Matching Items (135)
Description
The purpose of this thesis creative project was to create an educational video to present research findings on the increasingly important issue of human biospecimen preanalytic variables. When a human biospecimen, such as blood, urine, or tissue, is removed from the body, it is subjected to a plethora of variables that are not recorded or regulated in a vast majority of cases. Frequently, these samples arrive at the research or pathology lab with an unknown history, then undergo analysis for translational research purposes, or to guide clinical management decisions. Thus, compromised specimen quality caused by preanalytic variables has substantial, and potentially devastating, downstream effects. To identify the preanalytic variables with the greatest impact on blood and tissue specimen quality, 45 articles were gathered using PubMed and Google Scholar databases and cited. Based on the articles, the top five variables with the most detrimental effects were identified for both blood and tissue samples. Multiple sets of parameters ensuring specimen fitness were compared for each of the five variables for each specimen type. Then, specific parameters guaranteeing the fitness of the greatest number of analytes were verified. To present the research findings in greater detail, a paper was written that focused on identifying the top variables and key parameters to ensure analyte fitness. To present the overall issue in an easy-to-digest format, a storyboard and script were created as a guideline for a final video project. Ultimately, two alternate versions of the video were created to pertain to the audience of choice (one version for patients, one version for professionals). It is the hope that these videos will be used as educational tools to continue efforts to standardize and enforce human biospecimen preanalytic variable parameters. This is a necessary step to improve the accuracy of our biomedical research data and the healthcare of patients worldwide.
ContributorsAzcarate, Heather (Author) / Compton, Carolyn (Thesis director) / LaBaer, Joshua (Committee member) / Borges, Chad (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2018-12
Description
More than 40% of all U.S. opioid overdose deaths in 2016 involved a prescription opioid, with more than 46 people dying every day from overdoses involving prescription opioids, (CDC, 2017). Over the years, lawmakers have implemented policies and laws to address the opioid epidemic, and many of these vary from state to state. This study will lay out the basic guidelines of common pieces of legislation. It also examines relationships between 6 state-specific prescribing or preventative laws and associated changes in opioid-related deaths using a longitudinal cross-state study design (2007-2015). Specifically, it uses a linear regression to examine changes in state-specific rates of opioid-related deaths after implementation of specific policies, and whether states implementing these policies saw smaller increases than states without these policies. Initial key findings of this study show that three policies have a statistically significant association with opioid related overdose deaths are—Good Samaritan Laws, Standing Order Laws, and Naloxone Liability Laws. Paradoxically, all three policies correlated with an increase in opioid overdose deaths between 2007 and 2016. However, after correcting for the potential spurious relationship between state-specific timing of policy implementation and death rates, two policies have a statistically significant association (alpha <0.05) with opioid overdose death rates. First, the Naloxone Liability Laws were significantly associated with changes in opioid-related deaths and was correlated with a 0.33 log increase in opioid overdose death rates, or a 29% increase. This equates to about 1.39 more deaths per year per 100,000 people. Second, the legislation that allows for 3rd Party Naloxone prescriptions correlated with a 0.33 log decrease in opioid overdose death rates, or a 29% decrease. This equates to 1.39 fewer deaths per year per 100,000 people.
ContributorsDavis, Joshua Alan (Author) / Hruschka, Daniel (Thesis director) / Gaughan, Monica (Committee member) / School of Human Evolution & Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
In the development of personalized medicine and many other clinical studies, biospecimen integrity serves as the prerequisite for not only the accurate derivation of patient- and disease-specific molecular data from biological specimens but the meaningful downstream validation of biomarkers. However, a large number of preanalytical variables may influence the quality of biospecimens in an undesired way and ultimately render the samples unsuitable for molecular analysis. The limited ability to directly reduce discrepancies caused by preanalytical variables gives rise to the need for development and retrospective application of appropriate tests for assessment of biospecimen integrity. Nevertheless, the most standard approaches to assessing biospecimen integrity involve nontrivial procedures. Thus, the need for quality control tools or tests that are readily applicable and can produce results in a straightforward way becomes critical. As one of the major ex vivo biomolecular degradation mechanisms, oxidation that occurs when blood plasma and serum samples are exposed to thawed states during storage and processing is hard to forestall and detect. In an attempt to easily detect and monitor the degree of oxidation, the technique of Fluorescence Resonance Energy Transfer (FRET) was examined to determine whether this concept could be employed to monitor exposure of samples to thawed conditions when controlled by spontaneous oxidative disulfide bonding. The intended mode of usage was envisioned as a fluorescence liquid being stored in a separate compartment but within the same test tube as archived plasma and serum samples. This would allow the assessment of sample integrity by direct visualization of fluorescence under a hand-held black light. The fluorescent dynamic range as well as kinetic control of the reaction were studied. While the addition of Cu(II) proved to facilitate excellent dynamic range with regard to fluorescence quenching, the kinetics of the reaction were too rapid for practical use. Further investigation revealed that the fluorescence quenching mechanism might have actually occurred via Intramolecular Charge Transfer (ICT) rather than FRET mediated by oxidative disulfide bond formation. Introduction of Cu(II) via copper metal slowed fluorescence quenching to the point of practical utility; facilitating demonstration that storing at room temperature, refrigerating or freezing the samples delayed fluorescence quenching to different extents. To establish better kinetic control, future works will focus on establishing controlled, thoroughly understood kinetic release of Cu(II) from copper metal.
