Theses and Dissertations
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Item Open Access Relative response of alanine and filtered alanine electron paramagnetic resonance dosimetry in mixed neutron-gamma fields(Colorado State University. Libraries, 2025) Witter, Paige K., author; Brandl, Alexander, advisor; Johnson, Thomas E., committee member; Brazile, William, committee member; Chicco, Adam, committee memberAn electron paramagnetic resonance (EPR) spectroscopy procedure was investigated for use in novel mixed neutron and gamma radiation fields. L-α-alanine ("alanine") is an amino acid that develops stable unpaired electrons when exposed to ionizing radiation. The number of unpaired electrons, measured via EPR, is proportional to the absorbed dose in tissue from photons. The EPR signal dependence on neutrons across different spectra, especially in specific moderated experimental conditions, is less well characterized than for gamma dosimetry. Alanine was exposed to gamma and neutron sources, a variety of neutron spectra, and escalating doses to develop calibration curves for sources at Colorado State University and determine the specific neutron source sensitivity. Neutron exposures have lower cumulative signals than gamma exposures for the same dose and alanine mass, with sensitivities ranging from 0.056 ±0.085 for the Bare PuBe source to 0.245 ±0.212 for the bare 252Cf. These values are on the low end of literature ranges or below literature sensitivity values for other neutron sources, leading to a hypothesis of a low dose-rate effect in alanine that should be investigated further. Thermal-neutron sensitive filters of cadmium and gadolinium metal foils were added to alanine dosimeters to investigate the signal response. A comparison of the bare- versus filtered signal response in the known mixed fields showed that the filters did not consistently increase the thermal-neutron sensitivity of alanine. At low total doses, where the gamma contribution to the total dose was very low, the cadmium and gadolinium foils increased the alanine response to the field. When the gamma dose contribution rose to a source-specific point, photon interactions in the foils decreased the photon fluence in the alanine pellets, leading to a decreased dosimeter response. This dual-effect of the thermal-neutron sensitive foils is a novel finding, and should be investigated with source specific gamma spectra. While a filtered-alanine dosimeter is not usable at the current stage, bare alanine calibration curves for the neutron sources at CSU were created and available for subsequent irradiations in various fields at unknown doses.Item Embargo Characterizing the lung-brain axis inflammatory response to agriculture dust and utilizing aspirin-triggered Resolvin D1 as a novel therapeutic(Colorado State University. Libraries, 2025) Threatt, Alissa Nicole, author; Moreno, Julie, advisor; Constan, Alex, committee member; Nordgren, Tara, committee member; Schaeffer, Joshua, committee member; Schenkel, Alan, committee memberOccupational exposure to agriculture dust is strongly linked to the development of chronic pulmonary diseases such as asthma and chronic obstructive pulmonary disease (COPD). The organic dust inhaled in agricultural settings, known as organic dust exposure (ODE), contains high concentrations of immunogenic compounds that lead to immune-mediated chronic lung disease. These pulmonary inflammatory responses to agriculture dust exposure have been extensively characterized, however there is emerging evidence that agriculture dust exposure increases workers' risk for the development of dementia and other neurological disorders. Occupational agriculture dust exposure has been strongly linked to an increased risk of developing dementia and COPD patients experience high rates of memory loss, confusion, depression, and anxiety symptoms. Given this new evidence, we aimed to characterize the neuroinflammatory response to agriculture dust in vitro in cultured microglia and in vivo in mouse models of repetitive agriculture dust exposure. We also evaluated the behavioral outcomes in mice exposed to agriculture dust to link the exposure with reported patient outcomes. There are additional risk factors that have been identified in patients with ODE, one of which is the production of the cytokine interleukin-22 (IL-22), which has been shown to have various functions in pulmonary disease. Some models have demonstrated that IL-22 is elevated in certain disease states and may contribute to susceptibility to secondary exposures, while other models have shown that IL-22 knock-out mouse models experience more severe disease states. We aimed to understand the link between IL-22 and neurological inflammation in an ODE mouse model. Both COPD and dementia are progressive and fatal diseases with limited effective therapies. The development of novel therapeutics to treat these diseases is urgently needed to address these patients' needs. Omega-3 fatty acid metabolites, such as Aspirin-Triggered Resolvin D1 (AT-RvD1) have shown efficacy in reducing inflammation in models of ODE and other inflammatory exposures. We aimed to evaluate the efficacy of AT-RvD1 as a novel therapeutic for the reduction of pulmonary and neurological inflammation elicited by agriculture dust exposure. We aimed to accomplish this through in vitro alveolar macrophage culture and an in vivo repetitive ODE, AT-RvD1 treatment mouse model. We also aimed to determine the role of IL-22 in agriculture dust-induced pulmonary and neurological inflammation utilizing an IL-22 knock-out mouse model of repetitive ODE and AT-RvD1 treatment. Through our investigations, we observed that ODE in macrophages and microglia produce a strong immune response characterized by the secretion of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) and that co-treatment with AT-RvD1 significantly reduces its production. In our in vivo mouse models, we determined that exposure to agriculture dust produced increased numbers of microglia and astrocytes, confirming our hypothesis that agriculture dust exposure leads to neuroinflammation. We also found that AT-RvD1 treatment in these animals reduced the number of microglia and astrocytes. Additionally, we found that knock-out of IL-22 produced increased inflammation compared to wildtype controls and that AT-RvD1 treatment significantly reduced this inflammation. Our behavioral assessment of mice exposed to agriculture dust revealed limited changes in anxiety and memory, warranting further investigation into the effects of ODE on animal behavior. Overall, our investigations revealed that exposure to agricultural dust leads to neurological inflammation in the form of microglia an astrocyte proliferation and pro-inflammatory cytokine production, that IL-22 plays an important role in the regulation of these inflammatory processes, and that AT-RvD1 may be an effective novel therapeutic for agricultural dust exposure-induced inflammatory diseases.Item Embargo Improving smoking cessation for vulnerable populations in low-resourced settings(Colorado State University. Libraries, 2025) Keke, Chukwudi, author; Elf, Jessica L., advisor; Lee, Debbie, committee member; Koslovsky, Matt, committee member; Rojas-Rueda, David, committee memberTobacco smoking remains one of the leading causes of death and disability worldwide. Global estimates indicate that there are approximately 1.3 billion smokers worldwide; tobacco smoking contributed to an estimated 7.7 million deaths and 200 million disability-adjusted life years (DALYs) in 2019, primarily through ischemic heart disease, chronic obstructive pulmonary disease (COPD), cancer, and stroke. Low and middle-income countries (LMICs), including sub-Saharan Africa, shoulder a disproportionate burden of the global tobacco epidemic, where over 80% of the world's tobacco users live. The implementation of evidence-based programs and policies have led to a substantial decline in tobacco smoking and tobacco-related diseases in many high-resource countries over the past three decades; however, tobacco use continues to rise in sub-Saharan Africa due to its rapidly shifting demographic profile, increasing influence of tobacco industry, and competing public health challenges such as HIV. In South Africa, a leading economy in sub-Saharan Africa, there are approximately 7.6 million people with HIV (PWH). Advances in anti-retroviral therapy (ART) have significantly improved the life expectancy of PWH, however, PWH remains at a greater risk for cardiovascular disease and pulmonary comorbidities, including tuberculosis (TB) and chronic obstructive pulmonary disease (COPD). These co-morbid conditions are exacerbated by tobacco smoking. Alarmingly, smoking prevalence is much higher among PWH, with estimates ranging from 24%–74% compared to 25% in the general population. Despite the high burden of tobacco use among PWH in South Africa, evidence is limited on effective smoking cessation strategies in this setting. South Africa has ratified the Framework Convention on Tobacco Control (FCTC) and has since implemented several anti-tobacco legislations, including advertising bans, tobacco