A crucial concern of toxicologists is to determine an acceptable exposure level(s) to a hazardous... more A crucial concern of toxicologists is to determine an acceptable exposure level(s) to a hazardous substance(s). Often lab experiments produce data featuring multiple hazards and multiple outcome measures. The current practice evaluates each hazard and outcome combination separately, which leads to multiple statistical tests that suffer from inflated Type I error rates. This paper introduces a Bayesian model-based approach for analyzing data of similar nature. This approach is dimension-preserving in that it permits simultaneous quantification of an acceptable exposure level among multiple hazards. Furthermore , we introduce the concept of significance probabilities to assess the importance of the outcomes in determining an acceptable exposure level. The proposed methodology is motivated and illustrated through analyzing the dataset from a rodent study of pesticides on neurotoxicity conducted by Moser et al. (2005).
Background and Objectives: Preclinical studies show serotonin (5-HT) 5-HT2C receptor (5-HT2CR) ag... more Background and Objectives: Preclinical studies show serotonin (5-HT) 5-HT2C receptor (5-HT2CR) agonists reduce cocaine-seeking and cocaine intake. This study examined safety of the 5-HT2CR agonist lorcaserin administered with cocaine in participants with cocaine use disorder (CocUD). Secondarily, subjective response to cocaine and choice of cocaine vs. money were examined.Methods: A double-blind, randomized, placebo-controlled trial of 25 inpatient non-treatment seeking participants with CocUD. Participants were randomized to either lorcaserin (n = 17) or placebo (n = 8). Primary outcome measures included cardiovascular measures and plasma cocaine levels. Secondary measures of subjective response to cocaine were assessed using a visual analog scale (VAS) and cocaine vs. money progressive ratio choice sessions.Results: Thirteen randomized participants were included in the final analysis. No serious or unexpected adverse events were related to lorcaserin. There were no significant int...
To understand how time and temperature could affect latent fingerprints, wooden pallets were used... more To understand how time and temperature could affect latent fingerprints, wooden pallets were used to construct five units that each housed ten 60-watt incandescent light bulbs. Fingerprints were deposited on the top, middle, and base of the globes. The bulbs were powered on (except the control bulb in each unit) for 18, 48, 72, 120, 168, 336, 504, and 672 h. Fingerprints recovered from the bulbs by tape lift after black powder processing were given a quality score. A thermal imaging camera determined temperatures on three areas of the bulbs. Fingerprints on the top of the globe (156.3°C) had the lowest quality score, and fingerprints on the middle of the globe (112.6°C) had the highest quality score. The mean quality scores of the three temperature classes were within one standard deviation of one another, meaning there is no way to estimate fingerprint age based on its quality after heat exposure.
International Journal of Environmental Research and Public Health
Computational models are valuable tools for predicting the population effects prior to Food and D... more Computational models are valuable tools for predicting the population effects prior to Food and Drug Administration (FDA) authorization of a modified risk claim on a tobacco product. We have developed and validated a population model using best modeling practices. Our model consists of a Markov compartmental model based on cohorts starting at a defined age and followed up to a specific age accounting for 29 tobacco-use states based on a cohort members transition pathway. The Markov model is coupled with statistical mortality models and excess relative risk ratio estimates to determine survival probabilities from use of smokeless tobacco. Our model estimates the difference in premature deaths prevented by comparing Base Case (“world-as-is”) and Modified Case (the most likely outcome given that a modified risk claim is authorized) scenarios. Nationally representative transition probabilities were used for the Base Case. Probabilities of key transitions for the Modified Case were estim...
