Development of safety performance functions for empirical Bayes estimation of crash reduction factors

Crash reduction factors (CRFs) are used to estimate the potential number of traffic crashes expected to be prevented from investment in safety improvement projects. The method used to develop CRFs in Florida has been based on the commonly used before-and-after approach. This approach suffers from a widely recognized problem known as regression-to-the-mean (RTM). The Empirical Bayes (EB) method has been introduced as a means to addressing the RTM problem. This method requires the information from both the treatment and reference sites in order to predict the expected number of crashes had the safety improvement projects at the treatment sites not been implemented. The information from the reference sites is estimated from a safety performance function (SPF), which is a mathematical relationship that links crashes to traffic exposure. The objective of this dissertation was to develop the SPFs for different functional classes of the Florida State Highway System. Crash data from years 2001 through 2003 along with traffic and geometric data were used in the SPF model development. SPFs for both rural and urban roadway categories were developed. The modeling data used were based on one-mile segments that contain homogeneous traffic and geometric conditions within each segment. Segments involving intersections were excluded. The scatter plots of data show that the relationships between crashes and traffic exposure are nonlinear, that crashes increase with traffic exposure in an increasing rate. Four regression models, namely, Poisson (PRM), Negative Binomial (NBRM), zero-inflated Poisson (ZIP), and zero-inflated Negative Binomial (ZINB), were fitted to the one-mile segment records for individual roadway categories. The best model was selected for each category based on a combination of the Likelihood Ratio test, the Vuong statistical test, and the Akaike's Information Criterion (AIC). The NBRM model was found to be appropriate for only one category and the ZINB model was found to be more appropriate for six other categories. The overall results show that the Negative Binomial distribution model generally provides a better fit for the data than the Poisson distribution model. In addition, the ZINB model was found to give the best fit when the count data exhibit excess zeros and over-dispersion for most of the roadway categories. While model validation shows that most data points fall within the 95% prediction intervals of the models developed, the Pearson goodness-of-fit measure does not show statistical significance. This is expected as traffic volume is only one of the many factors contributing to the overall crash experience, and that the SPFs are to be applied in conjunction with Accident Modification Factors (AMFs) to further account for the safety impacts of major geometric features before arriving at the final crash prediction. However, with improved traffic and crash data quality, the crash prediction power of SPF models may be further improved.

Real-time biosensor for the assessment of nanotoxicity and cancer electrotherapy

Knowledge of cell electronics has led to their integration to medicine either by physically interfacing electronic devices with biological systems or by using electronics for both detection and characterization of biological materials. In this dissertation, an electrical impedance sensor (EIS) was used to measure the electrode surface impedance changes from cell samples of human and environmental toxicity of nanoscale materials in 2D and 3D cell culture models. The impedimetric response of human lung fibroblasts and rainbow trout gill epithelial cells when exposed to various nanomaterials was tested to determine their kinetic effects towards the cells and to demonstrate the biosensor's ability to monitor nanotoxicity in real-time. Further, the EIS allowed rapid, real-time and multi-sample analysis creating a versatile, noninvasive tool that is able to provide quantitative information with respect to alteration in cellular function. We then extended the application of the unique capabilities of the EIS to do real-time analysis of cancer cell response to externally applied alternating electric fields at different intermediate frequencies and low-intensity. Decreases in the growth profiles of the ovarian and breast cancer cells were observed with the application of 200 and 100 kHz, respectively, indicating specific inhibitory effects on dividing cells in culture in contrast to the non-cancerous HUVECs and mammary epithelial cells. We then sought to enhance the effects of the electric field by altering the cancer cell's electronegative membrane properties with HER2 antibody functionalized nanoparticles. An Annexin V/EthD-III assay and zeta potential were performed to determine the cell death mechanism indicating apoptosis and a decrease in zeta potential with the incorporation of the nanoparticles. With more negatively charged HER2-AuNPs attached to the cancer cell membrane, the decrease in membrane potential would thus leave the cells more vulnerable to the detrimental effects of the applied electric field due to the decrease in surface charge. Therefore, by altering the cell membrane potential, one could possibly control the fate of the cell. This whole cell-based biosensor will enhance our understanding of the responsiveness of cancer cells to electric field therapy and demonstrate potential therapeutic opportunities for electric field therapy in the treatment of cancer.

Real-time Biosensor for the Assessment of Nanotoxicity and Cancer Electrotherapy

Knowledge of cell electronics has led to their integration to medicine either by physically interfacing electronic devices with biological systems or by using electronics for both detection and characterization of biological materials. In this dissertation, an electrical impedance sensor (EIS) was used to measure the electrode surface impedance changes from cell samples of human and environmental toxicity of nanoscale materials in 2D and 3D cell culture models. The impedimetric response of human lung fibroblasts and rainbow trout gill epithelial cells when exposed to various nanomaterials was tested to determine their kinetic effects towards the cells and to demonstrate the biosensor’s ability to monitor nanotoxicity in real-time. Further, the EIS allowed rapid, real-time and multi-sample analysis creating a versatile, noninvasive tool that is able to provide quantitative information with respect to alteration in cellular function. We then extended the application of the unique capabilities of the EIS to do real-time analysis of cancer cell response to externally applied alternating electric fields at different intermediate frequencies and low-intensity. Decreases in the growth profiles of the ovarian and breast cancer cells were observed with the application of 200 and 100 kHz, respectively, indicating specific inhibitory effects on dividing cells in culture in contrast to the non-cancerous HUVECs and mammary epithelial cells. We then sought to enhance the effects of the electric field by altering the cancer cell’s electronegative membrane properties with HER2 antibody functionalized nanoparticles. An Annexin V/EthD-III assay and zeta potential were performed to determine the cell death mechanism indicating apoptosis and a decrease in zeta potential with the incorporation of the nanoparticles. With more negatively charged HER2-AuNPs attached to the cancer cell membrane, the decrease in membrane potential would thus leave the cells more vulnerable to the detrimental effects of the applied electric field due to the decrease in surface charge. Therefore, by altering the cell membrane potential, one could possibly control the fate of the cell. This whole cell-based biosensor will enhance our understanding of the responsiveness of cancer cells to electric field therapy and demonstrate potential therapeutic opportunities for electric field therapy in the treatment of cancer.

