Temperature, air pollution and total mortality during summers in Sydney, 1994-2004

This study investigated the effect of temperature and air pollutants on total mortality in summers in Sydney, Australia. Daily data on weather variables, mortality and air pollution for the Sydney metropolitan area from 1 January 1994 to 31 December 2004 were supplied by Australian Bureau of Meteorology, Australian Bureau of Statistics, and Environment Protection Agency of New South Wales, respectively. We examined the association of total mortality with weather indicators and air pollution using generalised additive models (GAMs). A time-series classification and regression tree (CART) model was developed to explore the interaction effects of temperature and air pollution that impacted on mortality. Our results show that the average increase in total daily mortality was 0.9% [95% confidence interval (CI): 0.6–1.3%] and 22% (95% CI: 6.4–40.5%) for a 1 °C increase in daily maximum temperature and 1 part per hundred million (pphm) increase in daily average concentration of sulphur dioxide (SO2), respectively. Time-series CART results show that maximum temperature and SO2 on the current day had significant interaction effects on total mortality. There were 7.3% and 12.1% increases in daily average mortality when maximum temperature was over 32°C and mean SO2 exceeded 0.315 pphm, respectively. Daily maximum temperature was statistically significantly associated with daily deaths in Sydney during summers between 1994 and 2004. Elevated daily maximum temperature combined with high SO2 concentrations appeared to have contributed to the increased mortality observed in Sydney during this period

Genome-wide allele-specific methylation is enriched at gene regulatory regions in a multi-generation pedigree from the Norfolk Island isolate

Background: Allele-specific methylation (ASM) occurs when DNA methylation patterns exhibit asymmetry among alleles. ASM occurs at imprinted loci, but its presence elsewhere across the human genome is indicative of wider importance in terms of gene regulation and disease risk. Here, we studied ASM by focusing on blood-based DNA collected from 24 subjects comprising a 3-generation pedigree from the Norfolk Island genetic isolate. We applied a genome-wide bisulphite sequencing approach with a genotype-independent ASM calling method to map ASM across the genome. Regions of ASM were then tested for enrichment at gene regulatory regions using Genomic Association Test (GAT) tool. Results: In total, we identified 1.12 M CpGs of which 147,170 (13%) exhibited ASM (P ≤ 0.05). When including contiguous ASM signal spanning ≥ 2 CpGs, this condensed to 12,761 ASM regions (AMRs). These AMRs tagged 79% of known imprinting regions and most (98.1%) co-localised with known single nucleotide variants. Notably, miRNA and lncRNA showed a 3.3- and 1.8-fold enrichment of AMRs, respectively (P < 0.005). Also, the 5′ UTR and start codons each showed a 3.5-fold enrichment of AMRs (P < 0.005). There was also enrichment of AMRs observed at subtelomeric regions of many chromosomes. Five out of 11 large AMRs localised to the protocadherin cluster on chromosome 5. Conclusions: This study shows ASM extends far beyond genomic imprinting in humans and that gene regulatory regions are hotspots for ASM. Future studies of ASM in pedigrees should help to clarify transgenerational inheritance patterns in relation to genotype and disease phenotypes.</p

Using simulation methods for bayesian econometric models: inference, development,and communication

This paper surveys the fundamental principles of subjective Bayesian inference in econometrics and the implementation of those principles using posterior simulation methods. The emphasis is on the combination of models and the development of predictive distributions. Moving beyond conditioning on a fixed number of completely specified models, the paper introduces subjective Bayesian tools for formal comparison of these models with as yet incompletely specified models. The paper then shows how posterior simulators can facilitate communication between investigators (for example, econometricians) on the one hand and remote clients (for example, decision makers) on the other, enabling clients to vary the prior distributions and functions of interest employed by investigators. A theme of the paper is the practicality of subjective Bayesian methods. To this end, the paper describes publicly available software for Bayesian inference, model development, and communication and provides illustrations using two simple econometric models.

Estimating Nonlinear Dynamic Equilibrium Economies: A Likelihood Approach

This paper presents a framework to undertake likelihood-based inference in nonlinear dynamic equilibrium economies. The authors develop a sequential Monte Carlo algorithm that delivers an estimate of the likelihood function of the model using simulation methods. This likelihood can be used for parameter estimation and for model comparison. The algorithm can deal both with nonlinearities of the economy and with the presence of non-normal shocks. The authors show consistency of the estimate and its good performance in finite simulations. This new algorithm is important because the existing empirical literature that wanted to follow a likelihood approach was limited to the estimation of linear models with Gaussian innovations. The authors apply their procedure to estimate the structural parameters of the neoclassical growth model

Bayesian latent trait modelling of migraine symptom data

Definition of disease phenotype is a necessary preliminary to research into genetic causes of a complex disease. Clinical diagnosis of migraine is currently based on diagnostic criteria developed by the International Headache Society. Previously, we examined the natural clustering of these diagnostic symptoms using latent class analysis (LCA) and found that a four-class model was preferred. However, the classes can be ordered such that all symptoms progressively intensify, suggesting that a single continuous variable representing disease severity may provide a better model. Here, we compare two models: item response theory and LCA, each constructed within a Bayesian context. A deviance information criterion is used to assess model fit. We phenotyped our population sample using these models, estimated heritability and conducted genome-wide linkage analysis using Merlin-qtl. LCA with four classes was again preferred. After transformation, phenotypic trait values derived from both models are highly correlated (correlation = 0.99) and consequently results from subsequent genetic analyses were similar. Heritability was estimated at 0.37, while multipoint linkage analysis produced genome-wide significant linkage to chromosome 7q31-q33 and suggestive linkage to chromosomes 1 and 2. We argue that such continuous measures are a powerful tool for identifying genes contributing to migraine susceptibility