Form-function relationships underlie rapid dietary changes in a lizard.

Macroevolutionary changes such as variation in habitat use or diet are often associated with convergent, adaptive changes in morphology. However, it is still unclear how small-scale morphological variation at the population level can drive shifts in ecology such as observed at a macroevolutionary scale. Here, we address this question by investigating how variation in cranial form and feeding mechanics relate to rapid changes in diet in an insular lizard (Podarcis siculus) after experimental introduction into a new environment. We first quantified differences in the skull shape and jaw muscle architecture between the source and introduced population using three-dimensional geometric morphometrics and dissections. Next, we tested the impact of the observed variation in morphology on the mechanical performance of the masticatory system using computer-based biomechanical simulation techniques. Our results show that small differences in shape, combined with variation in muscle architecture, can result in significant differences in performance allowing access to novel trophic resources. The confrontation of these data with the already described macroevolutionary relationships between cranial form and function in these insular lizards provides insights into how selection can, over relatively short time scales, drive major changes in ecology through its impact on mechanical performance.

A biomechanical analysis of prognathous and orthognathous insect head capsules: evidence for a many-to-one mapping of form to function.

Insect head shapes are remarkably variable, but the influences of these changes on biomechanical performance are unclear. Among 'basal' winged insects, such as dragonflies, mayflies, earwigs and stoneflies, some of the most prominent anatomical changes are the general mouthpart orientation, eye size and the connection of the endoskeleton to the head. Here, we assess these variations as well as differing ridge and sclerite configurations using modern engineering methods including multibody dynamics modelling and finite element analysis in order to quantify and compare the influence of anatomical changes on strain in particular head regions and the whole head. We show that a range of peculiar structures such as the genal/subgenal, epistomal and circumocular areas are consistently highly loaded in all species, despite drastically differing morphologies in species with forward-projecting (prognathous) and downward-projecting (orthognathous) mouthparts. Sensitivity analyses show that the presence of eyes has a negligible influence on head capsule strain if a circumocular ridge is present. In contrast, the connection of the dorsal endoskeletal arms to the head capsule especially affects overall head loading in species with downward-projecting mouthparts. Analysis of the relative strains between species for each head region reveals that concerted changes in head substructures such as the subgenal area, the endoskeleton and the epistomal area lead to a consistent relative loading for the whole head capsule and vulnerable structures such as the eyes. It appears that biting-chewing loads are managed by a system of strengthening ridges on the head capsule irrespective of the general mouthpart and head orientation. Concerted changes in ridge and endoskeleton configuration might allow for more radical anatomical changes such as the general mouthpart orientation, which could be an explanation for the variability of this trait among insects. In an evolutionary context, many-to-one mapping of strain patterns onto a relatively similar overall head loading indeed could have fostered the dynamic diversification processes seen in insects.

Masticatory loadings and cranial deformation in Macaca fascicularis: a finite element analysis sensitivity study.

Biomechanical analyses are commonly conducted to investigate how craniofacial form relates to function, particularly in relation to dietary adaptations. However, in the absence of corresponding muscle activation patterns, incomplete muscle data recorded experimentally for different individuals during different feeding tasks are frequently substituted. This study uses finite element analysis (FEA) to examine the sensitivity of the mechanical response of a Macaca fascicularis cranium to varying muscle activation patterns predicted via multibody dynamic analysis. Relative to the effects of varying bite location, the consequences of simulated variations in muscle activation patterns and of the inclusion/exclusion of whole muscle groups were investigated. The resulting cranial deformations were compared using two approaches; strain maps and geometric morphometric analyses. The results indicate that, with bite force magnitude controlled, the variations among the mechanical responses of the cranium to bite location far outweigh those observed as a consequence of varying muscle activations. However, zygomatic deformation was an exception, with the activation levels of superficial masseter being most influential in this regard. The anterior portion of temporalis deforms the cranial vault, but the remaining muscles have less profound effects. This study for the first time systematically quantifies the sensitivity of an FEA model of a primate skull to widely varying masticatory muscle activations and finds that, with the exception of the zygomatic arch, reasonable variants of muscle loading for a second molar bite have considerably less effect on cranial deformation and the resulting strain map than does varying molar bite point. The implication is that FEA models of biting crania will generally produce acceptable estimates of deformation under load as long as muscle activations and forces are reasonably approximated. In any one FEA study, the biological significance of the error in applied muscle forces is best judged against the magnitude of the effect that is being investigated.

