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In order to ensure the quality and the relevance of irradiation programs in the future Jules Horowitz Reactor (JHR), the French Alternative Energies and Atomic Energy Commission (CEA) has significantly increased its research and development effort in the field of in-pile instrumentation during the last decade. Major progress has been achieved in the capability to perform accurate in-pile measurements using reliable and updated techniques. A significant part of this effort has been conducted in the framework of the Joint Instrumentation Laboratory between the CEA and the Belgian Nuclear Research Centre (SCK $\cdot$ CEN). In order to improve measurement techniques for neutron flux assessment, a unique system for online measurement of fast neutron flux has been developed and recently qualified in-pile. The fast-neutron-detection-system (FNDS) has been designed to monitor accurately high-energy neutron flux (E > 1 MeV) in typical material testing reactor (MTR) conditions, where neutron flux levels can be as high as $10^{15}\,\,\text {N}\cdot \text {cm}^{-2}\cdot \text {s}^{-1}$ and are generally dominated by thermal neutrons. Moreover, the neutron flux is coupled with a high gamma flux of typically a few $10^{15} \gamma \cdot \text {cm}^{-2}\cdot \text {s}^{-1}$ , which can be highly disturbing for the online measurement of neutron fluxes. The patented FNDS system is based on two detectors allowing the simultaneous detection of both thermal- and fast-neutron flux. Thermal neutrons can be measured using a self-powered neutron detector or a 235U miniature fission chamber, while fast neutron detection requires a miniature fission chamber with a special fissile material presenting an energy threshold near 1 MeV, which can be 242Pu for MTR conditions. Fission chambers are operated in Campbelling mode for an efficient gamma rejection. FNDS also includes a specific software that processes measurements to compensate online the fissile material depletion and to adjust the sensitivity of the detectors, in order to produce a precise evaluation of both thermal and fast neutron flux even after long-term irradiation. FNDS has been validated through a two-step experimental program. A first set of tests was performed at BR2 reactor operated by SCK $\cdot$ CEN in Belgium. Two FNDS prototypes were operated in-pile during nearly 1000 h. These tests exhibited the consistency of the measurement of thermal to fast neutron flux ratio with Monte Carlo neutron and photon transport calculations, as well as the right compensation of fissile material depletion. This paper describes a second test recently completed at ISIS reactor operated by CEA in France. For this irradiation, FNDS signal was compared to reference thermal- and fast-neutron flux measurements using activation dosimeters analyzed under COFRAC Quality Certification. During this latter test, FNDS proved its ability to measure online the fast neutron flux with an overall accuracy better than 5%. FNDS is now operational and is assumed to be the first and unique acquisition system able to provide an online measurement of the fast neutron flux in MTR conditions. This system will be used to perform spectral neutron characterization of JHR channels, but it may also be implemented in future irradiation experiments, for a better and real-time evaluation of the fast neutron flux received by material and fuel samples.

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Neutron and gamma flux levels are key parameters in nuclear research reactors. In Material Testing Reactors, such as the future Jules Horowitz Reactor, under construction at the French Alternative Energies and Atomic Energy Commission (CEA Cadarache, France), the expected gamma flux levels are very high (nuclear heating is of the order of 20 W/g at 100 MWth). As gamma rays deposit their energy in the reactor structures and structural materials it is important to take them into account when designing irradiation devices. There are only a few sensors which allow measurements of the nuclear heating [12]; a recent development at the CEA Cadarache allows measurements of the gamma flux using a miniature ionization chamber (MIC) [3]. The measured MIC response is often compared with calculation using modern Monte Carlo (MC) neutron and photon transport codes, such as TRIPOLI-4 and MCNP6. In these calculations only the production of prompt gamma rays in the reactor is usually modelled thus neglecting the delayed gamma rays. Hence calculations and measurements are usually in better accordance for the neutron flux than for the gamma flux. In this paper we study the contribution of delayed gamma rays to the total MIC signal in order to estimate the systematic error in gamma flux MC calculations. In order to experimentally determine the delayed gamma flux contributions to the MIC response, we performed gamma flux measurements with CEA developed MIC at three different research reactors: the OSIRIS reactor (MTR — 70 MWth at CEA Saclay, France), the TRIGA MARK II reactor (TRIGA — 250 kWth at the Jozef Stefan Institute, Slovenia) and the MARIA reactor (MTR — 30 MWth at the National Center for Nuclear Research, Poland). In order to experimentally assess the delayed gamma flux contribution to the total gamma flux, several reactor shut down (scram) experiments were performed specifically for the purpose of the measurements. Results show that on average about 30 % of the MIC signal is due to the delayed gamma rays. In this paper we describe experiments in each of the three reactors and how we estimate delayed gamma rays with MIC measurements. The results and perspectives are discussed.

