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  • ItemOpen Access
    Tumor microenvironment in spontaneously occuring tumors and in vitro evaluation of hypoxia associated mutagenesis
    (Colorado State University. Libraries, 2008) Trncic, Nadira, author; LaRue, Susan M., advisor
    The importance of the tumor oxygenation status in tumor progression and tumor response to radiation and other forms of treatment has been investigated in many experimental and clinical studies. Oxygen status can impact cell killing associated with radiation treatment and, interestingly radiation can also impact subsequent oxygen levels. Part I of my dissertation is concerned with this phenomenon of reoxygenation. A multiparameter study was conducted in naturally occurring canine tumors to evaluate physiological changes in the tumor microenvironment following a 3 Gy fraction of radiation. Pre-treatment values of partial pressure of oxygen, interstitial fluid pressure, microvascular perfusion, level of apoptosis, and microvessel density were compared to the 24 hours post-radiation measurements in the same location. I analyzed changes in all parameters and evaluated the relationship between parameters and pO2. In disagreement with my working hypothesis, I only found inverse correlation between changes in oxygen level and changes in IFP. In Part II, I used the CHO AL mutation assay to investigate the role of hypoxia alone in the induction of mutagenesis. After exposing cells to different hypoxic conditions I found that only severe hypoxia can cause mutations in human-hamster hybrid cells (AL). Level of oxygen that induced mutations was less than 0.63 mm Hg. Both the complement-mediated AL mutation assay and the flow cytometry mutation assay were done. Mutant cells were sorted from the mutant peak, and the clonal populations of cells were analyzed with the AL flow cytometry assay to determine if cells were really mutated (negative for CD59) and not just downregulated in hypoxia. Quantitative analysis of mutations that were performed did not detect any changes in the CD59 gene. Tumor reoxygenation, as shown here, may not be associated with improved tumor perfusion, but rather with other factors such as decreased oxygen consumption. These studies proved that severe hypoxia can cause mutations and possibly tumor genetic instability, and that those levels of oxygenation can be found in spontaneous tumors in dogs, which are a great tumor model for translating findings to human cancers.
  • ItemOpen Access
    Analyses and exposure assessment of bacterial endotoxin in agricultural environments
    (Colorado State University. Libraries, 2008) Saito, Rena, author; Reynolds, Stephen J., advisor
    Endotoxins, or lipopolysaccharides (LPS), found in organic dust are a component of the cell membrane of Gram-negative bacteria that play an important role in respiratory disease. However, accurate endotoxin measurements are difficult in agricultural environments since agricultural dusts contain a complex mixture of biological and chemical agents. This dissertation research was designed to improve the understanding of the variability in endotoxin measurements in agricultural environments. The first study determined patterns of 3-OHFA distribution in dusts from dairy farms, cattle feedlots, grain elevators, and farms, and evaluated correlations between the GC/EI-MS and the rFC bioassay results. Patterns of 3-OHFA distribution varied by dust type; livestock dusts contained approximately two times higher concentrations of 3-OHFAs than grain dusts. Pearson correlations and multiple regressions showed higher correlations between GC/EI-MS and rFC results for livestock dusts than for grain dusts. Odd-chain length 3-OHFAs were found to correlate with rFC responses, as well as with even-chain length 3-OHFAs. The second study evaluated traditional LAL and novel rFC assay responses to endotoxins in chicken, dairy, horse, swine, and turkey dusts, and investigated potential interference with assays using GC/EI-MS. Strong positive correlations existed between LAL and rFC results, but responses to assays varied by dust type. LAL overestimated/rFC underestimated endotoxin exposures in chicken and horse dusts, and LAL underestimated/rFC overestimated endotoxin concentrations in dairy, swine, and turkey dusts. The variability in assay responses might be explained by differences in bacterial composition and other dust components; the rFC assay may react positively with Actinobacteria. The third study characterized agricultural tasks and evaluated determinants of personal dust and endotoxin exposures in dairy farms, cattle feedlots, grain elevators, and farms. Dust and endotoxin exposures differed by agricultural environment and by task and combinations of tasks varied by environment. Regression analysis indicated that hours at running legs in grain elevators was the major determinant of dust. Hours at running legs in grain elevator and hours at feeding livestock in cattle feedlots were two major determinants in endotoxin measurements. This dissertation addressed the need for understanding differences in agricultural environments for endotoxin exposure assessment.
  • ItemOpen Access
    Epidemiologic studies of hard tick-associated illness in the United States
    (Colorado State University. Libraries, 2009) Murphree, Rendi, author; Bachand, Annette M., advisor
    This dissertation describes three epidemiologic studies of hard tick-associated illness in the United States. The first is the prospective health assessment of Fort Campbell, Kentucky patrons bitten by ticks during 2004-2006. The study was designed to determine the frequency, clinical characteristics, and etiology of Amblyomma americanum-associated illness and to identify associated risk factors. Amblyomma americanum is an aggressive human biting tick associated with a Lyme disease-like illness of unknown etiology. Study findings suggested that a variety of symptoms were temporally associated with tick bite but data provided no clear evidence that symptoms were caused by an infectious process. Removing ticks by hand or being bitten on a limb may have been risk factors for illness. The second examines 248,074 cases of Lyme disease reported to the Centers for Disease Control during 1992-2006 using descriptive and inferential statistics. In the United States, Lyme disease is caused by Borrelia burgdorferi sensu stricto, a spirochete transmitted to humans by infected Ixodes scapularis and I. pacificus ticks. During the 15-year study period, the number of cases reported annually increased 101% and the majority of cases occurred in northeastern and north-central states. An increasing trend in the number of counties reporting at least one case annually was observed in Minnesota, Rhode Island, and Wisconsin. A disproportionate increasing trend in reported cases was observed in children and young males compared with other demographic groups. The third study is a pilot ecologic analysis of human social or economic factors affecting, or resulting from, Lyme disease emergence. The objectives were to identify space-time clusters of increased Lyme disease risk and determine if risk could be partially explained using existing data on environment, socioeconomics, and healthcare. As expected, Ixodes tick distribution was a significant predictor of counties with increased risk. Measures of socioeconomic status surfaced as predictors of ecologic risk, and it appeared that persons of high SES lived where ticks were reported in northeastern states and persons of low SES lived where ticks were reported in the north-central states.
