Bayesian Methods and Computation for Large Observational Datasets

Much health related research depends heavily on the analysis of a rapidly expanding universe of observational data. A challenge in analysis of such data is the lack of sound statistical methods and tools that can address multiple facets of estimating treatment or exposure effects in observational studies with a large number of covariates. We sought to advance methods to improve analysis of large observational datasets with an end goal of understanding the effect of treatments or exposures on health. First we compared existing methods for propensity score (PS) adjustment, specifically Bayesian propensity scores. This concept had previously been introduced (McCandless et al., 2009) but no rigorous evaluation had been done to evaluate the impact of feedback when fitting the joint likelihood for both the PS and outcome models. We determined that unless specific steps were taken to mitigate the impact of feedback, it has the potential to distort estimates of the treatment effect. Next, we developed a method for accounting for uncertainty in confounding adjustment in the context of multiple exposures. Our method allows us to select confounders based on their association with the joint exposure and the outcome while also accounting for the uncertainty in the confounding adjustment. Finally, we developed two methods to combine het- erogenous sources of data for effect estimation, specifically information coming from a primary data source that provides information for treatments, outcomes, and a limited set of measured confounders on a large number of people and smaller supplementary data sources containing a much richer set of covariates. Our methods avoid the need to specify the full joint distribution of all covariates

Allometric scaling of weight to height and resulting body mass index thresholds in two Asian populations.

BACKGROUND: Body mass index (BMI) represents a normalization of weight to height and is used to classify adiposity. While the capacity of BMI as an adiposity index has been experimentally validated in Caucasians, but there has been little testing Asian populations. METHODS: To determine whether weight scales to height squared in Asian Indians across the general population and in Asian Indian tribes an allometric analysis on the power law model, W = αH RESULTS: The unadjusted power was β = 2.08 (s = 0.02). The power for the general population (non-tribal) was β = 2.11 (s = 0.02). Powers when adjusted for tribe ranged from 1.87 to 2.35 with 24 of the 33 tribes resulting in statistically significant (p \u3c 0.05) differences in powers from the general population. The coefficients of the adjusted terms ranged from -0.22 to 0.26 and therefore the scaling exponent does not deviate far from 2. Thresholds for BMI classification of overweight in the KNHANES database were BMI = 21 kg/m CONCLUSIONS: Our study confirms that weight scales to height squared in Asian Indian males even after adjusting for tribe membership. We also demonstrate that optimal BMI thresholds are lower in a Korean population in comparison to currently used BMI thresholds. These results support the application of BMI in Asian populations with potentially lower thresholds

Incipient alcohol use in childhood: Early alcohol sipping and its relations with psychopathology and personality

Prior research has shown that sipping of alcohol begins to emerge during childhood and is potentially etiologically significant for later substance use problems. Using a large, community sample of 9- and 10-year-olds (N = 11,872; 53% female), we examined individual differences in precocious alcohol use in the form of alcohol sipping. We focused explicitly on features that are robust and well-demonstrated correlates of, and antecedents to, alcohol excess and related problems later in the lifespan, including youth- and parent-reported externalizing traits (i.e., impulsivity, behavioral inhibition and activation) and psychopathology. Seventeen percent of the sample reported sipping alcohol outside of a religiously sanctioned activity by age 9 or 10. Several aspects of psychopathology and personality emerged as small but reliable correlates of sipping. Nonreligious sipping was related to youth-reported impulsigenic traits, aspects of behavioral activation, prodromal psychotic-like symptoms, and mood disorder diagnoses, as well as parent-reported externalizing disorder diagnoses. Religious sipping was unexpectedly associated with certain aspects of impulsivity. Together, our findings point to the potential importance of impulsivity and other transdiagnostic indicators of psychopathology (e.g., emotion dysregulation, novelty seeking) in the earliest forms of drinking behavior

In silico toxicology protocols

The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates the information needed for protocols to support in silico predictions for major toxicological endpoints of concern (e.g., genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity) across several industries and regulatory bodies. Such novel in silico toxicology (IST) protocols, when fully developed and implemented, will ensure in silico toxicological assessments are performed and evaluated in a consistent, reproducible, and well-documented manner across industries and regulatory bodies to support wider uptake and acceptance of the approaches. The development of IST protocols is an initiative developed through a collaboration among an international consortium to reflect the state-of-the-art in in silico toxicology for hazard identification and characterization. A general outline for describing the development of such protocols is included and it is based on in silico predictions and/or available experimental data for a defined series of relevant toxicological effects or mechanisms. The publication presents a novel approach for determining the reliability of in silico predictions alongside experimental data. In addition, we discuss how to determine the level of confidence in the assessment based on the relevance and reliability of the information

Is Australia Neglecting the Local Topography When It Comes to Catastrophic Costs and Ending Tuberculosis?