Journal of Pharmacology and Experimental Therapeutics
Impulsivity and the attentional orienting response to cocaine-associated cues () promote relapse ... more Impulsivity and the attentional orienting response to cocaine-associated cues () promote relapse in cocaine-use disorder (CUD). A time-dependent escalation of cue reactivity () occurs during extended, forced abstinence from cocaine self-administration in rats. The investigational serotonin (5-HT) 5-HT receptor (5-HTR) antagonist/inverse agonist M100907 suppresses , or the inability to withhold premature responses, and cocaine-seeking behaviors. The present preclinical study was designed to establish the potential for repurposing the Food and Drug Administration-approved selective 5-HTR antagonist/inverse agonist pimavanserin as a therapeutic agent to forestall relapse vulnerability in CUD. In male Sprague-Dawley rats, pimavanserin suppressed impulsive action () measured in the 1-choice serial reaction time (1-CSRT) task, similarly to M100907. We also used the 1-CSRT task to establish baseline levels of impulsive action before cocaine self-administration and evaluation of cue reactivity (lever presses reinforced by the discrete cue complex previously paired with cocaine delivery). We observed an incubation of cocaine cue reactivity between day 1 and day 30 of forced abstinence from cocaine self-administration. Baseline levels of impulsive action predicted incubated levels of cocaine cue reactivity in late abstinence. We also found that baseline impulsive action predicted the effectiveness of pimavanserin to suppress incubated cue reactivity in late abstinence from cocaine self-administration at doses that were ineffective in early abstinence. These data suggest that integration of clinical measures of impulsive action may inform refined, personalized pharmacotherapeutic intervention for the treatment of relapse vulnerability in CUD.
When deaths occur in water, soft tissue decomposes after a temperature-dependent period, making D... more When deaths occur in water, soft tissue decomposes after a temperature-dependent period, making DNA identification dependent on bone. This study examined the effects of water on bone DNA purity and quantity, and determined the best of three extraction methods for isolating DNA. The organic phenol-chloroform method consistently extracted DNA approximating the accepted 260/280 purity value (~1.8); ChargeSwitch® gDNA Plant Kit and DNeasy Blood and Tissue Kit produced fair and unacceptable values, respectively. The purity value for humerus and rib samples was consistent across accumulated degree days (ADD). Significant differences in quantification among extraction methods and between bone types were identified. Ribs and ChargeSwitch® gDNA Plant Kit samples produced the lowest mean Ct values of the bone types and the extraction methods, respectively. Therefore, this study proposes that magnetic bead technology extraction methods and ribs be considered when processing bones that have bee...
Previous working memory (WM) studies found that relative to controls, subjects with cannabis use ... more Previous working memory (WM) studies found that relative to controls, subjects with cannabis use disorder (CUD) showed greater brain activation in some regions (e.g., left [L] and right [R] ventrolateral prefrontal cortex [VLPFC], and L dorsolateral prefrontal cortex [L-DLPFC]), and lower activation in other regions (e.g., R-DLPFC). In this study, effective connectivity (EC) analysis was applied to functional magnetic resonance imaging data acquired from 23 CUD subjects and 23 controls (two groups matched for sociodemographic factors and substance use history) while performing an n-back WM task with interleaved 2-back and 0-back periods. A 2-back minus 0-back modulator was defined to measure the modulatory changes of EC corresponding to the 2-back relative to 0-back conditions. Compared to the controls, the CUD group showed smaller modulatory change in the R-DLPFC to L-caudate pathway, and greater modulatory changes in L-DLPFC to L-caudate, R-DLPFC to R-caudate, and R-VLPFC to L-cau...
Previous diffusion tensor imaging (DTI) studies have consistently shown that subjects with cocain... more Previous diffusion tensor imaging (DTI) studies have consistently shown that subjects with cocaine use disorder (CocUD) had altered white matter microstructure in the corpus callosum. It is believed that these alterations are due to preexisting factors, chronic cocaine use, or both. However, there is no published longitudinal DTI study on human cocaine users yet which could shed light on the relationship between cocaine use and DTI findings. This study used a longitudinal design and DTI to test if the white matter microstructure shows quicker alteration in CocUD subjects than controls. DTI data were acquired from eleven CocUD subjects who participated a treatment study and eleven non-drug-using controls at baseline (Scan 1) and after ten weeks (Scan 2). The baseline fractional anisotropy (FA), a general measure of white matter microstucture, and the change in FA (ΔFA, equals Scan 1 FA minus Scan 2 FA) were both compared between groups. The two groups did not show a difference in FA ...
