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PubMed1987

Molecular dynamics simulations of cyclosporin A: the crystal structure and dynamic modelling of a structure in apolar solution based on NMR data.

The conformation of the immunosuppressive drug cyclosporin A (CPA), both in apolar solution and in crystalline state, has been studied by computer simulation techniques. Three molecular dynamics (MD) simulations have been performed: one modelling the crystal structure and two modelling the structure in apolar solution, using a restrained MD approach in which data from nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy are taken into account. The simulation of the crystalline state (MDC) concerns a system of 4 unit cells containing 16 cyclosporin A molecules and 22 water molecules, which is simulated using crystalline periodic boundary conditions. The simulations modelling the apolar solvent conformation (MDS) concern one isolated cyclosporin A molecule. In these simulations an extra term in the interatomic potential function is used, which forces the molecule to satisfy a set of 57 atom-atom distance constraints originating from nuclear Overhauser effects (NOEs) obtained from NMR spectroscopy and one distance constraint deduced from IR spectroscopy. From a comparison of the results of the crystal simulation to those of the X-ray experiment in terms of structure, atomic fluctuations, hydrogen bond pattern, etc., it is concluded that the force field that is used yields an adequate representation of crystalline cyclosporin A. Secondly, it is shown that the dynamic modelling technique that is used to obtain a structure in a polar solution from NMR distance information works well. Starting from initial conformations which have a root mean square difference of 0.14 nm both distance restrained MD simulations converge to the same final solution structure. A comparison of the crystal structure of cyclosporin A and the one in apolar solution shows that there are significant differences. The overall difference in atomic positions is 0.09 nm for the C alpha atoms and 0.17 nm for all atoms. In apolar solution, the molecule is slightly more bent and the side chains of 1 MeBmt and 10 MeLeu adopt a different conformation.

Computer Simulation↗
PubMed1996

Computer simulation of cerebrovascular circulation: assessment of intracranial hemodynamics during induction of anesthesia.

OBJECTIVE: The purpose of this project was to develop a computer model of cerebrovascular hemodynamics interacting with a pharmacokinetic drug model to examine the effects of various stimuli on cerebral blood flow and intracranial pressure during anesthesia. METHODS: The mathematical model of intracranial hemodynamics is a seven-compartment, constant-volume system. A series of resistance relate blood and cerebrospinal fluid fluxes to pressure gradients between compartments. Arterial, venous, and tissue compliance are also included. Autoregulation is modeled by transmural pressure-dependent, arterial-arteriolar resistance. The effect of a drug (thiopental) on cerebrovascular circulation was simulated by a variable arteriolar-capillary resistance. Thiopental concentration was predicted by a three-compartment, pharmacokinetic model. The effect site compartment was included to account for a disequilibrium between drug plasma and biophase concentrations. The model was validated by comparing simulation results with available experimental observations. The simulation program is written in VisSim dynamic simulation language for an IBM-compatible PC. RESULTS: The model developed was used to calculate the cerebral blood flow and intracranial pressure changes that occur during the induction phase of general anesthesia. Responses to laryngoscopy and intubation were predicted for simulated patients with elevated intracranial pressure and non-autoregulated cerebral circulation. Simulation shows that the induction dose of thiopental reduces intracranial pressure up to 15%. The duration of this effect is limited to less than 3 minutes by rapid redistribution of thiopental and cerebral autoregulation. Subsequent laryngoscopy causes acute intracranial hypertension, exceeding the initial intracranial pressure. Further simulation predicts that this untoward effect can be minimized by an additional dose of thiopental administered immediately prior to intubation. CONCLUSION: The presented simulation allows comparison of various drug administration schedules to control intracranial pressure and preserve cerebral blood flow during induction of anesthesia. The model developed can be extended to analyze more complex intraoperative events by adding new submodels.

Anesthesia, General↗
PubMed2004

Full scale computer simulators in anesthesia training and evaluation.

