Choosing cutoff values for correlated continuous diagnostic data to estimate sensitivity and specificity

This dissertation includes two projects and an R package for the 1st project, focusing on choosing cutoff values to estimate the sensitivity and specificity for continuous diagnostic tests. A continuous diagnostic test needs to be dichotomized to generate positive and negative test outcomes by choosing a cutoff value. The choice of the cutoff value depends on the estimates of the sensitivity and specificity of the dichotomized test with this cutoff. There are two challenges during this process: 1) a typical experiment to validate a new diagnostic test usually involves multiple observations from the same subjects, resulting in correlated data values. This correlation increases the complexity of calculating the confidence intervals of the sensitivity and specificity given the true statuses. 2) In many diagnostic trials, the true statuses are unknown, which make it difficult even to calculate the point estimates of the sensitivity and specificity. In the 1st project (Chapter 2), we propose a method to calculate the confidence intervals of sensitivity and specificity with the true statuses of subjects given based on a parametric model for the correlated continuous diagnostic test data. In the second project (Chapter 3), we focus on the challenge of unknown statuses. Due to the lack of the statuses, only the model-based method can be used to estimate the sensitivity and specificity. However, the estimations of model parameters are difficult because of the unknown statuses. We propose a Bayesian model with latent variables to model the unknown statuses. In Chapter 4, I create an R package for the 1st project for future uses

X-ray diffuse scattering measurements of chemical short-range order and lattice strains in a highly magnetostrictive Fe0.813Ga0.187 alloy in an applied magnetic field

The rapid growth of the magnetostriction coefficient of ferromagnetic Fe1−xGax alloys that occurs at a composition range from

Effect of carbon addition on the single crystalline magnetostriction of Fe-X (X = Al and Ga) alloys

The effect of carbon addition on the magnetostriction of Fe–Ga and Fe–Al alloys was investigated and is summarized in this study. It was found that the addition of carbon generally increased the magnetostriction over binary alloys of Fe–Ga and Fe–Al systems. The formation of carbide in the Fe–Ga–C alloys with a composition near D03 phase region decreased the magnetostriction drastically. Fe–Al–C and Fe–Ga–C alloys responded differently to thermal treatments; the magnetostriction in the quenched Fe–Al–C alloys is equal to or slightly lower than that of the slow cooled as is observed in binary Fe–Al alloy; in contrast, the magnetostriction is generally higher in quenched Fe–Ga–C alloys than slow cooled condition, consistent with the behavior of binary alloys of Fe–Ga. A significant increase in magnetostriction between 25% and 165% depending on the phase region in Fe–Ga–C alloys by quenching was observed in the A2+D03 two-phase region and D03 single phase region

Correlating Gastrointestinal Histopathologic Changes to Clinical Disease Activity in Dogs With Idiopathic Inflammatory Bowel Disease

Prior studies have failed to detect a convincing association between histologic lesions of inflammation and clinical activity in dogs with inflammatory bowel disease (IBD). We hypothesized that use of a simplified histopathologic scoring system would improve the consistency of interpretation among pathologists when describing histologic lesions of gastrointestinal inflammation. Our aim was to evaluate the correlation of histopathologic changes to clinical activity in dogs with IBD using this new system. Forty-two dogs with IBD and 19 healthy control dogs were enrolled in this retrospective study. Endoscopic biopsies from the stomach, duodenum, ileum, and colon were independently scored by 8 pathologists. Clinical disease activity was scored using the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) or the Canine Chronic Enteropathy Clinical Activity Index (CCECAI), depending on the individual study center. Summative histopathological scores and clinical activity were calculated for each tissue (stomach, duodenum, ileum, and colon) and each tissue histologic score (inflammatory/morphologic feature). The correlation between CCECAI/CIBDAI and summative histopathologic score was significant (P < .05) for duodenum (r = 0.42) and colon (r = 0.33). In evaluating the relationship between histopathologic scores and clinical activity, significant (P < .05) correlations were observed for crypt dilation (r = 0.42), lamina propria (LP) lymphocytes (r = 0.40), LP neutrophils (r = 0.45), mucosal fibrosis (r = 0.47), lacteal dilation (r = 0.39), and villus stunting (r = 0.43). Compared to earlier grading schemes, the simplified scoring system shows improved utility in correlating histopathologic features (both summative histology scores and select histologic scores) to IBD clinical activity

