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Pellet injection represents, to date, the most promising option for core fuelling of the EU-DEMO tokamak. Simulations with the HPI2 pellet ablation/deposition code indicate, however, that sufficiently deep fuel deposition requires injection from the High Field Side (HFS) at velocities ≳1 km/s. Two complementary inboard injection schemes are being explored: one makes use of guide tubes with curvature radii ≥6 m in the attempt of preserving pellet integrity at speeds of ˜1 km/s, the other is investigating the feasibility of injecting high-speed (˜3 km/s) pellets along “direct line of sight” (DLS) trajectories, from either the HFS or a vertical port. Options using quasi-vertical DLS paths routed across the upper vertical port have been explored first, as they can be more easily integrated, Unfortunately, the radial position of the available vertical access (≳9 m from the machine axis) turns out to be unfavorable; further simulations with the HPI2 code predict indeed that vertical injection may be effective only if pellets trajectories are well inboard the magnetic axis. High-speed injection through oblique inboard “DLS” paths, not interfering with the Central Solenoid (CS), are instead predicted to yield good performance, provided that the injection location is ≲2.5 m from the equatorial mid-plane. The angular spread of high-speed free-flight pellets, recently measured using an existing facility, turns out to be enclosed within ˜ 0.7°. This scatter cone may require significant cut off volume of the Breeding Blanket (BB). Moreover, DLS in-vessel conical penetrations may increase the neutron flux outside of the bio-shield, and also result in a significant heat load in the cryogenic pellet source. These issues are being investigated, to identify suitable shielding strategies; preliminary results are reported. The suitability of straight guide tubes to reduce the scatter cone, and hence the corresponding open cross section on BB penetration and the neutron streaming, will be explored as a further step. © 2019 Elsevier B.V.

Presents the introductory welcome message from the conference proceedings. May include the conference officers' congratulations to all involved with the conference event and publication of the proceedings record.

The four-barrel, two-stage gun Ignitor Pellet Injector (IPI) was developed in collaboration between ENEA and ORNL. The prototype injector is presently located at Oak Ridge (TN, USA), and is normally operated locally through a control and data acquisition system developed in LabVIEW. More recently, a remote-control system has been set up, based on RealVNC®, which allows to operate the IPI from a control room in Italy. Tools for data transfer and storage into ENEA ICT area have also been provided. A Staging, Storage and Sharing system, named E3S, developed using OwnCloud as architectural component, is used for file synchronization and sharing of the data acquired by the diagnostic systems. It provides a homogeneous platform able to store and share heterogeneous data produced by many data acquisition systems in large nuclear fusion experiments. This paper reports about the implementation of the IPI remote control, and presents the application of E3S to this specific case, allowing easy storage and sharing of experimental data onto a wide-area distributed file-system, as well as remote data access via web-services based on MDS+ tool, integrated with MySQL metadata. A performance analysis of the architectural components is also introduced.

The Nearcticissid species Thionia simplex (Germar, 1830) is recorded for the first time from Europe. Other alien Auchenorrhyncha species in Europe are listed and discussed.

The first ignition experiments on the Laser Megajoule facility will use an indirect drive scheme. Our A1040 point design target is a graded doped plastic capsule filled by permeation within a gold cylinder. The deuterium-tritium ice layer may be formed either by classical slow cooling at 1.5 K below triple point, or by rapid cooling at 2.3 K below triple point. To complete the specifications, we first studied the robustness to all technological defects with the current CEA capabilities for these two options of ice formation. The technological imperfections taken into account are regrouped into ID errors, which keep the implosion spherical, and 3D errors, which induce a deformation of the shell. The 3D robustness is expressed in terms of deformation at peak velocity and compared to the deformation threshold obtained with 2D simulations. The ID robustness is given by the probability of exceeding 50% of nominal yield. We have taken into account 22 ID parameters and the fusion energy is approximated by a neural network based on 2000 simulations. Although the studies are not finished yet, the first results show that the A1040 design with rapid cooling has sufficient margins with respect to technological defects.

The adoption of a non-uniform dopant profile has substantially increased the tolerance to high mode deformations of our baseline indirect-drive design. In addition, a low deuterium–tritium (DT) gas density, obtained by 'dynamic quenching' at 2.3 K below triple point, could partly compensate for the decrease in robustness due to DT ageing. Finally, the net margin regarding all laser and target technological defects is about 2. As soon as a sufficient amount of laser beams and diagnostics is available, we will shoot pre-ignition experiments to tune the point design. We are studying new targets which need less energy for these campaigns.We have estimated different direct-drive schemes using indirect-drive beams. The optimal LMJ polar direct-drive configuration is a 2-cone one and leads to marginally igniting targets. A new 2-cone direct-drive scheme, associated with focal spot zooming, allows us to reach ignition with enough margin.

This article sums up the theoretical and experimental studies about ignition. Three experiments are salient this year on the Omega laser in collaboration with DOE laboratories (1) 3 cones of beams allow to mimic the LMJ configuration and to get symmetry measurements. (2) We measured perturbations due to hydro-instability in CHGe planar samples with face-on and side-on radiographs. (3) We improved our nuclear diagnostics, particularly the neutron image system tested on direct drive implosions. As far as LMJ target design is concerned, we defined a preliminary domain corresponding to the possible operation at 2ω. At 3ω we studied the low mode instability effects on the DT deformation (due to the laser or to the target) and on the yield. The stability is clearly improved with graded doped CH for our nominal capsule L1215.

