Modeling suggests that virion production cycles within individual cells is key to understanding acute hepatitis B virus infection kinetics.

Hepatitis B virus (HBV) infection kinetics in immunodeficient mice reconstituted with humanized livers from inoculation to steady state is highly dynamic despite the absence of an adaptive immune response. To recapitulate the multiphasic viral kinetic patterns, we developed an agent-based model that includes intracellular virion production cycles reflecting the cyclic nature of each individual virus lifecycle. The model fits the data well predicting an increase in production cycles initially starting with a long production cycle of 1 virion per 20 hours that gradually reaches 1 virion per hour after approximately 3-4 days before virion production increases dramatically to reach to a steady state rate of 4 virions per hour per cell. Together, modeling suggests that it is the cyclic nature of the virus lifecycle combined with an initial slow but increasing rate of HBV production from each cell that plays a role in generating the observed multiphasic HBV kinetic patterns in humanized mice.

Brook trout distributional response to unconventional oil and gas development: Landscape context matters.

We conducted a large-scale assessment of unconventional oil and gas (UOG) development effects on brook trout (Salvelinus fontinalis) distribution. We compiled 2231 brook trout collection records from the Upper Susquehanna River Watershed, USA. We used boosted regression tree (BRT) analysis to predict occurrence probability at the 1:24,000 stream-segment scale as a function of natural and anthropogenic landscape and climatic attributes. We then evaluated the importance of landscape context (i.e., pre-existing natural habitat quality and anthropogenic degradation) in modulating the effects of UOG on brook trout distribution under UOG development scenarios. BRT made use of 5 anthropogenic (28% relative influence) and 7 natural (72% relative influence) variables to model occurrence with a high degree of accuracy [Area Under the Receiver Operating Curve (AUC)=0.85 and cross-validated AUC=0.81]. UOG development impacted 11% (n=2784) of streams and resulted in a loss of predicted occurrence in 126 (4%). Most streams impacted by UOG had unsuitable underlying natural habitat quality (n=1220; 44%). Brook trout were predicted to be absent from an additional 26% (n=733) of streams due to pre-existing non-UOG land uses (i.e., agriculture, residential and commercial development, or historic mining). Streams with a predicted and observed (via existing pre- and post-disturbance fish sampling records) loss of occurrence due to UOG tended to have intermediate natural habitat quality and/or intermediate levels of non-UOG stress. Simulated development of permitted but undeveloped UOG wells (n=943) resulted in a loss of predicted occurrence in 27 additional streams. Loss of occurrence was strongly dependent upon landscape context, suggesting effects of current and future UOG development are likely most relevant in streams near the probability threshold due to pre-existing habitat degradation.

A detailed risk assessment of shale gas development on headwater streams in the Pennsylvania portion of the Upper Susquehanna River Basin, U.S.A.

The development of unconventional oil and gas (UOG) involves infrastructure development (well pads, roads and pipelines), well drilling and stimulation (hydraulic fracturing), and production; all of which have the potential to affect stream ecosystems. Here, we developed a fine-scaled (1:24,000) catchment-level disturbance intensity index (DII) that included 17 measures of UOG capturing all steps in the development process (infrastructure, water withdrawals, probabilistic spills) that could affect headwater streams (<200km2 in upstream catchment) in the Upper Susquehanna River Basin in Pennsylvania, U.S.A. The DII ranged from 0 (no UOG disturbance) to 100 (the catchment with the highest UOG disturbance in the study area) and it was most sensitive to removal of pipeline cover, road cover and well pad cover metrics. We related this DII to three measures of high quality streams: Pennsylvania State Exceptional Value (EV) streams, Class A brook trout streams and Eastern Brook Trout Joint Venture brook trout patches. Overall only 3.8% of all catchments and 2.7% of EV stream length, 1.9% of Class A streams and 1.2% of patches were classified as having medium to high level DII scores (>50). Well density, often used as a proxy for development, only correlated strongly with well pad coverage and produced materials, and therefore may miss potential effects associated with roads and pipelines, water withdrawals and spills. When analyzed with a future development scenario, 91.1% of EV stream length, 68.7% of Class A streams and 80.0% of patches were in catchments with a moderate to high probability of development. Our method incorporated the cumulative effects of UOG on streams and can be used to identify catchments and reaches at risk to existing stressors or future development.

Agent-Based Model Forecasts Aging of the Population of People Who Inject Drugs in Metropolitan Chicago and Changing Prevalence of Hepatitis C Infections.

People who inject drugs (PWID) are at high risk for blood-borne pathogens transmitted during the sharing of contaminated injection equipment, particularly hepatitis C virus (HCV). HCV prevalence is influenced by a complex interplay of drug-use behaviors, social networks, and geography, as well as the availability of interventions, such as needle exchange programs. To adequately address this complexity in HCV epidemic forecasting, we have developed a computational model, the Agent-based Pathogen Kinetics model (APK). APK simulates the PWID population in metropolitan Chicago, including the social interactions that result in HCV infection. We used multiple empirical data sources on Chicago PWID to build a spatial distribution of an in silico PWID population and modeled networks among the PWID by considering the geography of the city and its suburbs. APK was validated against 2012 empirical data (the latest available) and shown to agree with network and epidemiological surveys to within 1%. For the period 2010-2020, APK forecasts a decline in HCV prevalence of 0.8% per year from 44(± 2)% to 36(± 5)%, although some sub-populations would continue to have relatively high prevalence, including Non-Hispanic Blacks, 48(± 5)%. The rate of decline will be lowest in Non-Hispanic Whites and we find, in a reversal of historical trends, that incidence among non-Hispanic Whites would exceed incidence among Non-Hispanic Blacks (0.66 per 100 per years vs 0.17 per 100 person years). APK also forecasts an increase in PWID mean age from 35(± 1) to 40(± 2) with a corresponding increase from 59(± 2)% to 80(± 6)% in the proportion of the population >30 years old. Our studies highlight the importance of analyzing subpopulations in disease predictions, the utility of computer simulation for analyzing demographic and health trends among PWID and serve as a tool for guiding intervention and prevention strategies in Chicago, and other major cities.