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Description
In an effort to begin validating the large number of discovered candidate biomarkers, proteomics is beginning to shift from shotgun proteomic experiments towards targeted proteomic approaches that provide solutions to automation and economic concerns. Such approaches to validate biomarkers necessitate the mass spectrometric analysis of hundreds to thousands of human samples. As this takes place, a serendipitous opportunity has become evident. By the virtue that as one narrows the focus towards "single" protein targets (instead of entire proteomes) using pan-antibody-based enrichment techniques, a discovery science has emerged, so to speak. This is due to the largely unknown context in which "single" proteins exist in blood (i.e. polymorphisms, transcript variants, and posttranslational modifications) and hence, targeted proteomics has applications for established biomarkers. Furthermore, besides protein heterogeneity accounting for interferences with conventional immunometric platforms, it is becoming evident that this formerly hidden dimension of structural information also contains rich-pathobiological information. Consequently, targeted proteomics studies that aim to ascertain a protein's genuine presentation within disease- stratified populations and serve as a stepping-stone within a biomarker translational pipeline are of clinical interest. Roughly 128 million Americans are pre-diabetic, diabetic, and/or have kidney disease and public and private spending for treating these diseases is in the hundreds of billions of dollars. In an effort to create new solutions for the early detection and management of these conditions, described herein is the design, development, and translation of mass spectrometric immunoassays targeted towards diabetes and kidney disease. Population proteomics experiments were performed for the following clinically relevant proteins: insulin, C-peptide, RANTES, and parathyroid hormone. At least thirty-eight protein isoforms were detected. Besides the numerous disease correlations confronted within the disease-stratified cohorts, certain isoforms also appeared to be causally related to the underlying pathophysiology and/or have therapeutic implications. Technical advancements include multiplexed isoform quantification as well a "dual- extraction" methodology for eliminating non-specific proteins while simultaneously validating isoforms. Industrial efforts towards widespread clinical adoption are also described. Consequently, this work lays a foundation for the translation of mass spectrometric immunoassays into the clinical arena and simultaneously presents the most recent advancements concerning the mass spectrometric immunoassay approach.
ContributorsOran, Paul (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Ros, Alexandra (Committee member) / Williams, Peter (Committee member) / Arizona State University (Publisher)
Created2011
Description
Signal processing techniques have been used extensively in many engineering problems and in recent years its application has extended to non-traditional research fields such as biological systems. Many of these applications require extraction of a signal or parameter of interest from degraded measurements. One such application is mass spectrometry immunoassay (MSIA) which has been one of the primary methods of biomarker discovery techniques. MSIA analyzes protein molecules as potential biomarkers using time of flight mass spectrometry (TOF-MS). Peak detection in TOF-MS is important for biomarker analysis and many other MS related application. Though many peak detection algorithms exist, most of them are based on heuristics models. One of the ways of detecting signal peaks is by deploying stochastic models of the signal and noise observations. Likelihood ratio test (LRT) detector, based on the Neyman-Pearson (NP) lemma, is an uniformly most powerful test to decision making in the form of a hypothesis test. The primary goal of this dissertation is to develop signal and noise models for the electrospray ionization (ESI) TOF-MS data. A new method is proposed for developing the signal model by employing first principles calculations based on device physics and molecular properties. The noise model is developed by analyzing MS data from careful experiments in the ESI mass spectrometer. A non-flat baseline in MS data is common. The reasons behind the formation of this baseline has not been fully comprehended. A new signal model explaining the presence of baseline is proposed, though detailed experiments are needed to further substantiate the model assumptions. Signal detection schemes based on these signal and noise models are proposed. A maximum likelihood (ML) method is introduced for estimating the signal peak amplitudes. The performance of the detection methods and ML estimation are evaluated with Monte Carlo simulation which shows promising results. An application of these methods is proposed for fractional abundance calculation for biomarker analysis, which is mathematically robust and fundamentally different than the current algorithms. Biomarker panels for type 2 diabetes and cardiovascular disease are analyzed using existing MS analysis algorithms. Finally, a support vector machine based multi-classification algorithm is developed for evaluating the biomarkers' effectiveness in discriminating type 2 diabetes and cardiovascular diseases and is shown to perform better than a linear discriminant analysis based classifier.
ContributorsBuddi, Sai (Author) / Taylor, Thomas (Thesis advisor) / Cochran, Douglas (Thesis advisor) / Nelson, Randall (Committee member) / Duman, Tolga (Committee member) / Arizona State University (Publisher)
Created2012
Description
Cancer claims hundreds of thousands of lives every year in US alone. Finding ways for early detection of cancer onset is crucial for better management and treatment of cancer. Thus, biomarkers especially protein biomarkers, being the functional units which reflect dynamic physiological changes, need to be discovered. Though important, there are only a few approved protein cancer biomarkers till date. To accelerate this process, fast, comprehensive and affordable assays are required which can be applied to large population studies. For this, these assays should be able to comprehensively characterize and explore the molecular diversity of nominally "single" proteins across populations. This information is usually unavailable with commonly used immunoassays such as ELISA (enzyme linked immunosorbent assay) which either ignore protein microheterogeneity, or are confounded by it. To this end, mass spectrometric immuno assays (MSIA) for three different human plasma proteins have been developed. These proteins viz. IGF-1, hemopexin and tetranectin have been found in reported literature to show correlations with many diseases along with several carcinomas. Developed assays were used to extract entire proteins from plasma samples and subsequently analyzed on mass spectrometric platforms. Matrix assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) mass spectrometric techniques where used due to their availability and suitability for the analysis. This resulted in visibility of different structural forms of these proteins showing their structural micro-heterogeneity which is invisible to commonly used immunoassays. These assays are fast, comprehensive and can be applied in large sample studies to analyze proteins for biomarker discovery.
