Theses and Dissertations

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Open Access
²²⁶Ra contamination of soil and foliage as a function of distance downwind from uranium mill tailings
(Colorado State University. Libraries, 1982) Skinner, Dawn J., author; Whicker, F. Ward, advisor; Olson, H. G., committee member; Ibrahim, Shawki A., committee member
This study concerned 226Ra contamination of soils and foliage as a function of distance downwind from a uranium mill tailings pile. In soils the radium contamination was primarily associated with particle sizes < 0.045 mm and mainly found within the 0-0.6 cm soil horizon. The 0-0.6 cm soil horizon showed a decrease in activity concentration with distance. The 0-15 cm and 0-30 cm soil depth samples also showed a significant decrease with distance. An attempt was made using ultrasonic washing to separate internal from external 226Ra contamination in Artemisia tridentata. Internal contamination appeared to be a larger contributor to total contamination at distances ? 0.16 km downwind from the tailings pile. At distances > 0.16 km, external contamination became a larger contributor to the total 226Ra contamination. Concentration ratios (based on total contamination and internal contamination) were determined as a function of distance downwind from the tailings pile. Concentration ratios appeared to be highly site specific, however higher values (0.8-2.8) were generally associated with distances ? 0.16 km from the mill. At distances > 0.16 km. In most soil samples 226Ra concentrations approached background levels at a distance of 1.1 km from the tailings pile. Total vegetation contamination approached background at 6.6 km. A trend of decreasing internal and external 226Ra contamination with distance downwind was found to be significant (p < 5%). This study suggested that a combination of root uptake and foliar absorption were responsible for internal contamination and further studies were suggested.
Open Access
A characterization of foodborne illness data, Denver Metropolitan Area, Colorado, 1986-1989
(Colorado State University. Libraries, 1994) Higgins, Charles L., author; Salman, Mowafak Dauod, advisor; Savage, Eldon P., committee member; Reif, John S., committee member
A records search was conducted for foodborne illness complaints to local health departments in the Denver, Colorado Metropolitan Area, defined as Adams, Arapahoe, Boulder, Denver, Douglas, and Jefferson counties. Records for the four-year period beginning with 1986 through 1989 were searched for reports in which two or more persons were alleged to have become ill, experienced similar symptoms and had a common food exposure. Program administrators were interviewed about the procedures used to investigate these complaint reports. The documented cases of foodborne illness in the Denver Metropolitan Area are not sufficient to justify regulatory activities or to target prevention. The assistance of the public, academic and medical community appears to be needed in order to increase the percentage of complaints that can be properly investigated.
Open Access
The biological and physiological effects of excess copper in juvenile mallards (Anas platyrhynchos): an investigation of the toxicity of acid mine drainage in waterfowl
(Colorado State University. Libraries, 1999) Foster, Stiven Daniel, author; Ramsdell, Howard, advisor; Tessari, John D. (John Domenic), committee member
In the early 1990's, concentrations of copper in the Alamosa River were increased by the release of acid mine drainage from the Summitville Mine site. Concern about the potential impact to resident waterfowl led to an investigation of copper toxicity in juvenile mallards. The investigation described in this thesis included a small field survey and six laboratory studies. The field survey provided an indication of potential exposure concentrations and a relative measurement of copper exposures in mallards from the Alamosa River. The laboratory studies examined the biological and physiological effects of excess copper in juvenile mallards and the relationship between copper exposure and tissue copper accumulation. Acute copper toxicity produced mortality in juvenile mallards that received a drinking water dose of 800 milligrams of copper per kilogram body weight per day (mg Cu/kg BW/d). Sublethal copper toxicity was quantified by decreased weight gain. Mallards experienced minor reductions in weight gain (10-20%) with exposures ranging from 70-210 mg Cu/kg BW/d. Weight gain was substantially decreased, by more than 50% compared with control birds, in mallards that received larger doses of copper(≥250 mg Cu/kg BW/d). Based on decreased weight gain, a dose of 20 mg Cu/kg BW/d was determined to be a No Observed Adverse Effect Level (NOAEL) for copper in juvenile mallards. Tissue copper concentrations were measured by flame atomic absorption spectrophotometry. Untreated mallards accumulated substantial concentrations of copper in their livers, up to 700 μg Cu/g on a dry weight basis. Hepatic copper increased significantly in mallards that received a dose greater than or equal to 160 mg Cu/kg BW/d. Feather copper concentrations were significantly correlated with both dietary (R2 = 0.99, p < 0.001) and drinking water exposure (R2 = 0.76, p < 0.001). Analysis of feather tissue was determined to be the most sensitive method for evaluating copper exposure. Feather copper concentrations were significantly increased in mallards that received a dose greater than or equal to 70 mg Cu/kg BW/d. Concentrations of copper in both liver and feather tissue reached their peak at a dose below the highest treatment level. Copper accumulation appears to be diminished in birds that received doses greater than or equal to 340 mg Cu/kg BW/d. Drinking water pH was investigated for its ability to influence copper absorption. Copper accumulation in feather tissue was significantly reduced when exposure pH was decreased. In addition to influencing tissue copper accumulation, acidic water (pH≤3.5) produced signs of direct toxicity in juvenile mallards. Weight gain was significantly reduced in mallards exposed to drinking water at pH 3.5. Drinking water at pH 3.0 exceeded the LC50 for very young mallards (< 5 days old). Evaluation of liver tissue from mallards that were collected on the Alamosa River indicated that these birds had increased exposure when compared to mallards from uncontaminated areas. Vegetation collected from the Alamosa River below the Wightman Fork contained a substantial concentration of copper, 463 mg Cu/kg. A diet that consisted solely of this copper-rich vegetation would provide mallards with approximately 88 mg Cu/kg BW/d. A similar dose of copper significantly reduced weight gain in laboratory mallards.
