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Computed tomographic simulation of craniospinal fields in pediatric patients: improved treatment accuracy and patient comfort.

PURPOSE: To reduce the time required for planning and simulating craniospinal fields through the use of a computed tomography (CT) simulator and virtual simulation, and to improve the accuracy of field and shielding placement. METHODS AND MATERIALS: A CT simulation planning technique was developed. Localization of critical anatomic features such as the eyes, cribriform plate region, and caudal extent of the thecal sac are enhanced by this technique. Over a 2-month period, nine consecutive pediatric patients were simulated and planned for craniospinal irradiation. Four patients underwent both conventional simulation and CT simulation. Five were planned using CT simulation only. The accuracy of CT simulation was assessed by comparing digitally reconstructed radiographs (DRRs) to portal films for all patients and to conventional simulation films as well in the first four patients. RESULTS: Time spent by patients in the CT simulation suite was 20 min on average and 40 min maximally for those who were noncompliant. Image acquisition time was <10 min in all cases. In the absence of the patient, virtual simulation of all fields took 20 min. The DRRs were in agreement with portal and/or simulation films to within 5 mm in five of the eight cases. Discrepancies of > or =5 mm in the positioning of the inferior border of the cranial fields in the first three patients were due to a systematic error in CT scan acquisition and marker contouring which was corrected by modifying the technique after the fourth patient. In one patient, the facial shield had to be moved 0.75 cm inferiorly owing to an error in shield construction. CONCLUSIONS: Our analysis showed that CT simulation of craniospinal fields was accurate. It resulted in a significant reduction in the time the patient must be immobilized during the planning process. This technique can improve accuracy in field placement and shielding by using three-dimensional CT-aided localization of critical and target structures. Overall, it has improved staff efficiency and resource utilization.

Adolescent↗

Validation of a computer-based colonoscopy simulator.

BACKGROUND: The computer-based colonoscopy simulator is intended to provide a realistic colonoscopic experience and feedback to operators regarding procedure skills. Advocates hope that computer-based colonoscopy simulators will enhance the mastery of colonoscopy by trainees. Before this hypothesis can be tested, the claims made for a simulator must be validated. The aims of this study were to answer the following: Does a computer-based colonoscopy simulator provide a "realistic" experience? Do computer-based colonoscopy simulators' performance parameters differentiate varying levels of experience? METHODS: Ten staff gastroenterologists, 6 gastroenterology fellows, and 6 residents each performed 2 computer-based colonoscopy simulator colonoscopies and performance parameters were recorded. Staff colonoscopists then completed a 6-item survey grading the "realism" of the simulation and procedure difficulty. Survey responses and performance scores were compared with the Wilcoxon rank-sum test. RESULTS: Faculty found the computer-based colonoscopy simulator experience to be realistic despite the "cases" being markedly easier than actual colonoscopy. The computer-based colonoscopy simulator distinguishes subjects according to endoscopic experience with 3 of its measured parameters (total procedure time, insertion time, time in "red-out"). No significant difference in the ability to distinguish among user types was found for the other 10 computer-based colonoscopy simulator measurements for which data were analyzable. CONCLUSION: The computer-based colonoscopy simulator provides a favorable degree of virtual realism with regard to visual simulation and colonoscope mechanics, although the "cases" were regarded as considerably easier than actual colonoscopy. The computer-based colonoscopy simulator has only limited capability for distinguishing varying levels of competence at actual colonoscopy. These findings suggest that a study to determine the role of computer-based colonoscopy simulators in the curriculum of trainees is warranted.

Clinical Competence↗

Using flight simulators aboard ships: human side effects of an optimal scenario with smooth seas.

