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The addition of rituximab to standard combination chemotherapy in children with high-grade (mainly Burkitt’s) lymphoma improved 3-year event-free survival (94% vs. 82%). The incidence of myelotoxic effects was somewhat higher, without a higher incidence of death from toxic effects; the incidence of hypogammaglobulinemia was higher.

Host actin cytoskeleton is often targeted by pathogenic bacteria through the secretion of effectors. Legionella pneumophila virulence relies on the injection of the largest known arsenal of bacterial proteins, over 300 Dot/Icm type 4 secretion system effectors, into the host cytosol. Here, we define the functional interactions between VipA and LegK2, two effectors with antagonistic activities towards actin polymerization that have been proposed to interfere with the endosomal pathway. We confirmed the prominent role of LegK2 effector in Legionella infection, as the deletion of legK2 results in defects in the inhibition of actin polymerization at the Legionella-containing vacuole, as well as in endosomal escape of bacteria and subsequent intracellular replication. More importantly, we observed the restoration of the ΔlegK2 mutant defects, upon deletion of vipA gene, making LegK2/VipA a novel example of effector-effector suppression pair that targets the actin cytoskeleton and whose functional interaction impacts L. pneumophila virulence. We demonstrated that LegK2 and VipA do not modulate each other’s activity in a “metaeffector” relationship. Instead, the antagonistic activities of the LegK2/VipA effector pair would target different substrates, Arp2/3 for LegK2 and G-actin for VipA, to temporally control actin polymerization at the LCV and interfere with phagosome maturation and endosome recycling, thus contributing to the intracellular life cycle of the bacterium. Strikingly, the functional interaction between LegK2 and VipA is consolidated by an evolutionary history that has refined the best effector repertoire for the benefit of L. pneumophila virulence.

This work presents the results following the first irradiation of ITER materials samples in a tokamak D–T plasma environment operating at significant fusion power. The materials exposed to this nuclear environment at the Joint European Torus during the DTE2 experimental campaign that took place in 2021 include representative ITER samples from various components such as poloidal field coil jacket samples, toroidal field coil radial closure plate steels, EUROFER 97 steel, W and CuCrZr materials from the divertor, Inconel-718 and 316L stainless steel for blanket modules, as well as vacuum vessel forging samples. The experimental results discussed include high-resolution gamma spectrometry measurements and analysis conducted with the post-irradiated samples, of which there were 68 in total. These samples were exposed through different experimental campaigns, including deuterium, deuterium–tritium and tritium phases. Diagnostics that supported the analysis included 25 dosimetry foil-based neutron diagnostics and two ‘VERDI’ neutron spectrometry diagnostics. A further 12 samples for positron annihilation spectroscopy were also irradiated. The irradiation of all these samples took place in a long-term irradiation assembly located near the JET vacuum vessel. The post-irradiation analysis of the ITER material samples has yielded valuable insights into their material activation levels and radiation fields. Comparative assessments between experimental measurements and comprehensive neutronics simulations have demonstrated a significant level of agreement in this work, while also revealing some discrepancies in specific material instances. The data and interpretation from this work not only serve as a robust experimental foundation for enhancing the precision and predictability of neutronics simulation approaches for ITER and next-step devices but also present some opportunities for the refinement of simulation methodologies. In light of these findings, a series of recommendations have been proposed, aimed at improving confidence in nuclear predictions associated with materials that have been exposed to fusion nuclear environments and advancing understanding in this important domain.

The Frascati Neutron Generator (FNG) started operations in November 1992 making available to EU fusion community 14 MeV neutrons at an emission rate of 1011 s-1. The fusion community strongly supported the idea of international collaboration in neutronics experiments, data base and code improvement, development of (new) experimental techniques and detectors. FNG was designed and built in ENEA that also operates the machine at its own expenses. FNG is extensively used to perform benchmarks or mock-up experiments of interest to Fusion neutronics in turn validating nuclear data and codes. A number of activities in different fields within a series of collaborations are carried out at FNG so far.