Intraluminal thrombus has a selective influence on matrix metalloproteinases and their inhibitors (tissue inhibitors of matrix metalloproteinases) in the wall of abdominal aortic aneurysms.

BACKGROUND: The influence of intraluminal thrombus (ILT) on the proteolytic environment within the wall of an abdominal aortic aneurysm (AAA) is unknown. This is the first study to examine the correlation between ILT thickness and the levels of matrix metalloproteinases (MMPs) and their natural inhibitors (tissue inhibitors of matrix metalloproteinases [TIMPs]) within the adjacent AAA wall. METHODS: Thirty-five patients undergoing elective repair of AAAs were studied. A single full-thickness infrarenal aortic sample was obtained uniformly from the arteriotomy site from each patient. All samples were snap frozen and analyzed for total and active MMP 2, 8, and 9 and TIMP 1 and 2. Thrombus thickness at the specimen site was measured on the preoperative contrast computed tomographic angiograms. RESULTS: There was a statistically significant correlation between ILT thickness, concentration of TIMP 1, and active concentration of MMP 9. MMP 2 (active and total) and TIMP 2 demonstrated a positive correlation with ILT thickness, although not statistically significant. CONCLUSION: In this novel study, we found a significant positive correlation of ILT thickness with active MMP 9 and TIMP 1 concentration in the adjacent AAA wall, and this may have implications for AAA expansion and eventual rupture.

Modeling and control of anterior-posterior and medial-lateral sways in standing posture.

To study essential anterior-posterior and medial-lateral sways of the stance caused by rotational movements about the ankle and hip joints, a mathematical model is developed for the 3D postural kinematics and dynamics. The model is in the form of nonlinear differential-algebraic equations corresponding to a biomechanical system with holonomic constraints. A nonlinear feedback control law is further derived for stabilizing the upright stance, whilst eliminating internal torques induced by the constraints on postural movements. Numerical simulations of the model parametrized with experimental data of human body segments illustrate the performance of postural balancing with the proposed control.

Finite element modelling of squirrel, guinea pig and rat skulls: using geometric morphometrics to assess sensitivity.

Rodents are defined by a uniquely specialized dentition and a highly complex arrangement of jaw-closing muscles. Finite element analysis (FEA) is an ideal technique to investigate the biomechanical implications of these specializations, but it is essential to understand fully the degree of influence of the different input parameters of the FE model to have confidence in the model's predictions. This study evaluates the sensitivity of FE models of rodent crania to elastic properties of the materials, loading direction, and the location and orientation of the models' constraints. Three FE models were constructed of squirrel, guinea pig and rat skulls. Each was loaded to simulate biting on the incisors, and the first and the third molars, with the angle of the incisal bite varied over a range of 45°. The Young's moduli of the bone and teeth components were varied between limits defined by findings from our own and previously published tests of material properties. Geometric morphometrics (GMM) was used to analyse the resulting skull deformations. Bone stiffness was found to have the strongest influence on the results in all three rodents, followed by bite position, and then bite angle and muscle orientation. Tooth material properties were shown to have little effect on the deformation of the skull. The effect of bite position varied between species, with the mesiodistal position of the biting tooth being most important in squirrels and guinea pigs, whereas bilateral vs. unilateral biting had the greatest influence in rats. A GMM analysis of isolated incisor deformations showed that, for all rodents, bite angle is the most important parameter, followed by elastic properties of the tooth. The results here elucidate which input parameters are most important when defining the FE models, but also provide interesting glimpses of the biomechanical differences between the three skulls, which will be fully explored in future publications.

Validation of a morphometric reconstruction technique applied to a juvenile pelvis.