INTRODUCTION: The U.S. Navy is considering placing flight simulators aboard ships. It is known that certain types of flight simulators can elicit motion adaptation syndrome (MAS), and also that certain types of ship motion can cause MAS. The goal of this study was to determine if using a flight simulator during ship motion would cause MAS, even when the simulator stimulus and the ship motion were both very mild. METHODS: All participants in this study completed three conditions. Condition 1 (Sim) entailed "flying" a personal computer-based flight simulator situated on land. Condition 2 (Ship) involved riding aboard a U.S. Navy Yard Patrol boat. Condition 3 (ShipSim) entailed "flying" a personal computer-based flight simulator while riding aboard a Yard Patrol boat. Before and after each condition, participants' balance and dynamic visual acuity were assessed. After each condition, participants filled out the Nausea Profile and the Simulator Sickness Questionnaire. RESULTS: Following exposure to a flight simulator aboard a ship, participants reported negligible symptoms of nausea and simulator sickness. However, participants exhibited a decrease in dynamic visual acuity after exposure to the flight simulator aboard ship (T[25] = 3.61, p < 0.05). Balance results were confounded by significant learning and, therefore, not interpretable. DISCUSSION: This study suggests that flight simulators can be used aboard ship. As a minimal safety precaution, these simulators should be used according to current safety practices for land-based simulators. Optimally, these simulators should be designed to minimize MAS, located near the ship's center of rotation and used when ship motion is not provocative.

Adaptation, Physiological↗

Villchur revisited: another look at automatic gain control simulation of recruiting hearing loss.

An algorithm to simulate the effects of sensorineural hearing impairment on speech reception was investigated. Like that described by Villchur [J. Acoust. Soc. Am. 62, 665-674 (1977)], this simulation employs automatic gain control in independent frequency bands to reproduce the elevated audibility thresholds and loudness recruitment that are characteristic of this type of loss. In the present implementation, band gains are controlled in an effort to simulate loudness recruitment directly, using recruitment functions that depend only on the magnitude of hearing loss in the band. In a preliminary evaluation, two normal-hearing subjects listened to the simulation matched to hearing losses studied previously [Zurek and Delhorne, J. Acoust. Soc. Am. 82, 1548-1559 (1987)] with noise-masking simulations. This evaluation indicated that the present automatic gain control simulation yielded scores roughly similar to those of both the hearing-impaired listeners and the masked-normal listeners. In the more-detailed evaluation, the performance of three listeners with severe sensorineural hearing loss on several speech intelligibility tests was compared to that of normal-hearing subjects listening to the output of the simulation. These tests included consonant-vowel syllable identification and sentence keyword identification for several combinations of speech-to-noise ratio, frequency-gain characteristic, and overall level. Generally, the simulation algorithm reproduced speech intelligibility well, though there was a clear trend for the simulation to result in better intelligibility than observed for impaired listeners when high-frequency emphasis placed more of the speech spectrum above threshold at higher frequencies. Also, the hearing-impaired listener with the greatest loss showed the largest discrepancies with the simulation. Overall, however, the simulation provides a very good approximation to speech reception by hearing-impaired listeners. The results of this study, together with previous studies of noise-making simulation, suggest that threshold elevation and recruitment, which are necessary features of a simulation of cochlear hearing loss, can also be largely sufficient for simulating the speech-reception performance of listeners with moderate to severe hearing impairments.

Adult↗

Refolding of potato carboxypeptidase inhibitor by molecular dynamics simulations with disulfide bond constraints.

The folding of the potato carboxypeptidase inhibitor (PCI) from partially unfolded conformations by the introduction of native disulfide bond constraints was studied by molecular dynamics simulations in explicit solvent. PCI consists of a globular core (Cys8 to Cys34), two flexible terminal regions (Glu1 to Ile7 and Glu35 to Gly39) and three loop regions characteristic of the family of proteins known as knottins. To generate unfolded conformations, two high temperature (600 K) simulations were performed; one with the native disulfide bonds intact (N600), and one with the disulfide bonds broken (ND600). For comparison purposes, two simulations at 300 K were done; one with the native disulfide bonds (N300), and one with the disulfide bonds broken (ND300). The N300 simulation reached an energetic equilibrium within a few picoseconds and maintained a stable structure during the 500 ps simulation. The three other simulations led to partial unfolding. The largest changes were observed in ND600 simulation with an rms deviation of over 5 A and radius of gyration 12.5% larger than the crystal structure value. Six structures from the ND600 simulation and one from the N600 simulation were used as starting structures for nine refolding simulations with somewhat different protocols for reforming the native disulfide bonds; in all cases the disulfides were reformed at 600 K and the temperature was decreased to 300 K for equilibration of the folded structures. Except for one structure that was significantly misfolded (final rms of 6.64 A with respect to N300), the other folding simulations recovered the native simulation structure (N300) to within rms differences ranging from 1.8 to 3.2 A for the main-chain of the core, relative to the N300, the X-ray and the NMR structures. Of particular interest is the internal and overall refolding behavior of the three loop regions. The more unfolded starting structures led to smaller rms values for the folded structures. Several energetic and solvation models were used to evaluate the X-ray, NMR, N300 and refolded structures. Although most models can distinguish the X-ray, NMR and N300 from the refolded structures, there is no correlation between the rms values of the latter and their estimated stability. Implications of the present results for protein folding by simulations and database search methods are discussed.