product taxes, and restrictions on public smoking; however, recent surveillance data suggests that almost half of young men initiate tobacco smoking by the age of 20. Given that tobacco-related diseases can be avoided with cessation at younger ages, intervention during this time would help prevent the nearly 1 billion deaths expected from tobacco use in the 21st century. The work in this dissertation addresses the burden of tobacco use among vulnerable populations that experience greater tobacco-related health disparities by informing effective strategies or combinations of strategies to improve cessation efforts among PWH and adolescents in low-resource settings. In Aim 1, we examine the association between urine nicotine metabolite ratio (NMR) and response to smoking cessation treatment among people with HIV in South Africa, using data from a large randomized controlled trial for smoking cessation among Black South African smokers with HIV. In the primary trial, participants were randomly assigned to receive either behavioral counseling alone (BC) or BC plus combination nicotine replacement therapy (nicotine patches and gum, c-NRT). Bio-banked urine samples collected at baseline were used to determine cotinine (COT) and 3-hydroxycotinine (3HC) levels; we then calculated the NMR as a ratio of 3HC to COT. We evaluated NMR as a categorical variable (high versus normal metabolizers), using a cut-off of the fourth quartile (≥0.3174 ng/mL). Self-reported smoking abstinence at 6 months was biochemically verified using exhaled breath carbon monoxide (CO) and urine cotinine test. Modified Poisson regression models examined the association between NMR (high vs. normal) and 6-month abstinence. Effect modification (on the additive and multiplicative scale) examined the role of treatment arm as a potential modifier of the relationship between NMR and smoking abstinence at 6 months. Linear regression models were used to examine the relationship between NMR (high vs normal) and secondary outcomes, including changes in exhaled carbon monoxide breath test, urine cotinine, and nicotine withdrawal at 6 months. NMR was not associated with smoking abstinence (adjusted risk ratio (aRR) = 0.82; 95% CI: 0.45, 1.49; p = 0.53). No evidence of effect modification by treatment conditions was observed on the multiplicative scale (aRR =1.17; 95% CI: 0.32, 4.30; p = 0.81) or additive scale (adjusted relative excess risk due to interaction (aRERI) = 0.10; 95% CI: -1.16, 1.36; p = 0.44). There was no association with changes in nicotine withdrawal (β = 1.01, 95% CI: (-1.91, 3.93; p = 0.49), exhaled breath CO (β = -1.38, 95% CI: (-4.52, 1.76, 1.01; p = 0.39) or urine cotinine (OR = 0.98, 95% CI : (-1.18, 3.15; p = 0.37). The results in AIM 1 showed no associations between NMR and response to smoking cessation treatment among Black South Africans with HIV in South Africa. Overall, our results do not provide further support for the potential use of the NMR as a tool in selecting smoking cessation treatment among PWH in this setting. In AIM 2, we assessed the efficacy of a repeat treatment of BC with or without cNRT for smoking cessation among PWH with prior treatment failure in South Africa. We used data from the second phase of the randomized controlled trial for smoking cessation among PWH described in Aim 1. Participants in each arm who were still smoking at the 6-month follow-up visit were offered a second round of their group-assigned intervention. The primary outcome was self-reported smoking abstinence biochemically verified using exhaled breath CO and urine cotinine test at 6 months post-treatment. Secondary outcomes include smoking abstinence at 2 months post-retreatment and changes in exhaled breath CO at 2 months and 6 months post-retreatment. We assessed the proportions of participants who were abstinent at 6 months (and 2 months post-retreatment as a secondary outcome) based on the intent-to-treat analysis. Modified Poisson regression models were used to examine treatment effects on smoking abstinence and other secondary outcomes. Additionally, we assessed the association between treatment adherence and smoking abstinence at 6 months post-retreatment. At 6 months post-retreatment, a total of 35 participants (9%) were abstinent, including 15 (8%) participants in the BC group and 20 (11%) participants in the BC+cNRT group; p = 0.63. There was no significant difference in abstinence rates between treatment groups (RD = 3%; 95% CI: -9%, 3%; p = 0.40). This remained consistent after adjusting for potential confounders (aRR = 1.16, 95% CI: 0.39, 3.47; p = 0.79). We found no significant difference between the treatment groups in the median (IQR) changes in exhaled breath CO (BC: -1 (-6, 3) vs. BC+cNRT: -1 (-5, 4); p = 0.38; or urine cotinine (BC: -0.90 (-4, 0.4) vs. BC+cNRT: -1.4 (-4, 0.3); p = 0.42. At 2 months post-retreatment, 6 (3%) participants in the BC group were abstinent compared to 8 (4%) participants in the BC+cNRT group; p = 0.94. There was also no significant difference in abstinence rates between treatment groups (RD = 1%; 95% CI: -6%, 3%; p = 0.71) and after adjusting for potential confounders (aRR = 1.21, 95% CI: 0.42, 3.84; p = 0.79). We found no significant difference between the treatment groups in exhaled breath CO (BC: -2 (-7, 4) vs. BC+cNRT: -2 (-7, 2); p = 0.38) or urine cotinine (BC:-0.70 (-2.8, 0.9) vs. BC+cNRT: -0.9 (-4, 0.5); p = 0.52). Overall, the counseling sessions were moderately attended; there were no significant differences in median counseling sessions attended over the 6 months of retreatment between BC (4, IQR: 0, 5) and BC+cNRT groups (3, IQR: 0, 5) (p = 0.49). Self-reported patch use in the BC+cNRT group was low, with patch use reported by 64 (34%) participants at 2 weeks, 77 (41%) at 1 month, 70 (37%) at 2 months, and 68 (36%) at 3 months follow-up visit. We found no statistically significant associations between adherence and smoking abstinence at 6 months post-retreatment. The results in AIM 2 indicate that a moderate proportion of participants successfully quit following a second round of intervention. Abstinence rates in both treatment groups were low, with just 11% of participants in the BC+cNRT and 8% of participants abstinent at 6 months post-retreatment. Notably, adherence to the intervention was low. PWH in this setting who are unsuccessful after a first round of a smoking cessation intervention will likely benefit from repeat treatment, especially with attention to increasing adherence. In AIM 3, we used a qualitative and quantitative mixed-method approach to explore reasons for tobacco use maintenance, interest in quitting, barriers to cessation, and preferred quitting methods among adolescent smokers in South Africa. We conducted 6 focus groups (n = 38) to assess adolescents' opinions on tobacco maintenance and interest in quitting, as well as perceived barriers to and preferred methods for quitting tobacco. We then administered a structured questionnaire in a larger sample (n = 200) to collect information on socio-demographic characteristics, extent of tobacco use, previous quit attempts, interest in quitting, self-efficacy, and other substance use. Participants were adolescent smokers (aged 14-20) in South Africa. Focus group transcripts were analyzed using thematic analysis to identify major themes related to reasons for tobacco maintenance, interest in quitting, barriers, and preferred methods for quitting. Descriptive statistics were used to summarize participants' socio-demographic, tobacco, and substance use behavior. In the focus groups, we identified themes related to reasons for tobacco maintenance (i.e., dealing with stress, easy availability of cigarettes, household and peer smoking, personal wellbeing), interest in quitting (i.e., health concern, high cost of cigarettes, and social stigma), barriers to quitting (lack of social support from family and friends, co-use of substances and other tobacco products and social stigma) and preferred strategies to quitting (i.e., counseling, peer support). The survey data showed that most participants had low tobacco use dependence (n = 150; 75%) measured by the heaviness of smoking index (HSI). Participants reported moderate motivation to quit with a median motivation to quit score of 7 (IQR: 6, 8), and 122 (61%) participants reported a quit attempt in the past year, of which 92 (75%) tried quitting without any help. The result in AIM 3 suggests low levels of tobacco use dependence but moderate motivation to quit among adolescents in this population, indicating a critical window of opportunity to intervene before smoking behaviors become deeply entrenched in adulthood. Strategies to increase motivation to quit and peer counseling support should be considered when developing smoking cessation interventions for adolescents in this setting. Further, issues and needs that are specific to adolescents in low-resource settings, including mental health disorders and substance misuse, must be considered when developing smoking cessation programs for adolescents in this setting.Item Open Access Radiation characterization at laser wakefield accelerators(Colorado State University. Libraries, 