Design of the ELIMAIA ion collection system

A system of permanent magnet quadrupoles (PMQs) is going to be realized byINFNLNS to be used as a collection system for the injection of laser driven ionbeams up to 60 AMeV in an energy selector based on four resistive dipoles. Thissystem is the first element of the ELIMED (ELI-Beamlines MEDical andMultidisciplinary applications) beam transport, dosimetry and irradiation linethat will be developed by INFN-LNS (It) and installed at the ELI-Beamlinesfacility in Prague (Cz). ELIMED will be the first users open transportbeam-line where a controlled laser-driven ion beam will be used formultidisciplinary researches. The definition of well specified characteristics,both in terms of performances and field quality, of the magnetic lenses iscrucial for the system realization, for the accurate study of the beam dynamicsand for the proper matching with the magnetic selection system which will bedesigned in the next months. Here, we report the design of the collection system and the adopted solutionsin order to realize a robust system form the magnetic point of view. Moreover,the first preliminary transport simulations are also described

Safety and Efficacy of a Single Procedure of Extraction and Reimplantation of Infected Cardiovascular Implantable Electronic Device (CIED) in Comparison with Deferral Timing: An Observational Retrospective Multicentric Study

(1) Background: Infections are among the most frequent and life-threatening complications of cardiovascular implantable electronic device (CIED) implantation. The aim of this study is to compare the outcome and safety of a single-procedure device extraction and contralateral implantation versus the standard-of-care (SoC) two-stage replacement for infected CIEDs. (2) Methods: We retrospectively included 66 patients with CIED infections who were treated at two Italian hospitals. Of the 66 patients enrolled in the study, 27 underwent a single procedure, whereas 39 received SoC treatment. All patients were followed up for 12 months after the procedure. (3) Results: Considering those lost to follow-up, there were no differences in the mortality rates between the two cohorts, with survival rates of 81.5% in the single-procedure group and 84.6% in the SoC group (p = 0.075). (4) Conclusions: Single-procedure reimplantation associated with an active antibiofilm therapy may be a feasible and effective therapeutic option in CIED-dependent and frail patients. Further studies are warranted to define the best treatment regimen and strategies to select patients suitable for the single-procedure reimplantation

Prognostic relevance of a T-type calcium channels gene signature in solid tumours: A correlation ready for clinical validation

BackgroundT-type calcium channels (TTCCs) mediate calcium influx across the cell membrane. TTCCs regulate numerous physiological processes including cardiac pacemaking and neuronal activity. In addition, they have been implicated in the proliferation, migration and differentiation of tumour tissues. Although the signalling events downstream of TTCC-mediated calcium influx are not fully elucidated, it is clear that variations in the expression of TTCCs promote tumour formation and hinder response to treatment.MethodsWe examined the expression of TTCC genes (all three subtypes; CACNA-1G, CACNA-1H and CACNA-1I) and their prognostic value in three major solid tumours (i.e. gastric, lung and ovarian cancers) via a publicly accessible database.ResultsIn gastric cancer, expression of all the CACNA genes was associated with overall survival (OS) among stage I-IV patients (all pConclusionsAlterations in CACNA gene expression are linked to tumour prognosis. Gastric cancer represents the most promising setting for further evaluation

Impaired Mitochondrial ATP Production Downregulates Wnt Signaling via ER Stress Induction

Wnt signaling affects fundamental development pathways and, if aberrantly activated, promotes the development of cancers. Wnt signaling is modulated by different factors, but whether the mitochondria! energetic state affects Wnt signaling is unknown. Here, we show that sublethal concentrations of different compounds that decrease mitochondrial ATP production specifically downregulate Wnt/beta-catenin signaling in vitro in colon cancer cells and in vivo in zebrafish reporter lines. Accordingly, fibroblasts from a GRACILE syndrome patient and a generated zebrafish model lead to reduced Wnt signaling. We identify a mitochondria-Wnt signaling axis whereby a decrease in mitochondria! ATP reduces calcium uptake into the endoplasmic reticulum (ER), leading to endoplasmic reticulum stress and to impaired Wnt signaling. In turn, the recovery of the ATP level or the inhibition of endoplasmic reticulum stress restores Wnt activity. These findings reveal a mechanism that links mitochondria! energetic metabolism to the control of the Wnt pathway that may be beneficial against several pathologie

Impaired Mitochondrial ATP Production Downregulates Wnt Signaling via ER Stress Induction

Wnt signaling affects fundamental development pathways and, if aberrantly activated, promotes the development of cancers. Wnt signaling is modulated by different factors, but whether the mitochondria! energetic state affects Wnt signaling is unknown. Here, we show that sublethal concentrations of different compounds that decrease mitochondrial ATP production specifically downregulate Wnt/beta-catenin signaling in vitro in colon cancer cells and in vivo in zebrafish reporter lines. Accordingly, fibroblasts from a GRACILE syndrome patient and a generated zebrafish model lead to reduced Wnt signaling. We identify a mitochondria-Wnt signaling axis whereby a decrease in mitochondria! ATP reduces calcium uptake into the endoplasmic reticulum (ER), leading to endoplasmic reticulum stress and to impaired Wnt signaling. In turn, the recovery of the ATP level or the inhibition of endoplasmic reticulum stress restores Wnt activity. These findings reveal a mechanism that links mitochondria! energetic metabolism to the control of the Wnt pathway that may be beneficial against several pathologie

Time of Flight based diagnostics for high energy laser driven ion beams

Nowadays the innovative high power laser-based ion acceleration technique is one of the most interesting challenges in particle acceleration field, showing attractive characteristics for future multidisciplinary applications, including medical ones. Nevertheless, peculiarities of optically accelerated ion beams make mandatory the development of proper transport, selection and diagnostics devices in order to deliver stable and controlled ion beams for multidisciplinary applications. This is the main purpose of the ELIMAIA (ELI Multidisciplinary Applications of laser-Ion Acceleration) beamline that will be realized and installed within 2018 at the ELI-Beamlines research center in the Czech Republic, where laser driven high energy ions, up to 60 MeV/n, will be available for users. In particular, a crucial role will be played by the on-line diagnostics system, recently developed in collaboration with INFN-LNS (Italy), consisting of TOF detectors, placed along the beamline (at different detection distances) to provide online monitoring of key characteristics of delivered beams, such as energy, fluence and ion species. In this contribution an overview on the ELIMAIA available ion diagnostics will be briefly given along with the preliminary results obtained during a test performed with high energy laser-driven proton beams accelerated at the VULCAN PW-laser available at RAL facility (U.K.)

Filling the Gap: New Precise Early Cretaceous Radioisotopic Ages from the Andes

Two tuffs in the Lower Cretaceous Agrio Formation, Neuquén Basin, provided U–Pb zircon radioisotopic ages of 129.09 ± 0.16 Ma and 127.42 ± 0.15 Ma. Both horizons are well constrained biostratigraphically by ammonites and nannofossils and can be correlated with the ‘standard’ sequence of the Mediterranean Province. The lower horizon is very close to the base of the Upper Hauterivian and the upper horizon to the Hauterivian/Barremian boundary, indicating that the former lies at c. 129.5 Ma and the latter at c. 127 Ma. These new radioisotopic ages fill a gap of over 8 million years in the numerical calibration of the current global Early Cretaceous geological time scale