Computer Simulation↗

Operational departmentwide picture archiving communication system analysis using discrete event-driven block-oriented network simulation.

The accurate prediction of image throughput is a critical issue in planning for and acquisition of any successful picture archiving and communication system (PACS). Simulation plays an important role in this effort. The PACS image management chain is decomposed into eight subsystems. These subsystems include network transfers over three different networks and five software programs and/or queueing structures. This decomposition is used to create a simulation model that was effectuated using commercially available block-oriented network simulation software. From the PACS database, the traffic generation patterns of the imaging modality devices are used to drive the simulation. The simulation models the image file flow through the PACS for a 24-hour period. The behavior of the simulated traffic generators agreed well with the values derived from the PACS database. The mean delay for the simulated PACS is found to be 225 +/- 59 seconds. The delay time was found to vary during the simulated 24-hour cycle in a consistent manner with observations. This simulation provides estimates on what a radiological department can expect from a PACS in terms of throughput, utilization, and delay. The block-oriented network simulator (BONeS, Comdisco Systems Inc, Foster City, CA) simulation model of the modeled PACS is highly accurate. The models for the imaging modality traffic sources are validated with a high degree of accuracy. The simulation model allows for the study of what happens to the delay time under various loads. In this simulation, the reformatting process was determined to be the bottleneck causing a large increase in delay time under heavy loads.

Computer Communication Networks↗

Molecular dynamics simulation of the unfolding of the human prion protein domain under low pH and high temperature conditions.

Four 10-ns molecular dynamics (MD) simulations of the human prion protein domain (HuPrP 125-228) in explicit water solution have been performed. Each of the simulations mimicked a different environment of the protein: the neutral pH environment was simulated with all histidine residues neutral and bearing a ND proton and with other titratable side chains charged, the weakly acidic environment was simulated with all titratable side chains charged, the strongly acidic environment was simulated with all titratable side chains protonated. The protein in neutral pH environment was simulated at both ambient (298 K) and higher (350 K) temperatures. The native fold is stable in the neutral pH/ambient temperature simulation. Through out all other simulations, a quite stable core consisted of 10-20 residues around the disulfide bond retain their initial conformations. However, the secondary structures of the protein show changes of various degrees compared to the native fold, parts of the helices unfolded and the beta-sheets extended. Our simulations indicated that the heat-induced unfolding and acid-induced unfolding of HuPrP might follow different pathways: the initial stage of the acid-induced unfolding may include not only changes in secondary structures, but also changes in the tertiary structures. Under the strongly acidic condition, obvious tertiary structure changes take place after 10-ns simulation, the secondary structure elements and the loops becoming more parallel to each other, resulting in a compact state, which was stabilized by a large number of new, non-native side chain-side chain contacts. Such tertiary structure changes were not observed in the higher temperature simulation, and intuitively, they may favor the further extension of the beta-sheets and eventually the agglomeration of multiple protein molecules. The driving forces for this tertiary structure changes are discussed. Two additional 10-ns MD simulations, one with Asp202 protonated and the other with Glu196 protonated compared to the neutral pH simulation, were carried out. The results showed that the stability of the native fold is very subtle and can be strongly disturbed by eliminating a single negative charge at one of such key sites. Correlations of our results with previous experimental and theoretical studies are discussed.

Computer Simulation↗

Evaluation of anesthesia residents using mannequin-based simulation: a multiinstitutional study.

