Time Series of Counts under Censoring: A Bayesian Approach.

Censored data are frequently found in diverse fields including environmental monitoring, medicine, economics and social sciences. Censoring occurs when observations are available only for a restricted range, e.g., due to a detection limit. Ignoring censoring produces biased estimates and unreliable statistical inference. The aim of this work is to contribute to the modelling of time series of counts under censoring using convolution closed infinitely divisible (CCID) models. The emphasis is on estimation and inference problems, using Bayesian approaches with Approximate Bayesian Computation (ABC) and Gibbs sampler with Data Augmentation (GDA) algorithms.

Real-time surveillance for abnormal events: the case of influenza outbreaks.

This paper introduces a method of surveillance using deviations from probabilistic forecasts. Realised observations are compared with probabilistic forecasts, and the "deviation" metric is based on low probability events. If an alert is declared, the algorithm continues to monitor until an all-clear is announced. Specifically, this article addresses the problem of syndromic surveillance for influenza (flu) with the intention of detecting outbreaks, due to new strains of viruses, over and above the normal seasonal pattern. The syndrome is hospital admissions for flu-like illness, and hence, the data are low counts. In accordance with the count properties of the observations, an integer-valued autoregressive process is used to model flu occurrences. Monte Carlo evidence suggests the method works well in stylised but somewhat realistic situations. An application to real flu data indicates that the ideas may have promise. The model estimated on a short run of training data did not declare false alarms when used with new observations deemed in control, ex post. The model easily detected the 2009 H1N1 outbreak. Copyright © 2016 John Wiley & Sons, Ltd.

FaSTR DNA: a new expert system for forensic DNA analysis.

The automation of DNA profile analysis of reference and crime samples continues to gain pace driven in part by a realisation by the criminal justice system of the positive impact DNA technology can have in aiding in the solution of crime and the apprehension of suspects. Expert systems to automate the profile analysis component of the process are beginning to be developed. In this paper, we report the validation of a new expert system FaSTR DNA, an expert system suitable for the analysis of DNA profiles from single source reference samples and from crime samples. We compare the performance of FaSTR DNA with that of other equivalent systems, GeneMapper ID v3.2 (Applied Biosystems, Foster City, CA) and FSS-i(3) v4 (The Forensic Science Service((R)) DNA expert System Suite FSS-i(3), Forensic Science Service, Birmingham, UK) with GeneScan Analysis v3.7/Genotyper v3.7 software (Applied Biosystems, Foster City, CA, USA) with manual review. We have shown that FaSTR DNA provides an alternative solution to automating DNA profile analysis and is appropriate for implementation into forensic laboratories. The FaSTR DNA system was demonstrated to be comparable in performance to that of GeneMapper ID v3.2 and superior to that of FSS-i(3) v4 for the analysis of DNA profiles from crime samples.

Reproducibility of gas chromatography-mass spectrometry measurements of 2H labeling of water: application for measuring body composition in mice.

Deuterium-labeled water (2H2O) has emerged as a novel isotope tracer. Following the administration of 2H2O, it is possible to study the dynamics of carbohydrate, protein, lipid, and DNA and to determine body composition. Those studies require reliable measurements of the 2H labeling of water. Although simple gas chromatography-mass spectrometry (GC-MS) methods have been developed for measuring the 2H enrichment of biological fluids, investigators have not reported on the intra- and/or interdaily variability of the measurements. We have experimentally examined the reproducibility of one GC-MS method for measuring the 2H labeling of water. Briefly, hydrogen (deuterium) atoms in water were exchanged with those bound to acetone, and the 2H labeling of acetone was then determined under electron impact ionization. We found that the coefficient of variation is generally less than 0.5% when water is labeled between 0 and 2.8 mole percentage excess 2H. We demonstrated that this highly reproducible result allows one to use 2H2O and the "acetone method" to measure physiological parameters such as body composition in mice.