Diabet. Med. 29, 1047–1054 (2012) Background Decreased function of the exocrine pancreas is frequent in patients with diabetes. Our aim was to investigate clinical correlates of pancreatic exocrine failure in patients with diabetes. Patients and methods We investigated exocrine function by assaying both elastase-1 concentration and chymotrypsin activity in 667 patients. We conducted separate analysis on patients with Type 1 diabetes and patients with Type 2 diabetes. Patients were separated into three groups according to whether both elastase-1 concentration and chymotrypsin activity were normal, or one or both were altered. Results A total of 667 consecutive patients were analysed, including 195 with Type 1 and 472 with Type 2 diabetes. Elastase-1 concentration was 200 μg/g and chymotrypsin activity > 6U/g. One test was below threshold in 19%, both in 15%. In patients with Type 1 diabetes, the three groups defined by results of elastase-1 concentration and chymotrypsin activity differed with regard to duration of diabetes and prevalence of glutamic acid decarboxylase antibodies, but not BMI or HbA1c, or prevalence of retinopathy, neuropathy, nephropathy or vascular disease. In patients with Type 2 diabetes, the three groups differed with regard to BMI, use of insulin and vascular disease, but not known duration. Conclusion Factors associated with pancreatic exocrine failure differ in patients with Type 1 diabetes compared with patients with type 2 diabetes. In patients with Type 2 diabetes, association of decreased pancreatic exocrine function with BMI and vascular disease suggests a role of pancreatic arteriopathy.

Background & Aims: Tube feeding, recommended for patients with short bowel syndrome in only the postoperative period, has not been compared with oral feeding for absorption. We studied whether tube feeding increased absorption in patients with short bowel syndrome following the postoperative period. Methods: A randomized crossover study compared absorption between isocaloric tube feeding and oral feeding in 15 short bowel syndrome patients more than 3 months after short bowel constitution. An oral feeding period combined with enriched (1000 kcal ● day 1 ) tube feeding was also tested. We measured the net intestinal absorption rates of proteins, lipids, and total calories using elemental nitrogen, Van de Kamer, and bomb calorimetry methods, respectively. Results: Tube feeding increased the mean (SD) percent absorption (P < .001) of proteins (72% 13% vs 57% 18%), lipids (69% 25% vs 41% 27%), and energy (82% 12% vs 65% 16%) compared with oral feeding. In the group given the combined feedings (n 9), the total enteral intake and net percent absorption increased (P < .001) for proteins (67% 10%), lipids (59% 19%), and total energy (75% 8%) compared with oral feeding. Absorption (kcal ● day 1 ) was greater (P < .001) with tube (2225 457) and combined feedings (2323 491) than with oral feeding (1638 458). Conclusions: In patients with short bowel syndrome, continuous tube feeding (exclusively or in conjunction with oral feeding) following the postoperative period significantly increased net absorption of lipids, proteins, and energy compared with oral feeding.

Resume Depuis 1994, la qualite dans les laboratoires de biologie medicale est definie par decret dans le Guide de Bonne Execution des Analyses (GBEA). Les contraintes propres a la coprologie rendent difficiles l’application de certains points du GBEA. En particulier, aucun controle de qualite n’est disponible dans ce domaine. Or la matrice fecale est complexe, heterogene et variable en fonction des pathologies, des interventions chirurgicales, de l’alimentation et des therapeutiques. Les controles de qualite seriques du commerce ne permettent pas de mettre en evidence les interferences analytiques liees a un effet matrice. Ceci nous a conduit a developper notre propre controle de qualite a partir d’un melange de selles de patients lyophilisees pour ameliorer l’assurance de qualite de la phase analytique. Les techniques utilisees en coprologie sont manuelles ou semi-automatisees et impliquent une phase pre-analytique qui n’est pas toujours prise en compte par les controles de qualite. Une approche semi-quantitative par analyse microscopique des selles est donc couplee au dosage. Cela constitue un temoin interne pour chaque echantillon. La demarche qualite est poursuivie au niveau post-analytique : les analyses sont confrontees entre elles et remises dans le contexte clinique et therapeutique du patient. La mise en œuvre de l’ensemble des outils decrits precedemment assure la fiabilite des resultats rendus et permet le suivi a long terme d’un patient.

Resume La recherche de sang dans les selles reste l’examen le plus prescrit en coprologie, essentiellement dans le cadre du depistage du cancer colorectal, et le developpement de techniques immunologiques permet une nette amelioration de la specificite de ces tests comparativement aux techniques chromogeniques classiques. Une nouvelle voie de travail s’oriente aujourd’hui vers l’exploitation de l’ADN isole a partir des selles. Un autre domaine phare du developpement des marqueurs coprologiques est represente par les pathologies a composante inflammatoire. Le dosage du TNFα et celui de la calprotectine, proteine issue de la degranulation des polynucleaires neutrophiles, sont maintenant proposes comme marqueurs discriminants des maladies « organiques » de l’intestin et pour evaluer le degre d’infiltration inflammatoire de la muqueuse digestive. Enfin, concernant le diagnostic des syndromes de maldigestion/malabsorption, le dosage de l’elastase fecale a represente un reel progres pour le depistage et l’evaluation des insuffisances pancreatiques exocrines. Le developpement de marqueurs fecaux non invasifs, est donc un secteur en rapide evolution car il presente l’interet de fournir des informations objectives portant sur l’ensemble du tube digestif qui seront importantes pour selectionner les patients necessitant des investigations complementaires ou pour suivre l’efficacite des therapeutiques, tant chez l’adulte que chez l’enfant.

