Allogeneic hematopoietic stem cell transplantation (HSCT) is still needed for many children with very high-risk acute leukemia. An HLA-haploidentical family donor is a suitable option for those ...without an HLA-matched donor. Here we present outcomes of a novel HLA-haploidentical HSCT (haplo-HSCT) strategy with adoptive immunotherapy with thymic-derived CD4
CD25
FoxP3
regulatory T cells (Tregs) and conventional T cells (Tcons) performed between January 2017 and July 2021 in 20 children with high-risk leukemia. Median age was 14.5 years (range, 4-21), 15 had acute lymphoblastic leukemia, 5 acute myeloid leukemia. The conditioning regimen included total body irradiation (TBI), thiotepa, fludarabine, cyclophosphamide. Grafts contained a megadose of CD34+ cells (mean 12.4 × 10
/Kg), Tregs (2 × 10
/Kg) and Tcons (0.5-1 × 10
/Kg). All patients achieved primary, sustained full-donor engraftment. Only one patient relapsed (5%). The incidence of non-relapse mortality was 15% (3/20 patients). Five/20 patients developed ≥ grade 2 acute Graft versus Host Disease (aGvHD). It resolved in 4 who are alive and disease-free; 1 patient developed chronic GvHD (cGvHD). The probability of GRFS was 60 ± 0.5% (95% CI: 2.1-4.2) (Fig. 6), CRFS was 79 ± 0.9% (95% CI: 3.2-4.9) as 16/20 patients are alive and leukemia-free. The median follow-up was 2.1 years (range 0.5 months-5.1 years). This innovative approach was associated with very promising outcomes of HSCT strategy in pediatric patients.
The e-ASTROGAM mission De Angelis, A.; Tatischeff, V.; Tavani, M. ...
Experimental astronomy,
10/2017, Letnik:
44, Številka:
1
Journal Article
Recenzirano
Odprti dostop
e-ASTROGAM (‘enhanced ASTROGAM’) is a breakthrough Observatory space mission, with a detector composed by a Silicon tracker, a calorimeter, and an anticoincidence system, dedicated to the study of ...the non-thermal Universe in the photon energy range from 0.3 MeV to 3 GeV – the lower energy limit can be pushed to energies as low as 150 keV, albeit with rapidly degrading angular resolution, for the tracker, and to 30 keV for calorimetric detection. The mission is based on an advanced space-proven detector technology, with unprecedented sensitivity, angular and energy resolution, combined with polarimetric capability. Thanks to its performance in the MeV-GeV domain, substantially improving its predecessors, e-ASTROGAM will open a new window on the non-thermal Universe, making pioneering observations of the most powerful Galactic and extragalactic sources, elucidating the nature of their relativistic outflows and their effects on the surroundings. With a line sensitivity in the MeV energy range one to two orders of magnitude better than previous generation instruments, e-ASTROGAM will determine the origin of key isotopes fundamental for the understanding of supernova explosion and the chemical evolution of our Galaxy. The mission will provide unique data of significant interest to a broad astronomical community, complementary to powerful observatories such as LIGO-Virgo-GEO600-KAGRA, SKA, ALMA, E-ELT, TMT, LSST, JWST, Athena, CTA, IceCube, KM3NeT, and the promise of eLISA.
The Mediterranean spearfish ( Tetrapturus belone ) is a highly migratory predator, also exploited by commercial and recreational fisheries although its catches are poorly reported. The fishing ...pressure on this species is currently unknown because catch and landing data are fragmentary. Furthermore, more ecological information (e.g. migratory movements) is needed to establish eventual management measures, and ICCAT has not examined the population status yet. Understanding species migratory movements is crucial for addressing conservation challenges and supporting management decisions. In this study we investigated the migratory movements, seasonal patterns, vertical behavior, and thermal preference of T. belone , with the aim to improve information on its ecology and behavior. Overall, six individuals were tagged in the Strait of Messina and Tyrrhenian Sea with pop-up satellite tags and their movements were mainly restricted to the central Mediterranean. Utilization distributions derived from geolocation revealed an overall and seasonal importance of the Tyrrhenian Sea and Strait of Sicily, as well as variability in winter habitat use. While the fish exhibited similar depth preference, spending the majority of time at depths ≤ 10 m, we observed that the Mediterranean spearfish is also able to perform sporadic deep dives below 200 m. Vertical movement showed a bimodal pattern common in other billfish species, characterized by occupation of shallower, warmer waters during the night and deeper, cooler waters during the day. This research increases knowledge on the migration ecology and habitat preference of T. belone which is important for management of this understudied species.
