Application of ensemble methods to analyse the decline of organochlorine pesticides in relation to the interactions between age, gender and time.

Organochlorine pesticides (OCPs) are toxic chemicals that persist in human tissue. Short and long term exposure to OCPs have been shown to have adverse effects on human health. This motivates studies into the concentrations of pesticides in humans. However these studies typically emphasise the analysis of the main effects of age group, gender and time of sample collection. The interactions between main effects can distinguish variation in OCP concentration such as the difference in concentrations between genders of the same age group as well as age groups over time. These are less studied but may be equally or more important in understanding effects of OCPs in a population. The aim of this study was to identify interactions relevant to understanding OCP concentrations and utilise them appropriately in models. We propose a two stage analysis comprising of boosted regression trees (BRTs) and hierarchical modelling to study OCP concentrations. BRTs are used to discover influential interactions between age group, gender and time of sampling. Hierarchical models are then employed to test and infer the effect of the interactions on OCP concentrations. Results of our analysis show that the best fitting model of an interaction effect varied between OCPs. The interaction between age group and gender was most influential for hexachlorobenzene (HCB) concentrations. There was strong evidence of an interaction effect between age group and time for ß-hexachlorocyclohexane (ß-HCH) concentrations in >60 year olds as well as an interaction effect between age group and gender for HCB concentrations for adults aged >45 years. This study highlights the need to consider appropriate interaction effects in the analysis of OCP concentrations and provides further insight into the interplay of main effects on OCP concentration trends.

Concentrations of organochlorine pesticides in pooled human serum by age and gender.

Organochlorine pesticides (OCPs) have been used for many decades in Australia with cessation of selected persistent and bioaccumulative OCPs ranging from the 1970s to as recently as 2007. The specific aims of this study were to use samples representative of an Australian population to assess age and gender differences in the concentration of OCPs in human blood sera and to investigate temporal trends in these chemicals. Serum was collected from de-identified, surplus pathology samples over five time periods (2002/03, 2006/07, 2008/09, 2010/11 and 2012/13), with 183 serum pools made from 12,175 individual samples; 26 pools in 2002/03, 85 pools in 2006/07 and 24 pools each in 2008/09, 2010/11 and 2012/13. Samples were analyzed for hexachlorobenzene (HCB), ß-hexachlorocyclohexane (ß-HCH), γ -hexachlorocyclohexane (lindane) (γ-HCH), oxy-chlordane, trans-nonachlor, p,p'-DDE, o,p'-DDT, p,p'-DDT and Mirex. Stratification criteria included gender and age (0-4; 5-15; 16-30; 31-45; 46-60; and >60 years) with age additionally stratified by adults >16 years and children 0-4 and 5-15 years. All pools from all collection periods had detectable concentrations of OCPs with a detection frequency of >60% for HCB, ß-HCH, trans-nonachlor, p,p'-DDT and p,p'-DDE. The overall OCP concentrations increased with age with the highest concentrations in the >60 years groups. Females did not have higher mean OCP concentrations than males except for HCB concentrations (p=0.0006). Temporal trends showed overall decreasing serum concentrations by collection period with the exception of an increase in OCP concentrations between 2006/07 and 2008/09. Excluding this data point, HCB decreased from year to year by 7-76%; ß-HCH concentrations decreased by 14 - 38%; trans-nonachlor concentrations decreased by 10 - 65%; p,p'-DDE concentrations decreased by 6 - 52%; and p,p'-DDT concentrations decreased by 7 - 30%. The results indicate that OCP concentrations have decreased over time as is to be expected following the phase out of these chemicals in Australia.

Lowering of Intraocular Pressure After Phacoemulsification in Primary Open-Angle and Angle-Closure Glaucoma: A Bayesian Analysis.

Phacoemulsification as treatment for primary open-angle glaucoma (POAG) remains more controversial than for primary angle-closure glaucoma (PACG). If the objective of glaucoma surgery is an additional greater than or equal to 5 to 6 mm Hg reduction of intraocular pressure (IOP), the role of phacoemulsification should be based on the probability of achieving this. A Bayesian analysis of available data was performed to calculate the change in IOP after phacoemulsification in POAG and PACG. Standard meta-analysis formulation with prephacoemulsification and postphacoemulsification IOP-assumed to have normal distributions, with study-specific means and SDs-was used. Absolute and relative change in IOP was calculated using different priors, and sensitivity analyses were performed. The prior that just included a decrease of greater than or equal to 6 mm Hg in the 95% credible interval was identified. The probability of achieving greater than or equal to 5 to 6 mm Hg decrease in IOP (and other levels) was calculated. Depending on the prior, the probability of achieving a greater than or equal to 5 mm Hg reduction in IOP in POAG varied from 0.1% to 3%. Confidence in a greater than or equal to 6 mm Hg decrease required a prior belief that phacoemulsification produces a mean decrease of 7 mm Hg. The probability of a decrease in IOP was greater in PACG: approximately 50% probability of a greater than or equal to 5 mm Hg decrease in PACG uncontrolled on medications. Phacoemulsification in POAG has a high probability of producing a small decrease in IOP that may be useful in early, well-controlled disease. The probability of a clinically significant decrease of greater than or equal to 5 to 6 mm Hg-required for advanced/uncontrolled disease-is low. Results support the role of phacoemulsification in PACG.

Understanding the causation of primary angle closure disease using the sufficient component cause model.

BACKGROUND: Several risk factors have been associated with primary angle closure disease, but their actual role in causation of an individual case is not clear. DESIGN: Concept paper. PARTICIPANTS/SAMPLES: No patient participation. METHODS: The sufficient component cause model is briefly explained in the context of primary angle closure disease. The framework is used to conceptualize the role of individual mechanisms of disease. The possibility of personalized treatment for primary angle closure disease is discussed in this context. MAIN OUTCOME MEASURES: Qualitative concepts in disease causality may refine research and treatment in primary angle closure disease. RESULTS: The minimum set of conditions that are sufficient for primary angle closure disease to occur is considered the sufficient component cause model for that individual case. Described risk factors (including genes) as well as currently unknown influences play a role in the model. There may be many such models and all complementary components in any sufficient-cause model must be present for disease to occur. Interruption of any one component in that model can be used for treatment. Pupillary block is likely a component of most such models and may currently be considered a universally necessary component of these models. CONCLUSIONS: The sufficient component cause model can be used as a framework to explain the role of individual mechanisms of causation and treatment of primary angle closure disease. It also aids understanding of the proportion of disease due to specific causes.