PURPOSE: With the advent of competency-based curriculum, technology such as full scale computer simulators have acquired an increasingly important role in anesthesia both in training and evaluation. This article reviews the current role of full scale computer simulators in teaching and evaluation in anesthesia. SOURCE: This review draws from existing anesthesia and medical education literature in order to examine and assess the current role of full scale computer simulators in anesthesia education today. PRINCIPAL FINDINGS: The last decade has witnessed a major increase in the use of full scale computer simulators in anesthesia. Many applications have been found for these simulators including teaching and training, evaluation and research. Despite the increasing use and application of full scale computers in anesthesia in the area of teaching and training, definitive studies evaluating its cost effectiveness, its efficacy compared to traditional training methods or its impact on patient outcome are still pending. Although there is some preliminary evidence of reliability and validity in using the simulator to evaluate clinical competence, development in this area has not progressed enough to justify its use in formal, summative evaluation of competence in anesthesia at this time. CONCLUSIONS: As technology acquires an increasingly important role in medical education, full scale computer simulators represent an exciting potential in anesthesia. However, the full potential and role of simulators in anesthesia is still in development and will require a dovetailing of clinical theory and practice with current research in medical education.

Anesthesiology↗
PubMedDate not supplied

Pharmacometrics: modelling and simulation tools to improve decision making in clinical drug development.

There is broad recognition within the pharmaceutical industry that the drug development process, especially the clinical part of it, needs considerable improvement to cope with rapid changes in research and health care environments. Modelling and simulation are mathematically founded techniques that have been used extensively and for a long time in other areas than the pharmaceutical industry (e.g. automobile, aerospace) to design and develop products more efficiently. Both modelling and simulation rely on the use of (mathematical and statistical) models which are essentially simplified descriptions of complex systems under investigation. It has been proposed to integrate pharmacokinetic (PK) and pharmacodynamic (PD) principles into drug development to make it more rational and efficient. There is evidence from a survey on 18 development projects that a PK/PD guided approach can contribute to streamline the drug development process. This approach extensively relies on PK/PD models describing the relationships among dose, concentration (and more generally exposure), and responses such as surrogate markers, efficacy measures, adverse events. Well documented empirical and physiologically based PK/PD models are becoming available more and more, and there are ongoing efforts to integrate models for disease progression and patient behavior (e.g. compliance) as well. Other types of models which are becoming increasingly important are population PK/PD models which, in addition to the characterization of PK and PD, involve relationships between covariates (i.e. patient characteristics such as age, body weight) and PK/PD parameters. Population models allow to assess and to quantify potential sources of variability in exposure and response in the target population, even under sparse sampling conditions. As will be shown for an anticancer agent, implications of significant covariate effects can be evaluated by computer simulations using the population PK/PD model. Stochastic simulation is widely used as a tool for evaluation of statistical methodology including for example the evaluation of performance of measures for bioequivalence assessment. Recently, it was suggested to expand the use of simulations in support of clinical drug development for predicting outcomes of planned trials. The methodological basis for this approach is provided by (population) PK/PD models together with random sampling techniques. Models for disease progression and behavioral features like compliance, drop-out rates, adverse event dependent dose reductions, etc. have to be added to population PK/PD models in order to mimic the real situation. It will be shown that computer simulation helps to evaluate consequences of design features on safety and efficacy assessment of the drug, enabling identification of statistically valid and practically realisable study designs. For both modelling and simulation a guidance on 'best practices' is currently worked out by a panel of experts comprising representatives from academia, regulatory bodies and industry, thereby providing a necessary condition that model-based analysis and simulation will further contribute to streamlining pharmaceutical drug development processes.

Clinical Trials as Topic↗
PubMed2003

A study to validate the colonoscopy simulator.

