Meshless algorithm for soft tissue cutting in surgical simulation

Computation of soft tissue mechanical responses for surgery simulation and image-guided surgery has been dominated by the finite element (FE) method that utilises a mesh of interconnected elements as a computational grid. Shortcomings of such mesh-based discretisation in modelling of surgical cutting include high computational cost and the need for re-meshing in the vicinity of cutting-induced discontinuity. The meshless total Lagrangian adaptive dynamic relaxation (MTLADR) algorithm we present here does not exhibit such shortcomings, as it relies on spatial discretisation in a form of a cloud of nodes. The cutting-induced discontinuity is modelled solely through changes in nodal domains of influence, which is done through efficient implementation of the visibility criterion using the level set method. Accuracy of our MTLADR algorithm with visibility criterion is confirmed against the established nonlinear solution procedures available in the commercial FE code Abaqus.     

Evaluation of accuracy of non-linear finite element computations for surgical simulation: study using brain phantom

In this paper, the accuracy of non-linear finite element computations in application to surgical simulation was evaluated by comparing the experiment and modelling of indentation of the human brain phantom. The evaluation was realised by comparing forces acting on the indenter and the deformation of the brain phantom. The deformation of the brain phantom was measured by tracking 3D motions of X-ray opaque markers, placed within the brain phantom using a custom-built bi-plane X-ray image intensifier system. The model was implemented using the ABAQUS^TM finite element solver. Realistic geometry obtained from magnetic resonance images and specific constitutive properties determined through compression tests were used in the model. The model accurately predicted the indentation force–displacement relations and marker displacements. Good agreement between modelling and experimental results verifies the reliability of the finite element modelling techniques used in this study and confirms the predictive power of these techniques in surgical simulation.     

Influence of varnish application on a tissue conditioner: analysis of biofilm adhesion

doi:10.1111/j.1741‐2358.2009.00290.x
Influence of varnish application on a tissue conditioner: analysis of biofilm adhesion Purpose: The aim of this study was to evaluate if the use of a varnish on a tissue conditioner would affect biofilm adhesion. Background: After the surgery has been performed, before the delivery of a complete denture, it is often necessary to use materials such as tissue conditioners on the surgical wound. However, these materials present deficient physico‐mechanical properties, which allow biofilm development. Methods: Forty elderly volunteers wearing complete maxillary dentures were selected. They were randomly allocated into two groups (n = 20), G1 and G2. In both groups, a silicone‐based tissue conditioner was placed in a recess created at the base of the denture, according to the manufacturer’s guidelines. In group G1, a varnish was applied to the tissue conditioner, while in group G2, no treatment was applied. All volunteers performed daily hygiene of the prosthesis with a soft toothbrush, and toothpaste. Quantification of the mean score values of biofilm formed at different time points (baseline, 1 week and 3 weeks) was statistically analysed using anova (α = 0.05). Results: Group G2 (1.6 ± 1.2) showed the lowest mean score values of biofilm formation and there was a statistical difference between the groups (p = 0.03). The highest mean score values were found after 3 weeks (2.7 ± 1.4) and were statistically different from the other time points studied (baseline and 1 week). Conclusion: The use of a varnish had a detrimental effect on the tissue conditioner studied, allowing higher biofilm formation.     

Release of mechanical tension triggers apoptosis of human fibroblasts in a model of regressing granulation tissue

In an in vitro model of granulation tissue, early passage human diploid fibroblasts under mechanical tension showed little or no apoptosis. Release of mechanical tension triggered an apoptotic response that occurred within 3-6 h and reached a plateau by 24 h. The percentage of apoptotic cells (approximately 15%) remained constant up to 7 days, and after 3 days, total cell number declined. Identification of mechanical unloading as a stimulus for apoptosis, without application of pharmacologic or genetic intervention, is a novel observation that permits us to model similar events that occur during wound healing. Studies on the mechanism regulating apoptosis under these conditions established that the apoptotic response does not require differentiation of cells into myofibroblasts but is governed by a combination of mechanical tension and growth factors in the collagen matrix.     

