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Title: Contribution to epidemiological research on the use of heroin and other opioid compounds
Creator: Yeh, Hsueh-Han
Date: 2017
Collection: Electronic Theses & Dissertations
Description: Patterns of heroin use and extra-medical (EM) use of other opioid compounds have re-surfaced as important public health issues in the United States (US) and in many countries. Midway through a 21st century epidemic of death due to heroin overdose in the US, there are many gaps in epidemiological evidence. For example, experts have already have concluded that heroin often becomes an alternative or substitute for other prescription opioids because an unit dose of heroin has become less...
Show morePatterns of heroin use and extra-medical (EM) use of other opioid compounds have re-surfaced as important public health issues in the United States (US) and in many countries. Midway through a 21st century epidemic of death due to heroin overdose in the US, there are many gaps in epidemiological evidence. For example, experts have already have concluded that heroin often becomes an alternative or substitute for other prescription opioids because an unit dose of heroin has become less expensive and now is more readily available than diverted prescription opioids (Cicero et al., 2012; Jones 2013; Muhuri et al., 2013). Nonetheless, the evidence on this issue largely is based on case reports, and provides little basis for causal inference. This problem is compounded by the lack of published population-level estimates on heroin incidence rates, akin to estimates derived by Hunt & Chambers (1976), based upon treatment admissions during the US heroin epidemic of the 1960s and 1970s. The first aim of this dissertation addresses this incidence rate gap in epidemiological evidence for the US. It seeks to estimate heroin incidence for 1992-2012 using the Hunt-Chambers method based on opioid treatment admissions. The second dissertation aim is concentrated on a causal inference about the process of becoming a newly incident heroin user, and whether this process might be triggered by prior EM use of OxyContin®, a specific prescription opioid. Thus, the second specific aim is to conduct a case-crossover study to investigate a "triggering hypothesis" that links antecedent EM OxyContin® use with later heroin onset in the US. The third study of this dissertation aims to predict the probability of transitioning from EM prescription pain reliever use to heroin onset using survival analysis models, with attention to hypothesized subgroup variation (i.e., population density).Based on Hunt's model via re-calibration approaches using Treatment Episode Data Set - Admissions datasets (TEDS-A), heroin onset increased 160% from 2000 to its peak in 2010; the incidence rate in 2012 is similar to the first heroin epidemic in 1969. As for opioids other than heroin (e.g., prescription opioids), the incidence increased more than 250% from 2000 to 2010. The second study investigates whether EM OxyContin® use might have triggered heroin onset among 12-25 year olds in the period of 2004-2014. The excess risk of newly incident heroin use is seen in a four-month interval right after onset of EM OxyContin® use (case-crossover risk ratio = 1.9). Post-estimation exploratory analyses suggest no excess risk for EM users of other prescription pain relievers, and indicate no excess risk correlated with new formulations of OxyContin® per se. In the third study, the peak risk for transitioning from onset of extra-medical prescription pain reliever use (EMPPR) to heroin onset within 10 years emerged at the third year since first EMPPR use. Approximately 5% of participants initiated heroin use in 10 years since EMPPR onset. The estimates of these subgroups remain similar regardless of population density. EMPPR users who are male, White, and with early EMPPR onset have an increased risk of initiating heroin use. Heroin outbreaks and epidemics revisited the US in the 2010s after the first US heroin epidemic of the 1970s. If successful, this project's new evidence on heroin in the US population in recent epidemic years should improve our understanding of heroin epidemiology, and may be an aid to new public health responses for primary prevention, outreach, and treatment resources with respect to heroin in the current epidemic and during future epidemics.
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Title: Advanced classification methods for large spatial-temporal data : applications to neuroimaging
Creator: Karim, Rejaul
Date: 2019
Collection: Electronic Theses & Dissertations
Description: Ecological research, geological studies, image analysis are a few examples of high resolution spatial data where proximity describes the relationship between data points collected at various locations. Such dependencies play a vital role in modeling the data accurately to improve both its predictive capacity and parameter estimation. Rapid technological advancement has brought about an abundance of such information. To better understand this information, we are in need of feature selection...
