Theses and Dissertations at Montana State University (MSU)
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Item Assessing a novel approach to pharmaceutical removal from wastewater: aerobic granular sludge(Montana State University - Bozeman, College of Engineering, 2024) Bodle, Kylie Brigitta; Chairperson, Graduate Committee: Catherine Kirkland; This is a manuscript style paper that includes co-authored chapters.Pharmaceutical concentrations in various environmental matrices are increasing across the globe. Effluent discharge from wastewater treatment plants is a major vector by which pharmaceuticals enter the environment, as many of these compounds are not biodegradable under conventional wastewater treatment conditions. Although concentrations are currently low (ng/L to ?g/L levels), pharmaceutical contamination poses risks to both human and animal health, as many pharmaceuticals can have toxic effects on fish, birds, and small mammals, as well as contribute to the proliferation of antibiotic resistance genes in bacteria. Aerobic granular sludge (AGS), an emerging biofilm-based wastewater treatment biotechnology and the subject of this dissertation, may be capable of enhancing pharmaceutical removal from wastewater. Scientific literature indicates that AGS uses a mixture of both biodegradation and adsorption to remove pharmaceuticals, but thus far, studies on this topic are limited. The research detailed herein investigated how AGS was affected by a mixture of three common, but relatively unstudied, pharmaceuticals: diclofenac (anti-inflammatory), erythromycin (antibiotic), and gemfibrozil (lipid regulator). Studies described herein examined how AGS grown in two different environments--the lab versus a full-scale wastewater treatment plant--responded to pharmaceuticals. Pharmaceutical effects on wastewater treatment efficacy, active microbial populations, and biofilm structures were investigated. Pharmaceutical fates in both the aqueous and solid phases were also tracked. In general, lab-grown AGS was more negatively impacted by pharmaceutical exposure, evidenced by reduced wastewater treatment efficacy, declines in key wastewater-treating microbial populations, and reductions in biofilm lipid content. Pharmaceuticals were also poorly removed by lab-grown granules. In contrast, key microbial populations and biofilm structures remained stable throughout dosing in environmentally-grown AGS, and gemfibrozil was completely biodegraded. An important caveat to comparison of the two studies, however, is that the pharmaceutical dose to lab-grown AGS was approximately double that to environmental granules. Altogether, the research described herein demonstrates the promise of AGS as a dual wastewater and pharmaceutical treatment technology, but illustrates the importance of conducting experiments under conditions as environmentally relevant as possible.Item The expansion and optimization of ZN(II)-mediated intramolecular metalloamination and subsequent CU(I)-catalyzed functionalization for the construction of pyrrolidines and piperidines(Montana State University - Bozeman, College of Letters & Science, 2023) Frabitore, Christian Ames; Chairperson, Graduate Committee: Thomas S. Livinghouse; This is a manuscript style paper that includes co-authored chapters.Nitrogen-containing heterocycles (azacycles) are ubiquitous in pharmaceutical agents. Their ability to moderate and modulate the activity of drugs in the body make them especially powerful, and thus sought after, synthetic targets. While the synthesis of many popular azacycles has been greatly improved in recent years, the production of pyrrolidines and piperidines has not received as much attention despite their standing as the 1st and 5th most common azacycles in FDA-approved drugs. The intramolecular Zn(II)-mediated metalloamination/cyclization of N,Ndimethylhydrazinoalkenes provides structurally diverse pyrrolidines and piperidines with the added advantage of a subsequent functionalization step, efficiently building molecular complexity in one reaction sequence. Herein, this method is optimized and improved by the addition of a new hydrazone reduction method, the inclusion of 1-bromoalkynes in the functionalization step, and multiple key discoveries in the reagents used to effect these transformations. Furthermore, preliminary results adding N,N-dimethylhydrazinoallenes as substrates for this powerful method are presented.Item Increasing oncology patient engagement in treatment decisions: a CNL driven educational approach(Montana State University - Bozeman, College of Nursing, 2022) Northrop, Kayla Marie; Chairperson, Graduate Committee: Denise RiveraCancer is the second leading cause of death in Montana affecting 40% of men and 38% of women (MCTR, 2019). In the state of Montana Cancer is attributed to 452 new cancer cases per every 100,000 people, or one in every four persons (MCTR, 2019). Current best practice treatment options for cancer include chemotherapy and biosimilar medications of chemotherapy also known as Biologicals. Biosimilar