ContributorsRai, Samita (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Borges, Chad (Committee member) / Ros, Alexandra (Committee member) / Arizona State University (Publisher)
Created2012
Description
I conducted a qualitative, comparative study on the nursing education systems in the United Kingdom and the United States, focusing on two universities—Arizona State University in Phoenix, Arizona and Leeds Beckett University in Leeds, England. The goals of my thesis included comparing the educational, economic, and cultural aspects of the countries and how those aspects impact nursing students on both sides of the pond. The educational and economic aspects were compared by utilizing existing literature and open data sources such as the university websites and publications from comparative education journals, while the cultural differences were evaluated by conducting short, one-on-one interviews with students enrolled in the Adult Health courses at both universities. The findings from the interviews were transcribed and coded, and findings from the sites were compared. While there is an extensive amount of research published regarding comparative education, there has not been much published comparing these developed countries. While there is a significant difference in the structure and cost of the nursing programs, there are more similarities than differences in culture between nursing students interviewed in the US and those interviewed in the UK.
ContributorsTahiliani, Shreja (Author) / Hagler, Debra (Thesis director) / Allen, Angela (Committee member) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The goal of this creative project is to explain the different roles of advanced practice nursing as well as the role of a registered nurse. Advanced practice nursing roles include Certified Nurse Practitioner, Certified Registered Nurse Anesthetist, Certified Clinical Nurse Specialist, and Certified Nurse Midwife. The role of the registered nurse is included in this website because this role is the foundation for becoming an advanced practice nurse and is an equally important role. The target audience for the website is potential nursing students, current nursing students, and licensed nurses who desire to advance their career and are looking for more information about each role. This comprehensive website includes the scope of practice, salary, educational programs, and an interview with a nurse in each role. The description of each advanced practice role includes audio and visual aids to appeal to different types of learners. In depth education regarding advanced practice nursing roles will make current and future nurses more aware of the endless possibilities of a career in nursing. Nurses provide education to patients every day, but there is rarely adequate education provided to nurses regarding their profession or professional advancement opportunities. Nursing is a patient-focused career and sometimes nurses forget to focus on their own personal growth while caring for others. This one-stop website promotes nurse to nurse education by thoroughly explaining each advanced practice role. All of the information in this website is publically available through the internet and this website is meant solely for educational purposes.
ContributorsThompson, Rachel (Co-author) / Banchik, Jennifer (Co-author) / Peterson, Katherine (Thesis director) / Kriz, Lindsey (Committee member) / Spahr, Nancy (Committee member) / School of Community Resources and Development (Contributor) / School of Social Transformation (Contributor) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
Colorectal cancer (CRC) is the third most prevalent form of cancer in both genders and second highest cause of cancer-related death in the United States. Despite the availability of preventative CRC screening, Latinos as a group are of particular concern for CRC as they tend to have a lower screening rate, contributing to the possibility of late-stage diagnosis or even death. However, little is known about the perceptions of CRC screening and factors which contribute to beliefs about CRC in Latinos. Most studies are quantitative and rarely include a qualitative approach focusing on cultural aspects and communication with physicians. The purpose of this study was to explore participants' perceived facilitators and barriers to CRC screening, as well as perspectives on physician recommendation and fatalism, using a qualitative approach. A convenience and snowball sampling were used to collect the data. Eight English-speaking Latino individuals (M age=56 years; 75% female) in the Phoenix, Arizona area were invited to 60-90 minute in-depth interviews on perceptions of the colorectal cancer screening process. Ten major themes emerged from the interviews: (1) lacking awareness and knowledge of CRC screening, (2) attitude toward CRC and screening, (3) availability of preventive care, (4) physician trust, (5) fear, (6) desire for increased information, (7) personal learning, (8) lifestyle factors, (9) cultural impact, and (10) willingness to change lifestyle. Results indicated varying levels of perceived knowledge of colorectal cancer, little perceived risk of diagnosis, desire for more information, and a high level of physician trust. Implications for nursing included increased need for CRC screening educational resources, as well as further investigation of the influence of fatalistic belief in CRC screening compliance for the Latino population.
