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ANSWERS® is developing a set of uncertainty quantification (UQ) tools for use with its major physics codes: WIMS/PANTHER (reactor physics), MONK (criticality and reactor physics) and MCBEND (shielding and dosimetry). The Visual Workshop integrated development environment allows the user to construct and edit code inputs, launch calculations, post-process results and produce graphs, and recently uncertainty quantification and optimisation tools have been added. Prior uncertainties due to uncertainties in nuclear data or manufacturing tolerances can be estimated using the sampling method or using the sensitivity options in the physics codes combined with appropriate covariance matrices. To aid the user in the choice of appropriate validation experiments, the MONK categorisation scheme and/or a similarity index can be used. An interactive viewer has been developed which allows the user to search through, and browse details of, over 2,000 MONK validation experiments that have been analysed from the ICSBEP and IRPhE validation sets. A Bayesian updating approach is used to assimilate the measured data with the calculated results. It is shown how this process can be used to reduce bias in calculated results and reduce the calculated uncertainty on those results. This process is illustrated by application to a PWR fuel assembly.

Until recently, criticality safety assessment codes had a minimum temperature at which calculations can be performed. Where criticality assessment has been required for lower temperatures, indirect methods, including reasoned argument or extrapolation, have been required to assess reactivity changes associated with these temperatures. The ANSWERS Software Service MONK® version 10B Monte Carlo criticality code, is capable of performing criticality calculations at any temperature, within the temperature limits of the underlying nuclear data in the BINGO continuous energy library. The temperature range of the nuclear data has been extended below the traditional lower limit of 293.6 K to 193 K in a prototype BINGO library, primarily based on JEFF-3.1.2 data. The temperature range of the thermal bound scattering data of the key moderator materials was extended by reprocessing the NJOY LEAPR inputs used to produce bound data for JEFF-3.1.2 and ENDF/B-VIII.0. To give confidence in the low temperature nuclear data, a series of MONK and MCBEND calculations have been performed and results compared against external data sources. MCBEND is a Monte Carlo code for shielding and dosimetry and shares commonalities to its sister code MONK including the BINGO nuclear data library. Good agreement has been achieved between calculated and experimental cross sections for ice, k-effective results for low temperature criticality benchmarks and calculated and experimentally determined eigenvalues for thermal neutron diffusion in ice. To quantify the differences between ice and water bound scattering data a number of MONK criticality calculations were performed for nuclear fuel transport flask configurations. The results obtained demonstrate good agreement with extrapolation methods. There is a discernible difference in the use of ice and water data.

The ANSWERS Software Service is developing a number of techniques to better understand and quantify uncertainty on calculations of the neutron multiplication factor, k-effective, in nuclear fuel and other systems containing fissile material. The uncertainty on the calculated k-effective arises from a number of sources, including nuclear data uncertainties, manufacturing tolerances, modelling approximations and, for Monte Carlo simulation, stochastic uncertainty. For determining the uncertainties due to nuclear data, a set of application libraries have been generated for use with the MONK10 Monte Carlo and the WIMS10 deterministic criticality and reactor physics codes. This paper overviews the generation of these nuclear data libraries by Latin hypercube sampling of JEFF-3.1.2 evaluated data based upon a library of covariance data taken from JEFF, ENDF/B, JENDL and TENDL evaluations. Criticality calculations have been performed with MONK10 and WIMS10 using these sampled libraries for a number of benchmark models of fissile systems. Results are presented which show the uncertainty on k-effective for these systems arising from the uncertainty on the input nuclear data.

Two peptides, pramlintide (37 amino acids), an analog of human amylin, and exenatide, synthetic exendin-4 (39 amino acids), are both in late-stage clinical development as potential new treatments for people with diabetes. Both are potential long-term treatments, and there is the likelihood that some women will become pregnant while using one of these peptide therapies. Therefore, it was important to evaluate the potential for each peptide to cross the placental barrier and thereby result in exposure to the fetus. This was examined using ex vivo perfusions of human placentas. The fetal and maternal side of a cotyledon were cannulated and perfused first with buffer, and then with radioactive antipyrine in order to establish the integrity of the system and the perfusion constants. Either pramlintide or exenatide was then added to each acceptable cotyledon perfusate on the maternal side. Each peptide was evaluated at an initial concentration near the therapeutic plasma concentration and at approximately 10-50 times that concentration in each of the three cotyledons. Maternal and fetal perfusate samples were assayed for peptide concentrations using an immunoassay. The ratio of fetal-to-maternal peptide concentrations during equilibrium perfusion were extremely low (pramlintide ≤ 0.006, exenatide ≤ 0.017). These data demonstrate negligible passage of either peptide across the placental barrier. It is, therefore, likely that maternal use of either peptide during gestation will result in negligible exposure to the fetus. [ABSTRACT FROM AUTHOR]

To evaluate the physiological effects and toxicity of epidural clonidine·HCl, male Beagle dogs were prepared with chronic lumbar epidural catheters and administered constant infusions of either saline ( = 10), or 80 μg/hr ( = 6), 200 μg/hr ( = 6), or 320 μg/hr ( = 12) clonidine·HCl at a rate of 4 ml/24 hr for 28 days. Saline infusion had no effect upon any behavioral measure. Epidural clonidine produced a dose-dependent increase in thermal skin-twitch response latency (antinociception), lowering of respiration rate, heart rate, and blood pressure, and increased sedation. The effects were maximum from approximately Day 1 to Day 3 when, with the exception of respiration which remained depressed, a progressive adaptation was observed over the course of the study. There were no negative effects on body weight, body temperature, motor function, bowel or bladder function, or clinical pathology values. After 28 days of continuous infusion, the dogs were deeply anesthetized and terminated. Cistemal cerebrospinal fluid taken at termination displayed no clinically significant differences in protein or glucose concentration. All groups, including control, had dogs which had a chronic inflammatory response in the epidural space, as represented by fibrosis, foreign body giant cells, and lymphocytes, but no spinal cord pathology. Both the steadystate plasma and CSF concentrations of clonidine were proportional to the dose; the ratio of CSF to plasma concentration was approximately 0.5. The failure to see any change in CSF composition, significant spinal cord pathology, or signs of tissue or organ toxicity emphasizes the safety of epidurally administered clonidine at infusion rates up to 320 μg/hr and at infusate concentrations up to 2 mg/ml. [ABSTRACT FROM PUBLISHER]