A biophysical model of atrial fibrillation ablation: what can a surgeon learn from a computer model?

AIMS: Surgical ablation procedures for treating atrial fibrillation have been shown to be highly successful. However, the ideal ablation pattern still remains to be determined. This article reports on a systematic study of the effectiveness of the performance of different ablation line patterns. METHODS AND RESULTS: This study of ablation line patterns was performed in a biophysical model of human atria by combining basic lines: (i) in the right atrium: isthmus line, line between vena cavae and appendage line and (ii) in the left atrium: several versions of pulmonary vein isolation, connection of pulmonary veins, isthmus line, and appendage line. Success rates and the presence of residual atrial flutter were documented. Basic patterns yielded conversion rates of only 10-25 and 10-55% in the right and the left atria, respectively. The best result for pulmonary vein isolation was obtained when a single closed line encompassed all veins (55%). Combination of lines in the right/left atrium only led to a success rate of 65/80%. Higher rates, up to 90-100%, could be obtained if right and left lines were combined. The inclusion of a left isthmus line was found to be essential for avoiding uncommon left atrial flutter. CONCLUSION: Some patterns studied achieved a high conversion rate, although using a smaller number of lines than those of the Maze III procedure. The biophysical atrial model is shown to be effective in the search for promising alternative ablation strategies.

Learning through Computer Model Improvisations

It has been convincingly argued that computer simulation modeling differs from traditional science. If we understand simulation modeling as a new way of doing science, the manner in which scientists learn about the world through models must also be considered differently. This article examines how researchers learn about environmental processes through computer simulation modeling. Suggesting a conceptual framework anchored in a performative philosophical approach, we examine two modeling projects undertaken by research teams in England, both aiming to inform flood risk management. One of the modeling teams operated in the research wing of a consultancy firm, the other were university scientists taking part in an interdisciplinary project experimenting with public engagement. We found that in the first context the use of standardized software was critical to the process of improvisation, the obstacles emerging in the process concerned data and were resolved through exploiting affordances for generating, organizing, and combining scientific information in new ways. In the second context, an environmental competency group, obstacles were related to the computer program and affordances emerged in the combination of experience-based knowledge with the scientists' skill enabling a reconfiguration of the mathematical structure of the model, allowing the group to learn about local flooding.

Development of an erythropoietin prescription simulator to improve abilities for the prescription of erythropoietin stimulating agents: is it feasible?

BACKGROUND: The increasing use of erythropoietins with long half-lives and the tendency to lengthen the administration interval to monthly injections call for raising awareness on the pharmacokinetics and risks of new erythropoietin stimulating agents (ESA). Their pharmacodynamic complexity and individual variability limit the possibility of attaining comprehensive clinical experience. In order to help physicians acquiring prescription abilities, we have built a prescription computer model to be used both as a simulator and education tool. METHODS: The pharmacokinetic computer model was developed using Visual Basic on Excel and tested with 3 different ESA half-lives (24, 48 and 138 hours) and 2 administration intervals (weekly vs. monthly). Two groups of 25 nephrologists were exposed to the six randomised combinations of half-life and administration interval. They were asked to achieve and maintain, as precisely as possible, the haemoglobin target of 11-12 g/dL in a simulated naïve patient. Each simulation was repeated twice, with or without randomly generated bleeding episodes. RESULTS: The simulation using an ESA with a half-life of 138 hours, administered monthly, compared to the other combinations of half-lives and administration intervals, showed an overshooting tendency (percentages of Hb values > 13 g/dL 15.8 ± 18.3 vs. 6.9 ± 12.2; P < 0.01), which was quickly corrected with experience. The prescription ability appeared to be optimal with a 24 hour half-life and weekly administration (ability score indexing values in the target 1.52 ± 0.70 vs. 1.24 ± 0.37; P < 0.05). The monthly prescription interval, as suggested in the literature, was accompanied by less therapeutic adjustments (4.9 ± 2.2 vs. 8.2 ± 4.9; P < 0.001); a direct correlation between haemoglobin variability and number of therapy modifications was found (P < 0.01). CONCLUSIONS: Computer-based simulations can be a useful tool for improving ESA prescription abilities among nephrologists by raising awareness about the pharmacokinetic characteristics of the various ESAs and recognizing the factors that influence haemoglobin variability.

Effect of humeral stem design on humeral position and range of motion in reverse shoulder arthroplasty.

