| 1. |
|
|
| 2. |
- Elhai, M, et al.
(author)
-
Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study
- 2019
-
In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:7, s. 979-987
-
Journal article (peer-reviewed)abstract
- To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.MethodsWe performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.Results254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47–5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55–1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56–3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83–9.62]; p=0.019 as compared with controls vs 3 [0.66–5.35]; p=0.012).ConclusionRituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.
|
|
| 3. |
|
|
| 4. |
- Shepherd, L., et al.
(author)
-
Infection-related and -unrelated malignancies, HIV and the aging population
- 2016
-
In: HIV Medicine. - : Wiley. - 1464-2662 .- 1468-1293. ; 17:8, s. 590-600
-
Journal article (peer-reviewed)abstract
- Objectives: HIV-positive people have increased risk of infection-related malignancies (IRMs) and infection-unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on future IRM and IURM incidence. Methods: People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence. Results: A total of 15 648 people contributed 95 033 person-years of follow-up, of whom 610 developed 643 malignancies [IRMs: 388 (60%); IURMs: 255 (40%)]. After adjustment, a higher IRM incidence was associated with a lower CD4 count [adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/μL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/μL], independent of age, while a CD4 count < 200 cells/μL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40–4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5-year period from 3.1 (95% CI 1.5–5.9) per 1000 person-years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2–7.2) per 1000 person-years over the same period. Conclusions: Demographic and HIV-related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV-infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost−benefit of screening for IURMs in HIV-infected populations.
|
|
| 5. |
|
|
| 6. |
- Ambrosio, M, et al.
(author)
-
The MACRO detector at Gran Sasso
- 2002
-
In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 486:3, s. 663-707
-
Journal article (peer-reviewed)abstract
- MACRO was an experiment that ran in the Laboratori Nazionali del Gran Sasso from 1988 to 2000. Its principal goal was to observe magnetic monopoles or set significantly lower experimental flux limits than had been previously available in the velocity range from about beta = 10(-4) to unity. In addition it made a variety of other observations. Examples are: setting flux limits on other so far unobserved particles such as nuclearites and lightly ionizing particles, searching for WIMP annihilations in the Earth and the Sun and for neutrino bursts from stellar collapses in or near our Galaxy, and making measurements relevant to high energy muon and neutrino astronomy and of the flux of up-going muons as a function of nadir angle showing evidence for neutrino oscillations. The apparatus consisted of three principal types of detectors: liquid scintillator counters, limited streamer tubes, and nuclear track etch detectors. In addition, over part of its area it contained a transition radiation detector. The general design philosophy emphasized redundancy and complementarity. This paper describes the technical aspects of the complete MACRO detector, its operational performance, and the techniques used to calibrate it and verify its proper operation. It supplements a previously published paper which described the first portion of the detector that was built and operated. (C) 2002 Elsevier Science B.V. All rights reserved.
|
|
| 7. |
|
|
| 8. |
- Aglietta, M, et al.
(author)
-
The cosmic ray primary composition between 10(15) and 10(16) eV from Extensive Air Showers electromagnetic and TeV muon data
- 2004
-
In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 20:6, s. 641-652
-
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.
|
|
| 9. |
- Aglietta, M, et al.
(author)
-
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
-
In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 21:3, s. 223-240
-
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.
|
|
| 10. |
- Ambrosio, M, et al.
(author)
-
Muon energy estimate through multiple scattering with the MACRO detector
- 2002
-
In: Nuclear Instruments and Methods in Physics Research Section A. - 0168-9002 .- 1872-9576. ; 492:3, s. 376-386
-
Journal article (peer-reviewed)abstract
- Muon energy measurement represents an important issue for any experiment addressing neutrino-induced up-going muon studies. Since the neutrino oscillation probability depends on the neutrino energy, a measurement of the muon energy adds an important piece of information concerning the neutrino system. We show in this paper how the MACRO limited streamer tube system can be operated in drift mode by using the TDCs included in the QTPs, an electronics designed for magnetic monopole search. An improvement of the space resolution is obtained, through an analysis of the multiple scattering of muon tracks as they pass through our detector. This information can be used further to obtain an estimate of the energy of muons crossing the detector. Here we present the results of two dedicated tests, performed at CERN PS-T9 and SPS-X7 beam lines, to provide a full check of the electronics and to exploit the feasibility of such a multiple scattering analysis. We show that by using a neural network approach, we are able to reconstruct the muon energy for E-mu < 40 GeV. The test beam data provide an absolute energy calibration, which allows us to apply this method to MACRO data. (C) 2002 Elsevier Science B.V. All rights reserved.
|
|
| 11. |
- Ambrosio, M, et al.
(author)
-
Atmospheric neutrino oscillations from upward throughgoing muon multiple scattering in MACRO
- 2003
-
In: Physics Letters B. - 0370-2693 .- 1873-2445. ; 566:1-2, s. 35-44
-
Journal article (peer-reviewed)abstract
- The energy of atmospheric neutrinos detected by MACRO was estimated using multiple Coulomb scattering of upward throughgoing muons. This analysis allows a test of atmospheric neutrino oscillations, relying on the distortion of the muon energy distribution. These results have been combined with those coming from the upward throughgoing muon angular distribution only. Both analyses are independent of the neutrino flux normalization and provide strong evidence, above the for level, in favour of neutrino oscillations. (C) 2003 Published by Elsevier B.V.
|
|
| 12. |
- Ambrosio, M, et al.