  • ItemOpen Access
    Characterizing in vitro propagation and radiation response of murine mammary stem cells
    (Colorado State University. Libraries, 2009) Magers, Tonya Sirisalee, author; Ullrich, Robert L., advisor
    Stem cells in breast tissue may be sensitive to known carcinogens (i.e. ionizing radiation), which impact their susceptibility to transformation. The involvement of mammary stem cells in tumorigenesis could explain the heterogeneity and molecular complexity of breast cancer. However, the involvement and the underlying mechanisms of such targets have yet to be fully elucidated. This study was designed to investigate mammary stem cells as plausible targets of radiation-induced damage in radiation-induced mammary carcinogenesis. We utilized an in vitro system (mammospheres) that was developed for the detection of mammary stem cells. We expanded the applicability of this in vitro assay through the development of a methodology and novel size criteria to address specific radiation biology endpoints. We applied the methodology and size criteria to analyze the effects of ionizing radiation (IR) on the survival of mammary stem cells derived from mice carrying one mutated copy of Atm. Our results demonstrated that mammary stem cells derived from Atm-ΔSRI heterozygous mice (Atm(+/ΔSRI)) do not exhibit increased radiation sensitivity compared to their wildtype littermates (Atm(+/+)). In fact, mammary stem cells derived from Atm-ΔSRI heterozygous mice exhibited increased radioresistance. To our knowledge, this is the first study to examine the radiation response of mammary stem cells as mammospheres using Atm heterozygous mice carrying a known missense mutation found in human A-T. These studies demonstrated the proof of principle for this model development and the utility of this methodology. Our improved methodology has expanded the feasibility and the applicability of this model to examine numerous functional in vitro endpoints. We believe the methodology described here will facilitate investigating the radiation response of mammary stem cells and their progeny, and key components involved in early events of the carcinogenic process in murine model systems.
  • ItemOpen Access
    Physiologically-based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling of 3,3',4,4',5-pentachlorobiphenyl (PCB126)
    (Colorado State University. Libraries, 2008) Lohitnavy, Manupat, author; Yang, Raymond H. S., advisor; Reisfeld, Brad, advisor
    3,3',4',4',5-Pentachlorobiphenyl (PCB126) is a persistent environment carcinogen. Despite its high lipophilicity, PCB126 was primarily recovered from liver. In addition, PCB126 could achieve its steady state in the liver in a relatively short period of time. Using a three-dimensional quantitative structure-activity relationship (3D-QSAR) model, PCB126 was predicted to be a Mrp2 substrate with a relatively high binding affinity (Km) value. With this newly emerging knowledge, we incorporated a Mrp2-mediated excretion process into our physiologically-based pharmacokinetic (PBPK) model of PCB126. Our model could describe numerous tissue concentration-time courses in different dosing conditions. Our PBPK model revealed an important role of Mrp2 in PCB126 disposition. In addition, to establish a correlation between PCB126 pharmacokinetics and its pharmacodynamic (PD) endpoint (i.e. hepatocarcinogenic effect), we used a chosen internal dose surrogate [i.e. area under the curve of PCB126 in liver (AUCLiver)] to predict the PD effect of PCB126. With this PBPK/PD model, correlation between the AUCLiver and our liver glutathione- S-transferase placental form positive (GSTP+) foci development data was demonstrated. We also conducted a pharmacokinetic interaction study between PCB126 and methotrexate (MTX), a known Mrp2 substrate, by exposing rats with multiple oral doses of PCB126 followed by an oral single dose of MTX. Liver samples were collected and analyzed for hepatic MTX and PCB126 concentration levels. Using a PBPK modeling technique incorporating with competitive inhibition processes between the two chemicals at the level of hepatic Mrp2, liver concentration-time courses of both chemicals were successfully simulated. To further investigate PD effects of PCB126 within liver GSTP + foci, we conducted an experiment by exposing rats with PCB126 using our modified liver foci bioassay up to 6 months. Liver foci positive or negative for GSTP+, transforming growth factor-α+ (TGFα+) and transforming growth factor-β Type 2 receptor (TGFβ2Rc-) were investigated. In rats treated with PCB126, time-dependent changes in all of three biomarkers were observed. Interestingly, when the GSTP+ foci were categorized into four phenotypic groups according to their TGFα and TGFβ2Rc expression, GSTP+ foci with TGFα expression and absence of TGFβ2Rc expression had significantly higher hepatocyte division rates than those of GSTP+ foci without TGFα expression and with TGFβ2Rc expression.
  • ItemOpen Access
    Comparison of occupational and environmental exposures at Colorado dairies
    (Colorado State University. Libraries, 2008) Lester, Bradley Raymond, author; Reynolds, Stephen J., advisor
    Occupational contaminant levels and environmental emissions were compared at two Colorado dairies. Along with meteorological conditions, analytes measured included odor, hydrogen sulfide, ammonia, total and inhalable particulate and endotoxin, and bioaerosols including fungi, mesophilic bacteria, and gram-negative bacteria. Meteorologic conditions varied widely in temperature (range: -12.5 - 4 1.1°C), relative humidity (range: 0.6 - 92.3%) and wind speeds during sampling (range: 0.48 - 8.66 m/s). Geometric mean bioaerosol concentrations for the Anderson sampler and SKC Biosampler include: mesophilic bacteria, 1282 and 383 CFU/m3, gram-negative bacteria, 667 and 265 CFU/m 3, and fungi, 781 and 252 CFU/m3. The Anderson sampler collected significantly (p<0.001) higher bioaerosol concentrations for all three categories. Peak ammonia levels at the study and control dairies ranged from 2.0 - 142 and 2.0 - 23 ppm. Peak ammonia was significantly (p<0.05) higher at the study dairy. Mean hydrogen sulfide levels at the study and control dairies ranged from 4.0 - 394 and 4.0 - 890 ppb. Peak hydrogen sulfide levels at the study and control dairies ranged from 37 - 17,000 and 210 - 5,200 ppb. Mean peak hydrogen sulfide was significantly (p<0.05) higher at the control dairy. Odor measures ranged from 0-15 D/T at both dairies. Inhalable particulate at study and control dairy lagoons ranged from < LOD - 2.3 mg/m3. Inhalable endotoxin at study and control dairy lagoons ranged from 2.1 - 487.2 EU/m3. Total particulate at study and control dairy lagoons ranged from < LOD to 2.4 mg/m3. Total endotoxin at study and control lagoons ranged from 2.5 - 6587 EU/m3. Inhalable particulate for tasks at both dairies ranged from 0.06 - 8.0 mg/m3. Total particulate for tasks at both dairies ranged from 0.03 - 6.9 mg/m 3. Inhalable endotoxin for tasks at both dairies ranged from 2.0 - 11096 EU/m3. Total endotoxin for tasks at both dairies ranged from 5.9 - 6758 EU/m3. Supported by NIOSH Grant 5U500H008085.