Efforts to eliminate tuberculosis as a public health problem require reductions in mortality, incidence, and the eradication of associated catastrophic costs; however, the question of catastrophic costs is often neglected, particularly in the context of low-incidence settings like Australia. This study reviews the financial support provided to those identified as in need, and in receipt, of economic aid from the Victorian Tuberculosis Program. The study design used Epstein’s clinical data mining framework to produce descriptive statistics which were supplemented by clinical collaboration. A consistent one-third of those receiving care from the Program due to a notification of active tuberculosis received emergency financial relief over the study period. Overwhelmingly, funds were used to relieve financial distress, and each year approximately one-third of the expenditure was used to support 2% of those people notified as affected by tuberculosis (or 7⁻9% of those in receipt of funds). Many of this 2% experienced income loss and expenditure that may be considered catastrophic. Further investigation is needed to better define and understand the nature of catastrophic costs in the context of universal health care and existing low tuberculosis incidence

Modeling the use of the Adaptive Joint C4ISR Node in a tactical environment

The Adaptive Joint Command, Control, Communications, Computers, Intelligence, Surveillance and Reconnaissance (C4ISR) Node (AJCN) is a new C4ISR system with four functional capabilities: communications, signal intelligence (SIGINT), electronic warfare (EW) and Information Operations. This thesis evaluates the first three capabilities of the AJCN: communications, SIGINT and EW. Simulation is used as a time- and cost-effective way to model the AJCN's capabilities. Eleven communications and combat effectiveness MOE are used to evaluate the AJCN's performance. Point of Attack 2, a tactical simulation with an extensive database is used to replicate the AJCN and UA operations. Results of the analysis include: 1) the AJCN significantly increased friendly detection of enemy forces; 2) the AJCN significantly decreased average message transmittal time and the number of failed messages; 3) the AJCN increased the friendly force's capability to jam and intercept enemy messages.http://archive.org/details/modelinguseofajc109451876Approved for public release; distribution is unlimited

Perspectives of Vietnamese, Sudanese and South Sudanese immigrants on targeting migrant communities for latent tuberculosis screening and treatment in low-incidence settings: A report on two Victorian community panels

Background: Tuberculosis (TB) elimination strategies in Australia require a focus on groups who are at highest risk of TB infection, such as immigrants from high-burden settings. Understanding attitudes to different strategies for latent TB infection (LTBI) screening and treatment is an important element of justifiable elimination strategies. Method: Two community panels were conducted in Melbourne with members of the Vietnamese (n = 11), Sudanese and South Sudanese communities (n = 9). Panellists were provided with expert information about LTBI and different screening and health communication strategies, then deliberated on how best to pursue TB elimination in Australia. Findings: Both panels unanimously preferred LTBI screening to occur pre-migration rather than in Australia. Participants were concerned that post-migration screening would reach fewer migrants, noted that conducting LTBI screening in Australia could stigmatize participants and that poor awareness of LTBI would hamper participation. If targeted screening was to occur in Australia, the Vietnamese panel preferred ‘place-based’ communication strategies, whereas the Sudanese and South Sudanese panel emphasized that community leaders should lead communication strategies to minimize stigma. Both groups emphasized the importance of maintaining community trust in Australian health service providers, and the need to ensure targeting did not undermine this trust. Conclusion: Pre-migration screening was preferred. If post-migration screening is necessary, the potential for stigma should be reduced, benefit and risk profile clearly explained and culturally appropriate communication strategies employed. Cultural attitudes to health providers, personal health management and broader social vulnerabilities of targeted groups need to be considered in the design of screening programs