2025) Clawson, Soren Baines, author; Brandl, Alexander, advisor; Johnson, Thomas, committee member; Mooney, Michael, committee member; Mann, Jenelle, committee memberLaser wakefield acceleration (LWFA) is a rapidly evolving technology that enables the compact acceleration of electrons to relativistic velocities using intense, high repetition laser pulses in plasma. These high-energy electrons interact with surrounding materials to produce complex, pulsed radiation fields composed of bremsstrahlung photons, neutrons, and in some cases, exotic mesons and leptons. Accurately characterizing these radiation environments is essential for radiation protection and facility safety planning in LWFA environments. This thesis presents a computational framework for estimating the spectral distributions of secondary radiation generated by monoenergetic electron beams. The geometric basis of the simulations presented is of the Advanced Beam Laboratory, room 103, at Colorado State University. Using the Monte Carlo N-Particle (MCNP) transport code, a two-stage simulation approach was developed to mitigate inefficiencies in electron transport. In the first stage, electron interactions in a tungsten target were used to construct angle- and energy-resolved photon spectra, as photons are the primary generator of mesons, leptons, and neutrons. These photon distributions were then used as sources in secondary simulations to estimate effective dose from photons and neutrons throughout the laboratory environment. Near the main laboratory entrance, for a 10 pC bundle of accelerated electrons accelerated between 100 MeV and 10 GeV, combined photon and neutron effective doses are found to range between 2.69 pSv and 506 pSv. This method accounts for directional asymmetries in emission, uncertainty propagation, and applies fluence-to-dose conversion factors for photon and neutron fluences at point detectors. Results include dose estimates per incident electron as a function of beam energy. This study supports the development of predictive dose models and provides data-driven tools for the for the design of radiological controls in future high-energy LWFA experiments.Item Embargo The neuroinflammatory nexus: glial dysfunction in the pathogenesis and therapeutic targeting of neurodegenerative and neurodevelopmental disorders(Colorado State University. Libraries, 2025) Risen, Sydney J., author; Moreno, Julie, advisor; Tjalkens, Ronald, committee member; LaRocca, Tom, committee member; Nordgren, Tara, committee memberChronic neuroinflammation is increasingly recognized as a fundamental driver of both neurodegenerative and neurodevelopmental disorders, linking immune dysregulation, glial dysfunction, and disease progression. In neurodegenerative protein misfolding disorders (NPMDs), including Alzheimer's disease, Parkinson's disease, and prion diseases, sustained microglial and astrocytic activation exacerbates protein aggregation, synaptic dysfunction, and neuronal loss, accelerating cognitive decline. Similarly, in neurodevelopment, aberrant inflammatory signaling during critical windows of brain maturation impairs synaptic formation, alters neurotransmitter systems, and predisposes individuals to long-term cognitive and behavioral deficits. Despite distinct manifestations, both disease categories share a pathological feature: a maladaptive neuroimmune response disrupting neural homeostasis. While neuroinflammation is widely implicated in these disorders, defining its molecular mechanisms, identifying therapeutic targets, and understanding environmental contributions remain critical research needs. This dissertation begins to address these gaps by investigating neuroinflammation as both a therapeutic target in NPMDs and a mechanistic link between environmental exposures and neurodevelopmental disruption. The first investigation evaluates SB_NI_112, a novel brain-penetrant RNA-based therapeutic designed to selectively inhibit NF-κB and NLRP3 inflammasome pathways, key regulators of glial activation and chronic neuroinflammation. Pharmacokinetic and biodistribution studies in small- and large-animal models were first conducted to assess SB_NI_112's CNS penetration and safety. These studies confirmed robust brain bioavailability (~30%) and a favorable safety profile, supporting its viability for therapeutic application. Following these findings, SB_NI_112 was tested in a murine prion disease model, where treatment significantly reduced microglial and astrocytic activation in disease-relevant brain regions, preserved hippocampal neurons, and mitigated neurodegeneration. These neuroprotective effects corresponded with improved cognitive performance in novel object recognition tasks, indicating functional preservation despite ongoing prion pathology. Notably, SB_NI_112 treatment extended survival, reinforcing inflammasome inhibition as a viable therapeutic strategy for NPMDs. These findings provide strong proof-of-concept for targeting neuroinflammatory pathways to slow disease progression and preserve cognitive function in neurodegenerative protein misfolding disorders. The second investigation examines the role of environmental neurotoxicants in triggering neuroinflammation and impairing neurodevelopment. Using a juvenile mouse model, this study demonstrates that chronic low-dose manganese (Mn) exposure (50 mg/kg via drinking water) first alters gut microbiome composition, depleting the relative abundance of beneficial Lactobacillaceae, and increasing the relative abundance of pro-inflammatory Erysipelotrichaceae, contributing to gut-brain axis dysfunction. These microbial shifts coincide with significant gliosis in the enteric nervous system, suggesting early neuroimmune activation at the gut interface. This inflammatory response extends to the brain, where widespread microglial and astrocytic activation is observed alongside disruptions in neurotransmitter production and metabolism, including altered dopamine and serotonin homeostasis. Functionally, these neuroimmune and neurochemical disruptions correspond with changes in behavior, indicating impaired neural processing. The presence of inflammatory lesions in the intestinal lining further implicates gut inflammation as a mediator of Mn-induced neurodevelopmental deficits. These findings highlight the systemic impact of Mn exposure, reinforcing the link between environmental toxins, neuroinflammation, and behavioral dysregulation. Together, these studies further support the growing body of evidence that neuroinflammation is a primary driver of neurological disease rather than a secondary consequence, reinforcing the need for targeted neuroimmune interventions. By examining shared inflammatory features across NPMDs and environmentally induced neurodevelopmental disruptions, this work provides additional insight into how glial dysfunction contributes to neurological pathology. These findings support the continued development of neuroimmune-modulating therapeutics, emphasize early intervention, and highlight the importance of environmental risk mitigation. By bridging molecular, pharmacological, and environmental perspectives, this dissertation contributes to the broader understanding of neuroinflammation in disease progression, challenging traditional distinctions between neurological disorders and providing a foundation for future studies. The implications extend beyond basic science, offering translational potential for clinical intervention, public health strategies, and regulatory policies to reduce the burden of neuroinflammatory disease.Item Embargo Investigating the relationship between ionizing radiation and neurodegenerative mortality: addressing issues of bias, data pooling, and effect modification(Colorado State University. Libraries, 2025) Zbysinski, Tony J., III, author; Neophytou, Andreas, advisor; Rosecrance, John, advisor; Magzamen, Sheryl, committee member; Wilson, Ander, committee memberBackground Much of the current understanding of the adverse health effects of ionizing radiation (IR) exposure comes from studies of Japanese atomic bomb survivors who experienced acute, high doses of IR. However, these findings may not be generalizable to populations exposed to chronic low doses of IR such as workers and the general population. The U.S. Million Person Study (MPS) was founded to investigate the effects of chronic low dose IR for improved guidance of radiation safety. To address this gap in knowledge, worker cohort studies have been and continue to be conducted to assess the potential risks associated with chronic low dose IR, including neurodegenerative diseases. These studies aim to improve the understanding of IR dose ranges and risks that underly current radiation safety policy. Recent findings underscore a potential increase in risk of neurodegenerative disease from chronic low dose IR which may be of great concern considering the significant burden of such diseases. However, there are inconsistencies in prior research findings regarding the relationship between chronic low dose IR exposure and neurodegenerative disease. Several factors we focus on that can contribute to these inconsistencies are co-exposures