(author)
-
Final results of magnetic monopole searches with the MACRO experiment
- 2002
-
In: European Physical Journal C. - : Springer. - 1434-6044 .- 1434-6052. ; 25:4, s. 511-522
-
Journal article (peer-reviewed)abstract
- We present the final results obtained by the MACRO experiment in the search for GUT magnetic monopoles in the penetrating cosmic radiation, for the range 4 x 10(-5) < 3 < 1. Several searches with all the MACRO sub-detectors (i.e. scintillation counters, limited streamer tubes and nuclear track detectors) were performed, both in stand alone and combined ways. No candidates were detected and a 90% Confidence Level (C.L.) upper limit to the local magnetic monopole flux was set at the level of 1.4 x 10(-16) cm(-2) s(-1) sr(-1). This result is the first experimental limit obtained in direct searches which is well below the Parker bound in the whole 3 range in which GUT magnetic monopoles are,expected.
|
|
| 13. |
- Ambrosio, M, et al.
(author)
-
Measurement of the residual energy of muons in the Gran Sasso underground laboratories
- 2003
-
In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 19:3, s. 313-328
-
Journal article (peer-reviewed)abstract
- The MACRO detector was located in the Hall B of the Gran Sasso underground laboratories under an average rock overburden of 3700 hg/cm(2). A transition radiation detector composed of three identical modules, covering a total horizontal area of 36 m(2), was installed inside the empty upper part of the detector in order to measure the residual energy of muons. This paper presents the measurement of the residual energy of single and double muons crossing the apparatus. Our data show that double muons are more energetic than single ones. This measurement is performed over a standard rock depth range from 3000 to 6500 hg/cm(2). (C) 2002 Elsevier Science B.V. All rights reserved.
|
|
| 14. |
- Ambrosio, M, et al.
(author)
-
Moon and Sun shadowing effect in the MACRO detector
- 2003
-
In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 20:2, s. 145-156
-
Journal article (peer-reviewed)abstract
- Using data collected by the MACRO experiment from 1989 to the end of its operations in 2000, we have studied in the underground muon flux the shadowing. effects due to both the Moon and the Sun. We have observed the shadow cast by the Moon at its apparent position with a significance of 6.5sigma. The Moon shadowing effect has been used to verify the pointing capability of the detector and to determine the instrument resolution for the search of muon excesses from any direction of the celestial sphere. The dependence of the effect on the geomagnetic field is clearly shown by splitting the data sample in day and night observations. The Sun shadow, observed with a significance of 4.6sigma is displaced by about 0.6degrees from its apparent position. In this case however the explanation resides in the configuration of the Solar and Interplanetary Magnetic Fields, which affect the propagation of cosmic ray particles between the Sun, and the Earth. The displacement of the Sun shadow with respect to the real Sun position has been used to establish an upper limit on the antimatter flux in cosmic rays of about 48% at 68% c.l. and primary energies of about 20 TeV. (C) 2003 Elsevier B.V. All rights reserved.
|
|
| 15. |
- Ambrosio, M, et al.
(author)
-
Search for cosmic ray sources using muons detected by the MACRO experiment
- 2003
-
In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 18:6, s. 615-627
-
Journal article (peer-reviewed)abstract
- The MACRO underground detector at Gran Sasso Laboratory recorded 60 million secondary cosmic ray muons from February 1989 until December 2000. Different techniques were used to analyze this sample in search for density excesses from astrophysical point-like sources. No evidence for DC excesses for any source in an all-sky survey is reported. In addition, searches for muon excess correlated with the known binary periods of Cygnus X-3 and Hercules X-1, and searches for statistically significant bursting episodes from known gamma-ray sources are also proved negative. (C) 2002 Elsevier Science B.V. All rights reserved.
|
|
| 16. |
- Ambrosio, M, et al.
(author)
-
Search for diffuse neutrino flux from astrophysical sources with MACRO
- 2003
-
In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 19:1, s. 1-13
-
Journal article (peer-reviewed)abstract
- Many galactic and extragalactic astrophysical sources are currently considered promising candidates as high-energy neutrino emitters. Astrophysical neutrinos can be detected as upward-going muons produced in charged-current interactions with the medium surrounding the detector. The expected neutrino fluxes from various models start to dominate on the atmospheric neutrino background at neutrino energies above some tens of TeV. We present the results of a search for an excess of high-energy upward-going muons among the sample of data collected by MACRO during similar to5.8 years of effective running time. No significant evidence for this signal was found. As a consequence, an upper limit on the flux of upward-going muons from high-energy neutrinos was set at the level of 1.7 x 10(-14) cm(-2) s(-1) sr(-1). The corresponding upper limit for the diffuse neutrino flux was evaluated assuming a neutrino power law spectrum. Our result was compared with theoretical predictions and upper limits from other experiments. (C) 2002 Elsevier Science B.V. All rights reserved.
|
|
| 17. |
- Ambrosio, M, et al.
