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- Creators: Jehn, Megan
- Creators: Legutki, Bart
- Creators: W. P. Carey School of Business
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
Description
Memory CD8+ T-cells can persist in the absence of antigen, primed for immediate activation and proliferation if later exposed to the same antigen. These cytotoxic lymphocytes provide long-term immunity following an acute infection. Studies have observed that intermediate levels of general T cell transfer prior to infection may cause an inappropriate response resulting in increased pathology rather than prevention. Therefore, our study focused on a memory CD8 T-cell therapy using lymphocytic choriomeningitis virus (LCMV) specific splenocytes, which activate and proliferate at an accelerated pace compared to that of naive T-cells. LCMV is a natural murine pathogen which also poses a zoonotic infection threat to humans, and the effect of immune cell vaccination therapies for LCMV is not fully understood. We observed the effect of multiple memory CD8 T cell dosage levels on overall disease and memory CD8 T-cell response to the virus. Infection by exposure to a carrier was shown to have a reduced impact on mice receiving higher doses of memory T cells prior to infection compared to mice receiving less or no memory cells. Higher presence of activated memory cells were shown to correlate with less disease-related weight loss and accelerated recovery times. Survival rate after exposure to carriers was not shown to be affected by dosage level, warranting further research regarding the prevalence of the immunopathology observed in other studies in natural murine transmission models.
ContributorsMiller, Charles (Author) / Blattman, Joseph (Thesis director) / Holechek, Susan (Committee member) / Carmen, Joshua (Committee member) / W. P. Carey School of Business (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Tools that accurately assess physical activity and sedentary behaviors have broad implications relative to understanding the association of adverse health outcomes and these behaviors. Given the ease of distribution and inexpensive nature of self-report tools, they are the most widely used means to assess human behavior in large-scale populations. The purpose of this study was to validate the ACT24 online self-report recall for measures of sedentary and active behavior against criterion measure. Participants of a larger study were asked to complete the ACT24 recall on a random day in three different weeks during which they were wearing the criterion device. A total of 16 recalls were completed that were used to assess ACT24 measures of sedentary, active, and MVPA behavior. Four different comparisons afforded this analysis: criterion sitting time to ACT24 sedentary time, criterion standing time to ACT24 active behavior, criterion stepping time to ACT24 active behavior, and criterion stepping of 3.0+METs to ACT24 MVPA. Results for the comparisons made between ACT24 sedentary time versus criterion sitting time and ACT24 active time to criterion active time showed little systematic differences at the group level, but the limits of agreement were relatively wide. The comparisons made between ACT24 active time to criterion stepping time and ACT24 MVPA to criterion stepping time at 3.0+ METs both showed a positive systematic difference. Increased incidence of physical activity was correlated with more difference between the measures, likely due to an underestimation of criterion active time measurement. These results are important in the preliminary validity analysis of ACT24 measures of active and sedentary time. Future directions include implementing validation protocols in larger and more diverse samples.
ContributorsBrinkman, Joseph Connor (Author) / Buman, Matthew P. (Thesis director) / Hekler, Eric (Committee member) / Matthews, Charles E. (Committee member) / Barrett, The Honors College (Contributor) / W. P. Carey School of Business (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Background: While research has quantified the mortality burden of the 1957 H2N2 influenza pandemic in the United States, little is known about how the virus spread locally in Arizona, an area where the dry climate was promoted as reducing respiratory illness transmission yet tuberculosis prevalence was high.
Methods: Using archival death certificates from 1954 to 1961, this study quantified the age-specific seasonal patterns, excess-mortality rates, and transmissibility patterns of the 1957 pandemic in Maricopa County, Arizona. By applying cyclical Serfling linear regression models to weekly mortality rates, the excess-mortality rates due to respiratory and all-causes were estimated for each age group during the pandemic period. The reproduction number was quantified from weekly data using a simple growth rate method and generation intervals of 3 and 4 days. Local newspaper articles from The Arizona Republic were analyzed from 1957-1958.