Show moreEcological research, geological studies, image analysis are a few examples of high resolution spatial data where proximity describes the relationship between data points collected at various locations. Such dependencies play a vital role in modeling the data accurately to improve both its predictive capacity and parameter estimation. Rapid technological advancement has brought about an abundance of such information. To better understand this information, we are in need of feature selection techniques for spatially dependent data that can tease out relevant predictors associated with the response of interest. When the response variable at the various sites is in the form of discrete binary or count data we are faced with an added layer of complexity due to the inability of explicitly describing a joint parametric distribution. This dissertation explores the benefits of adopting a penalized quasi-likelihood approach to model a fixed number (p) or an expanding dimension (pn) of predictor variables with regard to a discrete spatial response variable. In the past this approach has been extensively studied in longitudinal data analysis. Introducing random fields that exhibit certain rho-mixing conditions we are able to provide some general theoretical results of the estimator obtained from the solving the penalized score equation. The oracle properties of the estimator are provided, followed by an algorithm to successfully implement the method. Multiple simulation studies showcase the effectiveness of the method under covariance misspecification. We apply this technique to real data obtained from the Michigan Natural Features Inventory.Variable selection in neuroimaging has a unique formulation that leads to selection of activated regions of a brain in Task-based fMRI. As one of the most non-invasive formats of studying an active brain, Task-based fMRI provides a unique opportunity in neuroscience to study the dynamic aspects of brain function. Crude statistical techniques such as voxel-wise regression analysis have been used in the past with some success to identify active brain regions based on the blood-oxygen-level dependent (BOLD) signal of the image. Inspired by graphical covariate models proposed for genetic data we incorporate a similar idea and expand our understanding of penalized regression of weighted least squares with a separable space-time covariance model in this setup. Two penalty terms are introduced as a result; one for selection (LASSO) and another for smoothing (Ridge-type). We explore the interpretability of the proposed model as opposed to its Bayesian counterparts, its computational feasibility and various approaches to selecting an optimal tuning parameter in the case of a Single-subject study. The description of the model and its implementation are presented with discussions about theoretical implications. Extensive simulation studies and a real data example of a human brain subject to two visual stimuli are also given to provide evidence of the capability of this method.
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Title: Investigating the importance of vertebrate hosts for Lyme disease ecology : a natural experiment presented by Lake Michigan islands at Sleeping Bear Dunes National Lakeshore
Creator: Sidge, Jennifer Lois
Date: 2016
Collection: Electronic Theses & Dissertations
Description: ABSTRACTINVESTIGATING THE IMPORTANCE OF VERTEBRATE HOSTS FOR LYME DISEASE ECOLOGY: A NATURAL EXPERIMENT PRESENTED BY LAKE MICHIGAN ISLANDS AT SLEEPING BEAR DUNES NATIONAL LAKESHORE ByJennifer Lois Sidge In eastern North America, Lyme disease is caused by the bacterium, Borrelia burgdorferi, and is transmitted by the blacklegged tick, Ixodes scapularis. In Michigan’s Lower Peninsula, the blacklegged tick and the bacterium are invading from the southwest corner, northward along the Lake...
Show moreABSTRACTINVESTIGATING THE IMPORTANCE OF VERTEBRATE HOSTS FOR LYME DISEASE ECOLOGY: A NATURAL EXPERIMENT PRESENTED BY LAKE MICHIGAN ISLANDS AT SLEEPING BEAR DUNES NATIONAL LAKESHORE ByJennifer Lois Sidge In eastern North America, Lyme disease is caused by the bacterium, Borrelia burgdorferi, and is transmitted by the blacklegged tick, Ixodes scapularis. In Michigan’s Lower Peninsula, the blacklegged tick and the bacterium are invading from the southwest corner, northward along the Lake Michigan coast with the presumed leading edge at Sleeping Bear Dunes National Lakeshore (SLBE). How the tick spreads and becomes established is of great public health importance. White-tailed deer (Odocoileus virginianus) are believed to be the most important hosts for adult I. scapularis and critical for its spread and maintenance, but few opportunities exist to investigate tick and pathogen dynamics in their absence. Two Lake Michigan islands, at SLBE, one with deer and one without, presented this opportunity. The overall objective of this dissertation was to establish a baseline of abundance for the tick and pathogen on both islands and compare it to the ecologically diverse mainland, and assess the role of other mammals as alternative hosts for the adult stage of the tick in areas absent of deer. My hypothesis was that in locations devoid of deer, the blacklegged tick would not be established and/or would exist at much lower densities in comparison to areas with resident deer populations. Also, other medium-sized mammals would serve as hosts for the adult ticks that theoretically could support a tick population. In Chapter 1, I continued to track the invasion of the Lyme disease pathogen and vector at SLBE over a nine-year period. I found that there was a four year delay between the first detection of blacklegged ticks and the presence of B. burgdorferi and there was a trend illustrating an increase in I. scapularis and B. burgdorferi over time. At an additional site on SLBE’s mainland, the tick and the pathogen were detected at the same time supporting the “dual-invasion” scenario of invasion, yet, this may have been a consequence of when sampling began. At recently-invaded Lyme disease areas, such as these two SLBE mainland locations, I found eastern chipmunks (Tamias striatus) to be an earlier indicator of the pathogen’s presence in comparison to white-footed mice (Peromyscus leucopus). SLBE’s two offshore islands, one with white-tailed deer and the other devoid, were the focus of Chapter 2 as a means to evaluate the success of mammalian hosts for maintaining I. scapularis in the absence of deer. I found that although the island with the deer had a greater density of ticks and greater B. burgdorferi infection prevalence, the island that was deer-free had all three life stages of the blacklegged tick and B. burgdorferi was present. Thus, alternative hosts for the adult tick, including snowshoe hares (Lepus americanus), passerine birds, and coyotes (Canis latrans), were captured and it was determined that coyotes were maintaining the established tick population on the island. Eastern chipmunks played a crucial role with maintaining the juvenile stages of the tick on the islands. Chapter 3 then compared SLBE’s host-diverse mainland to the host-limited islands, testing the dilution and multiple niche polymorphism hypotheses. In order to test the dilution effect, the larval I. scapularis prevalence on white-footed mice between the two locations was compared. The proportion of mice infested with at least one I. scapularis larvae nor the larval burden on the mice supported the dilution hypothesis. However, on the islands and the mainland, more eastern chipmunks were captured than anticipated and this consequently reduced the larval burden on the mice in each community, thus, supporting the dilution effect at the location level. Host-seeking I. scapularis adult/nymphal infection prevalence and adult/nymphal density of infected ticks were greater on the host-limited islands, supporting the dilution hypothesis. However, B. burgdorferi IGS strain diversity was greater on the islands in comparison to the host-diverse mainland, which was unlike what was predicted by the multiple niche polymorphism hypothesis. Future studies to better estimate the island mammalian population sizes and diversity, in addition to comparing the B. burgdorferi island diversity to an area with a known long-established population of ticks would be advantageous to further our Lake Michigan island Lyme disease ecology knowledge. Also, given that SLBE is now most likely not at the leading edge of the Lyme disease invasion, future work should evaluate if the tick and bacterium have spread into neighboring counties.