(author)
-
Search for nucleon decays induced by GUT magnetic monopoles with the MACRO experiment
- 2002
-
In: European Physical Journal C. - : Springer. - 1434-6044 .- 1434-6052. ; 26:2, s. 163-172
-
Journal article (peer-reviewed)abstract
- The interaction of a Grand Unification Magnetic Monopole with a nucleon can lead to a barion-number violating process in which the nucleon decays into a lepton and one or more mesons (catalysis of nucleon decay). In this paper we report an experimental study of the effects of a catalysis process in the MACRO detector. Using a dedicated analysis we obtain new magnetic monopole (MM) flux upper limits at the level of similar to 3 (.) 10(-16) cm(-2) s(-1) sr(-1) for 1.1(.) 10(-4) less than or equal to \beta\ less than or equal to 5 (.) 10(-3), based on the search for catalysis events in the MACRO data. We also analyze the dependence of the MM flux limit on the catalysis cross section.
|
|
| 18. |
- Ambrosio, M, et al.
(author)
-
Search for the sidereal and solar diurnal modulations in the total MACRO muon data set
- 2003
-
In: Physical Review D. Particles and fields. - : American Physical Society. - 0556-2821 .- 1089-4918. ; 67:4
-
Journal article (peer-reviewed)abstract
- We have analyzed 44.3M single muons collected by MACRO from 1991 through 2000 in 2145 live days of operation. We have searched for the solar diurnal, apparent sidereal, and pseudosidereal modulation of the underground muon rate by computing hourly deviations of the muon rate from 6 month averages. We find evidence for statistically significant modulations with the solar diurnal and the sidereal periods. The amplitudes of these modulations are <0.1%, and are at the limit of the detector statistics. The pseudosidereal modulation is not statistically significant. The solar diurnal modulation is due to the daily atmospheric temperature variations at 20 km, the altitude of primary cosmic ray interactions with the atmosphere; MACRO is the deepest experiment to report this result. The sidereal modulation is in addition to the expected Compton-Getting modulation due to solar system motion relative to the local standard of rest; it represents motion of the solar system with respect to the galactic cosmic rays toward the galactic plane.
|
|
| 19. |
- Becker, M, et al.
(author)
-
Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: a European Scleroderma Trials and Research (EUSTAR) analysis
- 2019
-
In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:9, s. 1242-1248
-
Journal article (peer-reviewed)abstract
- Mortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database.MethodsInclusion criteria were diagnosis of diffuse SSc and follow-up over 12±3 months. Disease worsening/organ progression was fulfilled if any of the following events occurred: new renal crisis; decrease of lung or heart function; new echocardiography-suspected pulmonary hypertension or death. In total, 42 clinical parameters were chosen as predictors for the analysis by using (1) imputation of missing data on the basis of multivariate imputation and (2) least absolute shrinkage and selection operator regression.ResultsOf 1451 patients meeting the inclusion criteria, 706 had complete data on outcome parameters and were included in the analysis. Of the 42 outcome predictors, eight remained in the final regression model. There was substantial evidence for a strong association between disease progression and age, active digital ulcer (DU), lung fibrosis, muscle weakness and elevated C-reactive protein (CRP) level. Active DU, CRP elevation, lung fibrosis and muscle weakness were also associated with a significantly shorter time to disease progression. A bootstrap validation step with 10 000 repetitions successfully validated the model.ConclusionsThe use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trials.
|
|
| 20. |
|
|
| 21. |
- Togo, V, et al.
(author)
-
Calibrations of CR39 and Makrofol nuclear track detectors and search for exotic particles
- 2003
-
In: Nuclear physics B, Proceedings supplements. - : Elsevier. - 0920-5632 .- 1873-3832. ; 125, s. 217-221
-
Journal article (peer-reviewed)abstract
- We present the final results of the search for exotic massive particles in the cosmic radiation performed with the MACRO underground experiment. Magnetic monopoles and nuclearites flux upper limits obtained with the CR39 nuclear track subdetector, the scintillation and streamer tube subdetectors are given. Searches at high altitude with the SLIM experiment are in progress.
|
|
| 22. |
- Lønborg, C., et al.
(author)
-
A global database of dissolved organic matter (DOM) concentration measurements in coastal waters (CoastDOM v1)
- 2024
-
In: Earth System Science Data. - : Copernicus Publications. - 1866-3508 .- 1866-3516. ; 16:2, s. 1107-1119
-
Journal article (peer-reviewed)abstract
- Measurements of dissolved organic carbon (DOC), nitrogen (DON), and phosphorus (DOP) concentrations are used to characterize the dissolved organic matter (DOM) pool and are important components ofbiogeochemical cycling in the coastal ocean. Here, we present the first edition of a global database (CoastDOMv1; available at https://doi.org/10.1594/PANGAEA.964012, Lønborg et al., 2023) compiling previously published and unpublished measurements of DOC, DON, and DOP in coastal waters. These data are complementedby hydrographic data such as temperature and salinity and, to the extent possible, other biogeochemical variables(e.g. chlorophyll a, inorganic nutrients) and the inorganic carbon system (e.g. dissolved inorganic carbon andtotal alkalinity). Overall, CoastDOM v1 includes observations of concentrations from all continents. However,most data were collected in the Northern Hemisphere, with a clear gap in DOM measurements from the SouthernHemisphere. The data included were collected from 1978 to 2022 and consist of 62 338 data points for DOC,20 356 for DON, and 13 533 for DOP. The number of measurements decreases progressively in the sequenceDOC > DON > DOP, reflecting both differences in the maturity of the analytical methods and the greater focuson carbon cycling by the aquatic science community. The global database shows that the average DOC concentration in coastal waters (average ± standard deviation (SD): 182±314 µmolC L−1; median: 103 µmolC L−1) is13-fold higher than the average coastal DON concentration (13.6 ± 30.4 µmol N L−1; median: 8.0 µmol N L−1),which is itself 39-fold higher than the average coastal DOP concentration (0.34 ± 1.11 µmol P L−1; median:0.18 µmol P L−1). This dataset will be useful for identifying global spatial and temporal patterns in DOM and willhelp facilitate the reuse of DOC, DON, and DOP data in studies aimed at better characterizing local biogeochemical processes; closing nutrient budgets; estimating carbon, nitrogen, and phosphorous pools; and establishing abaseline for modelling future changes in coastal waters.
