Theses and Dissertations at Montana State University (MSU)
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Item Increasing statin utilization in patients at high risk of atherosclerotic cardiovascular disease in remote physiological monitoring program(Montana State University - Bozeman, College of Nursing, 2023) Ottemoeller, Christopher Michael; Chairperson, Graduate Committee: Lindsay BenesStatement of the problem: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality worldwide costing the United States an estimated $200 billion a year. Dyslipidemia, a leading risk factor for ASCVD, is well controlled by statin medications. Despite high efficacy, low cost, and a favorable safety profile, statins are underutilized. A healthcare facility in Montana aimed to increase utilization of statins in high-risk populations through pharmacist chart reviews. Methods: The quality improvement case manager at the healthcare facility conducted a review of patient charts to identify those at high risk for ASCVD who were not receiving statin therapy based on MIPS #438 recommendations. The case manager identified patients that would benefit from a statin and referred them to a pharmacist for a medication chart review. The pharmacist then called the patient to complete a medication chart review and sent recommendations for medication changes to the patient's primary care provider (PCP). Results: Twenty-two patients were initially identified for statin therapy with 13 deemed eligible. Six of them (46%) agreed to a pharmacist chart review and were contacted by the pharmacist, all of whom agreed to statin therapy. The pharmacist made an average of two additional medication changes recommendations per review. Thus far, three patients followed up with their provider and started statin and one patient completed a repeat lipid panel. Conclusion: Pharmacist outreach can increase statin utilization in patients at high-risk of ASCVD. Further research should focus on improving statin tolerability and ability to contact patients.Item Widefield micro-camera integrated into the objective lens of a reflectance confocal microscope for concurrent image registration(Montana State University - Bozeman, College of Engineering, 2023) Aist, Joseph Nicholas; Chairperson, Graduate Committee: David L. DickensheetsWith millions of new skin disease cases reported annually, non-invasive imaging methods have been developed to diagnose skin disease accurately. Reflectance confocal microscopes (RCM) have led these new technologies with high sensitivity and specificity. However, current methods use multiple devices: a digital camera, a dermoscope, and an RCM, which are not co-registered. Therefore, locating small, microscopic RCM fields-of-view (0.5x0.5 mm) at specific suspicion sites within the larger dermoscopic field-of-view (10x10 mm) is extremely difficult. This 'blind' RCM imaging results in lower and more variable diagnostic accuracy, particularly sensitivity, where positive and negative predictive values can drop by up to 30%. Our team has designed a new objective lens with an integrated micro-camera to deliver a concurrent widefield image of the skin surface surrounding the location of microscopic RCM imaging. The widefield image can be used directly to provide context for RCM or can be registered to a previously stored high-resolution clinical image to show where RCM imaging is occurring. In this thesis, the micro-camera is characterized and tested in laboratory and clinical settings. In addition, this thesis investigates a co- and cross-polarized micro-camera and LED system. It compares them to the non-polarized system to explore whether the cross-polarized version enhances feature contrast and enables better dermoscopic imaging. Non-polarized, co-polarized, and cross-polarized mock-up probes of the objective lens with a micro-camera were designed and built for testing. Images of resolution targets, color charts, and skin were taken to obtain modulation transfer function (MTF) measurements, color analysis data, and representative skin images. The results showed improvement in the MTF for the cross- polarized probe when compared to the co- and non-polarized probes. It was also found that the polarization of the imaging system did not significantly affect the color quality of the images. When tested by scientists at Memorial Sloan Kettering Cancer Center, sub-surface features not seen with the co- and non-polarized probes were observed with the cross-polarized probe. The cross-polarized probe suppressed the surface reflections, allowing for sub-surface information to be captured.Item Evaluation of interdisciplinary patient care conferences for the complex patient population in a rural state(Montana State University - Bozeman, College of Nursing, 2021) Posada, Britt Kristen; Chairperson, Graduate Committee: Wade G. HillPrimary care practice in the 21st century requires innovative and visionary transformation. With the prevalence of chronic diseases continuing to increase, the management of diseases and patients has to change in order to make an impact on outcomes and healthcare costs. As needs for primary care expand, the population ages and patient complexity increases, collaborative care is vital in providing optimum patient care. In 2018, the United States healthcare costs were $3.6 trillion, averaging $11,000 per person and are projected to increase to $6.2 trillion by year 2028. With care that is often fragmented between large hospital systems and community resources, rural states have shown that coordinated care teams have had a dramatic impact on healthcare costs. Monthly de-identified interdisciplinary patient care conferences were evaluated using the Collaborative Case Conference form. In the spring of 