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Title: Relationships among maternal serum uric acid in mid-pregnancy, maternal blood pressure, fetal growth, and placental pathology
Creator: Zhou, Guoli
Date: 2016
Collection: Electronic Theses & Dissertations
Description: "In this study, we investigated whether there is a J-shaped association between maternal serum uric acid in mid-pregnancy and three outcomes, mothers' blood pressure, birth weight for gestational age (Z-score), and placental pathology." -- Abstract.

Title: Viral genomics for identification of signals of disease in environmental samples
Creator: McCall, Camille
Date: 2020
Collection: Electronic Theses & Dissertations
Description: Viruses have been responsible for some of the most notorious outbreaks and pandemics in modern history. With increases in urbanization and global transportation we can expect viruses to remain a major concern both now and in the future. It is important to establish new ways to monitor virus circulation in communities and forecast the onset of a potential outbreak. Since centralized wastewater treatment facilities have the capacity to collect wastewater from thousands or millions of...
Show moreViruses have been responsible for some of the most notorious outbreaks and pandemics in modern history. With increases in urbanization and global transportation we can expect viruses to remain a major concern both now and in the future. It is important to establish new ways to monitor virus circulation in communities and forecast the onset of a potential outbreak. Since centralized wastewater treatment facilities have the capacity to collect wastewater from thousands or millions of inhabitants per day, a wastewater-based epidemiology (WBE) system can serve as an indicator of population health. This work aims to identify signals of disease in wastewater and potential for early detection of viral disease outbreaks in communities using molecular approaches and optimized sequencing strategies. Untreated wastewater samples were collected from a wastewater treatment plant situated in a large metropolitan area in the United States. Viral pathogens were identified in samples using qPCR and viral metagenomics (viromics). Mechanistic modeling and statistical approaches were used to determine the potential for early detection of select viral diseases. Public health data was applied to confirm the incidence of diseases associated with pathogens found in wastewater. Overall findings from this work suggests that WBE can be used to detect early peaks in select viral disease cases within a community before health care facilities are notified. Optimized metagenomic approaches and qPCR suggest that important viruses classified as enteric, respiratory, bloodborne, vector-borne and others are excreted in wastewater and can be monitored to make inferences about population health and potential for emerging disease outbreaks. Moreover, results indicate that specific public reporting of important viruses causing flu-like and gastrointestinal illness can enhance the efficacy of WBE to assess the burden of pathogens causing nonspecific illnesses. WBE along with molecular approaches and viral metagenomics has the potential to revolutionize public health and government responses to outbreaks. New approaches of this nature can be implemented in communities across the globe in an effort to mitigate the impacts of viral disease outbreaks on the economy and public health.
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Title: Molecular diagnostics, epidemiology, and population genetics of the soybean sudden death syndrome pathogen, Fusarium virguliforme
Creator: Wang, Jie (Graduate of Michigan State University)
Date: 2016
Collection: Electronic Theses & Dissertations
Description: Soybean sudden death syndrome (SDS), caused by Fusarium virguliforme, is one of the most devastating diseases of soybean responsible for yield losses in both North America and South America. In the United States, F. virguliforme is the predominant SDS causal pathogen, while four Fusarium species including F. virguliforme can cause SDS in South America. All four SDS-causing Fusarium species are located in clade2 of the Fusarium solani species complex (FSSC) along with three bean root rot (BRR)...