Fecal analysis includes qualitative and quantitative studies which allows quantification and labelling of numerous pathophysiologic phenomenona. Malabsorption and over-absorption of water and electrolytes give rise to six types of watery diarrheas, and two types of constipations; malabsorption of nutriments and maldigestion of food, give rise to two types of fatty and nitrogenous diarrheas with metabolic consequences. Fecal analysis often discriminates organic from non-organic diseases and brings informations on increase or decrease of caloric losses, to the nutritionist. Microscopic observations which requires a high degree of competence and experience, allows the recognition of malabsorption/maldigestion phenomenona, of fortuitous presence of parasites and a good interpretation of a fecal file.

Cryptosporidium parvum infection induces amino acid malnutrition leading to growth retardation in children. Owing to the nutritional efficiency of peptides compared to free amino acids and the resistance of the di-tripeptide transporter PepT1 to mucosal injury, we analyzed the intestinal expression of PepT1 during experimental acute cryptosporidiosis in suckling rats from day 4 to day 50. PepT1 mRNA levels were increased at the peak of infection (day 10) all along the small intestine and normalized after spontaneous clearance of the parasite (day 21). Immunolocalization of PepT1 showed that its expression was maintained in the brush border membrane of enterocytes in infected rats from day 4 to day 50 all along the small intestine. Our results suggest a transcriptional up-regulation during acute cryptosporidiosis in response to both C. parvum-induced malnutrition and parasite implantation. As no treatment is available, a semi-elemental diet should be considered part of the treatment of cryptosporidiosis.

The importance of B-isoform of leptin receptor (LEPR-B) signaling in the hypothalamus, pancreas, or liver has been well characterized, but in the intestine, a unique site of entry for dietary nutrition into the body, it has been relatively ignored. To address this question, we characterized a mouse model deficient for LEPR-B specifically in intestinal epithelial cells (IECs). IECLEPR-B-knockout (KO) and wild-type (WT) mice were generated by Cre-Lox strategy and fed a normal or high-fat diet (HFD). The analyses of the animals involved histology and immunohistochemistry of intestinal mucosa, indirect calorimetric measurements, whole-body composition, and expression and activities of nutrient transporters. IECLEPR-B-KO mice exhibited a 2-fold increase in length of jejunal villi and have normal growth on a normal diet but were less susceptible (P

In the present study. we explored the nutritional consequences of cryptosporidiosis. In order to ascertain the direct responsibility of C. parvum for impairment of staturoponderal development observed during the infection in neonatal animals, we investigated the absorption of two major components of the total amino acids in dam's milk (leucine and glutamate) across the ileal mucosa. The infection resulted in significant (47% and 34%, respectively) reductions in leucine and glutamate fluxes (P

We found that the magnesium salt of ilimaquinone, named 201-F, specifically disassembled dynamically unstable microtubules in fibroblasts and various epithelial cell lines. Unlike classical tubulin- interacting drugs such as nocodazole or colchicine which affect all classes of microtubules, 201-F did not depolymerize stable microtubules. In WIF-B–polarized hepatic cells, 201-F disrupted the Golgi complex and inhibited albumin and alpha1-antitrypsin secretion to the same extent as nocodazole. By contrast, 201-F did not impair the transport of membrane proteins to the basolateral surface, which was only affected by the total disassembly of cellular microtubules. Transcytosis of two apical membrane proteins—the alkaline phosphodiesterase B10 and dipeptidyl peptidase IV—was affected to the same extent by 201-F and nocodazole. Taken together, these results indicate that only dynamically unstable microtubules are involved in the transport of secretory proteins to the plasma membrane, and in the transcytosis of membrane proteins to the apical surface. By contrast, stable microtubules, which are not functionally affected by 201-F treatment, are involved in the transport of membrane proteins to the basolateral surface. By specifically disassembling highly dynamic microtubules, 201-F is an invaluable tool with which to study the functional specialization of stable and dynamic microtubules in living cells.

