Effect of surgical approach on bone vascularisation, fracture and soft tissue healing : comparison of less invasive to open approach

Over the past ten years, minimally invasive plate osteosynthesis (MIPO) for the fixation of long bone fractures has become a clinically accepted method with good outcomes, when compared to the conventional open surgical approach (open reduction internal fixation, ORIF). However, while MIPO offers some advantages over ORIF, it also has some significant drawbacks, such as a more demanding surgical technique and increased radiation exposure. No clinical or experimental study to date has shown a difference between the healing outcomes in fractures treated with the two surgical approaches. Therefore, a novel, standardised severe trauma model in sheep has been developed and validated in this project to examine the effect of the two surgical approaches on soft tissue and fracture healing. Twenty four sheep were subjected to severe soft tissue damage and a complex distal femur fracture. The fractures were initially stabilised with an external fixator. After five days of soft tissue recovery, internal fixation with a plate was applied, randomised to either MIPO or ORIF. Within the first fourteen days, the soft tissue damage was monitored locally with a compartment pressure sensor and systemically by blood tests. The fracture progress was assessed fortnightly by x-rays. The sheep were sacrificed in two groups after four and eight weeks, and CT scans and mechanical testing performed. Soft tissue monitoring showed significantly higher postoperative Creatine Kinase and Lactate Dehydrogenase values in the ORIF group compared to MIPO. After four weeks, the torsional stiffness was significantly higher in the MIPO group (p=0.018) compared to the ORIF group. The torsional strength also showed increased values for the MIPO technique (p=0.11). The measured total mineralised callus volumes were slightly higher in the ORIF group. However, a newly developed morphological callus bridging score showed significantly higher values for the MIPO technique (p=0.007), with a high correlation to the mechanical properties (R2=0.79). After eight weeks, the same trends continued, but without statistical significance. In summary, this clinically relevant study, using the newly developed severe trauma model in sheep, clearly demonstrates that the minimally invasive technique minimises additional soft tissue damage and improves fracture healing in the early stage compared to the open surgical approach method.

The effect of red blood cell orientation on the electrical impedance of pulsatile blood with implications for impedance cardiography

