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Michael Fagan

    Michael Fagan

    The relationship between skull shape and the forces generated during feeding is currently under widespread scrutiny and increasingly involves the use of computer simulations such as finite element analysis. The computer models used to... more
    The relationship between skull shape and the forces generated during feeding is currently under widespread scrutiny and increasingly involves the use of computer simulations such as finite element analysis. The computer models used to represent skulls are often based on computed tomography data and thus are structurally accurate; however, correctly representing muscular loading during food reduction remains a major problem. Here, we present a novel approach for predicting the forces and activation patterns of muscles and muscle groups based on their known anatomical orientation (line of action). The work was carried out for the lizard-like reptile Sphenodon (Rhynchocephalia) using a sophisticated computer-based model and multi-body dynamics analysis. The model suggests that specific muscle groups control specific motions, and that during certain times in the bite cycle some muscles are highly active whereas others are inactive. The predictions of muscle activity closely correspond to data previously recorded from live Sphenodon using electromyography. Apparent exceptions can be explained by variations in food resistance, food size, food position and lower jaw motions. This approach shows considerable promise in advancing detailed functional models of food acquisition and reduction, and for use in other musculoskeletal systems where no experimental determination of muscle activity is possible, such as in rare, endangered or extinct species.
    The skull is composed of many bones that come together at sutures. These sutures are important sites of growth, and as growth ceases some become fused while others remain patent. Their mechanical behaviour and how they interact with... more
    The skull is composed of many bones that come together at sutures. These sutures are important sites of growth, and as growth ceases some become fused while others remain patent. Their mechanical behaviour and how they interact with changing form and loadings to ensure balanced craniofacial development is still poorly understood. Early suture fusion often leads to disfiguring syndromes, thus is it imperative that we understand the function of sutures more clearly. By applying advanced engineering modelling techniques, we reveal for the first time that patent sutures generate a more widely distributed, high level of strain throughout the reptile skull. Without patent sutures, large regions of the skull are only subjected to infrequent low-level strains that could weaken the bone and result in abnormal development. Sutures are therefore not only sites of bone growth, but could also be essential for the modulation of strains necessary for normal growth and development in reptiles.
    Background: Sea turtles (Chelonoidea) are a charismatic group of marine reptiles that occupy a range of important ecological roles. However, the diversity and evolution of their feeding anatomy remain incompletely known.... more
    Background:
    Sea turtles (Chelonoidea) are a charismatic group of marine reptiles that occupy a range of important ecological roles. However, the diversity and evolution of their feeding anatomy remain incompletely known.

    Methodology/Principal Findings:
    Using computed tomography and classical comparative anatomy we describe the cranial anatomy in two sea turtles, the loggerhead (Caretta caretta) and Kemp’s ridley (Lepidochelys kempii), for a better understanding of sea turtle functional anatomy and morphological variation. In both taxa the temporal region of the skull is enclosed by bone and the jaw joint structure and muscle arrangement indicate that palinal jaw movement is possible. The tongue is relatively small, and the hyoid apparatus is not as conspicuous as in some freshwater aquatic turtles. We find several similarities between the muscles of C. caretta and L. kempii, but comparison with other turtles suggests only one of these characters may be derived: connection of the m. adductor mandibulae internus into the Pars intramandibularis via the Zwischensehne. The large fleshy origin of the m. adductor mandibulae externus Pars superficialis from the jugal seems to be a characteristic feature of sea turtles.

    Conclusions/Significance:
    In C. caretta and L. kempii the ability to suction feed does not seem to be as well developed as that found in some freshwater aquatic turtles. Instead both have skulls suited to forceful biting. This is consistent with the observation that both taxa tend to feed on relatively slow moving but sometimes armoured prey. The broad fleshy origin of the m. adductor mandibulae externus Pars superficialis may be linked to thecheek region being almost fully enclosed in bone but the relationship is complex.