medication is a product that contains a similar but not identical, version of an active compound of that of the originator medication authorized by the FDA for treatment of cancer (Edwards and Bellinvia, 2020). A literature review was conducted containing fifteen journal articles that included: four systemic reviews, a randomized double-blind study, two observational studies, and one retrospective study. When evaluating the information gathered, it was clear that due to the recent development and lack of public knowledge of biosimilars there is missing and unknown information. The missing information could alter the education needed and topics patients may want to know in an educational program. The plan for this quality improvement project is to create an educational program for biosimilars in oncology offices for providers to use with patients that may need to switch to a biosimilar in their treatment plan and allow for increase patient outcome and safety.Item Interactive policy effects of the 2010 Oxycontin reformulation(Montana State University - Bozeman, College of Agriculture, 2021) Baan, Joseph Bradford; Chairperson, Graduate Committee: Isaac SwensenIn this paper I estimate the additional effects counties with active Prescription Drug Monitoring Programs and Medical Marijuana Laws felt after the 2010 OxyContin reformulation compared to counties without these laws. I also estimate the effect of each additional Substance Abuse Treatment facility as well after the reformulation. I find that counties with PDMPs and MMLs see the morphine equivalent of a 6.557 and 4.681 grams decrease in the Oxycodone shipped to pharmacies for every 1000 people. Each additional SAT is associated with a 0.11 Morphine Grams Equivalent decrease. For reference 6.557 represents about 3% of the county average of MGE in Oxycodone.Item Standardizing documention of schedule II prescription in a primary care clinic(Montana State University - Bozeman, College of Nursing, 2019) Taylor, Lindsey Beth; Chairperson, Graduate Committee: Wade G. HillStandardization of processes and documentation in healthcare has continually been linked to quality of care. Implementation of new electronic health records (EHR), inadequate training, and lack of processes in place can all effect nursing documentation. The purpose of this project is to standardize documentation of charting the destruction of schedule II prescriptions in an Internal Medicine Clinic. Prior to the implementation of this project there was no standardized workflow for how or where to document the destruction of schedule II prescriptions. Lack of standardization and protocol contributed to prolonged time to complete refills, increased risk of duplicates, increased risk of harm to patients, and high nurse utilization. A pre and post-test was utilized to evaluate the nurse practice on documenting the destruction of controlled prescriptions. The pre-intervention results demonstrated inconsistent documentation which included: documenting in a communication encounter, documenting in the medication tab, a mixture of both documenting in the communication encounter and medication tab, or just not documenting. A standardized workflow was developed, presented to nursing staff, and competency assessment completed. The post-test demonstrated 100% compliance in documentation and made locating the documentation in the chart faster and easier reducing nurse workload.Item Characterizing excited state dynamics and carrier transport in hybrid organic-inorganic lead halide perovskites via ultrafast microscopy(Montana State University - Bozeman, The Graduate School, 2018) Hill, Andrew Hinson; Chairperson, Graduate Committee: Erik Grumstrup; Kori E. Smyser, Casey L. Kennedy, Eric S. Massaro and Erik M. Grumstrup were co-authors of the article, 'Ultrafast microscopy of methylammonium lead iodide perovskite thin films: heterogeneity of excited state spatial and temporal evolution' which is contained within this thesis.; Kori E. Smyser, Casey L. Kennedy, Eric S. Massaro and Erik M. Grumstrup were co-authors of the article, 'Screened charge carrier transport in methylammonium lead iodide perovskite thin films' in the journal 'Journal of physical chemistry letters' which is contained within this thesis.; Casey L. Kennedy, Eric S. Massaro and Erik M. Grumstrup were co-authors of the article, 'Perovskite carrier transport: disentangling the impacts of effective mass and scattering time through microscopic optical detection' in the journal 'Journal of physical chemistry letters' which is contained within this thesis.; Casey L. Kennedy and Erik M. Grumstrup were co-authors of the article, 'Determining the effects of A-site cation substitution on the optical response and transport properties of lead tri-bromide perovskites' submitted to the journal 'Journal of physical chemistry letters' which is contained within this thesis.Lead tri-halide perovskites have recently emerged as cost-effective alternatives to silicon for use in photovoltaic devices. A large contributor to their reduced cost