BACKGROUND: The aim of this study was to investigate the relation between clinical experience and performance with regard to colonoscopic procedures performed on the HT Immersion Medical Colonoscopy Simulator. The hypothesis is that the performance of novice, intermediate, and experienced operators is different on simulators, just as it is on real patients. METHODS: 25 Postgraduate doctors were recruited and divided into three groups according to their level of colonoscopic experience. Candidates were asked at random to perform colonoscopy on module 3 or 4 of the HT Immersion Medical Colonoscopy Simulator. Modules 3 and 4 have built-in complex loops, and can demonstrate the candidate's ability either to avoid or undo the loop. Candidates in the first group, termed "novice," each had performed fewer than 10 colonoscopies and included four preregistration house officers (PRHOs), five specialist trainee resistrars (SpRs) and two consultants. This novice group had completed 80 episodes among them. In the second group, termed "intermediate," each candidate had performed between 11 and 100 colonoscopies, and the candidates included five SpRs and two research fellows. This intermediate group had completed 65 episodes. Members of the third group, termed "experienced" each had performed more than 101 colonoscopies, and included one SpR and six consultants. This experienced group had completed 45 episodes between them. A time result of 3,600 s (1 h) was used to denote perforation. RESULTS: The experienced group were shown to perform better than the intermediate group, which in turn performed better than the novice group. The assessment was based on multiple factors including time taken to complete the test, percentage of the colonic mucosa visualized, incidence of colonic perforations, and path length used. The results were highly significant statistically for all these factors ( p < 0.000) except in path length used. CONCLUSIONS: This study demonstrated that operators who differ in terms of their clinical experience and technical ability also differ in their performance of simulated colonoscopy. Thus, the findings have shown the simulator technology to be a powerful discriminator of manipulative skills in colonoscopy. The clinical differences that exist between novices and experts in terms of experience and technical expertise in endoscopic procedures are reflected by statistically significant differences in performance on the simulator. It is therefore reasonable to argue that improving proficiency on the simulator may translate into improvements in clinical practice. This study has validated the use of the HT Medical Immersion Colonoscopy Simulator to discriminate among subjects with different levels of experience.

Colonoscopy↗
PubMed2001

Accomplishments and challenges of surgical simulation.

For nearly a decade, advanced computer technologies have created extraordinary educational tools using three-dimensional (3D) visualization and virtual reality. Pioneering efforts in surgical simulation with these tools have resulted in a first generation of simulators for surgical technical skills. Accomplishments include simulations with 3D models of anatomy for practice of surgical tasks, initial assessment of student performance in technical skills, and awareness by professional societies of potential in surgical education and certification. However, enormous challenges remain, which include improvement of technical fidelity, standardization of accurate metrics for performance evaluation, integration of simulators into a robust educational curriculum, stringent evaluation of simulators for effectiveness and value added to surgical training, determination of simulation application to certification of surgical technical skills, and a business model to implement and disseminate simulation successfully throughout the medical education community. This review looks at the historical progress of surgical simulators, their accomplishments, and the challenges that remain.

Anatomy, Cross-Sectional↗
PubMed2005

Fundamental study of ultrasonic-measurement-integrated simulation of real blood flow in the aorta.

Acquisition of detailed information on the velocity and pressure fields of the blood flow is essential to achieve accurate diagnosis or treatment for serious circulatory diseases such as aortic aneurysms. A possible way to obtain such information is integration of numerical simulation and color Doppler ultrasonography in the framework of a flow observer. This methodology, namely, Ultrasonic-Measurement-Integrated (UMI) Simulation, consists of the following processes. At each time step of numerical simulation, the difference between the measurable output signal and the signal indicated by numerical simulation is evaluated. Feedback signals are generated from the difference, and numerical simulation is updated applying the feedback signal to compensate for the difference. This paper deals with a numerical study on the fundamental characteristics of UMI simulation using a simple two-dimensional model problem for the blood flow in an aorta with an aneurysm. The effect of the number of feedback points and the feedback formula are investigated systematically. It is revealed that the result of UMI simulation in the feedback domain rapidly converges to the standard solution, even with usually inevitable incorrect upstream boundary conditions. Finally, an example of UMI simulation with feedback from real color Doppler measurement also shows a good agreement with measurement.