Journal of Statistical Computation and Simulation, 2016
The problem of statistical calibration of a measuring instrument can be framed both in a statisti... more The problem of statistical calibration of a measuring instrument can be framed both in a statistical context as well as in an engineering context. In the first, the problem is dealt with by distinguishing between the "classical" approach and the "inverse" regression approach. Both of these models are static models and are used to estimate "exact" measurements from measurements that are affected by error. In the engineering context, the variables of interest are considered to be taken at the time at which you observe it. The Bayesian time series analysis method of Dynamic Linear Models (DLM) can be used to monitor the evolution of the measures, thus introducing an dynamic approach to statistical calibration. The research presented employs the use of Bayesian methodology to perform statistical calibration. The DLM's framework is used to capture the time-varying parameters that maybe changing or drifting over time. Two separate DLM based models are presented in this paper. A simulation study is conducted where the two models are compared to some well known 'static' calibration approaches in the literature from both the frequentist and Bayesian perspectives. The focus of the study is to understand how well the dynamic statistical calibration methods performs under various signal-to-noise ratios, r. The posterior distributions of the estimated calibration points as well as the 95% coverage intervals are compared by statistical summaries. These dynamic methods are applied to a microwave radiometry dataset.
considering gender and race, provides a basis for training, hiring, and retention for police offi... more considering gender and race, provides a basis for training, hiring, and retention for police officers. The purpose of this study is to identify muscular strength differences among racial groups from initial-recruit to in-service tests. Strength variables included bench press, bench press/lean mass and bench press/body mass. Scores were retrieved for the 1990 to 1995 recruit classes and were paired to the 2006 in-service fitness log. Sample included 309 officers: 30 females (13 black, 17 white) and 279 males (41 black, 238 white). Mean age of recruit was 24.6 ± 3.4 years and for in-service was 37.1 ± 3.7 years. Time between tests was 12.5 ± 2.0 years. Bench press strength significantly increased for all gender and racial groups. Black males were significantly stronger in bench press at initial-recruit and at in-service than white males. All racial and gender groups increased in bench press/lean mass, however, the increase in white females was not significant. No differences were found between black and white females in all strength variables at both testing periods. Black males were significantly stronger than white males in bench press/body mass only at the initial-recruit test. White males showed a significant increase in bench press/body mass over time, but they did not reach the strength level of the black males at in-service. Police departments, with a properly designed physical fitness program, can expect to see increases in strength of personnel over the first half of their careers; however, there are gender and racial differences.
2007 International Joint Conference on Neural Networks, 2007
Quantitative trait loci mapping is a growing field in genetic statistics. However, dealing with t... more Quantitative trait loci mapping is a growing field in genetic statistics. However, dealing with this type of data from a statistical perspective is often perilous. This work considers a model selection approach to quantitative trait loci analysis of the Arabidopsis Bay-O by Shahdara using a Bayesian framework, Markov Chain Monte Carlo method composition. The efficacy of this technique is demonstrated
Assessing the linear relationship between a set of continuous predictors and a continuous re- spo... more Assessing the linear relationship between a set of continuous predictors and a continuous re- sponse is a well studied problem in statistics and is applied in many data mining situations. L2 based methods such as ordinary least squares and principal components regression can be used to determine this relationship. However, both of these methods become impaired when mul- ticollinearity
Journal of Statistical Computation and Simulation, Jan 22, 2014
ABSTRACT Bayesian analysis often requires the researcher to employ Markov Chain Monte Carlo (MCMC... more ABSTRACT Bayesian analysis often requires the researcher to employ Markov Chain Monte Carlo (MCMC) techniques to draw samples from a posterior distribution which in turn is used to make inferences. Currently, several approaches to determine convergence of the chain as well as sensitivities of the resulting inferences have been developed. This work develops a Hellinger distance approach to MCMC diagnostics. An approximation to the Hellinger distance between two distributions f and g based on sampling is introduced. This approximation is studied via simulation to determine the accuracy. A criterion for using this Hellinger distance for determining chain convergence is proposed as well as a criterion for sensitivity studies. These criteria are illustrated using a dataset concerning the Anguilla australis, an eel native to New Zealand.
