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The advancement of the design of ALFRED beyond the conceptual phase, passes through the analysis of the impact of uncertainties, notably to what concerns safety-related conditions. Compliancy of plant safety to Design Extension Conditions is, according to IAEA and in line with the meaning itself of these beyond-design conditions, usually investigated by best estimates only. Due however to the demonstration nature of ALFRED, it was decided to assess the actual safety performances of this system even in ultimate conditions. To this regard, the emphasis was put on unprotected events like the UTOP (unprotected transient of over-power) and ULOOP (unprotected loss of offsite power, resulting from the combination of a loss of flow and loss of heat sink under unprotected conditions), pinpointed as the most challenging situations sought for the plant. The purpose of the present work, which has been divided in three parts, was then to assess the ultimate ALFRED safety margins against failure of the key core components and systems (Part III). To target this objective, the evaluation of uncertainties coming, on one hand, from nuclear data was performed at first, to retrieve their impact on the reactivity coefficients, thereby on the transient behavior driven by the latter (Part I); then, uncertainties from material properties, fabrication procedures, operation and computational tools were propagated to assess their influence on the thermal-hydraulics of the system (Part II). In this paper, presenting the first part of the work, the focus is on nuclear data. As such, a sensitivity/uncertainty analysis of the ALFRED core on key elementary reactivity effects, forming the basis for computing the feedback coefficients, has been performed. The sensitivity analysis allowed pointing out firstly the most relevant cross-sections for every response function. Uncertainty analysis allowed then establishing a possible range of confidence for the reactivity effects. The adjoint-based technique implemented in the TSUNAMI-3D module of the SCALE6 system was used. The confidence intervals identified for each reactivity effect have been combined then into confidence intervals for the feedback coefficients. Finally, the most conservative, yet physically sound (i.e., where correlations among coefficients, stemming from dependencies on common nuclear data, are taken into account), set of reactivity coefficients has been picked out from the confidence intervals, enabling transient calculations to propagate uncertainties into transient behavior. Using this off-nominal set, and comparing results with the reference ones, exploiting the system codes SIM-LFR and RELAP, a negligible effect of nuclear data uncertainties has been found for the ULOOP, while an increase of the maximum achieved power of around 6% has been computed for the UTOP. Overall, a modest contribution of nuclear data uncertainties for these transients has been found which, however, must be combined with the thermal-hydraulics one so to finally assess safety margins. [ABSTRACT FROM AUTHOR]

The advancement of the design of the Advanced Lead-cooled Fast Reactor European Demonstrator (ALFRED) beyond the conceptual phase, passes through the analysis of the impact of uncertainties, notably to what concerns safety-related conditions. Compliancy of plant safety to Design Extension Conditions is, according to IAEA and in line with the meaning itself of these beyond-design conditions, usually investigated by best estimates only. Due however to the demonstration nature of ALFRED, it was decided to assess the actual safety performances of this system even in ultimate conditions. To this regard, the emphasis was put on unprotected events like the UTOP (unprotected transient of over-power) and ULOOP (unprotected loss of offsite power, resulting from the combination of a loss of flow and loss of heat sink under unprotected conditions), pinpointed as the most challenging situations sought for the plant. The purpose of the present work, which has been divided in three parts, was then to assess the ultimate ALFRED safety margins against failure of the key core components and systems (Part III). To target this objective, the evaluation of uncertainties coming, on one hand, from nuclear data was performed at first, to retrieve their impact on the reactivity coefficients, thereby on the transient behavior driven by the latter (Part I); then, uncertainties from material properties, fabrication procedures, operation and measurement, and computational tools were propagated to assess their influence on the thermal-hydraulics of the system (Part II). In this work the efforts of Parts I and II are merged together and the effect of uncertainties on safety margins and salient parameters assessed. The retrieved uncertainties are propagated to the expected number of pins experiencing fuel melting during an UTOP and to the clad time-to-failure during an ULOOP. The former has been found to be quite affected by uncertainties, but still under limits not directly posing hazards to the people and the environment, even when extremely conservative assumptions are put forward; the latter shows a milder response to uncertainties, but always guaranteeing more than an order of magnitude of safety margin relative to WENRA recommendations. [ABSTRACT FROM AUTHOR]

The advancement of the design of the Advanced Lead-cooled Fast Reactor European Demonstrator (ALFRED) beyond the conceptual phase, passes through the analysis of the impact of uncertainties, notably to what concerns safety-related conditions. Compliancy of plant safety to Design Extension Conditions is, according to IAEA and in line with the meaning itself of these beyond-design conditions, usually investigated by best estimates only. Due however to the demonstration nature of ALFRED, it was decided to assess the actual safety performances of this system even in ultimate conditions. To this regard, the emphasis was put on unprotected events like the UTOP (unprotected transient of over-power) and ULOOP (unprotected loss of offsite power, resulting from the combination of a loss of flow and loss of heat sink under unprotected conditions), pinpointed as the most challenging situations sought for the plant. The purpose of the present work, which has been divided in three parts, was then to assess the ultimate ALFRED safety margins against failure of the key core components and systems (Part III). To target this objective, the evaluation of uncertainties coming, on one hand, from nuclear data was performed at first, to retrieve their impact on the reactivity coefficients, thereby on the transient behavior driven by the latter (Part I); then, uncertainties from material properties, fabrication procedures, operation and computational tools were propagated to assess their influence on the thermal-hydraulics of the system (Part II). In this work the focus is on the latter uncertainties. The adopted methodology is presented at first, namely the semi-statistical vertical approach – characterized by an optimal degree of conservatism among the classical approaches – targeting a 3σ confidence interval. Then, the identification and propagation of each effect are shown, by means of the heat equations, so to retrieve the actual uncertainties on the parameters of interest (the temperatures themselves). Finally, a hot spot analysis to quantify the uncertainty-distorted temperature field is elaborated and presented. The performed analysis has revealed the great impact of fabrication tolerances for the coolant, film and clad temperature rises, particularly affecting safety margins during an ULOOP, while models and material properties uncertainties seem to dominate for the gap and fuel rises, which concur notably in challenging the respect of the fuel melting limit in an UTOP. [ABSTRACT FROM AUTHOR]