Three-dimensional reconstructions of bone geometry from microCT (computed tomography) data are frequently used in biomechanical and finite element analyses. Digitization of bone models is usually a simple process for specimens with a complete geometry, but in instances of damage or disarticulation it can be very challenging. Subsequent to digitization, further imaging techniques are often required to estimate the geometry of missing bone or connecting cartilage. This paper presents an innovative approach to the reconstruction of incomplete scan data, to reproduce proper anatomical arrangements of bones, including absent connecting cartilaginous elements. Utilizing geometric morphometric tools, the reconstruction technique is validated through comparison of a reconstructed 9 year old pelvis, to the original CT data. A principal component analysis and an overlay of the two pelves provide a measure of the accuracy of the reconstructed model. Future work aims to investigate the biomechanical effects of any minor positional error on the bone's predicted structural properties through the use of finite element analysis.

Assessments of bilateral asymmetry with application in human skull analysis.

As a common feature, bilateral symmetry of biological forms is ubiquitous, but in fact rarely exact. In a setting of analytic geometry, bilateral symmetry is defined with respect to a point, line or plane, and the well-known notions of fluctuating asymmetry, directional asymmetry and antisymmetry are recast. A meticulous scheme for asymmetry assessments is proposed and explicit solutions to them are derived. An investigation into observational errors of points representing the geometric structure of an object offers a baseline reference for asymmetry assessment of the object. The proposed assessments are applicable to individual, part or all point pairs at both individual and collective levels. The exact relationship between the developed treatments and the widely used Procrustes method in asymmetry assessment is examined. An application of the proposed assessments to a large collection of human skull data in the form of 3D landmark coordinates finds: (a) asymmetry of most skulls is not fluctuating, but directional if measured about a plane fitted to shared landmarks or side landmarks for balancing; (b) asymmetry becomes completely fluctuating if one side of a skull could be slightly rotated and translated with respect to the other side; (c) female skulls are more asymmetric than male skulls. The methodology developed in this study is rigorous and transparent, and lays an analytical base for investigation of structural symmetries and asymmetries in a wide range of biological and medical applications.

Masticatory loading and bone adaptation in the supraorbital torus of developing macaques.

Research on the evolution and adaptive significance of primate craniofacial morphologies has focused on adult, fully developed individuals. Here, we investigate the possible relationship between the local stress environment arising from masticatory loadings and the emergence of the supraorbital torus in the developing face of the crab-eating macaque Macaca fascicularis. By using finite element analysis (FEA), we are able to evaluate the hypothesis that strain energy density (SED) magnitudes are high in subadult individuals with resulting bone growth in the supraorbital torus. We developed three micro-CT-based FEA models of M. fascicularis skulls ranging in dental age from deciduous to permanent dentitions and validated them against published experimental data. Applied masticatory muscle forces were estimated from physiological cross-sectional areas of macaque cadaveric specimens. The models were sequentially constrained at each working side tooth to simulate the variation of the bite point applied during masticatory function. Custom FEA software was used to solve the voxel-based models and SED and principal strains were computed. A physiological superposition SED map throughout the face was created by allocating to each element the maximum SED value from each of the load cases. SED values were found to be low in the supraorbital torus region throughout ontogeny, while they were consistently high in the zygomatic arch and infraorbital region. Thus, if the supraorbital torus arises to resist masticatory loads, it is either already adapted in each of our subadult models so that we do not observe high SED or a lower site-specific bone deposition threshold must apply.

Combined finite element and multibody dynamics analysis of biting in a Uromastyx hardwickii lizard skull.

Lizard skulls vary greatly in shape and construction, and radical changes in skull form during evolution have made this an intriguing subject of research. The mechanics of feeding have surely been affected by this change in skull form, but whether this is the driving force behind the change is the underlying question that we are aiming to address in a programme of research. Here we have implemented a combined finite element analysis (FEA) and multibody dynamics analysis (MDA) to assess skull biomechanics during biting. A skull of Uromastyx hardwickii was assessed in the present study, where loading data (such as muscle force, bite force and joint reaction) for a biting cycle were obtained from an MDA and applied to load a finite element model. Fifty load steps corresponding to bilateral biting towards the front, middle and back of the dentition were implemented. Our results show the importance of performing MDA as a preliminary step to FEA, and provide an insight into the variation of stress during biting. Our findings show that higher stress occurs in regions where cranial sutures are located in functioning skulls, and as such support the hypothesis that sutures may play a pivotal role in relieving stress and producing a more uniform pattern of stress distribution across the skull. Additionally, we demonstrate how varying bite point affects stress distributions and relate stress distributions to the evolution of metakinesis in the amniote skull.