  • ItemOpen Access
    Depressive symptoms, drinking patterns and farm-work injury among Colorado farm residents
    (Colorado State University. Libraries, 2008) Leff, Marilyn Grace Petersen, author; Stallones, Lorann, advisor
    Introduction. Farm-work injury is a major occupational health problem. The purposes of this study were to (1) describe farm residents who are heavy drinkers with high depressive symptoms and (2) assess the association between farm-work injury and depressive symptoms, farm-work injury and drinking pattern, and farm-work injury and the interaction of these two in cross-sectional and prospective analysis. Methods. A population-based sample of farm residents within Colorado was followed for three years. Information on socio-demographic and health related variables were gathered including farm-work injuries, depressive symptoms, and alcohol use. Multinomial logistic regression was used to describe differences and similarities between farm residents with high depressive symptoms and heavy drinking, high depressive symptoms only, and heavy drinking only compared to those without either. Poisson regression with repeated measures was conducted to estimate the effect of depressive symptoms and alcohol use and the interaction between the two variables on farm-work injury. Results. An association between smoking and co-occurring heavy drinking and high depressive symptoms was found (OR 3.69, 95% CI 1.0, 13.1) that was not seen among those with heavy drinking only or high depressive symptoms only. Time spent in farm work was also associated with depressive symptoms and with co-occurring heavy alcohol use. In both the cross-sectional and prospective regression analyses, no association was found between drinking pattern and injury for men or for women. After adjusting for age and smoking status, high depressive symptoms was associated with farm-work injuries among women (OR 3.6, 95% CI 1.8-6.9) in the cross-sectional analysis but not in the prospective analysis. No association between farm-work injuries and depressive symptoms was found for men. No interaction between drinking pattern and depressive symptoms in relation to injuries was seen in either men or women. Discussion/Conclusions. The association between smoking and co-occurrence of heavy drinking and high depressive symptoms may provide useful information for smoking cessation efforts. Depressive symptoms were more likely a result of farm-work injury in women rather than a cause. Future studies are needed to understand the impact of farm-work injuries in the context of differences in the roles of men and women farmers.
  • ItemOpen Access
    Understanding the association between the Abbreviated Injury Scale score for the head region and outcomes following traumatic brain injury, Colorado 1998-2000
    (Colorado State University. Libraries, 2007) Gujral, Indira Beatrice, author; Stallones, Lorann, advisor
    Annually, an estimated 1.4 million Americans are affected by traumatic brain injury (TBI). It is the leading cause of morbidity and mortality among trauma individuals. While advances in medicine have helped to decrease mortality from TBI, less is known about the long-term outcomes following TBI. The goal of this research was to further ourunderstanding of long-term outcomes following TBI by identifying associations betweenone anatomical coding system and one-year outcomes following TBI. The Abbreviated Injury Severity Score is an anatomical scoring system used by injury researchers throughout the United States and the world to characterize individual injury. One attribute of this measure is the ability to independently characterize injury severity for one body region, for this study, specifically, the head region. Although the Abbreviated Injury Severity Score for the Head region (HAIS) is ananatomic measure of TBI severity, no study has assessed the inter- and intra-rater agreement of HAIS between trauma registrars at hospitals and trained state coders. Further, no studies have specifically assessed the association between HAIS and longterm outcomes following TBI using population-based data. The objectives of this study were to utilize data from two Colorado population-based studies containing HAIS scores to investigate the reliability of HAIS and its ability to predict long-term physical and cognitive outcomes after traumatic brain injury. The purposes of this study were: 1) to describe the intra-rater reliability of HAIS scores by having a trained coder employed by the Colorado Department of Public Health and Environment recode HAIS scores for traumatic brain injured cases from the Colorado Traumatic Brain Injury Surveillance system for the years 1999-2000; 2) to describe the inter-rater reliability of HAIS scores by comparing HAIS scores from cases in the Colorado Traumatic Brain Injury Surveillance system for 2000 to HAIS scores from trauma registrars at hospitals throughout Colorado; and, 3) to use HAIS scores to evaluate functional outcomes of traumatic brain injured individuals in Colorado who were enrolled between 1998 and 1999 in the Colorado Traumatic Brain Injury Registry and Follow-up System. Cases were defined using the International Classification of Diseases, 9th Revision, Clinical Modification diagnostic codes for TBI (800 - 801.9, 803 - 804.9, or 850 854.1, and 959.01) and included Colorado residents who were either admitted to hospitals or died prior to reaching the hospital from a TBI. To assess inter- and intra-rater agreement, data was selected from the Colorado Traumatic Brain Injury Surveillance system for years 1999 - 2000. A sample of 250 cases was randomly selected to assess intra-rater agreement. Approximately 624 cases were selected to assess inter-rater agreement. Weighted and non-weighted kappa statistics were used to assess inter- and intra-rater agreement, respectively. Landis and Koch (1977) cut points were used to interpret agreement findings. To identify long-term outcomes following TBI, 1,802 cases were used from the Colorado Traumatic Brain Injury Registry and Follow-up System (CTBIRFS), 1998 - 1999. Outcomes selected for this study were based on the conceptual model of function and disability developed by the World Health Organization. Logistic regression models were used to determine the association between TBI severity categories (HAIS) and one-year activity and societal participation outcomes. Logistic regression was used to determine the association between HAIS and cognitive outcomes one-year following TBI. All statistical analyses were conducted using SAS 9.1©. Results of this study found intra-rater agreement of HAIS to be “almost perfect” while inter-rater agreement between the trained state coder and the hospital trauma registrars was “substantial.” This finding was surprising given that individuals performing the coding often have varying levels of education and training, experience,and use and knowledge of database systems. Factors that potentially affect agreement thatwere not tested include injury factors such as impact forces, multi-system trauma, pharmaceutical drug usage, and use of personal protective equipment, such as helmets. Future studies should be conducted to identify the role of these factors when coding HAIS. In order to accurately assess function and disability following TBI, the severity of the TBI must be taken into account. Using HAIS categories mild, moderate, and severe TBI, individuals with moderate TBI (5.04 [95% confidence interval (1.67, 15.6)]) and severe TBI (4.08 [95% confidence interval (1.29, 12.7)]), were five times as likely to report needing help with Activities of Daily Living throughout the study period as compared to those with mild TBI, after adjusting for identified potential confounders. Similarly, subjects with moderate and severe TBI were more than 60% as likely to report needing help with Instrumental Activities of Daily Living throughout the study period as compared to those with mild TBI. The odds ratios for moderate and severe TBI were 1.90 [95% confidence interval (1.01, 3.57)] and 1.62 [95% confidence interval (0.81, 3.26)], respectively. Adjusting for identified potential confounders, subjects with moderate and severe TBI were more than 50% as likely to report diminished societal participation throughout the study period as compared to those with mild TBI. The odds ratios for moderate and severe TBI were 1.72 [95% confidence interval (1.18, 2.51)] and 1.58 [95% confidence interval (1.01, 2.47)], respectively. However, moderate and severe TBI were not associated with cognitive dysfunction. The results of this study indicate that HAIS is a good predictor of function and disability at the individual and societal levels, as measured by the activities and participation domains. The study failed to find an association between HAIS and cognitive disability. The results of this study support the need for individuals with a moderate and severe TBI (HAIS score greater than three) to participate in some form of rehabilitation to increase function and reduce disability following TBI. The objective of this study was to use data from the CTBIRFS and the CO TBI Surveillance system to expand upon the literature regarding outcomes following TBI. Specifically, the purpose of this study was to increase understanding of the Abbreviated Injury Scale for the head (HAIS) - an anatomical scoring system that potentially could be a predictor for long-term outcomes following TBI. As medicine advances and more individuals survive TBI, demands on rehabilitation resources will rise. The results of this study indicate that HAIS is a reliable scoring system that is associated with one-year outcomes following TBI. Using HAIS to assess severity of TBI will allow clinicians to identify and target rehabilitative efforts for TBI individuals and help individuals receive the rehabilitation services they need. Future research is needed to expand upon these findings to identify barriers to rehabilitation, such as cost and access to care, and to assess the role of rehabilitation on quality of life following TBI.
