ElePhant: an anatomic-electronic simulation system for the evaluation of computer assisted interventions and surgical education]

BACKGROUND: Suitable simulation systems providing realistic conditions are required for preclinical evaluation of computer assisted interventions and surgical training. Techniques are necessary for an objective detection of injuries to the structures at risk. The aim of this study was the technical realization of a simulation system for the ENT intervention, mastoidectomy.MATERIALS AND METHODS: The basis of the simulation system was a CT scan of a cadaver skull. Using 3D printing, an anatomical phantom with realistic bone-like properties was created. Electronic detection systems were integrated into the structures at risk. A study with 16 ENT surgeons was conducted to prove the system's suitability for surgical training.RESULTS: The creation of simulation systems for the objective evaluation of surgical intervention qualities is feasible. A modular structure enables economic and simple replacement of the simulation area. The modules are cost effective and reproducible with high accuracy. The present study shows that the simulation system can be applied in surgical education and evaluation as an alternative to cadavers.CONCLUSION: Objective evaluation of injured structures at risk can be realized in real time. The simulation system permits preclinical evaluation studies of computer assisted instruments and surgical education. Reproducibility of the results makes multi-center studies possible.     

On the interpretation of biochemical data by molecular dynamics computer simulation.

The application of computer simulation to molecular systems of biochemical interest is reviewed. It is shown that computer simulation is a tool complementary to experimental methods, which can be used to access atomic details inaccessible to experimental probes. Examples are given in which computer simulation augments the experimental information by providing an atomic picture of high resolution with respect to space, energy or time. The usefulness of a computer simulation largely depends on its quality. The most important factors that limit the accuracy of simulated results are discussed. The accuracy of different simulation studies can differ by orders of magnitude. The accuracy will depend on the type of biomolecular system and process studied. It will also depend on the choice of force field, the simulation set-up and the protocol that is used. A list of quality-determining factors is given, which may be useful when interpreting simulation studies appearing in the literature.     

Simulation tools for biochemical networks: evaluation of performance and usability

MOTIVATION: Simulation of dynamic biochemical systems is receiving considerable attention due to increasing availability of experimental data of complex cellular functions. Numerous simulation tools have been developed for numerical simulation of the behavior of a system described in mathematical form. However, there exist only a few evaluation studies of these tools. Knowledge of the properties and capabilities of the simulation tools would help bioscientists in building models based on experimental data. RESULTS: We examine selected simulation tools that are intended for the simulation of biochemical systems. We choose four of them for more detailed study and perform time series simulations using a specific pathway describing the concentration of the active form of protein kinase C. We conclude that the simulation results are convergent between the chosen simulation tools. However, the tools differ in their usability, support for data transfer to other programs and support for automatic parameter estimation. From the experimentalists' point of view, all these are properties that need to be emphasized in the future.     

Structure and dynamics of the water around myoglobin.

The interplay between simulations at various levels of hydration and experimental observables has led to a picture of the role of solvent in thermodynamics and dynamics of protein systems. One of the most studied protein-solvent systems is myoglobin, which serves as a paradigm for the development of structure-function relationships in many biophysical studies. We review here some aspects of the solvation of myoglobin and the resulting implications. In particular, recent theoretical and simulation studies unify much of the diverse set of experimental results on water near proteins.     

The (human) science of medical virtual learning environments

The uptake of virtual simulation technologies in both military and civilian surgical contexts has been both slow and patchy. The failure of the virtual reality community in the 1990s and early 2000s to deliver affordable and accessible training systems stems not only from an obsessive quest to develop the 'ultimate' in so-called 'immersive' hardware solutions, from head-mounted displays to large-scale projection theatres, but also from a comprehensive lack of attention to the needs of the end users. While many still perceive the science of simulation to be defined by technological advances, such as computing power, specialized graphics hardware, advanced interactive controllers, displays and so on, the true science underpinning simulation--the science that helps to guarantee the transfer of skills from the simulated to the real--is that of human factors, a well-established discipline that focuses on the abilities and limitations of the end user when designing interactive systems, as opposed to the more commercially explicit components of technology. Based on three surgical simulation case studies, the importance of a human factors approach to the design of appropriate simulation content and interactive hardware for medical simulation is illustrated. The studies demonstrate that it is unnecessary to pursue real-world fidelity in all instances in order to achieve psychological fidelity--the degree to which the simulated tasks reproduce and foster knowledge, skills and behaviours that can be reliably transferred to real-world training applications.     

