49 research outputs found
Multicentre observational study on multisystem inflammatory syndrome related to COVID-19 in Argentina
Background: The impact of the pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in low- and middle-income countries remains poorly understood. Our aim was to understand the characteristics and outcomes of PIMS-TS in Argentina. Methods: This observational, prospective, and retrospective multicenter study enrolled patients younger than 18 years-old manifesting PIMS-TS, Kawasaki disease (KD) or Kawasaki shock syndrome (KSS) between March 2020 and May 2021. Patients were followed-up until hospital discharge or death (one case). The primary outcome was pediatric intensive care unit (PICU) admission. Multiple logistic regression was used to identify variables predicting PICU admission. Results: Eighty-one percent, 82%, and 14% of the 176 enrolled patients fulfilled the suspect case criteria for PIMS-TS, KD, and KSS, respectively. Temporal association with SARS-CoV-2 was confirmed in 85% of the patients and 38% were admitted to the PICU. The more common clinical manifestations were fever, abdominal pain, rash, and conjunctival injection. Lymphopenia was more common among PICU-admitted patients (87% vs. 51%, p < 0.0001), who also showed a lower platelet count and higher plasmatic levels of inflammatory and cardiac markers. Mitral valve insufficiency, left ventricular wall motion alterations, pericardial effusion, and coronary artery alterations were observed in 30%, 30%, 19.8%, and 18.6% of the patients, respectively. Days to initiation of treatment, rash, lymphopenia, and low platelet count were significant independent contributions to PICU admission. Conclusion: Rates of severe outcomes of PIMS-TS in the present study agreed with those observed in high-income countries. Together with other published studies, this work helps clinicians to better understand this novel clinical entity.Fil: Vainstein, Eduardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Baleani, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Urrutia, Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Affranchino, Nicolás. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Ackerman, Judith. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Cazalas, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Goldsman, Alejandro. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Sardella, Angela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Tolin, Ana Laura. Gobierno de la Provincia de Mendoza. Hospital Pediátrico Humberto Notti; ArgentinaFil: Goldaracena, Pablo. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Fabi, Mariana. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Cosentino, Mariana. Hospital Británico de Buenos Aires; ArgentinaFil: Magliola, Ricardo. Hospital Británico de Buenos Aires; ArgentinaFil: Roggiero, Gustavo. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Manso, Paula. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Triguy, Jésica. Gobierno de la Provincia de Mendoza. Hospital Pediátrico Humberto Notti; ArgentinaFil: Ballester, Celeste. Gobierno de la Provincia de Mendoza. Hospital Pediátrico Humberto Notti; ArgentinaFil: Cervetto, Vanesa. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Vaccarello, María. Sanatorio de la Trinidad; ArgentinaFil: De Carli, Domingo Norberto. Clínica del Niño de Quilmes; ArgentinaFil: De Carli, Maria Estela. Clínica del Niño de Quilmes; ArgentinaFil: Ciotti, Ana Laura. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Sicurello, María Irene. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Rios Leiva, Cecilia. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Villalba, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Hortas, María. Sanatorio de la Trinidad; ArgentinaFil: Peña, Sonia. Gobierno de la Provincia de Mendoza. Hospital Pediátrico Humberto Notti; ArgentinaFil: González, Gabriela. Gobierno de la Provincia de Mendoza. Hospital Pediátrico Humberto Notti; ArgentinaFil: Zold, Camila Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Grippo, M.. No especifíca;Fil: Vázquez, H.. No especifíca;Fil: Morós, C.. No especifíca;Fil: Di Santo, M.. No especifíca;Fil: Villa, A.. No especifíca;Fil: Lazota, P.. No especifíca;Fil: Foti, M.. No especifíca;Fil: Napoli, N.. No especifíca;Fil: Katsikas, M. M.. No especifíca;Fil: Tonello, L.. No especifíca;Fil: Peña, J.. No especifíca;Fil: Etcheverry, M.. No especifíca;Fil: Iglesias, D.. No especifíca;Fil: Alcalde, A. L.. No especifíca;Fil: Bruera, M.J.. No especifíca;Fil: Bruzzo, V.. No especifíca;Fil: Giordano, P.. No especifíca;Fil: Pena Acero, F.. No especifíca;Fil: Netri Pelandi, G.. No especifíca;Fil: Pastaro, D.. No especifíca;Fil: Bleiz, J.. No especifíca;Fil: Rodríguez, M. F.. No especifíca;Fil: Laghezza, L.. No especifíca;Fil: Molina, M. B.. No especifíca;Fil: Patynok, N.. No especifíca;Fil: Chatelain, M. S.. No especifíca;Fil: Aguilar, M. J.. No especifíca;Fil: Gamboa, J.. No especifíca;Fil: Cervan, M.. No especifíca;Fil: Ruggeri, A.. No especifíca;Fil: Marinelli, I.. No especifíca;Fil: Checcacci, E.. No especifíca;Fil: Meregalli, C.. No especifíca;Fil: Damksy Barbosa, J.. No especifíca;Fil: Fernie, L.. No especifíca;Fil: Fernández, M. J.. No especifíca;Fil: Saenz Tejeira, M.M.. No especifíca;Fil: Cereigido, C.. No especifíca;Fil: Nunell, A.. No especifíca;Fil: Villar, D.. No especifíca;Fil: Mansilla, A. D.. No especifíca;Fil: Darduin, M. D.. No especifíca
Snowmass Neutrino Frontier: DUNE Physics Summary
