Geostatistical modeling of the spatial variability of arsenic in groundwater of southeast Michigan

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94929/1/wrcr10188.pd

Use of attribute association error probability estimates to evaluate quality of medical record geocodes

BACKGROUND: The utility of patient attributes associated with the spatiotemporal analysis of medical records lies not just in their values but also the strength of association between them. Estimating the extent to which a hierarchy of conditional probability exists between patient attribute associations such as patient identifying fields, patient and date of diagnosis, and patient and address at diagnosis is fundamental to estimating the strength of association between patient and geocode, and patient and enumeration area. We propose a hierarchy for the attribute associations within medical records that enable spatiotemporal relationships. We also present a set of metrics that store attribute association error probability (AAEP), to estimate error probability for all attribute associations upon which certainty in a patient geocode depends. METHODS: A series of experiments were undertaken to understand how error estimation could be operationalized within health data and what levels of AAEP in real data reveal themselves using these methods. Specifically, the goals of this evaluation were to (1) assess if the concept of our error assessment techniques could be implemented by a population-based cancer registry; (2) apply the techniques to real data from a large health data agency and characterize the observed levels of AAEP; and (3) demonstrate how detected AAEP might impact spatiotemporal health research. RESULTS: We present an evaluation of AAEP metrics generated for cancer cases in a North Carolina county. We show examples of how we estimated AAEP for selected attribute associations and circumstances. We demonstrate the distribution of AAEP in our case sample across attribute associations, and demonstrate ways in which disease registry specific operations influence the prevalence of AAEP estimates for specific attribute associations. CONCLUSIONS: The effort to detect and store estimates of AAEP is worthwhile because of the increase in confidence fostered by the attribute association level approach to the assessment of uncertainty in patient geocodes, relative to existing geocoding related uncertainty metrics

Global, local and focused geographic clustering for case-control data with residential histories

BACKGROUND: This paper introduces a new approach for evaluating clustering in case-control data that accounts for residential histories. Although many statistics have been proposed for assessing local, focused and global clustering in health outcomes, few, if any, exist for evaluating clusters when individuals are mobile. METHODS: Local, global and focused tests for residential histories are developed based on sets of matrices of nearest neighbor relationships that reflect the changing topology of cases and controls. Exposure traces are defined that account for the latency between exposure and disease manifestation, and that use exposure windows whose duration may vary. Several of the methods so derived are applied to evaluate clustering of residential histories in a case-control study of bladder cancer in south eastern Michigan. These data are still being collected and the analysis is conducted for demonstration purposes only. RESULTS: Statistically significant clustering of residential histories of cases was found but is likely due to delayed reporting of cases by one of the hospitals participating in the study. CONCLUSION: Data with residential histories are preferable when causative exposures and disease latencies occur on a long enough time span that human mobility matters. To analyze such data, methods are needed that take residential histories into account

A mathematical model for breath gas analysis of volatile organic compounds with special emphasis on acetone

Recommended standardized procedures for determining exhaled lower respiratory nitric oxide and nasal nitric oxide have been developed by task forces of the European Respiratory Society and the American Thoracic Society. These recommendations have paved the way for the measurement of nitric oxide to become a diagnostic tool for specific clinical applications. It would be desirable to develop similar guidelines for the sampling of other trace gases in exhaled breath, especially volatile organic compounds (VOCs) which reflect ongoing metabolism. The concentrations of water-soluble, blood-borne substances in exhaled breath are influenced by: (i) breathing patterns affecting gas exchange in the conducting airways; (ii) the concentrations in the tracheo-bronchial lining fluid; (iii) the alveolar and systemic concentrations of the compound. The classical Farhi equation takes only the alveolar concentrations into account. Real-time measurements of acetone in end-tidal breath under an ergometer challenge show characteristics which cannot be explained within the Farhi setting. Here we develop a compartment model that reliably captures these profiles and is capable of relating breath to the systemic concentrations of acetone. By comparison with experimental data it is inferred that the major part of variability in breath acetone concentrations (e.g., in response to moderate exercise or altered breathing patterns) can be attributed to airway gas exchange, with minimal changes of the underlying blood and tissue concentrations. Moreover, it is deduced that measured end-tidal breath concentrations of acetone determined during resting conditions and free breathing will be rather poor indicators for endogenous levels. Particularly, the current formulation includes the classical Farhi and the Scheid series inhomogeneity model as special limiting cases.Comment: 38 page

Spatial-temporal analysis of non-Hodgkin lymphoma in the NCI-SEER NHL case-control study