We studied the prognostic value of minimal disseminated disease (MDD) and anti-ALK immune response in children with NPM-ALK-positive anaplastic-large cell lymphoma (ALCL) and evaluated their potential for risk stratification. NPM-ALK transcripts were analyzed by RT-PCR in bone marrow/peripheral blood of 128 ALCL patients at diagnosis, whereas ALK antibody titers in plasma were assessed using an immunocytochemical approach. MDD was positive in 59% of patients and 96% showed an anti-ALK response. Using MDD and antibody titer results, patients could be divided into three biological risk groups (bRG) with different prognosis: high risk (bHR): MDD-positive and antibody titer ⩽1/750, 26/128 (20%); low risk (bLR): MDD negative and antibody titer >1/750, 40/128 (31%); intermediate risk (bIR): all remaining patients, 62/128 (48%). Progression-free survival was 28% (s.e., 9%), 68% (s.e., 6%) and 93% (s.e., 4%) for bHR, bIR and bLR, respectively ( P <0.0001). Survival was 71% (s.e., 9%), 83% (s.e., 5%) and 98% (s.e., 2%) for bHR, bIR and bLR ( P =0.02). Only bHR and histology other than common type were predictive of higher risk of failure (hazard ratio 4.9 and 2.7, respectively) in multivariate analysis. Stratification of ALCL patients based on MDD and anti-ALK titer should be considered in future ALCL trials to optimize treatment.

In the decommissioning of nuclear facilities, it is necessary to assess the radioactivity inventory for waste classification and management. For nuclear fusion experiments or accelerator-driven neutron sources, the main contribution to the radiological inventory comes from activation products and tritium. When water is used as coolant of components, it may be activated by neutrons with the consequent production of tritium, and short-lived oxygen and nitrogen isotopes. In most cases several chemical elements may be in solution or suspension in water, because of metallic pipes corrosion when occurring, or functional reasons, e.g. chemical conditioning, addition of antifreeze agent, etc. In this case other activation products could be present and need to be characterized. In this case study, a sample of the coolant of the ENEA Frascati Neutron Generator (FNG) has been radiologically, chemically and physically characterized. In such a facility, during the operation, a beam of deuterons is accelerated up to 300 keV and impacts on a tritiated target for producing 14 MeV neutrons exploiting the fusion reaction T(d,n)α. To avoid overheating in the area around the target, a water-cooling loop is used. After several years of operation, a sample of the fluid has been extracted to undergo a qualitative and quantitative analysis of the radionuclides inventory. Gamma spectrometry has not shown any presence of gamma emitters. On the other hand, Liquid Scintillation Counting (LSC) has provided evidence of the presence of beta emitters. It is known that tritium is expected to occur in the sample because of releases from the tritiated titanium target. This work concerns the development of a method to discriminate the tritium contribution with respect to the total beta activity within the FNG coolant. Since it is known that an unspecified percentage of an unknown anticorrosive agent was added to the water coolant, vacuum distillation has been used to extract purified water (containing only tritium) from the coolant sample leaving any (activated) non-volatile compound in the undistilled fraction. After distillation, any fraction has been investigated by Raman spectroscopy, to determine: a) the chemical composition of the colored anticorrosive agent, b) the efficiency of the separation. Afterwards, both fractions have been analysed by means of LSC, and results showed that the main contribution to sample activity is due to tritium and the activity values are consistent with the theoretical H atomic concentration in both fractions.

Quite often, detectors for measuring nuclear performance and radiation quantities of relevance in fusion experiments are requested to withstand harsh working conditions due to intense neutron and gamma radiation fields. High temperature constitutes a further harsh element in some locations of the machine, where it is necessary to perform some on-line measurements, as expected in the breeding blanket. This is an essential component in future fusion power plants to provide tritium self-sufficiency and its performance must be continuously monitored. Some Test Blanket Modules (TBMs) will be installed in ITER to provide the first experimental data to validate the predictions on tritium production and recovery. In the meantime, within EUROfusion program, the mock-up of the Helium Cooled Pebble Bed Test Blanket Module (HCPB TBM), previously used for the TBM experiment at the Frascati Neutron Generator (FNG), had been installed at JET to test some detectors and for benchmarking numerical codes used for breeding blanket assessment during DTE2 campaign. A diamond detector, calibrated to measure the tritium production through neutron detection inside the HCPB TBM mock-up, was tested during some plasma pulses of the DTE2 campaign at JET. The main outcome is that, as far as neutron emission rate is below 10 15  s −1 , neutrons are properly detected along the plasma discharge evolution by TBM diamond detector, consistently with the JET neutron monitor KN1. Moreover, the amount of tritium measured ( E ) is 1.40 × 10 –12 tritons per source neutron and the comparison with MCNP radiation transport simulation ( C ) gives a ratio C / E  = 0.77. Such measurements, considered promising, and their comparison with calculations are discussed in the present work. Criticalities emerged are analyzed and some improvements proposed with the main purpose of speeding up signal processing to make the system capable of working at higher plasma neutron emission rates.