    Finite element analysis (FEA) is a modelling technique increasingly used in anatomical studies investigating skeletal form and function. In the case of the cranium this approach has been applied to both living and fossil taxa to (for... more
    Finite element analysis (FEA) is a modelling technique increasingly used in anatomical studies investigating skeletal form and function. In the case of the cranium this approach has been applied to both living and fossil taxa to (for example) investigate how form relates to function or infer diet or behaviour. However, FE models of complex musculoskeletal structures always rely on simplified representations because it is impossible completely to image and represent every detail of skeletal morphology, variations in material properties and the complexities of loading at all spatial and temporal scales. The effects of necessary simplifications merit investigation. To this end, this study focuses on one aspect, model geometry, which is particularly pertinent to fossil material where taphonomic processes often destroy the finer details of anatomy or in models built from clinical CTs where the resolution is limited and anatomical details are lost. We manipulated the details of a finite element (FE) model of an adult human male cranium and examined the impact on model performance. First, using digital speckle interferometry, we directly measured strains from the infraorbital region and frontal process of the maxilla of the physical cranium under simplified loading conditions, simulating incisor biting. These measured strains were then compared with predicted values from FE models with simplified geometries that included modifications to model resolution, and how cancellous bone and the thin bones of the circum-nasal and maxillary regions were represented. Distributions of regions of relatively high and low principal strains and principal strain vector magnitudes and directions, predicted by the most detailed FE model, are generally similar to those achieved in vitro. Representing cancellous bone as solid cortical bone lowers strain magnitudes substantially but the mode of deformation of the FE model is relatively constant. In contrast, omitting thin plates of bone in the circum-nasal region affects both mode and magnitude of deformation. Our findings provide a useful frame of reference with regard to the effects of simplifications on the performance of FE models of the cranium and call for caution in the interpretation and comparison of FEA results.
    Feeding in Sphenodon, the New Zealand tuatara, is of interest for several reasons. First, Sphenodon is threatened by extinction, and some populations are in competition for food with Pacific rats. Second, Sphenodon demonstrates a unique... more
    Feeding in Sphenodon, the New Zealand tuatara, is of interest for several reasons. First, Sphenodon is threatened by extinction, and some populations are in competition for food with Pacific rats. Second, Sphenodon demonstrates a unique feeding apparatus. It involves an extra row of teeth on its palate running parallel to those of the upper jaw; teeth that are fused to crest of the jawbone without sockets; large chisel-like front teeth; a strong lower jaw and jaw joint that allows the lower jaw to slide forward after the jaws have closed. Third, ...
    Multiple myeloma bone disease is devastating for patients and a major cause of morbidity. The disease leads to bone destruction by inhibiting osteoblast activity while stimulating osteoclast activity. Recent advances in multiple myeloma... more
    Multiple myeloma bone disease is devastating for patients and a major cause of morbidity. The disease leads to bone destruction by inhibiting osteoblast activity while stimulating osteoclast activity. Recent advances in multiple myeloma research have improved our understanding of the pathogenesis of multiple myeloma-induced bone disease and suggest several potential therapeutic strategies. However, the effectiveness of some potential therapeutic strategies still requires further investigation and optimization. In this paper, a recently developed mathematical model is extended to mimic and then evaluate three therapies of the disease, namely: bisphosphonates, bortezomib and TGF-β inhibition. The model suggests that bisphosphonates and bortezomib treatments not only inhibit bone destruction, but also reduce the viability of myeloma cells. This contributes to the current debate as to whether bisphosphonate therapy has an anti-tumour effect. On the other hand, the analyses indicate that...
    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,... more
    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 morphometri...
    ABSTRACT A set of algorithms has been developed and evaluated for 3D and 2½D rapid prototyping replication of 3D reconstructions of cancellous bone samples. The algorithms replicate a voxel map without any loss of fidelity,... more
    ABSTRACT A set of algorithms has been developed and evaluated for 3D and 2½D rapid prototyping replication of 3D reconstructions of cancellous bone samples. The algorithms replicate a voxel map without any loss of fidelity, so as to increase the validity of the comparison of mechanical tests on the 3D reconstructed models with those predicted by finite element analyses. The evaluation is both in terms of algorithmic complexity and the resultant data set size. The former determines the feasibility of the conversion process, whereas the latter the potential success of the manufacturing process
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    Bone remodelling is a vital process which enables bone to repair, renew and optimize itself. Disorders in the bone remodelling process are inevitably manifested in bone-related diseases, such as hypothyroidism, primary hyperparathyroidism... more
    Bone remodelling is a vital process which enables bone to repair, renew and optimize itself. Disorders in the bone remodelling process are inevitably manifested in bone-related diseases, such as hypothyroidism, primary hyperparathyroidism and osteoporosis. In our previous work, a predator-prey based mathematical model was developed to simulate bone remodelling cycles under normal and two pathological conditions, hypothyroidism and primary hyperparathyroidism, for trabecular bone at a fixed point. However, the biochemical meanings of the model parameters were not fully explored. This article first extends the previous work by proposing relationships between the model parameters and biochemical factors involved in the bone remodelling process and by examining whether those relationships do predict the behaviours observed in vivo. The model is then applied to the simulation and investigation of bone remodelling of postmenopausal osteoporosis. The proposed connections are supported by g...