The Deep Underground Neutrino Experiment (DUNE) is a next-generation long-baseline neutrino oscillation experiment with a primary physics goal of observing neutrino and antineutrino oscillation patterns to precisely measure the parameters governing long-baseline neutrino oscillation in a single experiment, and to test the three-flavor paradigm. DUNE's design has been developed by a large, international collaboration of scientists and engineers to have unique capability to measure neutrino oscillation as a function of energy in a broadband beam, to resolve degeneracy among oscillation parameters, and to control systematic uncertainty using the exquisite imaging capability of massive LArTPC far detector modules and an argon-based near detector. DUNE's neutrino oscillation measurements will unambiguously resolve the neutrino mass ordering and provide the sensitivity to discover CP violation in neutrinos for a wide range of possible values of δCP. DUNE is also uniquely sensitive to electron neutrinos from a galactic supernova burst, and to a broad range of physics beyond the Standard Model (BSM), including nucleon decays. DUNE is anticipated to begin collecting physics data with Phase I, an initial experiment configuration consisting of two far detector modules and a minimal suite of near detector components, with a 1.2 MW proton beam. To realize its extensive, world-leading physics potential requires the full scope of DUNE be completed in Phase II. The three Phase II upgrades are all necessary to achieve DUNE's physics goals: (1) addition of far detector modules three and four for a total FD fiducial mass of at least 40 kt, (2) upgrade of the proton beam power from 1.2 MW to 2.4 MW, and (3) replacement of the near detector's temporary muon spectrometer with a magnetized, high-pressure gaseous argon TPC and calorimeter
Snowmass Neutrino Frontier: DUNE Physics Summary
The Deep Underground Neutrino Experiment (DUNE) is a next-generation
long-baseline neutrino oscillation experiment with a primary physics goal of
observing neutrino and antineutrino oscillation patterns to precisely measure
the parameters governing long-baseline neutrino oscillation in a single
experiment, and to test the three-flavor paradigm. DUNE's design has been
developed by a large, international collaboration of scientists and engineers
to have unique capability to measure neutrino oscillation as a function of
energy in a broadband beam, to resolve degeneracy among oscillation parameters,
and to control systematic uncertainty using the exquisite imaging capability of
massive LArTPC far detector modules and an argon-based near detector. DUNE's
neutrino oscillation measurements will unambiguously resolve the neutrino mass
ordering and provide the sensitivity to discover CP violation in neutrinos for
a wide range of possible values of . DUNE is also uniquely
sensitive to electron neutrinos from a galactic supernova burst, and to a broad
range of physics beyond the Standard Model (BSM), including nucleon decays.
DUNE is anticipated to begin collecting physics data with Phase I, an initial
experiment configuration consisting of two far detector modules and a minimal
suite of near detector components, with a 1.2 MW proton beam. To realize its
extensive, world-leading physics potential requires the full scope of DUNE be
completed in Phase II. The three Phase II upgrades are all necessary to achieve
DUNE's physics goals: (1) addition of far detector modules three and four for a
total FD fiducial mass of at least 40 kt, (2) upgrade of the proton beam power
from 1.2 MW to 2.4 MW, and (3) replacement of the near detector's temporary
muon spectrometer with a magnetized, high-pressure gaseous argon TPC and
calorimeter.Comment: Contribution to Snowmass 202
A Gaseous Argon-Based Near Detector to Enhance the Physics Capabilities of DUNE
This document presents the concept and physics case for a magnetized gaseous argon-based detector system (ND-GAr) for the Deep Underground Neutrino Experiment (DUNE) Near Detector. This detector system is required in order for DUNE to reach its full physics potential in the measurement of CP violation and in delivering precision measurements of oscillation parameters. In addition to its critical role in the long-baseline oscillation program, ND-GAr will extend the overall physics program of DUNE. The LBNF high-intensity proton beam will provide a large flux of neutrinos that is sampled by ND-GAr, enabling DUNE to discover new particles and search for new interactions and symmetries beyond those predicted in the Standard Model
A Gaseous Argon-Based Near Detector to Enhance the Physics Capabilities of DUNE
This document presents the concept and physics case for a magnetized gaseous
argon-based detector system (ND-GAr) for the Deep Underground Neutrino
Experiment (DUNE) Near Detector. This detector system is required in order for
DUNE to reach its full physics potential in the measurement of CP violation and
in delivering precision measurements of oscillation parameters. In addition to
its critical role in the long-baseline oscillation program, ND-GAr will extend
the overall physics program of DUNE. The LBNF high-intensity proton beam will
provide a large flux of neutrinos that is sampled by ND-GAr, enabling DUNE to
discover new particles and search for new interactions and symmetries beyond
those predicted in the Standard Model.Comment: Contribution to Snowmass 202
Identification and reconstruction of low-energy electrons in the ProtoDUNE-SP detector
Measurements of electrons from interactions are crucial for the Deep
Underground Neutrino Experiment (DUNE) neutrino oscillation program, as well as
searches for physics beyond the standard model, supernova neutrino detection,
and solar neutrino measurements. This article describes the selection and
reconstruction of low-energy (Michel) electrons in the ProtoDUNE-SP detector.