Results: Excess-mortality rates varied between waves, age groups, and causes of death, but overall remained low. From October 1959-June 1960, the most severe wave of the pandemic, the absolute excess-mortality rate based on respiratory deaths per 10,000 population was 17.85 in the elderly (≥65 years). All other age groups had extremely low excess-mortality and the typical U-shaped age-pattern was absent. However, relative risk was greatest (3.61) among children and young adolescents (5-14 years) from October 1957-March 1958, based on incidence rates of respiratory deaths. Transmissibility was greatest during the same 1957-1958 period, when the mean reproduction number was 1.08-1.11, assuming 3 or 4 day generation intervals and exponential or fixed distributions.
Conclusions: Maricopa County largely avoided pandemic influenza from 1957-1961. Understanding this historical pandemic and the absence of high excess-mortality rates and transmissibility in Maricopa County may help public health officials prepare for and mitigate future outbreaks of influenza.
Methods: Using archival death certificates from 1954 to 1961, this study quantified the age-specific seasonal patterns, excess-mortality rates, and transmissibility patterns of the 1957 pandemic in Maricopa County, Arizona. By applying cyclical Serfling linear regression models to weekly mortality rates, the excess-mortality rates due to respiratory and all-causes were estimated for each age group during the pandemic period. The reproduction number was quantified from weekly data using a simple growth rate method and generation intervals of 3 and 4 days. Local newspaper articles from The Arizona Republic were analyzed from 1957-1958.
Results: Excess-mortality rates varied between waves, age groups, and causes of death, but overall remained low. From October 1959-June 1960, the most severe wave of the pandemic, the absolute excess-mortality rate based on respiratory deaths per 10,000 population was 17.85 in the elderly (≥65 years). All other age groups had extremely low excess-mortality and the typical U-shaped age-pattern was absent. However, relative risk was greatest (3.61) among children and young adolescents (5-14 years) from October 1957-March 1958, based on incidence rates of respiratory deaths. Transmissibility was greatest during the same 1957-1958 period, when the mean reproduction number was 1.08-1.11, assuming 3 or 4 day generation intervals and exponential or fixed distributions.
Conclusions: Maricopa County largely avoided pandemic influenza from 1957-1961. Understanding this historical pandemic and the absence of high excess-mortality rates and transmissibility in Maricopa County may help public health officials prepare for and mitigate future outbreaks of influenza.
ContributorsCobos, April J (Author) / Jehn, Megan (Thesis director) / Chowell-Puente, Gerardo (Committee member) / Barrett, The Honors College (Contributor) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
The influenza virus is the main cause of thousands of deaths each year in the United States, and far more hospitalizations. Immunization has helped in protecting people from this virus and there are a number of therapeutics which have proven effective in aiding people infected with the virus. However, these therapeutics are subject to various limitations including increased resistance, limited supply, and significant side effects. A new therapeutic is needed which addresses these problems and protects people from the influenza virus. Synbodies, synthetic antibodies, may provide a means to achieve this goal. Our group has produced a synbody, the 5-5 synbody, which has been shown to bind to and inhibit the influenza virus. The direct pull down and western blot techniques were utilized to investigate how the synbody bound to the influenza virus. Our research showed that the 5-5 synbody bound to the influenza nucleoprotein (NP) with a KD of 102.9 ± 74.48 nM. It also showed that the synbody bound strongly to influenza viral extract from two different strains of the virus, the Puerto Rico (H1N1) and Sydney (H3N2) strains. This research demonstrated that the 5-5 synbody binds with high affinity to NP, which is important because influenza NP is highly conserved between various strains of the virus and plays an important role in the replication of the viral genome. It also demonstrated that this binding is conserved between various strains of the virus, indicating that the 5-5 synbody potentially could bind many different influenza strains. This synbody may have potential as a therapeutic in the future if it is able to demonstrate similar binding in vivo.