A theory of constraints service systems improvement method: Case of the airline turnaround problem

This dissertation develops a process improvement method for service operations based on the Theory of Constraints (TOC), a management philosophy that has been shown to be effective in manufacturing for decreasing WIP and improving throughput. While TOC has enjoyed much attention and success in the manufacturing arena, its application to services in general has been limited. The contribution to industry and knowledge is a method for improving global performance measures based on TOC principles. The method proposed in this dissertation will be tested using discrete event simulation based on the scenario of the service factory of airline turnaround operations. To evaluate the method, a simulation model of aircraft turn operations of a U.S. based carrier was made and validated using actual data from airline operations. The model was then adjusted to reflect an application of the Theory of Constraints for determining how to deploy the scarce resource of ramp workers. The results indicate that, given slight modifications to TOC terminology and the development of a method for constraint identification, the Theory of Constraints can be applied with success to services. Bottlenecks in services must be defined as those processes for which the process rates and amount of work remaining are such that completing the process will not be possible without an increase in the process rate. The bottleneck ratio is used to determine to what degree a process is a constraint. Simulation results also suggest that redefining performance measures to reflect a global business perspective of reducing costs related to specific flights versus the operational local optimum approach of turning all aircraft quickly results in significant savings to the company. Savings to the annual operating costs of the airline were simulated to equal 30% of possible current expenses for misconnecting passengers with a modest increase in utilization of the workers through a more efficient heuristic of deploying them to the highest priority tasks. This dissertation contributes to the literature on service operations by describing a dynamic, adaptive dispatch approach to manage service factory operations similar to airline turnaround operations using the management philosophy of the Theory of Constraints.

Positron emission tomography (PET) tumor segmentation and quantification: Development of new algorithms

Tumor functional volume (FV) and its mean activity concentration (mAC) are the quantities derived from positron emission tomography (PET). These quantities are used for estimating radiation dose for a therapy, evaluating the progression of a disease and also use it as a prognostic indicator for predicting outcome. PET images have low resolution, high noise and affected by partial volume effect (PVE). Manually segmenting each tumor is very cumbersome and very hard to reproduce. To solve the above problem I developed an algorithm, called iterative deconvolution thresholding segmentation (IDTS) algorithm; the algorithm segment the tumor, measures the FV, correct for the PVE and calculates mAC. The algorithm corrects for the PVE without the need to estimate camera's point spread function (PSF); also does not require optimizing for a specific camera. My algorithm was tested in physical phantom studies, where hollow spheres (0.5-16 ml) were used to represent tumors with a homogeneous activity distribution. It was also tested on irregular shaped tumors with a heterogeneous activity profile which were acquired using physical and simulated phantom. The physical phantom studies were performed with different signal to background ratios (SBR) and with different acquisition times (1-5 min). The algorithm was applied on ten clinical data where the results were compared with manual segmentation and fixed percentage thresholding method called T50 and T60 in which 50% and 60% of the maximum intensity respectively is used as threshold. The average error in FV and mAC calculation was 30% and -35% for 0.5 ml tumor. The average error FV and mAC calculation were ~5% for 16 ml tumor. The overall FV error was ∼10% for heterogeneous tumors in physical and simulated phantom data. The FV and mAC error for clinical image compared to manual segmentation was around -17% and 15% respectively. In summary my algorithm has potential to be applied on data acquired from different cameras as its not dependent on knowing the camera's PSF. The algorithm can also improve dose estimation and treatment planning.^

Positron Emission Tomography (PET) Tumor Segmentation and Quantification: Development of New Algorithms

Tumor functional volume (FV) and its mean activity concentration (mAC) are the quantities derived from positron emission tomography (PET). These quantities are used for estimating radiation dose for a therapy, evaluating the progression of a disease and also use it as a prognostic indicator for predicting outcome. PET images have low resolution, high noise and affected by partial volume effect (PVE). Manually segmenting each tumor is very cumbersome and very hard to reproduce. To solve the above problem I developed an algorithm, called iterative deconvolution thresholding segmentation (IDTS) algorithm; the algorithm segment the tumor, measures the FV, correct for the PVE and calculates mAC. The algorithm corrects for the PVE without the need to estimate camera’s point spread function (PSF); also does not require optimizing for a specific camera. My algorithm was tested in physical phantom studies, where hollow spheres (0.5-16 ml) were used to represent tumors with a homogeneous activity distribution. It was also tested on irregular shaped tumors with a heterogeneous activity profile which were acquired using physical and simulated phantom. The physical phantom studies were performed with different signal to background ratios (SBR) and with different acquisition times (1-5 min). The algorithm was applied on ten clinical data where the results were compared with manual segmentation and fixed percentage thresholding method called T50 and T60 in which 50% and 60% of the maximum intensity respectively is used as threshold. The average error in FV and mAC calculation was 30% and -35% for 0.5 ml tumor. The average error FV and mAC calculation were ~5% for 16 ml tumor. The overall FV error was ~10% for heterogeneous tumors in physical and simulated phantom data. The FV and mAC error for clinical image compared to manual segmentation was around -17% and 15% respectively. In summary my algorithm has potential to be applied on data acquired from different cameras as its not dependent on knowing the camera’s PSF. The algorithm can also improve dose estimation and treatment planning.