Hereditary nonpolyposis colorectal cancer: an approach to the selection of candidates to genetic testing based on clinical and molecular characteristics

OBJECTIVE: Identification of clinical and molecular characteristics associated with constitutional MLH1 and MSH2 mutations and definition of a stepwise strategy for the selection of colorectal cancer (CRC) patients amenable to MLH1 and MSH2 genetic testing. METHODS: 90 unrelated CRC patients were initially selected on the basis of either familial or early onset occurrence of CRC. They were screened for the presence of constitutional MLH1 and MSH2 mutations and for microsatellite instability (MSI). RESULTS: 16 pathogenetic mutations (9 MLH1 and 7 MSH2) were identified in 41% of Amsterdam hereditary nonpolyposis colorectal cancer (HNPCC) families, 5% of suspected HNPCC families, and 14% of sporadic early-onset CRC patients. The presence of the mutations correlated with MSI, with early age of onset and proximal location of the tumor, and with the presence of some extracolonic tumors of the HNPCC spectrum and/or multiple tumors in the family. CONCLUSIONS: Evaluation of clinical and molecular characteristics is useful for the identification of candidates to MLH1 and MSH2 mutational analysis and allows the application of a rational approach to genetic testing.     

Economic evaluation of the familial cancer programme in Western Australia: predictive genetic testing for familial adenomatous polyposis and hereditary non-polyposis colorectal carcinoma

AIM: To evaluate costs and outcomes of genetic testing for familial colorectal cancer through services provided by Genetic Services of Western Australia (GSWA). METHODS: Costs and outcomes of predictive DNA-based testing for inherited colorectal cancers (CRC) were assessed, specifically for familial adenomatous polyposis (FAP) and hereditary non-polyposis CRC (HNPCC) using a decision-analysis model. Costs were assigned according to standards of care in Western Australia (WA). Cancer risks and the efficacy of surveillance on long-term outcomes were derived from the published literature. RESULTS: The cost-effectiveness of genetic testing was compared in first-degree relatives of known mutation carriers who have a 50% risk of carrying the mutated gene (intervention group) to individuals with the same risk but who do not undergo a genetic test (control subjects). Compared with control subjects undergoing the same high-level surveillance and surgery, the FAP and HNPCC intervention groups provided total savings of 13,390 US dollars and 14,783-15,460 per person (males-females), respectively. HPNCC mutation carriers also gained 1 CRC-free year. Compared to control subjects having only population surveillance, individuals in the FAP intervention group delayed the onset of CRC by 40 years for a net cost of 9,042 US dollars. Individuals in the HNPCC intervention group delayed the onset of CRC by 8 years at a net cost of 12,141 US dollars for males and 12,596 US dollars for females. CONCLUSIONS: Genetic testing for familial CRC in WA allows targeted surveillance for mutation carriers, which ensures the efficient use of resources and reduces cancer-related morbidity, if clinical recommendations for intervention are adopted.     

A STUDY OF THE CATASTROPHE AND THE CAVITATION FOR A SPHERICAL CAVITY IN HOOKE’S MATERIAL WITH 1/2 POISSON’S RATIO

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Effects of the number and distribution of fins on the storage characteristics of a cylindrical latent heat energy storage system: a numerical study

A numerical study of the effects of the number and distribution of fins on the storage characteristics of a cylindrical latent heat energy storage system (LHESS) was conducted. Due to the low thermal conductivity of phase change materials (PCMs) used in LHESS, fins were added to the system to increase the rate of heat transfer and charging. Finite elements were used to implement the developed numerical method needed to study and solve for the phase change heat transfer (melting of PCM) encountered in a LHESS during charging. The effective heat capacity method was applied in order to account for the large amount of latent energy stored during melting of the PCM and the moving interface between the solid and liquid phases. The effects of increasing the number and distribution of fins on the melting rate of the PCM were studied for configurations having between 0 and 27 fins for heat transfer fluid (HTF) velocities of 0.05 and 0.5?m/s. Results show that the overall heat transfer rate to the PCM increases with an increase in the number of fins irrespective of the HTF velocity. It was also observed that the total amount of energy stored after 12?h increases nearly linearly with the addition of fins up to 12 fins; further addition of fins increasing the total energy stored by ever smaller amounts.     

