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- Aglietta, M, et al.
(author)
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The cosmic ray primary composition between 10(15) and 10(16) eV from Extensive Air Showers electromagnetic and TeV muon data
- 2004
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In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 20:6, s. 641-652
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Journal article (peer-reviewed)abstract
- The cosmic ray primary composition in the energy range between 10(15) and 10(16) eV, i.e., around the "knee" of the primary spectrum, has been studied through the combined measurements of the EAS-TOP air shower array (2005 m a. s.l., 10(5) m(2) collecting area) and the MACRO underground detector (963 m.a.s.l., 3100 m w.e. of minimum rock overburden, 920 m(2) effective area) at the National Gran Sasso Laboratories. The used observables are the air shower size (N-c) measured by EAS-TOP and the muon number (N-mu) recorded by MACRO. The two detectors are separated on average by 1200 m of rock, and located at a respective zenith angle of about 30degrees. The energy threshold at the surface for muons reaching the MACRO depth is approximately 1.3 TeV. Such muons are produced in the early stages of the shower development and in a kinematic region quite different from the one relevant for the usual N-mu - N-e studies. The measurement leads to a primary composition becoming heavier at the knee of the primary spectrum, the knee itself resulting from the steepening of the spectrum of a primary light component (p, He) of Deltay = 0.7 +/- 0.4 at E-0 similar to 4 x 10(15) eV. The result confirms the ones reported from the observation of the low energy muons at the surface (typically in the GeV energy range), showing that the conclusions do not depend on the production region kinematics. Thus, the hadronic interaction model used (CORSIKA/QGSJET) provides consistent composition results from data related to secondaries produced in a rapidity region exceeding the central one. Such an evolution of the composition in the knee region supports the "standard" galactic acceleration/propagation models that imply rigidity dependent breaks of the different components.. and therefore breaks occurring at lower energies in the spectra of the light nuclei. (C) 2003 Elsevier B.V. All rights reserved.
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- Aglietta, M, et al.
(author)
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The cosmic ray proton, helium and CNO fluxes in the 100 TeV energy region from TeV muons and EAS atmospheric Cherenkov light observations of MACRO and EAS-TOP
- 2004
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In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 21:3, s. 223-240
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Journal article (peer-reviewed)abstract
- The primary cosmic ray (CR) proton, helium and CNO fluxes in the energy range 80-300 TeV are studied at the National Gran Sasso Laboratories by means of EAS-TOP (Campo Imperatore, 2005 m a.s.l.) and MACRO (deep underground, 3100 m w.e., the surface energy threshold for a muon reaching the detector being E-mu(th) approximate to 1.3 TeV). The measurement is based on: (a) the selection of primaries based on their energy/nucleon (i.e., with energy/nucleon sufficient to produce a muon with energy larger than 1.3 TeV) and the reconstruction of the shower geometry by means of the muons recorded by MACRO in the deep underground laboratories; (b) the detection of the associated atmospheric Cherenkov light (C.l.) signals by means of the C.l. detector of EAS-TOP. The C.l. density at core distance r > 100 m is directly related to the total primary energy E-0. Proton and helium ("p + He") and proton, helium and CNO ("p + He + CNO") primaries are thus selected at E-0 approximate to 80 TeV, and at E-0 similar or equal to 250 TeV, respectively. Their flux is measured: J(p+He)(80 TeV) = (1.8 +/- 0.4) x 10(-6) m(-1)-s(-1) sr(-1) TeV-1, and J(p+He+CNO)(250 TeV) = (1.1 +/- 0.3) x 10(-7) m(-2)-s(-1) sr(-1) TeV-1, their relative weights being J(p+He)(J(p+He+CNO)) over bar (250 TeV) = 0.78 +/- 0.17. By using the measurements of the proton spectrum obtained from the direct experiments and hadron flux data in the atmosphere, we obtain for the relative weights of the three components at 250 TeV: J(p) : J(He) : J(CNO) = (0.20 +/- 0.08) : (0.58 +/- 0.19) : (0.22 +/- 0.17). This corresponds to the dominance of helium over proton primaries at 100-1000 TeV, and a possible non-negligible contribution from CNO. The lateral distribution of Cherenkov light in Extensive Air Showers (EASs), which is related to the rate of energy deposit of the primary in the atmosphere, is measured for a selected proton and helium primary beam, and good agreement is found when compared with the one calculated with the CORSIKA/QGSJET simulation model. (C) 2004 Elsevier B.V. All rights reserved.