We have studied the single dose pharmacokinetics of 5 mg clotiazepam drops, oral tablets, and sublingual tablets in a cross-over study in 6 healthy volunteers (median age 28 years). The formulations had similar systemic availability. Compared with oral tablets the sublingual route gave a lower peak concentration and a delayed peak time, while drops gave a greater maximum concentration with a similar peak time. The use of drops is suggested for a more marked initial effect and the sublingual route for easier administration, especially in the elderly. [ABSTRACT FROM AUTHOR]

Abstract: In the last years 68Ga has got into the focus of researchers and clinicians especially for radio-labeling of biomolecules; an important characteristic of this positron emitting isotope is its availability via the 68Ge/68Ga generator system: the long-lived 68Ge (t 1/2=270.8d) produces the short-lived 68Ga (t 1/2=67.63min) which decays to stable 68Zn. 68Ge breakthrough compromises 68Ga radionuclidic purity, while 68Zn might affect the specific activity of the radiopharmaceutical. In this paper we investigated the weight of these impurities in 68Ga-DOTANOC synthesis. 65Zn (t 1/2=244.26d; decay mode: EC 98.3%, β + 1.7%) was used as a radiotracer of stable 68Zn; samples of the purification columns, wastes and product were recovered and measured with a calibrated HPGe gamma-ray spectrometry system. The results showed that 68Zn competes with 68Ga in labeling DOTANOC with a (95±2)% labeling yield; they also proved the effectiveness of the STRATA X-C cationic post-processing of the generator eluate in lowering the amount of this impurity to less than 1%. Moreover this approach, along with the purification of the final product through a STRATA X cartridge, effectively removes 68Ge breakthrough providing a 68Ga-DOTANOC radionuclidic purity of (99.9999986±0.0000006)%, superior to 99.9% required by the Pharmacopoeia Monograph on 68Ga Edotreotide injection. [Copyright &y& Elsevier]

Abstract: Introduction: The fine detection of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH) in hair matrix remains one of the most important topics in hair analysis. This relevance lies in the necessity to obtain evidence of effective drug consumption and dispel any doubt of environmental contamination. THCCOOH is the highest and mainly represented Δ9-THC metabolite, but its concentration in hair is very low. A sensitive method for quantitative determination of THCCOOH in hair was developed. As first step, the method was tested with different SPE/LLE conditions, but the best results were obtained with a simple ad hoc LLE extraction. The final method was fully validated, evaluating parameters like extraction recovery, linearity, specificity and sensitivity. More than one hundred hair samples were then analyzed with the validated method. Data analysis was performed so as to determine respective concentrations of the metabolite and active molecule. Methods: Hair was washed and cut into small pieces (2–4mm). Samples (20–50mg) were spiked with deuterated internal standard (THC-d3 and THCCOOH-d3) and then hydrolyzed at 90°C in 1mL of 1M NaOH for 15min. THC was isolated by a LLE basic extraction with n-hexane:ethyl acetate (9:1). Next the aqueous solution was acidified (pH 4) adding concentrated acetic acid. THCCOOH was extracted with the same mixture. Dried extracts were derivatized with pentafluoropropionic anhydride and hexafluoroisopropanol and analyzed by GC/MS/MS (Agilent 7000B triple quadrupole) in NCI mode. Results: The linear range of THCCOOH is 0.1–5pg/mg, with good correlation coefficients (r 2 >0.9993). This method has great sensitivity (LOD 0.01pg/mg to LOQ 0.04pg/mg), high recovery, reproducibility and robustness. Conclusions: Based on these results, the method proved to be effective for the rapid determination of THC and THCCOOH in hair specimens. [Copyright &y& Elsevier]

Abstract: Somatostatin receptors 1–5 are over expressed in neuroendocrine tumours (NETs). 68Ga-labelled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-Octreotide (DOTA NOC), a recent synthesized somatostatin analogue, shows high affinity for those receptors. Herein, modifications of a commercial module for the labelling of DOTA NOC with 68Ga, as well as the assessment of time course of the radiochemical purity variation are described. The evaluation of radiochemical stability was done by two different chromatographic methods: reversed-phase radio HPLC and fast TLC analysis. Labelled compound has been found radiochemically stable within 3h from the end of labelling (EOL) and radiochemical purity was always higher than 99%. After 73 labelling sessions the system showed great reproducibility and high radiochemical yield. [Copyright &y& Elsevier]