Choosing cutoff values for correlated continuous diagnostic data to estimate sensitivity and specificity

This dissertation includes two projects and an R package for the 1st project, focusing on choosing cutoff values to estimate the sensitivity and specificity for continuous diagnostic tests. A continuous diagnostic test needs to be dichotomized to generate positive and negative test outcomes by choosing a cutoff value. The choice of the cutoff value depends on the estimates of the sensitivity and specificity of the dichotomized test with this cutoff. There are two challenges during this process: 1) a typical experiment to validate a new diagnostic test usually involves multiple observations from the same subjects, resulting in correlated data values. This correlation increases the complexity of calculating the confidence intervals of the sensitivity and specificity given the true statuses. 2) In many diagnostic trials, the true statuses are unknown, which make it difficult even to calculate the point estimates of the sensitivity and specificity. In the 1st project (Chapter 2), we propose a method to calculate the confidence intervals of sensitivity and specificity with the true statuses of subjects given based on a parametric model for the correlated continuous diagnostic test data. In the second project (Chapter 3), we focus on the challenge of unknown statuses. Due to the lack of the statuses, only the model-based method can be used to estimate the sensitivity and specificity. However, the estimations of model parameters are difficult because of the unknown statuses. We propose a Bayesian model with latent variables to model the unknown statuses. In Chapter 4, I create an R package for the 1st project for future uses.</p

A Permutation Test of Genetic Association between Salmonella Isolated On-farm and At-abattoir using Amplified Fragment Length Polymorphism

Pork and pork products have been identified as a significant source of Salmonella infection, which is a major public health concern. The contamination of Salmonella on pork can happen both on farms (before slaughter) and at abattoirs (after slaughter). Salmonella isolates were collected from both feces on farms and lymph nodes in the abattoir to determine if contamination at abattoirs can be linked back to the farms of origin. Molecular subtyping of the isolated Salmonella was performed using amplified fragment length polymorphism (AFLP), a Polymerase chain reaction-based, high-throughput, relatively inexpensive method. In this paper, we develop a permutation test for the genetic association of Salmonella isolated on-farm and at-abattoir using the AFLP data. Simulation studies show that the proposed permutation test controls the type I error rate appropriately as well as possesses high power. An application of the proposed permutation test to the real Salmonella ALFP data results in a p-value of 0.038 which shows strong evidence of association between Salmonella isolated on-farm and at-abattoir.This article is from Biometrics & Biostatistics 5 (2014); 204, doi: 10.472/2155-6180.1000204. Posted with permission.</p

X-ray diffuse scattering measurements of chemical short-range order and lattice strains in a highly magnetostrictive Fe0.813Ga0.187 alloy in an applied magnetic field

The rapid growth of the magnetostriction coefficient of ferromagnetic Fe1−xGax alloys that occurs at a composition range from 0This article is from Physical Review B 85, no. 21 (2012): 214437, doi:10.1103/PhysRevB.85.214437.</p

Effect of carbon addition on the single crystalline magnetostriction of Fe-X (X = Al and Ga) alloys

The effect of carbon addition on the magnetostriction of Fe–Ga and Fe–Al alloys was investigated and is summarized in this study. It was found that the addition of carbon generally increased the magnetostriction over binary alloys of Fe–Ga and Fe–Al systems. The formation of carbide in the Fe–Ga–C alloys with a composition near D03 phase region decreased the magnetostriction drastically. Fe–Al–C and Fe–Ga–C alloys responded differently to thermal treatments; the magnetostriction in the quenched Fe–Al–C alloys is equal to or slightly lower than that of the slow cooled as is observed in binary Fe–Al alloy; in contrast, the magnetostriction is generally higher in quenched Fe–Ga–C alloys than slow cooled condition, consistent with the behavior of binary alloys of Fe–Ga. A significant increase in magnetostriction between 25% and 165% depending on the phase region in Fe–Ga–C alloys by quenching was observed in the A2+D03 two-phase region and D03 single phase region.The following article appeared in Journal of Applied Physics 107 (2010): 053520 and may be found at http://dx.doi.org/10.1063/1.3311884.</p