Aortic Aneurysm, Thoracic↗
PubMed2006

Interactive cell modeling web-resource, iCell, as a simulation-based teaching and learning tool to supplement electrophysiology education.

An interactive cell modeling web site, iCell (http://ssd1.bme.memphis.edu/icell/), that integrates research and education, was developed to present and to disseminate JAVA-coded models of cellular activities, and to supplement physiology education. iCell can be used to supplement the text-book material as a simulation-based teaching and learning tool. Specifically, iCell allows the students to supplement their learning experiences of the text-book cellular physiology material by running simulations in an interactive environment. The site consists of JAVA-coded models of various cardiac cells and neurons, and provides simulation data of their bioelectric transport activities at cellular level. Each JAVA-coded model allows the user to go through menu options to change model parameters, run and view simulation results. The site also has a glossary section for the scientific terms. iCell has been used as a teaching and learning tool for seven graduate courses at the Joint Biomedical Engineering Program of University of Memphis and University of Tennessee. This modeling tool was also used as a collaboration site among our physiology colleagues interested in simulations of cell membrane activities. Scientists from the fields of biosciences, engineering, life sciences and medical sciences in 17 countries have tested and utilized iCell as a simulation-based teaching, learning and collaboration environment. iCell provides us with an interactive, platform-independent, and user-friendly teaching and learning resource, and also a collaboration environment for electrophysiology to be shared over the Internet. The usage of simulations for teaching and learning will continue advancing simulation-based engineering and sciences for research and development.

Animals↗
PubMed1991

The portable virtual simulator.

The Virtual Simulator is a software tool for support and management of the geometric component of 3-dimensional radiotherapy treatment design. The Virtual Simulator is a software implementation of a physical simulator with additional functionality not currently available on physical simulators. Treatment of a virtual patient, derived from CT or other source, is simulated using the Virtual Simulator in the same way a physical simulator would be used. The intent of this approach is to provide the user with a familiar working environment for radiotherapy treatment design. Key features include an effective and efficient user interface, and the use of computing techniques and software standards which enhance portability to a variety of computer workstations. The Virtual Simulator is implemented in the C programming language using the X Window System, and has been written with the generic UNIX workstation in mind. It has been demonstrated that it can be installed and run without modification on workstations from a number of vendors.

Computer Simulation↗
PubMed1996

A methodology for solving physiologically based pharmacokinetic models without the use of simulation softwares.

The objective of the present study was to develop and validate a methodology for solving physiologically based pharmacokinetic (PBPK) models without the use of simulation software. The approach involves keying the parameter values and model equations into Microsoft Excel spreadsheets, and conducting simulations by solving the model equations according to Euler's method of numerical integration. This approach was applied to simulate the pharmacokinetics of styrene in rats exposed to 80 and 600 ppm for 6 h. The simulation results were plotted along with experimental data using the regular graphic features available in Excel, and validated by comparing them with simulation results obtained using a commercially available software (Advanced Continuous Simulation Language, ACSL). The simulations obtained with ACSL and Excel, in general, differed by <1%. The methodology developed in the present study should help informed individuals understand and solve PBPK models, without having to use "black-box' kind of computer programs and simulation softwares.

Algorithms↗
PubMed2004

Bronchoscopy simulator effectively prepares junior residents to competently perform basic clinical bronchoscopy.