Rigid-body analysis of a lizard skull: modelling the skull of Uromastyx hardwickii.

Lizard skulls vary greatly in their detailed morphology. Theoretical models and practical studies have posited a definite relationship between skull morphology and bite performance, but this can be difficult to demonstrate in vivo. Computer modelling provides an alternative approach, as long as hard and soft tissue components can be integrated and the model can be validated. An anatomically accurate three-dimensional computer model of an Uromastyx hardwickii skull was developed for rigid-body dynamic analysis. The Uromastyx jaw was first opened under motion control, and then muscle forces were applied to produce biting simulations where bite forces and joint forces were calculated. Bite forces comparable to those reported in the literature were predicted, and detailed muscular force information was produced along with additional information on the stabilizing role of temporal ligaments in late jaw closing.

Development of a (silent) speech recognition system for patients following laryngectomy.

Surgical voice restoration post-laryngectomy has a number of limitations and drawbacks. The present gold standard involves the use of a tracheo-oesophageal fistula (TOF) valve to divert air from the lungs into the throat, which vibrates, and from this, speech can be formed. Not all patients can use these valves and those who do are susceptible to complications associated with valve failure. Thus there is still a place for other voice restoration options. With advances in electronic miniaturization and portable computing power a computing-intensive solution has been investigated. Magnets were placed on the lips, teeth and tongue of a volunteer causing a change in the surrounding magnetic field when the individual mouthed words. These changes were detected by 6 dual axis magnetic sensors, which were incorporated into a pair of special glasses. The resulting signals were compared to training data recorded previously by means of a dynamic time warping algorithm using dynamic programming. When compared to a small vocabulary database, the patterns were found to be recognised with an accuracy of 97% for words and 94% for phonemes. On this basis we plan to develop a speech system for patients who have lost laryngeal function.

New insights into the biomechanics of Legg-Calvé-Perthes' disease: The Role of Epiphyseal Skeletal Immaturity in Vascular Obstruction.

OBJECTIVES: Legg-Calvé-Perthes' disease (LCP) is an idiopathic osteonecrosis of the femoral head that is most common in children between four and eight years old. The factors that lead to the onset of LCP are still unclear; however, it is believed that interruption of the blood supply to the developing epiphysis is an important factor in the development of the condition. METHODS: Finite element analysis modelling of the blood supply to the juvenile epiphysis was investigated to understand under which circumstances the blood vessels supplying the femoral epiphysis could become obstructed. The identification of these conditions is likely to be important in understanding the biomechanics of LCP. RESULTS: The results support the hypothesis that vascular obstruction to the epiphysis may arise when there is delayed ossification and when articular cartilage has reduced stiffness under compression. CONCLUSION: The findings support the theory of vascular occlusion as being important in the pathophysiology of Perthes disease.Cite this article: M. Pinheiro, C. A. Dobson, D. Perry, M. J. Fagan. New insights into the biomechanics of Legg-Calvé-Perthes' disease: The Role of Epiphyseal Skeletal Immaturity in Vascular Obstruction. Bone Joint Res 2018;7:148-156. DOI: 10.1302/2046-3758.72.BJR-2017-0191.R1.

Three dimensional stereolithography models of cancellous bone structures from muCT data: testing and validation of finite element results.

Stereolithography (STL) models of complex cancellous bone structures have been produced from three-dimensional micro-computed tomography data sets of human cancellous bone histological samples from four skeletal sites. The STL models have been mechanically tested and the derived stiffness compared with that predicted by finite element analysis. The results show a strong correlation (R2 = 0.941) between the predicted and calculated stiffnesses of the structures and show promise for the use of STL as an additional technique to complement the use of finite element models, for the assessment of the mechanical properties of complex cancellous bone structures.