Open Access
Alteration of differentiation and growth of normal human epidermal keratinocytes by benzo[a]pyrene and arsenic
(Colorado State University. Libraries, 2005) Perez, Damon Scott, author; Campain, Julie, advisor; Yang, Raymond Shih-hsien, 1940-, advisor; Legare, Marie E., committee member; Fox, Michael, committee member; Ranu, Rajinder S., committee member
Normal human epidermal keratinocytes (NHEK) were chosen as an in vitro model for mechanistic studies into how altered regulation of differentiation may play a role in the malignant transformation process in human cells. Initially, the cytotoxicity of four petroleum-derived hydrocarbons [benzo[a]pyrene (BaP), carbazole, dibenzothiophene, and isoquinoline] was investigated using the MTT assay; however, the research direction changed to focusing on examining the cellular effects, in NHEK, of BaP, the most toxic and carcinogenic polycyclic aromatic hydrocarbon among the four, and arsenic, another high priority skin carcinogen. This work demonstrates that BaP and arsenic inhibit terminal differentiation in NHEK. Arsenic also decreases proliferation in a manner suggestive of a G2 block. In contrast, BaP increases proliferation rates and induces rapid progression through the cell cycle, possibly by a shortened G2 phase. Differentiation is more sensitive to chemically-mediated perturbations than is proliferation, indicating that the former process may be the initial target at environmentally prevalent concentrations. To identify molecular alterations that are responsible for the observed chemical-specific effects, microarray analysis was carried out on NHEK treated with each carcinogen. From this analysis, BaP and arsenic altered 103 and 122 genes respectively. More sensitive real-time PCR revealed that BaP-treatment perturbed the expression of genes involved in cellular differentiation and growth. Altered genes include; α-integrin binding protein-63, interleukin-1α, interleukin-1β, Ras guanyl releasing protein-1, retinoic acid- and interferon-inducible protein, and YY1-associated factor-2. Arsenic altered the expression of genes involved in cell cycle checkpoint regulation. These genes include; MAX binding protein, RAD50, retinoblastoma-1, retinoblastoma-binding protein-1, and transforming growth factor β-stimulated protein. Gene expression results suggest that BaP and arsenic target different steps in the pathways to growth and differentiation in this cell type and provide mechanistic clues as to how these chemicals favor transformation in target cells. Moreover, a quantitative biologically-based computer model of NHEK was developed providing an in silico experimental platform with which one can test chemical-mediated effects on cell cycle kinetics and differentiation. A clearer understanding of cellular growth and differentiation, both from a normal standpoint and from alterations induced by chemical exposure, will greatly aid the risk assessment process for environmental contaminants.
Open 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.
Open 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.
Open 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.
Open Access
Microdosimetric measurements of shielding effects for iron particles at 500 MeV/nucleon incident upon aluminum and polyethylene
(Colorado State University. Libraries, 2007) Farrar, David R., author; Borak, Thomas B., advisor; Heilbronn, Lawrence K., committee member; Hulpke, Alexander J., committee member
The radiation environment in space is very different than on the earth. One portion of the radiation present in space is galactic cosmic radiation (GCR). GCR is composed of protons, alpha particles, and high Z and energy (HZE) particles. One of the most significant HZE particle species in terms of absorbed dose is iron. One of the dosimetry instruments used on the Space Shuttle and the International Space Station is the tissue equivalent proportional counter (TEPC). It is used to measure absorbed dose and estimate the average quality factor of radiation exposure during manned space missions. TEPCs measure energy deposition in volumes of simulated tissue with dimensions on the order of microns. Spectra of energy depositions are used to calculate values of frequency mean lineal energy, ȳF, and dose mean lineal energy, ȳD. The value of ȳF can be used to calculate the absorbed dose per particle. Previous studies have found that the choice of ȳF or ȳD to approximate particle linear energy transfer (LET), and thus the quality factor, depends on the momentum of the particle and for iron, the value of ȳD is equivalent. However, the presence of material causes HZE particles to slow down and/or fragment. Thus radiation of one HZE particle species incident on one side of shielding material, insufficient to stop all radiation, will produce a wide range of particles and energies on the other side. This study exposed a spherical TEPC, in conjunction with a particle spectrometer, to iron particles at 500 MeV/nucleon, produced at the Heavy Ion Medical Accelerator in Chiba, Japan, with and without shielding material. The shielding material used, in separate measurements, was 1.65 cm Al and 5 cm polyethylene (each has 4.5 g cm-2 density thickness). The density thickness is similar to what is used on the Space Shuttle and International Space Station. The absorbed dose per particle was measured and the average LET of the radiation was estimated for each shielding scenario. For iron particles at 500 MeV/nucleon, the shielding did not cause a change in the absorbed dose per particle. But the shielding reduced the average quality factor of the radiation and polyethylene was better than aluminum, at the same density thickness.
