Donor‐derived infections due to multidrug‐resistant bacteria are a growing problem in solid organ transplantation, and optimal management options are not clear. In a 2‐year period, 30/214 (14%) ...recipients received an organ from 18/170 (10.5%) deceased donors with infection or colonization caused by a carbapenem‐resistant gram‐negative bacteria that was unknown at the time of transplantation. Among them, 14/30 recipients (47%) received a transplant from a donor with bacteremia or with infection/colonization of the transplanted organ and were considered at high risk of donor‐derived infection transmission. The remaining 16/30 (53%) recipients received an organ from a nonbacteremic donor with colonization of a nontransplanted organ and were considered at low risk of infection transmission. Proven transmission occurred in 4 of the 14 high‐risk recipients because donor infection was either not recognized, underestimated, or not communicated. These recipients received late, short or inappropriate posttransplant antibiotic therapy. Transmission did not occur in high‐risk recipients who received appropriate and prompt antibiotic therapy for at least 7 days. The safe use of organs from donors with multidrug‐resistant bacteria requires intra‐ and inter‐institutional communication to allow appropriate management and prompt treatment of recipients in order to avoid transmission of infection.
The authors review donor‐derived transmission events related to carbapenem‐resistant gram‐negative bacterial infection in a highly endemic region, and suggest strategies to minimize this emerging threat in the vulnerable population of solid organ transplant recipients.
Muon detector for a Muon Collider Aimè, C.; Calzaferri, S.; Casarsa, M. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
01/2023, Volume:
1046
Journal Article
Peer reviewed
A Muon Collider represents a promising possibility to combine the high energy and luminosity of hadron machines with very precise measurements of lepton colliders. The main challenges, that impact ...both the machine and detector design, arise from the short muon lifetime and the harsh Beam-induced Background (BIB).
Therefore, a full simulation is crucial to understand the feasibility of the experiment implementation. Focusing in particular on the muon system, a preliminary simulation of sensitivity and hit rate reveals that the technology inherited from CLIC, i.e. glass Resistive Plate Chambers, is already at the limit of its rate capability. Thus, alternative MicroPattern Gaseous Detector solutions are under investigation to try to match the required performance. In parallel, studies of muon reconstruction are ongoing.
Results of the muon reconstruction efficiency and BIB sensitivity are presented for multimuon final state processes at a centre-of-mass energy of 1.5TeV. Besides, PICOSEC technology, based on a Micromegas detector coupled to a Cherenkov radiator and equipped with a photocathode, is discussed.
•Notch-1 intervenes in the reparative processes of the airway mucosa.•cigarette smoke exposure limits Notch-1 signaling activation in bronchial epithelial cells.•cigarette smoke exposure hinders ...repair processes in bronchial epithelial cells.
Notch-1 intervenes in the reparative processes of mucosa by controlling cell proliferation, differentiation and stem cell maintenance. Cigarette smoke alters airway epithelial homeostasis.
The present study explored whether: Smokers showed altered Notch-1 expression; and whether in bronchial epithelial cells (16HBE): a) cigarette smoke extracts (CSE) altered the expression of Notch-1, of its ligand Jagged-1 (Jag-1) and the nuclear translocation of Notch-1; b) Notch-1 signaling activation as well as CSE modified Ki67, PCNA, p21, IL-33 expression, cell proliferation and repair processes.
Notch-1 expression was assessed in the epithelium from large airway surgical samples from non-smoker and smoker subjects by immunohistochemistry.16HBE were cultured with/without CSE and Jag-1. A Notch-1 inhibitor (DAPT) was used as control. The expression of Notch-1, Jag-1, Ki67, PCNA, p21, IL-33 and cell proliferation (by CFSE) were all assessed by flow cytometry. Notch-1 nuclear expression was evaluated by immunofluorescence and western blot analysis. Repair processes were assessed by wound assay.
Smokers had cytoplasmic but not nuclear Notch-1 expression. Although CSE increased Notch-1 expression, it counteracted Notch-1 signaling activation since it reduced Jag-1 expression and Notch-1 nuclear translocation. Notch-1 signaling activation by Jag-1 increased Ki67, PCNA and repair processes but reduced intracellular IL-33 and p21 expression without affecting cell proliferation. DAPT counteracted the effects of Notch-1 activation on PCNA and IL-33. CSE increased Ki67, PCNA, p21 and IL-33 expression but reduced cell proliferation and repair processes.
In conclusion, cigarette smoke exposure, limiting Notch-1 signaling activation and hindering repair processes, amplifies injury processes in bronchial epithelial cells.
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.
Lung fibroblasts are crucial for the integrity of alveolar structure. Cigarette smoking, the major risk factor for chronic obstructive pulmonary disease, impairs the repair functions of lung ...fibroblasts.
The study simultaneously assessed for the first time cell cycle, p53, p21, p38, ERK 1/2 and IL-8.
Primary foetal lung fibroblasts (HFL-1) and primary lung fibroblasts from former (n=5) and current (n=5) smokers with/without cigarette smoke extracts (CSEs) and inhibitors of p38 and ERK1/2 were studied for cell cycle events and for marker expression by flow-cytometry, western-blot analysis and ELISA.
CSE exposure did not induce caspase 3 cleavage or DNA laddering but reduced S phase, and increased G1 and G2/M in HFL-1. Furthermore CSE increased: p53 and p21 expression; p38 and ERK 1/2 pathway activation; and IL-8 release. Inhibitors of p38 and ERK 1/2 reversed the effects of CSE on cell cycle and on IL-8 release. ERK 1/2 inhibitor was able to reverse the effects of CSE on p21 expression. Primary lung fibroblasts from current smokers had higher ERK 1/2 activation in comparison to normal primary fibroblasts and higher percentage of cells in G1 phase and lower percentage of cells in S phase in comparison to former smoker fibroblasts.
Cigarette smoke may affect the reparative potential of lung fibroblasts altering the expression of p53 and p21 and the progression of the cell cycle to S phase. All these events are promoted by the activation of pro-inflammatory pathways.
Everolimus is a proliferation signal inhibitor with immunosuppressive activity that may reduce the rate of progression of chronic rejection, bronchiolitis obliterans syndrome (BOS), after lung ...transplantation. In a randomized, double‐blind clinical trial, 213 BOS‐free maintenance patients received everolimus (3 mg/day) or azathioprine (AZA, 1–3 mg/kg/day) in combination with cyclosporine and corticosteroids. The prospectively defined primary endpoint was the incidence of efficacy failure (decline in FEV1 >15%ΔFEV1 >15%, graft loss, death or loss to follow‐up) at 12 months. Incidence of efficacy failure at 12 months was significantly lower in the everolimus group than AZA (21.8% vs. 33.9%; p = 0.046); at 24 months, rates of efficacy failure became similar between the groups. At 12 months, the everolimus group had significantly reduced incidences of ΔFEV1 >15%, ΔFEV1 >15% with BOS, and acute rejection. At 24 months, only incidence of acute rejection remained significantly less in the everolimus group. Treatment discontinuations (particularly due to adverse events), serious adverse events and high serum creatinine values were more common with everolimus. For the first time, a drug has demonstrated significant slowing of loss in lung function, suggesting that patients kept on prolonged maintenance treatment with everolimus may benefit from replacing AZA with everolimus 3 months after lung transplantation.
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).
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).
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.
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.
NCT02803580.
Diamond-Like Carbon for the Fast Timing MPGD Colaleo, A.; De Robertis, G.; Licciulli, F. ...
Journal of physics. Conference series,
04/2020, Volume:
1498, Issue:
1
Journal Article
Peer reviewed
Open access
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.
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