|
|
| 23. |
- Senage, T., et al.
(author)
-
The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration
- 2022
-
In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 28, s. 283-294
-
Journal article (peer-reviewed)abstract
- Bioprosthetic heart valves (BHVs) are commonly used to replace severely diseased heart valves but their susceptibility to structural valve degeneration (SVD) limits their use in young patients. We hypothesized that antibodies against immunogenic glycans present on BHVs, particularly antibodies against the xenoantigens galactose-alpha 1,3-galactose (alpha Gal) and N-glycolylneuraminic acid (Neu5Gc), could mediate their deterioration through calcification. We established a large longitudinal prospective international cohort of patients (n = 1668, 34 +/- 43 months of follow-up (0.1-182); 4,998 blood samples) to investigate the hemodynamics and immune responses associated with BHVs up to 15 years after aortic valve replacement. Early signs of SVD appeared in <5% of BHV recipients within 2 years. The levels of both anti-alpha Gal and anti-Neu5Gc IgGs significantly increased one month after BHV implantation. The levels of these IgGs declined thereafter but anti-alpha Gal IgG levels declined significantly faster in control patients compared to BHV recipients. Neu5Gc, anti-Neu5Gc IgG and complement deposition were found in calcified BHVs at much higher levels than in calcified native aortic valves. Moreover, in mice, anti-Neu5Gc antibodies were unable to promote calcium deposition on subcutaneously implanted BHV tissue engineered to lack alpha Gal and Neu5Gc antigens. These results indicate that BHVs manufactured using donor tissues deficient in alpha Gal and Neu5Gc could be less prone to immune-mediated deterioration and have improved durability. In a large cohort of patients who underwent aortic valve replacement, antibody responses to glycans present in bioprosthetic heart valves, notably galactose-alpha 1,3-galactose and N-glycolylneuraminic acid, were implicated in valve calcification and deterioration.
|
|
| 24. |
|
|
| 25. |
- Battistoni, G, et al.
(author)
-
Search for a Lorentz invariance violation contribution in atmospheric neutrino oscillations using MACRO data
- 2005
-
In: Physics Letters B. - : Elsevier. - 0370-2693 .- 1873-2445. ; 615:1-2, s. 14-18
-
Journal article (peer-reviewed)abstract
- The energy spectrum of neutrino-induced upward-going muons in MACRO has been analysed in terms of relativity principles violating effects, keeping standard mass-induced atmospheric neutrino oscillations as the dominant source of v(u) -> v(tau) transitions. The data disfavor these exotic possibilities even at a subdominant level, and stringent 90% C.L. limits are placed on the Lorentz invariance violation parameter vertical bar Delta v vertical bar < 6 x 10(-24) at sin2 theta(v) = 0 and vertical bar Delta(v)vertical bar < 2.5-5 x 10(-26) at sin 2 theta(v) = +/- 1. These limits can also be re-interpreted as upper bounds on the parameters describing violation of the equivalence principle. (c) 2005 Elsevier B.V. All rights reserved.
|
|
| 26. |
- Battistoni, G, et al.
(author)
-
Search for exotic contributions to atmospheric neutrino oscillations
- 2005
-
In: 29th International Cosmic Ray Conference. - Mumbai : Tata Institute of Fundamental Research. ; , s. 171-174
-
Conference paper (other academic/artistic)abstract
- The energy spectrum of neutrino-induced upward-going muons in MACRO was analysed in terms of relativity principles violating effects, keeping standard mass-induced atmospheric neutrino oscillations as the dominant source of v(mu) -> v(tau) transitions. The data disfavor these possibilities even at a sub-dominant level; stringent 90% C.L. limits are placed on the Lorentz invariance violation parameter vertical bar Delta v vertical bar < 6 x 10(-24) at sin 2 theta(v) = 0 and vertical bar Delta v vertical bar < 2.5 divided by 5 x 10(-26) at sin 2 theta(v) = +/- 1. The limits can be re-interpreted as bounds on the Equivalence Principle violation parameters.
|
|
| 27. |
- Becherini, Yvonne, et al.