Finite element simulation of an artificial intervertebral disk using fiber reinforced laminated composite model

Degeneration of intervertebral disk (IVD) has been increased in recent years. The lumbar herniation can be cured using conservative and surgical procedures. Surgery is considered after failure of conservative treatment. Partial discectomy, fusion, and total disk replacement (TDR) are also common surgical treatments for degenerative disk disease. However, due to limitations and disadvantages of the current treatments, many studies have been carried out to approach the best design of mimicking natural disk. Recently, a new method of TDRs has been introduced using nature deformation of IVD by reinforced fibers of annulus fibrosis. Nonetheless, owing to limitations of experimental works on the human body, numerical studies of IVD may help to understand load transfer and biomechanical properties within the disks with reinforced fibers. In this study, a three-dimensional (3D) finite element model of the L2-L3 disk vertebrae unit with 12 vertical fibers embedded into annulus fibrosis was constructed. The IVD was subjected to compressive force, bending moment, and axial torsion. The most important parameters of disk failures were compared to that of experimental data. The results showed that the addition of reinforced fibers into the disk invokes a significant decrease of stress in the nucleus and annulus. The findings of this study may have implications not only for developing IVDs with reinforced fibers but also for the application of fiber reinforced IVD in orthopedics surgeries as a suitable implant.     

Effect of three different bariatric obesity surgery procedures on nutrient and energy digestibility using a swine experimental model

Morbid obesity is a worldwide health concern that compromises life quality and health status of obese human subjects. Bariatric surgery for treating morbid obesity remains as one of the best alternatives to promote excess weight loss and to reduce co-morbidities. We have not found studies reporting nutrients and energy balance considering digestibility trials in humans following surgery. The purpose of this study was to determine protein, lipid, fiber, energy, calcium, and phosphorous digestibility in a swine model that underwent ileal transposition (IT), sleeve gastrectomy with ileal transposition (SGIT), Roux-en-Y gastric bypass (RYGBP), and with sham operated animals (SHAM). Thirty-two pigs were randomly assigned to four laparoscopic procedures: IT (n = 8), RYGBP (n = 8), SGIT (n = 8), and Sham-operated pigs (n = 8). From day 0 postsurgery to 130, pigs were weighed monthly to determine live weight and weight gain was calculated for each month postsurgery until day 130. Food intake in a metabolic weight basis was calculated by measuring ad libitum food intake at day 130. Swine were fitted into metabolic crates to determine digestibility coefficients of dry matter, protein, fat, fiber, ash, energy, calcium, and phosphorous from day 130. A one-way ANOVA and Student–Newman–Keuls were used to detect differences in weight, food intake, and digestibility coefficients. Digestibility values for dry matter, fiber, phosphorus, and energy showed no differences among groups (P > 0.05). However, significant differences (P ≤ 0.05) were encountered among groups for fat, protein, ash, and calcium digestibilities. The RYGBP procedure, when applied to the pig model, significantly reduced calcium, fat, and ash digestibility, which did not occur with SGIT or IT procedure, when compared with Sham-operated animals.     

Transplantation of engineered bone tissue using a rotary three-dimensional culture system

Bone is a complex, highly structured, mechanically active, three-dimensional (3-D) tissue composed of cellular and matrix elements. We previously published a report on in situ collagen gelation using a rotary 3-D culture system (CG–RC system) for the construction of large tissue specimens. The objective of the current study was to evaluate the feasibility of bone tissue engineering using our CG–RC system. Osteoblasts from the calvaria of newborn Wistar rats were cultured in the CG–RC system for up to 3 wk. The engineered 3-D tissues were implanted into the backs of nude mice and calvarial round bone defects in Wistar rats. Cell metabolic activity, mineralization, and bone-related proteins were measured in vitro in the engineered 3-D tissues. Also, the in vivo histological features of the transplanted, engineered 3-D tissues were evaluated in the animal models. We found that metabolic activity increased in the engineered 3-D tissues during cultivation, and that sufficient mineralization occurred during the 3 wk in the CG–RC system in vitro. One mo posttransplantation, the transplants to nude mice remained mineralized and were well invaded by host vasculature. Of particular interest, 2 mo posttransplantation, the transplants into the calvarial bone defects of rats were replaced by new mature bone. Thus, this study shows that large 3-D osseous tissue could be produced in vitro and that the engineered 3-D tissue had in vivo osteoinductive potential when transplanted into ectopic locations and into bone defects. Therefore, this system should be a useful model for bone tissue engineering.     