compared to silicon is the simple solution processed techniques employed in their fabrication. While these methods can produce effective photovoltaic devices, heterogeneity endemic to solution processing makes characterization of tri-halide perovskites a challenging task. Most spectroscopic techniques use large sample interrogation volumes which often results in the indiscriminate sampling of grain boundaries and other heterogeneities which impact the spectroscopic observable. To circumvent this issue, pump-probe microscopy is used to dramatically shrink the sample volume, reducing the contributions from chemical and morphological heterogeneities and providing a more accurate measure of the sample's inherent properties. This work begins with a study of the recombination and transport dynamics methylammonium lead tri-iodide (MAPbI 3) perovskite. After identifying the main recombination pathways and contributions to the transient signal, experimental focus is shifted to the transport properties of MAPbI 3. The key contributing factors to the high diffusivities reported in MAPbI 3 are found to be strong electron-phonon coupling and a high static dielectric constant which serves to screen carriers from interactions with charged defects and other carriers. Then the development a new all-optical method capable of uniquely determining the two fundamental parameters that govern carrier transport (the mean scattering time and optical mass of photogenerated carriers) is reported. This method was applied to a series of different perovskite materials including MAPbI 3, cesium lead bromide di-iodide (CsPbBrI 2), methylammonium lead tri-bromide (MAPbBr 3), formamidinium lead tri-bromide (FAPbBr 3), and cesium lead tri-bromide (CsPbBr 3). The results of these experiments have led to the characterization of the role each perovskite constituent (namely, the identity of the organic cation and the halide stoichiometry) plays in determining the transport properties of the resulting material. The work presented in this dissertation characterizes the transport properties of lead halide perovskites. Measurements collected across multiple discrete and highly crystalline domains of multiple perovskite species have helped establish a relationship between the functionality and the local structure of these materials. Additionally, the design and first application of a new methodology to disentangle the effects of mean scattering time and the photogenerated carrier mass on carrier transport is reported. This technique will not only continue to aid in the characterization of lead-halide perovskites but will likely also see use on a host of other material systems to advance understanding of carrier transport in a variety of materials.Item Attention deficit hyperactivity disorder treatment for pediatrics(Montana State University - Bozeman, College of Nursing, 2018) Brewer, John Mikkel; Chairperson, Graduate Committee: Tracy HellemAttention deficit, hyperactivity disorder (ADHD) is commonly diagnosed in children, and the frequency of this disorder being diagnosed and treated continues to rise each year. The research regarding treatment for pediatric ADHD has shown varied results ranging from pharmacological and behavioral therapies producing positive effects when combined to standalone behavioral therapy or medication producing positive effects with no therapeutic intervention. There are two published guidelines on the management of pediatric ADHD. The American Academy of Pediatrics and the National Collaborating Centre for Mental Health each created a guideline for evaluating, diagnosing, and treating pediatric patients with ADHD. This project analyzed ADHD treatments for children ages 4 to 18 years in an acute, inpatient psychiatric setting, and in an inpatient, residential-treatment-care setting. A comparison of these treatments with the national guidelines was conducted. This scholarly project compared pediatric ADHD treatment in an inpatient, acute-care unit versus a residential-care unit of a psychiatric children's hospital. Readmission rates within 30 days of discharge from a psychiatric children's hospital have been analyzed, and care practices have been compared with the national guidelines. Data was extracted from electronic medical records from the psychiatric children's hospital's healthcare record system. The types of data that were extracted included demographics, such as age, comorbid diagnoses, and concomitant medications; in addition to types of treatment, readmission rates, and treatment setting. Type-of-treatment data included type of medication versus treatment setting. The findings suggest that medications other than methylphenidate may have similar efficacy as methylphenidate for treating pediatric ADHD. The inpatient psychiatric unit is not necessarily following the National Clinical Guidelines for treating pediatric and adolescent ADHD, but the results reveal that methylphenidate versus non-methylphenidate treatment for ADHD does not demonstrate a statistically significant difference with respect to