(author)
-
Time correlations of high energy muons in an underground detector
- 2005
-
In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 23:3, s. 341-348
-
Journal article (peer-reviewed)abstract
- We present the result of a search for correlations in the arrival times of high energy muons collected from 1995 till 2000 with the streamer tube system of the complete MACRO detector at the underground Gran Sasso Lab. Large samples of single muons (8.6 million), double muons (0.46 million) and multiple muons with multiplicities from 3 to 6 (0.08 million) were selected. These samples were used to search for time correlations of cosmic ray particles coming from the whole upper hemisphere or from selected space cones. The results of our analyses confirm with high statistics a random arrival time distribution of high energy cosmic rays. (c) 2005 Elsevier B.V. All rights reserved.
|
|
| 28. |
- Becherini, Yvonne, et al.
(author)
-
Time variations in the deep underground muon flux measured by MACRO
- 2005
-
In: 29th International Cosmic Ray Conference. - Mumbai : Tata Institute of Fundamental Research. ; , s. 157-160
-
Conference paper (other academic/artistic)abstract
- More than 30 million high-energy muons collected with the MACRO detector at the underground Gran Sasso Laboratory have been used to search for flux variations of different nature. Two kinds of studies were carried out: search for periodical variations and for the occurrence of clusters of events. Different analysis methods, including Lomb-Scargle spectral analysis and scan statistics have been applied to the data.
|
|
| 29. |
- Fripiat, F., et al.
(author)
-
Macro-nutrient concentrations in Antarctic pack ice: Overall patterns and overlooked processes
- 2017
-
In: Elementa. - : University of California Press. - 2325-1026. ; 5
-
Journal article (peer-reviewed)abstract
- Antarctic pack ice is inhabited by a diverse and active microbial community reliant on nutrients for growth. Seeking patterns and overlooked processes, we performed a large-scale compilation of macro-nutrient data (hereafter termed nutrients) in Antarctic pack ice (306 ice-cores collected from 19 research cruises). Dissolved inorganic nitrogen and silicic acid concentrations change with time, as expected from a seasonally productive ecosystem. In winter, salinity-normalized nitrate and silicic acid concentrations (C∗) in sea ice are close to seawater concentrations (Cw), indicating little or no biological activity. In spring, nitrate and silicic acid concentrations become partially depleted with respect to seawater (C∗ < Cw), commensurate with the seasonal build-up of ice microalgae promoted by increased insolation. Stronger and earlier nitrate than silicic acid consumption suggests that a significant fraction of the primary productivity in sea ice is sustained by flagellates. By both consuming and producing ammonium and nitrite, the microbial community maintains these nutrients at relatively low concentrations in spring. With the decrease in insolation beginning in late summer, dissolved inorganic nitrogen and silicic acid concentrations increase, indicating imbalance between their production (increasing or unchanged) and consumption (decreasing) in sea ice. Unlike the depleted concentrations of both nitrate and silicic acid from spring to summer, phosphate accumulates in sea ice (C∗ > Cw). The phosphate excess could be explained by a greater allocation to phosphorus-rich biomolecules during ice algal blooms coupled with convective loss of excess dissolved nitrogen, preferential remineralization of phosphorus, and/or phosphate adsorption onto metal-organic complexes. Ammonium also appears to be efficiently adsorbed onto organic matter, with likely consequences to nitrogen mobility and availability. This dataset supports the view that the sea ice microbial community is highly efficient at processing nutrients but with a dynamic quite different from that in oceanic surface waters calling for focused future investigations. Copyright © 2017 The Author(s).
|
|
| 30. |
|
|
| 31. |
- Le Bas-Bernardet, S, et al.
(author)
-
Bortezomib, C1-Inhibitor and Plasma Exchange Do Not Prolong the Survival of Multi-Transgenic GalT-KO Pig Kidney Xenografts in Baboons.
- 2015
-
In: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. - : Elsevier BV. - 1600-6143. ; 15:2, s. 358-70
-
Journal article (peer-reviewed)abstract
- Galactosyl-transferase KO (GalT-KO) pigs represent a potential solution to xenograft rejection, particularly in the context of additional genetic modifications. We have performed life supporting kidney xenotransplantation into baboons utilizing GalT-KO pigs transgenic for human CD55/CD59/CD39/HT. Baboons received tacrolimus, mycophenolate mofetil, corticosteroids and recombinant human C1 inhibitor combined with cyclophosphamide or bortezomib with or without 2-3 plasma exchanges. One baboon received a control GalT-KO xenograft with the latter immunosuppression. All immunosuppressed baboons rejected the xenografts between days 9 and 15 with signs of acute humoral rejection, in contrast to untreated controls (n=2) that lost their grafts on days 3 and 4. Immunofluorescence analyses showed deposition of IgM, C3, C5b-9 in rejected grafts, without C4d staining, indicating classical complement pathway blockade but alternate pathway activation. Moreover, rejected organs exhibited predominantly monocyte/macrophage infiltration with minimal lymphocyte representation. None of the recipients showed any signs of porcine endogenous retrovirus transmission but some showed evidence of porcine cytomegalovirus (PCMV) replication within the xenografts. Our work indicates that the addition of bortezomib and plasma exchange to the immunosuppressive regimen did not significantly prolong the survival of multi-transgenic GalT-KO renal xenografts. Non-Gal antibodies, the alternative complement pathway, innate mechanisms with monocyte activation and PCMV replication may have contributed to rejection.
|
|
| 32. |
|
|
| 33. |
- Schiaffino, Simone, et al.