The nominal configuration of inertial confinement fusion with the Laser MegaJoule (LMJ) uses a cylindrical hohlraum with two polar holes for the entrance of 60 laser quads. But the LMJ facility makes it possible to use a spherical hohlraum with more than two holes. We have studied two alternate configurations, in which 56 and 44 laser quads enter a spherical hohlraum through four and six holes respectively, with the same wall surface as in the nominal cylindrical hohlraum. We have estimated the intrinsic and random radiation asymmetries on the nominal capsule A 1040 in these two configurations.

This work addresses the analytical calculation of the irradiation coming from a cylindrical surface to a spherical one. This exact solution of the x-ray transport equation allows one to connect the emitted and the received fluxes, expanded as Fourier modes, by coefficients called Fourier view factors. Such a calculation is well suited to a symmetry study in the Laser Megajoule configuration [P.-A. Holstein, M. Andre, M. Casanova et al., C. R. Acad. Sci. Paris 1, 693 (2000)] where a cylindrical hohlraum and a spherical capsule are irradiated. Indeed, this 60 quad laser system induces an azimuthal asymmetry of the hohlraum lighting depending on the laser focal spot size. Thus, the Fourier view factors allow one to express the modes of the capsule irradiation as functions of the elliptic spot dimensions.

A total of 182 migrants were followed-up from 1999 until 2007 by the Bologna-west Transcultural Psychiatric Team (BoTPT). Most of these patients came from North and sub-Saharan Africa (54%), were suffering from adjustment disorders and were referred by social or voluntary services, while only 16% came through general practitioners. Clinical diagnoses, psychopathology and pathways to care were closely related to socio-demographic features and ethnic groups. More efforts should be made to ameliorate pathways to care among migrants. In particular we should provide ethnic minorities with information about mental illness and services and we should teach primary and secondary levels of care to acquire greater cultural awareness.

Medium size HPC clusters play an important role in the HPC landscape in that they provide both the training environment for system scalability and a flexible production field for a large class of numerical problems. In this poster we present CRESCO4, the latest medium size HPC cluster purchased by ENEA, in operation since few months. CRESCO4 is part of a family of HPC systems, all integrated within ENEAGRID, a large infrastructure for cloud computing, which includes all the computational facilities installed at several ENEA sites in Italy.

We recall the main features of the LMJ. By using a simple but global model we determined different shells able to give a thermonuclear yield larger than 15 MJ; this model delimited an operating domain for the laser with a 25% margin to take into account the poorly understood phenomena. The different issues are related to the physics of the shell and to the physics of the hohlraum: optimisation of the shell implosion; laser–plasma interaction in the hohlraum; irradiation uniformity given by the hohlraum (2D simulations); implosion with non-uniformities; robustness against the experimental uncertainties; hydrodynamic instabilities during implosion.

In a personal series of 107 patients, we describe clinical presentations, methods of recognition and therapeutic management of inherited fatty acid oxidation (FAO) defects. As a whole, FAO disorders appear very severe: among the 107 patients, only 57 are still living. Including 47 siblings who died early in infancy, in total 97 patients died, of whom 30% died within the first week of life and 69% before 1 year. Twenty-eight patients presented in the neonatal period with sudden death, heart beat disorders, or neurological distress with various metabolic disturbances. Hepatic presentations were observed in 73% of patients (steatosis, hypoketotic hypoglycaemia, hepatomegaly, Reye syndrome). True hepatic failure was rare (10%); cholestasis was observed in one patient with LCHAD deficiency. Cardiac presentations were observed in 51% of patients: 67% patients presented with cardiomyopathy, mostly hypertrophic, and 47% of patients had heart beat disorders with various conduction abnormalities and arrhythmias responsible for collapse, near-miss and sudden unexpected death. All enzymatic blocks affecting FAO except CPT I and MCAD were found associated with cardiac signs. Muscular signs were observed in 51% of patients (of whom 64% had myalgias or paroxysmal myoglobinuria, and 29% had progressive proximal myopathy). Chronic neurologic presentation was rare, except in LCHAD deficiency (retinitis pigmentosa and peripheral neuropathy). Renal presentation (tubulopathy) and transient renal failure were observed in 27% of patients. The diagnosis of FAO disorders is generally based on the plasma acylcarnitine profile determined by FAB-MS/MS from simple blood spots collected on a Guthrie card. Urinary organic acid profile and total and free plasma carnitine can also be very helpful, mostly in acute attacks. If there is no significant disturbance between attacks, the diagnosis is based upon a long-chain fatty acid loading test, fasting test, and in vitro studies of fatty acid oxidation on fresh lymphocytes or cultured fibroblasts. Treatment includes avoiding fasting or catabolism, suppressing lipolysis, and carnitine supplementation. The long-term dietary therapy aims to prevent periods of fasting and restrict long-chain fatty acid intake with supplementation of medium-chain triglycerides. Despite these therapeutic measures, the long-term prognosis remains uncertain.