Effects of elevated CO2 concentration and increased temperature on winter wheat: test of ARCWHEAT1 simulation model

Winter wheat (Triticum aestivum L., ev. Mercia) was grown in a controlled-environment facility at two CO₂ concentrations (targets 350 and 700 μmol mol^?1), and two temperature regimes (tracking ambient and ambient + 4°C). Observations of phenology, canopy growth, dry matter production and grain yield were used to test the ARCWHEAT1 simulation model. Dry-matter production and grain yield were increased at elevated CO₂ concentration (27 and 39%, respectively) and reduced at increased temperature (?16 and ?35%, respectively). ARCWHEAT1 substantially underestimated canopy growth for all treatments. However, differences in the facility environment from field conditions over the winter, indicated by the unusually rapid canopy growth observed in this period, meant that empirical model relationships were being used outside the conditions for which they were developed. The ARCWHEAT productivity submodel, given observed green area indices as inputs, overestimated the effect of CO₂ on productivity. An alternative, more mechanistic submodel of productivity, based on the SUCROS87 and Farquhar & von Caemmerer models, simulated observed crop biomass very closely. When these productivity simulations were inputed into the ARCWHEAT1 partitioning and grain-fill submodels, grain yield was predicted poorly, mainly as a result of the assumption that the number of grains is proportional to total growth during a short pre-anthesis phase. While yield was not correlated with growth in this phase, it was correlated with growth in longer pre-anthesis phases, indicating that ARCWHEAT1 could be improved by taking into account the contribution of earlier growth in determining yield.     

Validation of the European corn borer damage model on maize using X rays

In order to explain and predict yield losses caused by European corn borer larvae, Ostrinia nubilalis Hbn. (Lepidoptera: Pyralidae), a mechanistic model was proposed to describe cavity appearance, their lengthwise extension, and their within-plant distribution. It integrates main dynamical processes of larvae: mortality, development and within-plant distribution. After its estimation and test under field conditions in 1988 and 1989, its validation, based upon X-ray photographs, is presented. This method allows cavity appearance and lengthwise extension to be followed without damaging the plants. This study confirms the relevance of the damage model and the rate of cavity lengthwise extension estimated with it.     

Understanding the regulation of aspartate metabolism using a model based on measured kinetic parameters

The aspartate‐derived amino‐acid pathway from plants is well suited for analysing the function of the allosteric network of interactions in branched pathways. For this purpose, a detailed kinetic model of the system in the plant model Arabidopsis was constructed on the basis of in vitro kinetic measurements. The data, assembled into a mathematical model, reproduce in vivo measurements and also provide non‐intuitive predictions. A crucial result is the identification of allosteric interactions whose function is not to couple demand and supply but to maintain a high independence between fluxes in competing pathways. In addition, the model shows that enzyme isoforms are not functionally redundant, because they contribute unequally to the flux and its regulation. Another result is the identification of the threonine concentration as the most sensitive variable in the system, suggesting a regulatory role for threonine at a higher level of integration.     

Isolated effect of geometry on mitral valve function for in silico model development

Computational models for the heart's mitral valve (MV) exhibit several uncertainties that may be reduced by further developing these models using ground-truth data-sets. This study generated a ground-truth data-set by quantifying the effects of isolated mitral annular flattening, symmetric annular dilatation, symmetric papillary muscle (PM) displacement and asymmetric PM displacement on leaflet coaptation, mitral regurgitation (MR) and anterior leaflet strain. MVs were mounted in an in vitro left heart simulator and tested under pulsatile haemodynamics. Mitral leaflet coaptation length, coaptation depth, tenting area, MR volume, MR jet direction and anterior leaflet strain in the radial and circumferential directions were successfully quantified at increasing levels of geometric distortion. From these data, increase in the levels of isolated PM displacement resulted in the greatest mean change in coaptation depth (70% increase), tenting area (150% increase) and radial leaflet strain (37% increase) while annular dilatation resulted in the largest mean change in coaptation length (50% decrease) and regurgitation volume (134% increase). Regurgitant jets were centrally located for symmetric annular dilatation and symmetric PM displacement. Asymmetric PM displacement resulted in asymmetrically directed jets. Peak changes in anterior leaflet strain in the circumferential direction were smaller and exhibited non-significant differences across the tested conditions. When used together, this ground-truth data-set may be used to parametrically evaluate and develop modelling assumptions for both the MV leaflets and subvalvular apparatus. This novel data may improve MV computational models and provide a platform for the development of future surgical planning tools.     

