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Pulmonary hypertension (PH) is a frequent complication of chronic lung disease (CLD). However, PH is difficult to diagnose early since accompanying symptoms overlap and are similar to those of the underlying CLD. In most cases the PH is mild to moderate and therefore physical signs may be absent or subtle. This consensus paper provides insight into the clues that might suggest the presence of occult PH in patients with CLD. An overview of current diagnostic tools and emerging diagnostic technologies is provided as well as guidance for the work‐up and diagnosis of PH in patients with CLD.

The muon collider offers a great discover potential for the future of high energy physics. Indeed, it combines the advantages of a lepton collider, with clean signatures and maximum available center of mass energy, with those of a hadron collider, such as low synchrotron radiation. However, it poses interesting challenges, manly related to the fact that muons decay and their product interact with the material of the machine producing the socalled Beam-induced-Background. For this reason, a careful design of the experiments running at a muon collider must be performed, starting from simulation, and moving to the R&D on dedicated technologies. This contribution will focus on the muon system of a muon collider experiment: the current design limitations will be presented, together with the alternative solutions that are being considered. In particular, we are proposing to use the Picosec Micromegas technology for a dedicated timing layer in the muon system, which will improve the muon reconstruction performance in that region. The R&D on this technology will be discussed and preliminary results will be presented.

Background FIBRONET was an observational, multicentre, prospective cohort study investigating the baseline characteristics, clinical course of disease and use of antifibrotic treatment in Italian patients with idiopathic pulmonary fibrosis (IPF). Methods Patients aged ≥ 40 years diagnosed with IPF within the previous 3 months at 20 Italian centres were consecutively enrolled and followed up for 12 months, with evaluations at 3, 6, 9 and 12 months. The primary objective was to describe the clinical course of IPF over 12 months of follow-up, including changes in lung function measured by % predicted forced vital capacity (FVC% predicted). Results 209 patients (82.3% male, mean age 69.54 ± 7.43 years) were enrolled. Mean FVC% predicted was relatively preserved at baseline (80.01%). The mean time between IPF diagnosis and initiation of antifibrotic therapy was 6.38 weeks; 72.3% of patients received antifibrotic therapy within the first 3 months of follow-up, and 83.9% within 12 months of follow-up. Mean FVC% predicted was 80.0% at baseline and 82.2% at 12 months, and 47.4% of patients remained stable (i.e. had no disease progression) in terms of FVC% predicted during the study. Conclusions FIBRONET is the first prospective, real-life, observational study of patients with IPF in Italy. The short time between diagnosis and initiation of antifibrotic therapy, and the stable lung function between baseline and 12 months, suggest that early diagnosis and prompt initiation of antifibrotic therapy may preserve lung function in patients with IPF. Trial registration: NCT02803580

The present generation of Micro-Pattern Gaseous Detectors (MPGDs) are radiation hard detectors, capable of detecting effciently particle rates of several MHz/cm2, while exhibiting good spatial resolution (≤ 50 µm) and modest time resolution of 5-10 ns, which satisfies the current generation of experiments (High Luminosity LHC upgrades of CMS and ATLAS) but it is not sufficient for bunch crossing identification of fast timing systems at FCC-hh. Thanks to the application of thin resistive films such as Diamond-Like Carbon (DLC) a new detector concept was conceived: Fast Timing MPGD (FTM). In the FTM the drift volume of the detector has been divided in several layers each with their own amplification structure. The use of resistive electrodes makes the entire structure transparent for electrical signals. After some first initial encouraging results, progress has been slowed down due to problems with the wet-etching of DLC-coated polyimide foils. To solve these problems a more in-depth knowledge of the internal stress of the DLC together with the DLC-polyimide adhesion is required. We will report on the production of DLC films produced in Italy with Ion Beam Sputtering and Pulsed Laser Deposition, where we are searching to improve the adhesion of the thin DLC films, combined with a very high uniformity of the resistivity values.