<p>Abstract</p> <p>Background</p> <p>Exploring spatial-temporal patterns of disease incidence through cluster analysis identifies areas of significantly elevated or decreased risk, providing potential clues about disease risk factors. Little is known about the etiology of non-Hodgkin lymphoma (NHL), or the latency period that might be relevant for environmental exposures, and there are no published spatial-temporal cluster studies of NHL.</p> <p>Methods</p> <p>We conducted a population-based case-control study of NHL in four National Cancer Institute (NCI)-Surveillance, Epidemiology, and End Results (SEER) centers: Detroit, Iowa, Los Angeles, and Seattle during 1998-2000. Using 20-year residential histories, we used generalized additive models adjusted for known risk factors to model spatially the probability that an individual had NHL and to identify clusters of elevated or decreased NHL risk. We evaluated models at five different time periods to explore the presence of clusters in a time frame of etiologic relevance.</p> <p>Results</p> <p>The best model fit was for residential locations 20 years prior to diagnosis in Detroit, Iowa, and Los Angeles. We found statistically significant areas of elevated risk of NHL in three of the four study areas (Detroit, Iowa, and Los Angeles) at a lag time of 20 years. The two areas of significantly elevated risk in the Los Angeles study area were detected only at a time lag of 20 years. Clusters in Detroit and Iowa were detected at several time points.</p> <p>Conclusions</p> <p>We found significant spatial clusters of NHL after allowing for disease latency and residential mobility. Our results show the importance of evaluating residential histories when studying spatial patterns of cancer.</p

Plug-and-play inference for disease dynamics: measles in large and small populations as a case study

Statistical inference for mechanistic models of partially observed dynamic systems is an active area of research. Most existing inference methods place substantial restrictions upon the form of models that can be fitted and hence upon the nature of the scientific hypotheses that can be entertained and the data that can be used to evaluate them. In contrast, the so-called plug-and-play methods require only simulations from a model and are thus free of such restrictions. We show the utility of the plug-and-play approach in the context of an investigation of measles transmission dynamics. Our novel methodology enables us to ask and answer questions that previous analyses have been unable to address. Specifically, we demonstrate that plug-and-play methods permit the development of a modelling and inference framework applicable to data from both large and small populations. We thereby obtain novel insights into the nature of heterogeneity in mixing and comment on the importance of including extra-demographic stochasticity as a means of dealing with environmental stochasticity and model misspecification. Our approach is readily applicable to many other epidemiological and ecological systems

Unscented Kalman filter with parameter identifiability analysis for the estimation of multiple parameters in kinetic models

In systems biology, experimentally measured parameters are not always available, necessitating the use of computationally based parameter estimation. In order to rely on estimated parameters, it is critical to first determine which parameters can be estimated for a given model and measurement set. This is done with parameter identifiability analysis. A kinetic model of the sucrose accumulation in the sugar cane culm tissue developed by Rohwer et al. was taken as a test case model. What differentiates this approach is the integration of an orthogonal-based local identifiability method into the unscented Kalman filter (UKF), rather than using the more common observability-based method which has inherent limitations. It also introduces a variable step size based on the system uncertainty of the UKF during the sensitivity calculation. This method identified 10 out of 12 parameters as identifiable. These ten parameters were estimated using the UKF, which was run 97 times. Throughout the repetitions the UKF proved to be more consistent than the estimation algorithms used for comparison

Heavy episodic drinking on college campuses: Does changing the legal drinking age make a difference

ABSTRACT. Objective: This article extends the compartmental model previously developed by Scribner et al. in the context of college drinking to a mathematical model of the consequences of lowering the legal drinking age. Method: Using data available from 32 U.S. campuses, the analyses separate underage and legal age drinking groups into an eight-compartment model with different alcohol availability (wetness) for the underage and legal age groups. The model evaluates the likelihood that underage students will incorrectly perceive normative drinking levels to be higher than they actually are (i.e., misperception) and adjust their drinking accordingly by varying the interaction between underage students in social and heavy episodic drinking compartments. Results: The results evaluate the total heavy episodic drinker population and its dependence on the difference in misperception, as well as its dependence on underage wetness, legal age wetness, and drinking age. Conclusions: Results suggest that an unrealistically extreme combination of high wetness and low enforcement would be needed for the policies related to lowering the drinking age to be effective. (J. Stud. Alcohol Drugs, 72

Fractional dynamics pharmacokinetics–pharmacodynamic models

While an increasing number of fractional order integrals and differential equations applications have been reported in the physics, signal processing, engineering and bioengineering literatures, little attention has been paid to this class of models in the pharmacokinetics–pharmacodynamic (PKPD) literature. One of the reasons is computational: while the analytical solution of fractional differential equations is available in special cases, it this turns out that even the simplest PKPD models that can be constructed using fractional calculus do not allow an analytical solution. In this paper, we first introduce new families of PKPD models incorporating fractional order integrals and differential equations, and, second, exemplify and investigate their qualitative behavior. The families represent extensions of frequently used PK link and PD direct and indirect action models, using the tools of fractional calculus. In addition the PD models can be a function of a variable, the active drug, which can smoothly transition from concentration to exposure, to hyper-exposure, according to a fractional integral transformation. To investigate the behavior of the models we propose, we implement numerical algorithms for fractional integration and for the numerical solution of a system of fractional differential equations. For simplicity, in our investigation we concentrate on the pharmacodynamic side of the models, assuming standard (integer order) pharmacokinetics