    Multiple myeloma (MM)-induced bone disease is mortal for most MM patients. Bisphosphonates are first-line treatment for MM-induced bone disease, since it can inhibit osteoclast activity and the resultant bone resorption by suppressing the... more
    Multiple myeloma (MM)-induced bone disease is mortal for most MM patients. Bisphosphonates are first-line treatment for MM-induced bone disease, since it can inhibit osteoclast activity and the resultant bone resorption by suppressing the differentiation of osteoclast precursors into mature osteoclasts, promoting osteoclast apoptosis and disrupting osteoclast function. However, it is still unclear whether bisphosphonates have an anti-tumour effect. In our previous work, a computational model was built to simulate the pathology of MM-induced bone disease. This paper extends this proposed computational model to investigate the efficacy of bisphosphonates treatment and then clear the controversy of this therapy. The extended model is validated through the good agreement between simulation results and experimental data. The simulation results suggest that bisphosphonates indeed have an anti-tumour effect.
    Multiple myeloma (MM) is the second most common haematological malignancy and results in destructive bone lesions. The interaction between MM cells and the bone microenvironment plays an important role in the development of the tumour... more
    Multiple myeloma (MM) is the second most common haematological malignancy and results in destructive bone lesions. The interaction between MM cells and the bone microenvironment plays an important role in the development of the tumour cells and MM-induced bone disease and forms a 'vicious cycle' of tumour development and bone destruction, intensified by suppression of osteoblast activity and promotion of osteoclast activity. In this paper, a mathematical model is proposed to simulate how the interaction between MM cells and the bone microenvironment facilitates the development of the tumour cells and the resultant bone destruction. It includes both the roles of inhibited osteoblast activity and stimulated osteoclast activity. The model is able to mimic the temporal variation of bone cell concentrations and resultant bone volume after the invasion and then removal of the tumour cells and explains why MM-induced bone lesions rarely heal even after the complete removal of MM ce...
    Neck muscle fatigue has been shown to alter an individual's balance in a similar way to that reported in subjects suffering from neck pain or subjects that have suffered a neck injury. The main purpose of the present study was to... more
    Neck muscle fatigue has been shown to alter an individual's balance in a similar way to that reported in subjects suffering from neck pain or subjects that have suffered a neck injury. The main purpose of the present study was to quantify the effects of neck fatigue on neck muscle electromyography (EMG) activity, balance, perceived fatigue and perceived stability. Forty four elite amateur rugby league players resisted with their neck muscles approximately 35% maximum voluntary isometric contraction (MVIC) force for 15 minutes in eight different directions. Sway velocity and surface electromyography were measured. Questionnaires were used to record perceived effort and stability. Repeated measures ANOVA showed that after 15 minutes isometric contraction, significant changes were seen in sway velocity, perceived sway and EMG median frequency. There were no differences in perceived efforts. The changes in sway velocity and median frequency were more pronounced after extension and r...
    Many areas of biomedical engineering involve the modelling of biological systems, often using data from medical scanning techniques such as computed microtomography (microCT), and the prediction of the mechanical properties of these... more
    Many areas of biomedical engineering involve the modelling of biological systems, often using data from medical scanning techniques such as computed microtomography (microCT), and the prediction of the mechanical properties of these systems via finite element models. These models, and also those produced from remodelling simulations on idealized bone structures, are inherently highly pixelated and therefore have a high degree of surface roughness. The purpose of this paper is to demonstrate that this surface roughness need not necessarily have an influence on the predicted properties of the object under examination. To demonstrate this, two-dimensional idealized models of cancellous bone structures were used that were initially depleted and then rebuilt stochastically. A hysteresis effect was observed such that a significant amount of rebuilding beyond the original density was required to regain the initial intact stiffness. To ensure that this effect was not an artefact of the high...
    Three dimensional finite element models with realistic loading conditions were used to analyse the role of the collar of cemented total hip stems. Three types of implant were considered: large collared stems, small collared stems and... more
    Three dimensional finite element models with realistic loading conditions were used to analyse the role of the collar of cemented total hip stems. Three types of implant were considered: large collared stems, small collared stems and totally collarless stems. A computer model of the natural femur provided an indication of the bone stresses before hip replacement, and thus aided the identification of possible mechanisms of bone resorption. In particular, resorption of the medial femoral neck was examined, and its effect on the stress distribution within the stem-cement-bone structure is discussed. The results indicate that loss of bone at the femoral neck is a serious symptom for any design of implant. The factors leading to the resorption are complex but it is clear that it is not a consequence of simple stress shielding of the bone. The most likely cause is the manner in which the stem moves within the femoral shaft, which is a function of whether the stem is collared or not.
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