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Description
Due to artificial selection, dogs have high levels of phenotypic diversity, yet, there appears to be low genetic diversity within individual breeds. Through their domestication from wolves, dogs have gone through a series of population bottlenecks, which has resulted in a reduction in genetic diversity, with a large amount of

Due to artificial selection, dogs have high levels of phenotypic diversity, yet, there appears to be low genetic diversity within individual breeds. Through their domestication from wolves, dogs have gone through a series of population bottlenecks, which has resulted in a reduction in genetic diversity, with a large amount of linkage disequilibrium and the persistence of deleterious mutations. This has led to an increased susceptibility to a multitude of diseases, including cancer. To study the effects of artificial selection and life history characteristics on the risk of cancer mortality, we collected cancer mortality data from four studies as well as the percent of heterozygosity, body size, lifespan and breed group for 201 dog breeds. We also collected specific types of cancer breeds were susceptible to and compared the dog cancer mortality patterns to the patterns observed in other mammals. We found a relationship between cancer mortality rate and heterozygosity, body size, lifespan as well as breed group. Higher levels of heterozygosity were also associated with longer lifespan. These results indicate larger breeds, such as Irish Water Spaniels, Flat-coated Retrievers and Bernese Mountain Dogs, are more susceptible to cancer, with lower heterozygosity and lifespan. These breeds are also more susceptible to sarcomas, as opposed to carcinomas in smaller breeds, such as Miniature Pinschers, Chihuahuas, and Pekingese. Other mammals show that larger and long-lived animals have decreased cancer mortality, however, within dog breeds, the opposite relationship is observed. These relationships could be due to the trade-off between cellular maintenance and growing fast and large, with higher expression of growth factors, such as IGF-1. This study further demonstrates the relationships between cancer mortality, heterozygosity, and life history traits and exhibits dogs as an important model organism for understanding the relationship between genetics and health.
ContributorsBalsley, Cassandra Sierra (Author) / Maley, Carlo (Thesis director) / Wynne, Clive (Committee member) / Tollis, Marc (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
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Description
Physician-assisted suicide occurs when a physician facilitates a patient's death by prescribing a lethal medication that they understand will be used for the purpose of ending the patient's life. It is a highly contentious subject and, with the recent addition of California to the list of states that allow physician-assisted

Physician-assisted suicide occurs when a physician facilitates a patient's death by prescribing a lethal medication that they understand will be used for the purpose of ending the patient's life. It is a highly contentious subject and, with the recent addition of California to the list of states that allow physician-assisted suicide, is an increasingly relevant subject. Physician-assisted suicide is rarely framed as a healthcare experience, despite being a choice in the process of end-of-life care. The research seeks to bring together the debates about physician-assisted suicide with conversations about health care experiences. The experiences and perspectives of young people are particularly valuable to evaluate now, as their voices will soon be the leaders in the debate over physician-assisted suicide. Within this research, there is an underlying theme of independence of individuals that is present through both the literature review and the body of data collected and analyzed. The study found that there was no significant relationship between the quality of a person's healthcare and their perspectives about physician-assisted suicide.
ContributorsMoeur, Katherine Elizabeth (Author) / Brian, Jennifer (Thesis director) / Graff, Sarah (Committee member) / Stevenson, Christine (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
This study investigates how the patient-provider relationship between lesbian, gay, and bisexual women and their healthcare providers influences their access to, utilization of, and experiences within healthcare environments. Nineteen participants, ages 18 to 34, were recruited using convenience and snowball sampling. Interviews were conducted inquiring about their health history and