BACKGROUND: Neonatal hyperinsulinemic hypoglycemia is often resistant to medical therapy and is often treated with near-total pancreatectomy. However, the pancreatic lesions may be focal and treatable by partial pancreatic resection. METHODS: We studied 52 neonates with hyperinsulinism who were treated surgically. The type and location of the pancreatic lesions were determined by preoperative pancreatic catheterization and intraoperative histologic studies. Partial pancreatectomy was performed in infants with focal lesions, and near-total pancreatectomy was performed in those with diffuse lesions. The postoperative outcome was determined by measurements of plasma glucose and glycosylated hemoglobin and by oral glucose-tolerance tests. RESULTS: Thirty neonates had diffuse beta-cell hyperfunction, and 22 had focal adenomatous islet-cell hyperplasia. Among the latter, the lesions were in the head of the pancreas in nine, the isthmus in three, the body in eight, and the tail in two. The clinical manifestations were similar in both groups. The infants with focal lesions had no symptoms of hypoglycemia and had normal preprandial and postprandial plasma glucose and glycosylated hemoglobin values and normal results on oral glucose-tolerance tests after partial pancreatectomy (performed in 19 of 22 neonates). By contrast, after near-total pancreatectomy, 13 of the patients with diffuse lesions had persistent hypoglycemia, type 1 diabetes mellitus developed in 8, and hyperglycemia developed in another 7; overall, only 2 patients with diffuse lesions had normal plasma glucose concentrations in the first year after surgery. CONCLUSIONS: Among neonates with hyperinsulinism, about half may have focal islet-cell hyperplasia that can be treated with partial pancreatectomy. These neonates can be identified through pancreatic catheterization and intraoperative histologic studies.

Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is the most frequent cause of hypoglycaemia in infancy. Clinical presentation is heterogeneous, with variable onset of hypoglycaemia and response to diazoxide, and presence of sporadic or familial forms. Underlying histopathological lesions can be focal or diffuse. Focal lesions are characterised by focal hyperplasia of pancreatic islet-like cells, whereas diffuse lesions implicate the whole pancreas. The distinction between the two forms is important because surgical treatment and genetic counselling are radically different. Focal lesions correspond to somatic defects which are totally cured by limited pancreatic resection, whereas diffuse lesions require a subtotal pancreatectomy exposing to high risk of diabetes mellitus. Diffuse lesions are due to functional abnormalities involving several genes and different transmission forms. Recessively inherited PHHI have been attributed to homozygote mutations for the beta-cell sulfonylurea receptor (SUR1) or the inward-rectifying potassium-channel (Kir6.2) genes. Dominantly inherited PHHI can implicate the glucokinase gene, particularly when PHHI is associated with diabetes, the glutamate dehydrogenase gene when hyperammonaemia is associated, or another locus.

Primary persistent hyperinsulinaemic hypoglycaemia of infancy is rare. Diazoxide treatment remains the mainstay of medical therapy in long-term management. We reviewed 77 cases of primary persistent hyperinsulinism in neonates and infants who were treated with diazoxide and studied criteria predictive of therapeutic efficacy. The only criterion identified was age at manifestation. All but 1 of the 31 neonatal cases were unresponsive to diazoxide. Responsiveness increased with age: 12 of 39 early-infantile cases, and all seven late-infantile cases were diazoxide-responsive. In responders, a diazoxide dose of 10-15 mg/kg per day was always effective, suggesting an "all or none" response. Diazoxide-resistant hyperinsulinism is characterized by its severity with higher plasma insulin levels. The analysis of 46 surgically treated patients showed that the efficacy of diazoxide is not related to the aetiology of the pancreatic lesions. In six cases, after many years of management, diazoxide treatment was stopped without recurrence of hypoglycaemia. CONCLUSION: Diazoxide is an efficient treatment in the long-term management of most persistent hyperinsulinaemic hypoglycaemia of infancy revealed in infants and children but is usually ineffective in neonatal forms. Drug efficacy does not correlate with anatomical lesions. Medical treatment can sometimes be stopped after many years of management without recurrence of disease manifestations.

AIMS: To determine whether the presence of abnormal B-cell nuclei predicts the existence of a focal or of a diffuse form of persistent neonatal and infantile hyperinsulinaemic hypoglycaemia in a series of 20 infants. METHODS AND RESULTS: Intra-operative frozen sections were performed on small specimens from the pancreatic head, isthmus and tail. In 13 cases, abnormal B-cell nuclei were identified, but even a near-total pancreatectomy was insufficient to cure some of these patients, in whom no focal lesion was detected. On the other hand, abnormal insular B-cell nuclei were not found in seven cases; based on the results of selective venous catheterization, a limited resection was performed, sufficient to cure each patient, and a focal adenomatous hyperplasia was found in each resected specimen. CONCLUSIONS: Intra-operative examination of small pancreatic specimens taken from the different parts of the gland allows one to determine the type of lesion (focal or diffuse) in neonatal onset hyperinsulinaemic hypoglycaemia, and to decide on the most appropriate surgical treatment.

Sporadic persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or nesidioblastosis is a heterogeneous disorder characterized by profound hypoglycemia due to inappropriate hypersecretion of insulin. An important diagnostic goal is to distinguish patients with a focal hyperplasia of islet cells of the pancreas (FoPHHI) from those with a diffuse abnormality of islets (DiPHHI) because management strategies differ significantly. 16 infants with sporadic PHHI resistant to diazoxide and who underwent pancreatectomy were investigated. Selective pancreatic venous sampling coupled with peroperative surgical examination and analysis of extemporaneous frozen sections allowed us to identify 10 cases with FoPHHI and 6 cases with DiPHHI. We show here that in cases of FoPHHI, but not those of DiPHHI, there was specific loss of maternal alleles of the imprinted chromosome region 11p15 in cells of the hyperplastic area of the pancreas but not in normal pancreatic cells. This somatic event is consistent with a proliferative monoclonal lesion. It involves disruption of the balance between monoallelic expression of several maternally and paternally expressed genes. Thus, we provide the first molecular explanation of the heterogeneity of sporadic forms of PHHI such that it is possible to perform only partial pancreatectomy, limited to the focal somatic lesion, so as to avoid iatrogenic diabetes in patients with focal adenomatous hyperplasia.

