Browsing by Author "Grubb, Christopher"
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- Age-dependent ventilator-induced lung injury: Mathematical modeling, experimental data, and statistical analysisHay, Quintessa; Grubb, Christopher; Minucci, Sarah; Valentine, Michael S.; Van Mullekom, Jennifer H.; Heise, Rebecca L.; Reynolds, Angela M. (PLOS, 2024-02-22)A variety of pulmonary insults can prompt the need for life-saving mechanical ventilation; however, misuse, prolonged use, or an excessive inflammatory response, can result in ventilator-induced lung injury. Past research has observed an increased instance of respiratory distress in older patients and differences in the inflammatory response. To address this, we performed high pressure ventilation on young (2-3 months) and old (20-25 months) mice for 2 hours and collected data for macrophage phenotypes and lung tissue integrity. Large differences in macrophage activation at baseline and airspace enlargement after ventilation were observed in the old mice. The experimental data was used to determine plausible trajectories for a mathematical model of the inflammatory response to lung injury which includes variables for the innate inflammatory cells and mediators, epithelial cells in varying states, and repair mediators. Classification methods were used to identify influential parameters separating the parameter sets associated with the young or old data and separating the response to ventilation, which was measured by changes in the epithelial state variables. Classification methods ranked parameters involved in repair and damage to the epithelial cells and those associated with classically activated macrophages to be influential. Sensitivity results were used to determine candidate in-silico interventions and these interventions were most impact for transients associated with the old data, specifically those with poorer lung health prior to ventilation. Model results identified dynamics involved in M1 macrophages as a focus for further research, potentially driving the age-dependent differences in all macrophage phenotypes. The model also supported the pro-inflammatory response as a potential indicator of age-dependent differences in response to ventilation. This mathematical model can serve as a baseline model for incorporating other pulmonary injuries.
- Subsewershed SARS-CoV-2 Wastewater Surveillance and COVID-19 Epidemiology Using Building-Specific Occupancy and Case DataCohen, Alasdair; Maile-Moskowitz, Ayella; Grubb, Christopher; Gonzalez, Raul A.; Ceci, Alessandro; Darling, Amanda; Hungerford, Laura L.; Fricker, Ronald D. Jr.; Finkielstein, Carla V.; Pruden, Amy; Vikesland, Peter J. (American Chemical Society, 2022-05-01)To evaluate the use of wastewater-based surveillance and epidemiology to monitor and predict SARS-CoV-2 virus trends, over the 2020-2021 academic year we collected wastewater samples twice weekly from 17 manholes across Virginia Tech's main campus. We used data from external door swipe card readers and student isolation/quarantine status to estimate building-specific occupancy and COVID-19 case counts at a daily resolution. After analyzing 673 wastewater samples using reverse transcription quantitative polymerase chain reaction (RT-qPCR), we reanalyzed 329 samples from isolation and nonisolation dormitories and the campus sewage outflow using reverse transcription digital droplet polymerase chain reaction (RT-ddPCR). Population-adjusted viral copy means from isolation dormitory wastewater were 48% and 66% higher than unadjusted viral copy means for N and E genes (1846/100 mL to 2733/100 mL/100 people and 2312/100 mL to 3828/100 mL/100 people, respectively; n = 46). Prespecified analyses with random-effects Poisson regression and dormitory/cluster-robust standard errors showed that the detection of N and E genes were associated with increases of 85% and 99% in the likelihood of COVID-19 cases 8 days later (incident-rate ratio (IRR) = 1.845, p = 0.013 and IRR = 1.994, p = 0.007, respectively; n = 215), and one-log increases in swipe card normalized viral copies (copies/100 mL/100 people) for N and E were associated with increases of 21% and 27% in the likelihood of observing COVID-19 cases 8 days following sample collection (IRR = 1.206, p < 0.001, n = 211 for N; IRR = 1.265, p < 0.001, n = 211 for E). One-log increases in swipe normalized copies were also associated with 40% and 43% increases in the likelihood of observing COVID-19 cases 5 days after sample collection (IRR = 1.403, p = 0.002, n = 212 for N; IRR = 1.426, p < 0.001, n = 212 for E). Our findings highlight the use of building-specific occupancy data and add to the evidence for the potential of wastewater-based epidemiology to predict COVID-19 trends at subsewershed scales.
- Subterranean Survivorship and Seasonal Emergence of Laricobius spp. (Coleoptera: Derodontidae), Biological Control Agents for the Hemlock Woolly AdelgidFoley, Jeremiah R.; McAvoy, Thomas J.; Grubb, Christopher; Mayfield, Albert E., III; Strahm, Brian D.; Salom, Scott M. (Oxford University Press, 2022-02-16)Following the adventive arrival, subsequent spread, and ensuing impact of Adelges tsugae Annand (Hemiptera: Adelgidae), the hemlock woolly adelgid (HWA) in the eastern United States, a robust initiative was launched with the goal of decreasing ecosystem impacts from the loss of eastern hemlock (Pinales: Pinaceae). This initiative includes the use of biological control agents, including Laricobius spp. (Insecta: Coleoptera). Laboratory production of these agents is limited by subterranean mortality and early emergence. Therefore, the subterranean survivorship and timing of emergence of a mixture of Laricobius spp. was investigated. PVC traps internally lined with a sticky card and covered with a mesh screen were inserted into the soil to measure the percent emergence of adults based on the number of larvae placed within. The number of emerged adults in the field and laboratory-reared larval treatments was adjusted based on emergence numbers in the control and used as the response variable. Independent variables included in the final model were: treatment (field-collected vs. laboratory-reared), organic layer depth (cm), soil pH, and April-to-December mean soil moisture. No differences were found in survivorship between field-collected and laboratory-reared treatments. As pH and organic layer increased survivorship decreased, significantly. Although the majority of emergence occurred in the fall, emergence also occurred in spring and summer. The occurrence of spring and summer emergence and low survivorship (17.1 +/- 0.4%) in the field across all treatments suggests that these are characteristics of Laricobius spp. field biology in their introduced range and not artifacts of the laboratory rearing process.