Options for change in the Australian cervical cancer screening program in context of HPV detection and vaccination

Introduction:
Cervical cancer screening has been implemented for over a decade in Australia and has significantly reduced the mortality and morbidity of the disease. The emergence of new technologies for cervical cancer, such as the Human Papillomavirus (HPV) vaccine and DNA testing has encouraged debate regarding the effective use of resources in cervical cancer prevention. The present study evaluates the cost-effectiveness, from a health sector perspective, of various screening strategies in the era of these new technologies.

Methods:
A stochastic epidemiological model using a discrete event and continuous algorithm was developed to describe the natural history of cervical cancer. By allowing one member of the cohort into the model at a time, this micro-simulation model encompasses the characteristics of heterogeneity and can track individual life histories. To evaluate the cost-effectiveness of the HPV vaccine a Markov model was built to simulate the effect on the incidence of HPV and subsequent cervical cancer. A number of proposed screening strategies were evaluated with the stochastic model for the application of HPV DNA testing, with changes in the screening interval and target population. Health outcomes were measured by Disability-Adjusted Life-Years (DALYs), adjusted for application within an evaluation setting (i.e. the mortality component of the DALY was adjusted by a disability weight when early mortality due to cervical cancer is avoided). Costs in complying with the Australian updated guidelines were assessed by pathway analysis to estimate the resources associated with cervical cancer and its pre-cancerous lesion treatment. Sensitivity analyses were performed to investigate the key parameters that influenced the cost-effectiveness results.

Results:
Current practice has already brought huge health gain by preventing more than 4,000 deaths and saving more than 86,000 life-years in a cohort of a million women. Any of the alternative screening strategies alter the total amount of health gain by a small margin compared to current practice. The results of incremental analyses of the alternative screening strategies compared to current practice suggest the adoption of the HPV DNA test as a primary screening tool every 3 years commencing at age 18, or the combined pap smear/HPV test every 3 years commencing at age 25, are more costly than current practice but with reasonable ICERs (AUD$1,810 per DALY and AUD$18,600 per DALY respectively). Delaying commencement of Pap test screening to age 25 is less costly than current practice, but involves considerable health loss. The sensitivity analysis shows, however, that the screening test accuracy has a significant impact on these conclusions. Threshold analysis indicates that a sensitivity ranging from 0.80 to 0.86 for the combined test in women younger than 30 is required to produce an acceptable incremental cost-effectiveness ratio.

Conclusions:
The adoption of HPV and combined test with an extended screening interval is more costly but affordable, resulting in reasonable ICERs. They appear good value for money for the Australian health care system, but need more information on test accuracy to make an informed decision. Potential screening policy change under current Australian HPV Vaccination Program is current work in progress. A Markov model is built to simulate the effect on the incidence of HPV and subsequent cervical cancer. Adoption of HPV DNA test as a primary screening tool in the context of HPV vaccination is under evaluation.

A finite element simulation of micro-mechanical frictional behaviour in metal forming

Friction is a critical factor for sheet metal forming (SMF). The Coulomb friction model is usually used in most finite element (FE) simulation for SMF. However, friction is a function of the local contact deformation conditions, such as local pressure, roughness and relative velocity. Frictional behaviour between contact surfaces can be based on three cases: boundary, hydrodynamic and mixed lubrication. In our microscopic friction model based on the finite element method (FEM), the case of dry contact between sheet and tool has been considered. In the view of microscopic geometry, roughness depends upon amplitude and wavelength of surface asperities of sheet and tool. The mean pressure applied on the surface differs from the pressure over the actual contact area. The effect of roughness (microscopic geometric condition) and relative speed of contact surfaces on friction coefficient was examined in the FE model for the microscopic friction behaviour. The analysis was performed using an explicit FE formulation. In this study, it was found that the roughness of deformable sheet decreases during sliding and the coefficient of friction increases with increasing roughness of contact surfaces. Also, the coefficient of friction increases with the increase of relative velocity and adhesive friction coefficient between contact surfaces.

Finite element simulation of deformation processes of micro-components

The aim of this paper is to improve the understanding of deformation of micro medical needle and thread during assembly and then to develop an economical and flexible deformation method. Therefore, the swaging process is computationally simulated with the finite element method in this paper. A commercially available explicit nonlinear finite element analysis code, LS-Dyna, is used to model the 3-D deformation and contact problem. As the firmness of the assembly on the needle depends on the contact force and friction, the contact and the slide between the needle and thread are taken into account in the simulation. The general surface-to-surface contact algorithm (STS) is used to simulate the contact. The paper provides an insight into the deformation of the micro products.