PURPOSE: The impacts of humeral offset and stem design after reverse shoulder arthroplasty (RSA) have not been well-studied, particularly with regard to newer stems which have a lower humeral inclination. The purpose of this study was to analyze the effect of different humeral stem designs on range of motion and humeral position following RSA. METHODS: Using a three-dimensional computer model of RSA, a traditional inlay Grammont stem was compared to a short curved onlay stem with different inclinations (155°, 145°, 135°) and offset (lateralised vs medialised). Humeral offset, the acromiohumeral distance (AHD), and range of motion were evaluated for each configuration. RESULTS: Altering stem design led to a nearly 7-mm change in humeral offset and 4 mm in the AHD. Different inclinations of the onlay stems had little influence on humeral offset and larger influence on decreasing the AHD. There was a 10° decrease in abduction and a 5° increase in adduction between an inlay Grammont design and an onlay design with the same inclination. Compared to the 155° model, the 135° model improved adduction by 28°, extension by 24° and external rotation of the elbow at the side by 15°, but led to a decrease in abduction of 9°. When the tray was placed medially, on the 145° model, a 9° loss of abduction was observed. CONCLUSIONS: With varus inclination prostheses (135° and 145°), elevation remains unchanged, abduction slightly decreases, but a dramatic improvement in adduction, extension and external rotation with the elbow at the side are observed.

Computer-Aided Business Model Design

There is a lack of dedicated tools for business model design at a strategic level. However, in today's economic world the need to be able to quickly reinvent a company's business model is essential to stay competitive. This research focused on identifying the functionalities that are necessary in a computer-aided design (CAD) tool for the design of business models in a strategic context. Using design science research methodology a series of techniques and prototypes have been designed and evaluated to offer solutions to the problem. The work is a collection of articles which can be grouped into three parts: First establishing the context of how the Business Model Canvas (BMC) is used to design business models and explore the way in which CAD can contribute to the design activity. The second part extends on this by proposing new technics and tools which support elicitation, evaluation (assessment) and evolution of business models design with CAD. This includes features such as multi-color tagging to easily connect elements, rules to validate coherence of business models and features that are adapted to the correct business model proficiency level of its users. A new way to describe and visualize multiple versions of a business model and thereby help in addressing the business model as a dynamic object was also researched. The third part explores extensions to the business model canvas such as an intermediary model which helps IT alignment by connecting business model and enterprise architecture. And a business model pattern for privacy in a mobile environment, using privacy as a key value proposition. The prototyped techniques and proposition for using CAD tools in business model modeling will allow commercial CAD developers to create tools that are better suited to the needs of practitioners.

Business model design: an evaluation of paper-based and computer-aided canvases

In recent years, Business Model Canvas design has evolved from being a paper-based activity to one that involves the use of dedicated computer-aided business model design tools. We propose a set of guidelines to help design more coherent business models. When combined with functionalities offered by CAD tools, they show great potential to improve business model design as an ongoing activity. However, in order to create complex solutions, it is necessary to compare basic business model design tasks, using a CAD system over its paper-based counterpart. To this end, we carried out an experiment to measure user perceptions of both solutions. Performance was evaluated by applying our guidelines to both solutions and then carrying out a comparison of business model designs. Although CAD did not outperform paper-based design, the results are very encouraging for the future of computer-aided business model design.

Predicting trabecular bone microdamage initiation and accumulation using a non-linear perfect damage model

Studies evaluating the mechanical behavior of the trabecular microstructure play an important role in our understanding of pathologies such as osteoporosis, and in increasing our understanding of bone fracture and bone adaptation. Understanding of such behavior in bone is important for predicting and providing early treatment of fractures. The objective of this study is to present a numerical model for studying the initiation and accumulation of trabecular bone microdamage in both the pre- and post-yield regions. A sub-region of human vertebral trabecular bone was analyzed using a uniformly loaded anatomically accurate microstructural three-dimensional finite element model. The evolution of trabecular bone microdamage was governed using a non-linear, modulus reduction, perfect damage approach derived from a generalized plasticity stress-strain law. The model introduced in this paper establishes a history of microdamage evolution in both the pre- and post-yield regions

An objective anisotropic elastic plastic model and Algorithm applicable to bone mechanics

The implicit projection algorithm of isotropic plasticity is extended to an objective anisotropic elastic perfectly plastic model. The recursion formula developed to project the trial stress on the yield surface, is applicable to any non linear elastic law and any plastic yield function.A curvilinear transverse isotropic model based on a quadratic elastic potential and on Hill's quadratic yield criterion is then developed and implemented in a computer program for bone mechanics perspectives. The paper concludes with a numerical study of a schematic bone-prosthesis system to illustrate the potential of the model.

A hierarchical approach to model parameter optimization for developmental systems.

In the context of Systems Biology, computer simulations of gene regulatory networks provide a powerful tool to validate hypotheses and to explore possible system behaviors. Nevertheless, modeling a system poses some challenges of its own: especially the step of model calibration is often difficult due to insufficient data. For example when considering developmental systems, mostly qualitative data describing the developmental trajectory is available while common calibration techniques rely on high-resolution quantitative data. Focusing on the calibration of differential equation models for developmental systems, this study investigates different approaches to utilize the available data to overcome these difficulties. More specifically, the fact that developmental processes are hierarchically organized is exploited to increase convergence rates of the calibration process as well as to save computation time. Using a gene regulatory network model for stem cell homeostasis in Arabidopsis thaliana the performance of the different investigated approaches is evaluated, documenting considerable gains provided by the proposed hierarchical approach.