This study investigates how the patient-provider relationship between lesbian, gay, and bisexual women and their healthcare providers influences their access to, utilization of, and experiences within healthcare environments. Nineteen participants, ages 18 to 34, were recruited using convenience and snowball sampling. Interviews were conducted inquiring about their health history and their experiences within the healthcare system in the context of their sexual orientation. The data collected from these interviews was used to create an analysis of the healthcare experiences of those who identify as queer. Although the original intention of the project was to chronicle the experiences of LGB women specifically, there were four non-binary gender respondents who contributed interviews. In an effort to not privilege any orientation over another, the respondents were collectively referred to as queer, given the inclusive and an encompassing nature of the term. The general conclusion of this study is that respondents most often experienced heterosexism rather than outright homophobia when accessing healthcare. If heterosexism was present within the healthcare setting, it made respondents feel uncomfortable with their providers and less likely to inform them of their sexuality even if it was medically relevant to their health outcomes. Gender, race, and,socioeconomic differences also had an effect on the patient-provider relationship. Non-binary respondents acknowledged the need for inclusion of more gender options outside of male or female on the reporting forms often seen in medical offices. By doing so, medical professionals are acknowledging their awareness and knowledge of people outside of the binary gender system, thus improving the experience of these patients. While race and socioeconomic status were less relevant to the context of this study, it was found that these factors have an affect on the patient-provider relationship. There are many suggestions for providers to improve the experiences of queer patients within the healthcare setting. This includes nonverbal indications of acknowledgement and acceptance, such as signs in the office that indicate it to be a queer friendly space. This will help in eliminating the fear and miscommunication that can often happen when a queer patient sees a practitioner for the first time. In addition, better education on medically relevant topics to queer patients, is necessary in order to eliminate disparities in health outcomes. This is particularly evident in trans health, where specialized education is necessary in order to decrease poor health outcomes in trans patients. Future directions of this study necessitate a closer look on how race and socioeconomic status have an effect on a queer patient's relationship with their provider.
Created2016-05
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Description
Healthcare systems and health insurance are both concepts implemented in every country to provide access to the general population. Countries undergo healthcare reforms in order to increase the performance of the system. In 2010, the Affordable Care Act (ACA) was introduced in the United States to increase coverage and create

Healthcare systems and health insurance are both concepts implemented in every country to provide access to the general population. Countries undergo healthcare reforms in order to increase the performance of the system. In 2010, the Affordable Care Act (ACA) was introduced in the United States to increase coverage and create a more inclusive health insurance market. For comparison, the recent reforms in Chile and Singapore were observed as points to determine what concepts work well and what can be implemented in the U.S. system. Unlike the United States, Chile and Singapore completely altered the system that was previously in use. In Chile, the reforms began in the 1970s and made two more major changes in 1973 and early 2000s. Singapore began its reform in the 1960s and created the medical savings account system that is still in use today. To analyze the system further, the medical professions of neurology, physician assistants and optometry were compared in each country. In regards to neurology, the coverage of services in Chile and Singapore are similar in that select medical procedures are covered. In contrast, the United States offers coverage on a case-by-case basis. For physician assistants, such a profession does not exist in Chile or Singapore. In the United States, the profession is rapidly expanding, and coverage is offered for most services provided. Optometry is a stand-alone profession in both the U.S. and Singapore. The services provided by the optometrists are selectively covered by insurance, depending on whether it is considered a medical problem. Chile covers the services often provided by optometrists, however, the ophthalmologist is the provider, as optometry does not exist. This study concluded that the U.S. should continue to provide a more inclusive healthcare system that includes vision and dental care. The U.S., like Singapore, should also adopt a more integrative system. Under this system, patient care would be provided in a way that professionals specializing in the care are included in every step of the process.
ContributorsLa, Jenny (Co-author) / Feruj, Farihah (Co-author) / Morrison, Sarah (Co-author) / Gaughan, Monica (Thesis director) / Essary, Alison (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
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Description
Introduction: Human papillomavirus (HPV) infection is seen in up to 90% of cases of cervical cancer, the third leading cancer cause of death in women. Current HPV screening focuses on only two HPV types and covers roughly 75% of HPV-associated cervical cancers. A protein based assay to test for antibody