ContributorsKombe, Albert E. (Author) / Diehnelt, Chris (Thesis director) / Woodbury, Neal (Committee member) / Legutki, Bart (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of International Letters and Cultures (Contributor)
Created2014-05
Description
The influenza virus, also known as "the flu", is an infectious disease that has constantly affected the health of humanity. There is currently no known cure for Influenza. The Center for Innovations in Medicine at the Biodesign Institute located on campus at Arizona State University has been developing synbodies as a possible Influenza therapeutic. Specifically, at CIM, we have attempted to design these initial synbodies to target the entire Influenza virus and preliminary data leads us to believe that these synbodies target Nucleoprotein (NP). Given that the synbody targets NP, the penetration of cells via synbody should also occur. Then by Western Blot analysis we evaluated for the diminution of NP level in treated cells versus untreated cells. The focus of my honors thesis is to explore how synthetic antibodies can potentially inhibit replication of the Influenza (H1N1) A/Puerto Rico/8/34 strain so that a therapeutic can be developed. A high affinity synbody for Influenza can be utilized to test for inhibition of Influenza as shown by preliminary data. The 5-5-3819 synthetic antibody's internalization in live cells was visualized with Madin-Darby Kidney Cells under a Confocal Microscope. Then by Western Blot analysis we evaluated for the diminution of NP level in treated cells versus untreated cells. Expression of NP over 8 hours time was analyzed via Western Blot Analysis, which showed NP accumulation was retarded in synbody treated cells. The data obtained from my honors thesis and preliminary data provided suggest that the synthetic antibody penetrates live cells and targets NP. The results of my thesis presents valuable information that can be utilized by other researchers so that future experiments can be performed, eventually leading to the creation of a more effective therapeutic for influenza.
ContributorsHayden, Joel James (Author) / Diehnelt, Chris (Thesis director) / Johnston, Stephen (Committee member) / Legutki, Bart (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-05
Description
Advancements in both the medical field and public health have substantially minimized the detrimental impact of infectious diseases. Health education and disease prevention remains a vital tool to maintain and propagate this success. In order to determine the relationship between knowledge of disease and reported preventative behavior 180 participants amongst the ASU student population were surveyed about their knowledge and prevention behavior for 10 infectious diseases. Of the 180 participants only 138 were completed surveys and used for analysis. No correlation was found between knowledge or perceived risk and preventative measures within the total sample of 138 respondents, however there was a correlation found within Lyme disease and Giardia exposure to information and prevention. Additionally, a cultural consensus analysis was used to compare the data of 17 US-born and 17 foreign-born participants to analyze patterns of variation and agreement on disease education based on national origins. Cultural consensus analysis showed a strong model of agreement among all participants as well as within the US-born and foreign-born student groups. There was a model of agreement within the questions pertaining to transmission and symptoms. There was not however a model of agreement within treatment questions. The findings suggest that accurate knowledge on infectious diseases may be less impactful on preventative behavior than social expectations.
ContributorsVernon, Samantha (Author) / Maupin, Jonathan (Thesis director) / Jehn, Megan (Committee member) / Barrett, The Honors College (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2018-05
Description
Objective: To provide insight into the World Health Organization SAGE Working Group Vaccine Hesitancy Survey by applying the tool to populations across Maricopa County, Arizona. Design: An online survey was conducted using the Qualtrics Survey Software, of individuals residing in Maricopa County, Arizona during the month of October 2019. Results: Of 209 respondents, the followed demonstrated to be the top 3 reasons for either having not received the flu shot yet or having not planned to receive the flu shot: “I’m healthy, I don’t need it”(20.1%); “Worried I might get the flu from it”(17.7%); “I don’t think it works”(17.7%) Statistical analysis demonstrated that vaccine hesitant and non-hesitant respondents are likely to respond differently to topics covering: safety of vaccines; self-perceived health status; importance of the flu shot among one’s peers; flu vaccine related knowledge Conclusions: The WHO VHS applied to the population of Maricopa County, Arizona reported little hesitancy towards the seasonal flu vaccine. Statistical analysis of Vaccine Hesitant respondents vs. Non-Hesitant respondents demonstrates that specified public health education focused on the immunological implications of vaccines may be needed for the hesitant population to gain confidence in vaccine efficacy. A more diverse respondent group that consists of residents beyond the county lines of Maricopa is needed to understand the full scope of vaccine hesitancy that exists in Arizona.
ContributorsMaroofi, Hanna (Co-author, Co-author) / Jehn, Megan (Thesis director) / Muabyi, Anuj (Committee member) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor) / School of Human Evolution & Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05