When compared with BMT, umbilical cord blood transplantation (UCBT) is associated with a lower rate of engraftment and delayed hematological/immunological recovery. This leads to increased risk of ...TRM in the early post transplantation period due to infection. Acute GVHD, although occurring less frequently in UCBT compared with BMT, is also significantly associated with increased rate of early TRM. BM MSCs are known to support normal in vivo hematopoiesis, and co-transplantation of MSCs has been shown to enhance engraftment of human cord blood hematopoietic cells in nonobese diabetic/SCID mice. In 13 children with hematological disorders (median age 2 years) undergoing UCBT, we co-transplanted paternal, HLA-disparate MSCs with the aim of improving hematological recovery and reducing rejection. We observed no differences in hematological recovery or rejection rates compared with 39 matched historical controls, most of whom received G-CSF after UCBT. However, the rate of grade III and IV acute GVHD was significantly decreased in the study cohort when compared with controls (P=0.05), thus resulting in reduced early TRM. Although these data do not support the use of MSCs in UCBT to support hematopoietic engraftment, they suggest that MSCs, possibly because of their immunosuppressive effect, may abrogate life-threatening acute GVHD and reduce early TRM.
Mini-EUSO is part of the JEM-EUSO program and operates on board the International Space Station (ISS). It is a UV-telescope with single-photon counting capability looking at nighttime downwards to ...the Earth through a nadir-facing UV-transparent window. As part of the pre-flight tests, the Mini-EUSO engineering model, a telescope with 1/9 of the original focal surface and a lens of 2.5 cm diameter, has been built and tested. Tests of the Mini-EUSO engineering model have been made in laboratory and in open-sky conditions. Laboratory tests have been performed at the TurLab facility, located at the Physics Department of the University of Turin, equipped with a rotating tank containing different types of materials and light sources. In this way, the configuration for the observation of the Earth from space was emulated, including the Mini-EUSO trigger schemes. In addition to the qualification and calibration tests, the Mini-EUSO engineering model has also been used to evaluate the possibility of using a JEM-EUSO-type detector for applications such as observation of space debris. Furthermore, observations in open-sky conditions allowed the studies of natural light sources such as stars, meteors, planets, and artificial light sources such as airplanes, satellites reflecting the sunlight, and city lights. Most of these targets could be detected also with Mini-EUSO. In this paper, the tests in laboratory and in open-sky conditions are reported, as well as the obtained results. In addition, the contribution that such tests provided to foresee and improve the performance of Mini-EUSO on board the ISS is discussed.
Summary
Mesenchymal stromal cell (MSC) infusions have been reported to be effective in patients with steroid‐refractory, acute graft‐versus‐host disease (aGvHD) but comprehensive data on paediatric ...patients are limited. We retrospectively analysed a cohort of 37 children (aged 3 months‐17 years) treated with MSCs for steroid‐refractory grade III–IV aGvHD. All patients but three received multiple MSC infusions. Complete response (CR) was observed in 24 children (65%), while 13 children had either partial (n = 8) or no response (n = 5). Cumulative incidence of transplantation‐related mortality (TRM) in patients who did or did not achieve CR was 17% and 69%, respectively (P = 0·001). After a median follow‐up of 2·9 years, overall survival (OS) was 37%; it was 65% vs. 0% in patients who did or did not achieve CR, respectively (P = 0·001). The median time from starting steroids for GvHD treatment to first MSC infusion was 13 d (range 5–85). Children treated between 5 and 12 d after steroid initiation showed a trend for better OS (56%) and lower TRM (17%) as compared with patients receiving MSCs 13–85 d after steroids (25% and 53%, respectively; P = 0·22 and 0·06, respectively). Multiple MSC infusions are safe and effective for children with steroid‐refractory aGvHD, especially when employed early in the disease course.
Aims
Treosulfan is an alkylating agent increasingly used prior to haematopoietic stem cell transplantation. The aim of this study was to develop a population pharmacokinetic (PK) model of treosulfan ...in paediatric haematopoietic stem cell transplantation recipients and to explore the effect of potential covariates on treosulfan PK. Also, a limited sampling model (LSM) will be developed to accurately predict treosulfan exposure suitable for a therapeutic drug monitoring setting.
Methods
In this multicentre study, 91 patients, receiving a total dose of 30, 36 or 42 g/m2 treosulfan, administered over 3 consecutive days, were enrolled. A population PK model was developed and demographic factors, as well as laboratory parameters, were included as potential covariates. In addition, a LSM was developed using data from 28 patients.
Results
A 2‐compartment model with first order elimination best described the data. Bodyweight with allometric scaling and maturation function were identified as significant predictors of treosulfan clearance. Treosulfan clearance reaches 90% of adult values at 4 postnatal years. A model‐based dosing table is presented to target an exposure of 1650 mg*h/L (population median) for different weight and age groups. Samples taken at 1.5, 4 and 7 hours after start of infusion resulted in the best limited sampling strategy.
Conclusions
This study provides a treosulfan population PK model in children and captures the developmental changes in clearance. A 3‐point LSM allows for accurate and precise estimation of treosulfan exposure.
The second generation Extreme Universe Space Observatory on a Super-Pressure Balloon (EUSO-SPB2) mission is on track to be approved by NASA for a long duration flight (up to 100 days) in 2023 from ...Wanaka, New Zealand. EUSO-SPB2 will monitor the night atmosphere of the Southern hemisphere from 33 km altitude to detect Ultra-High Energy Cosmic Rays (UHECRs) and search for astrophysical and cosmogenic neutrinos. EUSO-SPB2 features two telescopes, a Cherenkov (CT) and a Fluorescence (FT) Telescope. The hardware implementation and performance of the FT trigger logic were tested at the TurLab facility, hosted at the University of Turin. The tests proved the correct hardware implementation of the trigger logic and its ability to detect μs timescale transient signals.
