A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Objectives: There were two main objectives of this study. The first was to determine the diagnostic threshold of hemodynamic values derived from impedance cardiography (ICG) and whether these thresholds are sex specific in determining the etiology of shortness of breath (dyspnea) in patients presenting to the emergency department (ED). The second was to compare ICG hemodynamic values with the results of bedside cardiothoracic ultrasonography and B-type natriuretic peptide (BNP) levels in patients with dyspnea in the ED. Methods: A prospective cohort of 50 adult patients presenting to the Maricopa Medical Center ED with dyspnea were evaluated using ICG, bedside cardiothoracic ultrasound, and BNP to determine the etiology of their complaint. The final etiology was determined through review of the treating practitioner’s final diagnosis and evaluation of the data available from the patient’s ED visit. Cardiac and non-cardiac groups were then compared to determine the accuracy, sensitivity, and specificity of ICG, bedside cardiothoracic ultrasound and BNP in identifying the etiology of their complaint. Results: BNP at a threshold of 164 pg/mL proved to be the most accurate with a sensitivity of 84.21%, a specificity of 79.17% and an area under the curve (AUC) of 0.8684 when plotted on a receiver operating characteristics (ROC) curve. Right ventricle diameter during systole was the most accurate bedside ultrasound parameter; at a threshold of 1.71 cm it showed a sensitivity of 77.78%, a specificity of 60.00% and an AUC of 0.7489. Heather index (HI) was the most accurate ICG parameter; at a threshold of 9.2 Ohm/sec2 it showed a sensitivity of 72.41%, a specificity of 85.00%, and an AUC of 0.8405. Only HI showed a significant difference between male and female patients. HI in females at a threshold of 10.4 Ohm/sec2 was 87.50% sensitive and 87.50% specific with an AUC of 0.9297. In males a HI threshold of 6.9 Ohm/sec2 was 69.23% sensitive and 66.67% specific with an AUC of 0.7564. Conclusion: Bedside cardiac ultrasound was technically challenging and the least accurate modality. ICG demonstrated some sex specific thresholds and while an easy to use modality, it was slightly less accurate than BNP which proved to be a simple and accurate modality for determining a cardiac or non-cardiac etiology of dyspnea.

Prostate cancer is the most commonly diagnosed disease and second most commonly caused death among men in America. Although much controversy surrounds the current methods of detection, PSA test and biopsy, no new methods have been approved as an effective method of detection. Biomarkers and non-invasive means of detection are being investigated everyday in hopes of discovering new information that could be of use in the prostate cancer field. One such non-invasive technology is the use of an electronic nose. The electronic nose technology has been utilized in the agricultural, food, biomedical, and environmental. The objective of this current study is to determine the effectiveness of the electronic nose to discriminate between prostate cancer cells (DU-145 and PC-3) and non-tumor forming cells from the urinary tract (SVHUC). Specific factors that will be investigated are incubation period and cell population. For all three cell lines, two cell populations of 75,000 and 150,000 cells were cultured and tested after 2, 8, 12, and 24 hours using a conducting polymer based hand-held electronic nose. Multivariate analysis was performed on the data and determined that the greatest discrimination between incubation periods was between 2 hours of incubation and the remaining periods of 8, 12, and 24 hour periods. This presents the idea that by 8 hours, ample volatiles were produced to be detected by the electronic nose. Additionally, when compared to one another, all three cell lines showed distinct differences. The cell lines most closely related were PC-3 and DU-145, the prostate cancer cell lines. However some variation was seen between these cell lines, which may be attributed to the presence of PSA in PC-3 cells or other factors affecting prostate cancer patients. Finally, PCA plots clearly illustrated that after 2 hours of incubation, sufficient volatiles were produced to allow the electronic nose to clearly discriminate the three cell lines from one another, demonstrating the importance of incubation period on successful discrimination. Based on the findings that the electronic nose was effective at discriminating the three cell lines, testing was completed to determine if cell population or cell maturity had the greatest effect on discrimination. The cell lines were cultured and tested immediately using an initial cell population of the highest cell population observed after a 72 hour incubation period. The results concluded that when the cell lines were tested immediately after culturing, the Cyranose was able to detect the individual cell lines in culture while also determining a range of detection for each cell line. The range of detection for DU-145 was found to be 26,200 to 262,000 cells based on interclass m-distances of 6.829-9.170 for cell populations lower than 26,200. A range of detection of 51,400 to 514,000 cells was concluded for PC-3 cells based on interclass m-distances of 5.690-7.400 for cell populations lower than 51,400. Finally, the results showed a range of detection of 19,000 to 190,000 cells for SVHUC based on interclass m-distances of 5.520-9.076 for cell populations lower than 19,000. However, when attempting to discriminate the three cell lines against one another immediately after culture, the electronic nose was unable to make clear distinctions between the three cell lines. When testing cancerous and non-cancerous cells, incubation period of the cells should be the only factor considered. It is evident that the cells need time to metabolize and produce volatiles so that the electronic nose can clearly distinguish these cells from one another in culture. / Master of Science