to non-radiological substances, lack of power to investigate specific neurodegenerative disease outcomes, and selection mechanisms like the healthy worker survivor effect (HWSE) and competing events. This dissertation research introduces novel techniques to evaluate and improve the internal and external validity of prior and future occupational studies of IR and neurodegenerative-related mortality. The specific objectives of the present study include assessing the role of co-exposures as effect modifiers and/or confounders, enhancing the understanding of the trade-offs of pooling data diverse cohorts together, and addressing selection mechanism concerns. Methods Our first objective focused on assessing the role of co-exposures in the relationship between IR and neurodegenerative-related mortality among workers at the Fernald Feed Materials Plant, referred to as Fernald, and to investigate neurodegenerative-related mortality risk across different job categories. Individual-level, brain IR dose estimates were used alongside co-exposure data from job exposure matrix application to evaluate potential confounding and effect modification. Co-exposures for this evaluation were selected a-priori based on literature review. Cox proportional hazards regression models were used to observe risk of neurodegenerative-related mortality at 10 milligray (mGy) IR brain dose across different groupings of co-exposure status, while logistic regression models were used to calculate odds of neurodegenerative-related mortality across 9 job categories. In our second objective our goal was to evaluate the implications of data pooling in the context of the relationship between IR exposure and neurodegenerative-related mortality by combining data from the Fernald, Linde Ceramics Plant, hereafter called Linde, and Mallinckrodt Chemical Works (MCW) cohorts. The Linde cohort's data was updated to prepare for merging with Fernald and MCW. Extensive data harmonization, such as collapsing continuous IR exposure measurement into a categorical form, was undertaken. Cox proportional hazards regression was again used in data analysis across three distinctive steps that analyzed different aggregation parts between the cohorts, co-exposures of uranium and silica dusts were evaluated. A meta-analysis was also conducted of these same three cohort's individual studies to qualitatively compare overall analogous estimates to the pooled analysis. Lastly, our third objective employed the parametric g-formula to address selection mechanism concerns of HWSE and competing events. The parametric g-formula estimated the effect of hypothetical interventions on the risk of neurodegenerative-related mortality to evaluate the potential for HWSE by reducing IR exposure in hypothetical intervention scenarios. Expert interviews were conducted and supported with literature review to develop feasible hypothetical intervention endpoints of reducing IR exposure with possible real-world explanations including engineering and administrative controls. To investigate competing events, in one approach we modeled a likely competing event, cardiovascular disease (CVD) mortality, and compared cumulative incidence results to another approach without modeling for CVD mortality. Results Aim 1 findings highlighted that occupational exposure to machining fluids may act as an effect modifier of the relationship between IR and neurodegenerative-related mortality. Workers highly co-exposed to machining fluids showed significantly increased risk of neurodegenerative-related mortality at 10 mGy IR brain dose (HR 1.25, 95% CI 1.11, 1.40) compared to the overall baseline estimate (HR 1.01, 95% CI 0.96, 1.06). Additionally, certain job categories such as store and supply services had elevated odds of neurodegenerative-related mortality compared to administrative workers (OR 2.30, 95% CI 0.97, 4.96). Findings in Aim 2 revealed overall results consistent with Aim 1 of no increased risk of neurodegenerative-related mortality at low/moderate IR category (HR 0.95, 95% CI 0.73, 1.24) and high IR category (HR 1.05, 95% CI 0.80, 1.37). There was no evidence of confounding or effect modification by silica or uranium dusts. The meta-analytic estimate of these same cohort's individual studies had a similar summary estimate null finding compared to the pooled analysis finding for high categorical IR (HR 0.95, 95% CI 0.75, 1.20). Results of Aim 3's application of the parametric g-formula indicated that the HWSE may not be a key factor in the relationship between IR and neurodegenerative-related mortality as cumulative incidence (CI) did not change considerably between the natural course (cumulative incidence, 16.99%), engineering control (17.43%), and administrative control (17.14%) interventions in the application modeling for competing events. When comparing approaches that modeled and did not model for competing events, we did find evidence that CVD mortality acts as a competing event for neurodegenerative-related mortality. Conclusions This dissertation found that occupational co-exposures, such as machining fluids, may modify the relationship between IR and neurodegenerative-related mortality. In a pooled analysis of worker cohorts we encountered significant data harmonization challenges that emphasized the importance of careful selection of data pooling candidates and meta-analyses as an alternative to aggregating data for some research questions. Furthermore, the selection mechanism of HWSE may not be a key factor for IR and neurodegenerative-related mortality in Fernald, but CVD mortality appears to act as a competing event to neurodegenerative-related mortality. These findings offer potential explanations and insights into the inconsistencies in prior research of IR and neurodegenerative-related mortality and highlight the need to consider co-exposures, data aggregation approaches, and selection mechanisms. This research contributes by showing the importance of evaluating the role of co-exposures as effect modifiers, providing insights into the goals of multi-cohort pooling efforts by discussing trade-offs of data pooling versus meta-analytic approaches, and exemplified a relatively innovative and novel method of addressing selection mechanism concerns in the field of occupational radiation epidemiology. Future research should focus on replicating these approaches in different circumstances that may alleviate the limitations of the present investigations to continue the overarching goal of best informing radiation safety policy for the general population and modern workforce.Item Open Access Characterization of the performance of extraction chromatographic resins in high radiation environments(Colorado State University. Libraries, 2025) Mueller, Rebecca, author; Sudowe, Ralf, advisor; Johnson, Thomas, committee member; Brandl, Alexander, committee member; Borch, Thomas, committee memberThe overall goal of this work is to analyze the impacts of ionizing radiation on extraction chromatography resins. This includes analyzing how the retention of a particular radionuclide changes as the resin is exposed to increasing doses of ionizing radiation (0 to 50 kGy). The effects of the system and strength of the aqueous mobile phase are also investigated with batch contact studies carried out on 3M nitric acid, 1M nitric acid, 3M hydrochloric acid, and 1M hydrochloric acid. The changes to the surface functionality of the extraction chromatography resins are investigated via FTIR measurements. Changes in the physical structure of the resins and their fragmentation patterns are investigated via MALDI-TOF-MS (Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry, referenced as MALDI colloquially).Item Embargo The influence of reproductive access restrictions on health behaviors, infant mortality, and physician supply(Colorado State University. Libraries, 2025) DeBie, Kelly Ann, author; Neophytou, Andreas, advisor; Gutilla, Molly, committee member; Keller, Kayleigh, committee member; Peel, Jennifer, committee member; Rojas-Rueda, David, committee memberIn the past decade, there has been an increasing focus on restriction or elimination of abortion access in the United States. Of particular importance, the Dobbs v. Jackson Women's Health decision in 2022 overturned Roe v. Wade and eliminated the Constitutionally protected right to abortion. After Roe v. Wade became law in 1973, there was an observed decline in maternal mortality with highest impacts in Black maternal mortality, indicating differential impact of both the restriction and removal of reproductive access. It is hypothesized that removal of access will create many impacts and that those impacts may occur in a differential manner. This dissertation has explored the impacts of limiting reproductive care access on people in the United States. Utilizing a background in health policy, law, ethics, maternal mental health advocacy and doula care, I studied how these laws have impacted populations. Trends in out-of-state abortion seekers were analyzed corresponding with state based restrictions and the repeal of the constitutionally protected right to abortion in the Dobbs decision from 2022. Trends in infant mortality were studied to determine whether they are associated with state-level abortion restrictions in both aggregate data and data which has been disaggregated by race, ethnicity, and cause of death. Physician supply was analyzed to determine if there are changes in the overall supply of physicians as well as within the specialty of obstetricians and gynecologists practicing in impacted states. Reproductive care access is an essential component of healthcare, and it is crucial to understand how changes in state and federal law are impacting people's health and well-being.Item Embargo Association between socioeconomic status and PM₂.