2021 an electronic survey was delivered to 18 historical participants of the interdisciplinary patient care conferences via email with goals of obtaining formative and summative evaluations. Formative evaluation found that 100% of participants responded Very Good-Excellent in usefulness of discussions as well as collaborative nature. The summative evaluation revealed that 93.34% of participants Agreed-Strongly Agreed that, as a result of the care conferences, they had a clearer sense of other health professionals roles. All participants reported that they Agreed-Strongly Agreed that there was greater value in interprofessional collaboration after participating in the conferences. Limitations of the evaluation included technology, recall bias, poor survey choices, and low scalability of project. In conclusion, the evaluation of the interdisciplinary patient care conferences for complex patients in a rural state was an overall success. Unfortunately, the program is no longer ongoing as it was halted after funding ended, making sustainability one challenge of convening statewide care conferences of this type. On a positive note, after the initiative was finished individual organizations did implement similar localized care conferences within their settings.Item Experimental infection of specific pathogen-free domestic lambs with Mycoplasma ovipneumoniae(Montana State University - Bozeman, College of Agriculture, 2021) Johnson, Thea Haviland; Chairperson, Graduate Committee: Diane Bimczok; Diane Bimczok, Kerri Jones, Cassie Mosdal, Steven Jones, SK, CB, AS, and B. Tegner Jacobson were co-authors of the article, 'Immunoglobulin transfer, survival, and growth in motherless lambs fed a bovine serum-based colostrum replacer' which is contained within this thesis.; Kerri Jones, B. Tegner Jacobson, Julia Schearer, Noah Adams, Isaak Thornton, Cassie Mosdal, Steven Jones, Mark Jutila, Agnieszka Rynda-Apple, Thomas Besser and Diane Bimczok were co-authors of the article, 'Experimental infection of specific-pathogen-free domestic lambs with Mycoplasma ovipneumoniae causes asymptomatic colonization of the upper airways that is resistant to antibiotic treatment' in the journal 'Veterinary microbiology' which is contained within this thesis.Mycoplasma ovipneumoniae (M. ovi) is a respiratory pathogen commonly found in sheep and goats. It is associated with mild to moderate respiratory disease in domestic lambs, but severe pneumonia outbreaks in wild ruminants, specifically bighorn sheep. The goal of our study was to better understand the role of M. ovi as a respiratory pathogen in domestic sheep and to explore potential antibiotic treatment approaches. We first established a flock of specific pathogen-free (SPF) lambs through supervised lambing and motherless rearing in a Large Animal BSL-2 facility. Lambs were fed a colostrum replacer that yielded low mortality, steady weight gain and serum IgG and protein concentrations comparable to those of lambs raised on ewe colostrum. We inoculated the SPF lambs with field isolates of M. ovi and monitored the lambs for eight weeks for colonization with the bacteria, M. ovi-specific antibodies, clinical symptoms, and cellular and molecular correlates of lung inflammation. After eight weeks, lambs were treated with the macrolide antibiotic gamithromycin and observed for an additional four weeks. Stable colonization of the upper respiratory tract with M. ovi was established in all four M. ovi-inoculated, but in none of the four mock-infected lambs. All M. ovi-infected lambs developed a robust antibody response to M. ovi within 2 weeks. However, we did not observe significant clinical symptoms, evidence of lung damage or inflammation in any of the infected lambs. Interestingly, treatment with gamithromycin failed to reduce M. ovi colonization. These observations indicate that, in the absence of co-factors, M. ovi causes asymptomatic colonization of the upper respiratory tract of that is resistant to clearance by the host immune response as well as by gamithromycin treatment in domestic lambs.Item The horses with no names: lessons from the U.S. Civil War(Montana State University - Bozeman, College of Letters & Science, 2021) Boynton, Frank Robert; Chairperson, Graduate Committee: Brett WalkerHistorians have paid insufficient attention to horses in the study of military history. The US Civil War is no exception. Horses were central to the conduct and outcome of the Civil War. They provided the essential motive power for both armies. Without them, no military strategy was feasible. They carried the charging cavalrymen. They pulled the artillery through fields and mired roads with mud so deep the horses risked drowning in it. They supported command and control as they carried leaders and their staffs. They pulled the ambulances that carried stricken men from the battlefield to hospitals. They pulled the supply wagons that supplied the armies. The horse required a universe of support to sustain it. The frequent inability of armies to provide simple hay and grain caused thousands to starve to death. The time and distance imperatives of war often strained horses beyond their capacity -- thousands died from simple exhaustion Much like the soldiers who died in the thousands from diseases, horses died by the tens of thousands from diseases for which they had no defense and for which the men charged with their care had no ability to treat. Lastly, much like the human soldiers they shared the risk of the battlefield with horses were ripped by shot and shell. This is a highly interdisciplinary study and therefore I use material from beyond history. Papers in veterinary medicine provide information on equine disease and the 1860's understanding of it. Studies into equine