Simulation and development of a mock circulation loop with variable compliance

Heart disease is attributed as the highest cause of death in the world. Although this could be alleviated by heart transplantation, there is a chronic shortage of donor hearts and so mechanical solutions are being considered. Currently, many Ventricular Assist Devices (VADs) are being developed worldwide in an effort to increase life expectancy and quality of life for end stage heart failure patients. Current pre-clinical testing methods for VADs involve laboratory testing using Mock Circulation Loops (MCLs), and in vivo testing in animal models. The research and development of highly accurate MCLs is vital to the continuous improvement of VAD performance. The first objective of this study was to develop and validate a mathematical model of a MCL. This model could then be used in the design and construction of a variable compliance chamber to improve the performance of an existing MCL as well as form the basis for a new miniaturised MCL. An extensive review of literature was carried out on MCLs and mathematical modelling of their function. A mathematical model of a MCL was then created in the MATLAB/SIMULINK environment. This model included variable features such as resistance, fluid inertia and volumes (resulting from the pipe lengths and diameters); compliance of Windkessel chambers, atria and ventricles; density of both fluid and compressed air applied to the system; gravitational effects on vertical columns of fluid; and accurately modelled actuators controlling the ventricle contraction. This model was then validated using the physical properties and pressure and flow traces produced from a previously developed MCL. A variable compliance chamber was designed to reproduce parameters determined by the mathematical model. The function of the variability was achieved by controlling the transmural pressure across a diaphragm to alter the compliance of the system. An initial prototype was tested in a previously developed MCL, and a variable level of arterial compliance was successfully produced; however, the complete range of compliance values required for accurate physiological representation was not able to be produced with this initial design. The mathematical model was then used to design a smaller physical mock circulation loop, with the tubing sizes adjusted to produce accurate pressure and flow traces whilst having an appropriate frequency response characteristic. The development of the mathematical model greatly assisted the general design of an in vitro cardiovascular device test rig, while the variable compliance chamber allowed simple and real-time manipulation of MCL compliance to allow accurate transition between a variety of physiological conditions. The newly developed MCL produced an accurate design of a mechanical representation of the human circulatory system for in vitro cardiovascular device testing and education purposes. The continued improvement of VAD test rigs is essential if VAD design is to improve, and hence improve quality of life and life expectancy for heart failure patients.

3D lung and rib cage reconstruction using low dose CT scans of adolescent idiopathic scoliosis pre and post anterior thoracoscopic correction

Adolescent Idiopathic Scoliosis (AIS) has been associated with reduced pulmonary function believed to be due to a restriction of lung volume by the deformed thoracic cavity. A recent study by our group examined the changes in lung volume pre and post anterior thoracoscopic scoliosis correction using pulmonary function testing (1), however the anatomical changes in ribcage shape and left/right lung volume after thoracoscopic surgery which govern overall respiratory capacity are unknown. The aim of this study was to use 3D rendering from CT scan data to compare lung and ribcage anatomical changes from pre to two years post thoracoscopic anterior scoliosis correction. The study concluded that 3D volumetric reconstruction from CT scans is a powerful means of evaluating changes in pulmonary and thoracic anatomy following surgical AIS correction. Most likely, lung volume changes following thoracoscopic scoliosis correction are multifactorial and affected by changes in height (due to residual growth), ribcage shape, diaphragm positioning, Cobb angle correction in the thoracic spine. Further analysis of the 3D reconstructions will be performed to assess how each of these factors affect lung volume in this patient cohort.