Der Small-Punch-Test (SPT) ist eine vielversprechende minimalinvasive mechanische Prüfmethode, wenn nur sehr wenig Material für Proben zur Verfügung steht. Die vorliegende Arbeit hat das Ziel, aus Small-Punch-Kleinstproben wahre Materialparameter der elastisch-plastischen Verformung und des spröden Versagens zu bestimmen. Die Kraft-Verschiebungs-Kurve des Versuchs stellt die nichtlineare Materialantwort der inhomogen beanspruchten Probe dar. Das inverse Problem der Identifikation konstitutiver Materialparameter wird numerisch mit Hilfe von Finite-Elemente-Simulationen in Verbindung mit einem Response-Surface-Modell und nichtlinearer Optimierungsverfahren gelöst, indem die Abweichung zwischen gemessener und simulierter Kurve minimiert wird. Mit Hilfe einer eigens entwickelten Kühlapparatur wurden Versuche mit ferritischen Stählen von Raumtemperatur bis hinunter zu -191°C durchgeführt und die temperaturabhängigen Fließkurven identifiziert. Bei tiefen Temperaturen wurden die Weibull-Parameter der zufällig streuenden Sprödbruchfestigkeit bestimmt und die Bruchzähigkeitsverteilung durch Simulation einer CT-Probe vorhergesagt. Für eine Aluminiumoxidkeramik wurden ebenfalls die Weibull-Parameter bestimmt sowie mit Indenterrissen versehene Proben zur Abschätzung der Bruchzähigkeit verwendet. / The small punch test (SPT) is a promising minimally invasive material testing method, especially in cases where only small amounts of material are available. This thesis is aimed at identifying true material parameters of elastic-plastic deformation and brittle fracture. The load-displacement curve of the test represents the non-linear material response of the nonuniformly stressed specimen. The identification of material parameters of constitutive laws is an inverse problem, which is solved numerically. Finite element simulations together with a response surface model and nonlinear optimization techniques are applied to minimize the error between measured and simulated curves. A specially developed cooling apparatus was used to perform tests with ferritic steels from room temperature down to -191°C. The temperature dependent yield stresses and hardening curves were identified. At low temperatures the Weibull parameters of randomly distributed cleavage fracture strength were estimated. The fracture toughness distribution was then predicted by the help of a finite element simulation of a CT specimen. Furthermore the Weibull parameters of an alumina ceramic were determined and its fracture toughness was predicted using specimens prepared with indentation cracks.

Der Small-Punch-Test (SPT) ist eine vielversprechende minimalinvasive mechanische Prüfmethode, wenn nur sehr wenig Material für Proben zur Verfügung steht. Die vorliegende Arbeit hat das Ziel, aus Small-Punch-Kleinstproben wahre Materialparameter der elastisch-plastischen Verformung und des spröden Versagens zu bestimmen. Die Kraft-Verschiebungs-Kurve des Versuchs stellt die nichtlineare Materialantwort der inhomogen beanspruchten Probe dar. Das inverse Problem der Identifikation konstitutiver Materialparameter wird numerisch mit Hilfe von Finite-Elemente-Simulationen in Verbindung mit einem Response-Surface-Modell und nichtlinearer Optimierungsverfahren gelöst, indem die Abweichung zwischen gemessener und simulierter Kurve minimiert wird. Mit Hilfe einer eigens entwickelten Kühlapparatur wurden Versuche mit ferritischen Stählen von Raumtemperatur bis hinunter zu -191°C durchgeführt und die temperaturabhängigen Fließkurven identifiziert. Bei tiefen Temperaturen wurden die Weibull-Parameter der zufällig streuenden Sprödbruchfestigkeit bestimmt und die Bruchzähigkeitsverteilung durch Simulation einer CT-Probe vorhergesagt. Für eine Aluminiumoxidkeramik wurden ebenfalls die Weibull-Parameter bestimmt sowie mit Indenterrissen versehene Proben zur Abschätzung der Bruchzähigkeit verwendet. / The small punch test (SPT) is a promising minimally invasive material testing method, especially in cases where only small amounts of material are available. This thesis is aimed at identifying true material parameters of elastic-plastic deformation and brittle fracture. The load-displacement curve of the test represents the non-linear material response of the nonuniformly stressed specimen. The identification of material parameters of constitutive laws is an inverse problem, which is solved numerically. Finite element simulations together with a response surface model and nonlinear optimization techniques are applied to minimize the error between measured and simulated curves. A specially developed cooling apparatus was used to perform tests with ferritic steels from room temperature down to -191°C. The temperature dependent yield stresses and hardening curves were identified. At low temperatures the Weibull parameters of randomly distributed cleavage fracture strength were estimated. The fracture toughness distribution was then predicted by the help of a finite element simulation of a CT specimen. Furthermore the Weibull parameters of an alumina ceramic were determined and its fracture toughness was predicted using specimens prepared with indentation cracks.