There is a paucity of data available on small intestinal bacterial overgrowth (SIBO) in systemic sclerosis (SSc). The objectives of the study were to estimate the prevalence of SIBO in SSc patients exhibiting intestinal symptoms and identify patients at risk of SIBO regarding clinical and biological presentations and gastrointestinal symptoms captured by standardized questionnaires.Between 2011 and 2012, patients exhibiting intestinal complaints underwent glucose H2/CH4 breath tests (BT) and blood assays. They were interviewed using the University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument 2.0 (UCLA SCTC GTI) and the Short Form-36 (SF-36). For patients diagnosed with SIBO, BT was repeated 1 to 4 months after the end of antibiotics.Among 120 consecutive patients, 37 patients (29 women) exhibiting intestinal complaints were included (median age: 60 years). Fourteen patients (38%) were diagnosed with SIBO; patients from this subset had a longer disease duration (p=0.02), a significant weight loss within the past 6 months (p=0.03) and a higher total UCLA SCTC GTI score (p=0.03). The SF-36 assessment was not discriminant. Among the 14 patients treated for SIBO, 6 had a negative control BT, 4 remained positive, 2 failed to repeat the test and 2 patients died due to severe chronic malabsorption.SIBO is a not uncommon, late onset, severe and not easy to treat complication of SSc. Higher UCLA SCTC GTI score and weight loss appeared to be strongly associated with SIBO.

Clostridium difficile infection is a leading cause of antibiotic-related and healthcare-related diarrhoea. In the past decade, faecal microbiota transplantation or transfer has attracted increasing interest as an effective treatment strategy for severe recurrent C. difficile infection, with a global success rate of >80%. However, experience with this procedure is limited by a lack of randomized trials supporting its efficacy and the lack of standardization of the procedure. This review will address the practical aspects of the protocol.

Background: Calprotectin, a major component of soluble cytosolic proteins in human neutrophil granulocytes, is excreted in excess in stools during inflammatory bowel disease in adults and children. Faecal calprotectin concentrations are also higher during the first year of life than in adults. Objectives: To measure faecal calprotectin concentrations in the neonatal period and define reference values according to the mode of feeding: standard infant formula, prebiotic infant formula (Calisma, Bledina SA, France), or breast feeding. Patients and methods: A prospective study was carried out over three months in 69 full term, healthy newborns with a median gestational age of 39.8 weeks (range 37–41.5) and a birth weight of 3300 g (range 2600–4460). Three groups were formed depending on the mode of feeding: group 1 (n = 18) received a standard infant formula, group 2 (n = 19) the prebiotic infant formula, and group 3 (n = 32) was breast fed. One stool sample was taken from each newborn on day 4 (3–7), and faecal calprotectin analysed using a commercial enzyme linked immunoassay (Calprest, Eurospital, Italy). Results: Faecal calprotectin concentrations (median 167 µg/g) were higher than reference values in healthy adults. The concentration was below the upper reference limit for adults (50 µg/g) for three infants only, one fed the standard formula and two fed the prebiotic formula. Concentrations did not differ significantly according to method of feeding. Conclusions: Compared with healthy adults, newborns have high calprotectin concentrations in the first days of life. There is no obvious influence of the mode of feeding.

Decreased function of the exocrine pancreas is frequent in patients with diabetes. Our aim was to investigate clinical correlates of pancreatic exocrine failure in patients with diabetes.We investigated exocrine function by assaying both elastase-1 concentration and chymotrypsin activity in 667 patients. We conducted separate analysis on patients with Type 1 diabetes and patients with Type 2 diabetes. Patients were separated into three groups according to whether both elastase-1 concentration and chymotrypsin activity were normal, or one or both were altered.A total of 667 consecutive patients were analysed, including 195 with Type 1 and 472 with Type 2 diabetes. Elastase-1 concentration was200 μg/g in 23% of the patients. Chymotrypsin activity was6 U/g in 26% of the patients. In 66% of the patients elastase-1 concentration was200 ug/g and chymotrypsin activity6 U/g. One test was below threshold in 19%, both in 15%. In patients with Type 1 diabetes, the three groups defined by results of elastase-1 concentration and chymotrypsin activity differed with regard to duration of diabetes and prevalence of glutamic acid decarboxylase antibodies, but not BMI or HbA(1c) , or prevalence of retinopathy, neuropathy, nephropathy or vascular disease. In patients with Type 2 diabetes, the three groups differed with regard to BMI, use of insulin and vascular disease, but not known duration.Factors associated with pancreatic exocrine failure differ in patients with Type 1 diabetes compared with patients with type 2 diabetes. In patients with Type 2 diabetes, association of decreased pancreatic exocrine function with BMI and vascular disease suggests a role of pancreatic arteriopathy.

Previous works on pressurized water reactors show that the nitrogen 16 activation product can be used to measure thermal power. Power monitoring using a more stable indicator than ex-core neutron measurements is required for operational sodium-cooled fast reactors, in order to improve their economic efficiency at the nominal operating point. The fluorine 20 and neon 23 produced by (n,α) and (n,p) capture in the sodium coolant have this type of convenient characteristic, suitable for power measurements with low build-up effects and a potentially limited temperature, flow rate, burn-up and breeding dependence. This method was tested for the first time during the final tests program of the French Phénix sodium-cooled fast reactor at CEA Marcoule, using the ADONIS gamma pulse analyzer. Despite a non-optimal experimental configuration for this application, the delayed gamma power measurement was pre-validated, and found to provide promising results.