Show moreSoybean sudden death syndrome (SDS), caused by Fusarium virguliforme, is one of the most devastating diseases of soybean responsible for yield losses in both North America and South America. In the United States, F. virguliforme is the predominant SDS causal pathogen, while four Fusarium species including F. virguliforme can cause SDS in South America. All four SDS-causing Fusarium species are located in clade2 of the Fusarium solani species complex (FSSC) along with three bean root rot (BRR) Fusarium pathogens. Within this group of fungi, it is difficult to identify to species level based on morphological traits. We developed a specific and sensitive diagnostic real-time quantitative PCR assay (qPCR) for detection and quantification of F. virguliforme from plant or environmental samples. Furthermore, this assay was applied in characterization of temporal dynamics of F. virguliforme infection and colonization of soybean roots. The quantity of F. virguliforme increased over time and reached a plateau at the end of the season. The severity or appearance of SDS foliar symptoms was not associated with quantity of F. virguliforme infection, and cultivars with varied SDS resistance levels did not differ in their quantity of F. virguliforme in roots. The fungicide fluopyram has been demonstrated to be effective in reducing SDS foliar symptoms in field trials as a seed treatment; however, in vitro evaluation of fungicide baseline sensitivity of F. virguliforme had not been determined. In this study, 185 F. virguliforme isolates collected from multiple locations in the United States were selected for estimation of fungicide sensitivity to fluopyram. Overall, the US F. virguliforme population appears to be sensitive to fluopyram. The effective concentration to inhibit 50% growth for 95.1% of isolates was determined to be between 0.81 to 5 μg/ml, while only nine isolates were determined to be less sensitive.Since the first report of SDS in Arkansas in 1971, SDS had been reported in surrounding states with an apparent pattern of dispersal. To date, although SDS has been reported in most soybean producing areas in the United States, limited research had been conducted to study the population biology of F. virguliforme. We utilized 539 isolates from North and South America in a population genetics study to test the hypothesis that Arkansas was the center of introduction within the United States, and investigate possible intercontinental movement. The Arkansas population demonstrated the highest genotypic diversity and most diverse population structure. Coalescence based migration analysis also supported a directional migration model from Arkansas to Indiana and Michigan. Within the United States, there was a weak positive correlation (P = 0.08) between genetic dissimilarity and geographical distance, suggesting a mixed dispersal pattern of F. virguliforme in the United States. Although South America has been proposed as the center of origin in previous studies, this hypothesis was only supported in the migrate analysis, while the genotypic diversity and population structure compositions detected in the United States cannot be explained by this hypothesis. Therefore, Arkansas as the center of origin in the United States hypothesis is supported by the population genetic analyses, but the South America as the center of origin hypothesis does not have strong support in our analysis.
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Title: Bovine reproductive infectious disease in Ghana : prevalence and pathogenesis of early infection with an emphasis on trichomoniasis
Creator: Adu-Addai, Benjamin
Date: 2012
Collection: Electronic Theses & Dissertations
Description: Reproductive inefficiency is one of the most costly and production limiting problems facing the livestock development in Africa. Reproductive performance is influenced by a number of important factors, among which are infectious diseases, which result in lost production. Research in these diseases is critical in order to overcome these shortfalls.The objectives of the following studies were to provide a more in-depth epidemiological analysis of infectious reproductive diseases in Sub-Saharan...
Show moreReproductive inefficiency is one of the most costly and production limiting problems facing the livestock development in Africa. Reproductive performance is influenced by a number of important factors, among which are infectious diseases, which result in lost production. Research in these diseases is critical in order to overcome these shortfalls.The objectives of the following studies were to provide a more in-depth epidemiological analysis of infectious reproductive diseases in Sub-Saharan Africa and further investigate the cytokine environment and molecular factors involved in the innate immune response of the bovine reproductive tract to infectious agents which can play such an important role in livestock production in Africa, in particular Tritrichomonas foetus. The prevalence of important infectious reproductive diseases in a single herd using serology was investigated. Significantly, high seroprevalence of infectious bovine rhinotraechitis and trichomoniasis was demonstrated. The presence of coxiellosis, neosporosis, bovine viral diarrhea virus, and bovine herpesvirus-4, was demonstrated but not serological evidence of brucellosis. Significant associations were found between the seroprevalence of the different viral pathogens but no such association was noted between the other pathogens. The long calving interval in this herd could be due to the presence of these pathogens. Among the diseases we identified, we further studied trichomoniasis (T. foetus) and the host immune response in a mouse model. Serum and reproductive tissues for Th1 and Th2 cytokines (specifically INF-ã, TNF-á, IL-2, IL-4, and IL-5) via flow cytometry after 5 days of T. foetus infection were analyzed. Mice of varying ages which had different susceptibility to T. foetus infection were used to assess whether a Th1 or Th2 cytokine environment was significantly associated with successful infection. Both Th1 and Th2 cytokines (TNF-á, IL-4 and IL-2) were shown to be significantly altered in infected animals. Lastly, by using PCR and IHC techniques, the presence of the novel dual oxidase molecules (DUOX 1 and 2) in the reproductive tract of cows and in bovine endometrial and trophoblast cell cultures was documented. However, there was no significant difference in DUOX 1(P=0.296) or DUOX2 (P=0.480) expression in T. foetus infected cells versus their respective controls. In conclusion, several important infectious diseases in Ghanaian cattle which may affect reproduction, not the least of which is trichomoniasis, were detected. Further, it was demonstrated that the early infection has both Th1 and Th2 cytokine involvement and that while present in the reproductive tract, there is no evidence that the DUOX molecules play a role in early resistance, but they may be important at other time points.