Maple syrup urine disease results in accumulation of leucine and its metabolites, which may lead in the long term to neurological dysfunction. In acute neonatal crises, large amounts of leucine may be removed by continuous venovenous haemofiltration. This extracorporeal technique has its risks and hazards, which increase with duration of treatment. We report three neonates in life-threatening conditions due to maple syrup urine disease, treated for not more than 12 h with various continuous venovenous techniques: continuous haemofiltration, haemodiafiltration and haemodialysis. The efficiency of and tolerance to these techniques was evaluated. For all three patients, plasma leucine levels decreased dramatically from 2186, 3818 and 2536 mumol/L to 1131, 1275 and 488 mumol/L, respectively. Leucine clearance obtained was 4.28 ml/min in haemodiafiltration. Their patients' neurological status improved rapidly and they have a normal developmental quotient at 22 months, 13 months, and 11 months of age, respectively. Tolerance was good except for hypothermia and drop in haematocrit in all cases. Haemodiafiltration management was more cumbersome and time consuming because it required continual adjustment of the substitution fluid flow rate to precisely balance inflow and outflow rates. We recommend continuous venovenous haemodialysis as the therapy of choice. It might be anticipated that improvement of this technique, by increasing dialysate flow rate and blood flow rate, will allow leucine concentration to be decreased below 1000 mumol/L within 6-8 h, whatever the initial level.

We report studies of four patients with pyruvate dehydrogenase complex (PDH) deficiency caused by mutations in the E1 alpha subunit. Two unrelated male patients presented with Leigh syndrome and a R263G missense mutation in exon 8. This mutation has previously been described in males with the same phenotype. The two other patients had different novel mutations: (1) an 8-bp deletion at the C-terminus (exon 11) was found in one allele of a young girl suffering from microcephaly and (2) a C88S missense mutation (exon 3) in a boy who only presented with motor neuropathy. These mutations were not found in the mothers of any of the four cases. Immunoblot analysis revealed decreased immunoreactivity for the E1 alpha and E1 beta subunits in three out of the four patients. These findings confirm that: (1) PDH deficiencies are genetically heterogeneous, (2) the R263G mutation is more frequent in male cases than are other mutations and this amino acid is a hot spot for gene mutations, (3) the last eight amino acids may be important for the conformation of the tetrameric E1-PDH enzyme, and (4) the amino acids at positions 88, 263 and 382-387 are essential for the linking of the alpha subunit with the beta subunit and for the activity of the holoenzyme.

A number of acquired conditions including infections, severe catabolic states, tissue anoxia, severe dehydration and poisoning can give rise to hyperlactacidaemia. All these causes should be ruled out before considering inborn errors of metabolism. Carefully collected samples are necessary if artefacts that result in spuriously increased lactate/pyruvate (L/P) and 3-hydroxybutyrate/acetoacetate (B/A) ratios are to be avoided. When properly performed, 24-h studies of L/P and B/A ratios provide a useful tool in making a diagnosis. A few metabolic profiles when present are specific or highly suggestive of a given disorder. When the L/P ratio is normal or low, pyruvate dehydrogenase (PDH) deficiency is highly probable whatever the lactate concentration, which is often only moderately elevated after meal, may be. When the L/P ratio is very high in association with post-prandial hyperketonaemia and in contrast to a normal or low B/A ratio, pyruvate carboxylase (PC) deficiency and alpha-ketoglutarate dehydrogenase (KGDH) deficiency are the most likely diagnoses. The distinction between the two disorders relies upon amino acid and organic acid profiles (glutamate and alpha-ketoglutarate accumulations in KGDH deficiency and hyperammonaemia and hypercitrullinaemia in PC deficiency). When both L/P and B/A ratios are elevated and associated with significant post-prandial hyperketonaemia, respiratory-chain disorders should first be suspected. All other profiles, especially a high L/P ratio without hyperketonaemia, are compatible with respiratory-chain disorders but are not specific; all acquired anoxic conditions should also be ruled out. Clearly, the clinical utility of these profiles needs to be interpreted cautiously in very ill patients in relation to the cardiocirculatory condition and to therapy. Finally, a normal profile, even after stress and loading, does not rule out an inborn error of lactate/pyruvate oxidation.