This work deals with the final qualification of the IRINA in-core neutron flux measurement system in the MTR OSIRIS reactor. A specific irradiation device has been set up to validate the last changes in the complete system (electronic, transmitting cable and monitor). Experimental results shows the IRINA measurement system meet entirely the in-core reactor conditions requirements: a thermal neutron flux from 107 n.cm−2.s−1 up to 1014 n.cm−2.s−1 and a temperature of 300°C during a minimum operating time of 1000 hours.

Fecal pancreatic elastase determination is of routine use in infant population presenting with a neonatal diagnosis of cystic fibrosis and in those with poor weight gain and growth, in order to precociously detect pancreatic insufficiency. However, there are few data regarding the value of one spot measure of elastase to assess pancreatic status in this population. This retrospective study reports the follow-up of fecal elastase measurement in 236 infants during the 2 first years of life.Fecal elastase was over 200 microg/g (i.e. normal cut-off) in a first sample in 122 patients (51.7% of patients) and below 200 microg/g in the remaining 114 patients. An alteration of elastase concentration was then observed in 18/122 infants (14.8%), leading to the diagnosis of pancreatic insufficiency at the end of the follow-up. In contrast, a normalization of fecal elastase was observed in 52 (45.6%) infants presenting with a first measurement below normal cut-off.This study shows that special attention should be given to the analysis of fecal elastase concentrations in infants as a precocious diagnosis of pancreatic insufficiency is crucial for the early introduction of a pancreatic enzyme replacement therapy which will prevent further consequence of malabsorption. One spot measure does not totally exclude pancreatic insufficiency in this population and a further control measurement of fecal elastase may be necessary.

Fecal analysis includes qualitative and quantitative studies which allows quantification and labelling of numerous pathophysiologic phenomenona. Malabsorption and over-absorption of water and electrolytes give rise to six types of watery diarrheas, and two types of constipations; malabsorption of nutriments and maldigestion of food, give rise to two types of fatty and nitrogenous diarrheas with metabolic consequences. Fecal analysis often discriminates organic from non-organic diseases and brings informations on increase or decrease of caloric losses, to the nutritionist. Microscopic observations which requires a high degree of competence and experience, allows the recognition of malabsorption/maldigestion phenomenona, of fortuitous presence of parasites and a good interpretation of a fecal file.

Quality control in medical laboratories was defined in guidelines for good execution of laboratory analyses issued by the French health authorities in 1994. Application of these guidelines is difficult in coprology because the sample is a complex heterogeneous matrix which varies with disease, surgery, food intake, and treatment. In addition, commercial quality control kits are not available for stool biochemical analyses and a national quality control program has not been established. We thus developed our own fecal quality control technique using pooling lyophylized stool samples. Manual or partially automated methods are used in coprology, leading to a long pre-analysis phase which is not always taken into account in quality control. This implies the need for complementary tools to insure the quality of coprology analyses. For example, semi-quantitative microscopic lipid analysis can be used as an internal standard for a given specimen. Quality assurance also involves a post-analytical phase where results obtained for a given specimen are compared with other available data and interpreted in light of the patient's clinical and therapeutic status. This quality assurance strategy enables accurate reliable results useful for long-term patient management.

Fecal occult blood testing is the most widely prescribed screening test for colorectal cancer. Recent development of immunological tests has increased specificity. Fecal DNA analysis opens up a new field for early detection of this widespread neoplasia. Inflammatory bowel disease is another important area where the development of fecal markers provides an interesting alternative to the gold standard but costly and invasive endoscopic investigations with histological analysis of biopsy specimens. Fecal TNFalpha and calprotectin can now be proposed to distinguish organic from non-organic intestinal disease, so select candidates for further investigations, and to assess disease activity. Measurement of fecal elastase provides real progress in screening for exocrine pancreatic insufficiency in patients with malabsorption syndrome. The development of non-invasive fecal markers is thus of increasing interest, providing data about the entire gastrointestinal tract useful for screening and individual patient management.