ContributorsZhang, Zihan (Author) / Borges, Chad (Thesis director) / Emady, Heather (Committee member) / Williams, Peter (Committee member) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
In an increasingly interconnected world, the 17 Sustainable Development Goals are the United Nations’ framework for ensuring we continue to transform our world for the better, leaving no population behind. This study examines how the terminology of Sustainable Development Goal 17 for global partnership affects its implementation, focusing on “building capacity”—a widely referenced target in the development arena—and the involvement of the private sector. Key informant interviews with experts in the fields of conflict of interest, ethics, and development revealed a wide variety of (often conflicting) notions about partnership, frameworks for capacity development, and the interactions between public and private actors. A literature review of key policy documents examined the terminology and implementation of multistakeholder partnerships, and analysis offered considerations for risks and suggestions in policy terminology. Results indicate a need for increased attention to the use of partnership terminology as a catch-all term to encompass development work, and makes several recommendations for changes to combat misuse of the partnership label. Finally, this study acknowledges that there is a continued need for research-based evidence for effectiveness of the partnership-based development approach.
ContributorsThomson, Azalea Mae (Author) / Gaughan, Monica (Thesis director) / Hruschka, Daniel (Committee member) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The development of safe and effective vaccines has been one of the greatest public achievements of the 20th century. However, there is still considerable public debate about the relative health costs and benefits of vaccines, and the information and misinformation spread through these debates can have a direct impact on vaccination and whether or not herd immunity will continue in the United States for different diseases. To understand perceptions of vaccine risks and effectiveness among young adults in the U.S., this study describes Arizona State University students' perceptions of the harms and benefits of vaccines. A preliminary free list (n=30) identified what vaccines ASU college students were most likely to recall spontaneously. The six vaccines most commonly mentioned by ASU students were: influenza (flu), chickenpox, HPV, polio, MMR, and smallpox. Using these top six vaccines, we then developed a second survey about the knowledge and perceptions of each of these vaccines and vaccines as a whole. We found that students generally perceived vaccines as safe and important to their health, but they maintained an overall lack of understanding of how vaccines work and what they protect against. While this study is only a preliminary investigation into the perceptions of ASU college students on six commonly mentioned vaccines, this could lead to investigations on how to educate and promote the usage of vaccines to college students.
ContributorsGilson, Jacob (Co-author) / Sutton, Carly (Co-author) / Hruschka, Daniel (Thesis director) / Ruth, Alissa (Committee member) / W. P. Carey School of Business (Contributor) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
Biomarkers are the cornerstone of modern-day medicine. They are defined as any biological substance in or outside the body that gives insight to the body's condition. Doctors and researchers can measure specific biomarkers to diagnose and treat patients, such as the concentration of hemoglobin Alc and its connection to diabetes. There are a variety of methods, or assays, to detect biomarkers, but the most common assay is enzyme-linked immunosorbent assay (ELISA). A new-generation assay termed mass spectrometric immunoassay (MSIA) can measure proteoforms, the different chemical variations of proteins, and their relative abundance. ELISA on the other hand measures the overall concentration of protein in the sample. Measuring each of the proteoforms of a protein is important because only one or two variations could be biologically significant and/or cause diseases. However, running MSIA is expensive. For this reason, an alternative plate-based MSIA technique was tested for its ability to detect the proteoforms of a protein called apolipoprotein C-III (ApoC-III). This technique combines the protein capturing procedure of ELISA to isolate the protein with detection in a mass spectrometer. A larger amount of ApoC-III present in the body indicates a considerable risk for coronary heart disease. The precision of the assay is determined on the coefficient of variation (CV). A CV value is the ratio of standard deviation in relation to the mean, represented as a percentage. The smaller the percentage, the less variation the assay has, and therefore the more ability it has to detect subtle changes in the biomarker. An accepted CV would be less than 10% for single-day tests (intra-day) and less than 15% for multi-day tests (inter-day). The plate-based MSIA was started by first coating a 96-well round bottom plate with 2.5 micrograms of ApoC-III antibody. Next, a series of steps were conducted: a buffer wash, then the sample incubation, followed by another buffer wash and two consecutive water washes. After the final wash, the wells were filled with a MALDI matrix, then spotted onto a gold plate to dry. The dry gold target was then placed into a MALDI-TOF mass spectrometer to produce mass spectra for each spot. The mass spectra were calibrated and the area underneath each of the four peaks representing the ApoC-III proteoforms was exported as an Excel file. The intra-day CV values were found by dividing the standard deviation by the average relative abundance of each peak. After repeating the same procedure for three more days, the inter-day CVs were found using the same method. After completing the experiment, the CV values were all within the acceptable guidelines. Therefore, the plate-based MSIA is a viable alternative for finding proteoforms than the more expensive MSIA tips. To further validate this, additional tests will need to be conducted with different proteins and number of samples to determine assay flexibility.