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Title: Risk factors for sporadic non-typhoidal Salmonella infections in Michigan children : a population-based case-control study
Creator: Younus, Muhammad
Date: 2008
Collection: Electronic Theses & Dissertations

Title: The descriptive epidemiology of norwalk-like viruses
Creator: Gorch, Diane H.
Date: 2000
Collection: Electronic Theses & Dissertations

Title: Are there "hot spots" of bovine tuberculosis in the free-ranging white-tailed deer (Odocoileus virginianus) herd of northeastern Michigan?
Creator: Hughey, Brandi Danielle
Date: 2003
Collection: Electronic Theses & Dissertations

Title: Epidemiological study of Neisseria gonorrheae co-infection among males with HIV/AIDS residing in the State of Michigan
Creator: Francis, Matthew Joseph
Date: 2014
Collection: Electronic Theses & Dissertations
Description: Background: Epidemiological evidences suggest a synergistic relationship between Human Immunodeficiency Virus (HIV) and N. gonorrheae in co-infected individuals. The objectives of this study were; 1) to test whether age at HIV between those with a history of N. gonorrheae infection was younger as compared to those with no history of reported N. gonorrheae infection, 2) to test whether age at HIV progression event (death or Acquired Immune Deficiency Syndrome (AIDS)) was younger as well as...
Show moreBackground: Epidemiological evidences suggest a synergistic relationship between Human Immunodeficiency Virus (HIV) and N. gonorrheae in co-infected individuals. The objectives of this study were; 1) to test whether age at HIV between those with a history of N. gonorrheae infection was younger as compared to those with no history of reported N. gonorrheae infection, 2) to test whether age at HIV progression event (death or Acquired Immune Deficiency Syndrome (AIDS)) was younger as well as time from HIV diagnosis to HIV progression event was reduced in individuals with a history of N. gonorrheae infection as compared to those without, 3) to investigate the geospatial distribution of HIV and N. gonorrheae in the State of Michigan, and 4) to investigate the differences in biological markers (CD4 cell count and viral load) in a sub-population of HIV N. gonorrheae co-infected individuals.Methods: A retrospective cohort study from 2005-2011 was conducted in collaboration with Michigan Department of Community Health on Michigan HIV positive males with a history of N. gonorrheae infection between 2005-2011 as well as HIV positive males with no history of N. gonorrheae infection who were alive at the start of 2005. A sub-group analysis of Michigan HIV positive males with a reported N. gonorrheae infection between 2011 and 2013 to investigate biological markers of HIV progression. Spatial, survival, and linear regression analyses were performed on the data to evaluate the objectives of the study.Results: Mean age at HIV diagnosis was found to be younger in individuals with pre-HIV N. gonorrheae infections. On average males with 2 or more pre-HIV N. gonorrheae infections were 10.2 years younger than individuals with no N. gonorrheae infections, and males with only one pre-HIV N. gonorrheae infection were 7.3 years younger at HIV diagnosis. Hazard of AIDS increased in males with post-HIV N. gonorrheae infections, with individuals with multiple post-HIV N. gonorrheae infections having increase in hazard of progression to AIDS. A longer HIV to AIDS lag time period was observed in males with multiple post-HIV gonorrhea. Geospatial analysis showed that the area around the City of Detroit and the Tri-County area of Oakland, Macomb, and Wayne have the highest burden of disease due to co-infection as well as represent the most likely clusters for HIV N. gonorrheae co-infections. CD4 cell count was found to increase in the year during N. gonorrheae infection as well as in the years after as compared to pre-gonorrhea levels. Similarly viral load was found to increase in the year during N. gonorrheae infection, however, it did not remain elevated as compared to the pre-gonorrhea states. Conclusion: This study is a first step in documenting the possible synergistic relationship between N. gonorrheae infection and HIV. The study found that age at HIV and age at HIV progression event were reduced (younger at event) than in those with no history of gonorrhea. The study also identified areas of concern using geospatial analysis where resources should be focused to try and reduce and disease. Paradoxically the time from HIV to HIV progression event was increased in those with N. gonorrheae infections as compared to those without. Finally the study found that CD4 cell count was increased in the time period during and after N. gonorrheae infection, and that viral load was increased in the year during N. gonorrheae infection, but returned to pre-gonorrhea levels in the years following.
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Title: Improving secondary prevention of coronary heart disease using decision support interventions in outpatient settings : a grant proposal submitted to National Heart Lung and Blood Institute
Creator: Olomu, Adesuwa B.
Date: 2007
Collection: Electronic Theses & Dissertations

Title: Experimental and epidemiological approaches to Campylobacter jejuni-associated Guillain Barré Syndrome
Creator: St. Charles, Jessica L.
Date: 2013
Collection: Electronic Theses & Dissertations
Description: Guillain Barré Syndrome (GBS), an immune-mediated acute polyneuropathy of the peripheral nerves, is the leading cause of acute autoimmune neuromuscular paralysis in the Western world. Approximately two-thirds of patients report a prior respiratory or gastrointestinal infection; Campylobacter jejuni is the most commonly reported antecedent infection. C. jejuni is the leading cause of foodborne bacterial gastrointestinal infection; transmission is by ingestion...