A crucial concern of toxicologists is to determine an acceptable exposure level(s) to a hazardous... more A crucial concern of toxicologists is to determine an acceptable exposure level(s) to a hazardous substance(s). Often lab experiments produce data featuring multiple hazards and multiple outcome measures. The current practice evaluates each hazard and outcome combination separately, which leads to multiple statistical tests that suffer from inflated Type I error rates. This paper introduces a Bayesian model-based approach for analyzing data of similar nature. This approach is dimension-preserving in that it permits simultaneous quantification of an acceptable exposure level among multiple hazards. Furthermore , we introduce the concept of significance probabilities to assess the importance of the outcomes in determining an acceptable exposure level. The proposed methodology is motivated and illustrated through analyzing the dataset from a rodent study of pesticides on neurotoxicity conducted by Moser et al. (2005).
Background and Objectives: Preclinical studies show serotonin (5-HT) 5-HT2C receptor (5-HT2CR) ag... more Background and Objectives: Preclinical studies show serotonin (5-HT) 5-HT2C receptor (5-HT2CR) agonists reduce cocaine-seeking and cocaine intake. This study examined safety of the 5-HT2CR agonist lorcaserin administered with cocaine in participants with cocaine use disorder (CocUD). Secondarily, subjective response to cocaine and choice of cocaine vs. money were examined.Methods: A double-blind, randomized, placebo-controlled trial of 25 inpatient non-treatment seeking participants with CocUD. Participants were randomized to either lorcaserin (n = 17) or placebo (n = 8). Primary outcome measures included cardiovascular measures and plasma cocaine levels. Secondary measures of subjective response to cocaine were assessed using a visual analog scale (VAS) and cocaine vs. money progressive ratio choice sessions.Results: Thirteen randomized participants were included in the final analysis. No serious or unexpected adverse events were related to lorcaserin. There were no significant int...
To understand how time and temperature could affect latent fingerprints, wooden pallets were used... more To understand how time and temperature could affect latent fingerprints, wooden pallets were used to construct five units that each housed ten 60-watt incandescent light bulbs. Fingerprints were deposited on the top, middle, and base of the globes. The bulbs were powered on (except the control bulb in each unit) for 18, 48, 72, 120, 168, 336, 504, and 672 h. Fingerprints recovered from the bulbs by tape lift after black powder processing were given a quality score. A thermal imaging camera determined temperatures on three areas of the bulbs. Fingerprints on the top of the globe (156.3°C) had the lowest quality score, and fingerprints on the middle of the globe (112.6°C) had the highest quality score. The mean quality scores of the three temperature classes were within one standard deviation of one another, meaning there is no way to estimate fingerprint age based on its quality after heat exposure.
International Journal of Environmental Research and Public Health
Computational models are valuable tools for predicting the population effects prior to Food and D... more Computational models are valuable tools for predicting the population effects prior to Food and Drug Administration (FDA) authorization of a modified risk claim on a tobacco product. We have developed and validated a population model using best modeling practices. Our model consists of a Markov compartmental model based on cohorts starting at a defined age and followed up to a specific age accounting for 29 tobacco-use states based on a cohort members transition pathway. The Markov model is coupled with statistical mortality models and excess relative risk ratio estimates to determine survival probabilities from use of smokeless tobacco. Our model estimates the difference in premature deaths prevented by comparing Base Case (“world-as-is”) and Modified Case (the most likely outcome given that a modified risk claim is authorized) scenarios. Nationally representative transition probabilities were used for the Base Case. Probabilities of key transitions for the Modified Case were estim...