ContributorsTieu, Luc (Author) / Borges, Chad (Thesis director) / Nedelkov, Dobrin (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
Brown adipose tissue (BAT) is thought to be important in combating obesity as it can expend energy in the form of heat, e.g. thermogenesis. The goal of this study was to study the effect of injected norepinephrine (NE) on the activation of BAT in rats that were fed a high fat diet (HFD). A dose of 0.25 mg/kg NE was used to elicit a temperature response that was measured using transponders inserted subcutaneously over the BAT and lower back and intraperitoneally to measure the core temperature. The results found that the thermic effect of the BAT increased after the transition from low fat diet to a high fat diet (LFD) yet, after prolonged exposure to the HFD, the effects resembled levels found with the LFD. This suggests that while a HFD may stimulate the effect of BAT, long term exposure may have adverse effects on BAT activity. This may be due to internal factors that will need to be examined further.
ContributorsSion, Paul William (Author) / Herman, Richard (Thesis director) / Borges, Chad (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
A major recurring issue with aid-providing nonprofit organizations is the lack of accountability to recipients. In many cases, there are not clear-cut ways of measuring the efficiency or effectiveness of aid or to determine when and how the aid is failing to meet the needs of recipients. This study focused on one particular non-governmental organization, Project C.U.R.E., that provides medical aid to developing countries in the form of devices and equipment. It investigated the causes of misalignments observed in Project C.U.R.E.'s medical aid process, specifically with three loads that were shipped to the Ahwiaa, Akoti, Bassengele, Chirano, Humjibre, Ntrentrenso, Paboase, and Wenchi clinics as well as the Bibiani hospital in Ghana between June 2015 and May 2016. The medical aid donation process was observed at the each of its steps. Data was collected through interviews with Project C.U.R.E. employees and associates, and was organized and analyzed using Lean Six Sigma tools in order to find areas where the process broke down or failed. These tools included process mapping, root cause analysis through the use of Pareto charts and process failure mode and effects analysis (PFMEA). Once all of the issues from the shipment were categorized, it was found that the three most common types of issues were the preparation of the device being unclear or being unloaded incorrectly, power issues, and misalignment in terms training, needs, and infrastructure. The PFMEAs identified high-priority issues with missing fields in the Needs Assessment Booklet in the needs assessment step, misaligned products in terms of power availability in the planning step, and a lack of standardization in the warehouse operations step. 50 unique solutions were brainstormed in order to address these issues, as well as others. This means that Lean Six Sigma tools such as Pareto charts and PFMEA can be used to identify problems, identify causes and effects of problems, and help to produce solutions to the identified problems. In the future, more in-depth research into Project C.U.R.E.'s impact evaluation process could be pursued.
