Waste In-Situ Stabilization/Entombment Research and Development Project

The technical basis and stakeholder acceptance of entombment technology is necessary before entombment becomes a decontamination and decommissioning (D and D) option for nuclear reactors. The authors present a research and development (R and D) approach addressing technical basis and stakeholder acceptance of entombment technology. The approach includes a consortium and the conceptual R and D program

Efficient History Matching of a High Dimensional Individual-Based HIV Transmission Model

History matching is a model (pre-)calibration method that has been applied to computer models from a wide range of scientific disciplines. In this work we apply history matching to an individual-based epidemiological model of HIV that has 96 input and 50 output parameters, a model of much larger scale than others that have been calibrated before using this or similar methods. Apart from demonstrating that history matching can analyze models of this complexity, a central contribution of this work is that the history match is carried out using linear regression, a statistical tool that is elementary and easier to implement than the Gaussian process--based emulators that have previously been used. Furthermore, we address a practical difficulty with history matching, namely, the sampling of tiny, nonimplausible spaces, by introducing a sampling algorithm adjusted to the specific needs of this method. The effectiveness and simplicity of the history matching method presented here shows that it is a useful tool for the calibration of computationally expensive, high dimensional, individual-based models

Bayesian history matching of complex infectious disease models using emulation: A tutorial and a case study on HIV in Uganda

Advances in scientific computing have allowed the development of complex models that are being routinely applied to problems in disease epidemiology, public health and decision making. The utility of these models depends in part on how well they can reproduce empirical data. However, fitting such models to real world data is greatly hindered both by large numbers of input and output parameters, and by long run times, such that many modelling studies lack a formal calibration methodology. We present a novel method that has the potential to improve the calibration of complex infectious disease models (hereafter called simulators). We present this in the form of a tutorial and a case study where we history match a dynamic, event-driven, individual-based stochastic HIV simulator, using extensive demographic, behavioural and epidemiological data available from Uganda. The tutorial describes history matching and emulation. History matching is an iterative procedure that reduces the simulator's input space by identifying and discarding areas that are unlikely to provide a good match to the empirical data. History matching relies on the computational efficiency of a Bayesian representation of the simulator, known as an emulator. Emulators mimic the simulator's behaviour, but are often several orders of magnitude faster to evaluate. In the case study, we use a 22 input simulator, fitting its 18 outputs simultaneously. After 9 iterations of history matching, a non-implausible region of the simulator input space was identified that was times smaller than the original input space. Simulator evaluations made within this region were found to have a 65% probability of fitting all 18 outputs. History matching and emulation are useful additions to the toolbox of infectious disease modellers. Further research is required to explicitly address the stochastic nature of the simulator as well as to account for correlations between outputs

Use of the analysis of the volatile faecal metabolome in screening for colorectal cancer

Diagnosis of colorectal cancer is an invasive and expensive colonoscopy, which is usually carried out after a positive screening test. Unfortunately, existing screening tests lack specificity and sensitivity, hence many unnecessary colonoscopies are performed. Here we report on a potential new screening test for colorectal cancer based on the analysis of volatile organic compounds (VOCs) in the headspace of faecal samples. Faecal samples were obtained from subjects who had a positive faecal occult blood sample (FOBT). Subjects subsequently had colonoscopies performed to classify them into low risk (non-cancer) and high risk (colorectal cancer) groups. Volatile organic compounds were analysed by selected ion flow tube mass spectrometry (SIFT-MS) and then data were analysed using both univariate and multivariate statistical methods. Ions most likely from hydrogen sulphide, dimethyl sulphide and dimethyl disulphide are statistically significantly higher in samples from high risk rather than low risk subjects. Results using multivariate methods show that the test gives a correct classification of 75% with 78% specificity and 72% sensitivity on FOBT positive samples, offering a potentially effective alternative to FOBT

Développements récents dans les études de la lipogenèse chez l’Homme et chez les animaux

National audienceD’après le rapport présenté lors du Symposium satellite "Lipogenèse chez les animaux domestiques" dans le cadre des 3èmes Journées franco-britanniques de Nutrition (Nancy, 30 septembre - 2 octobre 1998), publié en langue anglaise dans Proceedings of the Nutrition Society, 1999, volume 58, p 541-549

Waste In-Situ Stabilization/Entombment Research and Development Project

The technical basis and stakeholder acceptance of entombment technology is necessary before entombment becomes a decontamination and decommissioning (D and D) option for nuclear reactors. The authors present a research and development (R and D) approach addressing technical basis and stakeholder acceptance of entombment technology. The approach includes a consortium and the conceptual R and D program

Neuropeptide Y is increased in appetite-regulating hypothalamic areas of lactating rats

Neuropeptide Y (NPY), a thirty-six amino acid peptide, is a potent centrally-acting appetite-stimulating agent which is believed to regulate eating behaviour and body weight (Williams et al. 1991). Lactation in rodents is associated with increased nutrient requirements which are met by extraordinary increases in food intake (Vernon, 1989). The aim of the present study was to investigate whether hyperphagia in lactating rats is associated with increased hypothalamic NPY levels, as in the case of other hyperphagic states such as starvation and diabetes. Twenty female Wistar rats, initially matched for age and weight, were studied. The experiment began when the lactating group (n 10) was on average at day 16 of lactation (range, 13-17). The lactating rats’ food intake was over 330% that of the controls (P<0.001). Body weight in the lactating group was 22% more than in non-lactating rats (P<0.00l); most of this weight gain is known to be due to hypertrophy of the mammary gland. Final plasma insulin was significantly lower in the lactating rats (6.6 (SD 0.6) v. 11.7 (SD 2.1) pmo/l; P<0.05). In lactating and non-lactating rats the plasma glucose (7.1 (SD 0.5) v. 6-6 (SD 0.3) mmol/l) and corticosterone (187 (SD 61) v. 232 (SD 42) pmol/l) levels were comparable (both P>0.05). Four of the eight hypothalamic areas showed significantly increased NPY levels in the lactating rats compared with controls, namely: the arcuate nucleus-median eminence (+41%; P<0.001); the paraventricular nucleus (+35%; P<0.00l); the ventromedial nucleus (+66% ; P=0.003); the dorsomedial nucleus (+78%; P<0.00l). Other hypothalamic regions showed no differences between the two groups. Increased NPY levels in the arcuate nucleus (its principal hypothalamic site of synthesis) and in the paraventricular and dorsomedial nuclei (NPY-sensitive sites to which the arcuate nucleus projects) suggest increased activity of the NPY-ergic system in lactation. NPY may therefore mediate the markedly increased food intake in lactation. \u