In order to assess the impact of Cryptosporidium parvum on host intestinal physiology, we investigated absorption of the two principal amino acids in dam′s milk (leucine, glutamate), using Ussing chambers and RT-PCR analyses. Experiments were performed in both heavily (ileum) and mildly (duodenum) infected segments of the small intestine at the peak of infection [day 8 post-infection (PI)] and after spontaneous clearance of the parasite (day 17 PI). At day 8 PI, amino acid fluxes across the mucosa were decreased throughout the small intestine (P

Cryptosporidiosis is an important cause of diarrhea associated with growth retardation in children and severe malnutrition in immunocompromised patients. The pathophysiology is poorly understood. In the suckling rat model, we show that C. parvum infection impairs net electrogenic transport across the ileal mucosa without involvement of prostaglandins, as well as trans- and paracellular permeability and leucine and glutamate absorption. These results provide evidence for the development of an intestinal malabsorptive syndrome during cryptosporidiosis. Unspecific process such as villous atrophy and inflammatory cytokines secretion should be regarded as possible mediators of this syndrome. However, specific mechanisms have to be considered since C. parvum induces a rearrangement of the host enterocyte cytoskeleton which might impaired intracellular trafficking thus reducing the membrane expression of nutrient transporters. Infection and malnutrition are known to be tightly associated, making each other worse. As no specific efficient therapy exists, cryptosporidiosis-induced malnutrition must be taken into account when establishing therapeutic scheme.

1. In the conscious rat, three tachykinin NK3 receptor antagonists, namely SR142801 ((S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)pro pyl)-4-phenylpiperidin-4-yl)-N-methylacetamide), R820 (3-indolylcarbonyl-Hyp-Phg-N(Me)-Bzl) and R486 (H-Asp-Ser-Phe-Trp-beta-Ala-Leu-Met-NH2) were assessed against the intracerebroventricular (i.c.v.) effects induced by senktide, a selective NK3 receptor agonist, on mean arterial blood pressure (MAP), heart rate (HR) and motor behaviour. 2. Senktide (10-650 pmol per animal; i.c.v; n = 4-16) at the lowest dose caused a significant fall in MAP (-10 +/- 6 mmHg), while at the highest doses (100 and 650 pmol), senktide caused a rise in MAP (9 +/- 3 and 12 +/- 1 mmHg, respectively) when compared to vehicle. The intermediate doses (25 and 65 pmol) had no effect on MAP. The highest two doses caused a tachycardia of 62 +/- 15 and 88 +/- 8 beats min(-1), respectively. The dose of 65 pmol had a biphasic effect on HR, an initial bradycardia of 47 +/- 12 beats min(-1) followed by a tachycardia of 46 +/- 14 beats min(-1). The lowest doses caused either a rise of 52 +/- 10 beats min(-1) (25 pmol) or no effect (10 pmol) on HR. All doses of senktide caused similar increases in face washing, sniffing and wet dog shakes except at the dose of 100 pmol, when wet dog shakes were more than double those observed with the other doses. 3. The antagonist SR142801 (100 pmol -65 nmol per animal; i.c.v.; n = 6-8) caused increases in MAP at the highest two doses (6.5 and 65 nmol) while HR, dose-dependently, increased (23 +/- 6 to 118 +/- 26 beats min[-1]) and the onset dose-dependently decreased. The (R)-enantiomer, SR142806 (100 pmol - 65 nmol per animal; i.c.v.; n = 6-8) only caused rises in MAP (13 +/- 2 mmHg) and HR (69 +/- 11 beats min[-1]) at the highest dose. These drugs had no apparent effect on behaviour, except for the highest dose of SR142801 which increased sniffing. The antagonist R820 (650 pmol - 6.5 nmol per animal; i.c.v.; n = 6) had no effect on MAP or HR and only increased sniffing behaviour at 6.5 nmol. At 650 pmol (n = 6), R486 had no effect on any variable, but at 3.25 nmol, i.c.v. (n = 4) a delayed tachycardia and a significant increase in all behavioural variables were observed. 4. The cardiovascular responses induced by 6.5 nmol SR142801 and 25 pmol senktide were inhibited by R820 (6.5 nmol, 5 min earlier i.c.v.). In contrast, R820 failed to affect the central cardiovascular and behavioural responses induced by 10 pmol [Sar9, Met(O2)11]substance P, a NK1 receptor selective agonist. The senktide-induced behavioural changes were not inhibited by R820 (6.5 nmol, i.c.v.) while R486 (650 pmol, i.c.v.) blocked both the cardiovascular and behavioural responses to 25 pmol senktide. A mixture of antagonists for NK1 (RP67580; 6.5 nmol) and NK2 (SR48968; 6.5 nmol) receptors injected i.c.v. did not affect the cardiovascular response to SR142801. Cross-desensitization was shown between the central responses to SR142801 and senktide, but not between SR142801 and [Sar9, Met(O2)11]substance P. 5. The antagonists SR142801 and SR142806 (6.5-650 nmol kg(-1); n = 5-7), given i.v., did not evoke any cardiovascular or behavioural changes, except a delayed bradycardia for SR142806 (650 nmol kg[-1]), and also failed to inhibit the increase in MAP evoked by senktide (4 nmol kg(-1), i.v.). However, at the highest dose, both drugs slightly reduced the senktide-induced tachycardia. 6. Although the present data are consistent with the in vitro pharmacological bioassays and binding data, showing that SR142801 is a poor antagonist at rat peripheral NK3 receptors, they suggest that SR142801 has a partial agonist action at these receptors centrally. A separation of the cardiovascular and behavioural effects mediated by central NK3 receptor activation was achieved with SR142801 and R820 but not with R486. These results could be explained by the existence of NK3 receptor subtypes in the rat or by the differential activation and inhibition of the same receptor protein linked to the production of different second messengers. Differences in the pharmacokinetic or pharmacodynamic properties of the antagonists cannot be excluded at this time.