nutrition and about the recovery of horses from prolonged malnutrition or starvation, on the effects of sleep deprivation and others inform understanding of the horse at war. The 1860 Census and US Department of Agriculture crop reports provide insights into the ability of the Pennsylvania/Maryland/Virginia area to support large numbers of horses. This material is integrated into a framework which I use to assess the probable condition of both Union and Confederate horses. I use that assessment as a means take a fresh look at specific Civil War events and other military episodes through the lens of the condition of the horses supporting the armies.Item Preeclampsia and increased risk of cardiovascular disease: a practice guide for providers(Montana State University - Bozeman, College of Nursing, 2020) Toole, Brielle Ashli; Chairperson, Graduate Committee: Sandra Benavides-VaelloCardiovascular disease (CVD) is the leading cause of death among women, however this disease is preventable and treatable. Extant evidence has established that women with a history of preeclampsia are at an increased risk for developing CVD later in life, and yet preeclampsia is under-recognized as a risk factor for CVD. This is due to a knowledge gap amongst healthcare providers, and subsequently providers are not adequately educating their patients with a history of preeclampsia about their CVD risk and reducing this risk. There are no specific guidelines regarding long-term care or screening for CVD in women with a history of preeclampsia, so a guideline needs to be developed to assist providers in caring for this high-risk population. The first aim of this project is to develop a guideline for providers to use in practice while caring for women with a history of preeclampsia, and the second aim is to enhance providers' knowledge of the link between a history of preeclampsia and increased CVD risk later in life so they can provide improved, evidence-based care. This project used a pre-survey, educational content with dissemination of two practice guidelines in different formats and a patient educational handout, and post-survey approach. The project targeted healthcare providers who care for women with a history of preeclampsia at a small rural hospital. Providers who participated in this project did have knowledge of the link between preeclampsia and increased CVD later in life, but were not applying this knowledge to their practice, as they neither took a thorough pregnancy history from their patients in regards to preeclampsia nor provided counseling to women with a history of preeclampsia about their increased risk of CVD. Providers who reviewed the guideline presented in this project found it helpful and had or planned to implement a practice change because of the guideline. The practice guideline developed was an effective tool to help the providers in this project implement evidence-based care into their practice, and the patient handout was an additional resource they could use to educate their patients with a history of preeclampsia.Item Large-scale automated human protein-phenotype relation extraction from biomedical literature(Montana State University - Bozeman, College of Engineering, 2020) Pourreza Shahri, Morteza; Chairperson, Graduate Committee: Indika KahandaIdentifying protein-phenotype relations is of paramount importance for applications such as uncovering rare and complex diseases. Human Phenotype Ontology (HPO) is a recently introduced standardized vocabulary for describing disease-related phenotypic abnormalities in humans. While the official HPO knowledge base maintains known associations between human proteins and HPO terms, it is widely believed that this is incomplete. However, due to the exponential growth of biomedical literature, timely manual curation is infeasible, rendering the need for efficient and accurate computational tools for automated curation. In this work, we present HPcurator, a novel two-step framework for extracting relations between proteins and HPO terms from biomedical literature. First, we implement ProPheno, a comprehensive online dataset composed of human protein-phenotype co-mentions extracted from the entire set of biomedical articles. Subsequently, we show that these co-mentions are useful as a complementary source of input for a different, but highly related, task of automated protein-phenotype prediction. Next, we develop a supervised machine learning model called PPPred, which, to the best of our knowledge, is the first predictive model that can classify the validity of a given sentence-level protein-phenotype co-mention. Using a gold standard dataset composed of manually curated sentence co-mentions, we demonstrate that PPPred significantly outperforms several baseline methods. Finally, we propose SSEnet, a novel deep semi-supervised ensemble framework for relation extraction that combines deep learning, semi-supervised learning, and ensemble learning. This framework is motivated by the fact that while the manual annotation of co-mentions is extremely prohibitive, we have access to millions of unlabeled co-mentions. We develop a prototype of HPcurator by instantiating SSEnet with ProPheno, self-learning, pre-trained language models, as well as convolutional and recurrent neural networks. This system can successfully output a ranked list of relevant sentences for a user input protein-phenotype pair. Our experimental results indicate that this system provides state-of-the-art performance in human protein- HPO term relation extraction. The findings and the insight gained from this work have implications for biocurators, biologists, and the computer science community involved in developing biomedical text mining tools.Item Characterizing summer