Introduction: Human papillomavirus (HPV) infection is seen in up to 90% of cases of cervical cancer, the third leading cancer cause of death in women. Current HPV screening focuses on only two HPV types and covers roughly 75% of HPV-associated cervical cancers. A protein based assay to test for antibody biomarkers against 98 HPV antigens from both high and low risk types could provide an inexpensive and reliable method to screen for patients at risk of developing invasive cervical cancer. Methods: 98 codon optimized, commercially produced HPV genes were cloned into the pANT7_cGST vector, amplified in a bacterial host, and purified for mammalian expression using in vitro transcription/translation (IVTT) in a luminescence-based RAPID ELISA (RELISA) assay. Monoclonal antibodies were used to determine immune cross-reactivity between phylogenetically similar antigens. Lastly, several protein characteristics were examined to determine if they correlated with protein expression. Results: All genes were successfully moved into the destination vector and 86 of the 98 genes (88%) expressed protein at an adequate level. A difference was noted in expression by gene across HPV types but no correlation was found between protein size, pI, or aliphatic index and expression. Discussion: Further testing is needed to express the remaining 12 HPV genes. Once all genes have been successfully expressed and purified at high concentrations, DNA will be printed on microscope slides to create a protein microarray. This microarray will be used to screen HPV-positive patient sera for antibody biomarkers that may be indicative of cervical cancer and precancerous cervical neoplasias.
ContributorsMeshay, Ian Matthew (Author) / Anderson, Karen (Thesis director) / Magee, Mitch (Committee member) / Katchman, Benjamin (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
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Description
The introduction of novel information technology within contemporary healthcare settings presents a critical juncture for the industry and thus lends itself to the importance of better understanding the impact of this emerging "health 2.0" landscape. Simply, how such technology may affect the healthcare system is still not fully realized, despite

The introduction of novel information technology within contemporary healthcare settings presents a critical juncture for the industry and thus lends itself to the importance of better understanding the impact of this emerging "health 2.0" landscape. Simply, how such technology may affect the healthcare system is still not fully realized, despite the ever-growing need to adopt it in order to serve a growing patient population. Thus, two pertinent questions are posed: is HIT useful and practical and, if so, what is the best way to implement it? This study examined the clinical implementation of specific instances of health information technology (HIT) so as to weigh its benefits and risks to ultimately construct a proposal for successful widespread adoption. Due to the poignancy of information analysis within HIT, Information Measurement Theory (IMT) was used to measure the effectiveness of current HIT systems as well as to elucidate improvements for future implementation. The results indicate that increased transparency, attention to patient-focused approaches and proper IT training will not only allow HIT to better serve the community, but will also decrease inefficient healthcare expenditure.
ContributorsMaietta, Myles Anthony (Author) / Kashiwagi, Dean (Thesis director) / Kashiwagi, Jacob (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / School of Life Sciences (Contributor)
Created2015-05
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Description
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality in the USA and throughout the world. Two phenotypes that promote this deadly outcome are the invasive potential of NSCLC and the emergence of therapeutic resistance in this disease. There is an unmet clinical need to understand the

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality in the USA and throughout the world. Two phenotypes that promote this deadly outcome are the invasive potential of NSCLC and the emergence of therapeutic resistance in this disease. There is an unmet clinical need to understand the mechanisms that govern NSCLC cell invasion and therapeutic resistance, and to target these phenotypes towards abating the dismal five-year survival of NSCLC. The expression of the tumor necrosis factor receptor superfamily, member 12A (TNFRSF12A; Fn14) correlates with poor patient survival and invasiveness in many tumor types including NSCLC. We hypothesize that suppression of Fn14 will inhibit NSCLC cell motility and reduce cell viability. Here we demonstrate that atorvastatin calcium treatment reduces Fn14 expression in NSCLC cell lines. Prior to Fn14 protein suppression, atorvastatin calcium modulated the expression of the Fn14 modulators P-ERK1/2 and P-NF-κβ. Atorvastatin calcium treatment inhibited the migratory capacity in H1975, H2030 and H1993 cells by at least 55%. When chemotactic migration in H2030 cells was induced by the Fn14 ligand TNF-like weak inducer of apoptosis (TWEAK) treatment, atorvastatin calcium successfully negated any stimulatory effects. Inversely, treatment of NSCLC cells with cholesterol resulted in a statistically significant increase in migration. Depletion of Fn14 expression via siRNA suppressed the migratory effect of cholesterol. Finally, atorvastatin calcium treatment sensitized cells to radiation treatment, reducing cell survival. These data suggest that atorvastatin calcium may inhibit NSCLC invasiveness through a mechanism involving Fn14, and may be a novel therapeutic target in NSCLC tumors expressing Fn14.
ContributorsCornes, Victoria Elisabeth (Author) / Stout, Valerie (Thesis director) / Whitsett, Timothy (Committee member) / Carson, Vashti (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
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Description
Despite the 40-year war on cancer, very limited progress has been made in developing a cure for the disease. This failure has prompted the reevaluation of the causes and development of cancer. One resulting model, coined the atavistic model of cancer, posits that cancer is a default phenotype of the