inpatient readmission rates. The research identified that patients receiving residential care for ADHD had a higher likelihood of being readmitted to the hospital than patients receiving acute care, and patients' readmission rates were not statistically significantly different regarding methylphenidate versus non-methylphenidate medication-treatment regimens. Overall, this research identified that medications other than methylphenidate can be effective in treating patients with ADHD.Item Crystal pressure of pharmaceuticals in nanoscale pores(Montana State University - Bozeman, College of Engineering, 2017) Berglund, Emily Anne; Chairperson, Graduate Committee: James WilkingMany pharmaceutical compounds are poorly soluble in water. This is problematic because most pharmaceuticals are delivered orally and must dissolve in the gastrointestinal fluid to be absorbed by the body. Drug dissolution rate is proportional to surface area, so a common formulation strategy is to structure drugs as small as possible to maximize surface area. A simple approach to create very small particles is to structure the compounds within the nanoscale pore space of a colloidal packing. The resulting composite undergoes rapid disintegration in water and the exposed drug exhibits dramatically improved dissolution rates. We hypothesize that composite breakup is driven by the growth of nanoscale crystals, which exert a pressure on the walls of the confining pores. To test this hypothesis, we systematically vary the amount of water permitted into the composite and use calorimetry to monitor the evolution of the crystal size distribution as a function of water content. To exert sufficient pressure to overcome the tensile yield stress of the composite, the crystals must be fed by a supersaturated phase. Our results suggest that differences in crystal curvature due to crystal confinement and crystal size polydispersity generate the necessary supersaturation. These results are relevant not just for drug formulations, but for understanding physical processes such as salt damage to buildings and road damage due to frost heave.Item Effect of flunixin meglumine on early embryonic mortality in stressed beef female(Montana State University - Bozeman, College of Agriculture, 2004) Merrill, Melissa Lee; Chairperson, Graduate Committee: Raymond P. Ansotegui.The objectives of this study were to determine if an injection of flunixin meglumine (1.1 mg/kg BW) would affect early embryonic mortality in stressed beef females. Ninety-seven cows were assigned to one of three treatment groups (Experiment 1; El). Treatments were: 1.) control (CON) 2.) transportation stressed (S) and 3.) transportation stressed with flunixin meglumine (SFM). The following year 259 heifers (Experiment 2; E2) and 127 cows (Experiment 3; E3) were assigned to one of four treatments: the three treatments used in El plus control with flunixin meglumine (CONFM). Approximately 14 d following synchronization of estrus and artificial insemination (Al) treatments were applied in all three experiments. Rectal temperatures were recorded and blood samples were taken for serum concentration of progesterone, PGF metabolite, and cortisol. The CON and CONFM (NTS) remained at the ranch while S and SFM (TS) females were transported for 5-6 h. The SFM and CONFM (FM) treatments received an injection of flunixin meglumine (1.1 kg/mg BW, i.m.) while S and CON did not receive an injection of flunixin meglumine (NFM). Females were not exposed to clean-up bulls until after treatment. Transrectal ultrasonography was used to determine Al pregnancy status 33-35 d for heifers and 55-57 d for cows post-AI. Statistics were determined using a 2x2 factorial design. No differences were detected in progesterone or PGFM serum concentration (P>0.10) in El. Serum cortisol concentrations decreased for stressed animals (S and SFM) compared to control animals (CON) between pre- and post-treatment blood samplings (P<0.05) in El. In E2 and E3, serum cortisol concentrations were similar (P>0.10) at the initial blood sampling, increased for TS compared to NTS (P<0.01) at intermediate blood sampling and decreased greater for TS compared to NTS (PO.01) at the final blood sampling. Temperatures were similar for initial temperature collection among treatments of E2 and E3. At the E3 intermediate and E2 final temperature collection, FM was lower (P<0.05) than NFM. The Al pregnancy rates were higher (P=0.03) for FM (63%) than NFM (53%) when combining E2 and E3. The SFM cows had higher (P=0.06; 71%) Al pregnancy rates than S (60%) with CON (63%) being intermediate when combining El, E2, and E3. Final pregnancy rates did not differ. In conclusion, flunixin meglumine decreases the embryonic mortality in beef females that are transportation stressed d 12-14 post-AI but . the stress of handling needs to be explored.Item The effects of acute and chronic prenatal alcohol exposure on lymphoid organ development and immune function in C57BL/6 mice(Montana State University - Bozeman, College of Agriculture, 1990) Huang, Ching