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.
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 study identifies a new chronic form of immune neutropenia in the young with or without detectable indirect anti‐neutrophil antibodies, characterized by mild/moderate neutropenia low risk of ...severe infection (14%), tendency to develop autoimmune phenomena over the course of the disease (cumulative incidence of 58.6% after 20 years of disease duration), leukopenia, progressive reduction of absolute lymphocyte count and a T‐ and B‐cell profile similar to autoimmune disorders like Sjogren syndrome, rheumatoid arthritis, and systemic lupus erythematosus (increased HLADR+ and CD3 + TCRγδ cells, reduced T regulatory cells, increased double‐negative B and a tendency to reduced B memory cells). In a minority of patients, P/LP variants related to primary immuno‐regulatory disorders were found. This new form may fit the group of “Likely acquired neutropenia,” a provisional category included in the recent International Guidelines on Diagnosis and Management of Neutropenia of EHA and EUNET INNOCHRON ACTION 18233. The early recognition of this form of neutropenia would help clinicians to delineate better specific monitoring plans, genetic counseling, and potentially targeted therapies.
Main features of Autoimmune and Idiopathic Late Onset and Long Lasting Neutropenias.
We analyzed the outcome of 537 adolescents (age 12-18 years) with idiopathic aplastic anemia included in the database of the Severe Aplastic Anemia Working Party of the European Group for Blood and ...Marrow Transplantation comparing: i) matched family donor hematopoietic stem cell transplantation performed as first-line treatment with ii) front-line immunosuppressive therapy not followed by subsequent transplant given for failure and with iii) hematopoietic stem cell transplantation performed after failed front-line immunosuppressive therapy. Overall survival was 86% in the matched family donor hematopoietic stem cell transplantation group, 90% in patients given front-line immunosuppressive alone (those who did not fail this treatment and who did not receive subsequent rescue with hematopoietic stem cell transplantation) and 78% in subjects who underwent hematopoietic stem cell transplantation post failed front-line immunosuppressive therapy (P=0.14). Event-free survival in the same groups was respectively 83%, 64% and 71% (P=0.04). Cumulative incidence of rejection was 8% in matched family donor hematopoietic stem cell transplantation and 9% in transplants post failed front-line immunosuppression (P=0.62). Cumulative incidence of acute graft-versus-host disease was 12% in matched family donor transplants and 18% in transplants post failed immunosuppression (P=0.18). Chronic graft-versus-host disease was higher in matched family donor hematopoietic stem cell transplantation (8%) than in transplants post failed immunosuppressive therapy (20%) (P=0.0009). Cumulative incidence of post-therapy malignancies was 0.7% in matched family donor transplantations, 7% in transplantations post failed immunosuppression and 21% after front-line immunosuppression (P=0.0017). In the whole cohort, under multivariate analysis, the diagnosis to treatment interval of two months or under positively affected overall survival whereas up-front immunosuppression alone (with no subsequent rescue transplants) negatively affected event-free survival. In transplanted patients an interval from diagnosis to treatment of 2 months or under, bone marrow as source of cells and first-line matched family donor transplants provided a significant advantage in overall and event-free survival. Aplastic anemia in adolescents has a very good outcome. If a matched family donor is available, hematopoietic stem cell transplantation using bone marrow cells is the first choice treatment. If such a donor is not available, immunosuppressive treatment may still be an acceptable second choice, also because, in case of failure, hematopoietic stem cell transplantation is a very good rescue option.