Show moreGuillain Barré Syndrome (GBS), an immune-mediated acute polyneuropathy of the peripheral nerves, is the leading cause of acute autoimmune neuromuscular paralysis in the Western world. Approximately two-thirds of patients report a prior respiratory or gastrointestinal infection; Campylobacter jejuni is the most commonly reported antecedent infection. C. jejuni is the leading cause of foodborne bacterial gastrointestinal infection; transmission is by ingestion of contaminated water, milk, and poultry. The proposed mechanism of GBS is similarity of the lipo-oligosaccharide (LOS) on the outer surface of some C. jejuni strains to gangliosides, glycolipid structures found in the nervous system. This molecular mimicry results in an immune response directed at both the LOS and gangliosides. Current data surrounding molecular mimicry are conflicting, therefore suggesting that other surface structures of C. jejuni are involved in GBS pathogenesis. Epidemiological studies on isolates collected from patients that presented with either enteritis or neuropathy to define potential genetic relationships of GBS to the highly variable C. jejuni flagellar and major outer membrane proteins have given inconclusive and contradictory results. Therefore additional work is needed to improve molecular typing of C. jejuni isolates. The work reported here took two complementary directions: development of a murine model of GBS using C. jejuni strains of an LOS type known to be associated with GBS in humans and an epidemiological study of C. jejuni isolates from the U.S. with a focus in Michigan, in which the LOS biosynthetic locus, the flagellar protein, and the major outer membrane protein were all characterized in addition to standard multilocus sequence typing. To understand the role of the genetic factors of C. jejuni and potential host factors in the pathogenesis of GBS more in vivo studies are needed. However, current animal models to study GBS employ immunization of rabbits with purified LOS or mice with bovine myelin to initiate an immune response similar to that in GBS patients. These are not natural models of GBS following C. jejuni infection. In a more natural model in chickens, birds given GBS-associated strains of C. jejuni develop both clinical signs and immunological responses similar to those seen in GBS patients. However, chickens are anatomically and physiologically different from humans. The goal of the first half of my studies was development of a murine model secondary to C. jejuni infection; we found a strain of mouse that has the potential to be such a model, but more work must be done. The goal of the second half of my studies was to examine possible epidemiological relationships between other variable surface components of C. jejuni and LOS types associated with GBS. In epidemiological studies using molecular typing of both variable and conserved genes, we found that both human C. jejuni isolates from a limited collection from the U.S. with focus in Michigan and from calves on a Michigan dairy farm that had a C. jejuni outbreak had LOS biosynthetic loci characteristic of GBS-associated strains.
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Title: Maternal infections and development of preeclampsia : a systematic review of the epidemiological literature
Creator: Wajid, Abdul
Date: 2015
Collection: Electronic Theses & Dissertations
Description: We systematically reviewed the associations between H. pylori (HP), cytomegalovirus (CMV) and C. pneumoniae (CP) infection in pregnancy and preeclampsia (PE), a disorder found in 5-8% of pregnancies and a leading cause of maternal and perinatal mortality. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines and searched PubMed, EMBASE and Web of Science. We also assessed the studies for risk of bias by utilizing a modified version of A Cochrane Risk...
Show moreWe systematically reviewed the associations between H. pylori (HP), cytomegalovirus (CMV) and C. pneumoniae (CP) infection in pregnancy and preeclampsia (PE), a disorder found in 5-8% of pregnancies and a leading cause of maternal and perinatal mortality. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines and searched PubMed, EMBASE and Web of Science. We also assessed the studies for risk of bias by utilizing a modified version of A Cochrane Risk of Bias Assessment Tool for Non-Randomized Studies of Interventions (ACROBAT-NRSI). After exclusions based on criteria from these tools, 16 studies were reviewed in detail, of 1,031 initially identified by our search algorithm. Evidence of infection was based on serology (12 studies), Polymerase Chain Reaction (2) or both (2). All four studies of the association between HP and PE found significant odds ratios ranging from 2.7 – 9.2. Two of four studies of CMV and PE found significantly elevated odds ratios (1.9 and 2.7), while only three of ten studies of CP found significant odds ratios, ranging from 3.1 to 4.1. Not all studies controlled fully for confounding, and ten studies were at serious risk of bias.The available literature provides partial support for the association between these infectious agents and PE, especially for HP, but more rigorous studies are needed in this area, because more than half of the studies examined were at high risk of bias.
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Title: Epidemiology of Sclerotina homoeocarpa in Michigan : geostatistical and population biological approaches
Creator: Horvath, Brandon Joseph
Date: 2003
Collection: Electronic Theses & Dissertations

Title: The epidemiology of grapevine powdery mildew in Michigan and the effects of powdery and downy mildew on vine physiology
Creator: Miles, Laura Avila
Date: 2011
Collection: Electronic Theses & Dissertations
Description: Monitoring of the primary inoculum of the grape powdery mildew (Erysiphe necator) revealed that ascospores were caught almost continuously between bud break and fruit set, and release was best described as a function of degree-days. Monitoring of ascocarp production in the fall showed peaks in mid- to late September. This information can be used to optimize timing of fall eradicant sprays. A survey of fungicide sensitivity in E. necator in...