Dynamic stochastic simulation of cancellous bone resorption.

A stochastic simulation of cancellous bone resorption was developed and applied to a simple two-dimensional lattice structure representing the vertebral body. The simulation is based upon the concept of a basic multicellular unit (BMU) where net resorption (-deltaB.BMU) is considered at bone/marrow surfaces. The cancellous bone structure is defined as a binary matrix with the size of the pixels corresponding to a square element of approximately 20 microm dimension. The simulation considers both the probability that any surface pixel will be activated into a BMU and, if activated, the length of the resorption cavity. The relationship between relative stiffness and density for the simulation was predicted by finite element analysis. The stochastic simulation was iterated eight times with the mechanical properties assessed after each stage. Perforation of a single trabeculae was first observed at step 2, the structure completely lacking connectivity and mechanical integrity by step 8. The slope of the stiffness-porosity graph was greater than unity for the first five steps, but thereafter approached zero because the structure had lost connectivity and effectively collapsed. The eight-step simulation was repeated five times and demonstrated that, although the stiffness/density relationships were similar at the extremes of density, the dependence of stiffness upon density varied. This clearly demonstrates the stochastic nature of the simulation upon cancellous bone structure, and is probably indicative of a significant dependence of mechanical integrity upon perforation effects.

Stochastically simulated assessment of anabolic treatment following varying degrees of cancellous bone resorption.

The aim of this study was to investigate the recovery in cancellous bone stiffness resulting from anabolic treatment following varying degrees of resorption, using a stochastic simulation applied to a simplistic structure consisting of five vertical and five horizontal trabeculae. The structure was initially resorbed, and "bone" elements were stochastically removed until nominal resorptions of 10%, 15%, 20%, 25%, and 30% were achieved. A stochastic simulation of anabolic treatment was then applied where bone elements were added, continuing until the original stiffness had been regained, for example, simulating treatment of a patient with an anabolic agent after a period of postmenopausal resorption. The resorption and anabolic simulations were repeated three times for each of the nominal resorptions. The stiffness of the bone structure decreased linearly with resorption, with a slope of approximately -2 and an R(2) of 97.0%; hence, the stiffness fell at approximately twice the rate of the reduction in density. When the various structures regained their original density, the resultant stiffness also had a linear relationship with the original resorption, with a slope of -1 and a lower R(2) of 86.1%. This implies that the reduction in stiffness, when original density was regained, fell proportionately with the degree of initial resorption and, therefore, after a resorption of 30%, when original density was regained, the stiffness of the resultant structure was approximately 30% less than that of the original structure. The density required for the original stiffness to be regained increased linearly with the degree of initial resorption, with a slope of approximately 0.5 and an R(2) of 65.2%, lower than that observed for the previous relationships. This indicates a greater spread of data and suggests greater variability in the formation phase beyond the point of regained original density. Because irreversible connectivity reduction is widely considered to be one of the earliest manifestations of estrogen loss, these findings, although obtained on a simulation of a simplistic cancellous bone structure, support the concept of early intervention to prevent potentially irreversible deterioration of trabecular architecture after menopause.

Pediatric asthma care in US emergency departments. Current practice in the context of the National Institutes of Health guidelines.