  • ItemOpen Access
    Analysis of agriculture injuries using workers' compensation data
    (Colorado State University. Libraries, 2008) Douphrate, David Irvin, author; Rosecrance, John C., advisor
    Background. In the United States, agriculture is among the most hazardous of industries. The lack of information regarding agriculture injuries has been recognized as an obstacle to effective injury prevention efforts. Methods. Three separate but related studies analyzed workers' compensation data to elucidate injury and claimant characteristics associated with agriculture injuries. Specific emphasis was placed on tractor-related and livestock-handling injuries. Results. Results indicated high injury rates among workers employed by dairy farms, cattle/livestock raisers, and cattle dealers. Large proportions of injuries were associated with tractor mounting and dismounting, milking, cattle pinning/sorting, and horseback riding activities. Tractor-related and livestock-handling work injuries are a significant problem, more costly, and result in more time off work than other agriculture injuries. Conclusions. Injury prevention efforts should be directed at livestock-handler education, dairy parlor and livestock-handling facility design, and tractor design characteristics related to tractor mounting and dismounting.
  • ItemOpen Access
    Characterization of atrazine induced protein adducts
    (Colorado State University. Libraries, 2007) Dooley, Gregory, author; Tessari, John D., advisor
    Atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine) (ATRA) is the most commonly applied herbicide in the U.S. and is frequently detected in drinking water at significant levels. ATRA metabolism yields diaminochlorotriazine (DACT), an electrophilic molecule that can react with nucleophilic protein residues forming a covalent adduct. We first demonstrated this interaction with hemoglobin from rats exposed to 30-300 mg/kg ATRA. Mass spectrometry (MS) analysis of hemoglobin tryptic digests indicated a 110 Da adduct on Cys-125 of the β-subunit. Based on in vitro incubations of 90 ug/ml DACT and hemoglobin yielding the identical adduct observed with in vivo ATRA exposures, adduct formation was by a nucleophilic substitution reaction between DACT and Cys-125. Albumin was then investigated since it contains an exposed Cys-34 that could be targeted by DACT. Again using MS, a 110 Da adduct was located on Cys-34 of albumin from rats exposed to 20-200 mg/kg ATRA and rat and human albumin exposed in vitro to 90 ug/ml DACT. Immunochemical detection using a DACT adduct antibody also detected the adduct in albumin samples from rats given 5-200 mg/kg ATRA and rat and human albumin exposed in vitro to DACT. No adducts were detected in control animals or in the in vitro controls with this method. These data support a novel immunochemical detection system that could provide a rapid screening methodology for the detection of ATRA in exposed human populations. Finally, we used the DACT antibody to located modified proteins in the pituitaries of ATRA exposed rats and DACT exposed LβT2 rat pituitary cells. Since ATRA exposure suppresses the luteinizing Hormone (LH) surge, protein adducts in the pituitary may be involved in this mechanism of action. 2DE followed by Western blotting showed numerous spots (>30) that were not present in control from both exposed rats and LβT2 cells. Using MS analysis of matched protein spots, 8 unique proteins in the rats and 19 unique proteins in LβT2 cells were identified. Each of these proteins contained solvent exposed cysteine residues, making them targets for DACT. Future research will be necessary to elucidate the functional role of these adduct and their involvement in ATRA/DACT induced LH suppression.
  • ItemOpen Access
    Menstrual cycle characteristics in women exposed to atrazine in drinking water
    (Colorado State University. Libraries, 2009) Cragin, Lori Ann, author; Reif, John, advisor
    Introduction. Atrazine is the most commonly used herbicide in the United States and a wide-spread groundwater contaminant. Concern regarding potential health effects of human exposure to atrazine is based on its well recognized designation as an endocrine disruptor. Studies have shown that menstrual cycle characteristics are markers for reproductive conditions. The specific hypothesis tested in this research was: Exposure to atrazine in municipal drinking water is associated with menstrual cycle abnormalities which, in turn, are modulated through a diminution of the pre-ovulatory luteinizing hormone surge. In addition, the following secondary hypothesis was tested: There is agreement between retrospective menstrual cycle questionnaire data and data obtained prospectively from menstrual cycle diaries. This study was the first to examine the effects of drinking water exposure to atrazine on menstrual function in humans and the first to examine the underlying mechanism of this association.