Four steps are required for the transport of long-chain fatty acids (LCFA) into the mitochondrial matrix : a plasma membrane carnitine transporter maintains the intracellular supply of carnitine ; an outer mitochondrial membrane carnitine palmitoyltransferase I (CPT I) converts acyl-CoA compounds to their acylcarnitine analogues ; a carnitine-acylcarnitine translocase (CATR) mediates the transmembrane transfer of acylcarnitines ; an inner mitochondrial membrane carnitine palmitoyltransferase II (CPT II) allows the re-esterification of acylcarnitines to form acyl-CoA esters. Inherited metabolic diseases affecting CATR and CPT II are recognized as a contributing cause of life-threatening events in infancy. In these two disorders, long-chain acylcarnitines are not efficiently converted to their corresponding acyl-CoA esters, and prominent long-chain acylcarnitine species are seen in plasma. It has been speculated that increased concentrations of long-chain acylcarnitines may promote cardiac arrhythmia (Corr et al 1989). Tandem mass spectrometry has enabled quantitative analysis of acylcarnitines in small volumes of blood, including filter paper blood spots used for neonatal screening (Millington et al 1991). Determination of the acylcarnitine profile in the Guthrie card is particularly useful in case of sudden infant death when no other biological specimen had been preserved. The finding of abnormal accumulation of C 18 and C 16 species argues in favour of CATR or profound CPT II deficiency. However, the definitive diagnosis of these two disorders requires documentation of the specific enzymatic defect in cellular material. Both defects are transmitted as autosomal recessive traits. The enzymatic activities of obligate heterozygotes are approximately 50% of normal activity (Stanley et al 1992; Elpeleg et al 1993). Thus, enzymatic determinations in parents' cells can be used to establish the diagnosis.

Studies of human pyruvate dehydrogenase (PDH) deficiency have shown that defects in the E1 component are not common, with only a small number of defects associated specifically with the E3, E2, and component X subunits. We report here clinical, enzymatic, and immune studies of the PDH complex (PDHc) in a girl presenting with a primary defect in the component X. The patient, born from nonconsanguineous parents, presented with severe neonatal lactic acidosis, minor facial dysmorphia, and complete corpus callosum agenesis. The metabolic profile revealed marked hyperlactatemia and hyperpyruvic acidemia, with a normal lactate/pyruvate ratio and no detectable ketosis or hyperammonemia. The activity of total PDHc in cultured skin fibroblasts and in fresh mononuclear cells was markedly decreased by about 80% as compared with the controls and with the parents.

Orthotopic liver transplantation (OLT) was performed in two patients with propionic acidaemia, a 7-year-old boy and a 9-year-old girl, diagnosed with a severe neonatal form with high risk of metabolic decompensation. In both cases the metabolic liver functions recovered within the 12 postoperative hours; no clinical symptoms of propionic acid toxicity, metabolic acidosis, severe hyperammonaemia, hyperglycinaemia or haematological abnormalities were observed. In both cases insulin-dependent diabetes mellitus occurred early after OLT (persisting in the boy's case). Severe post-transplantation complications were observed (acute rejection and CMV infection in both patients) which did not trigger metabolic decompensation. The boy developed chronic rejection and vanishing bile duct syndrome due to incomplete hepatic arterial thrombosis. He required permanent in-patient care with chronic hyperammonaemia and neurological sequelae involving the basal ganglia and died 15 months after OLT. The girl left hospital after 2 months and is presently leading a normal life with almost no dietary protein restriction (40 g protein per day). Urinary urea excretion and daily protein intake increased after liver transplantation. Propionyl- and tiglylglycine disappeared immediately after OLT. Urinary methylcitrate and 3-hydroxypropionate remained at concentrations corresponding to those before OLT. However, the total of all characteristic metabolites of organic acid analysis was reduced to 50-60% of the values before OLT in both patients. Propionylcarnitine was still detected at significant concentrations. Plasma odd-chain fatty acid concentrations decreased continuously after OLT only in the girl's case. Tissue of both transplanted livers showed increased odd-chain fatty acid concentrations 9 and 15 months after OLT, respectively, in both patients. We consider that at present OLT should only be performed in severe forms of propionic acidaemia.

A thermodynamically consistent Equation Of State (EOS) was developed to predict and analyse the behaviour of multiphase metals under shock wave loading. Assuming the Mie-Gruneisen hypothesis together with the Birch (for example) formulation, the EOS gives the relation between pressure P, temperature T and atomic volume V. Experimental data (P,V,T) for each phase are provided mainly by X-ray diffraction measurements with diamond anvil cells. In this work, mathematical tools are designed to optimize the determination of the EOS parameters and evaluate uncertainty. The general EOS form is y = f ϑ (x ) where y = P, x = (V,T) and ϑ is the parameter vector to calibrate. Using experimental data (x i ,y i ), the least square (non-linear) regression provides an optimal value ϑ∗ for the fit parameters. The measurement errors on y and x give biased estimation of ϑ∗ with the standard method. Assuming centered and known variance laws for the errors, a statistical procedure is proposed to estimate ϑ∗ and determine confidence intervals. Thanks to a Bayesian approach it is possible to introduce physical interval knowledge of the parameters in this procedure. Moreover, various EOS f ϑ∗ formulations are evaluated with a chi-squared type statistical test. The present method is applied on experimental data for multi phase tin (β and γ phases and liquid state) in order to provide an optimized multi-phase model. Furthermore, the method is used to design further experimental campaign and to evaluate the gain of new experimental data with the corresponding estimated errors.

Primary care plays a key role in the detection and management of depression and anxiety. At present it is not clear if the prevalence of depression and anxiety in primary care differs between migrants and ethnic minorities (MI) and natives and ethnic majorities (MA). A systematic review and a meta-analysis of studies comparing the prevalence of depression and anxiety in MI and MA in primary care were performed. Studies were identified by searching MEDLINE, PsychINFO, EMBASE and through hand-search. We included 25 studies, most of which had a relatively small sample size. Significant variations were found in the prevalence of anxiety and depression across studies. Pooled analyses were carried out for 23 studies, based on random-effects models. Pooled RR of depression and anxiety in MI were 1.21 (95% CI 1.04-1.40, p=0.012) and 1.01 (95% CI 0.76-1.32, p=0.971), with high heterogeneity (I²=87.2% and I²=73%). Differences in prevalence rates among studies can be accounted for by inclusion criteria, sampling methods, diagnostic instruments and study design. Further research on larger samples and with culturally adapted instruments is needed to estimate the prevalence of depression and anxiety in MI seeking help for these disorders.