Background Gastro-Intestinal (GI) involvement is a well-known complication of Systemic Sclerosis (SSc). Small intestinal bacterial overgrowth (SIBO) is part of such involvement. It can compromise the patient quality of life and lead to severe outcomes (cachexia, high infectious risk). However, the prevalence of SIBO is not established and predictors remain unexplored. Objectives To estimate the prevalence of SIBO in patients with SSc exhibiting GI symptoms and identify subsets of patients at risk of SIBO regarding clinical and biological presentations and GI symptoms measured by standardised questionnaires. Methods Between 2011 and 2012, patients with SSc exhibiting GI complaints (pain, diarrhoea, bloating) underwent glucose hydrogen/methane breath tests (BT) and blood assays (CRP, ferritin, vitamins D, B9 and B12, albumin, calcium, phosphate, prothrombin and lipid profile). At the time of the BT, patients were asked to complete two questionnaires: the Short Form-36 (SF-36) and the University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument (UCLA SCTC GTI).1 Results Among 120 consecutive SSc patients, 38 patients (30 women) were included, (median age: 59 years (30-80)). Fourteen patients (37%) had a positive BT and were diagnosed with SIBO giving a point prevalence of 12% (14/120) in SSc and 37% (14/38) in SSc patients with GI symptoms. Among the 38 patients included, 18 (48%) had the diffuse cutaneous subset. Median disease duration was 8.5 years (1-35). Patients with SIBO showed a longer disease duration (13.5 years (4-29) vs. 6.5 (1-35), p=0.007); a higher frequency of pulmonary arterial hypertension confirmed by right heart catheterization (3/14, 21% vs. 0/24, 0%, p=0.01) and a lower frequency of anti-topoisomerase-I antibodies (1/14, 7% vs. 10/24, 42%, p=0.04). Median age (60.5 vs. 59 years, p=0.5) and cutaneous subset (36% vs. 54% patients with the diffuse form, p=0.5) did not differ between patients with or without SIBO. Of the most interest, significant weight-loss within the past 6 months (>5% of total body weight) was observed in patients with BT+ (6/14, 43% vs. 2/24, 8%, p=0.03). Despite normal median values, calcium (p=0.04), phosphate (p=0.04) and triglycerid levels (p=0.04) were lower in patients with SIBO. Focusing on GI manifestations, it is of note that the total UCLA SCTC GTI score was higher in patients suffering from SIBO (0.85 (0.24-2.22) vs. 0.30 (0.04-1.24), p=0.02). The SF-36 assessment was comparable between the 2 groups. Two patients died due to intestinal involvement with severe chronic malabsorption. Conclusions In our series, the prevalence of SIBO was 37% of SSc patients displaying GI symptoms. To our knowledge, this is the first study using the UCLA SCTC GTI to identify patients at risk of SIBO in SSc. Higher UCLA SCTC GTI score and weight-loss appeared to be strongly associated with SIBO. These results support the systematic use of this score, together with a regular weight evaluation in SSc patients. Further studies are needed to confirm these results on a larger scale and to assess the evolution of the UCLA SCTC GTI score after SIBO optimal treatment, which is currently ongoing in our unit. References Khanna D, et al. Reliability and validity of the University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument. Arthritis Rheum 2009; 61: 1257-63. Disclosure of Interest None Declared

Flux monitoring is of great interest for experimental studies in material testing reactors. Nowadays, only the thermal neutron flux can be monitored on line, e.g., using fission chambers or self-powered neutron detectors. In the framework of the Joint Instrumentation Laboratory between SCK-CEN and CEA, we have developed a fast neutron detector system (FNDS) capable of measuring on line the local high-energy neutron flux in fission reactor core and reflector locations. FNDS is based on fission chambers measurements in Campbelling mode. The system consists of two detectors, one detector being mainly sensitive to fast neutrons and the other one to thermal neutrons. On line data processing uses the CEA depletion code DARWIN in order to disentangle fast and thermal neutrons components, taking into account the isotopic evolution of the fissile deposit. The first results of FNDS experimental test in the BR2 reactor are presented in this paper. Several fission chambers have been irradiated up to a fluence of about 7 × 10(20) n∕cm(2). A good agreement (less than 10% discrepancy) was observed between FNDS fast flux estimation and reference flux measurement.