Numerical simulation of the static recrystalization at micro shear bands

The main aim of this work is application of the developed cellular automata (CA) model to investigate influence of the micro shear bands that are present in the heavily deformed material on the static recrystallization. This initial work is the results of recent experimental analyses indicating that the micro shear bands are preferred sites for nucleation of the recrystallization. The procedure of creation of the initial microstructure with features such as grains and micro shear bands as well as basis of the developed CA code for the static recrystallization are also presented in the paper. Finally, the simulation results obtained from different recrystallization temperatures for the microstructures with and without micro shear bands are compared with each other and differences are discussed.

Simulation of dynamic recrystallization using random grid cellular automata

Computer simulation is a powerful tool to predict microstructure and its evolution in dynamic and post-dynamic recrystallization. CAFE proposed as an appropriate approach by combining finite element (FE) method and cellular automata (CA) for recrystallization simulation. In the current study, a random grid cellular automaton (CA), as micro-scale model, based on finite element (FE), as macro-scale method, has been used to study initial and evolving microstructural features; including nuclei densities, dislocation densities, grain size and grain boundary movement during dynamic recrystallization in a C-Mn steel. An optimized relation has been established between mechanical variables and evolving microstructure features during recrystallization and grain growth. In this model, the microstructure is defined as cells located within grains and grain boundaries while dislocations are randomly dispersed throughout microstructure. Changes of dislocation density during deformation are described considering hardening, recovery and recrystallization. Recrystallization is assumed to initiate near grain boundaries and nucleation rate was considered constant (site-saturated condition). The model produced a mathematical formulation which captured the initial and evolving microstructural entities and linked their effects to measurable macroscopic variables (e.g. stress).

Simulation of a novel piezoelectric energy harvester

This paper focuses on a novel piezoelectric energy harvester for nanofiber PVDF to capture energy from vibration environment. A Resembling CMOS(R-CMOS) circuit consisting of two pMOS transistors and two nMOS transistors is presented, which can greatly increase the energy efficiency and reduce the power dissipation tremendously. Meanwhile, the novel harvester supplies smooth direct current. Simulation result of MULTISIM has shown that by using this novel piezoelectric energy harvester the input voltage (5v) can be rectified to be an output voltage (4.24v). The voltage conversion rate of the novel harvester is as high as 84.8% which is much larger than the rate of traditional rectifier circuit. Its potential application is in micro sensors, wireless transducers, and sensor networks.

Ethical trust and social moral norms simulation : a bio-inspired agent-based modelling approach

The understanding of the micro-macro link is an urgent need in the study of social systems. The complex adaptive nature of social systems adds to the challenges of understanding social interactions and system feedback and presents substantial scope and potential for extending the frontiers of computer-based research tools such as simulations and agent-based technologies. In this project, we seek to understand key research questions concerning the interplay of ethical trust at the individual level and the development of collective social moral norms as representative sample of the bigger micro-macro link of social systems. We outline our computational model of ethical trust (CMET) informed by research findings from trust, machine ethics and neural science. Guided by the CMET architecture, we discuss key implementation ideas for the simulations of ethical trust and social moral norms.

Three-dimensional numerical simulation of blood flow in mouse aortic arch around atherosclerotic plaques

Atherosclerosis is a progressive disease, involving the build-up of lipid streaks in artery walls, leading to plaques. Understanding the development of atherosclerosis and plaque vulnerability is critically important since plaque rupture can result in heart attack or stroke. Plaques can be divided into two distinct types: those likely to rupture (vulnerable) or less likely to rupture (stable). In the last decade, researchers have been interested in studying the influence of the mechanical effects (blood shear stress, pressure forces and structural stress) on the plaque formation, progression and rupture processes but no general agreement has been found. The purpose of the present work is to include more realistic conditions for the numerical calculations of the blood flow by implementing real geometries with plaques in the numerical model. Hemodynamical parameters are studied in both diseased and healthy configurations. The healthy configuration is obtained by removing numerically the plaques from three dimensional geometries obtained by micro-computed tomography. A new hemodynamical parameter is also introduced to relate the location of plaques to the characteristics of the flow in the healthy configuration. © 2014 .