₅ exposure concentrations in Matlosana, South Africa(Colorado State University. Libraries, 2025) Russell, Madison, author; Elf, Jessica, advisor; Neophytou, Andreas, committee member; Keller, Kayleigh, committee memberSouth Africa has the highest absolute burden of HIV in the world, with 7.5 million people living with the virus—equating to a prevalence of 19% (Pillay-van Wyk et al., 2016). Despite the use of antiretroviral therapies, HIV-seropositive individuals remain at a heightened risk for cardiovascular disease compared to their seronegative peers (Paisible et al., 2015; Bavinger et al., 2013; Freiberg et al., 2013). Exposure to fine particulate matter (PM2.5) further compounds this risk, as it is a known driver of cardiopulmonary disease, a leading cause of mortality worldwide. Notably, air pollution is responsible for 20% of cardiovascular disease deaths (Yusuf et al., 2019). Given that household and ambient air pollution contribute significantly to overall PM2.5 exposure—accounting for 5.2% and 2.9% of all global deaths, respectively (Health Effects Institute, 2019)—it is crucial to assess their impact on vulnerable populations. This study is part of a larger, overarching project investigating whether HIV infection modifies the relationship between PM2.5 exposure and both systolic blood pressure and percent predicted FEV₁ (forced expiratory volume), a key indicator of lung function. Specifically, this paper seeks to determine whether individuals living with HIV and/or those experiencing socioeconomic disadvantage experience disproportionate exposure to PM2.5. To characterize this study population, we categorized sociodemographic variables, assessed fuel use behaviors, and developed a weighted asset index. We also examined the distribution of both household and personal PM2.5 exposure across various socioeconomic indicators, utilizing the weighted asset index and fuel use composite scores as proxies for household fuel behaviors and stratifying by HIV status. Additionally, we conducted linear univariate and multivariate models separately for log-transformed personal and household PM2.5 measurements to quantify the impact of each variable on geometric mean PM2.5 concentrations. No significant differences in personal or household 24-hour PM2.5 exposure were observed by HIV status nor education level, sex, employment status, total family income, living situation, subjective financial security, adult hunger, child hunger, weighted asset index category, or cooking fuel type. However, a notable association was found for lighting sources: households using both candles and kerosene for lighting exhibited a 370% (95% CI: 121%, 1130%) higher geometric mean for household PM2.5 concentrations compared to those relying solely on clean (electric) lighting. The multivariate models explained 37% of the variability in household PM2.5 concentrations and 34% of the variability in personal PM2.5 concentrations. Notably, this study categorizes this peri-urban community in Matlosana, providing critical insights into socioeconomic disparities that exist in this population. However, our findings suggest that household and personal PM2.5 exposures are not distributed differently among different socioeconomic conditions nor among HIV status. Future research should explore the broader influence of urbanization and ambient air pollution, which may play a more significant role in shaping long-term health outcomes.Item Open Access Evaluating the impact of a train-the-trainer heat-related illness prevention training program among Colorado agricultural workers(Colorado State University. Libraries, 2025) Martinez, Yessica, author; Valley, Morgan, advisor; Stallones, Lorann, committee member; Brazile, William, committee memberAgricultural workers are at a high risk for heat-related illnesses due to exposure to extreme environmental conditions. In recent years, regulations for heat stress prevention in agricultural workers have been evolving, leading several states to implement rules that address the increasing risks. Although many efforts have been focused on establishing these strategies, adherence remains insufficient and the evaluation of the effectiveness of heat illness prevention trainings has been limited. The objective of this study was to evaluate the effectiveness of a training strategy focused on preventing heat-related illnesses among agricultural workers in Colorado under a train-the-trainer model adapted from the Western Agricultural Health and Safety Center at the University of California Davis materials in accordance with Colorado State regulations. In spring 2024, five virtual training sessions were held in English and Spanish, allowing 64 trainers to complete the training. During the same season, the trainers then trained over 750 farmworkers in Colorado. Using Kirkpatrick's framework and a series of surveys and focus groups, the evaluation assessed changes in the level of reaction, with trainers reporting high satisfaction with the training. The learning level assessment showed significant improvement in trainers' knowledge and the ability to recognize symptoms, understand the risk of heat stress, and strategies to prevent it. At the behavioral level, trainers and farmworkers reported adopting positive changes in their work practices. Finally, the results showed an increase in risk awareness, the importance of participatory leadership, and greater confidence among trainers and workers in protecting themselves from the risk of heat illness. The findings demonstrated that a strategically structured program adapted to agricultural worker's needs can lead to significant changes in learning, workplace behaviors and overall, a better-established safety culture. These activities not only protect workers' health but may also improve their well-being and productivity in the long term.Item Open Access Application of Fourier-transformed-infrared spectroscopy to quantitate amorphous silica in personal air samples in sugarcane cutters(Colorado State University. Libraries, 2025) Castro, Colton, author; Schaeffer, Joshua, advisor; Adgate, John, committee member; Chaparro, Jacqueline, committee memberIn recent years, chronic kidney disease of unknown origin (CKDu) has risen to an epidemic level in Latin America. Specifically, in agricultural communities of sugarcane cutters, the burden of the disease is unusually high. Several hypotheses exist as to the cause of the disease, focusing on various risk factors, including dehydration, nutrition, and thermal stress. Another important risk factor warranting further research is exposure to particulate matter (PM), given its nephrotoxic potential. PM can be defined as solid or liquid particles present in the environment, often microscopic. Sugarcane workers are exposed to high PM concentrations containing various contaminants, including amorphous silica. In sugarcane, the leaves and other excess plant material contain amorphous silica that can be released into the worker's environment during harvest. Quantitating this amorphous silica and determining if it can play a deleterious role in kidney health has become a priority. Still, amorphous silica is a challenging analyte that requires time- and cost-intensive analysis. A previous pilot project aimed to develop a predictive model using Fourier-Transformed-Infrared Spectroscopy (FTIR) to analyze amorphous silica non-destructively and cost-effectively compared to the currently accepted NIOSH method (e.g., X-ray diffraction). The model was created, and initial concentrations of amorphous silica were determined. During the analysis of samples, the need to ascertain the detection limit of the FTIR method was evident. This project, therefore, further aimed to evaluate and analyze amorphous silica using direct-on-filter FTIR spectroscopy. The point of analysis where several discrepancies occurred (i.e., inconsistency with detecting the peak, loading amounts detected, etc.) was determined to be approximately 500 micrograms before the FTIR began to over or underestimate the absorbance values based on concentration changes. This study is one of the first attempts to use FTIR to non-destructively analyze and quantitate air sampling filters. Additionally, the results will be compared to the current limit of detection values for the FTIR methods employed by NIOSH for their silica analysis tool, further contributing to the literature.Item Open Access Application of ambient dose equivalent estimation models in remediated cedar forests of Kawauchi