The effect of extent of local resection on patterns of disease progression in malignant pleural mesothelioma

Background We sought to determine whether or not there are differences in disease progression after radical or nonradical (debulking) surgical procedures for malignant pleural mesothelioma. Methods Over a 49-month period, 132 patients with malignant pleural mesothelioma underwent surgery. Fifty-three underwent extrapleural pneumonectomy and 79 underwent nonradical procedures. Time to evidence of clinical disease progression was recorded, as was the site(s) of that disease. Results One-hundred nineteen patients were evaluable, of which 59% (22 radical; 48 nonradical) had disease progression. Overall 30-day mortality was 8.5% (7.5% radical; 9% nonradical). The median time to overall disease progression was considerably longer after extrapleural pneumonectomy than debulking surgery (319 days vs 197 days, p = 0.019), as was the time to local disease progression (631 days vs 218 days, p = 0.0018). There was no preponderance of earlier stage disease in the radical surgery group. There was a trend toward prolonged survival in those undergoing radical surgery, but no significant difference between the groups (497 days vs 324 days, p = 0.079). In those who had extrapleural pneumonectomy, time-to-disease progression significantly decreased with N2 disease compared with N0/1 involvement (197 days vs 358 days, p = 0.02). Conclusions Extrapleural pneumonectomy may be preferable to debulking surgery in malignant pleural mesothelioma to delay disease progression and give greater control of local disease. Involvement of N2 nodes is associated with accelerated disease progression and is therefore a contraindication to extrapleural pneumonectomy. © 2004 by The Society of Thoracic Surgeons.

The invasive and metastatic properties of hormone-independent but hormone-responsive variants of MCF-7 human breast cancer cells

We have previously isolated a series of MCF-7 human breast cancer cell variants which no longer require estrogen-supplementation for tumor growth in nude mice (Clarke et al. Proc Natl Acad Sci USA 86: 3649-3653, 1989). We now report that these hormone-independent and hormone-responsive variants (MIII, MCF7/LCC1) can invade locally from solid mammary fat pad tumors, and produce primary extensions on the surface of intraperitoneal structures including liver, pancreas, and diaphragm. Both lymphatic and hematogenous dissemination are observed, resulting in the establishing of pulmonary, bone, and renal metastases. The pattern of metastasis by MIII and MCF7/LCC1 cells closely resembles that frequently observed in breast cancer patients, and provides the first evidence of metastasis from MCF-7 cells growing in vivo without supplementary estrogen. The interexperimental incidence of metastases, and the time from cell inoculation to the appearance of metastatic disease are variable. The increased metastatic potential is not associated with an increase in either the level of laminin attachment, laminin receptor mRNA expression, or secreted type IV collagenolytic activity. We also did not detect a significant decrease in the steady-state mRNA levels of the metastasis inhibitor nm23 gene. However, when growing without estrogen in vitro, MCF7/LCC1 cells produce elevated levels of the estrogen-inducible cathepsin D enzyme.

Behaviour of corrugated steel roof cladding under combined wind uplift and racking

During high wind events, crest-fixed profiled steel roof claddings in low-rise buildings can be subjected to combined cyclic wind uplift and in-plane racking (shear) forces. Static and cyclic tests of corrugated steel roof claddings were carried out to investigate the effect of in-plane racking force on the uplift strength, in particular, in relation to the fatigue cracking commonly observed under cyclic wind uplift. The presence of racking force appeared to have insignificant effect on the static and cyclic wind uplift strength. It may therefore be possible to include the diaphragm strength of these claddings in the design of low-rise buildings in a similar manner to valley-fixed claddings. This may lead to a reduction in bracing requirements.

Shear strength and stiffness of crest-fixed steel claddings

Diaphragm action of crest-fixed profiled steel claddings is present in low-rise buildings whether the designer acknowledges it or not. For the designers to take advantage of the diaphragm strength of the crest-fixed steel claddings in the design of low-rise buildings in a similar manner to valley-fixed claddings, and to design the buildings based on the true behaviour rather than the assumed behaviour, shear/racking behaviour of the three trapezoidal and corrugated steel claddings commonly used at present was investigated using large scale experiments. Crest-fixed claddings (up to a maximum size of 6 x 6.2m) with different aspect ratio and fastening systems were tested to failure, based on which suitable shear strength and stiffness values have been proposed for these claddings as they are used at present. A simple analytical model combined with basic connection data from small scale experiments was used to predict the shear strength of tested panels. Currently attempts are being made to develop general design formulae to determine shear strength and stiffness of crest-fixed steel claddings...