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BackgroundHigh-dose triple therapy with ICS/LABA/LAMA is recommended for adults with uncontrolled asthma in GINA Steps 4–5 and is often administered concomitant with or prior to initiation of biologic treatment. Previously, we reported in a post-hoc analysis of two large randomized clinical trials (TRIMARAN & TRIGGER) that patients with asthma uncontrolled on ICS/LABA and exhibiting persistent airflow limitation (PAL) may particularly benefit from the addition of LAMA (Singh D et al. Eur Respir J 2020). Here we explore the efficacy of high-dose ICS triple therapy in patients not controlled by high-dose ICS/LABA exhibiting both PAL and high blood eosinophil count, a phenotype that is considered for a step-up to biologic therapy.MethodsUsing the dataset from the TRIGGER study, we conducted a post-hoc analysis in subjects with asthma uncontrolled by high dose ICS/LABA exhibiting PAL (post-salbutamol FEV1≤80% and FEV1/FVC≤0.7) and a blood eosinophils count higher than 150 cell 109/L at screening, to evaluate the annualized rate of moderate to severe exacerbation following a 52 week treatment with high-dose extrafine beclometasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/GB 800mcg/24mcg/50mcg total daily dose pMDI) or high dose extrafine beclometasone dipropionate/formoterol fumarate (BDP/FF 800mcg/24mcg total daily dose pMDI).ResultsThe TRIGGER study population included 1142 patients on BDP/FF/GB or BDP/FF out of which 511 (44.7%) met the criteria of PAL and high blood eosinophil count. After 52 weeks of therapy, the reduction in the rate of ‘severe’ and ‘moderate and severe’ asthma exacerbations with BDP/FF/GB vs BDP/FF was 35.8% (rate ratio = 0.642; 95% CI: 0.445–0.926; p=0.018) and 28.3% (rate ratio = 0.717; 95% CI: 0.573–0.898; p=0.004), respectively.ConclusionTreatment with high-dose extrafine BDP/FF/GB is effective in patients with asthma uncontrolled on high-dose ICS/LABA who exhibit PAL and high blood eosinophils count. Exploring triple therapy before initiation of biologic treatment is an option that merits further investigation.Please refer to page A287 for declarations of interest related to this abstract.

. Time correlated events due to cosmic muons from extensive air showers have been detected by means of telescope pairs of the EEE (Extreme Energy Events) Project array. The coincidence rate, properly normalized for detector acceptance, efficiency and altitude location, has been extracted as a function of the relative distance between the telescopes. The results have been also compared with additional measurements carried out by small scintillator detectors at various distances.

The Extreme Energy Events Project (EEE Project) is an innovative experiment to study very high energy cosmic rays by means of the detection of the associated air shower muon component. It consists of a network of tracking detectors installed inside Italian High Schools. Each tracking detector, called EEE telescope, is composed of three Multigap Resistive Plate Chambers (MRPCs). At present, 43 telescopes are installed and taking data, opening the way for the detection of far away coincidences over a total area of about 3 × 10 5 km 2 . In this paper we present the Monte Carlo simulations that have been performed to predict the expected coincidence rate between distant EEE telescopes.

. The Extreme Energy Events Project is an experiment for the detection of Extensive Air Showers which exploits the Multigap Resistive Plate Chamber technology. At the moment 40 EEE muon telescopes, distributed all over the Italian territory, are taking data, allowing the relative analysis to produce the first interesting results, which are reported here. Moreover, this Project has a strong added value thanks to its effectiveness in terms of scientific communication, which derives from the peculiar way it was planned and carried on.

The Forbush decrease following the large X2 solar flare on mid-February 2011 has been observed by the muon telescopes of the EEE Project, which are located in several Italian sites and at CERN. Data from two different telescopes of the EEE network have been analyzed and compared to those measured by neutron monitor stations. The variation of the muon counting rate during the Forbush decrease was also extracted for different intervals of the azimuthal angle of the incoming muons.

The latest results from the FINUDA experiment on the Non-Mesonic Weak Decay (NMWD) channels of p-shell Λ-hypernuclei are presented and discussed. Spectra of protons from NMWD were obtained for 5ΛHe, 7ΛLi, 9ΛBe, 11ΛB, 12ΛC, 13ΛC, 15ΛN and 16ΛO. An estimation of the contributions of both Final State Interactions (FSI) and two-nucleon induced (2N) decay processes was performed, following a model independent approach. The previously published results are confirmed by a new analysis of the triple coincidence (π−, p, n) events.

. A search for long distance correlations between individual Extensive Air Showers (EAS) detected by pairs of MRPC telescopes of the Extreme Energy Events (EEE) network was carried out. The search for an anomaly in these events is the purpose of our work. A dataset obtained by all the possible 45 pairs between 10 EEE cluster sites (hosting at least two telescopes), located at relative distances between 86 and 1200km, was analyzed, corresponding to an overall period of 3968 days time exposure. To estimate the possible event excess with respect to the spurious rate, the number of coincidence events was extracted as a function of the time difference between the arrival of the showers in the two sites, from ± 10 s to the smallest time interval where events are still observed. The analysis was done taking into account both the time and orientation correlation between the showers detected by the telescope pairs. A few candidate events with unusually small time difference and angular distance were observed, with a p-value sensibly smaller than a confidence level of 0.05.

Distributions of secondary cosmic muons were measured by the Multigap Resistive Plate Chambers (MRPC) telescopes of the Extreme Energy Events (EEE) Project, spanning a large angular and temporal acceptance through its sparse sites, to test the possibility to search for any anomaly over long runs. After correcting for the time exposure and geometrical acceptance of the telescopes, data were transformed into equatorial coordinates, and equatorial sky maps were obtained from different sites on a preliminary dataset of 110M events in the energy range at sub-TeV scale.

The Extreme Energy Events project (EEE) is aimed to study Extensive Air Showers (EAS) from primary cosmic rays of more than 1018 eV energy detecting the ground secondary muon component using an array of telescopes with high spatial and time resolution. The second goal of the EEE project is to involve High School teachers and students in this advanced research work and to initiate them in scientific culture: to reach both purposes the telescopes are located inside High School buildings and the detector construction, assembling and monitoring - together with data taking and analysis - are done by researchers from scientific institutions in close collaboration with them. At present there are 42 telescopes in just as many High Schools scattered all over Italy, islands included, plus two at CERN and three in INFN units. We report here some preliminary physics results from the first two common data taking periods together with the outreach impact of the project.

The Extreme Energy Events observatory is an extended muon telescope array, covering more than 10 degrees both in latitude and longitude. Its 59 muon telescopes are equipped with tracking detectors based on Multigap Resistive Plate Chamber technology with time resolution of the order of a few hundred picoseconds. The recent restrictions on greenhouse gases demand studies for new gas mixtures in compliance with the relative requirements. Tetrafluoropropene is one of the candidates for tetrafluoroethane substitution, since it is characterized by a Global Warming Power around 300 times lower than the gas mixtures used up to now. Several mixtures have been tested, measuring efficiency curves, charge distributions, streamer fractions and time resolutions. Results are presented for the whole set of mixtures and operating conditions, %. A set of tests on a real EEE telescope, with cosmic muons, are being performed at the CERN-01 EEE telescope. The tests are focusing on identifying a mixture with good performance at the low rates typical of an EEE telescope.