Laser marked shadowgraphy: a novel optical planar technique for the study of microbubbles and droplets

A novel combination of backlighting and glare point velocimetry and sizing (GPVS) is proposed to measure the size distribution of microbubbles (or microdroplets). This new technique, which we will call laser marked shadowgraphy, avoids sizing out-of-focus bubbles (or droplets) and the associated bias error. Compared to backlighting, this combination also improves the precision of the diameter measurement and allows void fraction measurements. Compared with GPVS, a more robust image processing is obtained. The applicability of the developed technique is demonstrated on a cloud of electrochemically generated hydrogen bubbles.     

An inexpensive and versatile technique for wide frequency range surface pressure measurements: an application for the study of turbulent buffeting of a square cylinder

This work presents the development of an inexpensive measurement technique based on miniature microphones for the measurement of pressure fluctuations in a wide frequency range, starting from infrasound up to several kilohertz. Special emphasis has been put on achieving accurate calibration of the system at very low frequencies and good agreement with reference measurements have been achieved at frequencies as low as 1 Hz, therefore opening new low-budget research possibilities in many fields of fluid mechanics. The measurement technique proposed is specially indicated when the number of simultaneous pressure measurements is high since the sensors used are inexpensive, contrarily to common research equipment. One particular area in which this technique results useful is bluff-body aerodynamics. As an example of the potential of the technique, the structural response of a finite-square cylinder immersed in a turbulent flow is studied.     

Flow-induced nucleation in polymer melts: a study of the GO model for pure and bimodal blends, under shear and extensional flow

We present a rapid rescaling algorithm that enables a systematic comparison between the Graham and Olmsted (GO) model for flow-induced nucleation of polymer melts (Graham and Olmsted, Phys Rev Lett 103(11): 115702, 2009) and direct nucleation rate measurements from a flowing polymer melt. We consider polymer melts consisting of pure long chains and bimodal blends of long and short chains. We simulate the nucleation rate for a wide range of free energy barriers under a wide range of applied shear and extensional flows by using an accelerated nucleation algorithm. We then develop a semi-analytical technique to compute efficiently the nucleation rate under flow for monodisperse melts. We extend our approach to bimodal blends using a method to rescale reference data. This allows us to compare the GO model to experimentally measured nucleation rates at several different temperatures. The GO model is able to consistently account for the effect of temperature on flow-induced nucleation. Our modelling will also contribute to the derivation of computationally inexpensive molecular models of flow-induced nucleation in polymers.     

Comparative study of lattice‐Boltzmann and finite volume methods for the simulation of laminar flow through a 4:1 planar contraction

In the present paper, a comparative study of numerical solutions for Newtonian fluids based on the lattice‐Boltzmann method (LBM) and the classical finite volume method (FVM) is presented for the laminar flow through a 4:1 planar contraction at a Reynolds number of value one, Re=1. In this study, the stress field for LBM is directly obtained from the distribution function. The calculations of the stress based on the FVM‐data use the evaluations of velocity gradients with finite differences. The stress field for both LBM and FVM is expressed in the present study in terms of the shear stress and the first normal stress difference. The lateral and axial profiles of the velocity, the shear stress and the first normal stress difference for both methods are investigated. It is shown that the LBM results for the velocity and the stresses are in excellent agreement with the FVM results. Copyright © 2004 John Wiley & Sons, Ltd.     

A study of the strength characteristics of marine sediments utilizing a submersible: A. L. Inderbitzen and F. SimpsonASTM Spec. Techn. Publ. No. STP 501, 204–215 (1972)

One of the tasks of the Lockheed Missiles and Space Company's submersible Deep Quest has been to obtain detailed information on the strength characteristics of the sea floor. Continuing projects, carried out with a corer and a vane shear machine mounted on the submersible, are a comparison of in-place and laboratory vane shear strength values and an investigation of the lateral and vertical variability of in-place shear strength. The area being investigated for these projects is approximately 13 nautical miles southwest of San Diego, Calif., on the floor of the San Diego Trough at a depth of 4050 ft. Because the projects are still incomplete, no definitive conclusions can be made. However, initial results indicate inconsistencies in the difference between in-place and laboratory vane shear strength values. Lateral variability between in-place vane shear strength measurements does not appear to be related to distance test locations. Vertical variability in in-place vane shear strength values appears to decrease with depth into the sediment.