  • ItemOpen Access
    Indoor air pollution from cookstove smoke and adverse health effects among Honduran women
    (Colorado State University. Libraries, 2007) Clark, Maggie L., author; Peel, Jennifer, advisor
    Elevated indoor air pollution exposures associated with the burning of biomass fuels in developing countries are well established. Several studies have demonstrated the value of estimating exposures by evaluating stove type, personal cooking practices, and household parameters. Adverse health endpoints have been associated with cookstove exposures, although little research has been performed on cardiovascular health endpoints in these settings. We conducted a cross-sectional survey among 79 non-smoking Honduran women. Thirty-eight women cooked with traditional stoves and 41 with improved stoves with chimneys. For a subgroup of these women (N=54-58), carbon monoxide and particulate matter (PM2.5) levels were assessed via eight-hour indoor monitoring, as well as eight-hour personal PM2.5 monitoring. Stove quality was assessed using a four-level subjective scale representing the potential for indoor emissions. The stove scale and ventilation factors predicted more than 50% of the variation in personal and indoor PM2.5 and 85% of the variation in indoor carbon monoxide. In addition to the stove scale, other factors predicting exposure measurements were the age of the stove, the total area of the kitchen windows, the number of kitchen walls, the primary material of the kitchen walls, the volume of the kitchen, and the number of walls with eave spaces. Forced expiratory volume in one second and peak expiratory flow, as well as respiratory symptoms and demographic characteristics were assessed. Finger-stick blood samples were collected and dried on filter paper in order to assess a biomarker of inflammation, C-reactive protein (CRP). Women exposed to cookstove exposures reported symptoms of cough, phlegm, wheeze, headache, and shortness of breath more frequently than those not exposed. Associations consistent with a null association were observed between cookstove exposures and lung function and CRP. Results of the exposure assessment could provide a cost-effective alternative to air quality monitoring. The ease and convenience of collecting, storing, and transporting finger-stick blood samples, could prove to be a useful tool for larger community-based investigations, especially in developing countries.
  • ItemOpen Access
    An epidemiologic evaluation of risk factors associated with asthma severity and phenotypes
    (Colorado State University. Libraries, 2008) Busacker, Ashley A., author; Keefe, Thomas J., advisor
    Asthma is an inflammatory disorder of the airways characterized by airway hyperresponsiveness, periodic episodes of bronchoconstriction and airway obstruction. Severe asthma accounts for a minority of asthma, but utilizes a disproportionate amount of asthma-associated healthcare costs. Further studies are needed to identify risk factors associated with severe asthma, a very heterogeneous disease. Asthma-particularly severe asthma-consists of several different phenotypes. Limited epidemiologic studies have been conducted to identify risk factors specific to severe asthma. Factors associated with proposed asthma phenotypes have not been evaluated in a multivariate manner. This study investigated the risk factors associated with severe asthma, with specific phenotypes of asthma, and the association between a potential biomarker, C-reactive protein (CRP), and aspirin intolerant asthma. The project utilized data that were collected from National Institutes of Health funded studies and data collected from an electronic chart review. Data from questionnaires, histological, radiological and physiological studies were used to determine univariate associations between these factors and asthma severity and then to determine associations between the factors and different asthma phenotypes. Multiple logistic regression analysis was used to evaluate the differences between severe and non-severe asthma, early and late onset asthma, asthma subjects who did or did not exhibit air trapping, and aspirin intolerant and tolerant asthma with particular attention to CRP levels. This investigation found important clinical differences between severe and non-severe asthma that should be further evaluated as risk factors that may give insight into severe-asthma mechanisms to be targeted in asthma treatment. The analysis of asthma phenotypes also yielded important findings. Specifically, early onset asthmatics appear to be a relatively homogeneous group with strong genetic influences and presence of allergic responses, whereas late onset disease is more heterogeneous. The analysis of the air trapping phenotype demonstrated that quantitative CT-determined air trapping in asthmatic subjects identifies a group of individuals with a increased odds of intensive health care utilization. Additionally, several independent risk factors for the presence of this phenotype were identified, perhaps most interestingly history of pneumonia, neutrophilic inflammation, and atopy. Lastly, this study provides evidence that CRP may be elevated in aspirin intolerant subjects and that CRP deserves further study as a potential biomarker for the aspirin intolerant phenotype of asthma.
  • ItemOpen Access
    Long-term hematopoietic response in leukocyte counts and differentials for rhesus macaques (Macaca mulatta) from acute whole-body radiation exposure
    (Colorado State University. Libraries, 2023) Chino, Yuiko, author; Johnson, Thomas, advisor; Bailey, Susan, committee member; Kato, Takamitsu, committee member; Walrond, John, committee member
    Accumulating evidence from A-bomb survivors and radiation therapy patients suggest that survivors are at risk of developing delayed effects of acute radiation exposure (DEARE). In contrast to acute radiation syndrome (ARS), the underlying mechanisms of DEARE are largely unknown. Better understanding of DEARE is vital for improving estimates of risk and predictions of long-term health outcomes following a variety of radiation exposure scenarios, whether accidental or intentional, and including nuclear accidents, cancer treatment, and space travel. The hematopoietic system is highly sensitive to ionizing radiation (IR) exposure; leukocyte counts reach a nadir in days to several weeks post-acute exposure, followed by a recovery period from 4-8 weeks to a year. Accumulating evidence from the A-bomb survivor cohort and animal studies suggests residual damage in the hematopoietic system persists for a long time. Long-term effects in hematopoietic system are very likely the underlying cause of DEARE disease, although there is limited understanding of the process. In this study, archival leukocyte counts and differentials from the Non-Human Primate Radiation Late Effects Cohort (RLEC), were analyzed to evaluate long-term effects. The RLEC cohort consists of over 200 Rhesus Macaques (Macaca mulatta) previously exposed to acute whole body irradiation from 1.14 to 8.5 Gy and approximately 50 control animals. The dataset was created from blood sampling started approximately 1 year post-exposure and continued every 2-6 months. Linear mixed models were developed for total leukocyte count and the differentials