Design of gamma-ray spectrometers optimized for fast particle studies at ITER.

A set of gamma ray spectrometers has been designed for ITER within the Radial Gamma Ray Spectrometer (RGRS) project. The aim of this project is designing a system, integrated with the ITER radial neutron camera, which is able to measure the gamma-rays emitted from the plasma with a good energy resolution (about 1.5% at 4.44 MeV) and at high counting rates (in excess of 1 MHz). The RGRS will be able to operate both in the D phase and in the full-power DT phase and will measure gamma rays from (i) reactions between fast ions, such as α particles, and light impurities and (ii) bremsstrahlung emission generated by runaway electron interactions with both plasma bulk and tokamak walls. The RGRS detectors are arranged in nine lines of sights (able to cover a radial region with r < a/3), each featuring a large LaBr3 scintillator crystal. Due to the high neutron flux and magnetic field, several solutions have been adopted to guarantee a good signal to background ratio and MHz counting rate capabilities. The RGRS is capable to combine space and energy distribution measurements of α particles and runaway electrons, which will help the study of the fast particle physics in a burning plasma.

Fertility preservation in the male pediatric population: factors influencing the decision of parents and children.

STUDY QUESTION: How can the decision process for fertility preservation (FP) in adolescents and prepubertal boys be improved based on patient and parent feelings about FP counseling? SUMMARY ANSWER: The content of information given to patients and parents and hope for future parenthood appeared to positively impact on the decision to preserve fertility in the pediatric population and, therefore, deserves special attention to improve FP care. WHAT IS KNOWN ALREADY: A vast body of literature on adult cancer patients shows that reproductive capacity is a major quality-of-life issue. Patients also have a strong desire to be informed of available FP options with a view to future parenthood of their own genetic child, considering that <10% chose to adopt or used donated gametes. Furthermore, the quality of fertility counseling provided at the time of cancer diagnosis has been identified as a crucial factor in the decision-making process. By contrast, in the pediatric population, while it was shown that parents were able to make an informed and voluntary decision for their prepubertal sons despite the heavy emotional burden at the time of diagnosis, there is so far very limited information on patient expectations regarding FP. A lack of awareness often equates to suboptimal care by oncologists and FP specialists, and poor access to FP, therefore improving knowledge and identifying the expectations of pediatric patients and their parents are crucial for optimizing multidisciplinary collaborative care pathways (MCCPs), including counseling and access to FP methods, in the youngest population. STUDY DESIGN, SIZE, DURATION: A questionnaire survey was posted to an eligible population between May 2005 and May 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 348 prepubertal boys and adolescents aged 0-18 years, diagnosed with cancer in a university hospital setting, were eligible. Three different questionnaires for two age groups of children (<12 and 12-18 years) and parents were established based on information from focus groups. Questions were subsequently reviewed by the institutional ethics board before being sent. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 348 eligible patients, 44 died and 14 were lost to follow-up. Thus, 290 patients (77 aged 12-18 years and 213 aged <12 years) were sent a questionnaire. In total, 120 questionnaires were recovered, 45.5% (n = 35/77) from adolescents and 39.9% (n = 85/213) from children. FP acceptance rates were, respectively, 74 and 78.6% for boys aged <12 and 12-18 years. The content of information provided to patients and parents appeared to positively impact on the decision to preserve fertility (P = 0.04). While the majority of boys aged >12 years considered the information to be clear (72%), complete (80%) and understandable (90.9%), only 33.3% of boys aged <12 years were able to comprehend the information. Pressure from doctors to reduce the delay between diagnosis and cancer treatment increased the number of refusals (P<0.01), while hope for future parenthood favored acceptance (P < 0.01). Family support was considered important for 75% of adolescents and 58% of children, and medical support for 50% of adolescents and 42% of children. LIMITATIONS, REASON FOR CAUTION: This single-center survey does not allow extrapolation of the information to other settings. Recall bias and lack of full external validation of the questionnaires are further limitations. Modification of the current MCCP should be further evaluated according to our results. WIDER IMPLICATIONS OF THE FINDINGS: Acknowledging the issues faced and familiarizing oneself with the care of patients undergoing fertility-threatening therapies supply primary care providers with the appropriate quality management tools in the field of FP in centers for reproductive medicine. Expectations reported in the survey allow appropriate support to be included within the MCCP design. STUDY FUNDING/COMPETING INTERESTS: Funding by hospital/clinic(s); Cliniques Universitaires Saint Luc, Brussels, Belgium. The authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: NCT02411214.

Segmental chromosomal alterations lead to a higher risk of relapse in infants with MYCN-non-amplified localised unresectable/disseminated neuroblastoma (a SIOPEN collaborative study).

BACKGROUND: In neuroblastoma (NB), the presence of segmental chromosome alterations (SCAs) is associated with a higher risk of relapse. METHODS: In order to analyse the role of SCAs in infants with localised unresectable/disseminated NB without MYCN amplification, we have performed an array CGH analysis of tumours from infants enrolled in the prospective European INES trials. RESULTS: Tumour samples from 218 out of 300 enroled patients could be analysed. Segmental chromosome alterations were observed in 11%, 20% and 59% of infants enroled in trials INES99.1 (localised unresectable NB), INES99.2 (stage 4s) and INES99.3 (stage 4) (P<0.0001). Progression-free survival was poorer in patients whose tumours harboured SCA, in the whole population and in trials INES99.1 and INES99.2, in the absence of clinical symptoms (log-rank test, P=0.0001, P=0.04 and P=0.0003, respectively). In multivariate analysis, a SCA genomic profile was the strongest predictor of poorer progression-free survival. CONCLUSION: In infants with stage 4s MYCN-non-amplified NB, a SCA genomic profile identifies patients who will require upfront treatment even in the absence of other clinical indication for therapy, whereas in infants with localised unresectable NB, a genomic profile characterised by the absence of SCA identifies patients in whom treatment reduction might be possible. These findings will be implemented in a future international trial.

Neonatal acute myeloid leukemia in an infant whose mother was exposed to diethylstilboestrol in utero.

We report on an acute myeloid leukemia in a neonate whose mother was exposed to diethylstilboestrol in utero. The newborn presented with leukemia cutis, hemorrhagic skin lesions, hyperleucocytosis and disseminated intravascular coagulation. A bone marrow examination confirmed the diagnosis of acute monocytic leukemia with a t(11;19) MLL-ELL fusion transcript. Chemotherapy was initiated but the child developed a bilateral pulmonary infection that led to fatal respiratory distress. This case shows acute myeloid leukemia and the third pediatric leukemia reported after maternal diethylstilboestrol exposure.

Diagnostic components in harsh radiation environments: possible overlap in R&D requirements of inertial confinement and magnetic fusion systems.

The next generation of large scale fusion devices--ITER/LMJ/NIF--will require diagnostic components to operate in environments far more severe than those encountered in present facilities. This harsh environment is the result of high fluxes of neutrons, gamma rays, energetic ions, electromagnetic radiation, and in some cases, debris and shrapnel, at levels several orders of magnitude higher than those experienced in today's devices. The similarities and dissimilarities between environmental effects on diagnostic components for the inertial confinement and magnetic confinement fusion fields have been assessed. Areas in which considerable overlap have been identified are optical transmission materials and optical fibers in particular, neutron detection systems and electronics needs. Although both fields extensively use cables in the hostile environment, there is little overlap because the environments and requirements are very different.

Endocrine and metabolic disorders in young adult survivors of childhood acute lymphoblastic leukaemia (ALL) or non-Hodgkin lymphoma (NHL).

BACKGROUND: Treatments of acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma (NHL), involving various combinations of chemotherapy (chemo), cranial irradiation (CI) and/or bone marrow transplantation after total body irradiation (BMT/TBI), are often successful but may have several long-term harmful effects. OBJECTIVE: To evaluate late endocrine and metabolic complications in adult survivors of childhood ALL and NHL, in relation with the different therapeutic schemes received. DESIGN: Endocrine and metabolic parameters were determined in 94 patients (48 men, mean age: 24 +/- 5 years) with a former childhood ALL (n = 78) or NHL (n = 16) and subgrouped according to their previous treatment: chemo only (group I; n = 44), chemo + CI (group II; n = 32) and chemo + BMT/TBI (group III; n = 18). RESULTS: Severe GH deficiency (peak < 3.0 ng/ml after glucagon) was observed in 22% and 50% of patients of groups II and III, respectively, while hypothyroidism was mainly observed in group III (56%). Moreover, 83% of men developed hypogonadism after BMT/TBI, compared to 17% and 8% in groups I and II, respectively (P < 0.05), and all grafted women had ovarian failure, in contrast with other female patients in whom menarche had occurred spontaneously. Patients with BMT/TBI had also an adverse metabolic profile, with insulin resistance in 83% and dyslipidaemia in 61%. CONCLUSIONS: This study reveals a high prevalence of endocrine and metabolic disorders in young adult survivors of childhood ALL or NHL, this frequency mainly depending on the treatment received. Treatment with BMT/TBI is the most detrimental and many of these patients will develop GHD, hypothyroidism, hypogonadism, insulin resistance and dyslipidaemia.

Randomised revaccination with pneumococcal polysaccharide or conjugate vaccine in asplenic children previously vaccinated with polysaccharide vaccine.

OBJECTIVE: Asplenic children are at high risk of invasive pneumococcal infection. In this group, the American Academy of Pediatrics recommends a single revaccination with the 23-valent polysaccharide vaccine (PSV23) 3-5 years after a previous PSV23 dose. Despite potential advantages, there are few data available regarding the safety and immunogenicity of the heptavalent pneumococcal conjugate vaccine (PCV7) in this population. The aim of the study was to prospectively determine and to compare, in asplenic children, the vaccine specific antibody titres against the seven serotypes included in the PCV7 after administration of one dose of PCV7 or of PSV23, 3 years or more after an initial vaccination with PSV23. PATIENTS AND METHODS: In this randomised, single-centre study, antibody titres were monitored at baseline, at 1 and 6 months after revaccination in 21 children with anatomic or functional asplenia. Response was considered as positive when there was a four-fold increase in antibody titres from baseline. RESULTS: The most frequently reported adverse events were local reactions in 7/11 of PCV7 subjects and in 5/8 of PSV23 subjects, and general reactions (loss of appetite, sleepiness) in 5/11 of PCV7 subjects and in 1/8 of PSV23 subjects; without any serious adverse events. One child in the PCV7 group had increased temperature (38.4 degrees C). At least half of the PCV7 children responded to four or five serotypes, while more than half of the PSV23 subjects responded to less than 3 serotypes (p=0.285). After 1 month, the immune response for serotype 23F was significantly greater after PCV7 vaccination than after PSV23 vaccination (p=0.036). CONCLUSIONS: PCV7 revaccination is safe and immunogenic in asplenic children previously vaccinated with PSV23, and could provide appropriate booster response in this high-risk population. The clinical repercussion on invasive pneumococcal diseases remains to be demonstrated.

[A particular hereditary anemia in a two-month-old infant: elliptocytosis]. / Une forme particulière d'anémie constitutionnelle chez un nourrisson de deux mois: l'elliptocytose.

We report the case of a 2.5-month-old infant with severe anaemia discovered fortuitously during an acute febrile illness. The patient was admitted because of a septic arthritis of the knee. Initial biology showed a 3.5 g/dl haemoglobin concentration. The anaemia was microcytic and hypochromic, with obvious haemolysis and reticulocytosis. Standard analysis was not contributive. Further investigations allowed the diagnosis of elliptocytosis. The patient was treated by antibiotics, orthopaedic measures and iterative transfusions. Now, 18 months from the initial episode, she is in good health. With this history, we discuss the clinical process facing severe anaemia during infancy and review the particularities of such uncommon congenital anaemia. Elliptocytosis is a haemolytic anaemia caused by congenital anomalies of the erythrocyte membrane. Diagnosis requires morphological studies of the red blood cells on peripheral blood smear. The disease is often overlooked by membrane protein electrophoresis. The condition is heterogeneous concerning clinical, biochemical and genetic aspects. Most of the cases are linked to mutations of the alpha-spectrin gene, in autoassociation regions. Search of spectrin and protein 4.1 genes mutations can confirm the diagnosis but is not routinely performed.

Unusual evolution of an Epstein-Barr virus-associated leiomyosarcoma occurring after liver transplantation.

We report the case of a child who developed, 2 yr after orthotopic liver transplantation (OLTx) for biliary atresia, a multi-focal hepatic tumor with lymphonodular metastases, identified as an Epstein-Barr virus (EBV)-associated leiomyosarcoma. Chemotherapy was given without tumor response. Subsequently, slow growth of the tumor was observed. Immunosuppression was tapered and stopped 9 yr after transplantation. At the present time, 12 yr after the discovery of the first hepatic lesions, the patient is alive and completely symptom-free, the abdominal masses are stable, and liver function tests are completely normal. Smooth muscle tumors are increasingly recognized in children with various immunodeficiencies occurring after organ transplantation. This unusual evolution of a clinically aggressive tumor into a stable disease after restoration of immunity confirms that the immune status of the patient is a crucial factor.

[Bone marrow transplantation in Fanconi's anemia: report of seven cases]. / Greffe de moelle dans l'anémie de Fanconi: à propos de sept cas.

OBJECTS: Follow-up of patients with Fanconi's anemia treated in our unit and review of the literature concerning bone marrow transplantation in Fanconi's anemia. PATIENTS AND METHODS: Ten patients were followed in our unit for 20 years. We summarize their clinical features, treatment and clinical course. RESULTS: Among the ten patients, seven received allogeneic marrow transplantation. Only two patients are still alive. Two transplanted patients died from complications shortly after the transplantation. Three other patients died later after the transplantation, two of them from oropharyngeal carcinomas. DISCUSSION: The 5-year survival is about 70% in the transplantation with an HLA-identical sibling donor; it is only about 30% if the donor is an HLA-matched unrelated or mismatched related patient. Furthermore, retrospective studies have shown that the long-term outcome of carcinoma is a major complication after the transplantation. CONCLUSION: Our series of patients with Fanconi's anemia reflects fairly faithfully the complications encountered in this disease. Although the improvement of the graft technique may decrease the rate of death due to transplantation, the long-term development of solid tumors remains a problem for which no solution has been suggested up to now.

[Fanconi's anemia and molecular biology research]. / L'anémie de Fanconi à l'heure de la biologie moléculaire.

Fanconi's anemia is a rare autosomal recessive disease characterized by congenital abnormalities, a progressive pancytopenia and a predisposition to cancer. The diagnosis is based on an abnormal increase of spontaneous chromosome breakage, more specifically on a clear-cut increase of chromosome breakage in the presence of bifunctional alkylating agents. Eight complementation groups (A to H) have been defined, and the genes corresponding to four of these groups have been cloned (FANCA, FANCC, FANCF and FANCG). The function of the proteins encoded by the genes of Fanconi's anemia remains unknown. Numerous studies indicate that different cellular processes are probably involved, including DNA repair pathways, apoptosis, cell cycle regulation and oxygen metabolism. Nevertheless, the exact cellular and molecular mechanisms implicated in Fanconi's anemia remain a challenge for fundamental research. The treatment of Fanconi's anemia is also the subject of intense research, bearing principally upon bone marrow transplantation, which is successful in the case of HLA-identical sibling donors, and gene therapy, which is still at a preliminary stage on the clinical level.

Intracellular cytokine profile of cord and adult blood monocytes.

Cord blood (CB) transplantations are associated with low graft-versus-host disease (GVHD). The pathophysiology of GVHD involves interaction and activation of different cell types, as lymphocytes and monocytes, and results in a cascade of cytokine production. After antigen or mitogen stimulation, CB monocytes release lower levels of cytokines than adult blood (AB) monocytes. In this study, the detection of intracellular IL-1 beta and TNF-alpha produced by monocytes was evaluated in response to tuberculin PPD to investigate whether the reduced capacity of CB monocytes to secrete cytokines could be related to an impaired functional activity and to a particular phenotypic profile. Results showed that the percentage of CD64(+)monocytes producing intracellular IL-1 beta and TNF-alpha was significantly lower in CB and that the phenotypic profile of CB monocytes producing these cytokine (CD64(+)CD14(+)) was different to that of AB monocytes (CD64(+)CD14(+), CD64(+)CD33(+) and CD64(+) CD45RO(+)). These results suggest that the lower capacity of CB monocyte populations to produce IL-1 beta and TNF-alpha might be due to a functional immaturity of CB monocytes at the cellular level as reflected by the different phenotypic profile of CB monocytes.

Expression of HLA-DR, CAM and co-stimulatory molecules on cord blood monocytes.

Umbilical cord blood (CB) transplantations are associated with a lower risk of severe graft-versus-host disease (GVHD) compared to BMT. GVHD is an immune reaction that involves interaction between cell surface molecules resulting in cell activation and release of many cytokines. Monocytes are known to be an important source of cell adhesion (CAM) and co-stimulatory molecules which play a crucial role in the efficient activation of T and B cells. We analyzed the phenotype of CB monocytes in the presence or absence of an inflammatory signal (rIFN-gamma) and compared them to adult blood (AB); the expression of HLA-DR and 17 different markers (CD11a, CD11b, CD11c, CD18, CD29, CD40, CD44, CD49a, CD49d, CD49e, CD49f, CD54, CD58, CD62L, CD80, CD86 and CD102) was measured by flow cytometry. Statistical analysis showed that, compared to AB, CB monocytes did not express CD11b, CD11c, CD49d and after stimulation with rIFNgamma, they lost the expression of CD58 and CD102, whereas CD80 and CD86 expression was induced. The analysis of fluorescence intensity (MFI) revealed that CB monocytes expressed some CAM (CD29, CD54, CD102) with a lower intensity than AB monocytes except CD44. In conclusion, absence and reduced expression of some markers argue for a different phenotypic profile of CB monocytes compared to AB monocytes, which might partly contribute to their impaired immune response and to the low incidence of GVHD observed after CB transplantations. However, CB monocytes expressed CD80 and CD86 co-stimulatory molecules, but this expression did not prove a normal co-stimulatory function.

Smooth muscle tumor developing in an immunocompromised child after therapy for leukemia.

We report a 5.5-year-old boy who underwent autologous peripheral blood stem cell transplantation for high-risk acute lymphoblastic leukemia and who had two abdominal masses develop 6 months later. Macroscopically complete resection of the abdominal tumors was performed and revealed a well-differentiated leiomyosarcoma. Smooth muscle tumors, benign or malignant, are increasingly recognized in children with various immunodeficiencies; the association with acute lymphoblastic leukemia is rarely described.

Clonal monosomy 7 and 5q--in a child with myelodysplastic syndrome.

The authors report the case of a 5-year-old boy referred for thrombocytopenia and neutropenia. Bone marrow examination showed a myelodysplasia with clonal monosomy 7. The acceleration of the disease was marked by the appearance of an additional cytogenetic abnormality, i.e., the deletion of the long arm of chromosome 5 in the clonal cells. RAS gene mutation was not detected. Chemotherapy was started to achieve complete remission before a bone marrow transplantation. This treatment was complicated by a prolonged aplasia and the patient died of systemic mycotic infection.

Urachal neuroblastoma: first case report.

Tumours of the urachus are exceptional in children. They represent 0.01% of all tumours and consist of mucosecretory adenocarcinoma and, more rarely, transitional cell carcinoma. We report a 6-month-old child with a urachal mass which, following biopsy, was shown to be a neuroblastoma.

Circadian and seasonal variations of hematopoiesis in cord blood.

Cord blood hematopoietic progenitors undergo circadian and seasonal variations. The lowest values are obtained between 4:00 and 12:00, as well as between May and August. This represents the first observation of such rhythms before birth.