BACKGROUND: Teaching procedural skills in a clinical setting is becoming increasingly difficult. Simulators can provide safe and inexpensive skills training. This randomized study was conducted to evaluate the effectiveness of a bronchoscopy simulator in teaching clinical bronchoscopy. METHODS: Three groups of surgical residents were evaluated while performing an intraoperative flexible bronchoscopy. First year (PGY1) residents were randomly assigned to perform bronchoscopy either with (n = 5) or without (n = 5) preprocedural bronchoscopic simulator training (PreOp flexible bronchoscopic simulator, Immersion Medical, Gaithersburg, MD). Residents PGY2 to 3 (n = 3) with prior bronchoscopic experience (> or = 10 bronchoscopies) underwent evaluation without simulator training. Subjects were required to complete a systematic airway examination through a laryngeal mask airway with patients under general anesthesia. Evaluation criteria included procedure time, number of verbal and physical interventions by evaluator, and a rating of exam thoroughness, proficiency, and confidence. RESULTS: The PGY1 subjects who trained on the simulator required significantly fewer verbal (6.2 +/- 1.6 vs 3.2 +/- 0.8) and physical (1.6 +/- 0.2 vs 0.2 +/- 0.4) cues and performed more systematic examinations (2.6 +/- 0.5 vs 4.4 +/- 0.9 on scale 1 to 5) than those who did not use the trainer. The skill level of PGY1 subjects who worked with the simulator was similar to that of PGY2 to 3 residents experienced in bronchoscopy. Procedural times were not different between groups as the evaluator maintained the pace of the examination using verbal and physical assistance. CONCLUSIONS: One hour of training with the bronchoscopic simulator effectively taught residents basic bronchoscopy and familiarity with airway anatomy. Residents using the trainer performed first-time bronchoscopy nearly as competently as residents experienced with bronchoscopy.

Audiovisual Aids↗
PubMed2005

Biomechanical simulations of scoliotic spine correction due to prone position and anaesthesia prior to surgical instrumentation.

BACKGROUND: The positioning of patients during scoliosis surgery has been shown to affect the scoliosis curve, yet positioning has not been exploited to help improve surgical outcome from a biomechanics point of view. Biomechanical models have been used to study other aspects of scoliosis. The goal of this study is to simulate the specific influence of the prone operative position and anaesthesia using a finite element model with patient personalized material properties. METHODS: A finite element model of the spine, ribcage and pelvis was created from the 3D standing geometry of two patients. To this model various positions were simulated. Initially the left and right supine pre-operative bending were simulated. Using a Box-Benkin experimental design the material properties of the intervertebral disks were personalized so that the bending simulations best matched the bending X-rays. The prone position was then simulated by applying the appropriate boundary conditions and gravity loads and the 3D geometry was compared to the X-rays taken intra-operatively. Finally an anaesthesia factor was added to the model to relax all the soft tissues. FINDINGS: The behaviour of the model improved for all three positions once the material properties were personalized. By incorporating an anaesthesia factor the results of the prone intra-operative simulation better matched the prone intra-operative X-ray. However, the anaesthesia factor was different for both patients. For the prone position simulation with anaesthesia patient 1 corrected from 62 degrees to 47 degrees and 43 degrees to 31 degrees. Patient 2 corrected from 70 degrees to 55 degrees and 40 degrees to 32 degrees for the thoracic and lumbar curves respectively. INTERPRETATION: Positioning of the patient, as well as anaesthesia, provide significant correction of the spinal deformity even before surgical instrumentation is fixed to the vertebra. The biomechanical effect of positioning should be taken into consideration by surgeons and possibly modify the support cushions accordingly to maximise 3D curve correction. The positioning is an important step that should not be overlooked by when simulating surgical correction and biomechanical models could be used to help determine optimal cushion placement.

Adolescent↗
PubMed2004

Computer simulation tool for rhinoplasty planning.

Rhinoplasty is a collection of surgical procedures performed on nose for the purpose of correcting functional and shape deformities. Nose is a facial feature which naturally draws attention during everyday contact. Any operation performed on nose has to blend well with the other facial features of the face. For this reason rhinoplasty is a type of surgery which requires artistic skills from surgeon as well as surgical skills. In this paper we present an artistic simulation tool which manipulates the shape of the nose on the bases of rhinoplasty procedures to be used during the surgery. Unlike other artistic simulation tools which can modify shape with no constraints, this tool simulates the effect of individual operations. Simulation tool can be valuable only if it predicts the outcome of the surgery with accuracy. Ultimately the outcome of the simulation depends largely on the experience of the surgeon. This is also the case with the tool presented in this study, so with experience the tool can be useful for predicting outcome more and more accurately. In this paper, the mechanical model of the nose and tools used for simulation are discussed. The simulation results are compared with actual rhinoplasty results to see the fidelity of the approach. A flowchart of the decision process and how rhinoplastic simulation together with the ideal nose data can be used to aid actual rhinoplastic surgery is given at the end.