Connectivity effects for slit pores linked by a channel

This paper describes a Monte Carlo computer simulation study of connectivity effects in a system of two parallel slit pores and a quasi-one-dimensional joint. A numerical method for evaluation of accessible volume in computer simulation studies of adsorption in pores is presented and applied to simple slit pores and systems of interconnected pores. A local version of the grand canonical ensemble Monte Carlo method is used to study adsorption under conditions mimicking mass transfer limitations.     

Microcomputer simulation of antigen-antibody binding at a fixed antigen/antibody ratio

Computer simulation techniques were used to define the theoretical nature of the reaction of antigen with antibody at a constant degree of antigen excess. The simulation studies show that binding curves obtained under these conditions have unique features which are determined by antibody affinity, affinity heterogeneity and the concentrations of antigen and antibody. When analyzed by non-linear least squares regression these curves can be used to determine the affinity of antibody in homogeneous and heterogeneous systems.     

Role of modelling in improving nutrient efficiency in cropping systems

The applicability of models in addressing resource management issues in agriculture has been widely promoted by the research community, yet examples of real impacts of such modelling efforts on current farming practices are rare. Nevertheless, simulation models can compliment traditional field experimentation in researching alternative management options. The first objective of this paper is, therefore, to provide four case study examples of where models were used to help research issues relating to improved nutrient efficiency in low-input cropping systems. The first two cases addressed strategies of augmenting traditional farming practices with small applications of chemical fertilizer (N and P). The latter two cases explicitly addressed the question of what plant genetic traits can be beneficial in low-nutrient farming systems. In each of these case studies, the APSIM (Agricultural Production Systems Simulator) systems model was used to simulate the impacts of alternative crop management systems.The question of whether simulation models can assist the research community in contributing to purposeful change in farming practice is also addressed. Recent experiences in Australia are reported where simulation models have contributed to practice change by farmers. Finally, current initiatives aimed at testing whether models can also contribute to improving the nutrient efficiency of smallholder farmers in the SAT are discussed.     

Modeling stochastic noise in gene regulatory systems

The Master equation is considered the gold standard for modeling the stochastic mechanisms of gene regulation in molecular detail, but it is too complex to solve exactly in most cases, so approximation and simulation methods are essential. However, there is still a lack of consensus about the best way to carry these out. To help clarify the situation, we review Master equation models of gene regulation, theoretical approximations based on an expansion method due to N.G. van Kampen and R. Kubo, and simulation algorithms due to D.T. Gillespie and P. Langevin. Expansion of the Master equation shows that for systems with a single stable steady-state, the stochastic model reduces to a deterministic model in a first-order approximation. Additional theory, also due to van Kampen, describes the asymptotic behavior of multistable systems. To support and illustrate the theory and provide further insight into the complex behavior of multistable systems, we perform a detailed simulation study comparing the various approximation and simulation methods applied to synthetic gene regulatory systems with various qualitative characteristics. The simulation studies show that for large stochastic systems with a single steady-state, deterministic models are quite accurate, since the probability distribution of the solution has a single peak tracking the deterministic trajectory whose variance is inversely proportional to the system size. In multistable stochastic systems, large fluctuations can cause individual trajectories to escape from the domain of attraction of one steady-state and be attracted to another, so the system eventually reaches a multimodal probability distribution in which all stable steady-states are represented proportional to their relative stability. However, since the escape time scales exponentially with system size, this process can take a very long time in large systems.     

Modeling cation/anion-water interactions in functional aluminosilicate structures

A need for the computer simulation of hydration/dehydration processes in functional aluminosilicate structures has been noted. Full and realistic simulations of these systems can be somewhat ambitious and require the aid of interactive computer graphics to identify key structural/chemical units, both in the devising of suitable water-ion simulation potentials and in the analysis of hydrogen-bonding schemes in the subsequent simulation studies. In this article, the former is demonstrated by the assembling of a range of essential water-ion potentials. These span the range of formal charges from +4e to −2e, and are evaluated in the context of three types of structure: a porous zeolite, calcium silicate cement, and layered clay. As an example of the latter, the computer graphics output from Monte Carlo computer simulation studies of hydration/dehydration in calcium-zeolite A is presented.     

Simulation as experiment: a philosophical reassessment for biological modeling

Some scientific modelers suggest that complex simulation models that mimic biological processes should have a limited place in ecological and evolutionary studies. However, complex simulation models can have a role that is different from that of simpler models that are designed to be fit to data. Simulation can be viewed as another kind of experimental system and should be analyzed as such. Here, I argue that current discussions in the philosophy of science and in the physical sciences fields about the use of simulation as an experimental system have important implications for biology, especially complex sciences such as evolution and ecology. Simulation models can be used to mimic complex systems, but unlike nature, can be manipulated in ways that would be impossible, too costly or unethical to do in natural systems. Simulation can add to theory development and testing, can offer hypotheses about the way the world works and can give guidance as to which data are most important to gather experimentally.     