Open 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.
Open 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.
Open 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.
Open 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.
Open 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.
Open 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.
Open 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.
Open Access
Noise exposure, characterization, and comparison of three football stadiums
(Colorado State University. Libraries, 2009) Engard, Derek, author; Brazile, William Joseph, advisor; Gotshall, Robert W., committee member; Sandfort, Delvin R., committee member
The National Institute for Occupational Safety and Health and the occupational safety and health community named hearing loss as one of the 21 priority areas for research in the next century and maintains that work-related hearing loss continues to be a critical workplace safety and health issue. An overlooked group of employees are those that work in stadiums and arenas. Not only are the workers potentially exposed to high levels of hazardous noise, but the spectators attending these events may also be exposed. Five personal noise-exposure samples were collected from workers at Hughes Stadium (Fort Collins, CO) and Folsom Field (Boulder, CO) during three home football games for a total of 30 personal noise exposures. Five personal noise-exposure samples were collected from fans at Invesco Field (Denver, CO) and two samples from fans at Hughes Stadium and Folsom Field during three home football games for a total of 27 personal noise-exposure samples.
Open 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.
Open 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.
Open 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.
Open Access
Baseline evaluation of indoor air quality from Nicaraguan households using traditional cook stoves
(Colorado State University. Libraries, 2010) Bazemore, Heather, author; Reynolds, Stephen J., advisor; Peel, Jennifer L., advisor; Kreidenweis, Sonia M., committee member
Indoor cook stoves are still used as a primary energy source across the world in many developing countries. Inefficient stoves cause incomplete combustion of biomass fuel, resulting in an unhealthy increase of indoor air pollutants, including carbon monoxide (CO) and particle matter (PM). Use of these stoves is a global problem that must be addressed to help reduce indoor air pollutant exposures and combustion emissions. Most studies assessing traditional cook stoves are limited; the extended length and thorough exposure assessment of this study make it unique, providing better data for evaluation. This part of the study will assess the baseline exposure data from a longitudinal study of 123 Nicaraguan households collected over the summer of 2008. Fine particulate matter (PM2.5) was assessed continuously via 48-hour indoor monitoring using the UCB Particle Monitor. Indoor and personal carbon monoxide levels were assessed continuously via 48-hour indoor and personal monitoring using the lightweight, portable, data-logging Drager Pac 7000. PM2.5 and carbon monoxide indoor sampling devices were collocated inside the kitchen at a height representative of breathing zones. The personal carbon monoxide device was worn by the participant during the day and placed by her bedside overnight. Regression exposure models were developed using variables from the kitchen that can predict ventilation, including amount of eave space, kitchen volume, number of windows, number of doors, number of walls, and primary type of wall material. Cooking practices and activities were also considered in the models including exposure to environmental tobacco smoke, hours spent cooking per day, hours fire burns per day, and hours spent in the room with the fire burning per day. At the end of the summer baseline collection, improved cook stoves were installed in each participating household. High concentrations of indoor air pollution were recorded in households using traditional cook stoves. For indoor carbon monoxide, mean concentrations were 146 ppm (1-hour max), 67 ppm (8-hour max), and 26 ppm (48-hour). For personal CO, mean concentrations were 32 ppm (1-hour max), 8 ppm (8-hour max), and 2 ppm (48-hour). For indoor PM2.5, mean concentrations were 11,272 μg/m3 (1-hour max), 3655 μg/m3 (8-hour max), and 1364 μg/m3 (48-hour). In exposure assessment models, kitchen volume and exposure to environmental tobacco smoke were found to explain the most variation in indoor carbon monoxide levels. For personal carbon monoxide, number of doors and hours spent cooking per day influenced levels most. Amount of eave space and environmental tobacco smoke explained the most variation in indoor PM2.5 levels. Peaks in pollutant exposure were also evaluated in assessment models. However, all model results should be interpreted with caution. R-square values were very low for these models, meaning that the variables we collected data on did not explain much variation in pollutant concentrations. The data collected on exposure parameters did not explain much variation in indoor air quality. Further research is needed as to which housing factors and/or cooking practices affect pollutant levels most.