Village Japan(Colorado State University. Libraries, 2025) Grabowski, Christian Robert, author; Johnson, Thomas, advisor; Brandl, Alexander, committee member; Borch, Thomas, committee memberMany regions contaminated by the release of radionuclides following the 2011 Fukushima Daiichi Nuclear Power Plant disaster are still being investigated today. The mountainous forest areas surrounding Fukushima prefecture were most affected by fallout radionuclides, primarily radiocesium (Cs134 and Cs137), and remain a focus area for remediation and scientific research. Several models have been developed to estimate ambient dose equivalent rates (H*(10)) using data on the depth distribution of fallout radiocesium in the forest soils. Our hypothesis is that two different models will accurately predict radiation doses within 20% based on soil samples. The hypothesis was tested by applying the two models to a research plot in Kawauchi Village Japan, where forestry remediation such as clear-cutting and litter removal has been conducted. Using soil sampling data for radiocesium at the Kawauchi test site, these models were used to estimate H*(10) and compared to measurements taken using handheld instrumentation. The distribution of radiocesium in soil for each sampling locations at the test site was determined using an exponential expression of vertical distribution. These distribution values were then used in two different models, one estimating H*(10) using conversion coefficients from Bq/m2 to μSv/hr, and the other model estimating H*(10) using a "field of view" approach, estimating a surrounding area's contribution to total H*(10) measured at a central point within the test area. The results from this comparison provide a real-world test of computer model effectiveness. The conclusion was that both models could accurately predict radiation levels based on soil samples within 20% of measured values using field instrumentation but could improve if experimental conditions more closely matched those assumed in the model's design.Item Open Access Creating optically stimulated luminescence 3D printing filament and synthesizing radiosensitive optically stimulate luminescence crystals(Colorado State University. Libraries, 2025) DeVincenzo, Evan Ross Burson, author; Leary, Del, advisor; Boss, Keara, committee member; Sudowe, Ralph, committee member; Vickery, Kate, committee memberIn radiotherapy, radiation oncologists use Megavoltage (MV) photon beams to deliver dose to target areas of a patient due to the MV's skin-sparing characteristics, but if the target area is near the surface of the patient, material referred to as a bolus is added to the patient's surface to provide dose build up and bring the maximum dose delivered close to the patient surface. Boluses are 3D printed to minimize air gaps between the patient and the bolus to deliver the dose accurately. Optically stimulated dosimeters (OSLD) are passive dosimeters that collect dosimetric information and are read later by using a stimulating laser to stimulate luminescence from the dosimeter, while a photomultiplier tube (PMT) measures the intensity of the luminescing light. We theorized that it was possible to combine 3D printing technology with OSLD crystals to make OSLD 3D printing filament so that an oncologist could 3D print a patient-specific bolus for a patient receiving radiotherapy treatment, and this bolus would function as a patient-specific dosimeter, ensuring precise, accurate, and safe delivery of dose- enhancing the overall quality of radiation therapy treatment. The first chapter of this study explores how we incorporated OSLD crystals, Al2O3:C, which has a robust field of study exploring its radiosensitivity, with NinjaFlex TPU, a filament used to 3D print patient specific boluses, to create an OSLD filament for oncologists to use to 3D print a bolus which would read by a commercially available LANDAUER microSTAR reader, a reader that utilizes Pulsed Optically Stimulated Luminescence (POSL) technology. We did this by cutting LANDAUER nanoDots, whose primary component is alpha carbon-doped aluminum oxide, into 1 mm or smaller pieces and cutting clear NinjaFlex TPU 3D printing filament into small, less than 1 mm pieces, mixing both at a ratio of 1:90, adding the mixture to a Filabot EX2 extruder, and extruding the mixture at low speed at 180 degrees Celsius. Afterward, the extruded filament was cut and re-extruded 2 more times, then warmed on a hot plate, compressed between 2 glass microscope slides, and cut into 8 mm diameter dots to create Filament Dot (FD) dosimeters. The FDs' dosimetric properties were tested and compared to LANDAUER Dot (LD) dosimeters, whose primary component is Al2O3:C crystals, using a Precision small animal irradiator (SAI). We found that the FDs' dosimetric characteristics were mostly similar to those of the LDs. This is the first study of this type, and we conclude that the results warrant further exploration into integrating OSLD material into 3D printing filament to 3D print radiosensitive patient boluses and 3D other radiosensitive models. LANDAUER had recalled all their nanoDot dosimeters while we were conducting the first chapter of this study, so we decided to explore new ways to synthesize radiosensitive carbon-doped aluminum oxide crystals that the LANDAUER microSTAR could still read. We developed two methodologies: the Arc Furnace methodology, which utilizes an arc furnace to melt aluminum oxide (Al2O3) crystals with carbon (C) powder, and the Hot Acid methodology, which involves mixing alpha-phase aluminum oxide crystals with carbon powder in nitric acid and boiling the nitric acid off then firing the remaining powder in a muffle furnace. The Arc Furnace (AF), Hot Acid (HA), and unmodified aluminum oxide samples were exposed to 1940 cGy using the Precision Small Animal Irradiator. When read by the microSTAR, we found that the AF samples had the strongest luminescence compared to the unmodified aluminum oxide, and the HA samples had no significant difference compared to the unmodified aluminum oxide. Then, to assess if the samples were more sensitive to low energy x-rays, we exposed the samples to an unfiltered beam from the SAI, and we found that the AF samples had a stronger-than-expected increase in luminescence strength when read by the microSTAR, indicating that the AF samples are acutely sensitive to low energy x-rays. We conclude that the Arc Furnace and Hot Acid methodologies created radiosensitive crystals by which the dose can be measured with the LANDAUER microSTAR, and we conclude further research should be conducted to refine these methods. The first study chapter has shown that we can incorporate OSLD crystals into 3D printing filament and the second chapter explores two methodologies to synthesize the crystals. We conclude that further research should be conducted into the methods to synthesize the crystals and the method to integrate the OSLD into the 3D printing filament. This will lead to new methods to create OSLD filament, which can be 3D printed to make radiosensitive boluses that will improve patient outcomes and 3D printing of other objects that researchers will use in other radiotherapy research.Item Open Access Thermophysical property characterization of binary chloride salts for molten salt reactors(Colorado State University. Libraries, 2024) Harris, Michaella Skye, author; Sudowe, Ralf, advisor; Brandl, Alexander, committee member; Johnson, Thomas, committee member; Thorsett-Hill, Karen, committee memberThermophysical properties are of critical importance to the successful demonstration of a molten salt reactor (MSR) as they have the most impact on the design, hydraulic function and neutronic behavior. However, there are limited data regarding complex, multicomponent salt systems and no standardized methodologies. Method development has become vital to produce reliable, experimental data to provide evidence to aid in the licensing of next generation reactor materials. Binary, non-actinide salt systems have become the primary focus as the foundation for supplying experimental data for simulations and validating new methodologies and techniques in measurements. Much research is still needed to fully understand the efficacy and viability of salt systems used for the fuel and coolant loops in the MSR. This dissertation focuses on the development of new methodologies and success and failures therewithin. In addition to providing new and adapted methods and techniques, the effects of outside influences and containments on the salt systems have been uncovered during this process.Item Open Access Chemical separations of a flerovium homolog using macrocyclic extractants(Colorado State University. Libraries, 2024) Ahrens, Nicole Lynn, author; Sudowe, Ralf, advisor; Brandl, Alexander, committee member; Johnson, Thomas, committee member; Omur-Ozbek, Pinar, committee memberThe placement of elements on the Periodic Table is governed by their fundamental chemical properties, maintaining specific trends when they are situated in order of increasing atomic number according to periodic law. When it comes to the heaviest of elements like flerovium (Fl), however, relativistic effects have the potential to alter their chemical behavior relative to lighter elements of the same group. The chemistry of Fl must be studied in order to confirm its placement on the Periodic Table, posing a unique challenge due to its low production cross-sections and short half-life. A chemical system capable of exceptionally fast and selective separations is required to achieve this extreme chemistry task. Such a system can be developed for Fl using its lighter homolog Pb. Two classes of macrocyclic extractants were explored with the aim of developing a chemical separation system for ultimate use in a Fl experiment. Specifically, crown ethers and calixarenes were evaluated as extractants for Pb using extraction chromatography and solvent extraction techniques. In these studies, crown ethers containing both oxygen and sulfur as bridging atoms were found to be ineffective Pb extractants in hydrochloric acid matrices. Unsupported calix[4]arenes also possessing bridging oxygens and sulfurs in various oxidation states were observed to be similarly ineffective but illustrated that the selectivity of calixarenes for Pb can be enhanced by modification of the outer functional groups as well as the bridging atoms. Though not effective as Pb extractants on their own, a significant synergistic effect was observed in EXC studies of a mixed system employing Eichrom Pb resin and a mobile phase containing 4-sulfocalix[4]arene with kinetics suitable for a Fl experiment. A similar SX system was then developed using the same crown ether extractant found on Pb resin with carbon tetrachloride as the organic diluent, but Pb extraction by the system was negligible.Item Embargo Assessment and intervention strategies for agricultural inhalation exposures in occupational and community environments(Colorado State University. Libraries, 2024) Erlandson, Grant, author; Schaeffer, Joshua, advisor; Magzamen, Sheryl, committee member; Abdo, Zaid, committee member; Martenies, Sheena, committee memberAgriculture represents an industry vital to the U.S. economy, supplying the public with nutritious food and providing millions of workers with employment. Also characterized as one of the most hazardous industries for workers, agricultural environments contain a variety of inhalation hazards capable of impacting the health of workers and adjacent community residents. Agricultural inhalation hazards include airborne organic and inorganic dusts; livestock associated gases, pesticides, bacteria, viruses, and antibiotics. This study will focus on (1) bioaerosol exposures in dairy operations and (2) inorganic dust pesticide exposures from agricultural applications. In dairy environments, workers are regularly exposed to high levels of organic dust (bioaerosols) and their inflammatory constituents (e.g., endotoxin, muramic acid, and β-glucans). Dairy bioaerosol exposure is associated with increased prevalence of respiratory disease (e.g., asthma, rhinitis, and chronic obstructive pulmonary disease) in dairy workers. While bioaerosol exposure in dairy environments has been well characterized in previous research, efforts to identify hygienic interventions that control exposure remain unsuccessful. In crop production agriculture, it is well documented that workers are exposed to high levels of pesticides associated with adverse health outcomes (e.g., respiratory and neurologic diseases). Further, in agricultural adjacent community environments, where lower chronic pesticide exposures are found, there is mounting evidence linking adverse health effects (e.g., adult and iii childhood cancers, neurologic and respiratory diseases, and birth outcomes) in residents to exposure from agricultural pesticide applications. However, weak and sometimes inconsistent associations previously reported highlight the limitations of current community exposure assessment techniques used for pesticides. For specific Aim 1, we pilot tested a novel low-cost nasal rinse intervention to modulate airway inflammation in ten bioaerosol exposed dairy workers. Dairy workers were randomly split into treatment (n = 5) and control (n = 5) groups and administered saline nasal rinses before and after their shift for five consecutive days. Treatment group participants received pre-shift hypertonic saline rinses while the control group received normotonic saline rinses. Both received normotonic rinses post-shift. Pro and anti-inflammatory cytokines were measured from recovered saline rinses. Linear mixed model results indicated treatment group participants experienced significantly higher concentrations of anti- (IL-10) and pro-inflammatory cytokines (IL-6 and IL-8) than the control group (p < 0.02, p <0.04, and p < 0.01 respectively). This study demonstrates the capacity of hypertonic saline nasal rinses to successfully upregulate anti-inflammatory cytokine production. However, conflicting upregulation of pro-inflammatory markers cloud interpretations of efficacy. For Aim 2, we further evaluated the immunomodulatory effects of hypertonic saline rinses vs. normotonic saline rinses longitudinally (2-5 shifts) in 45 bioaerosol exposed dairy workers. However, in this aim, treatment group participants received hypertonic rinses pre- and post-shift and 16S sequencing was added to analyses to capture potential washout effects on microbial diversity. No significant differences were observed between group or day for any of the measured markers or microbiome diversity metrics. Yet, non-significant increases in anti-inflammatory IL-10 concentrations across the study period were observed independent of iv treatment group suggesting the rinse itself may be more impactful than tonicity. This study provided mixed but encouraging results that justify further research on nasal rinses as an intervention in bioaerosol exposed dairy workers. For Aim 3, we evaluated the agreement between three exposure assessment techniques used to estimate residential organophosphate (OP) exposure in agricultural adjacent communities located in the Central Valley of California. OP exposure was estimated from household dust samples, California Pesticide Use Report (CPUR) pesticide use modeling, and urinary DAP metabolites across two sampling campaigns. Simple correlation tests revealed moderate correlations (ρs = 0.46) between household dust and use model exposure estimates. Estimates from urinary DAP metabolites exhibited low to no correlation with the other two estimates. Linear mixed model results also indicated no association between urinary DAP metabolites and household dust or use model estimates. This study illustrates a lack of agreement between community pesticide exposure assessment techniques regularly used in research and motivates the development of more robust assessment techniques.Item Open Access Pathogens, pulmonary function, and the nasal microbiome of dairy workers(Colorado State University. Libraries, 2024) Seidel, James, author; Schaeffer, Joshua, advisor; Magzamen, Sheryl, committee member; Abdo, Zaid, committee member; Valley, Morgan, committee memberDairy workers are exposed to bioaerosols that are diverse in both size (0-100 µm in aerodynamic diameter) and inflammatory constituents (e.g. endotoxins, muramic acid, and β-glucans). Bioaerosol exposure at dairies is associated with a higher prevalence of chronic obstructive pulmonary disease (COPD), chronic bronchitis, asthma, respiratory pneumonitis, and asthma-like reductions in pulmonary function. More recently, opportunistic pathogens present at dairies such as the novel influenza D virus (IDV), influenza A (IAV), and livestock-associated Methicillin-resistant Staphylococcus aureus (MRSA) have also been a focus of research, as these pathogens can infect workers and pose a public health risk through community spread. Intrinsic factors such as genetics and childhood exposures likely play a major role in exposure response and respiratory disease pathology, but little research has been focused on the nasal microbiome's role in pathogen exposure and cross-shift changes of pulmonary function. From a longitudinal (2-5 working shifts) cohort of dairy workers in the High Plains Region of the US, this research analyzed pathogens found in the nares of dairy workers via pre- and post-shift nasal lavages. The same nasal lavages underwent targeted 16S rRNA gene sequencing to quantify the bacterial communities that comprise the nasal microbiome. Spirometry was also performed on dairy workers pre- and post-shift to measure cross-shift changes in pulmonary function. Overall, 32.1% (n=237) of nasal lavages tested positive for Methicillin-susceptible Staphylococcus aureus (MSSA), 11.4% tested positive for MRSA, 17.3% for IDV, 2.5% for IAV, and 1.3% for influenzas C virus (ICV). Only 1 of the original 31 participants never tested positive for a pathogen during their workweek. Differences in nasal microbiome characteristics emerged based on pathogen positivity, and differential abundance analysis revealed significant differences in genera based on the positivity of both bacterial and viral pathogens. The dairy workers in this study also experienced decreases in cross-shift pulmonary function. The