Modelling uptake and transport of therapeutic agents through the lymphatic system.

The ability of the lymphatic network to absorb large molecules and bypass the first-pass liver metabolism makes it appealing as a delivery system for therapeutic substances. In most cases, the drug is injected into the subcutaneous tissue and must negotiate the tissue space, before being drained via the lymphatics. Tracking the transport of drug molecules through this route is challenging, and computational models of lymphatic drainage can play an important role in assessing the efficacy of a proposed delivery strategy. The three-dimensional computational model we present here of the peripheral lymphatic network and surrounding interstitium is informed by anatomical data, and quantifies the degree to which uptake and transit times are affected by drug particle size, physiological flow rates, and specifics of drug injection.

Development of an in situ procedure to evaluate the reticulo-rumen morphology of sheep selected for divergent methane emissions.

Published studies have shown that methane yield (g CH4/kg dry matter) from sheep is positively correlated with the size (volume and surface area) of the reticulo-rumen (RR) and the weight of its contents. However, the relationship between CH4 yield and RR shape has not been investigated. In this work, shape analysis has been performed on a data set of computerised tomography (CT) scans of the RR from sheep having high and low CH4 yields (n=20 and n=17, respectively). The three-dimensional geometries of the RRs were reconstructed from segmented scan data and split into three anatomical regions. An iterative fitting technique combining radial basis functions and principal component (PC) fitting was used to create a set of consistent landmarks which were then used as variables in a PC analysis to identify shape variation within the data. Significant size differences were detected for regions corresponding to the dorsal and ventral compartments between sheep with high and low CH4 yields. When the analysis was repeated after scaling the geometries to remove the effect of size, there was no significant shape variation correlating with CH4 yield. The results have demonstrated the feasibility of CT-based computational shape determination for studying the morphological characteristics of the RR and indicate that size, but not shape correlates with CH4 yield in sheep.

Carbon dioxide insufflation deflects airborne particles from an open surgical wound model.

BACKGROUND: Surgical site infections remain a significant burden on healthcare systems and may benefit from new countermeasures. AIM: To assess the merits of open surgical wound CO2 insufflation via a gas diffuser to reduce airborne contamination, and to determine the distribution of CO2 in and over a wound. METHODS: An experimental approach with engineers and clinical researchers was employed to measure the gas flow pattern and motion of airborne particles in a model of an open surgical wound in a simulated theatre setting. Laser-illuminated flow visualizations were performed and the degree of protection was quantified by collecting and characterizing particles deposited in and outside the wound cavity. FINDINGS: The average number of particles entering the wound with a diameter of <5µm was reduced 1000-fold with 10L/min CO2 insufflation. Larger and heavier particles had a greater penetration potential and were reduced by a factor of 20. The degree of protection was found to be unaffected by exaggerated movements of hands in and out of the wound cavity. The steady-state CO2 concentration within the majority of the wound cavity was >95% and diminished rapidly above the wound to an atmospheric level (∼0%) at a height of 25mm. CONCLUSION: Airborne particles were deflected from entering the wound by the CO2 in the cavity akin to a protective barrier. Insufflation of CO2 may be an effective means of reducing intraoperative infection rates in open surgeries.

An Experimental and Numerical Investigation of CO2 Distribution in the Upper Airways During Nasal High Flow Therapy.

Nasal high flow (NHF) therapy is used to treat a variety of respiratory disorders to improve patient oxygenation. A CO2 washout mechanism is believed to be responsible for the observed increase in oxygenation. In this study, experimentally validated Computational Fluid Dynamics simulations of the CO2 concentration within the upper airway during unassisted and NHF assisted breathing were undertaken with the aim of exploring the existence of this washout mechanism. An anatomically accurate nasal cavity model was generated from a CT scan and breathing was reproduced using a Fourier decomposition of a physiologically measured breath waveform. Time dependent CO2 profiles were obtained at the entrance of the trachea in the experimental model, and were used as simulation boundary conditions. Flow recirculation features were observed in the anterior portion of the nasal cavity upon application of the therapy. This causes the CO2 rich gas to vent from the nostrils reducing the CO2 concentration in the dead space and lowering the inspired CO2 volume. Increasing therapy flow rate increases the penetration depth within the nasal cavity of the low CO2 concentration gas. A 65% decrease in inspired CO2 was observed for therapy flow rates ranging from 0 to 60 L min(-1) supporting the washout mechanism theory.

A boundary-integral representation for biphasic mixture theory, with application to the post-capillary glycocalyx.

We describe a new boundary-integral representation for biphasic mixture theory, which allows us to efficiently solve certain elastohydrodynamic-mobility problems using boundary element methods. We apply this formulation to model the motion of a rigid particle through a microtube which has non-uniform wall shape, is filled with a viscous Newtonian fluid, and is lined with a thin poroelastic layer. This is relevant to scenarios such as the transport of small rigid cells (such as neutrophils) through microvessels that are lined with an endothelial glycocalyx layer (EGL). In this context, we examine the impact of geometry upon some recently reported phenomena, including the creation of viscous eddies, fluid flux into the EGL, as well as the role of the EGL in transmitting mechanical signals to the underlying endothelial cells.

The small non-structural protein NS2 of the autonomous parvovirus minute virus of mice is required for virus growth in murine cells.

Mutants of the autonomous parvovirus minute virus of mice (MVM) strains MVM(p) and MVM(i) that either fail to produce or produce a truncated NS2 protein, were deficient in the production of infectious virus and attained lower levels of viral DNA synthesis than wild-type virus following infection of a series of normal and transformed murine cell lines. Mutant virus growth and the levels of DNA replication were similar to those of wild-type virus in the rat, hamster and human lines tested. These results suggest that the requirement of NS2 for the growth of MVM is murine species-specific.