roosts of male little brown myotis (Myotis lucifugus) in lodgepole pine-dominated forests(Montana State University - Bozeman, College of Letters & Science, 2020) Hilty, Shannon Lauree; Chairperson, Graduate Committee: Andrea LittAlthough bat roosts have been well-studied in the eastern United States, we know less about roosts in the west. Western bats may make use of trees and snags, as in the eastern US, but the Rocky Mountains provide more exposed rock, which could contribute to western bat species using different roosting features. Additionally, roost studies often focus on maternity colonies, and information on roosts used by male bats is limited. Given that roosting sites may be limiting, we aimed to quantify structural features of roosts used by male little brown myotis (Myotis lucifugus) in forests dominated by lodgepole pine (Pinus contorta) during the summer and determine whether bats are selecting roosts with particular features disproportionately to what is available on the landscape. We mist-netted for bats during the summers of 2017 and 2018 and attached transmitters to 34 male little brown myotis. We located at least 1 roost for 20 individuals (average = 2.85 roosts/bat, range = 1-6). Although snags were available, most bats roosted in rock features (86% in rocks, 14% in snags); rock roosts were mainly in crevices with vertical orientations (85%) instead of rock cavities (15%). Male bats were more likely to select roosts with less canopy closure (mean for used locations = 14.1%, SE = 2.3) that were closer to water (1063.1 m, SE = 136.2). They also selected roosts with more overall rock cover (77%, SE = 3), wider entrances (3.1 cm, SE = 0.3), and access to a skyward-facing crevice, creating warmer microclimates. Our work indicates that rock features provide essential summer habitat for male little brown myotis and that lodgepole pine in this landscape may not provide appropriate roosting features. Understanding how other bat species may be using rock features, during summer and other seasons, remains a sizeable information gap. Learning more about hibernacula is of great importance due to the spread of white-nose syndrome and rock features may be essential autumn transitional roosts and winter hibernacula at higher elevations. Roosts that provide variation in microclimate, including the potential for passive warming, could be very beneficial for bats recovering from white-nose syndrome.Item Microbial ecology of mosquitos and ticks(Montana State University - Bozeman, College of Letters & Science, 2017) Pinkham, Nicholas Vernon; Chairperson, Graduate Committee: Seth WalkHost evolutionary history has been shown to select for distinct host associated microbial communities over large evolutionary time scales. The microbiomes of disease vector have been shown to alter the capacity of their host to vector pathogens. Much remains to be understood about how the microbiome of mosquitos and ticks assemble in situ. We conducted a large-scale investigation of microbiome composition between mosquito species as well as a second investigation of microbiomes of brown dog ticks collected in Iquitos, Peru. Intraspecific and interspecific bacterial community diversity was compared across 26 species of mosquitoes collected in Montana. Previous studies of lab reared mosquitoes report greater variation in microbial communities between species than within. Using 16S rRNA sequencing we observed a large amount of intraspecific variation in microbiomes, as well as different species hosting very similar microbiomes. The tick microbiome was found to be dominated by a few select community members that were seen at an extremely high abundance and resembled intracellular tick-borne pathogens. It is common for ticks to host endosymbionts that closely to human pathogens but are not pathogenic themselves. Negative interactions were seen between the most abundant organism observed in the ticks.Item Post-prandial serum concentrations of Trimethylamine-N-oxide in overweight and obese adults with low and high systemic inflammation(Montana State University - Bozeman, College of Education, Health & Human Development, 2018) Wilson, Stephanie Michelle; Chairperson, Graduate Committee: Mary P. MilesPurpose: Elevated trimethylamine-N-oxide (TMAO) levels have been implicated in the development of atherosclerosis. The impact of a high-fat meal on the post-prandial TMAO response in healthy overweight and obese adults was explored, accounting for additional variables that may affect the rate of TMAO conversion. Methods: Forty overweight and obese men and women participated in a high-fat meal challenge containing 50 g fat. Blood samples were collected at fasting and hourly in the 4 hours after meal ingestion and tested for concentrations of TMAO, liver enzymes, lipids, creatinine, insulin, and inflammatory markers. An initial mixed-effects model was constructed to analyze TMAO changes in participants who classified as having low or high levels of systemic inflammation accounting for factors that may influence TMAO concentrations. Backward refinement of the initial model was performed based off p-values. Results: Model refinement found that the log TMAO response was best explained by inclusion of estimated glomerular filtration rate (eGFR), insulin over time, a linear interaction between time and inflammation phenotype, and random effects on subject. Log TMAO after the meal was not different between inflammation phenotypes (p = 0.33). Estimated GFR was the most important determinant in the log TMAO response (p = 0.03), with lower log TMAO observed with higher eGFR values. In conclusion, serum TMAO concentrations during a high fat-meal challenge were strongly determined by eGFR, but not by fasting inflammation status.