Wastewater-based epidemiology (WBE) has been implemented to monitor surges of COVID-19. Yet, multiple factors impede the usefulness of WBE and quantitative adjustment may be required.
We aimed to ...model the relationship between WBE data and incident COVID-19 cases, while adjusting for confounders and autocorrelation.
This nationwide WBE study includes data from 40 wastewater treatment plants (WWTPs) in Belgium (02/2021–06/2022). We applied ARIMA-based modelling to assess the effect of daily flow rate, pepper mild mottle virus (PMMoV) concentration, a measure of human faeces in wastewater, and variants (alpha, delta, and omicron strains) on SARS-CoV-2 RNA levels in wastewater. Secondly, adjusted WBE metrics at different lag times were used to predict incident COVID-19 cases. Model selection was based on AICc minimization.
In 33/40 WWTPs, RNA levels were best explained by incident cases, flow rate, and PMMoV. Flow rate and PMMoV were associated with −13.0 % (95 % prediction interval: −26.1 to +0.2 %) and +13.0 % (95 % prediction interval: +5.1 to +21.0 %) change in RNA levels per SD increase, respectively. In 38/40 WWTPs, variants did not explain variability in RNA levels independent of cases. Furthermore, our study shows that RNA levels can lead incident cases by at least one week in 15/40 WWTPs. The median population size of leading WWTPs was 85.1 % larger than that of non‑leading WWTPs. In 17/40 WWTPs, however, RNA levels did not lead or explain incident cases in addition to autocorrelation.
This study provides quantitative insights into key determinants of WBE, including the effects of wastewater flow rate, PMMoV, and variants. Substantial inter-WWTP variability was observed in terms of explaining incident cases. These findings are of practical importance to WBE practitioners and show that the early-warning potential of WBE is WWTP-specific and needs validation.
Display omitted
•Wastewater-based epidemiology (WBE) for COVID-19 was applied across Belgium.•Wastewater flow rate and population dynamics explain variability in RNA levels.•Variants did not explain variability in RNA levels in 38/40 WWTPs.•WBE metrics lead incident cases by at least one week in 15/40 WWTPs.•Inter-WWTP variability was observed in terms of lead time and optimal metric.
The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective ...in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD.
LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability.
Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some 'lessons learnt'. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted).
We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies.
Improved radiation tolerance of MAPS using a depleted epitaxial layer Dorokhov, A.; Bertolone, G.; Baudot, J. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
12/2010, Letnik:
624, Številka:
2
Journal Article
Recenzirano
Tracking performance of Monolithic Active Pixel Sensors (MAPS) developed at IPHC (Turchetta, et al., 2001)
1 have been extensively studied (Winter, et al., 2001; Gornushkin, et al., 2002)
2,3. ...Numerous sensor prototypes, called MIMOSA,
1
1
Standing for Minimum Ionising particle MOS Active pixel sensors.
were fabricated and tested since 1999 in order to optimise the charge collection efficiency and power dissipation, to minimise the noise and to increase the readout speed.
The radiation tolerance was also investigated. The highest fluence tolerable for a
10
μ
m
pitch device was found to be
∼
10
13
n
eq
/
cm
2
, while it was only
2
×
10
12
n
eq
/
cm
2
for a
20
μ
m
pitch device. The purpose of this paper is to show that the tolerance to non-ionising radiation may be extended up to
O(10
14) n
eq/cm
2. This goal relies on a fabrication process featuring a
15
μ
m
thin, high resistivity (
∼
1
k
Ω
cm
) epitaxial layer. A sensor prototype (MIMOSA-25) was fabricated in this process to explore its detection performance. The depletion depth of the epitaxial layer at standard CMOS voltages (
<
5
V
) is similar to the layer thickness. Measurements with m.i.p.s
2
2
Standing for minimum ionising particle.
show that the charge collected in the seed pixel is at least twice larger for the depleted epitaxial layer than for the undepleted one, translating into a signal-to-noise ratio (SNR) of
∼
50
. Tests after irradiation have shown that this excellent performance is maintained up to the highest fluence considered (
3
×
10
13
n
eq
/
cm
2
)
, making evidence of a significant extension of the radiation tolerance limits of MAPS.
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