including neutrophil, lymphocyte, and monocyte counts and their percentages. Preliminary analysis was conducted for animals with the same dose level, sex, and age at the time of exposure and age and sex matched control animals. The linear mixed models had statistically significant elevations in leukocyte and neutrophil counts and neutrophil% in irradiated animals compared to the controls. Lymphocyte% was significantly lower in irradiated animals. Longitudinal trends for both control and irradiated animals were consistent with expected trends of aging in hematopoiesis, which is skewed towards production of myeloid lineage cells such as neutrophils and monocytes rather than lymphoid cells. There was no statistical difference among the longitudinal trends of control and irradiated animals. Next analysis was extended from the preliminary analysis with a larger dataset including animals with different dose, sex, age at the time of exposure, as well as mitigator assignment. Longitudinal trends were estimated for different dose levels (control, LD50; 6.8 to 8.5 Gy), and adjusted for sex, age at the time of exposure, and status of mitigator use. All models suggested that dose levels were a statistically significant factor for the longitudinal trends of leukocytes and the differentials. Controls showed a slight decrease of total leukocyte count and monocyte skewed differentiation, consistent with changes estimated from aging in hematopoietic system. The LD50 animals than controls and
  • ItemOpen Access
    Noise exposure in steel stud construction: noise characterizations and tool limit guidance for commercial framers
    (Colorado State University. Libraries, 2023) Schutt, David, author; Brazile, William, advisor; Autenrieth, Daniel, committee member; Lipsey, Tiffany, committee member; Van Dyke, Mike, committee member
    Noise exposure in construction is well-demonstrated to be hazardous to hearing, with high rates among construction workers of occupational noise-induced hearing loss. This study focused on an under-studied population of construction workers: Commercial framers who cut and install steel studs as their primary task. This study used personal noise dosimetry and task assessments to characterize the noise exposures of this population, and to develop implementable recommendations to decrease hazardous occupational noise exposure for this population of workers. Sound pressure levels of common power saws at the framers' hearing zone was hazardous, with Leq log-transformed means of 107.2 dBA and Lpeak means of 120.1 dBC during saw use. Noise dose among this population ranged from 5.8 – 61.4% of the Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) and from 63.9 – 823.2% for the National Institute for Occupational Safety and Health (NIOSH) recommended exposure limit (REL). Mean ambient noise dose equivalent at the study sites was 1.4% for OSHA PEL criteria and 12.4% for NIOSH REL criteria. Overall, installers had significantly lower REL doses than cut persons (p = 0.016). Octave band analysis showed a slight upward trend of higher sound pressure levels at higher frequencies. Recommendations for task limitations were developed for isolated use of power saws, the powder-actuated tool (PAT) nailer, and the impact driver. Generalized cuts of steel studs without hearing protectors were limited to 13 – 14 cuts per worker per day for any saw and any stud type. Shots with the PAT nailer were limited to <2 shots per day per worker without hearing protectors, 10 – 13 shots per day with foam earplugs, 27 – 34 shots per day with earmuffs, and 86 – 108 shots per day with double hearing protection (earplugs plus earmuffs).
  • ItemOpen Access
    Characterization of X-ray transmission and scattering during equine radiology procedures at the Johnson Family Equine Hospital
    (Colorado State University. Libraries, 2023) Parajuli, Bal K., author; Brandl, Alexandar, advisor; Johnson, Thomas, committee member; Lindsay, James, committee member
    Personnel handling radioactive materials or radiation-emitting devices are at risk of exposure to ionizing radiation, directly from primary beams and indirectly from scattered beams. Hence, radiation workers are enrolled in a radiation dosimetry program to comply with regulations and effectively track exposures. Because X-ray radiation is used daily for diagnostics and therapeutics of animals at the Veterinary Teaching Hospital (VTH) of the Colorado State University (CSU), the Radiation Control Office (RCO) at CSU monitors the workers' radiation dose monthly to ensure safety and compliance. The RCO has set an ALARA Level 1 investigation at 150 millirems (mrem) in a month to keep doses As Low As Reasonably Achievable (ALARA). Personnel exceeding 150 mrem in a month are notified, and the dose is investigated. An investigation level of 150 mrem provides an opportunity for the RCO to intervene early and is low compared to the regulatory annual dose limit of 5000 mrem per year. Over the course of the last few years, the ALARA Level 1 has been exceeded on various occasions by radiology technicians at the Johnson Family Equine Hospital (JFEH), which is affiliated with the VTH at CSU. This project was designed to bridge a substantial knowledge gap regarding the procedures conducted at the JFEH, associated radiation doses, and the facility's suitability for large-animal veterinary applications. This experiment design characterizes the facility and anticipates radiation exposures across various spatial points within the radiology areas, facilitating the identification of radiation exposure hotspots. This study started with staff interview, comprehensive analysis of the daily diagnostic imaging procedures at the JFEH and cross-referencing months with elevated exposure to images. Radiation exposures in the primary beam were modelled for all Technique Factors (TFs) at various distances using SpekCalc® software generated photon fluence energy spectra. The output spectrum data were entered into an MCNP® model for dose assessment using effective dose conversion coefficients. The benchmarked outcome for Cesium-137 differed 3% from the theoretical value. An MCNP® model was used to replicate the direct measurements conducted at 1 meter. The results were consistent with exposure measured by a Biomedical Fluke 451P ionization chamber, previously published exposure measurement for the given kVp and mAs, the calculated exposure for X-ray using kVp and mAs, and the typical effective radiation dose from diagnostic X-ray published by NCRP 160. Finally, another simulation was conducted to recreate the conditions within the radiology facility using phantoms. This simulation facilitated the quantification of effective doses across various spatial points. The simulated absorbed dose was highest in the primary beam, then directly behind the X-ray source, and lowest at a 90-degree angle from the direction of the beam, at the same distance from the source. The absorbed dose also differed considerably in front of and behind the phantom due to photoelectric absorption. After analyzing data, to measure dose accurately, two dosimeters are recommended, one inside and one outside the lead vest. Absorbed dose can be minimized by avoiding primary beam exposure and standing behind the X-ray tube while operating the handheld X-ray switch.
