The City of Venice and the surrounding lagoonal ecosystem are highly vulnerable to variations in relative sea level. In the past ~150 years, this was characterized by a secular linear trend of about 2.5 mm/year resulting from the combined contributions of vertical land movement and sea-level rise. This literature review reassesses and synthesizes the progress achieved in understanding, estimating and predicting the individual contributions to local relative sea level, with focus on the most recent publications. The current best estimate of historical sea-level rise in Venice, based on tide-gauge data after removal of subsidence effects, is 1.23 ± 0.13 mm/year (period from 1872 to 2019). Subsidence thus contributed to about half of the observed relative sea-level rise over the same period. A higher – yet more uncertain – rate of sea-level rise is observed during recent decades, estimated from tide-gauge data to be about 2.76 ± 1.75 mm/year in the period 1993–2019 for the climatic component alone. An unresolved issue is the contrast between the observational capacity of tide gauges and satellite altimetry, with the latter tool not covering the Venice Lagoon. Water mass exchanges through the Gibraltar Strait currently constitute a source of substantial uncertainty for estimating future deviations of the Mediterranean mean sea-level trend from the global-mean value. Subsidence and regional atmospheric and oceanic circulation mechanisms can deviate Venetian relative sea-level trends from the global mean values for several decades. Regional processes will likely continue to determine significant interannual and interdecadal variability of Venetian sea level with magnitude comparable to that observed in the past, as well as non-negligible differential trends. Our estimate of the likely range of mean sea-level rise in Venice by 2100 due to climate change is presently estimated between 11 and 110 centimetres. An improbable yet possible high-end scenario linked to strong ice

The city of Venice and the surrounding lagoonal ecosystem are highly vulnerable to variations in relative sea level. In the past ∼150 years, this was characterized by an average rate of relative sea-level rise of about 2.5 mm/year resulting from the combined contributions of vertical land movement and sea-level rise. This literature review reassesses and synthesizes the progress achieved in quantification, understanding and prediction of the individual contributions to local relative sea level, with a focus on the most recent studies. Subsidence contributed to about half of the historical relative sea-level rise in Venice. The current best estimate of the average rate of sea-level rise during the observational period from 1872 to 2019 based on tide-gauge data after removal of subsidence effects is 1.23 ± 0.13 mm/year. A higher – but more uncertain – rate of sea-level rise is observed for more recent years. Between 1993 and 2019, an average change of about +2.76 ± 1.75 mm/year is estimated from tide-gauge data after removal of subsidence. Unfortunately, satellite altimetry does not provide reliable sea-level data within the Venice Lagoon. Local sea-level changes in Venice closely depend on sea-level variations in the Adriatic Sea, which in turn are linked to sea-level variations in the Mediterranean Sea. Water mass exchange through the Strait of Gibraltar and its drivers currently constitute a source of substantial uncertainty for estimating future deviations of the Mediterranean mean sea-level trend from the global-mean value. Regional atmospheric and oceanic processes will likely contribute significant interannual and interdecadal future variability in Venetian sea level with a magnitude comparable to that observed in the past. On the basis of regional projections of sea-level rise and an understanding of the local and regional processes affecting relative sea-level trends in Venice, the likely range of atmospherically corrected relative sea-level rise in Venice by

The City of Venice and the surrounding lagoonal ecosystem are highly vulnerable to variations in relative sea level. In the past ~150 years, this was characterized by a secular linear trend of about 2.5 mm/year resulting from the combined contributions of vertical land movement and sea-level rise. This literature review reassesses and synthesizes the progress achieved in understanding, estimating and predicting the individual contributions to local relative sea level, with focus on the most recent publications. The current best estimate of historical sea-level rise in Venice, based on tide-gauge data after removal of subsidence effects, is 1.23 ± 0.13 mm/year (period from 1872 to 2019). Subsidence thus contributed to about half of the observed relative sea-level rise over the same period. A higher – yet more uncertain – rate of sea-level rise is observed during recent decades, estimated from tide-gauge data to be about 2.76 ± 1.75 mm/year in the period 1993–2019 for the climatic component alone. An unresolved issue is the contrast between the observational capacity of tide gauges and satellite altimetry, with the latter tool not covering the Venice Lagoon. Water mass exchanges through the Gibraltar Strait currently constitute a source of substantial uncertainty for estimating future deviations of the Mediterranean mean sea-level trend from the global-mean value. Subsidence and regional atmospheric and oceanic circulation mechanisms can deviate Venetian relative sea-level trends from the global mean values for several decades. Regional processes will likely continue to determine significant interannual and interdecadal variability of Venetian sea level with magnitude comparable to that observed in the past, as well as non-negligible differential trends. Our estimate of the likely range of mean sea-level rise in Venice by 2100 due to climate change is presently estimated between 11 and 110 centimetres. An improbable yet possible high-end scenario linked to strong ice