Application of a simulation model of hydrobiological survey in complex analysis of in situ data

The model realizes the algorithm simulating the motions of a group of organisms with mutually independent, stochastic paths in a homogeneous medium, which results in the random distribution of the organisms in local areas in space (sampling units). Substitution of the mean abundance values of individual species found in the actual hydrobiological samples into the sample as one of its parameters produces a given set of artificial samples similar to the in situ sample with its elements possessing complete stochastic independence. They are further used to test the reliability of results obtained by statistical methods of data analysis and computations of threshold values for some indices and coefficients employed in ecology.     

General response patterns of fish populations to stress: an evaluation using an individual-based simulation model

General response patterns of fish populations tostress, originally proposed by Colby for fisheriesrehabilitation and later adapted by Munkittrick forcontaminants, were evaluated using an individual-basedsimulation model. General response patterns relatechanges in population-level variables to the type ofstress. The model follows the daily growth,mortality, and spawning of individual yellow perch andwalleye through their lifetime, and was corroboratedusing Oneida Lake data. Two versions of the model wereused: population (yellow perch only) and community(dynamic predation on yellow perch by walleye). Eightstresses were imposed on the population and communityversions of the model and 100-year simulations wereperformed. Response patterns were defined by changesin predicted yellow perch mean population abundance,mean age of adults, and mean adult growth (representedby mean length at age-7). Proposed response patternswere similar to those predicted using the populationversion of the model. Simulations using the communityversion of the model distorted the response patterns,either causing amplification, dampening, or reversalof many of the patterns. Predicted response patternsbecame unique when additional variables were included.Our model results suggest that caution is appropriatein interpreting general response patterns based onmean age, or when the population of interest plays amajor role in a relatively simple food web. The responsepattern approach may be better at identifying the lifestage impacted rather than the mechanism of the stress.     

Effect of mechanical perturbation on the biomechanics, primary growth and secondary tissue development of inflorescence stems of Arabidopsis thaliana

Background and Aims

Mechanical perturbation is known to inhibit elongation of the inflorescence stem of Arabidopsis thaliana. The phenomenon has been reported widely for both herbaceous and woody plants, and has implications for how plants adjust their size and form to survive in mechanically perturbed environments. While this response is an important aspect of the plant''s architecture, little is known about how mechanical properties of the inflorescence stem are modified or how its primary and secondary tissues respond to mechanical perturbation.

Methods

Plants of the Columbia-0 ecotype were exposed to controlled brushing treatments and then submitted to three-point bending tests to determine stem rigidity and stiffness. Contributions of different tissues to the inflorescence stem geometry were analysed.

Key Results

Perturbed plants showed little difference in stem diameter, were 50 % shorter, 75 % less rigid and 70 % less stiff than controls. Changes in mechanical properties were linked to significant changes in tissue geometry – size and position of the pith, lignified interfascicular tissue and cortex – as well as a reduction in density of lignified cells. Stem mechanical properties were modified by changes in primary tissues and thus differ from changes observed in most woody plants tested with indeterminate growth – even though a vascular cambium is present in the inflorescence axis.

Conclusions

The study suggests that delayed development of key primary developmental features of the stem in this ecotype of Arabidopsis results in a ‘short and flexible’ rather than a ‘short and rigid’ strategy for maintaining upright axes in conditions of severe mechanical perturbation. The mechanism is comparable with more general phenomena in plants where changes in developmental rate can significantly affect the overall growth form of the plant in both ecological and evolutionary contexts.     

Influence of viscosity on myocardium mechanical activity: a mathematical model

We have previously proposed and validated a mathematical model of myocardium contraction-relaxation cycle based on current knowledge of regulatory role of Ca2+ and cross-bridge kinetics in cardiac cell. That model did not include viscous elements. Here we propose a modification of the model, in which two viscous elements are added, one in parallel to the contractile element, and one more in parallel to the series elastic element. The modified model allowed us to simulate and explain some subtle experimental data on relaxation velocity in isotonic twitches and on a mismatch between the time course of sarcomere shortening/lengthening and the time course of active force generation in isometric twitches. Model results were compared with experimental data obtained from 28 rat LV papillary muscles contracting and relaxing against various loads. Additional model analysis suggested contribution of viscosity to main inotropic and lusitropic characteristics of myocardium performance.     