ContributorsMagdaleno, Claire Rose (Author) / Kim, Sunny (Thesis director) / McNulty, Julie (Committee member) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
This past summer, I met a young lady named Ashley (name has been changed) who has been diagnosed with chronic Lyme disease. Upon researching this condition in greater detail, I learned that many medical providers who base their practice on the best evidence do not support treating patients for a chronic Lyme infection, the existence of which has not been substantially supported with research. I inquired about the process that led her to seek treatment for chronic Lyme disease at Jemsek Specialty Clinic. I learned that after many inaccurate diagnoses and years of unhelpful treatments, Ashley finally rejected the help offered by traditional medical doctors because she felt they were uncaring and inattentive, and went somewhere she felt heard. What she deserved, however, was both care that was based in scientific research and care that felt compassionate, as has been promoted by the nursing field. Despite the lack of a confirmed medical diagnosis, Ashley's day to day symptoms and struggles could be addressed with nursing care. I then constructed a nursing care plan to be implemented by Ashley's family and friends to help her feel her best and live a fulfilling life despite chronic disease. Patients should not have to choose between a healthcare provider who utilizes the strongest scientific evidence and one they feel understands them, though many do. Nursing can unite these mindsets by alleviating the daily challenges patients face. Please see the website http://careplanforashley.blogspot.com
ContributorsKnochel, Amanda Marie (Author) / Panchmatia, Bella (Thesis director) / Mishark, Kenneth (Committee member) / Barrett, The Honors College (Contributor) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor)
Created2014-05
Description
The purpose of this study was to determine whether a peer nursing student who presents a longitudinal case study on warfarin in a pharmacology course classroom influences prelicensure and postbaccalaureate nursing students' knowledge and perceived knowledge about warfarin. The study was a descriptive design that used a convenience sample of baccalaureate nursing students enrolled in two pharmacology courses. All participating students answered warfarin case-study questions and completed a self-demographic questionnaire, a knowledge pretest and posttest, and a self-efficacy questionnaire after the activity, which evaluated students' knowledge and perceived knowledge on 11 warfarin concepts. For all students (N = 89), the number of correct answers improved significantly between pretests and posttests for Items 2-11 (p < .0001; Wilcoxon signed-rank tests), which evaluated students' knowledge on warfarin's site of action, associated laboratory values, use of vitamin K, and food-drug interactions. However, no significant difference was seen in the number of correct answers for warfarin's mechanism of action. Comparing prelicensure and postbaccalaureate groups by Mann-Whitney tests, no significant difference was seen for pretest total scores (median 7.00, n = 55; median 7.50, n = 34; respectively; p = .399). Similarly, no difference was seen for posttest total scores by groups (prelicensure: median = 9.00, n =54; postbaccalaureate: median = 10.00, n = 32; p = .344). Overall, students in both groups agreed that they could identify and explain all 11 warfarin concepts. The Pearson correlation between the total posttest and total self-efficacy scores for the combined group was .338 (p = .003), demonstrating a low but significant correlation between students' posttest total scores and their perceived warfarin knowledge, as evaluated by the self-efficacy questionnaire.
ContributorsLam, Wing Tung (Author) / Vana, Kimberly (Thesis director) / Holcomb, Cynthia (Committee member) / Silva, Graciela (Committee member) / Barrett, The Honors College (Contributor) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / W. P. Carey School of Business (Contributor)
Created2014-12
Description
The S.T.O.M.P. (Supporting Teen Outcomes Mentorship Program) program has been developed to provide assistance for the adolescent parenting dynamic. The purpose of S.T.O.M.P. is to serve as an additional aid to support a number of adolescent mothers participating in a group-based support program at Chandler Regional Medical Center, but to initiate core values, skills, and social networks for the young mothers. A collection of current literature in support of one-on-one mentorship programs, comprehensive needs as identified by the adolescent pregnant population, personal experience and findings, as well as collaborative discussions amongst health educators has supported the identification of the core objectives of this creative project; the development of a one-on-one mentorship program.
ContributorsThompson, Sarah Lynn (Author) / Jasper, Marcia (Thesis director) / Murphy, Ana Orrantia (Committee member) / Barrett, The Honors College (Contributor) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor)
Created2014-05
Description
Patients receive electroconvulsive therapy every day in the United States but negative media representations of the therapy put doubts in the minds of potential patients as to whether or not they should go through with the therapy or not. The purpose of this study was to explore how health care providers perceive the influence of media on patient decision-making regarding whether or not to receive electroconvulsive therapy (ECT) and how they might address the perceived effects of said media. A total of 16 articles were analyzed in a literature review regarding the media's portrayal of ECT and/or how it affected patients and one interview with a physician was conducted. It was found that while the current literature still largely focuses on the negative media and its implications on patient decision-making, the physician had a more positive viewpoint. As a whole, the literature and physician agreed that media played a role in patients' decisions, but the media's portrayal of the therapy was not seen as negatively by the physician.
ContributorsIssar, Stephanie Marie (Author) / Pickens, Judith (Thesis director) / Sayles, Judy (Committee member) / Fargotstein, Barbara (Committee member) / Barrett, The Honors College (Contributor) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / Department of Psychology (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2013-05