Introduction On decrit des atrophies du pancreas chez les diabetiques. On a aussi decrit des anomalies de la fonction exocrine du pancreas chez pres de 25 % des diabetique de type 1 et de type 2. Nous avons cherche des correlations entre ces deux constations. Patients et Methodes Deux groupes de patients ont participe a cette etude : Groupe 1, 35 patients selectionnes sur la base d'une concentration basse de l'elastase fecale, marqueur de dysfonction exocrine. Groupe 2, 17 patients consecutifs sans selection sur la fonction exocrine. Le scanner du pancreas ete fait en coupes de 1 mm jointives, sans injection de PDC a chaque fois que possible. Autres explorations : dosage fecal d'elastase-1 et chymotrypsine, test au glucagon. Resultats Cinquante deux patients ont participe : 34/18 H/F, Âge 54 [36–63] (mediane [IQR]), duree de diabete 15 [5–26] ans, IMC 25 [23,4–27,5] kg/m 2 , 24/28 type 1/2. Les deux groupes de patient ne differaient que pour l'elastase (53 vs 257 μg/g, P=6 10 −3 ) et chymotrypsine (3,8 vs 8,5 U/g, P=0,01). Comparee a des valeurs de reference, la distribution des volumes du pancreas differait des valeurs normales, avec 73 % de patients sous le 10 e percentile (P −6 ). En analyse univariee, une correlation (test de spearman) etait retrouvee entre volume du pancreas et duree de diabete, poids maximal, chymotrypsine et peptide C stimule, mais pas avec âge, dose d'insuline, BMI, HbA1c ou elastase. En analyse de regression multiple, seuls le peptide-C stimule et chymotrypsine etaient correles au volume du pancreas. Le volume du pancreas etait significativement plus bas chez les patients du groupe 1 (32 vs 57 cm 3 , P −6 ). Conclusion L'atrophie du pancreas chez les diabetiques est correlee a des marqueurs de fonction exocrine et endocrine. Les consequences cliniques restent incertaines.

Introduction Il a recemment ete decrit que 30 % des diabetiques, type 1 et type 2, ont a long terme un deficit du pancreas exocrine, cause potentielle de malnutrition, carence et instabilite glycemique. Le but de cette etude est de mieux caracteriser ces patients. Materiels et methodes Une analyse des selles avec dosage d'elastase (E) et d'activite chymotryptique (C) a ete effectuee chez 458 patients hospitalises en diabetologie. Les valeurs seuils de 200 μg/g (elastase) et 6 U/g (activite chymotryptique) ont ete retenues. On a evalue chez ces patients les anticorps anti GAD et IA2, les vitamines liposolubles A, D (25OH) et E, et classe les patients selon un phenotype apparent de diabete (type 1, type 2, pancreatite chronique). Resultats Cinquante-neuf patients avaient une baisse conjointe de E et C (groupe A), et 92 une baisse de l'un des 2, soit 33 % d'anomalies. Les 137 premiers patients ont ete analyses, dont 35 du groupe A. Parmi ces 35 patients, 3 avaient une pancreatite alcoolique et des calcifications pancreatiques, les autres (30/31) avaient un ASP normal et pas d'antecedent digestif. Les patients du groupe A etaient âges de 53 (20-87) ans, âge au diagnostic 36 (4-74) ans. Apres une duree moyenne de diabete de 17 (0-55) ans, 91 % etaient traites avec de l'insuline ; 20 etaient dits type 2, mais avec un âge median au diagnostic de 40 ans et un IMC de 27. Parmi les patients de type 1, un seul (1/12) avait des autoanticorps (GAD ou IA2), compare 11/16 type 1 avec A et E normaux (p=0,002), pour une duree de diabete pourtant inferieure (13 versus 27 ans). La carence en vitamine D (25 OH versus 22 % (p −3 ). De meme, la carence en vitamine A ( versus 25 %) (p=0,02). Enfin, un seul patient (du groupe A) avait un deficit en vitamine E (ratio vitamine E/cholesterol versus 6,1 ± 1,5 μmol/mmol ; p=0,03. Conclusion Un tiers des diabetiques ont un deficit exocrine du pancreas, avec une plus grande frequence de carences vitaminique. La rarete des autoanticorps chez ces patients suggere qu'il pourrait s'agir d'un cadre nosologique distinct.

As part of PWR life-time assessment project, a large R&D program, PV-CT50, has been carried out from 1995 to 2004, to assess pressure vessel (PV) steel's toughness curve using very large compact tension (CT) specimens (50 × 125 × 120 mm3) allowing measurements in the ductile to brittle transition range. A new high capacity irradiation rig was designed to meet the specific CT50 specimens loading requirements in the 70 MWth OSIRIS material testing reactor operated by CEA's Nuclear Energy Division at the Saclay Research Center. This paper presents the measurement and calculation developments required in these particular conditions. Spectrum characteristics and neutron flux levels were determined by a comprehensive dosimetry on mock-ups featuring activation foils and damage monitors. At the same time, a new calculation methodology based on the TRIPOLI-4.3 Monte Carlo code and IRDF-2002 dosimetry files was validated against calorimetric and neutron activation measurements.