Show moreMonitoring of the primary inoculum of the grape powdery mildew (Erysiphe necator) revealed that ascospores were caught almost continuously between bud break and fruit set, and release was best described as a function of degree-days. Monitoring of ascocarp production in the fall showed peaks in mid- to late September. This information can be used to optimize timing of fall eradicant sprays. A survey of fungicide sensitivity in E. necator in Michigan vineyards showed that strobilurin (QoI)-resistant isolates were most prevalent in research plots and some commercial wine grape vineyards and least prevalent in juice grape vineyards. The G143A mutation that confers resistance was detected in every isolate with an EC₅₀Show less

Title: Mitochondrial genetic epidemiology of lifespan in a population isolate
Creator: Bonner, Joseph Donald
Date: 2013
Collection: Electronic Theses & Dissertations
Description: Mitochondria play a crucial role in cellular processes. They are where oxidative phosphorylation (OXPHOS) occurs. OXPOHS produces ATP which powers most cellular functions. Mitochondria are also regulators of other cellular processes such as apoptosis, cell cycle regulation, calcium signaling and neuronal synaptic transmission. They contain the only extra-nuclear DNA in eukaryotes. Mitochondrial DNA (mtDNA) encodes crucial components required for OXPHOS. Reactive oxygen species (ROS) are a...
Show moreMitochondria play a crucial role in cellular processes. They are where oxidative phosphorylation (OXPHOS) occurs. OXPOHS produces ATP which powers most cellular functions. Mitochondria are also regulators of other cellular processes such as apoptosis, cell cycle regulation, calcium signaling and neuronal synaptic transmission. They contain the only extra-nuclear DNA in eukaryotes. Mitochondrial DNA (mtDNA) encodes crucial components required for OXPHOS. Reactive oxygen species (ROS) are a natural byproduct of OXPHOS. In healthy states, ROS production facilitates mitochondrial cell signaling. ROS levels are kept in homeostasis by naturally occurring anti-oxidants. When dysregulated, ROS can cause mutations in mtDNA ultimately thereby decreasing ATP production capacity. Aging in humans manifests as a gradual decline in cellular functioning, leading to loss of tissue function and eventual death. The rate at which humans age and eventually die, is a complex interplay between genes and environment. Mitochondria are closely related to cellular function and their decline mirrors the aging process. These observations suggest that mitochondrial dysfunction might play a role in the aging process.Human mtDNA is exclusively transmitted from mother to child with no possibility for paternal recombination. Certain patterns of mtDNA haplotypes cluster in geographic regions. Observing these geographic differences has allowed researchers to put groups of mtDNA haplotypes into phylogenic trees that mirror human migration patterns. Epidemiologic studies have sought to associate disease patterns with mtDNA haplotype groups. Some studies of longevity have found that carriers of certain mtDNA haplotype groups are more common among aged cases than younger controls. However, these studies leave many questions unsettled. Prior studies do not account for nuclear genetic factors, have not achieved sufficient statistical power, have been unable to account for changes in age-at-death that have occurred over time and have not use time-to-event analysis.This dissertation examines that hypothesis that mtDNA Haplogroup J carriers live longer than carriers of other haplogroups. This work focuses on a newly-identified population isolate in Mid-Michigan with a well-documented pedigree. It is within this pedigree that we propose to test the Haplogroup J and longevity or lifespan association. In Chapter 1, the case for the association is presented. It covers the evidence for a stronger maternal to the heritability of longevity over a paternal contribution. It details how mitochondria could be the biologic mechanism and mtDNA genetics the observable phenomena and testable material for the heritability differences. Further this chapter presents the role of mitochondria in biologic processes and how genetic variation presented by mtDNA haplogroup differences has been demonstrated as epidemiologic risk factors in several human health states. It also details why previous studies are not in the optimal context to best address these questions.In Chapter 2, the unique characteristics of the population isolate and their pedigree database are presented. The descendants of a small group of settlers have remained in a small geographic area for the past century and a half. Since these descendants reside in the small area and often to choose to marry others within the community, the population is isolated but not closed. Isolate populations are ideal for discovering occult heritability of human health states. Chapter 3 presents a meta-analysis and pooled effect-size estimate of mtDNA Haplogroup J carriers living longer lives than carriers of other groups. The association is more pronounced in European populations. However, even when all available studies are pooled into one effect estimate, there is still insufficient power to confirm or refute that one haplogroup confers a longevity benefit in the background of many others expected in a European population. Within this epidemiologic context, I hypothesize that a population isolate is a well-suited sampling frame for studying a mitochondrial genetic association because the background nuclear-genetic and environment factors have some homogeneity. Chapter 4 presents the results the "Mitochondrial DNA patterns and Lifespan" (MDPL) study, in which I test the Haplogroup J/Lifespan hypothesis in the population isolate using several statistical measures. The study assembled a direct population of living individuals, scored their mtDNA haplogroup, ascribed their haplogroup to the most distant maternal relative in the pedigree dataset and assembled all her descendants. From the deceased mitochondrial descendants of the maternal ancestors, we created an indirect population. From the ages at death of the indirect population, I tested several metrics of increased lifespan in Haplogroup J carriers contrasted with carriers of all other haplogroups combined and assess the differences when stratified by sex.Chapter 5 presents a summary of these findings and proposed future direction. In pursuing the test of my hypothesis I discovered points for others to ponder. I present these points and discuss my thoughts to guide future studies.
