The treatment of hydrocephalus often involves the placement of a shunt catheter into the cerebrospinal ventricular space, though such ventricular catheters often fail by tissue obstruction. While diverse cell types contribute to the obstruction, astrocytes are believed to contribute to late catheter failure that can occur months after shunt insertion. Using in vitro microfluidic cultures of astrocytes, we show that applied fluid shear stress leads to a decrease of cell confluency and the loss of their typical stellate cell morphology. Furthermore, we show that astrocytes exposed to moderate shear stress for an extended period of time are detached more easily upon suddenly imposed high fluid shear stress. In light of these findings and examining the range of values of wall shear stress in a typical ventricular catheter through computational fluid dynamics (CFD) simulation, we find that the typical geometry of ventricular catheters has low wall shear stress zones that can favour the growth and adhesion of astrocytes, thus promoting obstruction. Using high-precision direct flow visualization and CFD simulations, we discover that the catheter flow can be formulated as a network of Poiseuille flows. Based on this observation, we leverage a Poiseuille network model to optimize ventricular catheter design such that the distribution of wall shear stress is above a critical threshold to minimize astrocyte adhesion and growth. Using this approach, we also suggest a novel design principle that not only optimizes the wall shear stress distribution but also eliminates a stagnation zone with low wall shear stress, which is common to current ventricular catheters.
Tendinopathy is a debilitating disease that causes as much as 30% of all musculoskeletal consultations. Existing treatments for tendinopathy have variable efficacy, possibly due to incomplete characterization of the underlying pathophysiology. Mechanical load can have both beneficial and detrimental effects on tendon, as the overall tendon response depends on the degree, frequency, timing, and magnitude of the load. The clinical continuum model of tendinopathy offers insight into the late stages of tendinopathy, but it does not capture the subclinical tendinopathic changes that begin before pain or loss of function. Small animal models that use high tendon loading to mimic human tendinopathy may be able to fill this knowledge gap. The goal of this review is to summarize the insights from in-vivo animal studies of mechanically
The Blasingame typecurve in Fekete’s Rate Transient Analysis (RTA) software has been used at Santos to increase the understanding and integration of well and reservoir data; however, the authors have discovered that in some cases the tool produced anomalous results, such as permeability being too low. The potential consequence of this was incorrectly writing off reserves or making projects (in particular compression projects) fail economic tests. After testing various hypotheses, a simple yet unorthodox solution was only discovered in a field where the anomaly was more profound, and required integrating geology and geophysics to explain it. This solution has since been applied in RTA models across numerous other fields, and it has improved the quality and confidence of these models. The solution was the realisation that in many cases the accessed gas in place (GIP) increased over time, but the underlying model in RTA assumes a single tank, linear P/z. Matching the RTA model with the initial reservoir pressure and final accessed GIP results in over-predicting the reservoir pressures, resulting in an artificially low permeability. The authors discovered that the appropriate well and reservoir parameters could be obtained by matching the late time data using a lower initial reservoir pressure value corresponding to when the well had accessed the final GIP volume but not the initial reservoir pressure. This step was initially regarded to be counter-intuitive as the initial pressure is a measured property. Numerous reviews have endorsed this methodology, which is now being used as a standard at Santos.
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