Chemotherapy and irradiation can affect the gonads, leading to impairment of pubertal development and/or infertility. Fertility preservation (FP) is therefore a crucial endeavor in hematopoietic stem cell transplantation (HSCT) because of the severe impact of infertility on the quality of life of long-term survivors. Despite the existence of different international guidelines, FP counseling and procedures are not routinely implemented as part of patient care. We present herein a survey conducted by the Pediatric Working Party of the European Society for Blood and Marrow Transplantation (EBMT), which aims to analyze and compare different FP practices for children and adolescents across EBMT centers in 2013. A total of 177 pediatric centers reporting to the EBMT were contacted; of this number, 38 centers (21%) located in 16 different countries responded. These centers reported 834 patients receiving HSCT in 2013 (73% prepubertal), corresponding to 22% of all children ( n =3789) undergoing HSCT in EBMT reporting centers. Overall, 39% of the reported patients received counseling and 29% received an FP procedure. The increased need for FP programs, extended education for patient-care teams, and more personal resources and funding emerged from this survey as pivotal factors necessary to support and implement such programs.

We analyzed the outcome of 243 children with high-risk (HR) AML in first CR1 enrolled in the AIEOP-2002/01 protocol, who were given either allogeneic (ALLO; n =141) or autologous (AUTO; n =102) hematopoietic SCT (HSCT), depending on the availability of a HLA-compatible sibling. Infants, patients with AML-M7, or complex karyotype or those with FLT3-ITD, were eligible to be transplanted also from alternative donors. All patients received a myeloablative regimen combining BU, Cyclophosphamide and Melphalan; AUTO-HSCT patients received BM cells in most cases, while in children given ALLO-HSCT stem cell source was BM in 96, peripheral blood in 19 and cord blood in 26. With a median follow-up of 57 months (range 12–130), the probability of disease-free survival (DFS) was 73% and 63% in patients given either ALLO- or AUTO-HSCT, respectively ( P =NS). Although the cumulative incidence (CI) of relapse was lower in ALLO- than in AUTO-HSCT recipients (17% vs 28%, respectively; P =0.043), the CI of TRM was 7% in both groups. Patients transplanted with unrelated donor cord blood had a remarkable 92.3% 8-year DFS probability. Altogether, these data confirm that HSCT is a suitable option for preventing leukemia recurrence in HR children with CR1 AML.

Peripheral T cell lymphomas (PTCL) are rare in children and adolescents, and data about outcome and treatment results are scarce. The present study is a joint, international, retrospective analysis of 143 reported cases of non-anaplastic PTCL in patients <19 years of age, with a focus on treatment and outcome features. One hundred forty-three patients, between 0.3 and 18.7 years old, diagnosed between 2000 and 2015 were included in the study. PTCL not otherwise specified was the largest subgroup, followed by extranodal NK/T cell lymphoma, hepatosplenic T cell lymphoma (HS TCL), and subcutaneous panniculitis-like T cell lymphoma (SP TCL). Probability of overall survival (pOS) at 5 years for the whole group was 0.56 ± 0.05, and probability of event-free survival was (pEFS) 0.45 ± 0.05. Patients with SP TCL had a good outcome with 5-year pOS of 0.78 ± 0.1 while patients with HS TCL were reported with 5-year pOS of only 0.13 ± 0.12. Twenty-five percent of the patients were reported to have a pre-existing condition, and this group had a dismal outcome with 5-year pOS of 0.29 ± 0.09. The distribution of non-anaplastic PTCL subtypes in pediatric and adolescent patients differs from what is reported in adult patients. Overall outcome depends on the subtype with some doing better than others. Pre-existing conditions are frequent and associated with poor outcomes. There is a clear need for subtype-based treatment recommendations for children and adolescents with PTCL.