Department of Population Health Sciences

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https://hdl.handle.net/10919/24262

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Browsing Department of Population Health Sciences by Department "Fralin Life Sciences Institute"

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    Impact of demographic disparities in social distancing and vaccination on influenza epidemics in urban and rural regions of the United States
    Singh, Meghendra; Sarkhel, Prasenjit; Kang, Gloria J.; Marathe, Achla; Boyle, Kevin J.; Murray-Tuite, Pamela; Abbas, Kaja M.; Swarup, Samarth (2019-03-04)
    Background Self-protective behaviors of social distancing and vaccination uptake vary by demographics and affect the transmission dynamics of influenza in the United States. By incorporating the socio-behavioral differences in social distancing and vaccination uptake into mathematical models of influenza transmission dynamics, we can improve our estimates of epidemic outcomes. In this study we analyze the impact of demographic disparities in social distancing and vaccination on influenza epidemics in urban and rural regions of the United States. Methods We conducted a survey of a nationally representative sample of US adults to collect data on their self-protective behaviors, including social distancing and vaccination to protect themselves from influenza infection. We incorporated this data in an agent-based model to simulate the transmission dynamics of influenza in the urban region of Miami Dade county in Florida and the rural region of Montgomery county in Virginia. Results We compare epidemic scenarios wherein the social distancing and vaccination behaviors are uniform versus non-uniform across different demographic subpopulations. We infer that a uniform compliance of social distancing and vaccination uptake among different demographic subpopulations underestimates the severity of the epidemic in comparison to differentiated compliance among different demographic subpopulations. This result holds for both urban and rural regions. Conclusions By taking into account the behavioral differences in social distancing and vaccination uptake among different demographic subpopulations in analysis of influenza epidemics, we provide improved estimates of epidemic outcomes that can assist in improved public health interventions for prevention and control of influenza.
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    Multi-scale immunoepidemiological modeling of within-host and between-host HIV dynamics: systematic review of mathematical models
    Dorratoltaj, Nargesalsadat; Nikin-Beers, Ryan; Ciupe, Stanca M.; Eubank, Stephen G.; Abbas, Kaja M. (PeerJ, 2017-09-28)
    Objective The objective of this study is to conduct a systematic review of multi-scale HIV immunoepidemiological models to improve our understanding of the synergistic impact between the HIV viral-immune dynamics at the individual level and HIV transmission dynamics at the population level. Background While within-host and between-host models of HIV dynamics have been well studied at a single scale, connecting the immunological and epidemiological scales through multi-scale models is an emerging method to infer the synergistic dynamics of HIV at the individual and population levels. Methods We reviewed nine articles using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework that focused on the synergistic dynamics of HIV immunoepidemiological models at the individual and population levels. Results HIV immunoepidemiological models simulate viral immune dynamics at the within-host scale and the epidemiological transmission dynamics at the between-host scale. They account for longitudinal changes in the immune viral dynamics of HIV+ individuals, and their corresponding impact on the transmission dynamics in the population. They are useful to analyze the dynamics of HIV super-infection, co-infection, drug resistance, evolution, and treatment in HIV+ individuals, and their impact on the epidemic pathways in the population. We illustrate the coupling mechanisms of the within-host and between-host scales, their mathematical implementation, and the clinical and public health problems that are appropriate for analysis using HIV immunoepidemiological models. Conclusion HIV immunoepidemiological models connect the within-host immune dynamics at the individual level and the epidemiological transmission dynamics at the population level. While multi-scale models add complexity over a single-scale model, they account for the time varying immune viral response of HIV+ individuals, and the corresponding impact on the time-varying risk of transmission of HIV+ individuals to other susceptibles in the population.
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    A rapid and high content assay that measures cyto-ID-stained autophagic compartments and estimates autophagy flux with potential clinical applications
    Guo, Sujuan; Liang, Yanping; Murphy, Susan F.; Huang, Angela; Shen, Haihong; Kelly, Deborah F.; Sobrado, Pablo; Sheng, Zhi (Taylor & Francis, 2015-03-01)
    The lack of a rapid and quantitative autophagy assay has substantially hindered the development and implementation of autophagy-targeting therapies for a variety of human diseases. To address this critical issue, we developed a novel autophagy assay using the newly developed Cyto-ID fluorescence dye. We first verified that the Cyto-ID dye specifically labels autophagic compartments with minimal staining of lysosomes and endosomes. We then developed a new Cyto-ID fluorescence spectrophotometric assay that makes it possible to estimate autophagy flux based on measurements of the Cyto-ID-stained autophagic compartments. By comparing to traditional autophagy approaches, we found that this assay yielded a more sensitive, yet less variable, quantification of the stained autophagic compartments and the estimate of autophagy flux. Furthermore, we tested the potential application of this autophagy assay in high throughput research by integrating it into an RNA interference (RNAi) screen and a small molecule screen. The RNAi screen revealed WNK2 and MAP3K6 as autophagy-modulating genes, both of which inhibited the MTOR pathway. Similarly, the small molecule screen identified sanguinarine and actinomycin D as potent autophagy inducers in leukemic cells. Moreover, we successfully detected autophagy responses to kinase inhibitors and chloroquine in normal or leukemic mice using this assay. Collectively, this new Cyto-ID fluorescence spectrophotometric assay provides a rapid, reliable quantification of autophagic compartments and estimation of autophagy flux with potential applications in developing autophagy-related therapies and as a test to monitor autophagy responses in patients being treated with autophagy-modulating drugs.