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- Menden, MP, et al.
(author)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Journal article (peer-reviewed)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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- Cecchi, F., et al.
(author)
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Transcultural translation and validation of Fugl–Meyer assessment to Italian
- 2021
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In: Disability and Rehabilitation. - : Informa UK Limited. - 0963-8288 .- 1464-5165. ; 43:25, s. 3717-3722
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Journal article (peer-reviewed)abstract
- Purpose: The Fugl–Meyer Assessment is the most used and highly recommended clinical assessment of sensorimotor function after stroke. A standardized use of the scale in different countries requires translation and cultural validation to the target language. The objective of the study was to develop an official Italian version of the scale by transcultural translation and validation. Methods: A standardized multistep translation protocol was adopted to achieve optimal conceptual and semantic equivalence. The developed Italian version was validated in 10 post-stroke hemiparetic patients. Items with low intra- and interrater agreement, quantified as percentage of agreement <70% and/or statistically significant disagreement in relative position or concentration, between different raters were identified and revised. Results: All motor items received a high level of agreement with values well above 70%. Disagreements were observed in 6 items in the sensory, joint range and pain domains and 1 in one reflex item. Items showing disagreements were discussed and revised to establish the final Italian version. Conclusions: The culturally validated Italian Fugl–Meyer Assessment can reliably be used in research and in clinical practice. A standardized use will improve the quality of sensorimotor assessment in stroke across Italy and allow reliable comparisons of stroke populations internationally.Implications for rehabilitation The Fugl–Meyer Assessment is the gold standard for evaluation of sensorimotor impairment after stroke. Having access to a transculturally validated official Italian version of Fugl–Meyer Assessment will improve the quality of sensorimotor assessment after stroke among Italian health professionals and researchers. A wider standardized use of the Fugl–Meyer Assessment in Italy will allow reliable international comparison of stroke rehabilitation outcomes. © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.
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- Hochleitner, I., et al.
(author)
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Intra- and inter-rater reliability of the Italian Fugl-Meyer assessment of upper and lower extremity
- 2023
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In: Disability and Rehabilitation. - : Informa UK Limited. - 0963-8288 .- 1464-5165. ; 45:18, s. 2989-2999
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Journal article (peer-reviewed)abstract
- Purpose To assess the intra- and inter-rater reliability motor and sensory functioning, balance, joint range of motion and joint pain subscales of the Italian Fugl-Meyer Assessment (FMA) Upper Extremity (FMA-UE) and Lower Extremity (FMA-LE) at the item- subtotal- and total-level in patients with sub-acute stroke. Materials and methods The FMA was administered to 60 patients with sub-acute stroke (mean age +/- SD = 75.4 +/- 10.7 years; 58.3% men) and independently rated by two physiotherapists on two consecutive days. Intra- and inter-reliability was studied by a rank-based statistical method for paired ordinal data to detect any systematic or random disagreement. Results The item-level intra- and inter-rater reliability was satisfactory (>70%). Reliability level >70% was achieved at subscale and total score level when one- or two-points difference was considered. Systematic disagreements were reported for five items of the FMA-UE, but not for FMA-LE. Conclusions The Italian version of the FMA showed to be a reliable instrument that can therefore be recommended for clinical and research purposes.
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8. |
- Manry, Jérémy, et al.
(author)
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The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.
- 2022
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:21
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Journal article (peer-reviewed)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
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