  • ItemEmbargo
    Analyzing early cancer etiology in golden retrievers using Golden Retriever Lifespan Study (GRLS) data
    (Colorado State University. Libraries, 2023) Hodo, Kiara, author; Magzamen, Sheryl, advisor; LaRue, Susan, committee member; Gutilla, Margaret, committee member
    Background: Although cancer is a burden in both humans and dogs, humans medicine is characterized by established health care organizations, interdisciplinary networks, and databases from which data and research can be complied and shared. No such organization exists in veterinary medicine. Individual registries provide useful data and information on cancer in dogs, but no mechanism exists to summarize data to detect cancer trends, breed-specific measurements of occurrence, and treatment responses. Therefore, there are vast knowledge gaps related to cancers in dogs, especially among early cases. The Golden Retriever Lifetime Study (GRLS) data collected by Morris Animal Foundation is a unique opportunity to evaluate cancer prevalence in a large number of golden retrievers with known pedigree. Data were evaluated for each state and compared to human cancer prevalence provided by the CDC. Differences in cancer prevalence between young and old dogs was evaluated, along with their resident state, sex status, and cancer type. Golden retrievers were recruited from 2012-2015 to participate in the GRLS cohort study and were confirmed to be free of life limiting conditions by a veterinarian. Owners had to have at least a 3-generation pedigree of their dog to be enrolled. Information regarding the dog's health and condition were recorded annually via owner and veterinarian questionnaire, as well as sample collections, and added to the GRLS study data. The GRLS data was refined and cleaned in SAS and R studio evaluate state of diagnosis, age at diagnosis, and sex at diagnosis. The highest prevalence of cancer among GRLS participants was in Louisiana (38.5%) with Arizona as the second highest (17.5%). A cluster of higher prevalence regions were observed in the upper east coast, similarly to the CDC's human data. Although the prevalence was highest in Louisiana and Arizona, neither were found to be statistically significant based on the difference of proportion calculations. A statistically significant difference was found in average age at diagnosis between male neutered and intact cancer dogs, but not when comparing female spayed and intact cancer bearing dogs or when comparing all 4 sex statuses. The average age at diagnosis based on tumor types (mammary, hemangiosarcoma, histiocytoma, lymphoma) was significantly different, most likely due to higher numbers of hemangiosarcoma cases in older dogs and histiocytoma cases observed in younger dogs. Older, male neutered dogs were more susceptible to hemangiosarcoma development (85.5% of cases were old), and younger dogs that had been spayed or neutered were more susceptible to histiocytomas (100% of cases were young). Discussion: One of the interesting findings of this analysis was that there was a statistically significant difference in average age at diagnosis between intact and neutered male dogs, but not between intact and spayed females. Small sample size of cancer dogs could have impacted the power of statistical test results and been a contributor to statistical insignificance seen throughout the analysis. Dogs moving multiple times throughout the duration of the study can affect interpretations and implications from prevalence by state findings. Prevalence was also calculated using only the total GRLS study population the resided in respective states as the denominator, effecting generalizability of the analysis findings.
  • ItemOpen Access
    Employee noise exposure and octave band analysis in a manufacturing setting
    (Colorado State University. Libraries, 2023) Gieseck, Darren, author; Brazile, William, advisor; Autenrieth, Daniel, committee member; Gutilla, Margaret, committee member
    Worker exposure to hazardous levels of noise continues to be a concern in United States (US) industries. The National Institute for Occupational Safety and Health has estimated that twenty-two million US workers are exposed to hazardous levels of noise each year, increasing the risk for noise-induced hearing loss (NIHL). One industry sector of concern for worker exposure to noise is metal can manufacturing because of the types and number of machines used in the production areas. To help further characterize the risk NIHL in the metal can manufacturing sector, a comprehensive noise evaluation was performed at a manufacturing site that produced aluminum metal cans. The purpose of this study was to (1) determine if workers in a metal can manufacturing facility were overexposed to hazardous levels of noise that could potentially result in NIHL; (2) determine the machinery frequencies greater than 85 dBC to which employees were exposed; and (3) provide sound mitigation recommendations to the facility's safety team. Area noise levels were collected with a sound level meter (SLM) and personal noise samples were taken using wearable noise dosimeters. 30 production employees participated in sampling over the course of five days and their measured work shift noise exposures were compared to published occupational exposure limits to determine if they were at increased risk of hearing loss. Personal noise exposures were compared to the Occupational Safety and Health Administration's (OSHA) noise Action Level (AL) and Permissible Exposure Limit (PEL); the American Conference of Governmental Industrial Hygienists' (ACGIH) Threshold Limit Value (TLV); and the National Institute for Occupational Safety and Health's (NIOSH) Recommended Exposure Level (REL). Of the 30 employees sampled, 100% exceeded the OSHA AL, 100% exceeded the OSHA PEL, and 100% exceeded the NIOSH REL/ACGIH TLV. To provide statistical support of these findings, a 95% confidence interval was calculated for each occupational exposure standard along with upper and lower prediction limits. Additionally, the frequencies greater than 85 dBC obtained from the area noise samples associated with the production machinery ranged from 63 Hz – 6,300 Hz with noise levels that ranged from 97.1 dBC – 99.6 dBC and Z-weighted frequencies greater than 85 dB ranged from 32 Hz – 8,000 Hz. From these findings, noise mitigation recommendations were provided that were focused on establishing hearing attenuation to 80 dBA. This involved ongoing fit testing of hearing protection for employees, training, and addressing the specific frequencies associated with each machine type.
  • ItemOpen Access
    Occupational exposure to bioaerosols at Colorado dairies
    (Colorado State University. Libraries, 2023) Craig, Amanda, author; Brazile, William, advisor; Reynolds, Stephen, committee member; Clark, Maggie, committee member; Ellis, Bob, committee member; Autenrieth, Dan, committee member
    The dairy industry is vital to the American economy and impacts both the general population and the workers immediately involved in dairy production. The United States is a significant contributor to the global industry producing approximately 14.6% of the global milk supply. To accomplish this, large herd dairy operations (>1000 head of cattle) operate 24 hours a day, 365 days a year. The long production hours and large herd size result in an increase in the number of injuries and illness in dairy workers. One type of illness diagnosed in dairy farmers is respiratory disease. Multiple researchers have shown that some workers in modern dairy operations have pulmonary function cross-shift declines and lower pulmonary function as well as increased rates of obstructive respiratory conditions such as chronic bronchitis, organic dust toxicity syndrome, occupational asthma, chronic obstructive pulmonary disease, and hypersensitivity pneumonitis (Reynolds, Lundqvist et al. 2013, Reynolds, Nonnenmann et al. 2013).Respiratory disease is caused by exposure to bioaerosols that consist of bacteria, fungi (and the corresponding constituents), pollen, animal dander, feed, and manure. Although bioaerosol exposure can cause infection, the immunological response the body has to bioaerosols that result in decreased lung function is more prevalent in dairy workers. Although some researchers have examined culturable bacteria and fungi, the viable organisms only represent a small fraction of what is detected in the air at the dairies (Katja Radon and Jörg Hartung 2002). One method used to identify Gram-negative bacteria is the recombinant factor C (rFC) assay, a rapid diagnostic assay to identify concentrations of endotoxins present in dairy