ProtoDUNE-SP is one of the prototypes for the DUNE far detector, built and
operated at CERN as a charged particle test beam experiment. A sample of
low-energy electrons produced by the decay of cosmic muons is selected with a
purity of 95%. This sample is used to calibrate the low-energy electron energy
scale with two techniques. An electron energy calibration based on a cosmic ray
muon sample uses calibration constants derived from measured and simulated
cosmic ray muon events. Another calibration technique makes use of the
theoretically well-understood Michel electron energy spectrum to convert
reconstructed charge to electron energy. In addition, the effects of detector
response to low-energy electron energy scale and its resolution including
readout electronics threshold effects are quantified. Finally, the relation
between the theoretical and reconstructed low-energy electron energy spectrum
is derived and the energy resolution is characterized. The low-energy electron
selection presented here accounts for about 75% of the total electron deposited
energy. After the addition of lost energy using a Monte Carlo simulation, the
energy resolution improves from about 40% to 25% at 50~MeV. These results are
used to validate the expected capabilities of the DUNE far detector to
reconstruct low-energy electrons.Comment: 19 pages, 10 figure
Reconstruction of interactions in the ProtoDUNE-SP detector with Pandora
The Pandora Software Development Kit and algorithm libraries provide
pattern-recognition logic essential to the reconstruction of particle
interactions in liquid argon time projection chamber detectors. Pandora is the
primary event reconstruction software used at ProtoDUNE-SP, a prototype for the
Deep Underground Neutrino Experiment far detector. ProtoDUNE-SP, located at
CERN, is exposed to a charged-particle test beam. This paper gives an overview
of the Pandora reconstruction algorithms and how they have been tailored for
use at ProtoDUNE-SP. In complex events with numerous cosmic-ray and beam
background particles, the simulated reconstruction and identification
efficiency for triggered test-beam particles is above 80% for the majority of
particle type and beam momentum combinations. Specifically, simulated 1 GeV/
charged pions and protons are correctly reconstructed and identified with
efficiencies of 86.1% and 84.1%, respectively. The efficiencies
measured for test-beam data are shown to be within 5% of those predicted by the
simulation.Comment: 39 pages, 19 figure
Impact of cross-section uncertainties on supernova neutrino spectral parameter fitting in the Deep Underground Neutrino Experiment
A primary goal of the upcoming Deep Underground Neutrino Experiment (DUNE) is
to measure the MeV neutrinos produced by a Galactic
core-collapse supernova if one should occur during the lifetime of the
experiment. The liquid-argon-based detectors planned for DUNE are expected to
be uniquely sensitive to the component of the supernova flux, enabling
a wide variety of physics and astrophysics measurements. A key requirement for
a correct interpretation of these measurements is a good understanding of the
energy-dependent total cross section for charged-current
absorption on argon. In the context of a simulated extraction of
supernova spectral parameters from a toy analysis, we investigate the
impact of modeling uncertainties on DUNE's supernova neutrino
physics sensitivity for the first time. We find that the currently large
theoretical uncertainties on must be substantially reduced
before the flux parameters can be extracted reliably: in the absence of
external constraints, a measurement of the integrated neutrino luminosity with
less than 10\% bias with DUNE requires to be known to about 5%.
The neutrino spectral shape parameters can be known to better than 10% for a
20% uncertainty on the cross-section scale, although they will be sensitive to
uncertainties on the shape of . A direct measurement of
low-energy -argon scattering would be invaluable for improving the
theoretical precision to the needed level.Comment: 25 pages, 21 figure
Scintillation light detection in the 6-m drift-length ProtoDUNE Dual Phase liquid argon TPC
DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6 × 6 × 6 m 3 liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019-2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light. The scintillation light signal in these detectors can provide the trigger for non-beam events. In addition, it adds precise timing capabilities and improves the calorimetry measurements. In ProtoDUNE-DP, scintillation and electroluminescence light produced by cosmic muons in the LArTPC is collected by photomultiplier tubes placed up to 7 m away from the ionizing track. In this paper, the ProtoDUNE-DP photon detection system performance is evaluated with a particular focus on the different wavelength shifters, such as PEN and TPB, and the use of Xe-doped LAr, considering its future use in giant LArTPCs. The scintillation light production and propagation processes are analyzed and a comparison of simulation to data is performed, improving understanding of the liquid argon properties
Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial
Background:
Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB.
Methods:
We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921).
Findings:
Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir.
Interpretation:
Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB