First set of gated x-ray imaging diagnostics for the Laser Megajoule facility.

The Laser Megajoule (LMJ) facility located at CEA/CESTA started to operate in the early 2014 with two quadruplets (20 kJ at 351 nm) focused on target for the first experimental campaign. We present here the first set of gated x-ray imaging (GXI) diagnostics implemented on LMJ since mid-2014. This set consists of two imaging diagnostics with spatial, temporal, and broadband spectral resolution. These diagnostics will give basic measurements, during the entire life of the facility, such as position, structure, and balance of beams, but they will also be used to characterize gas filled target implosion symmetry and timing, to study x-ray radiography and hydrodynamic instabilities. The design requires a vulnerability approach, because components will operate in a harsh environment induced by neutron fluxes, gamma rays, debris, and shrapnel. Grazing incidence x-ray microscopes are fielded as far as possible away from the target to minimize potential damage and signal noise due to these sources. These imaging diagnostics incorporate microscopes with large source-to-optic distance and large size gated microchannel plate detectors. Microscopes include optics with grazing incidence mirrors, pinholes, and refractive lenses. Spatial, temporal, and spectral performances have been measured on x-ray tubes and UV lasers at CEA-DIF and at Physikalisch-Technische Bundesanstalt BESSY II synchrotron prior to be set on LMJ. GXI-1 and GXI-2 designs, metrology, and first experiments on LMJ are presented here.

A 140 mA cw deuteron electron cyclotron resonance source for the IFMIF-EVEDA project.

In the framework of the IFMIF-EVEDA phase (International Fusion Materials Irradiation Facility-Engineering Validation and Engineering Design Activities), the CEA-Saclay is in charged of the design and realization of the 140 mA cw deuteron source. The IFMIF EVEDA demonstrator will be installed in Japan in the next six years and will have to accelerate the deuteron beam up to 9 MeV. CEA will build the source and the low energy beam line (LEBT) and will test the cw high intensity deuteron production at Saclay. The SILHI source is an electron cyclotron resonance (ECR) source, operating at 2.45 GHz. In 2001, it produced more than 130 mA of deuteron beam in pulsed mode to minimize neutron production. Such a result pushes to develop a new ECR source based on the SILHI design and equipped with a specific extraction system. Several options of the accelerator column will be implemented in order to improve the reliability and the efficiency of the source. The IFMIF source and LEBT design will be reported.

Recessive hereditary methaemoglobinaemia, type II: delineation of the clinical spectrum.

Type II recessive hereditary methaemoglobinaemia (RHM) is a rare disease due to generalized NADH-cytochrome b5 reductase (cytb5r) deficiency. It results in mild cyanosis and severe neurological impairment. The clinical features and long-term outcome are poorly documented, and there are no systematic reviews. We examined six cases of type II RHM, four of which were new, together with 45 previously published cases, in order to establish the range of phenotypic expression. The clinical picture was very similar in most cases, with severe encephalopathy, microcephaly, generalized dystonia, movement disorders and mild cyanosis. The neurological prognosis was poor; in particular, none of the patients walked or spoke. In addition, the possibility of an atypical and milder phenotype was considered. We concluded that children with unexplained severe encephalopathy associated with generalized dystonia should be examined for cyanosis and have a methaemoglobinaemia assay performed. The diagnosis can be confirmed by very low cytb5r activity in both red and white blood cells. Here we report three novel mutations in the NADH-cytochrome b5 reductase gene. Prenatal diagnosis of this extremely severe disease should be proposed to affected families.

Acute clinical events in 299 homozygous sickle cell patients living in France. French Study Group on Sickle Cell Disease.

A subset of 299 patients with homozygous sickle cell anaemia, enrolled in the cohort of the French Study Group on sickle cell disease (SCD), was investigated in this study. The majority of patients were children (mean age 10.1 +/- 5.8 yr) of first generation immigrants from Western and Central Africa, the others originated from the French West Indies (20.2%). We report the frequency of the main clinical events (mean follow-up 4.2 +/- 2.2 yr). The prevalence of meningitis-septicaemia and osteomyelitis was, respectively, 11.4% and 12% acute chest syndrome was observed in 134 patients (44.8%). Twenty patients (6.7%) developed stroke with peak prevalence at 10-15 yr of age. One hundred and seventy-two patients (58%) suffered from one or more painful sickle cell crises, while the others (42.5%) never suffered from pain. The overall frequency of acute anaemic episodes was 50.5%, (acute aplastic anaemia 46%; acute splenic sequestration 26%). A group of 27 patients were asymptomatic (follow-up > 3 yr). Epistatic mechanisms influencing SCD were studied. Coinherited alpha-thalassemia strongly reduced the risk of stroke (p <0.001) and increased that of painful crises (p < 0.02). There was a low prevalence of Senegal and Bantu (CAR) betas-chromosomes in patients with meningitis (p <0.04) and osteomyelitis (p < 0.03). Prevalence of Senegal betas-chromosomes was lower in the asymptomatic group of 27 patients (p < 0.02). The patients come from a population of unmixed immigrants in whom the beta-globin gene haplotype strongly reflects the geographic origin and identifies subgroups with a homogenous genetic background. Thus the observed effects might result more from differences in as yet unidentified determinants in the genetic background than from the direct linkage with differences in the beta-globin gene locus.

[Hereditary methemoglobinemias]. / Les méthémoglobinémies héréditaires.

The different forms of hereditary methemoglobinemia are described. Dominant hereditary methemoglobinemia (hemoglobin M diseases) is due to punctual mutations on the alpha or beta globin chain leading to its permanent oxidation. Recessive hereditary methemoglobinemia is due to a deficit of the NADH-cytochrome b5 reductase, with two different clinical presentations according to whether the deficit is limited to blood cells (type I) or is generalized (type II); the latter is extremely severe and justifies a prenatal diagnosis. Finally, the only known case of recessive hereditary methemoglobinemia due to a deficit of b5 cytochrome is quoted.

[Prion diseases and blood transfusion]. / Maladies à Prion et transfusion sanguine.

Prion diseases are lethal disorders, some of which are transmissible by infectious route. Experimental data concerning neuroinvasion indicate that there is a viremia during the migration of the prion agent to the central nervous system. The possibility of accidental transmission via blood products and therefore potential transfusion risk thus arises. The analysis of experimental and epidemiological data available at present contributes to the following conclusion: the potential and theoretical risk for contamination from blood products is not null but mathematically very low, there is no indisputable experimental proof for that risk via systemic route and no case is definite and the risk is probably linked to leukocytes, and especially B lymphocytes. These conclusions are reassuring but nevertheless justify strict epidemiological survey and a reasonable discussion for each transfusion. Some groups of people have to be excluded from blood donors.

[Spasmus nutans: apropos of 16 cases]. / Spasmus nutans: à propos de 16 cas.

UNLABELLED: Spasmus nutans is a syndrome occurring in early childhood. It consists of a triad of symptoms: head nodding, ocular oscillations and anomalous head position. Ophthalmologic and neurological findings are otherwise normal. This syndrome is benign and has spontaneous resolution. PATIENTS AND METHOD: Sixteen patients with spasmus nutans seen from 1980 to 1995 were retrospectively studied. Their present status was evaluated by clinical examination or questionnaire. RESULTS: The age at onset ranged from 1 to 15 months (average 7 months). Thirteen of 16 patients were referred for head nodding, which was a constant manifestation; its direction was horizontal, vertical or rotatory. Nystagmus was present in 14 infants. It was acquired, asymmetrical, bilateral (or unilateral in three cases), rapid, fine, pendular and horizontal. Both head nodding and nystagmus were intermittent. Anomalous head position was present in seven cases, consisting of head tilt or a chin upon/chin down posture. Neuroimaging (13 cases) was always normal. The follow-up in 12 children (up to 2 years) showed a complete resolution of the syndrome in 6 months to 6 years (average 2.5 years). DISCUSSION: The diagnosis was established by the constancy of the characteristic triad and the elimination of the other causes of nystagmus. Isolated head nodding had to be distinguished from bobble head syndrome. In several reported cases, electronystagmography recordings have suggested that head nodding is a compensatory process against nystagmus and that the head tilt allows transient resolution of the nystagmus. CONCLUSION: Spasmus nutans is a self-limiting benign clinical entity. Normal complete ophthalmologic and neurological examination, as well as magnetic resonance imaging (MRI) are necessary to confirm the diagnosis.

The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria): case reports of 23 new patients.

OBJECTIVES: To further define the clinical spectrum of the disease for pediatric and metabolic specialists, and to suggest that the general pediatrician and pediatric neurologist consider succinic semialdehyde dehydrogenase (SSADH) deficiency in the differential diagnosis of patients with (idiopathic) mental retardation and emphasize the need for accurate, quantitative organic acid analysis in such patients. PATIENTS: The clinical features of 23 patients (20 families) with SSADH deficiency (4-hydroxybutyric acid-uria) are presented. The age at diagnosis ranged from 3 months to 25 years in the 11 male and 12 female patients; consanguinity was noted in 39% of families. OUTCOME MEASUREMENTS: The following abnormalities were observed (frequency in 23 patients): motor delay, including fine-motor skills, 78%; language delay, 78%; hypotonia, 74%; mental delay, 74%; seizures, 48%; decreased or absent reflexes, 39%; ataxia, 30%; behavioral problems, 30%; hyperkinesis, 30%; neonatal problems, 26%; and electroencephalographic abnormalities, 26%. Associated findings included psychoses, cranial magnetic resonance or computed tomographic abnormalities, and ocular problems in 22% or less of patients. Therapy with vigabatrin proved beneficial to varying degrees in 35% of the patients. Normal early development was noted in 30% of patients. CONCLUSIONS: Our data imply that two groups of patients with SSADH deficiency exist, differentiated by the course of early development. Our recommendation would be that accurate, quantitative organic acid analysis in an appropriate specialist laboratory be requested for any patients presenting with two or more features of mental, motor, or language delay and hypotonia of unknown cause. Such analyses are the only definitive way to diagnose SSADH deficiency; the diagnosis can be confirmed by determination of enzyme activity in white cells from whole blood. We think that increased use of organic acid determination will lead to increased diagnosis of SSADH deficiency and a more accurate representation of disease frequency. As additional patients are identified, we should have a better understanding of both the metabolic and clinical profiles of SSADH deficiency.

Trends in drug use among American Indian students and dropouts, 1975 to 1994.

OBJECTIVES: This 20-year surveillance project tracks the trends in substance abuse among American Indian students and examines the observed patterns to discover implications for prevention and treatment. The current phase of this work includes data on drug use among Indian school dropouts. METHODS: Anonymous drug use surveys are administered annually to a nationally representative sample of 7th- to 12th-grade Indian youths residing on or near reservations. An adjustment for dropouts is made to provide estimates for the entire age cohort. RESULTS: Indian youth continue to show very high rates of drug use compared with their non-Indian peers. The trends in rates during the last 20 years parallel those of non-Indian youth. While overall drug use may be decreasing, about 20% of Indian adolescents continue to be heavily involved with drugs, a proportion that has not changed since 1980. Adjustment for school dropouts increases the estimate for the entire age cohort. CONCLUSIONS: Indian youth, particularly school dropouts, remain at high risk for drug use. The similarity to trends for non-Indians indicates that prevention strategies effective with other youth can be effective with this population.

Differential levels of synovial fluid aggrecan aggregate components in experimental osteoarthritis and joint disuse.

The levels of proteoglycan aggregate components (link protein, keratan sulfate epitope, and total sulfated glycosaminoglycan) were determined in the synovial fluid lavages of dogs with experimental osteoarthritis or disuse atrophy. A model of experimental osteoarthritis was created by transection of the anterior cruciate ligament of the right knee; studies were carried out 6 and 12 weeks after surgery. Joint disuse was studied at 4 and 8 weeks after initiation of the disuse. Recovery after disuse also was studied in joints that had 3 weeks of remobilization after 4 or 8 weeks of disuse. Synovial fluid lavages from the right knee joints of untreated animals were used as controls. The concentrations of keratan sulfate epitope, sulfated glycosaminoglycan, and link protein in the synovial fluid lavages at 6 and 12 weeks after transection of the anterior cruciate were elevated compared with the control values. Similar analysis of the fluid after disuse showed that the levels of keratan sulfate epitope and sulfated glycosaminoglycan were increased compared with the control levels and the levels after transection. However, the concentration of link protein in the fluid after disuse was not significantly different from the control level. The levels of keratan sulfate epitope and sulfated glycosaminoglycan in the synovial fluid lavages after disuse with recovery were high, but the levels of link protein remained low. The results indicate that the catabolism of proteoglycan aggregates in articular cartilage during early osteoarthritis and disuse is different. The determination of keratan sulfate epitope in synovial fluid lavages appears to provide a relatively general indication of proteoglycan catabolism, whereas increased levels of link protein may be more indicative of cartilage degeneration.