Background. With the improvement in survival rates after lung transplantation, concern has arisen about evaluating quality of life (QoL). This multicenter cross-sectiol study aimed at describing QoL and identifying factors associated with it. Methods. We assessed QoL in 129 lung transplant recipients from 5 centres in Italy, during scheduled followup visits, using the SF-36, GHQ and St George's respiratory questionires (SGRQ). Results. The SF-36 elicited impaired QoL in the physical, but not in the mental domains (PCS=44; MCS=53). The GHQ identified 29 patients (23%) with psychological discomfort and the SGRQ scores were significantly better than those of patients with chronic respiratory disease. On multivariate alysis, exertiol dyspnea was an independent predictor of the PCS (adjusted Δ -6.3 (p5. Conclusions. The study identified exertiol dyspnea as the main determint of QoL as measured both by SF36 (PCS) and GHQ. Other objective measures contributed only to the PCS. Thus, the SF-36 (PCS) and GHQ were useful in identifying patients who needed treatment not only for complications but also psychological support and continued physical rehabilitation.

To investigate simultaneously localization and relative activity of MMPs during extracellular matrix (ECM) remodeling in bleomycin-induced pulmonary fibrosis in rat, we analyzed the time course of the expression, activity and/or concentration of gelatinases MMP-2 and MMP-9, collagenase MMP-1, matrylisin MMP-7, TIMP-1 and TIMP-2, both in alveolar space (cellular and extracellular compartments) and in lung tissue. MMP and TIMP expression was detected (immunohistochemistry) in lung tissue. MMP activity (zymography) and TIMP concentration (ELISA) were evaluated in lung tissue homogenate (LTH), BAL supernatant (BALs) and BAL cell pellet (BALp) 3, 7, 14, and 28 days after bleomycin intratracheal instillation. Immunohistochemistry showed an extensive MMP and TIMP expression from day 7 in a wide range of structural and inflammatory cells in treated rats. MMP-2 was present mainly in epithelia, MMP-9 in inflammatory cells. MMP-2 and MMP-9 activity was increased respectively in BAL fluid and BAL cells, with a peak at day 7. TIMP-1 and TIMP-2 concentration (ELISA) enhancement was delayed at day 14. In conclusion gelatinases and their inhibitors are significantly activated during bleomycin-induced pulmonary fibrosis. Marked changes in gelatinases activity are observed early in the alveolar compartment, with a prevailing extracellular activity of MMP-2 and a predominant intracellular distribution of MMP-9, while enzyme activity changes in lung parenchyma were less evident. In the repairing phase the reduction of gelatinases activity is synchronous with a peak of alveolar concentration of their inhibitors.

Sixty-five patients with hematological malignancies (25 multiple myeloma, 18 Hodgkin's disease, 22 non-Hodgkin's lymphomas) who received a carmustine-based regimen followed by autologous PBPC transplantation, were studied retrospectively to evaluate the incidence of post-transplant non-infective pulmonary complications (NIPCs), risk factors predictive of NIPCs, and response to steroids. Carmustine (BCNU) given i.v. at a dose of 600 mg/m2 was combined with etoposide and cyclophosphamide in 40 patients (BCV regimen) and with etoposide and melphalan in 25 patients (BEM regimen). Seventeen of 65 patients (26%) had one episode of NIPCs. The median time to NIPCs was 90 days (52-289). Factors that increased the risk of developing NIPCs on multivariate analysis were female sex (P < 0. 001) and BCV regimen (P < 0.05). All patients with NIPCs received prednisone at a dose of 1 mg/kg body weight for 10 days then tapered by 5 mg every two days; complete response to steroids was achieved in 15 of 17 patients; one unresponsive patient died of interstitial pneumonia. BCNU given at the dose of 600 mg/m2 is well tolerated when associated with melphalan and etoposide. In females and in patients receiving BCNU with cyclophosphamide, a BCNU dose reduction may be advisable. Bone Marrow Transplantation (2000) 25, 309-313.

A low cost gas-based charged particle detector, the Resistive Plate Counter (RPC) intensively used in fixed target and collider high energy experiments, is proposed as basic detector for Positron Emission Tomography. The performance of RPCs in terms of intrinsic space and time resolution and electronic pulse height response, makes it possible to transform standard RPCs into photon detectors and therefore to compensate for the photon sensitivity of scintillating crystals, when the efficiency of the complex crystal + photomultiplier is turned into standard quantum efficiency (q.e). Prototype multigap glass RPCs were developed which optimize γ detection efficiency and thus might substitute the traditional scintillators setups.