OBJECTIVES: To determine whether US emergency department care for pediatric asthma conforms to the National Institutes of Health guidelines and whether the guidelines are likely to be adopted in clinical practice. DESIGN: Mail survey conducted from January to April 1992, and stratified by hospital type (children's, public and community). SETTINGS: Emergency departments of US hospitals. PARTICIPANTS: Simple stratified random sample of emergency department directors from 376 sampled hospitals. MEASUREMENTS: Self-reported data on emergency department pediatric asthma care, and knowledge and attitudes about the National Institutes of Health guidelines. Data are reported as mean (+/- SE). RESULTS: Sixty-eight percent of the surveyed emergency department directors responded. During 1991, there were an estimated 1.6 million visits for pediatric asthma care. Asthma accounted for 16.9% (+/- 9.0%) of all pediatric emergency department visits. Only 2.1% (+/- 1.0%) reported the use of written protocols or guidelines, with significant variation by hospital type. Sixty-seven percent (+/- 3.0%) reported the use of pulse oximetry. Eighty percent reported the use of beta-agonists by inhalation as the initial treatment. Only 44.7% (+/- 2.9%) reported the use of steroids if there was a poor response to the initial treatment. An estimated 45.5% (+/- 3.9%) of respondents had heard of the guidelines at the time of this survey; approximately 24% reported that they had read the guidelines. Most respondents reported that the guidelines were credible, clear and concise, and likely to be adopted in their emergency department. CONCLUSIONS: These data suggest that reported pediatric asthma care in US emergency departments differs substantially from the National Institutes of Health guidelines, with considerable variation by hospital type. The guidelines appear to provide an acceptable tool for emergency departments to use in assessing their pediatric asthma care. However, in light of the lack of evidence that the guidelines will improve outcomes, the impact of national guideline adoption remains unclear.

Tropical pulmonary eosinophilia associated with pleural effusions.

A 28-year-old Indian female presented with shortness of breath, white cell count of 27,400 with 39% eosinophils, and increased interstitial markings and bilateral pleural effusions on chest x-ray. Although the clinical presentation was consistent with tropical pulmonary eosinophilia (TPE), to our knowledge there has been only one previous report in the world's literature of pleural effusion associated with TPE. We suggest that pleural effusions are not incompatible with the diagnosis of TPE and that TPE be added to the list of conditions causing eosinophilic pleural effusions.

Use of an open-ended question to supplement a patient satisfaction questionnaire in a medical residents' clinic.

OBJECTIVES: To determine (1) the proportion of responses to an open-ended question related to patient satisfaction that could be categorized into 1 or more of 9 previously developed domains of out-patient care and (2) whether any other important aspects of care could be identified by adding the open-ended question to a satisfaction questionnaire. STUDY DESIGN: A 3-month observational study was done at the internal medicine clinic of an urban teaching hospital. PATIENTS AND METHODS: As part of a patient satisfaction study, 511 visitors were asked after their visit, "What are the 1 or 2 things that are most important to you when you see a doctor?" The responses were categorized independently by 2 raters into 1 or more of the 9 domains. When these 2 raters disagreed, the responses were read to a third rater. When either all 3 raters disagreed, or at least 1 rater thought a new domain was mentioned, those responses were categorized by consensus. Interobserver reliability between raters 1 and 2 was calculated by using Cohen's kappa statistic. RESULTS: The 355 responses were categorized as follows: 303 (85.4%) identified one or more domains that were part of the previously developed taxonomy, 9 (2.5%) identified a new domain, 11 (3.1%) identified both old and new domains, and 32 (9.0%) could not be categorized. Cohen's kappa was 0.57 (P < .001). Cultural sensitivity and physician honesty were the additional domains identified, by 1.1% and 4.5% of respondents, respectively. CONCLUSIONS: The previously developed taxonomy of domains can be used in this setting to categorize the large majority of open-ended responses. Such responses can identify important aspects of care that were either previously unidentified or were already identified but given low ratings. This information then can help improve quality of care.

Enhanced emergency department referral improves primary care access.

OBJECTIVE: People who use the emergency department (ED) as their main source of medical care cite access barriers to primary care as the reason. The purpose of this study was to test an intervention designed to refer regular ED users to primary care. STUDY DESIGN: A prospective randomized clinical trial. PATIENTS AND METHODS: Adults who stated the ED is their regular source of care and have no primary care (n = 189) were randomized to 2 groups: the intervention being studied or usual care. The study took place over 3 months at a northeastern urban hospital. RESULTS: Subjects in the intervention group were more than twice as likely to keep the primary care appointment compared with the usual care group, and most also received some measure of preventive care. There was no significant difference in ED utilization by these patients in the 12-month period following study entry. CONCLUSION: Making an appointment with detailed instructions during a visit to the ED markedly improves show rates at follow-up appointments with a primary care provider and allowed for opportunity to provide important preventive services.