EUSO-TA is a cosmic ray detector developed by the JEM-EUSO (Joint Experiment Missions for Extreme Universe Space Observatory) Collaboration, observing during nighttime the fluorescence light emitted ...along the path of extensive air showers in the atmosphere. It is installed at the Telescope Array site in Utah, USA, in front of the fluorescence detector station at Black Rock Mesa. It serves as a ground-based pathfinder experiment for future space-based missions. EUSO-TA has an optical system with two Fresnel lenses and a focal surface with 6 × 6 multi-anode photomultiplier tubes with 64 channels each, for a total of 2304 channels. The overall field of view is ∼10.6°× 10.6°. This detector technology allows the detection of cosmic ray events with high spatial resolution, having each channel a field of view of about ∼0.2° × 0.2° and a temporal resolution of 2.5 µs. First observations of ultra-high energy cosmic rays revealed the cosmic ray detection capability of EUSO-TA. The foreseen upgrade of EUSO-TA will improve the efficiency of the detector and will increase the statistics of detected events. In this work we present recent results of the detection capability of EUSO-TA and its limits. Moreover, other results about the analysis of laser pulses, stars and meteors will be discussed.
EUSO-SPB1 was a balloon-borne mission of the JEM-EUSO (Joint Experiment Missions for Extreme Universe Space Observatory) Program aiming at the ultra-high energy cosmic ray (UHECR) observations from ...space. We operated the EUSO-SPB1 telescope consisting of 1 m
2
Fresnel refractive optics and multi-anode photomultiplier tubes. With a total of 2304 channels, each performed the photon counting every 2.5 µs, allowing for spatiotemporal imaging of the air shower events in an ~ 11°× 11° field of view. EUSO-SPB1 was the first balloon-borne fluorescence detector with a potential to detect air shower events initiated by the EeV energy cosmic rays. On 24 April 2017 UTC, EUSO-SPB1 was launched on the NASA’s Super Pressure Balloon that flew at ~16 – 33 km flight height for ~12 days. Before the flight was terminated, ~27 hours of data acquired in the air shower detection mode were transmitted to the ground. In the present work, we aim at evaluating the role of the clouds during the operation of EUSO-SPB1. We employ the WRF (Weather Research and Forecasting) model to numerically simulate the cloud distribution below EUSO-SPB1. We discuss the key results of the WRF model and the impact of the clouds on the air shower measurement and the efficiency of the cosmic ray observation. The present work is a part of the collaborative effort to estimate the exposure for air shower detections.
EUSO-TA is a ground-based telescope, installed at the Telescope Array (TA) site in Black Rock Mesa, Utah, USA. This is the first detector to successfully use a Fresnel lens based optical system and ...multi-anode photomultipliers (64 channels per tube, 2304 channels encompassing a 10.6° × 10.6° field of view) for detection of Ultra High Energy Cosmic Rays (UHECR). The telescope is located in front of one of the fluorescence detectors of the TA experiment. Since its installation in 2013, the detector has observed several ultra-high energy cosmic ray events and, in addition, meteors. The limiting magnitude of 5.5 on summed frames ( ∼ 3 ms) has been established. Measurements of the UV night sky emission in different conditions and moon phases and positions have been completed. The performed observations serve as a proof of concept for the future application of this detector technology.
The Probe of Extreme Multimessenger Astrophysics (POEMMA) is a potential NASA Astrophysics Probe-class mission designed to observe ultrahigh-energy cosmic rays (UHECRs) and cosmic neutrinos from ...space. POEMMA will monitor colossal volumes of the Earth's atmosphere to detect extensive air showers (EASs) produced by extremely energetic cosmic messengers: UHECRs above 20 EeV over the full sky and cosmic neutrinos above 20 PeV. We focus most of this study on the impact of POEMMA for UHECR science by simulating the detector response and mission performance for EAS from UHECRs. We show that POEMMA will provide a significant increase in the statistics of observed UHECRs at the highest energies over the entire sky. POEMMA will be the first UHECR fluorescence detector deployed in space that will provide high-quality stereoscopic observations of the longitudinal development of air showers. Therefore it will be able to provide event-by-event estimates of the calorimetric energy and nuclear mass of UHECRs. The particle physics in the interactions limits the interpretation of the shower maximum on an event-by-event basis. In contrast, the calorimetric energy measurement is significantly less sensitive to the different possible final states in the early interactions. POEMMA will increase by a factor of 30 fluorescence observations, with accurate measurements of the shower maximum. We study the prospects to discover the origin and nature of UHECRs using expectations for measurements of the energy spectrum, the distribution of arrival direction, and the atmospheric column depth at which the EAS longitudinal development reaches maximum. We also explore supplementary science capabilities of POEMMA through its sensitivity to particle interactions at extreme energies and its ability to detect ultrahigh-energy neutrinos and photons produced by top-down models including cosmic strings and superheavy dark matter particle decay in the halo of the Milky Way.
The determination of the primary energy of extensive air showers using the fluorescence detection technique requires an estimation of the energy carried away by particles that do not deposit all ...their energy in the atmosphere. This estimation is typically made using Monte Carlo simulations and thus depends on the assumed primary particle mass and on model predictions for neutrino and muon production. In this work we present a new method to obtain the invisible energy from events detected by the Pierre Auger Observatory. The method uses measurements of the muon number at ground level, and it allows us to significantly reduce the systematic uncertainties related to the mass composition and the high energy hadronic interaction models, and consequently to improve the estimation of the energy scale of the Pierre Auger Observatory.
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