Computer Simulation↗
PubMed2004

Optimisation of the superplastic forming of a dental implant for bone augmentation using finite element simulations.

OBJECTIVES: The phenomenon of superplasticity has made it possible to form complex shapes that require extremely high degrees of ductility in titanium alloy with minimal internal stresses. Combined with the use of an investment casting material as the die material, which makes possible the forming of re-entrant angles, it is possible to produce membranes for ridge augmentation. The aim is to characterise the metal alloy sheet and simulate the superplastic forming process in three dimensions to produce process parameters, namely gas pressure as a function of time, to accurately adapt the titanium sheet to the bone surface. METHOD: The surface of the die was digitised using a 3D laser scanning system (UBM-Keyence LC2450). Ti-6Al-4V sheet of 140 mm diameter was modelled using a grid of triangular membrane elements. This mesh was automatically refined during the simulations. Finite element simulation was carried out using the Superflag software program (University of Wales Swansea) Three different options for gas pressure control were adopted, namely, target flow stress, target strain rate and target energy dissipation. The pressure cycles produced from the simulation were used to form titanium alloy sheet at 900 degrees C using argon gas. The deformed regions of the formed sheet were then examined to determine the regions of contact with the die and to characterise surface damage. RESULTS: Comparison of the simulations with experiment showed that there was good agreement between simulated and experimental thickness distributions in most parts of the sheet that were examined. Interrupted tests showed that in the intermediate positions of the forming sheet the simulations were slightly ahead of the experiment. The target stress option was found to produce the best degree of adaptation and the sheet formed using this cycle showed good surface quality, whereas in highly deformed regions using the other target options, the sheet was found to have formed microcracks. The use of a solid lubricant on the surface of the forming sheet was not found to have a significant influence on the adaptation of the titanium alloy sheet except in areas of high deformation where the sheet perforated. SIGNIFICANCE: The finite element membrane formulation is well adapted to the superplastic forming of a ridge augmentation membrane prosthesis. The simulation accurately describes the evolution of the shape of the prosthesis and its thickness distribution with time, which allows the manufacturer to select an appropriate initial thickness of titanium alloy sheet prior to attempting to form the component. The investment dies are found to have sufficient strength to withstand the forming operation if a suitable orientation of the titanium sheet with respect to the die is adopted. A metal surface of good quality can be produced in the formed prosthesis using the appropriate gas control option.

Alloys↗
PubMed2006

Logistical considerations for endoscopy simulators.

A variety of endoscopy simulators have been produced during the last several decades. Multiple factors have influenced the types of simulators that have been developed and the ongoing evolution of existing models. Realistic simulation is only one issue in providing simulation-based training in GI endoscopy. Details such as cost, technologic limitations, management and availability of training facilities, personnel, animal welfare and the procurement, handling, and disposal of animal parts are all major factors when considering the options available among existing endoscopy simulators. Table 1 summarizes the logistical factors for the different types of endoscopy simulator. These considerations clearly are of major importance in simulator design and development and in the conceptualization and organization of simulator-based curricula and courses.

Animals↗
PubMed2005

Simulation of vegetation dynamics and management strategies on south Texas, semi-arid rangeland.