Journal of Pharmacology and Experimental Therapeutics
Impulsivity and the attentional orienting response to cocaine-associated cues () promote relapse ... more Impulsivity and the attentional orienting response to cocaine-associated cues () promote relapse in cocaine-use disorder (CUD). A time-dependent escalation of cue reactivity () occurs during extended, forced abstinence from cocaine self-administration in rats. The investigational serotonin (5-HT) 5-HT receptor (5-HTR) antagonist/inverse agonist M100907 suppresses , or the inability to withhold premature responses, and cocaine-seeking behaviors. The present preclinical study was designed to establish the potential for repurposing the Food and Drug Administration-approved selective 5-HTR antagonist/inverse agonist pimavanserin as a therapeutic agent to forestall relapse vulnerability in CUD. In male Sprague-Dawley rats, pimavanserin suppressed impulsive action () measured in the 1-choice serial reaction time (1-CSRT) task, similarly to M100907. We also used the 1-CSRT task to establish baseline levels of impulsive action before cocaine self-administration and evaluation of cue reactivity (lever presses reinforced by the discrete cue complex previously paired with cocaine delivery). We observed an incubation of cocaine cue reactivity between day 1 and day 30 of forced abstinence from cocaine self-administration. Baseline levels of impulsive action predicted incubated levels of cocaine cue reactivity in late abstinence. We also found that baseline impulsive action predicted the effectiveness of pimavanserin to suppress incubated cue reactivity in late abstinence from cocaine self-administration at doses that were ineffective in early abstinence. These data suggest that integration of clinical measures of impulsive action may inform refined, personalized pharmacotherapeutic intervention for the treatment of relapse vulnerability in CUD.
When deaths occur in water, soft tissue decomposes after a temperature-dependent period, making D... more When deaths occur in water, soft tissue decomposes after a temperature-dependent period, making DNA identification dependent on bone. This study examined the effects of water on bone DNA purity and quantity, and determined the best of three extraction methods for isolating DNA. The organic phenol-chloroform method consistently extracted DNA approximating the accepted 260/280 purity value (~1.8); ChargeSwitch® gDNA Plant Kit and DNeasy Blood and Tissue Kit produced fair and unacceptable values, respectively. The purity value for humerus and rib samples was consistent across accumulated degree days (ADD). Significant differences in quantification among extraction methods and between bone types were identified. Ribs and ChargeSwitch® gDNA Plant Kit samples produced the lowest mean Ct values of the bone types and the extraction methods, respectively. Therefore, this study proposes that magnetic bead technology extraction methods and ribs be considered when processing bones that have bee...
Previous working memory (WM) studies found that relative to controls, subjects with cannabis use ... more Previous working memory (WM) studies found that relative to controls, subjects with cannabis use disorder (CUD) showed greater brain activation in some regions (e.g., left [L] and right [R] ventrolateral prefrontal cortex [VLPFC], and L dorsolateral prefrontal cortex [L-DLPFC]), and lower activation in other regions (e.g., R-DLPFC). In this study, effective connectivity (EC) analysis was applied to functional magnetic resonance imaging data acquired from 23 CUD subjects and 23 controls (two groups matched for sociodemographic factors and substance use history) while performing an n-back WM task with interleaved 2-back and 0-back periods. A 2-back minus 0-back modulator was defined to measure the modulatory changes of EC corresponding to the 2-back relative to 0-back conditions. Compared to the controls, the CUD group showed smaller modulatory change in the R-DLPFC to L-caudate pathway, and greater modulatory changes in L-DLPFC to L-caudate, R-DLPFC to R-caudate, and R-VLPFC to L-cau...
Previous diffusion tensor imaging (DTI) studies have consistently shown that subjects with cocain... more Previous diffusion tensor imaging (DTI) studies have consistently shown that subjects with cocaine use disorder (CocUD) had altered white matter microstructure in the corpus callosum. It is believed that these alterations are due to preexisting factors, chronic cocaine use, or both. However, there is no published longitudinal DTI study on human cocaine users yet which could shed light on the relationship between cocaine use and DTI findings. This study used a longitudinal design and DTI to test if the white matter microstructure shows quicker alteration in CocUD subjects than controls. DTI data were acquired from eleven CocUD subjects who participated a treatment study and eleven non-drug-using controls at baseline (Scan 1) and after ten weeks (Scan 2). The baseline fractional anisotropy (FA), a general measure of white matter microstucture, and the change in FA (ΔFA, equals Scan 1 FA minus Scan 2 FA) were both compared between groups. The two groups did not show a difference in FA ...