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Title: Brucellosis in humans and livestock in rural Uganda : epidemiology and tools for resource-limited settings
Creator: Miller, RoseAnn
Date: 2016
Collection: Electronic Theses & Dissertations
Description: "Objectives: A cross-sectional study was undertaken to describe the epidemiology of zoonotic brucellosis in dairy farms in rural southwestern Uganda, and to evaluate the use of tools to address the challenges to disease surveillance programs faced in rural sub-Saharan Africa and other resource-limited settings." -- Abstract.

Title: Epidemiology of thyroid hormone abnormalities in extremely premature infants
Creator: Hong, Ting
Date: 2008
Collection: Electronic Theses & Dissertations

Title: EPIDEMIOLOGY OF ANTIBIOTIC RESISTANT SHIGA TOXIN-PRODUCING ESCHERICHIA COLI (STEC) AND NON-TYPHOIDAL SALMONELLA (NTS) IN MICHIGAN
Creator: Mukherjee, Sanjana
Date: 2018
Collection: Electronic Theses & Dissertations
Description: The enteric pathogens, Shiga toxin-producing E. coli (STEC) and non-typhoidal Salmonella (NTS), are leading causes of foodborne infections in the US, resulting in 265,000 and 1.2 million illnesses every year, respectively. The emergence of antibiotic resistance in these pathogens has been documented and is of great concern due to negative patient health outcomes and the possibility of transfer of resistance genes to other clinically relevant pathogens. However, there is a scarcity in...
Show moreThe enteric pathogens, Shiga toxin-producing E. coli (STEC) and non-typhoidal Salmonella (NTS), are leading causes of foodborne infections in the US, resulting in 265,000 and 1.2 million illnesses every year, respectively. The emergence of antibiotic resistance in these pathogens has been documented and is of great concern due to negative patient health outcomes and the possibility of transfer of resistance genes to other clinically relevant pathogens. However, there is a scarcity in information about frequencies of antibiotic resistant and factors associated with resistant STEC and NTS infections in Michigan. It is necessary to have a complete understanding about the of emerging antibiotic resistance and factors driving the rise of resistance in STEC and NTS to help develop effective control strategies. In this dissertation, 980 STEC isolates collected from patients in Michigan between 2001 and 2014 were examined for resistance to clinically relevant antibiotics. The examination of STEC strains for resistance, revealed high frequencies of resistance to ampicillin and trimethoprim-sulfamethoxazole, with significant increases in antibiotic resistance rates observed over this 14-year period. Multivariate logistic regression analysis identified non-O157 serotypes to be independently associated with antibiotic resistance. The recent increase in incidence of non-O157 serotypes observed in the US, coupled with the high frequencies of antibiotic resistance observed in this study, suggest the emergence of antibiotic resistant non-O157s as important human pathogens. Additionally, antibiotic resistant STEC isolates from patients in recent years (2010-2014) were more likely to cause hospitalizations than pansusceptible STEC isolates, suggesting that resistant STEC infections may result in adverse patient outcomes. Using whole genome sequencing, we also identified chromosomal mutations and 33 horizontally acquired genes present in the genomes of non-O157 STEC, likely conferring resistance. Importantly, by creating a co-occurrence network of these genes, we identified the co-occurrence of certain resistance genes, which are possibly present on the same mobile genetic element, thus resulting in multi-drug resistance. In addition to examining resistance in STEC, a total of 198 clinical NTS isolates collected between 2011 and 2014 were also examined for antibiotic resistance in this dissertation. Resistance to tetracycline, trimethoprim-sulfamethoxazole and ampicillin were commonly observed. Concerningly, high frequencies of multidrug resistant NTS were also observed with significant increases in their prevalence observed between 2011 and 2014. These high multidrug resistant rates have important implications on patient care as the efficacy of multiple antibiotics is reduced. Antibiotic resistant NTS isolates were also found to result in significantly longer mean hospital stays compared to pansusceptible NTS. Serovar specific differences in frequencies of antibiotic resistance were observed; S. Enteritidis were observed to have lower resistance frequencies than other serovars. Lastly, to better understand the role that cattle reservoirs play in harbouring antibiotic resistant STEC strains, we examined 121 STEC isolates collected in 2012 from six cattle farms in Michigan for antibiotic resistance. While high resistance frequencies to tetracycline and trimethoprim-sulfamethoxazole were observed in certain herds, no resistance to ampicillin was observed, unlike what was observed in STEC isolates collected from patients. While different populations of resistant STEC may be circulating in the clinical and agricultural environments, continuous monitoring of resistance in the cattle reservoir is warranted to determine if animal reservoirs can serve as potential sources of resistant infections in humans.
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