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The clinical management of pancreatic ductal adenocarcinoma (PDAC) is hampered by the lack of reliable biomarkers. This study investigated the value of soluble stroma-related molecules as PDAC biomarkers. In the first exploratory phase, 12 out of 38 molecules were associated with PDAC in a cohort of 25 PDAC patients and 16 healthy subjects. A second confirmatory phase on an independent cohort of 131 PDAC patients, 30 chronic pancreatitis patients, and 131 healthy subjects confirmed the PDAC association for MMP7, CCN2, IGFBP2, TSP2, sICAM1, TIMP1, and PLG Multivariable logistic regression model identified biomarker panels discriminating respectively PDAC versus healthy subjects (MMP7 + CA19.9, AUC = 0.99, 99% CI = 0.98-1.00) (CCN2 + CA19.9, AUC = 0.96, 99% CI = 0.92-0.99) and PDAC versus chronic pancreatitis (CCN2 + PLG+FN+Col4 + CA19.9, AUC = 0.94, 99% CI = 0.88-0.99). Five molecules were associated with PanIN development in two GEM models of PDAC (PdxCre/LSL-KrasG12D and PdxCre/LSL-KrasG12D/+/LSL-Trp53R172H/+), suggesting their potential for detecting early disease. These markers were also elevated in patient-derived orthotopic PDAC xenografts and associated with response to chemotherapy. The identified stroma-related soluble biomarkers represent potential tools for PDAC diagnosis and for monitoring treatment response of PDAC patients

We present intermediate-resolution (R$\sim$1000) spectra in the $\sim$3500-10,000 A range of 14 globular clusters in the magellanic irregular galaxy NGC 4449 acquired with the Multi Object Double Spectrograph on the Large Binocular Telescope. We derived Lick indices in the optical and the CaII-triplet index in the near-infrared in order to infer the clusters' stellar population properties. The inferred cluster ages are typically older than $\sim$9 Gyr, although ages are derived with large uncertainties. The clusters exhibit intermediate metallicities, in the range $-1.2\lesssim$[Fe/H]$\lesssim-0.7$, and typically sub-solar [$\alpha/Fe$] ratios, with a peak at $\sim-0.4$. These properties suggest that i) during the first few Gyrs NGC 4449 formed stars slowly and inefficiently, with galactic winds having possibly contributed to the expulsion of the $\alpha$-elements, and ii) globular clusters in NGC 4449 formed relatively "late", from a medium already enriched in the products of type Ia supernovae. The majority of clusters appear also under-abundant in CN compared to Milky Way halo globular clusters, perhaps because of the lack of a conspicuous N-enriched, second-generation of stars like that observed in Galactic globular clusters. Using the cluster velocities, we infer the dynamical mass of NGC 4449 inside 2.88 kpc to be M($<$2.88 kpc)=$3.15^{+3.16}_{-0.75} \times 10^9~M_\odot$. We also report the serendipitous discovery of a planetary nebula within one of the targeted clusters, a rather rare event., Comment: Accepted for publication in MNRAS; corrected typo in author list

We present intermediate-resolution (R$\sim$1000) spectra in the $\sim$3500-10,000 A range of 14 globular clusters in the magellanic irregular galaxy NGC 4449 acquired with the Multi Object Double Spectrograph on the Large Binocular Telescope. We derived Lick indices in the optical and the CaII-triplet index in the near-infrared in order to infer the clusters' stellar population properties. The inferred cluster ages are typically older than $\sim$9 Gyr, although ages are derived with large uncertainties. The clusters exhibit intermediate metallicities, in the range $-1.2\lesssim$[Fe/H]$\lesssim-0.7$, and typically sub-solar [$\alpha/Fe$] ratios, with a peak at $\sim-0.4$. These properties suggest that i) during the first few Gyrs NGC 4449 formed stars slowly and inefficiently, with galactic winds having possibly contributed to the expulsion of the $\alpha$-elements, and ii) globular clusters in NGC 4449 formed relatively "late", from a medium already enriched in the products of type Ia supernovae. The majority of clusters appear also under-abundant in CN compared to Milky Way halo globular clusters, perhaps because of the lack of a conspicuous N-enriched, second-generation of stars like that observed in Galactic globular clusters. Using the cluster velocities, we infer the dynamical mass of NGC 4449 inside 2.88 kpc to be M($<$2.88 kpc)=$3.15^{+3.16}_{-0.75} \times 10^9~M_\odot$. We also report the serendipitous discovery of a planetary nebula within one of the targeted clusters, a rather rare event., Comment: Accepted for publication in MNRAS; corrected typo in author list

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Il lavoro affronta l’analisi delle tipologie contrattuali in uso nel settore della nautica da diporto, con particolare riferimento ai modelli in uso da parte delle maggiori associazioni di brokeraggio internazionali in riferimento alla locazione ed al noleggio, analizzandone le clausole più peculiari. Brevi cenni sono stati rivolti anche ai profili assicurativi.