BACKGROUND: Anesthesia simulators can generate reproducible, standardized clinical scenarios for instruction and evaluation purposes. Valid and reliable simulated scenarios and grading systems must be developed to use simulation for evaluation of anesthesia residents. METHODS: After obtaining Human Subjects approval at each of the 10 participating institutions, 99 anesthesia residents consented to be videotaped during their management of four simulated scenarios on MedSim or METI mannequin-based anesthesia simulators. Using two different grading forms, two evaluators at each department independently reviewed the videotapes of the subjects from their institution to score the residents' performance. A third evaluator, at an outside institution, reviewed the videotape again. Statistical analysis was performed for construct- and criterion-related validity, internal consistency, interrater reliability, and intersimulator reliability. A single evaluator reviewed all videotapes a fourth time to determine the frequency of certain management errors. RESULTS: Even advanced anesthesia residents nearing completion of their training made numerous management errors; however, construct-related validity of mannequin-based simulator assessment was supported by an overall improvement in simulator scores from CB and CA-1 to CA-2 and CA-3 levels of training. Subjects rated the simulator scenarios as realistic (3.47 out of possible 4), further supporting construct-related validity. Criterion-related validity was supported by moderate correlation of simulator scores with departmental faculty evaluations (0.37-0.41, P < 0.01), ABA written in-training scores (0.44-0.49, < 0.01), and departmental mock oral board scores (0.44-0.47, P < 0.01). Reliability of the simulator assessment was demonstrated by very good internal consistency (alpha = 0.71-0.76) and excellent interrater reliability (correlation = 0.94-0.96; P < 0.01; kappa = 0.81-0.90). There was no significant difference in METI versus MedSim scores for residents in the same year of training. CONCLUSIONS: Numerous management errors were identified in this study of anesthesia residents from 10 institutions. Further attention to these problems may benefit residency training since advanced residents continued to make these errors. Evaluation of anesthesia residents using mannequin-based simulators shows promise, adding a new dimension to current assessment methods. Further improvements are necessary in the simulation scenarios and grading criteria before mannequin-based simulation is used for accreditation purposes.

Anaphylaxis↗

Simulators for use in anaesthesia.

There are many simulators available for use in anaesthetic-related education and research. Those who wish to purchase a simulator or to establish a simulation facility face a daunting task in understanding the differences between simulators. Recent reviews have focused on narrower areas of simulation, such as airway management or basic life support, or on the application of simulators. It would be difficult to deal in detail with every simulator ever made for anaesthesia, but in the present review we cover the spectrum of currently available anaesthetic simulators, provide an overview of different types of simulator, and discuss a selection of simulators of particular interest, including some of historical significance and some examples of 'home made' simulators. We have found no common terminology amongst authors for describing or classifying simulators, and propose a framework for describing (or classifying) them that is simple, clear and applicable to any simulator.

Anesthesiology↗

Assessment of a bronchoscopy simulator.

The study objective was to validate a flexible bronchoscopy simulator by determining if it could differentiate between expert and novice bronchoscopists. A subsequent evaluation phase was then done to determine whether use of the simulator would improve the rate of bronchoscopy skill acquisition for new pulmonary fellows. A multicenter prospective cohort study was performed using a bronchoscopy simulator. Three cohorts were evaluated based on the number of bronchoscopies previously performed: "experts" (> 500, n = 9), "intermediates" (25 to 500, n = 8), and "novices" (none, n = 11). Each participant performed two simulated cases with performance measures being recorded by the simulator. Performance measures that distinguished between groups were then used to evaluate the learning curve for new fellows training on the simulator. A randomized-controlled trial was then conducted comparing the quality of bronchoscopy performance for new pulmonary fellows who were trained either with conventional methods or with the simulator. Expert bronchoscopists performed better on the simulator than intermediates who performed better than novices in terms of procedure time, percentage of segments visualized, time in red-out, and wall collisions. Training of new fellows demonstrated that after performing 20 bronchoscopic simulations, the skill level acquired with the simulator significantly improved in terms of speed, percentage of segments visualized, time in red-out, and collisions. Fellows trained on the simulator performed better than fellows trained using conventional methods during their first actual bronchoscopies as assessed by procedure time (815 versus 1,168 s, p = 0.001), a bronchoscopy nurse's subjective quality assessment score (7.7 +/- 0.3 versus 3.7 +/- 2.5, p = 0.05), and by a quantitative bronchoscopy quality score (percentage of segments correctly identified/procedure time, 0.119 +/- 0.015 versus 0.046 +/- 034, p = 0.03). In conclusion, the bronchoscopy simulator was able to accurately assess bronchoscopy experience level. Training new fellows on the bronchoscopy simulator leads to more rapid acquisition of bronchoscopy expertise compared with conventional training methods. This technology has the potential to facilitate bronchoscopy training and to improve objective evaluations of bronchoscopy skills.