The extensional Val Roveto Fault, which is the longest exhumed potentially-seismogenic structure of central Apennines, Italy, is examined to constrain earthquake-related fluid circulation and fluid sources within shallow carbonate-hosted faults. The study focuses on fault-related comb and slip-parallel veins that are calcite-filled and cut through the principal surface of the Val Roveto Fault. We observe multiple crack-and-seal events characterized by several veining episodes, probably related to different slip increments along the fault plane. We show that vein calcite precipitated in Late Pleistocene time below the present-day outcrop level at a maximum depth of ∼350 m and temperatures between 32 and 64 °C from meteoric-derived fluids modified by reactions with crustal rocks and with a mantle contribution (up to ∼39%). The observed warm temperatures are not compatible with a shallow (≤∼350 m) precipitation depth, which, in this region, is dominated by circulation of cold meteoric water and/or shallow groundwater. Based on structural–geochemical data, we propose that deep-seated crust–mantle-derived warm fluids were squeezed upward during earthquakes and were hence responsible for calcite precipitation at shallow depths in co-seismic comb and slip-parallel fractures. As comb- and slip-parallel veins are rather common, particularly along seismogenic extensional faults, we suggest that further studies are necessary to test whether these veins are often of co-seismic origin. If so, they may become a unique and irreplaceable tool to unravel the seismic history of hazardous active faults.

AACR Annual Meeting 2015, Clinical Trials Minisymposium, Oral Presentation, April 19, 2015 CT135, info:eu-repo/semantics/published

Multifocal breast cancer (MFBC), defined as multiple synchronous unilateral lesions of invasive breast cancer, is relatively frequent and has been associated with more aggressive features than unifocal cancer. Here, we aimed to investigate the genomic heterogeneity between MFBC lesions sharing similar histopathological parameters. Characterization of different lesions from 36 patients with ductal MFBC involved the identification of non-silent coding mutations in 360 protein-coding genes (171 tumour and 36 matched normal samples). We selected only patients with lesions presenting the same grade, ER, and HER2 status. Mutations were classified as 'oncogenic' in the case of recurrent substitutions reported in COSMIC or truncating mutations affecting tumour suppressor genes. All mutations identified in a given patient were further interrogated in all samples from that patient through deep resequencing using an orthogonal platform. Whole-genome rearrangement screen was further conducted in 8/36 patients. Twenty-four patients (67%) had substitutions/indels shared by all their lesions, of which 11 carried the same mutations in all lesions, and 13 had lesions with both common and private mutations. Three-quarters of those 24 patients shared oncogenic variants. The remaining 12 patients (33%) did not share any substitution/indels, with inter-lesion heterogeneity observed for oncogenic mutation(s) in genes such as PIK3CA, TP53, GATA3, and PTEN. Genomically heterogeneous lesions tended to be further apart in the mammary gland than homogeneous lesions. Genome-wide analyses of a limited number of patients identified a common somatic background in all studied MFBCs, including those with no mutation in common between the lesions. To conclude, as the number of molecular targeted therapies increases and trials driven by genomic screening are ongoing, our findings highlight the presence of genomic inter-lesion heterogeneity in one-third, despite similar pathological features. This imp

AACR Annual Meeting 2015, Clinical Trials Minisymposium, Oral Presentation, April 19, 2015 CT135, info:eu-repo/semantics/published

info:eu-repo/semantics/nonPublished