A system of ordinary differential equations is formulated to describe the pathogenesis of HIV infection, wherein certain features that have been shown to be important by recent experimental research are incorporated in the model. These include the role of CD4+ memory cells that serve as a major reservoir of latently infected cells, a critical role for T-helper cells in the generation of CD8 memory cells capable of efficient recall response, and stimulation by antigens other than HIV. A stability analysis illustrates the capability of this model in admitting multiple locally asymptotically stable (locally a.s.) off-treatment equilibria. We show that this more biologically detailed model can exhibit the phenomenon of transient viremia experienced by some patients on therapy with viral load levels suppressed below the detection limit. We also show that the loss of CD4+ T-cell help in the generation of CD8+ memory cells leads to larger peak values for the viral load during transient viremia. Censored clinical data is used to obtain parameter estimates. We demonstrate that using a reduced set of 16 free parameters, obtained by fixing some parameters at their population averages, the model provides reasonable fits to the patient data and, moreover, that it exhibits good predictive capability. We further show that parameter values obtained for most clinical patients do not admit multiple locally a.s off-treatment equilibria. This suggests that treatment to move from a high viral load equilibrium state to an equilibrium state with a lower (or zero) viral load is not possible for these patients.
Differences in nasal anatomy among human subjects may cause significant differences in respiratory airflow patterns and subsequent dosimetry of inhaled gases and particles in the respiratory tract. This study used computational fluid dynamics (CFD) to study inter-individual differences in nasal airflow among four healthy individuals. Magnetic resonance imaging (MRI) scans were digitized and nasal-surface-area-to-volume ratios (SAVR) were calculated for 15 adults. Two males and two females, representative of the range of SAVR values, were selected for flow analysis. Nasal CFD models were constructed for each subject by a semi-automated process that provided input to a commercial mesh generator to generate structured hexahedral meshes (Gambit, Fluent, Inc., Lebanon, NH, USA). Steady-state inspiratory laminar airflow at 15 L/min was calculated using commercial CFD software (FIDAP, Fluent, Inc., Lebanon, NH, USA). Streamline patterns, velocities, and helicity values were compared. In all subjects, the majority of flow passed through the middle and ventral regions of the nasal passages; however, the amount and location of swirling flow differed among individuals. Cross-sectional flow allocation analysis also indicated inter-individual differences. Laboratory water-dye experiments confirmed streamlines and velocity magnitudes predicted by the computational model. These results suggest that significant inter-individual differences exist in bulk airflow patterns in the nose.
A system of ordinary differential equations is formulated to describe the pathogenesis of HIV infection, wherein certain important features that have been shown important by recent experimental research are incorporated in the model. These include the role of CD4+ memory cells that serve as a major reservoir of latently infected cells, a critical role for T-helper cells in the generation of CD8 memory cells capable of efficient recall response, and stimulation by antigens other than HIV. A stability analysis illustrates the capability of this model in admitting multiple locally asymptotically stable (locally a.s.) off-treatment equilibria. The phenomenon of "viral blips" experienced by some patients on therapy with viral load levels suppressed below the detection limit is also investigated. Censored clinical data is used to demonstrate that this model provides reasonable fits to all the patient data available for this study and, moreover, that it exhibits impressive predictive capability. Public reporting burden for the collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.