Adult↗

Computer-based patient simulations: hospital pharmacists' performance and opinions.

The performance of pharmacists in using an interactive computer-based patient simulation program and their attitudes toward the simulations are reported. The Institutional Patient Medication Simulation program is designed to enhance and evaluate the medication problem-solving skills of pharmacists. Each simulation consists of patient data-gathering, case question, and therapy decision modules with initial assessment and monitoring nodes. Five simulations were tested: gout, urinary-tract infection, congestive heart failure, antimicrobial prophylaxis in surgery, and hypertension. Pharmacists from nine hospitals were recruited for the study. Participants were asked to perform the simulations within a specified period and to complete attitudinal questionnaires. Of the 91 pharmacists who volunteered, 72 (79%) completed the simulations and the questionnaires. The practitioners indicated that the simulations adequately tested their knowledge and that they would recommend them to colleagues. Performance scores for data gathering were less than 70%, with no significant differences among the simulations. Case question scores exceeded 80% and again were consistent among simulations, whereas therapy decision scores were more variable, with the lowest scores being recorded for antimicrobial-related simulations. Pharmacists with more hospital experience tended to perform better. Pharmacists completing a patient simulation program found the simulations to be worthwhile. Performance scores indicated some difficulty in gathering patient data and showed that correct therapeutic decisions may not always occur even if adequate information is obtained.

Adult↗

Dynamic generation of surgery specific simulators -- a feasibility study.

Most of the current surgical simulators rely on preset anatomical virtual environments (VE). The functionality of a simulator is typically fixed to anatomy-based specific tasks. This rigid design principle makes it difficult to reuse an existing simulator for different surgeries. It also makes it difficult to simulate procedures for specific patients, since their anatomical features or anomalies cannot be easily replaced in the VE. In this paper, we demonstrate the reusability of a modular skill-based simulator, LapSkills, which allows dynamic generation of surgery-specific simulations. Task and instrument modules are easily reused from LapSkills and the three-dimensional VE can be replaced with other anatomical models. We build a nephrectomy simulation by reusing the simulated vessels and the clipping and cutting task modules from LapSkills. The VE of the kidney is generated with our anatomical model generation tools and then inserted into the simulation (while preserving the established tasks and evaluation metrics). An important benefit for the created surgery and patient-specific simulations is that reused components remain validated. We plan to use this faster development process to generate a simulation library containing a wide variety of laparoscopic surgical simulations. Incorporating the simulations into surgical training programs will help collect data for validating them.

Computer Simulation↗

Magnetic resonance imaging (MRI) simulation on EGEE grid architecture: a web portal design.

In this paper, we present a web portal that enables simulation of MRI images on the grid. Such simulations are done using the SIMRI MRI simulator that is implemented on the grid using MPI and the LCG2 middleware. MRI simulations are mainly used to study MRI sequence, and to validate image processing algorithms. As MRI simulation is computationally very expensive, grid technologies appear to be a real added value for the MRI simulation task. Nevertheless the grid access should be simplified to enable final user running MRI simulations. That is why we develop this specific web portal to propose a user friendly interface for MRI simulation on the grid. The web portal is designed using a three layers client/server architecture. Its main component is the process layer part that manages the simulation jobs. This part is mainly based on a java thread that screens a data base of simulation jobs. The thread submits the new jobs to the grid and updates the status of the running jobs. When a job is terminated, the thread sends the simulated image to the user. Through a client web interface, the user can submit new simulation jobs, get a detailed status of the running jobs, have the history of all the terminated jobs as well as their status and corresponding simulated image.