Despite the 40-year war on cancer, very limited progress has been made in developing a cure for the disease. This failure has prompted the reevaluation of the causes and development of cancer. One resulting model, coined the atavistic model of cancer, posits that cancer is a default phenotype of the cells of multicellular organisms which arises when the cell is subjected to an unusual amount of stress. Since this default phenotype is similar across cell types and even organisms, it seems it must be an evolutionarily ancestral phenotype. We take a phylostratigraphical approach, but systematically add species divergence time data to estimate gene ages numerically and use these ages to investigate the ages of genes involved in cancer. We find that ancient disease-recessive cancer genes are significantly enriched for DNA repair and SOS activity, which seems to imply that a core component of cancer development is not the regulation of growth, but the regulation of mutation. Verification of this finding could drastically improve cancer treatment and prevention.
ContributorsOrr, Adam James (Author) / Davies, Paul (Thesis director) / Bussey, Kimberly (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2015-05
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Description
With advances in biotechnology, personalized medicine has become an ever-expanding field. Even with so much growth, the critics equally match the proponents of personalized medicine. The source of their disagreement is rooted in the concept of empowerment. This analysis utilizes the personal genomics company 23andMe and their relationship with the

With advances in biotechnology, personalized medicine has become an ever-expanding field. Even with so much growth, the critics equally match the proponents of personalized medicine. The source of their disagreement is rooted in the concept of empowerment. This analysis utilizes the personal genomics company 23andMe and their relationship with the Federal Food and Drug Administration to illustrate varying views of empowerment. Specifically, the case study focuses on the ability to provide direct-to-consumer health reports to patients independent of physicians. In doing this, larger issues of what is at stake in personalized medicine are uncovered. These include but are not limited to: who determines what individuals get empowered and what information is determined good versus bad.
ContributorsSilverman, Adam Mattern (Author) / Brian, Jennifer (Thesis director) / Hurlbut, Ben (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Department of Psychology (Contributor)
Created2015-05
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Description
Cancer poses a significant burden on the global health system and represents a leading cause of death worldwide. For late-stage cancers, the traditional treatments of chemotherapy, radiation, and surgery are not always viable, and they can pose unnecessary health risks to the patients. New immunotherapies, such as adoptive cell transfer,

Cancer poses a significant burden on the global health system and represents a leading cause of death worldwide. For late-stage cancers, the traditional treatments of chemotherapy, radiation, and surgery are not always viable, and they can pose unnecessary health risks to the patients. New immunotherapies, such as adoptive cell transfer, are being developed and refined to treat such cancers. T cell immunotherapies in particular, where a patient’s T cell lymphocytes are isolated and amplified to be re-infused into the patient or where human cell lines are engineered to express T cell receptors for the recognition of common cancer antigens, are being expanded on because for some cancers, they could be the only option. Constructing an optimal pipeline for cloning and expression of antigen-specific TCRs has significant bearing on the efficacy of engineered cell lines for ACT. Adoptive T cell transfer, while making great strides, has to overcome a diverse T cell repertoire – cloning and expressing antigen-specific TCRs can mediate this understanding. Having identified the high frequency FluM1-specific TCR sequences in stimulated donor PBMCs, it was hypothesized that the antigen-specific TCR could be reconstructed via Gateway cloning methods and tested for expression and functionality. Establishing this pipeline would confirm an ability to properly pair and express the heterodimeric chains. In the context of downstream applications, neoantigens would be used to stimulate T cells, the α and β chains would be paired via single-cell or bulk methods, and instead of Gateway cloning, the CDR3 hypervariable regions α and β chains alone would be co-expressed using Golden Gate assembly methods.
ContributorsHirneise, Gabrielle Rachel (Author) / Anderson, Karen (Thesis director) / Mason, Hugh (Committee member) / Hariadi, Hugh (Committee member) / School of Life Sciences (Contributor, Contributor) / School of Sustainability (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05