Using isotope tracers to study metabolism: application in mouse models.

The application of isotope tracers for investigating metabolism in mice is discussed. To familiarize the reader, some basic principles regarding the use of tracer methods are outlined. Emphasis is placed on showing how investigators are using isotope tracers to study the regulation of carbohydrate, fat and/or protein turnover in vivo. Finally, some of the advantages of using labeled water (i.e., 2H(2)O and/or H(2)18O) to trace the kinetics of biological processes are considered. The background provided in this report should assist engineers in designing studies that enhance our understanding of conditions in which metabolism is altered (e.g., diabetes, cancer cachexia, failure to thrive and travel at zero-gravity).

Influence of diet on the modeling of adipose tissue triglycerides during growth.

We have studied the accretion of lipids in growing mice. We measured the rates of synthesis and degradation of triglycerides in epididymal fat pads of mice maintained for 44 days on a low-fat, high-carbohydrate diet (I) or a high-fat, low-carbohydrate diet (II). 2H2O was added to the drinking water for 14 days. Rates of incorporation/washout of 2H to/from C1 of triglyceride-glycerol showed that triglyceride synthesis was greater than triglyceride degradation (net triglyceride balance was approximately 2.5 times greater in II than in I). The data also show that the contribution of de novo lipogenesis to triglyceride-bound palmitate was approximately 3 times greater in I than in II. This was consistent with a greater relative intake of carbohydrate in I vs. II. The rates of incorporation and washout of newly synthesized (2H-labeled) palmitate into and from triglycerides were also measured. Those data suggested a remodeling of triglyceride-bound fatty acids. On measuring the profile of triglyceride-bound fatty acids, we observed a decrease in the relative abundance of triglyceride-bound palmitate and stearate and an increase in triglyceride-bound oleate and linoleate. This was observed in I and II. In summary, diet substantially affects the deposition and modeling of triglycerides in adipose tissue during growth. 2H2O can be used to examine the mechanisms responsible for the accumulation of triglycerides, e.g., factors that affect 1) triglyceride synthesis and degradation and 2) the source of fatty acids that are used in esterification.

Measuring gluconeogenesis using a low dose of 2H2O: advantage of isotope fractionation during gas chromatography.

The contribution of gluconeogenesis to glucose production can be measured by enriching body water with (2)H(2)O to approximately 0.5% (2)H and determining the ratio of (2)H that is bound to carbon-5 vs. carbon-2 of blood glucose. This labeling ratio can be measured using gas chromatography-mass spectrometry after the corresponding glucose carbons are converted to formaldehyde and then to hexamethylenetetramine (HMT). We present a technique for integrating ion chromatograms that allows one to use only 0.05% (2)H in body water (i.e., 10 times less than the current dose). This technique takes advantage of the difference in gas chromatographic retention times of naturally labeled HMT and [(2)H]HMT. We discuss the advantage(s) of using a low dose of (2)H(2)O to quantify the contribution of gluconeogenesis.

Gas chromatography-mass spectrometry assay of the (18)o enrichment of water as trimethyl phosphate.

We have developed an assay for determining the 18O enrichment of water in biological fluids. Urine, plasma, or whole blood is reacted with phosphorous pentachloride to yield phosphoric acid. Derivatization of phosphoric acid with diazomethane generates trimethyl phosphate. The enrichment of trimethyl phosphate is nearly four times that of water and is assayed using gas chromatography-mass spectrometry (electron impact ionization). Yang et al. (1998, Anal. Biochem. 258, 315-321) assayed the 2H enrichment of body water after exchange with acetone, by gas chromatography-mass spectrometry. The combination of our 18O method and the 2H method of Yang et al. allows one to measure energy expenditure via "doubly labeled" water (2H(2)O + H(2)18O), using small samples of body fluids. These techniques were used to measure energy expenditure in mice, in which the 18O enrichment of body water can be monitored down to 0.025%.