Improving alloreactive CTL immunotherapy for malignant gliomas using a simulation model of their interactive dynamics

Glioblastoma (GBM), a highly aggressive (WHO grade IV) primary brain tumor, is refractory to traditional treatments, such as surgery, radiation or chemotherapy. This study aims at aiding in the design of more efficacious GBM therapies. We constructed a mathematical model for glioma and the immune system interactions, that may ensue upon direct intra-tumoral administration of ex vivo activated alloreactive cytotoxic-T-lymphocytes (aCTL). Our model encompasses considerations of the interactive dynamics of aCTL, tumor cells, major histocompatibility complex (MHC) class I and MHC class II molecules, as well as cytokines, such as TGF-β and IFN-γ, which dampen or increase the pro-inflammatory environment, respectively. Computer simulations were used for model verification and for retrieving putative treatment scenarios. The mathematical model successfully retrieved clinical trial results of efficacious aCTL immunotherapy for recurrent anaplastic oligodendroglioma and anaplastic astrocytoma (WHO grade III). It predicted that cellular adoptive immunotherapy failed in GBM because the administered dose was 20-fold lower than required for therapeutic efficacy. Model analysis suggests that GBM may be eradicated by new dose-intensive strategies, e.g., 3 × 10⁸ aCTL every 4 days for small tumor burden, or 2 × 10⁹ aCTL, infused every 5 days for larger tumor burden. Further analysis pinpoints crucial bio-markers relating to tumor growth rate, tumor size, and tumor sensitivity to the immune system, whose estimation enables regimen personalization. We propose that adoptive cellular immunotherapy was prematurely abandoned. It may prove efficacious for GBM, if dose intensity is augmented, as prescribed by the mathematical model. Re-initiation of clinical trials, using calculated individualized regimens for grade III–IV malignant glioma, is suggested. An erratum to this article can be found at     

Evaluation of relative importance of different microbial reactions on organic matter removal in horizontal subsurface-flow constructed wetlands using a 2D simulation model

In this study, we used a two-dimensional (2D) mechanistic mathematical model in order to evaluate the relative contribution of different microbial reactions to organic matter removal (in terms of COD) in horizontal subsurface-flow constructed wetlands that treated urban wastewater. We also used the model to analyse the effect of increasing or decreasing the organic loading rate (changing the hydraulic loading rate (HLR) at a constant influent organic matter concentration, or changing the organic matter concentration at a constant HLR) on both the removal efficiency and the relative importance of the microbial reactions. The model is based on the code RetrasoCodeBright, which we modified to include the main microbial processes related to organic matter and nitrogen transformations in the wetlands: hydrolysis, aerobic respiration, nitrification, denitrification, sulphate reduction and methanogenesis. The model was calibrated and validated with data from two wetlands (each with a surface area of 55 m²) located in a pilot plant near Barcelona (Spain). According to the simulations, anaerobic processes (methanogenesis and sulphate reduction) are more widespread in the wetlands and contribute to a higher COD removal rate (60–70%) than anoxic (denitrification) and aerobic reactions do. These model results are confirmed by experimental observations. In all the cases tested, the reaction that most contributed to COD removal was methanogenesis (33–52%). According to our simulations, decreasing the HLR (for example, from 40 to 25 mm/d) while maintaining a constant COD influent concentration has a clear positive impact on COD removal efficiency (which increases from 65% to 89%). Changing influent COD concentration (for example, from 290 to 190 mg/L) while maintaining a constant HLR has a smaller impact, causing efficiency to increase from 79% to 84%. Changes in influent COD concentration (at a constant HLR) affect the relative contribution of the microbial reactions to organic matter removal. However, this trend is not seen when the HLR changes and the COD influent concentration remains constant.     

The efficiency of adaptive search tactics for different prey distribution patterns: a simulation model based on the behaviour of juvenile plaice

Juvenile plaice Pleuronectes platessa are particularly useful for studying forager search behaviour because their search paths are essentially two dimensional, and punctuated by natural stops. Their prey occur in a range of natural distributions from highly aggregated to over‐dispersed. Juvenile plaice use area‐restricted search near aggregated prey and extensive search, consisting of longer moves and fewer turns, between aggregations and when searching for dispersed prey. They search for less conspicuous prey items mainly in the pauses between movements. This saltatory search behaviour contrasts with the continuous search that is usually assumed in search models. A simulation model of saltatory search behaviour showed that a strategy combining extensive and intensive search allows the efficient exploitation of a range of natural prey distribution patterns, and that it is particularly effective when the search behaviour is controlled by perceived prey density. This allows the predator to respond to the localized aggregations which often occur in nature. The selective use of intensive search was more efficient than the continuous use of extensive search even in prey distribution patterns that were statistically over‐dispersed.