ContributorsFisk, Nicole Diane (Author) / Hruschka, Daniel (Thesis director) / Walters, Danielle (Committee member) / School of Human Evolution and Social Change (Contributor) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Almost every form of cancer deregulates the expression and activity of anabolic glycosyltransferase (GT) enzymes, which incorporate particular monosaccharides in a donor acceptor as well as linkage- and anomer-specific manner to assemble complex and diverse glycans that significantly affect numerous cellular events, including tumorigenesis and metastasis. Because glycosylation is not template-driven, GT deregulation yields heterogeneous arrays of aberrant intact glycan products, some in undetectable quantities in clinical bio-fluids (e.g., blood plasma). Numerous glycan features (e.g., 6 sialylation, β-1,6-branching, and core fucosylation) stem from approximately 25 glycan “nodes:” unique linkage specific monosaccharides at particular glycan branch points that collectively confer distinguishing features upon glycan products. For each node, changes in normalized abundance (Figure 1) may serve as nearly 1:1 surrogate measure of activity for culpable GTs and may correlate with particular stages of carcinogenesis. Complementary to traditional top down glycomics, the novel bottom-up technique applied herein condenses each glycan node and feature into a single analytical signal, quantified by two GC-MS instruments: GCT (time-of-flight analyzer) and GCMSD (transmission quadrupole analyzers). Bottom-up analysis of stage 3 and 4 breast cancer cases revealed better overall precision for GCMSD yet comparable clinical performance of both GC MS instruments and identified two downregulated glycan nodes as excellent breast cancer biomarker candidates: t-Gal and 4,6-GlcNAc (ROC AUC ≈ 0.80, p < 0.05). Resulting from the activity of multiple GTs, t-Gal had the highest ROC AUC (0.88) and lowest ROC p‑value (0.001) among all analyzed nodes. Representing core-fucosylation, glycan node 4,6-GlcNAc is a nearly 1:1 molecular surrogate for the activity of α-(1,6)-fucosyltransferase—a potential target for cancer therapy. To validate these results, future projects can analyze larger sample sets, find correlations between breast cancer stage and changes in t-Gal and 4,6-GlcNAc levels, gauge the specificity of these nodes for breast cancer and their potential role in other cancer types, and develop clinical tests for reliable breast cancer diagnosis and treatment monitoring based on t-Gal and 4,6-GlcNAc.
ContributorsZaare, Sahba (Author) / Borges, Chad (Thesis director) / LaBaer, Joshua (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Aberrant glycosylation has been shown to be linked to specific cancers, and using this idea, it was proposed that the levels of glycans in the blood could predict stage I adenocarcinoma. To track this glycosylation, glycan were broken down into glycan nodes via methylation analysis. This analysis utilized information from N-, O-, and lipid linked glycans detected from gas chromatography-mass spectrometry. The resulting glycan node-ratios represent the initial quantitative data that were used in this experiment.
For this experiment, two Sets of 50 µl blood plasma samples were provided by NYU Medical School. These samples were then analyzed by Dr. Borges’s lab so that they contained normalized biomarker levels from patients with stage 1 adenocarcinoma and control patients with matched age, smoking status, and gender were examined. An ROC curve was constructed under individual and paired conditions and AUC calculated in Wolfram Mathematica 10.2. Methods such as increasing size of training set, using hard vs. soft margins, and processing biomarkers together and individually were used in order to increase the AUC. Using a soft margin for this particular data set was proved to be most useful compared to the initial set hard margin, raising the AUC from 0.6013 to 0.6585. In regards to which biomarkers yielded the better value, 6-Glc/6-Man and 3,6-Gal glycan node ratios had the best with 0.7687 AUC and a sensitivity of .7684 and specificity of .6051. While this is not enough accuracy to become a primary diagnostic tool for diagnosing stage I adenocarcinoma, the methods examined in the paper should be evaluated further. . By comparison, the current clinical standard blood test for prostate cancer that has an AUC of only 0.67.
For this experiment, two Sets of 50 µl blood plasma samples were provided by NYU Medical School. These samples were then analyzed by Dr. Borges’s lab so that they contained normalized biomarker levels from patients with stage 1 adenocarcinoma and control patients with matched age, smoking status, and gender were examined. An ROC curve was constructed under individual and paired conditions and AUC calculated in Wolfram Mathematica 10.2. Methods such as increasing size of training set, using hard vs. soft margins, and processing biomarkers together and individually were used in order to increase the AUC. Using a soft margin for this particular data set was proved to be most useful compared to the initial set hard margin, raising the AUC from 0.6013 to 0.6585. In regards to which biomarkers yielded the better value, 6-Glc/6-Man and 3,6-Gal glycan node ratios had the best with 0.7687 AUC and a sensitivity of .7684 and specificity of .6051. While this is not enough accuracy to become a primary diagnostic tool for diagnosing stage I adenocarcinoma, the methods examined in the paper should be evaluated further. . By comparison, the current clinical standard blood test for prostate cancer that has an AUC of only 0.67.
ContributorsDe Jesus, Celine Spicer (Author) / Taylor, Thomas (Thesis director) / Borges, Chad (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05