Computer Simulation↗

Modeling SSI financial eligibility and simulating the effect of policy options.

This article simulates eligibility for Supplemental Security Income (SSI) among the elderly, analyzes factors affecting participation, and looks at the potential effects of various options to modify financial eligibility standards for the federal SSI program. We find that in the estimated noninstitutional elderly population of 30.2 million in the United States in 1991, approximately 2 million individuals aged 65 or older were eligible for SSI (a 6.6 percent rate of eligibility). Our overall estimate of the rate of participation among eligible elderly is approximately 63 percent, suggesting that more than a third of those who are eligible do not participate in the program. The results of our analysis of factors affecting participation among the eligible elderly show that expected SSI benefits and a number of demographic and socioeconomic variables are associated with the probability of participation. We also simulate the effects of various policy options on the poverty rate, poverty gap, annual program cost, the number of participants, and the average estimated benefits among participants. The simulations consider the potential effects of five policy alternatives: Increase the general income exclusion (GIE) from $20 to $80. Increase the earned income exclusion (EIE) from $65 to $260. Increase the federal benefit rate (FBR) by $50 for individuals and $75 for couples and eliminate the GIE. Increase the asset threshold to $3,000 for individuals and $4,500 for couples. Increase the asset threshold to $6,000 for individuals and $9,000 for couples. Using 1991 microdata from the Survey of Income and Program Participation (SIPP) matched to Social Security Administration administrative records and making adjustments reflecting aggregate program statistics, we present the results of our simulations for December 1999. The results show substantial variation in the simulated effects of the five policy alternatives along the various outcome dimensions considered. The simulated effects on the poverty gap of the elderly population range from a 7.9 percent reduction ("Increase the GIE from $20 to $80") to a 0.1 percent reduction ("Increase the EIE from $65 to $260"). All simulated interventions are expected to increase the rate of SSI participation among the elderly from a high of 20.3 percent ("Increase the GIE from $20 to $80") to a low of 0.5 percent ("Increase the EIE from $65 to $260"). We also find that the interventions that have greater estimated effects in terms of increased participation and reduced poverty tend to cost more. At the high end, we estimate that increasing the GIE from $20 to $80 could raise annual federal SSI cash benefit outlays by about 46 percent, compared with only 0.9 percent for increasing the EIE from $65 to $260. Similar to the EIE intervention, raising the resource thresholds by 50 percent would reduce the overall poverty gap of the elderly by only 0.2 percent, would increase SSI participation only modestly (by 1.3 percent), but would entail slightly higher program costs (by 1.4 percent). Increasing the asset threshold by 200 percent would have higher estimated effects on all three outcomes, but it would still be associated with relatively low increases in both costs and benefits. Finally, the simulated effects on the three key outcomes of increasing the FBR by $50 for individuals and $75 for couples, combined with eliminating the GIE, are relatively large but are clearly less substantial than increasing the GIE from $20 to $80. This work relies on data from the SIPP matched to administrative data on federal SSI benefits that provide a more accurate picture of SSI participation than has been feasible for previous studies. We simulate eligibility for federal SSI benefits by applying the program rules to detailed information on the characteristics of individuals and couples based on the rich array of demographic and socioeconomic data in the SIPP, particularly the comprehensive information SIPP provides on assets and monthly income. A probit model is estimated to analyze factors affecting participation among the eligible elderly. Finally, we conduct the policy simulations using altered program rules represented by the policy alternatives and predicted participation probabilities to estimate outcomes under simulated program rules. We compare those simulated outcomes to observed outcomes under current program rules. The results of our simulations are conditional on the characteristics of participants and eligibles in 1991, but they also reflect aggregate adjustments capturing substantial changes in overall participation and program benefit levels between 1991 and 1999.

Age Factors↗

General concepts in full scale simulation: getting started.