A generalized mechanistic codon model.

Models of codon evolution have attracted particular interest because of their unique capabilities to detect selection forces and their high fit when applied to sequence evolution. We described here a novel approach for modeling codon evolution, which is based on Kronecker product of matrices. The 61 × 61 codon substitution rate matrix is created using Kronecker product of three 4 × 4 nucleotide substitution matrices, the equilibrium frequency of codons, and the selection rate parameter. The entities of the nucleotide substitution matrices and selection rate are considered as parameters of the model, which are optimized by maximum likelihood. Our fully mechanistic model allows the instantaneous substitution matrix between codons to be fully estimated with only 19 parameters instead of 3,721, by using the biological interdependence existing between positions within codons. We illustrate the properties of our models using computer simulations and assessed its relevance by comparing the AICc measures of our model and other models of codon evolution on simulations and a large range of empirical data sets. We show that our model fits most biological data better compared with the current codon models. Furthermore, the parameters in our model can be interpreted in a similar way as the exchangeability rates found in empirical codon models.

Not one odour but two: A new model for nestmate recognition.

Recognition systems play a key role in a range of biological processes, including mate choice, immune defence and altruistic behaviour. Social insects provide an excellent model for studying recognition systems because workers need to discriminate between nestmates and non-nestmates, enabling them to direct altruistic behaviour towards closer kin and to repel potential invaders. However, the level of aggression directed towards conspecific intruders can vary enormously, even among workers within the same colony. This is usually attributed to differences in the aggression thresholds of individuals or to workers having different roles within the colony. Recent evidence from the weaver ant Oecophylla smaragdina suggests that this does not tell the whole story. Here I propose a new model for nestmate recognition based on a vector template derived from both the individual's innate odour and the shared colony odour. This model accounts for the recent findings concerning weaver ants, and also provides an alternative explanation for why the level of aggression expressed by a colony decreases as the diversity within the colony increases, even when odour is well-mixed. The model makes additional predictions that are easily tested, and represents a significant advance in our conceptualisation of recognition systems.

Cumulative cultural dynamics and the coevolution of cultural innovation and transmission: an ESS model for panmictic and structured populations.

When individuals in a population can acquire traits through learning, each individual may express a certain number of distinct cultural traits. These traits may have been either invented by the individual himself or acquired from others in the population. Here, we develop a game theoretic model for the accumulation of cultural traits through individual and social learning. We explore how the rates of innovation, decay, and transmission of cultural traits affect the evolutionary stable (ES) levels of individual and social learning and the number of cultural traits expressed by an individual when cultural dynamics are at a steady-state. We explore the evolution of these phenotypes in both panmictic and structured population settings. Our results suggest that in panmictic populations, the ES level of learning and number of traits tend to be independent of the social transmission rate of cultural traits and is mainly affected by the innovation and decay rates. By contrast, in structured populations, where interactions occur between relatives, the ES level of learning and the number of traits per individual can be increased (relative to the panmictic case) and may then markedly depend on the transmission rate of cultural traits. This suggests that kin selection may be one additional solution to Rogers's paradox of nonadaptive culture.

Computational fluid dynamics of the right ventricular outflow tract and of the pulmonary artery: a bench model of flow dynamics.

OBJECTIVES: The reconstruction of the right ventricular outflow tract (RVOT) with valved conduits remains a challenge. The reoperation rate at 5 years can be as high as 25% and depends on age, type of conduit, conduit diameter and principal heart malformation. The aim of this study is to provide a bench model with computer fluid dynamics to analyse the haemodynamics of the RVOT, pulmonary artery, its bifurcation, and left and right pulmonary arteries that in the future may serve as a tool for analysis and prediction of outcome following RVOT reconstruction. METHODS: Pressure, flow and diameter at the RVOT, pulmonary artery, bifurcation of the pulmonary artery, and left and right pulmonary arteries were measured in five normal pigs with a mean weight of 24.6 ± 0.89 kg. Data obtained were used for a 3D computer fluid-dynamics simulation of flow conditions, focusing on the pressure, flow and shear stress profile of the pulmonary trunk to the level of the left and right pulmonary arteries. RESULTS: Three inlet steady flow profiles were obtained at 0.2, 0.29 and 0.36 m/s that correspond to the flow rates of 1.5, 2.0 and 2.5 l/min flow at the RVOT. The flow velocity profile was constant at the RVOT down to the bifurcation and decreased at the left and right pulmonary arteries. In all three inlet velocity profiles, low sheer stress and low-velocity areas were detected along the left wall of the pulmonary artery, at the pulmonary artery bifurcation and at the ostia of both pulmonary arteries. CONCLUSIONS: This computed fluid real-time model provides us with a realistic picture of fluid dynamics in the pulmonary tract area. Deep shear stress areas correspond to a turbulent flow profile that is a predictive factor for the development of vessel wall arteriosclerosis. We believe that this bench model may be a useful tool for further evaluation of RVOT pathology following surgical reconstructions.