(author)
-
Axillary lymphadenopathy at the time of COVID-19 vaccination : ten recommendations from the European Society of Breast Imaging (EUSOBI)
- 2021
-
In: Insights into Imaging. - : Springer Science and Business Media LLC. - 1869-4101. ; 12:1
-
Journal article (peer-reviewed)abstract
- Unilateral axillary lymphadenopathy is a frequent mild side effect of COVID-19 vaccination. European Society of Breast Imaging (EUSOBI) proposes ten recommendations to standardise its management and reduce unnecessary additional imaging and invasive procedures: (1) in patients with previous history of breast cancer, vaccination should be performed in the contralateral arm or in the thigh; (2) collect vaccination data for all patients referred to breast imaging services, including patients undergoing breast cancer staging and follow-up imaging examinations; (3) perform breast imaging examinations preferentially before vaccination or at least 12 weeks after the last vaccine dose; (4) in patients with newly diagnosed breast cancer, apply standard imaging protocols regardless of vaccination status; (5) in any case of symptomatic or imaging-detected axillary lymphadenopathy before vaccination or at least 12 weeks after, examine with appropriate imaging the contralateral axilla and both breasts to exclude malignancy; (6) in case of axillary lymphadenopathy contralateral to the vaccination side, perform standard work-up; (7) in patients without breast cancer history and no suspicious breast imaging findings, lymphadenopathy only ipsilateral to the vaccination side within 12 weeks after vaccination can be considered benign or probably-benign, depending on clinical context; (8) in patients without breast cancer history, post-vaccination lymphadenopathy coupled with suspicious breast finding requires standard work-up, including biopsy when appropriate; (9) in patients with breast cancer history, interpret and manage post-vaccination lymphadenopathy considering the timeframe from vaccination and overall nodal metastatic risk; (10) complex or unclear cases should be managed by the multidisciplinary team.
|
|
| 34. |
- Schiaffino, Simone, et al.
(author)
-
European Society of Breast Imaging (EUSOBI) guidelines on the management of axillary lymphadenopathy after COVID-19 vaccination : 2023 revision
- 2023
-
In: Insights into Imaging. - 1869-4101. ; 14:1
-
Journal article (peer-reviewed)abstract
- Axillary lymphadenopathy is a common side effect of COVID-19 vaccination, leading to increased imaging-detected asymptomatic and symptomatic unilateral axillary lymphadenopathy. This has threatened to negatively impact the workflow of breast imaging services, leading to the release of ten recommendations by the European Society of Breast Imaging (EUSOBI) in August 2021. Considering the rapidly changing scenario and data scarcity, these initial recommendations kept a highly conservative approach. As of 2023, according to newly acquired evidence, EUSOBI proposes the following updates, in order to reduce unnecessary examinations and avoid delaying necessary examinations. First, recommendation n. 3 has been revised to state that breast examinations should not be delayed or rescheduled because of COVID-19 vaccination, as evidence from the first pandemic waves highlights how delayed or missed screening tests have a negative effect on breast cancer morbidity and mortality, and that there is a near-zero risk of subsequent malignant findings in asymptomatic patients who have unilateral lymphadenopathy and no suspicious breast findings. Second, recommendation n. 7 has been revised to simplify follow-up strategies: in patients without breast cancer history and no imaging findings suspicious for cancer, symptomatic and asymptomatic imaging-detected unilateral lymphadenopathy on the same side of recent COVID-19 vaccination (within 12 weeks) should be classified as a benign finding (BI-RADS 2) and no further work-up should be pursued. All other recommendations issued by EUSOBI in 2021 remain valid.
|
|
| 35. |
- Spolaor, A., et al.
(author)
-
Seasonality of halogen deposition in polar snow and ice
- 2014
-
In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 14, s. 9613-9622
-
Journal article (peer-reviewed)abstract
- The atmospheric chemistry of iodine and bromine in Polar regions is of interest due to the key role of halogens in many atmospheric processes, particularly tropospheric ozone destruction. Bromine is emitted from the open ocean but is enriched above first-year sea ice during springtime bromine explosion events, whereas iodine emission is at- tributed to biological communities in the open ocean and hosted by sea ice. It has been previously demonstrated that bromine and iodine are present in Antarctic ice over glacial– interglacial cycles. Here we investigate seasonal variability of bromine and iodine in polar snow and ice, to evaluate their emission, transport and deposition in Antarctica and the Arc- tic and better understand potential links to sea ice. We find that bromine and iodine concentrations and Br enrichment (relative to sea salt content) in polar ice do vary seasonally in Arctic snow and Antarctic ice. Although seasonal vari- ability in halogen emission sources is recorded by satellite- based observations of tropospheric halogen concentrations, seasonal patterns observed in snowpack are likely also in- fluenced by photolysis-driven processes. Peaks of bromine concentration and Br enrichment in Arctic snow and Antarc- tic ice occur in spring and summer, when sunlight is present. A secondary bromine peak, observed at the end of summer, is attributed to bromine deposition at the end of the polar day. Iodine concentrations are largest in winter Antarctic ice strata, contrary to contemporary observations of summer maxima in iodine emissions. These findings support previous observations of iodine peaks in winter snow strata attributed to the absence of sunlight-driven photolytic re-mobilisation of iodine from surface snow. Further investigation is required to confirm these proposed mechanisms explaining observa- tions of halogens in polar snow and ice, and to evaluate the extent to which halogens may be applied as sea ice proxies.