Journal of Statistical Computation and Simulation, 2016
The problem of statistical calibration of a measuring instrument can be framed both in a statisti... more The problem of statistical calibration of a measuring instrument can be framed both in a statistical context as well as in an engineering context. In the first, the problem is dealt with by distinguishing between the "classical" approach and the "inverse" regression approach. Both of these models are static models and are used to estimate "exact" measurements from measurements that are affected by error. In the engineering context, the variables of interest are considered to be taken at the time at which you observe it. The Bayesian time series analysis method of Dynamic Linear Models (DLM) can be used to monitor the evolution of the measures, thus introducing an dynamic approach to statistical calibration. The research presented employs the use of Bayesian methodology to perform statistical calibration. The DLM's framework is used to capture the time-varying parameters that maybe changing or drifting over time. Two separate DLM based models are presented in this paper. A simulation study is conducted where the two models are compared to some well known 'static' calibration approaches in the literature from both the frequentist and Bayesian perspectives. The focus of the study is to understand how well the dynamic statistical calibration methods performs under various signal-to-noise ratios, r. The posterior distributions of the estimated calibration points as well as the 95% coverage intervals are compared by statistical summaries. These dynamic methods are applied to a microwave radiometry dataset.
considering gender and race, provides a basis for training, hiring, and retention for police offi... more considering gender and race, provides a basis for training, hiring, and retention for police officers. The purpose of this study is to identify muscular strength differences among racial groups from initial-recruit to in-service tests. Strength variables included bench press, bench press/lean mass and bench press/body mass. Scores were retrieved for the 1990 to 1995 recruit classes and were paired to the 2006 in-service fitness log. Sample included 309 officers: 30 females (13 black, 17 white) and 279 males (41 black, 238 white). Mean age of recruit was 24.6 ± 3.4 years and for in-service was 37.1 ± 3.7 years. Time between tests was 12.5 ± 2.0 years. Bench press strength significantly increased for all gender and racial groups. Black males were significantly stronger in bench press at initial-recruit and at in-service than white males. All racial and gender groups increased in bench press/lean mass, however, the increase in white females was not significant. No differences were found between black and white females in all strength variables at both testing periods. Black males were significantly stronger than white males in bench press/body mass only at the initial-recruit test. White males showed a significant increase in bench press/body mass over time, but they did not reach the strength level of the black males at in-service. Police departments, with a properly designed physical fitness program, can expect to see increases in strength of personnel over the first half of their careers; however, there are gender and racial differences.
2007 International Joint Conference on Neural Networks, 2007
Quantitative trait loci mapping is a growing field in genetic statistics. However, dealing with t... more Quantitative trait loci mapping is a growing field in genetic statistics. However, dealing with this type of data from a statistical perspective is often perilous. This work considers a model selection approach to quantitative trait loci analysis of the Arabidopsis Bay-O by Shahdara using a Bayesian framework, Markov Chain Monte Carlo method composition. The efficacy of this technique is demonstrated
Assessing the linear relationship between a set of continuous predictors and a continuous re- spo... more Assessing the linear relationship between a set of continuous predictors and a continuous re- sponse is a well studied problem in statistics and is applied in many data mining situations. L2 based methods such as ordinary least squares and principal components regression can be used to determine this relationship. However, both of these methods become impaired when mul- ticollinearity
Journal of Statistical Computation and Simulation, Jan 22, 2014
ABSTRACT Bayesian analysis often requires the researcher to employ Markov Chain Monte Carlo (MCMC... more ABSTRACT Bayesian analysis often requires the researcher to employ Markov Chain Monte Carlo (MCMC) techniques to draw samples from a posterior distribution which in turn is used to make inferences. Currently, several approaches to determine convergence of the chain as well as sensitivities of the resulting inferences have been developed. This work develops a Hellinger distance approach to MCMC diagnostics. An approximation to the Hellinger distance between two distributions f and g based on sampling is introduced. This approximation is studied via simulation to determine the accuracy. A criterion for using this Hellinger distance for determining chain convergence is proposed as well as a criterion for sensitivity studies. These criteria are illustrated using a dataset concerning the Anguilla australis, an eel native to New Zealand.
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Papers by Edward Boone