•Two methodologies have been validated for water activation assessment using experimental data collected at the FNG•For the O-16 (n,p) reaction there is good agreement in the cross-sections between ...different nuclear data libraries•The O-16 (n,p) reaction was measured using different setups to provide comprehensive data for code validation•A good C/E agreement was found for both methodologies investigated in this work, hence validating both for simulating water activation assessments
During ITER operations the water coolant flowing through components such as the first wall, blanket modules, divertor cassettes and vacuum vessel will become activated by high energy neutrons. Two key neutron-induced reactions will occur with oxygen in the water producing the radioactive isotopes N-16 and N-17, which have relatively short half-lives of a few seconds. These nuclides are transported in coolant loops and, unmitigated, their decay emissions will induce additional nuclear heat in components, potentially including superconducting magnets, and lead to an increase in the occupational dose for workers and sensitive equipment outside the biological shield. Variations in irradiation, water flow rate and cooling circuit parameters make it difficult to predict nuclear heating. A water activation experiment has recently been performed at the 14 MeV Frascati Neutron Generator to accurately measure N-16 and N-17 produced by irradiating an ITER first wall mock-up. This experiment aimed to validate the methodology for water activation assessment used for ITER and to provide scientific justification to reduce safety factors, which have a large impact on ITER component design and qualification. This paper provides a detailed description of neutronics calculations performed together with the GammaFlow code to model the temporal evolution of activated water, along with MCNP6.1 and FISPACT-II to calculate the detector response. The calculated reaction rates associated with nuclear data from ten libraries have been compared with measured data, although as many cross-sections originated from the same library effectively five nuclear data libraries have been compared.
Acquired aplastic anemia (AA) is a rare heterogeneous disorder characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2–3 per million population per year in the Western world, ...but 3 times higher in East Asia. Survival in severe aplastic anemia (SAA) has improved significantly due to advances in hematopoietic stem cell transplantation (HSCT), immunosuppressive therapy, biologic agents, and supportive care. In SAA, HSCT from a matched sibling donor (MSD) is the first-line treatment. If a MSD is not available, options include immunosuppressive therapy (IST), matched unrelated donor, or haploidentical HSCT. The purpose of this guideline is to provide health care professionals with clear guidance on the diagnosis and management of pediatric patients with AA. A preliminary evidence-based document prepared by a group of pediatric hematologists of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Hemato-Oncology (AIEOP) was discussed, modified and approved during a series of consensus conferences that started online during COVID 19 and continued in the following years, according to procedures previously validated by the AIEOP Board of Directors.
A single crystal diamond detector was exposed to quasi mono-energetic neutron fields in the energy range from 5 to 20.5
MeV. Response functions of such a detector were measured for the first time for ...neutron energies above 14
MeV. The pulse height spectra showed sharp peaks at specific energies. These peaks result from neutron induced charged particle reactions occurring in carbon at different neutron energies. The centroid of the peaks due to the
12C(n,α)
9Be reaction permitted, by means of the reaction
Q-values, to point out a good linearity of the detector response versus neutron energy and a good intrinsic energy resolution of about 56
keV at full width at half maximum. The results reveal that single crystal diamond detectors are good candidates as high resolution fast neutron spectrometers for nuclear fusion applications and for systematic studies of beam and target characteristics for neutron-producing reactions.
•Development of detectors for harsh environments and High Temperature.•Artificial diamond and self-power detectors developed for tokamaks.•Several constrains and technological problems to be faced ...and solved.•Prototype diamond detectors developed and positively tested up to 240 °C.•Prototype SPD with Cr emitter developed and tested with 14 MeV neutrons.
The validation of calculation tools used for the nuclear design and analysis of future fusion machines requires the availability of nuclear instrumentation able to measure the nuclear quantities of interest in the harsh environments typical of tokamaks (e.g. ITER) characterized by high radiation level and high temperature. This instrumentation needs to be developed and properly tested under reactor-relevant working conditions. In the EU the activities to develop advanced nuclear detectors for the ITER-TBM are coordinated and supported by F4E and carried out under a collaborative effort between ENEA and KIT performed under the European Consortium on “Nuclear Data and Experimental Techniques”.
In this paper the activities carried out at ENEA Frascati to develop nuclear sensors (diamond and self-powered detectors) able to operate “in-core” under the harsh working conditions of the ITER-TBM are discussed. Furthermore, the performance of diamond detectors operated at T >300 °C, as well as the performance of a self-power neutron detector (SPND) made with Cr emitter are presented.
The open issues and the technological challenges to be faced to further develop the detectors are also addressed.
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 busulfan, cyclophosphamide and melphalan; corrected 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.
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