Pyruvate dehydrogenase (PDH)-Elα deficiency has recently been studied at the molecular-genetic level. The gene is situated on the X chromosome. We report on an unusual mutation in a familial Elα deficiency. In fibroblasts, PDH deficiency was diagnosed in a young infant presenting with Leigh's encephalomyelopathy and in a maternal nephew with episodes of “malaises.” In the two affected children as well as their mothers we found a silent mutation in exon 6 of the PDH-Elα and an aberrant splicing of exon 6 in some of the cDNA clones. This case emphasizes the need for both genomic and cDNA analysis in cases where a PDH-Elα deficiency is strongly suspected.

Summary Methylmalonic and propionic acidaemias are rare metabolic disorders with an autosomal recessive mode of inheritance. A number of aminoacidopathies may have cutaneous manifestations, but these are usually absent in methylmalonic and propionic acidaemia. We have studied 38 children with propionic and methylmalonic acidaemia in the last 10 years at the Hôpital Necker-Enfants Malades. Thirteen had cutaneous manifestations: acute superficial scalded skin and superficial desquamation, bilateral and periorificial dermatitis, psoriasiform eruptions, and alopecia. The relative uniformity of these manifestations (scalded skin and desquamation after metabolic decompensation, chronic bilateral and periorificial dermatitis) suggests that methylmalonic and propionic acidaemias should be included in the category of aminoacidopathies with cutaneous manifestations. All these patients were suffering from severe forms of these diseases, with no residual enzyme activity, and they were all subjected to a very severe natural protein-restricted diet. These cutaneous manifestations may therefore either be part of a complex multideficiency syndrome, or be due to the enzyme deficiency itself.

[Departement_IRSTEA]EA [TR1_IRSTEA]TEPSA / ENERFRI; International audience; For some years, European regulation concerning refrigerating systems has become more and more severe. Because of their design and technology, refrigeration units cannot avoid refrigerant leaks, and can thus have a harmful impact on the environment. Many studies aimed at minimizing the charge in a refrigerating machine were thus developed. On a global level, reduction of refrigerant charges must not affect energy aspects while respecting environmental constraints [Montreal 1987, Kyoto 1997]. The architecture and refrigerant charge distribution in the systems are of particular importance; their analyses permit the determination of the target elements and thus define those in which the refrigerant charge could be reduced (heat exchangers, liquid pipes, receivers, .). This paper presents a review of the refrigerant charge studies in a refrigerating plant(methodologies of charge measurement, void fraction correlations and characteristic values for various technologies). It also evaluates the influence of the refrigerant charge on the coefficient of performance (COP) and on the cooling capacity. Finally, it inventories the different means that allow the charge in a refrigerating system to be minimized.; Depuis quelques années, la réglementation européenne concernant les systèmes frigorifiques devient de plus en plus sévère. En raison de leur conception et de leur technologie, les unités frigorifiques génèrent des fuites de fluide frigorigène, et peuvent ainsi avoir un impact nocif sur l'environnement. Beaucoup d'études ayant pour but de minimiser la charge dans une machine frigorifique ont donc été développées. Si on adopte une approche globale, la réduction de la charge en frigorigène doit conduire à respecter les contraintes environnementales sans affecter les performances énergétiques [Montréal 1987, Kyoto 1997]. L'architecture du système et la répartition de la charge sont essentiels; leurs analyses permettent de déterminer les éléments cibles et de définir ainsi ceux dans lesquels la charge pourrait être réduite (échangeurs de chaleur, conduites de liquide, réservoirs, .). Dans ce travail, nous présentons une synthèse des études sur la charge en frigorigène dans une installation frigorifique (méthodes de mesure de charge, corrélations de taux de vide, valeurs caractéristiques pour les diverses technologies); on évalue aussi l'influence de la charge sur le coefficient de performance (COP) et sur la puissance frigorifique. Enfin, on propose un inventaire des différents moyens qui permettent de minimiser la charge d'un système frigorifique.

Ammonia is channelled into the urea cycle by means of carbamoyl-phosphate synthetase (CPS I). This initial step of urea synthesis takes place in the mitochondria of the liver cell and is catalysed by N-acetylglutamate (NAGA), the physiological allosteric activator of CPS 1I(Grisolia and Cohen 1953). Carbamylglutamate (CG) has a structural analogy with NAGA. Exogenously administered NAGA is ineffective because it cannot enter the mitochondria and is rapidly deacylated in the cytosol (Reglero et al 1977). CG is able to cross the mitochondrial membranes and, in addition, is not inactivated by cytosolic acylases (Kim et al 1953). So far, the first (Schubiger et al 1991) and only use of carbamylglutamate has been in N-acetylglutamate synthetase deficiency. Treatment with CG in a kinetic variant or a partial deficit of CPS has been discussed (Guffon et al 1995 ; O'Conner et al 1985), but has never been clinically proven until now.

Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is the most frequent cause of hypoglycaemia in infancy. Clinical presentation is heterogeneous, with variable onset of hypoglycaemia and response to diazoxide, and presence of sporadic or familial forms. Underlying histopathological lesions can be focal or diffuse. Focal lesions are characterised by focal hyperplasia of pancreatic islet-like cells, whereas diffuse lesions implicate the whole pancreas. The distinction between the two forms is important because surgical treatment and genetic counselling are radically different. Focal lesions correspond to somatic defects which are totally cured by limited pancreatic resection, whereas diffuse lesions require a subtotal pancreatectomy exposing to high risk of diabetes mellitus. Diffuse lesions are due to functional abnormalities involving several genes and different transmission forms. Recessively inherited PHHI have been attributed to homozygote mutations for the beta-cell sulfonylurea receptor (SUR1) or the inward-rectifying potassium-channel (Kir6.2) genes. Dominantly inherited PHHI can implicate the glucokinase gene, particularly when PHHI is associated with diabetes, the glutamate dehydrogenase gene when hyperammonaemia is associated, or another locus.

Background and aims:We describe the transcultural working method of the Bologna Multiethnic Mental Health Centre (University of Bologna, Italy). The team is composed by psychiatrists, psychologists, anthropologists, social workers and cultural mediators. The main approach is psychotherapy by means of group setting, which is used as for counselling as for longer and more structured psychotherapy.Methods:We carried out a chart review and clinician survey of social, clinical, and service use characteristics of all immigrant patients from 1999 through 2006. We also fulfilled the AMDP -SYSTEM (Manual for the Assessment and Documentation of Psychopathology) for all these patients.Results:A total of 135 clinic patients was followed up during this period. Most of these patients came from North Africa (32%) and Subsaharian Africa (25%) for financial purposes and 70% were in Italy for less than 10 years. More than ¼ are undocumented. One third of the patients were affected by adjustment disorders, an other third by psychotic disorders and the last third by depression or anxiety disorders. Group setting and helping relation have shown transcultural efficacy, especially during the first period after migration, on psychopathology and adjustment's abilities. This method was effective among every ethnic and diagnostic groups, except for cases in which cultural components, preceding migration, were responsible of suffering.Conclusions:Starting from therapeutic efficacy of our model, we propose that immigrants psychological distress in Italy is mainly due to cultural shock and role identification loss.

We study the mixing of two gases of different densities arising from the shock wave-induced Richtmyer-Meshkov instability (RMI). The RMI appears when a shock wave impulsively accelerates two gases separated by an interface generally parallel to the shock plane but presenting small perturbations. The RMI is a manifestation of the baroclinic instability: the production of voracity is proportional to the vector product of pressure gradient of the shock and the density gradient of the interface. It leads to an amplification of the interface perturbations, hence to the interpenetration of the two gases and eventually to the formation of a turbulent mixing zone. We seek to characterize the turbulent stage of the RMI in order to improve the modelization of this phenomenon. Measurements of mixing zone thickness and density profiles have already been performed in discontinuous heavy-light interfaces, where such a stage is observed [1] (see also the book of abstracts). Now, we try more direct measurements of turbulence, using laser Doppler velocimetry (LDV).

A retrospective study was performed on the clinical outcome and long-term treatment of 17 patients with propionic acidaemia diagnosed during the last 20 years in our hospital. The study group consisted of 12 patients with early onset type of disease and 5 patients with late onset. Seven (41%) patients died, five with early onset and two with late onset. The deceased early onset patients had a median survival of 0.4 years while the deceased late onset patients died at the age of 2.8 and 4 years respectively. Median age of the living early onset patients was 5.2 (1-9.25) years, the late onset patients were 4, 7 and 23 years old. Patients were all treated with natural protein restriction and in most cases carnitine and metronidazole were added. The early onset patients were almost all treated with daily home tube feeding. The mean natural protein intake of early onset patients (6.3 +/- 1.5 g/day) was significantly lower than the natural protein intake of late onset patients (17.6 +/- 5.3 g/day). Supplemental protein intake was higher in early onset patients. The general neurological outcome of our study group was satisfactory with a better outcome for early onset patients. As to growth, many patients showed a failure to thrive, this was particularly for height. The strong protein restriction during the first years of life probably contributed to this.The prognosis for patients with propionic acidaemia appeared to be satisfactory in terms of survival and outcome characteristics such as neurological and mental development. Despite these results the authors feel that the prognosis and quality of life of these patients might be improved with liver transplantation or possibly somatic gene therapy in the future.

Peroxisomal deficiency disorders, which are genetically transmitted, are assumed to be expressed in all cells, and the use of cultured skin fibroblasts for diagnosis and research is based on this assumption. We describe three patients with clinical, biochemical, and microscopic evidence of a peroxisomal disorder. However, their liver displays mosaicism, i.e., parenchymal cells with peroxisomes are adjacent to cells without peroxisomes. Ten percent (volume), 8%, and less than 1% of the parenchyma possessed peroxisomes that can be identified in immunocytochemical tests for six matrix and membrane proteins performed by light and electron microscopy. In the bulk of the parenchyma, catalase is localized in the cytoplasm, and in such cells no peroxisomes are evident by electron microscopy and immunolabeling for the 43-kd peroxisomal membrane protein (PMP) in two patients; in the third case, peroxisomal membrane ghosts are present. Immunoblots of peroxisomal beta-oxidation enzymes show a pattern similar to that from patients with a generalized peroxisomal deficiency. In contrast to the clinical and biochemical signs of peroxisomal dysfunction and hepatic histopathology, cultured fibroblasts from two patients demonstrate normal peroxisomal functions, including very-long-chain fatty acid oxidation and plasmalogen synthesis.

