A human time dose response model for Q fever.

The causative agent of Q fever, Coxiella burnetii, has the potential to be developed for use in biological warfare and it is classified as a bioterrorism threat agent by the Centers for Disease Control and Prevention (CDC) and as a category B select agent by the National Institute of Allergy and Infectious Diseases (NIAID). In this paper we focus on the in-host properties that arise when an individual inhales a dose of C. burnetii and establish a human time-dose response model. We also propagate uncertainty throughout the model allowing us to robustly estimate key properties including the infectious dose and incubation period. Using human study data conducted in the 1950's we conclude that the dose required for a 50% probability of infection is about 15 organisms, and that one inhaled organism of C. burnetti can cause infection in 5% of the exposed population. In addition, we derive a low dose incubation period of 17.6 days and an extracellular doubling time of half a day. In conclusion this paper provides a framework for detailing the parameters and approaches that would be required for risk assessments associated with exposures to C. burnetii that might cause human infection.

A Model for Interstitial Drainage Through a Sliding Lymphatic Valve.

This study investigates fluid flow and elastic deformation in tissues that are drained by the primary lymphatic system. A model is formulated based on the Rossi hypothesis that states that the primary lymphatic valves, which are formed by overlapping endothelial cells around the circumferential lining of lymphatic capillaries, open in response to swelling of the surrounding tissue. Tissue deformation and interstitial fluid flow through the tissue are treated using the Biot equations of poroelasticity and, the fluid flux (into the interstitium) across the walls of the blood capillaries, is assumed to be linearly related to the pressure difference across the walls via a constant of proportionality (the vascular permeability). The resulting model is solved in a periodic domain containing one blood capillary and one lymphatic capillary starting from a configuration in which the tissue is undeformed. On imposition of a constant pressure difference between blood and lymphatic capillaries, the solutions are found to settle to a steady state. Given that the magnitude of pressure fluctuations in the lymphatic system is much smaller than this pressure difference between blood and lymph, it is postulated that the resulting steady-state solution gives a good representation of the state of the tissue under physiological conditions. The effects of changes to the Young's modulus of the tissue, the blood-lymphatic pressure difference, vascular permeability and valve dimensions on the steady state are investigated and discussed in terms of their effects on oedema in the context of age- and pregnancy-related changes to the body.

A model for fluid drainage by the lymphatic system.

This study investigates the fluid flow through tissues where lymphatic drainage occurs. Lymphatic drainage requires the use of two valve systems, primary and secondary. Primary valves are located in the initial lymphatics. Overlapping endothelial cells around the circumferential lining of lymphatic capillaries are presumed to act as a unidirectional valve system. Secondary valves are located in the lumen of the collecting lymphatics and act as another unidirectional valve system; these are well studied in contrast to primary valves. We propose a model for the drainage of fluid by the lymphatic system that includes the primary valve system. The analysis in this work incorporates the mechanics of the primary lymphatic valves as well as the fluid flow through the interstitium and that through the walls of the blood capillaries. The model predicts a piecewise linear relation between the drainage flux and the pressure difference between the blood and lymphatic capillaries. The model describes a permeable membrane around a blood capillary, an elastic primary lymphatic valve and the interstitium lying between the two.