Recent developments in molecular simulation approaches to study spherical virus capsids

Viruses are particularly challenging systems to study via molecular simulation methods. Virus capsids typically consist of over 100 subunit proteins and reach dimensions of over 100 nm; solvated viruses capsid systems can be over 1 million atoms in size. In this review, I will present recent developments which have attempted to overcome the significant computational expense to perform simulations which can inform experimental studies, make useful predictions about biological phenomena and calculate material properties relevant to nanotechnology design efforts.     

Statistical model building and model criticism for human circadian data

Mathematical models have played an important role in the analysis of circadian systems. The models include simulation of differential equation systems to assess the dynamic properties of a circadian system and the use of statistical models, primarily harmonic regression methods, to assess the static properties of the system. The dynamical behaviors characterized by the simulation studies are the response of the circadian pacemaker to light, its rate of decay to its limit cycle, and its response to the rest-activity cycle. The static properties are phase, amplitude, and period of the intrinsic oscillator. Formal statistical methods are not routinely employed in simulation studies, and therefore the uncertainty in inferences based on the differential equation models and their sensitivity to model specification and parameter estimation error cannot be evaluated. The harmonic regression models allow formal statistical analysis of static but not dynamical features of the circadian pacemaker. The authors present a paradigm for analyzing circadian data based on the Box iterative scheme for statistical model building. The paradigm unifies the differential equation-based simulations (direct problem) and the model fitting approach using harmonic regression techniques (inverse problem) under a single schema. The framework is illustrated with the analysis of a core-temperature data series collected under a forced desynchrony protocol. The Box iterative paradigm provides a framework for systematically constructing and analyzing models of circadian data.     

In vitro model systems for exploring oral biofilms: From single-species populations to complex multi-species communities

Numerous in vitro biofilm model systems are available to study oral biofilms. Over the past several decades, increased understanding of oral biology and advances in technology have facilitated more accurate simulation of intraoral conditions and have allowed for the increased generalizability of in vitro oral biofilm studies. The integration of contemporary systems with confocal microscopy and 16S rRNA community profiling has enhanced the capabilities of in vitro biofilm model systems to quantify biofilm architecture and analyse microbial community composition. In this review, we describe several model systems relevant to modern in vitro oral biofilm studies: the constant depth film fermenter, Sorbarod perfusion system, drip–flow reactor, modified Robbins device, flowcells and microfluidic systems. We highlight how combining these systems with confocal microscopy and community composition analysis tools aids exploration of oral biofilm development under different conditions and in response to antimicrobial/anti-biofilm agents. The review closes with a discussion of future directions for the field of in vitro oral biofilm imaging and analysis.     

Uncovering channels in photosystem II by computer modelling: current progress, future prospects, and lessons from analogous systems

Even prior to the publication of the crystal structures for photosystem II (PSII), it had already been suggested that water, O(2) and H(+) channels exist in PSII to achieve directed transport of these molecules, and to avoid undesirable side reactions. Computational efforts to uncover these channels and investigate their properties are still at early stages, and have so far only been based on the static PSII structure. The rationale behind the proposals for such channels and the computer modelling studies thus far are reviewed here. The need to take the dynamic protein into account is then highlighted with reference to the specific issues and techniques applicable to the simulation of each of the three channels. In particular, lessons are drawn from simulation studies on other protein systems containing similar channels.     

Computer simulation of polymer and biopolymer self-assembly for drug delivery

Molecular simulation is an emerging tool to bridge relevant time- and length-scales in self-assembly and interfacial processes in soft matter and biological systems. In this review, we highlight mesoscale and coarse-grained molecular dynamics simulation techniques as applied to poly(ethylene oxide)-based diblock copolymer self-assembly. Moreover, we review recent progress pertaining to diblock copolymer and biopolymer self-assembly, stability, and finally, interactions of hydrophobic drugs with polymer membranes. We expect that these computational investigations should provide a useful complement to experimental studies that address open questions in the field of polymeric drug delivery.     

Development of a closed-loop artificial pancreas.

A closed-loop glucose controlled insulin infusion system was developed, consisting of elements for continuous blood glucose analysis, a computer control system, and infusion systems. Improvements include decreased size, cost reduction and better performance. The algorithm used was a piecewise linear representation of the sigmoidal curve commonly employed. The apparatus has been applied to simulation of the healthy beta cell and glucose clamp studies.