At least 21 genetic disorders have now been found that are linked to peroxisomal dysfunction. Whatever the genetic defect might be, peroxisomal disorders should be considered in various clinical conditions, dependent on the age of onset. The prototype of peroxisomal disorders is represented by 'classical' Zellweger syndrome (ZS) which is the most severe disorder combining all the characteristic symptoms. ZS is characterized by the association of errors of morphogenesis, severe neurological dysfunction, neurosensory defects, regressive changes, hepatodigestive involvement with failure to thrive, usually early death, and absence of recognizable liver peroxisomes. Other peroxisomal disorders (pseudo-Zellweger syndrome, neonatal adrenoleukodystrophy (NALD), pseudo-neonatal adrenoleukodystrophy, rhizomelic chondrodysplasia punctata (RCDP), and hyperpipecolic acidaemia) share some of these symptoms, but with varying organ involvement, severity of dysfunction, and duration of survival. The diagnosis should not cause difficulty when all the characteristic manifestations are present. Depending on the main presenting sign, peroxisomal disorders in neonates should be suspected in two categories of circumstances: polymalformative syndrome with craniofacial dysmorphism, and severe neurological dysfunction. During the first 6 months of life, the predominant symptoms may be hepatomegaly, prolonged jaundice, liver failure, anorexia, vomiting and diarrhoea leading to failure to thrive resembling a malabsorption syndrome; severe psychomotor retardation, hearing loss and ocular abnormalities become evident. Beyond 4 years of age, behavioural changes, intellectual deterioration, visual impairment and gait abnormalities may be the presenting symptoms. Independently of the clinical symptoms and age of onset, most peroxisomal disorders described so far can be clinically screened by recordings of electroretinogram, visual-evoked responses, and brain auditory-evoked responses, which are almost always abnormal. Nine of the 17 peroxisomal disorders with neurological involvement are associated with an accumulation of very long-chain fatty acids (VLCFA), which suggests that assay of plasma VLCFA should be used as a primary test. However, assays of plasma phytanic acid and plasma/urine bile acid intermediates should also be performed in view of the recent reports of atypical chondrodysplasia variants (without rhizomelic shortening) and isolated trihydroxycholestanoic aciduria. The differential diagnoses in various clinical conditions and age periods are discussed.

Peroxisomal deficiency disorders, which are genetically transmitted, are assumed to be expressed in all cells, and the use of cultured skin fibroblasts for diagnosis and research is based on this assumption. We describe three patients with clinical, biochemical, and microscopic evidence of a peroxisomal disorder. However, their liver displays mosaicism, i.e., parenchymal cells with peroxisomes are adjacent to cells without peroxisomes. Ten percent (volume), 8%, and less than 1% of the parenchyma possessed peroxisomes that can be identified in immunocytochemical tests for six matrix and membrane proteins performed by light and electron microscopy. In the bulk of the parenchyma, catalase is localized in the cytoplasm, and in such cells no peroxisomes are evident by electron microscopy and immunolabeling for the 43-kd peroxisomal membrane protein (PMP) in two patients; in the third case, peroxisomal membrane ghosts are present. Immunoblots of peroxisomal β-oxidation enzymes show a pattern similar to that from patients with a generalized peroxisomal deficiency. In contrast to the clinical and biochemical signs of peroxisomal dysfunction and hepatic histopathology, cultured fibroblasts from two patients demonstrate normal peroxisomal functions, including very-long-chain fatty acid oxidation and plasmalogen synthesis.

We performed a retrospective study of all patients with methylmalonic acidemia diagnosed during the past 20 years. Only those patients who were nonresponsive to vitamin B12 in vivo and in vitro were included. The final study group consisted of 26 patients, of whom 16 had a neonatal (early) onset; in 10 patients the diagnosis was made after 2 months to 2.2 years (late onset). Of the early-onset patients, 14 (87%) died, with a mean survival time of 1.5 years (range, 10 days to 2.5 years), whereas four of the late-onset patients (40%) died (range, 1.2 to 15 years). At present, eight patients are alive; their mean age is 4.6 years (range, 1 to 10 years). In the early 1970s, treatment was based on the principles of treating patients with phenylketonuria: restricting natural protein intake and supplementing essential amino acids, vitamins, and trace elements. After about 1980, nasogastric tube feeding became a mainstay of the therapy, natural protein restriction became stricter, and the use of essential amino acid mixtures diminished. Carnitine was added to the therapy and, in later years, metronidazole. Since these changes were implemented, the number of episodes of metabolic decompensation and hospitalizations has decreased. Mean survival time of the patients, in particular those with early onset, has only slightly improved, partly because of psychosocial problems in many of these families. Almost all the patients, especially those with early onset, had some degree of neurologic impairment and mental retardation, and many patients were at less than 2 SD for weight or height or both. In contrast, the neurologic and mental status of the late-onset patients was frequently normal, and their weight and height were more often within normal limits. Our results show that the treatment of methylmalonic acidemia still poses considerable problems; despite intense medical efforts and familial stress, the prognosis for the early-onset patients is disappointing. The patients with late-onset disease, however, appear to have a fairly good prognosis with the present therapeutic approach. Liver transplantation or possibly genetic therapy might improve our results in the future.