Design and simulation of a low-actuation-voltage MEMS switch

This paper presents a low-actuation-voltage micro-electromechanical system (MEMS) capacitive shunt switch which has a very large bandwidth (4 GHz to 24 GHz). In this work, the isolation of MEMS switch is improved by adding two short high impedance transmission lines at the beginning and end of a coplanar waveguide (CPW). Simulating the switch demonstrates that a return loss (S11) is less than -26 dB for the entire frequency band, and perfect matching at 20 GHz in upstate position. A ramp dual pulse driver is also designed for reducing the capacitive charge injection for considering the reliability of the switch. The simulation results show that the shifting of voltage due to the capacitive charge is reduced by more than 35% of the initial value. Finally, the dynamic behavior of the MEMS switch is simulated by modal analysis and using CoventorWare to calculate the natural frequencies of the switch and its mode shapes. The switching ON and OFF time are 4.48 and 2.43 μs, respectively, with an actuation voltage of less than 15 V.

Multi-scale simulation using a hybrid mass-spring system and finite element model

Ply-scale finite element (FE) models are widely used to predict the performance of a composite structure based on material properties of individual plies. When simulating damage, these models neglect microscopic fracture processes which may have a significant effect on how a crack progresses within and between plies of a multidirectional laminate. To overcome this resolution limitation a multi-scale modelling technique is employed to simulate the effect micro-scale damage events have on the macro-scale response of a structure. The current paper discusses the development and validation of a hybrid mass-spring system and finite element modelling technique for multi-scale analysis. The model developed here is limited to elastic deformations; however, it is the first key step towards an efficient multi-scale damage model well suited to simulation of fracture in fibre reinforced composite materials. Various load cases have been simulated using the model developed here which show excellent accuracy compared to analytical and FE results. Future work is discussed, including extension of the model to incorporate damage modelling.

Size effects in micro cup drawing

Experimental studies into the effect of blank thickness on the deep drawing response of the coarse-grained and ultrafine-grained copper demonstrated the occurrence of a size effect: the dependence of the maximum load and the limit drawing ratio on the blank thickness in sub-millimetre range. A dislocation based constitutive model taking into account the thickness effects was used for numerical simulations of the process. It was demonstrated that the occurrence of the blank thickness effect is governed by the ratio of the blank thickness t to the grain size D of the material. Critical values of the t/. D ratio below which the size effect comes to bearing were determined. The obtained results can be seen as a demonstration of more general suitability of the model developed for predicting microforming operations with full account of the specimen or work-piece dimensions.

Study of KJ-66 micro gas turbine compressor: steady and unsteady Reynolds-averaged Navier-Stokes approach

Numerical study on the compressor stage of a KJ-66 micro gas turbine was conducted in this paper through both steady and unsteady Reynolds-averaged Navier–Stokes. The study was conducted for the numerical prediction of micro gas turbine compressor performance at various operation conditions, with special attention given to the transient flow behaviors during compressor operation. The numerical results showed reasonable agreements with experimental data while providing predictions for the charting of compressor performance map at various operation speeds. The simulation results indicated that the increase of operation speed from 80 k r/min to 117 k r/min would leads to an increased peak total pressure ratio from 1.54 to 1.96, while decreasing the peak adiabatic efficiency from 0.73 to 0.55. This paper also provided discussion on details of transient flow field within the compressor stage as well as demonstrated the smooth flow transition through rotor–stator interactions.

Towards simulation of flapping wings using immersed boundary method

In this work the immersed boundary method is applied to simulate incompressible turbulent flows around stationary and moving objects. The goal is to demonstrate that the immersed boundary technique along with a large eddy simulation approach is capable of simulating the effect of the so-called leading edge vortex (LEV), which can be found in flapping wing aerodynamics. A Lagrangian method is used to approximatethe solutions in the freshly cleared cells that lay within solid objects at one time step and emerge into fluid domain at the next time step. Flow around a stationary cylinder at ReD D 20, 40, and 3900 (based oncylinder diameter D) is first studied to validate the immersed boundary solver based on the finite volume scheme using a staggered grid. Then, a harmonically oscillating cylinder at ReD D 10 000 is considered to test the solver after the Lagrangian method is implemented to interpolate the solution in the freshly cleared cells. Finally, this approach is used to study flows around a stationary flat-plate at several angles of attack and fast pitching flat-plate. The rapidly pitching plate creates a dynamic LEV that can be used to improve the efficiency of flapping wings of micro air vehicle and to determine the optimum flapping frequency.