In this paper, we describe a model designed to simulate seasonal dynamics of warm and cool season grasses and forbs, as well as the dynamics of woody plant succession through five seral stages, in each of nine different plant communities on the Rob and Bessie Welder Wildlife Refuge. The Welder Wildlife Refuge (WWR) is located in the Gulf Coastal Prairies and Marshes ecoregion of Texas. The model utilizes and integrates data from a wide array of research projects that have occurred in south Texas and WWR. It is designed to investigate the effects of alternative livestock grazing programs and brush control practices, with particular emphasis on prescribed burning, the preferred treatment for brush on the WWR. We evaluated the model by simulating changes in the plant communities under historical (1974-2000) temperature, rainfall, livestock grazing rotation, and brush control regimes, and comparing simulation results to field data on herbaceous biomass and brush canopy cover collected on the WWR over the same period. We then used the model to simulate the effects of 13 alternative management schemes, under each of four weather regimes, over the next 25 years. We found that over the simulation period, years 1974-2000, the model does well in simulating the magnitude and seasonality of herbaceous biomass production and changes in percent brush canopy cover on the WWR. It also does well in simulating the effects of variations in cattle stocking rates, grazing rotation programs, and brush control regimes on plant communities, thus providing insight into the combined effects of temperature, precipitation, cattle stocking rates, grazing rotation programs, and brush control on the overall productivity and state of woody plant succession on the WWR. Simulation of alternative management schemes suggests that brush canopy removal differs little between summer and winter prescribed burn treatments when precipitation remains near the long-term average, but during periods of low precipitation canopy removal is greater under winter prescribed burning. The model provides a useful tool to assist refuge personnel with developing long-term brush management and livestock grazing strategies.

Algorithms↗
PubMed1996

A comparison of structural and dynamic properties of different simulation methods applied to SH3.

The dynamic and static properties of molecular dynamics simulations using various methods for treating solvent were compared. The SH3 protein domain was chosen as a test case because of its small size and high surface-to-volume ratio. The simulations were analyzed in structural terms by examining crystal packing, distribution of polar residues, and conservation of secondary structure. In addition, the "essential dynamics" method was applied to compare each of the molecular dynamics trajectories with a full solvent simulation. This method proved to be a powerful tool for the comparison of large concerted atomic motions in SH3. It identified methods of simulation that yielded significantly different dynamic properties compared to the full solvent simulation. Simulating SH3 using the stochastic dynamics algorithm with a vacuum (reduced charge) force field produced properties close to those of the full solvent simulation. The application of a recently described solvation term did not improve the dynamic properties. The large concerted atomic motions in the full solvent simulation as revealed by the essential dynamics method were analyzed for possible biological implications. Two loops, which have been shown to be involved in ligand binding, were seen to move in concert to open and close the ligand-binding site.

Algorithms↗
PubMed2000

The use of a force-controlled dynamic knee simulator to quantify the mechanical performance of total knee replacement designs during functional activity.

The experimental evaluation of any total knee replacement (TKR) design should include the pre-implantation quantification of its mechanical performance during tests that simulate the common activities of daily living. To date, few dynamic TKR simulation studies have been conducted before implantation. Once in vivo, the accurate and reproducible assessment of TKR design mechanics is exceedingly difficult, with the secondary variables of the patient and the surgical technique hindering research. The current study utilizes a 6-degree-of-freedom force-controlled knee simulator to quantify the effect of TKR design alone on TKR mechanics during a simulated walking cycle. Results show that all eight TKR designs tested elicited statistically different measures of tibial/femoral kinematics, simulated soft tissue loading, and implant geometric restraint loading during an identical simulated gait cycle, and that these differences were a direct result of TKR design alone. Maximum ranges of tibial kinematics over the eight designs tested were from 0.8mm anterior to 6.4mm posterior tibial displacement, and 14.1 degrees internal to 6.0 degrees external tibial rotation during the walking cycle. Soft tissue and implant reaction forces ranged from 106 and 222N anteriorly to 19 and 127N posteriorly, and from 1.6 and 1.8Nm internally to 3.5 and 5.9Nm externally, respectively. These measures provide valuable experimental insight into the effect of TKR design alone on simulated in vivo TKR kinematics, bone interface loading and soft tissue loading. Future studies utilizing this methodology should investigate the effect of experimentally controlled variations in surgical and patient factors on TKR performance during simulated dynamic activity.

Biomechanical Phenomena↗