UNLABELLED: Over the past decade, medical simulation has developed to a point where it now is poised to become ubiquitous in teaching curricula. Despite this experience, there is little up-to-date information to help new instructors and operators learn the general principles of simulation. The purpose of this article is to provide prospective simulation instructors with basic concepts and a practical approach to patient simulation. The main focus is on full-scale or high fidelity simulation. The article is intended to (a). prepare instructors to use full-scale simulation to educate students; (b). teach some of the complexities and terminology of simulation; (c). prepare for and complement the curriculum of a formal instructor course; and (d). teach the basic elements required to run a successful simulation. This article should be used as an adjunct to practical experience gained from using simulation units. IMPLICATIONS: Medical simulation replicates normal and abnormal physiology and pathology. It is a tool that is intended to increase experiential learning. Establishing a functional and useful simulation program involves many factors. This paper presents a detailed introduction to the concepts and methodology of simulation in medicine.

Anesthesiology↗

How consistent are molecular dynamics simulations? Comparing structure and dynamics in reduced and oxidized Escherichia coli thioredoxin.

In this study we have examined several parameters that can be used for checking the consistency and accuracy of protein structures and molecular dynamics simulations. This is done by comparing: (1) three X-ray structures of oxidized Escherichia coli thioredoxin (Trx-S2); (2) 14 NMR structures of reduced E. coli thioredoxin (Trx-(SH)2); and (3) 30 different simulations, 15 of Trx-S2 and 15 of Trx-(SH)2. The energy, the agreement with NOE data, the root-mean-square deviation between structures, and the surface characteristics of all these structures are analyzed. The 30 simulations, four water simulations, 20 standard vacuum simulations and six alternative vacuum simulations, are examined with respect to mobility, temperature factors and aromatic side-chain mobility. It is shown that although vacuum simulations may reproduce some parameters, all the features of a water simulation cannot be reproduced in any of these simulations. Several of the parameters described above are shown to be good for discriminating between an accurate and an inaccurate simulation. It is also shown that 100 ps is too short a time to obtain statistically certain temperature factors and correlation functions of aromatic side-chain motions. The results also suggest that performing ten 100 ps simulations spans the conformation space better than one 1 ns simulation.

Computer Simulation↗

Errors associated with metabolic control analysis. Application Of Monte-Carlo simulation of experimental data.

The errors associated with experimental application of metabolic control analysis are difficult to assess. In this paper, we give examples where Monte-Carlo simulations of published experimental data are used in error analysis. Data was simulated according to the mean and error obtained from experimental measurements and the simulated data was used to calculate control coefficients. Repeating the simulation 500 times allowed an estimate to be made of the error implicit in the calculated control coefficients. In the first example, state 4 respiration of isolated mitochondria, Monte-Carlo simulations based on the system elasticities were performed. The simulations gave error estimates similar to the values reported within the original paper and those derived from a sensitivity analysis of the elasticities. This demonstrated the validity of the method. In the second example, state 3 respiration of isolated mitochondria, Monte-Carlo simulations were based on measurements of intermediates and fluxes. A key feature of this simulation was that the distribution of the simulated control coefficients did not follow a normal distribution, despite simulation of the original data being based on normal distributions. Consequently, the error calculated using simulation was greater and more realistic than the error calculated directly by averaging the original results. The Monte-Carlo simulations are also demonstrated to be useful in experimental design. The individual data points that should be repeated in order to reduce the error in the control coefficients can be highlighted.

Animals↗

Bellows-less lung system for the human patient simulator.

A new bellows-less lung simulator utilising a fixed-volume pressure controller to simulate spontaneous breathing is presented as an alternative to the traditional bellows-driven mechanical lung system in the human patient simulator (HPS). The HPS is a fully interactive, life-like simulator used to train medical students and anaesthesia residents. The lung simulator simulates carinal pressure, which allows for simulation of actively breathing or ventilated patients. In the current HPS implementation, breathing is physically simulated with a pair of bellows and a computer-controlled piston, but, owing to physical and dynamic constraints, the model suffers from a lot of dead space. Furthermore, the set-up incorporates several mechanical components that require time-consuming calibrations, which drives up manufacturing costs. A bellows-less lung simulator has been designed and built which successfully simulates airflow in and out of the mouth by controlling the carina pressure. The new system is able to simulate tidal volumes between 400 and 500 ml, with flow rates of 4.3-5.71 min(-1) at a respiratory rate of 12 breaths per minute. The new design not only matches the ventilation performance of the HPS, but also simulates at 60 breaths per minute, which the HPS cannot maintain.

Education, Medical↗