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
- Hansen, A. M. K., et al.
(author)
-
Organosulfates and organic acids in Arctic aerosols : speciation, annual variation and concentration levels
- 2014
-
In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 14:15, s. 7807-7823
-
Journal article (peer-reviewed)abstract
- Sources, composition and occurrence of secondary organic aerosols in the Arctic were investigated at Zeppelin Mountain, Svalbard, and Station Nord, northeastern Greenland, during the full annual cycle of 2008 and 2010, respectively. Speciation of organic acids, organosulfates and nitrooxy organosulfates - from both anthropogenic and biogenic precursors were in focus. A total of 11 organic acids (terpenylic acid, benzoic acid, phthalic acid, pinic acid, suberic acid, azelaic acid, adipic acid, pimelic acid, pinonic acid, diaterpenylic acid acetate and 3-methyl-1,2,3-butanetricarboxylic acid), 12 organosulfates and 1 nitrooxy organosulfate were identified in aerosol samples from the two sites using a high-performance liquid chromatograph (HPLC) coupled to a quadrupole Time-of-Flight mass spectrometer. At Station Nord, compound concentrations followed a distinct annual pattern, where high mean concentrations of organosulfates (47 +/- 14 ng m(-3)) and organic acids (11.5 +/- 4 ng m(-3)) were observed in January, February and March, contrary to considerably lower mean concentrations of organosulfates (2 +/- 3 ng m(3-)) and organic acids (2.2 +/- 1 ng m(-3)) observed during the rest of the year. At Zeppelin Mountain, organosulfate and organic acid concentrations remained relatively constant during most of the year at a mean concentration of 15 +/- 4 ng m(-3) and 3.9 +/- 1 ng m(-3), respectively. However during four weeks of spring, remarkably higher concentrations of total organosulfates (23-36 ng m(-3)) and total organic acids (7-10 ngm(-3)) were observed. Elevated organosulfate and organic acid concentrations coincided with the Arctic haze period at both stations, where northern Eurasia was identified as the main source region. Air mass transport from northern Eurasia to Zeppelin Mountain was associated with a 100% increase in the number of detected organosulfate species compared with periods of air mass transport from the Arctic Ocean, Scandinavia and Greenland. The results from this study suggested that the presence of organic acids and organosulfates at Station Nord was mainly due to long-range transport, whereas indications of local sources were found for some compounds at Zeppelin Mountain. Furthermore, organosulfates contributed significantly to organic matter throughout the year at Zeppelin Mountain (annual mean of 13 +/- 8 %) and during Arctic haze at Station Nord (7 +/- 2 %), suggesting organosulfates to be important compounds in Arctic aerosols.
|
|
| 40. |
|
|
| 41. |
- Mazzucato, M, et al.
(author)
-
Vascular PG-M/versican variants promote platelet adhesion at low shear rates and cooperate with collagens to induce aggregation
- 2002
-
In: FASEB Journal. - 1530-6860. ; 16:14, s. 1903-1916
-
Journal article (peer-reviewed)abstract
- We have identified a novel von Willebrand factor/fibrinogen/selectin-independent, platelet adhesion-promoting function of vascular PG-M/versicans that may be relevant in normal venous thrombosis and critical in atherosclerotic conditions. A purification scheme was devised to obtain vascular versicans, which by biochemical, immunochemical, and ultrastructural means were asserted to be 1) composed primarily of isoforms V1 and V2; 2) free of contaminants; 3) prevalently substituted with chondroitin-4-sulfate and dermatan sulfate (DS) chains; and 4) capable of binding hyaluronan to form link protein-stabilized ternary complexes. Real-time analysis of human platelet perfused under diverse shear forces showed that they largely failed to bind to several vascular and nonvascular proteoglycans (PGs). In contrast, they bound in a dose- and shear rate-dependent manner to vascular versicans, exhibiting a unique attachment-detachment kinetics and establishing a firm substrate tethering characterized with no significant aggregation. Digestion of these PGs with lyases and competition experiments with purified glycosaminoglycans revealed that platelet adhesion to vascular versicans was primarily mediated by their DS chains. Incorporation of the versicans into fibrillar collagen substrates augmented their adhesive activity and strongly promoted platelet aggregation at low and high shear rates. Affinity chromatography of platelet surfaces on DS columns identified a 120-140 kDa polypeptide complex that behaved as a specific vascular versican binding membrane ligand in solid-phase binding assays. These findings indicate that selective versican variants of the subendothelium may serve as ancillary GPIbalpha/integrin/selectin-independent platelet ligands in healthy and diseased vascular beds and may be directly responsible for the platelet accruing after rupture of atherosclerotic plaques., versican variants promote platelet adhesion at low shear rates and cooperate with collagens to induce aggregation.
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
|
|
| 45. |
- Reuven, E. M., et al.