environments. While endotoxins have explained a portion of the respiratory problems in dairy workers, they do not explain all of the respiratory diseases (May, Romberger et al. 2012). Little research has been performed to determine concentrations of fungi at dairies. Some work has been done using GC/MS to identify fungal markers, but the current research is the first study to use the rapid diagnostic (Glucatell) assay to quantify worker exposure to fungi at dairies. The primary goal of this study was to better characterize dairy worker exposure to bioaerosols through two sample analysis techniques: next generation sequencing (NGS) and rapid diagnostic assays (rFC and Gluactell). The specific aims of this dissertation were to 1) identify similarities and differences in bacterial communities between button samplers and biosamplers co-located inside a cattle pen, 2) characterize worker exposure to the microbial community on dairy farms in comparison to environmental sources, and 3) characterize worker exposure to two bioaerosols constituents based on dairy worker task. For Specific Aim 1, area air samples were taken for five consecutive days to compare the button and biosamplers co-located inside a fresh cow pen and then analyzed using NGS to determine the identity and quantity of bacteria. The current study was the first to compare the biosamplers and button samplers for NGS analysis at a dairy. The results from this study will help researchers make better decisions on the type of sampler that should be employed for collecting airborne bacteria. The researchers found that the biosampler was more effective at collecting samples for NGS. The two samplers had significantly different microbial communities that were identified based on the Principle Coordinate Analysis (PCoA) plot. However, upon further analysis the alpha diversity plot showed relatively similar Shannon and Inverse Simpson indices suggesting both samplers were sampling from the same core microbiome. Therefore, the difference between the samplers is likely due to the high variance in the samples and not actual differences in the microbial community. The alpha diversity plot also had a high operational taxonomic units (OTU) count indicating that the dairy microbiome has a high count of rare bacteria and a low count of dominant bacteria. The biosampler had a higher relative abundance of bacteria across all five sampling days. The majority of the top identified bacteria were Gram-positive. Currently, little research has been done to assess the impact of Gram-positive bacteria on worker respiratory health. Based on these results, future research should focus on Gram-positive bacteria as they may substantially contribute to respiratory disease. Some of the identified bacterial genera have potentially pathogenic species, but data on the species level is needed to determine the potential for infection. Both viable and non-viable bacteria and their corresponding constituents can act as inflammagens, potentially causing cross-shift lung function decline and respiratory disease (May, Romberger et al. 2012). Both samplers collected bacterial communities that could be analyzed and used for NGS, but the biosampler was identified as the better sampler because of the higher OTU counts and greater bacterial diversity. However, depending on the type of sample information required, the button sampler may be advantageous because it can be used for personal samples and throughout the entire day. For Specific Aim 2, personal and area air, hand swabs, and soil samples were collected at one dairy for five consecutive days and analyzed using NGS. The sample sets were then compared to identify differences and similarities between the sample type, identity of the bacteria, and potential for worker exposure. The difference between sampler (button vs biosamplers) was significantly different. The sample type explained more than 50% of the differences seen in the microbial community. The biosampler compared to the button sampler had a lot of variation within their respective types which could explain some of the differences between the communities due to the differences in sampling length and time of day. The variation in the biosampler was mainly due to the second sample taken on each day. The area air samples had the highest relative abundance between the sample types. Soil was thought to have the highest relative abundance but because the number of samples were biased toward air samples (n=60 vs n=15) when the most prevalent top bacteria were chosen they were driven by the air samples. The majority of the bacteria were also found to be Gram-positive across all the samples. The most common source of the bacteria based on the genera information was soil which was expected based on the dusty nature of the dairy environment. Some genera identified have potential pathogenic species, but this dataset did not provide information on the species level. No conclusions can be made on the possibility of infection from the bacteria in these samples. For Specific Aim 3, four dairies were recruited to assess airborne concentrations of Gram-negative bacteria, fungi and dust. Workers were binned into eight different tasks, and the task samples were compared to identify differences in exposure between the tasks. Differences in site and season were not statistically significant and were not included in subsequent analyses. The concentration of dust over a full work shift ranged from 0.95-5.6 mg/m3 and were lower than expected. The highest dust concentration was below the Occupational Safety Health Administration Permissible Exposure Limit (OSHA PEL) of 10 mg/m3 but was not below the suggested Occupational Exposure Limit (OEL) from the American Conference of Governmental Industrial Hygienists (ACGIH) of 2.4 mg/m3 indicating that dust exposure may be a concern for some of the tasks. Machine operators and milkers had the highest geometric mean dust concentrations with concentrations of 0.356 and 0.305 mg/m3 respectively. The endotoxin concentrations ranged from 0.078-40 EU/m3 which was lower than other research observing endotoxins concentrations at dairies and below the suggested OEL of 90 EU/m3. Multi-task workers and milkers had the highest endotoxin concentrations (Donham 2000). The β-glucan concentrations ranged from 0.2-212 pg/m3 with the highest task concentrations found in multi-task workers and machine operators. There is not a suggested OEL for β-glucans but concentrations measured in this study were higher than other studies in waste processing facilities (Douwes 2005). Ultimately, there was not one task that was consistently higher between the different exposure variables and there were no significant differences between any of the tasks. No conclusions or recommendations could be made on the task-based exposures at the dairies. However, even at low concentrations, exposure to agricultural dusts have been shown to induce responses from cytokines (Poole, Dooley et al. 2010). The genetic polymorphism TLR4 has also been demonstrated to cause workers to be more predisposed to sensitization to endotoxins at extremely low concentrations (Reynolds 2012).
  • ItemOpen Access
    Evaluation of sodium bismuthate chromatographic systems for the separation of americium from curium
    (Colorado State University. Libraries, 2023) Labb, Samantha A., author; Sudowe, Ralf, advisor; Brandl, Alexander, committee member; Johnson, Thomas, committee member; Henry, Charles, committee member
    The development of a successful and efficient americium (Am) and curium (Cm) separation method is necessary for stockpile stewardship science and for the simplification and improvement of currently proposed reprocessing schemes towards the closure of the nuclear fuel cycle. However, the similar chemical properties of these radionuclides (e.g., similar ionic radii, ionic bonding, and predominant trivalent oxidation states in acidic media) makes this difficult to achieve. Differences in redox chemistry can be exploited based on the fact that Am can be oxidized to higher oxidation states in acidic media while Cm cannot. Recently, the ability of solid sodium bismuthate to oxidize Am and its ion exchange properties were demonstrated in solvent extraction and chromatographic systems, but were limited by oxidation stability, kinetics, and flow rates. This dissertation focuses on evaluating and characterizing new solid-liquid chromatographic systems that combine both the oxidation and ion exchange mechanisms into one material for a continuous separation process. In addition, the solution behavior of NaBiO3 in nitric acid and the effect on acidity and dissolution kinetics is determined.