average decrease in forced expiratory volume in one second (FEV1) over 108 working shift was -74.4 ml, and the average decrease of forced vital capacity (FVC) was -92.5 ml. Significant differences in microbiome characteristics did emerge based on post-shift and cross-shift spirometry performances, and taxonomic differences were noted in participants performing poorly on cross-shift FVC. The nasal microbiomes of workers also underwent community state typing, and participants in CST3 showed the most resilience to cross-shift changes in lung function. This research also investigated the efficacy of a hypertonic saline nasal lavage in improving cross-shift changes in pulmonary function. From a cohort of 44 dairy workers, 22 workers received pre- and post-shift hypertonic saline nasal lavages with an osmotic concentration of 400 milliosmole (mOsm). The 22 participants in the control group received pre- and post-shift normotonic saline (308 mOsm) nasal lavages. Based on constructed mixed linear models, the treatment improved cross-shift outcomes of the forced expiratory flow at 25-75% of the vital capacity (FEF25-75%), but had little effect on FEV1 and FVC. The use of a pre- and post-shift lavage of any osmolarity, however, appeared to reduce the burden of cross-shift pulmonary function decline often experienced by dairy workers. For the first time, this research showed that both viral and bacterial pathogens are present in the nares of US dairy workers. This work also identified the nasal microbiome characteristics that may play a role in pathogen exposure and cross-shift lung function outcomes. The use of a saline nasal lavage as an intervention was also explored, and the intervention appeared to improve cross-shift pulmonary function outcomes.Item Open Access Characterizing stooped posture of agricultural tasks(Colorado State University. Libraries, 2024) Sanders, Denali, author; Rosecrance, John, advisor; Brazile, Bill, committee member; Hobbs-Murphy, Kayna, committee memberAgricultural field workers worldwide are often required to work in stooped postures during their working tasks. Stooped postures constitute a significant risk factor for the development of musculoskeletal disorders, specifically low back pathologies that cause pain. Chronic low back pain is a devastating disorder that can lead to depression, decreased mobility, lower quality of life, absenteeism from work, and decreased work productivity. Unfortunately, few studies have quantified stooped postures among agricultural workers, which makes it difficult to develop targeted work design improvements. The present study aimed to characterize stooped postures among workers engaged in several common agricultural tasks. Agricultural workers (N=43) were recruited from multiple Colorado farms and represented eight distinct work tasks. Participants wore a biomodule that contained a tri-axial accelerometer (Zephyr BioHarness) on their chests to record and log trunk postures in degrees for approximately two hours during specific work tasks. Data recorded on the sensor module were downloaded and analyzed in a customized RStudio program by participant and task to determine task cycle time, percentage of time spent in three posture categories (<0° to 30°, >30° to <60°, ≥60°), and mean trunk flexion. Stooped posture was defined as a trunk flexion equal to or greater than 60 degrees. The data indicated differences in task cycle time, percentage of time spent in posture categories, and mean trunk flexion across agricultural tasks. The results of the current study provide quantitative data that can help inform the development of targeted interventions aimed at reducing stooped postures in agricultural workers. Additionally, the methods developed in the present study may assist the Colorado Department of Agriculture and farm owners with evaluating the policies established in the Colorado Senate Bill (SB 21-087), which limits stooped postures during agricultural tasks that involve thinning and weeding during crop production.Item Open Access Community noise exposure from oil and gas drilling operations(Colorado State University. Libraries, 2024) Stepherson, Phillip, author; Brazile, William, advisor; VanDyke, Michael, advisor; Gutilla, Margaret, committee memberDue to an increase in oil and gas (O&G) extraction activity near residential areas in Colorado, many community members may be at a higher risk of harmful noise exposure. The Colorado Energy and Carbon Management Commission (ECMC) has identified multiple sources of high-volume sound associated with O&G site preparation, drilling, and fracking including engines, mud circulation systems, rig top drives, and ancillary equipment. Acute and chronic exposure to elevated levels of environmental noise has been found to cause adverse health effects such as sleep disturbance, annoyance, cognitive performance decline, heart disease, and self-reported impact to overall wellbeing. While there is existing literature quantifying the extent and consequences of community noise exposure from other environmental sources (e.g., air traffic, road traffic, and railway transportation) there are limited published studies on noise exposure from proximity to O&G extraction sites. Researchers suggest, however, that oil and gas extraction operations may be producing harmful levels of noise. It also appears that the noise produced includes substantial low-frequency noise which can make it difficult to control. In addition, low frequency noise exposure may exacerbate the health effects associated with general noise exposure. To assess community noise exposure, a comprehensive environmental noise survey was performed at a new O&G extraction site in Northern Colorado during the drilling phase of operations. The research team collected noise emission data 24 hours per day over two months that included 1-second measurements of sound-pressure level, 1/3 octave bands, and triggered audio recordings. Based on the noise-monitoring results, it was determined that the noise levels from the drilling activities exceeded ECMC published noise exposure limits and noise thresholds related to adverse health effects. Distance was found to be a crucial factor in establishing compliance and reducing exposure, especially for low frequency noise. Increasing the O&G operations setback from community residences to 2,000 feet, as compared to the previous setback distance of 350 feet, was estimated to reduce noise levels by 15dB, which, while a substantial improvement, was not entirely sufficient to eliminate the risk of health effects or establish compliance with low frequency noise limits. High noise levels were found to occur on days that the rig's hoisting mechanism and/or drill were likely in use.Item Open Access Effects of pH, temperature and competing ions on the adsorption of radiocesium on Prussian blue coated detonation nanodiamonds from aqueous solutions(Colorado State University. Libraries, 2024) Zaiger, Megan, author; Sudowe, Ralf, advisor; Johnson, Thomas, committee member; Lindsay, James, committee memberThe accident at the Fukushima Nuclear Powerplant, in 2011, resulted in the generation of radioactive contaminated water which is currently being stored on site. The Tokyo Electric Power Company (TEPCO), who owns the powerplant has begun treating and releasing the water into the ocean after most of the radioactivity has been removed by the Advanced Liquid Processing System (ALPS). Current techniques for preconcentration of radioisotopes, particularly radiocesium, from ocean waters are very labor and time intensive and often take months. Therefore, efficient, rapid, and reliable methods are needed for the determination of radiocesium in ocean water which represents a critical gap that this work seeks to address. A new technique using Prussian Blue (PB) coated detonation nanodiamonds (DND) to adsorb radiocesium from water samples is being investigated by the research group. The new technique takes hours to preconcentrate the radiocesium instead of months. The current study focuses on the effects of varying pH, temperature, competing ions, and stable cesium (Cs) on adsorption behavior of radiocesium. The results of the study show that high pH will result in a minimal decrease in Cs adsorption, while adsorption increases as pH increases, with the lowest adsorption of 95%. Temperature changes resulted in minimal decreases in Cs adsorption with the lowest adsorption of 98% measured at 4°C. Presence of potassium chloride (KCl), sodium chloride (NaCl), and lithium chloride (LiCl) at concentrations up to 1.0 M had no effect on the uptake of radiocesium showing adsorption of above 97% for all elements. However, adsorption decreased significantly in the presence of rubidium chloride (RbCl) as interferent concentration increased, with the lowest adsorption of 68% recorded for 1.0 M RbCl. The addition of stable Cs to low amounts of Cs-137 (1 Bq) saw high uncertainties and low adsorption reflecting the difficulty to obtain consistent results at very low concentrations. The study has shown promise for the use of DND in environmental settings with a continued need to be able to detect low levels of Cs-137.