(author)
-
Characterization of immunogenic Neu5Gc in bioprosthetic heart valves
- 2016
-
In: Xenotransplantation. - : Wiley. - 0908-665X. ; 23:5, s. 381-392
-
Journal article (peer-reviewed)abstract
- Background: The two common sialic acids (Sias) in mammals are N-acetylneuraminic acid (Neu5Ac) and its hydroxylated form N-glycolylneuraminic acid (Neu5Gc). Unlike most mammals, humans cannot synthesize Neu5Gc that is considered foreign and recognized by circulating antibodies. Thus, Neu5Gc is a potential xenogenic carbohydrate antigen in bioprosthetic heart valves (BHV) that tend to deteriorate in time within human patients. Methods: We investigated Neu5Gc expression in non-engineered animal-derived cardiac tissues and in clinically used commercial BHV, and evaluated Neu5Gc immunogenicity on BHV through recognition by human anti-Neu5Gc IgG. Results: Neu5Gc was detected by immunohistochemistry in porcine aortic valves and in porcine and bovine pericardium. Qualitative analysis of Sia linkages revealed Siaα2-3>Siaα2-6 on porcine/bovine pericardium while the opposite in porcine aortic/pulmonary valve cusps. Similarly, six commercial BHV containing either porcine aortic valve or porcine/bovine/equine pericardium revealed Siaα2-3>Siaα2-6 expression. Quantitative analysis of Sia by HPLC showed porcine/bovine pericardium express 4-fold higher Neu5Gc levels compared to the porcine aortic/pulmonary valves, with Neu5Ac at 6-fold over Neu5Gc. Likewise, Neu5Gc was expressed on commercial BHV (186.3±16.9 pmol Sia/μg protein), with Neu5Ac at 8-fold over Neu5Gc. Affinity-purified human anti-Neu5Gc IgG showing high specificity toward Neu5Gc-glycans (with no binding to Neu5Ac-glycans) on a glycan microarray, strongly bound to all tested commercial BHV, demonstrating Neu5Gc immune recognition in cardiac xenografts. Conclusions: We conclusively demonstrated Neu5Gc expression in native cardiac tissues, as well as in six commercial BHV. These Neu5Gc xeno-antigens were recognized by human anti-Neu5Gc IgG, supporting their immunogenicity. Altogether, these findings suggest BHV-Neu5Gc/anti-Neu5Gc may play a role in valve deterioration warranting further investigation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
- Luo, Dan, et al.
(author)
-
Oxidation and cyclization of casbene in the biosynthesis of Euphorbia factors from mature seeds of Euphorbia lathyris L.
- 2016
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:34, s. E5082-E5089
-
Journal article (peer-reviewed)abstract
- The seed oil of Euphorbia lathyris L. contains a series of macrocyclic diterpenoids known as Euphorbia factors. They are the current industrial source of ingenol mebutate, which is approved for the treatment of actinic keratosis, a precancerous skin condition. Here, we report an alcohol dehydrogenase-mediated cyclization step in the biosynthetic pathway of Euphorbia factors, illustrating the origin of the intramolecular carbon-carbon bonds present in lathyrane and ingenane diterpenoids. This unconventional cyclization describes the ring closure of the macrocyclic diterpene casbene. Through transcriptomic analysis of E. lathyris L. mature seeds and in planta functional characterization, we identified three enzymes involved in the cyclization route from casbene to jolkinol C, a lathyrane diterpene. These enzymes include two cytochromes P450 from the CYP71 clan and an alcohol dehydrogenase (ADH). CYP71D445 and CYP726A27 catalyze regio-specific 9-oxidation and 5-oxidation of casbene, respectively. When coupled with these P450-catalyzed monooxygenations, E. lathyris ADH1 catalyzes dehydrogenation of the hydroxyl groups, leading to the subsequent rearrangement and cyclization. The discovery of this nonconventional cyclization may provide the key link to complete elucidation of the biosynthetic pathways of ingenol mebutate and other bioactive macrocyclic diterpenoids.
|
|
| 49. |
- Pavey, S, et al.
(author)
-
Microarray expression profiling in melanoma reveals a BRAF mutation signature
- 2004
-
In: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 23:23, s. 4060-4067
-
Journal article (peer-reviewed)abstract
- We have used microarray gene expression pro. ling and machine learning to predict the presence of BRAF mutations in a panel of 61 melanoma cell lines. The BRAF gene was found to be mutated in 42 samples (69%) and intragenic mutations of the NRAS gene were detected in seven samples (11%). No cell line carried mutations of both genes. Using support vector machines, we have built a classifier that differentiates between melanoma cell lines based on BRAF mutation status. As few as 83 genes are able to discriminate between BRAF mutant and BRAF wild-type samples with clear separation observed using hierarchical clustering. Multidimensional scaling was used to visualize the relationship between a BRAF mutation signature and that of a generalized mitogen-activated protein kinase ( MAPK) activation ( either BRAF or NRAS mutation) in the context of the discriminating gene list. We observed that samples carrying NRAS mutations lie somewhere between those with or without BRAF mutations. These observations suggest that there are gene-specific mutation signals in addition to a common MAPK activation that result from the pleiotropic effects of either BRAF or NRAS on other signaling pathways, leading to measurably different transcriptional changes.
|
|
| 50. |
|
|