Impedance cardiography is an application of bioimpedance analysis primarily used in a research setting to determine cardiac output. It is a non invasive technique that measures the change in the impedance of the thorax which is attributed to the ejection of a volume of blood from the heart. The cardiac output is calculated from the measured impedance using the parallel conductor theory and a constant value for the resistivity of blood. However, the resistivity of blood has been shown to be velocity dependent due to changes in the orientation of red blood cells induced by changing shear forces during flow. The overall goal of this thesis was to study the effect that flow deviations have on the electrical impedance of blood, both experimentally and theoretically, and to apply the results to a clinical setting. The resistivity of stationary blood is isotropic as the red blood cells are randomly orientated due to Brownian motion. In the case of blood flowing through rigid tubes, the resistivity is anisotropic due to the biconcave discoidal shape and orientation of the cells. The generation of shear forces across the width of the tube during flow causes the cells to align with the minimal cross sectional area facing the direction of flow. This is in order to minimise the shear stress experienced by the cells. This in turn results in a larger cross sectional area of plasma and a reduction in the resistivity of the blood as the flow increases. Understanding the contribution of this effect on the thoracic impedance change is a vital step in achieving clinical acceptance of impedance cardiography. Published literature investigates the resistivity variations for constant blood flow. In this case, the shear forces are constant and the impedance remains constant during flow at a magnitude which is less than that for stationary blood. The research presented in this thesis, however, investigates the variations in resistivity of blood during pulsataile flow through rigid tubes and the relationship between impedance, velocity and acceleration. Using rigid tubes isolates the impedance change to variations associated with changes in cell orientation only. The implications of red blood cell orientation changes for clinical impedance cardiography were also explored. This was achieved through measurement and analysis of the experimental impedance of pulsatile blood flowing through rigid tubes in a mock circulatory system. A novel theoretical model including cell orientation dynamics was developed for the impedance of pulsatile blood through rigid tubes. The impedance of flowing blood was theoretically calculated using analytical methods for flow through straight tubes and the numerical Lattice Boltzmann method for flow through complex geometries such as aortic valve stenosis. The result of the analytical theoretical model was compared to the experimental impedance measurements through rigid tubes. The impedance calculated for flow through a stenosis using the Lattice Boltzmann method provides results for comparison with impedance cardiography measurements collected as part of a pilot clinical trial to assess the suitability of using bioimpedance techniques to assess the presence of aortic stenosis. The experimental and theoretical impedance of blood was shown to inversely follow the blood velocity during pulsatile flow with a correlation of -0.72 and -0.74 respectively. The results for both the experimental and theoretical investigations demonstrate that the acceleration of the blood is an important factor in determining the impedance, in addition to the velocity. During acceleration, the relationship between impedance and velocity is linear (r2 = 0.98, experimental and r2 = 0.94, theoretical). The relationship between the impedance and velocity during the deceleration phase is characterised by a time decay constant, ô , ranging from 10 to 50 s. The high level of agreement between the experimental and theoretically modelled impedance demonstrates the accuracy of the model developed here. An increase in the haematocrit of the blood resulted in an increase in the magnitude of the impedance change due to changes in the orientation of red blood cells. The time decay constant was shown to decrease linearly with the haematocrit for both experimental and theoretical results, although the slope of this decrease was larger in the experimental case. The radius of the tube influences the experimental and theoretical impedance given the same velocity of flow. However, when the velocity was divided by the radius of the tube (labelled the reduced average velocity) the impedance response was the same for two experimental tubes with equivalent reduced average velocity but with different radii. The temperature of the blood was also shown to affect the impedance with the impedance decreasing as the temperature increased. These results are the first published for the impedance of pulsatile blood. The experimental impedance change measured orthogonal to the direction of flow is in the opposite direction to that measured in the direction of flow. These results indicate that the impedance of blood flowing through rigid cylindrical tubes is axisymmetric along the radius. This has not previously been verified experimentally. Time frequency analysis of the experimental results demonstrated that the measured impedance contains the same frequency components occuring at the same time point in the cycle as the velocity signal contains. This suggests that the impedance contains many of the fluctuations of the velocity signal. Application of a theoretical steady flow model to pulsatile flow presented here has verified that the steady flow model is not adequate in calculating the impedance of pulsatile blood flow. The success of the new theoretical model over the steady flow model demonstrates that the velocity profile is important in determining the impedance of pulsatile blood. The clinical application of the impedance of blood flow through a stenosis was theoretically modelled using the Lattice Boltzman method (LBM) for fluid flow through complex geometeries. The impedance of blood exiting a narrow orifice was calculated for varying degrees of stenosis. Clincial impedance cardiography measurements were also recorded for both aortic valvular stenosis patients (n = 4) and control subjects (n = 4) with structurally normal hearts. This pilot trial was used to corroborate the results of the LBM. Results from both investigations showed that the decay time constant for impedance has potential in the assessment of aortic valve stenosis. In the theoretically modelled case (LBM results), the decay time constant increased with an increase in the degree of stenosis. The clinical results also showed a statistically significant difference in time decay constant between control and test subjects (P = 0.03). The time decay constant calculated for test subjects (ô = 180 - 250 s) is consistently larger than that determined for control subjects (ô = 50 - 130 s). This difference is thought to be due to difference in the orientation response of the cells as blood flows through the stenosis. Such a non-invasive technique using the time decay constant for screening of aortic stenosis provides additional information to that currently given by impedance cardiography techniques and improves the value of the device to practitioners. However, the results still need to be verified in a larger study. While impedance cardiography has not been widely adopted clinically, it is research such as this that will enable future acceptance of the method.

Evidence of multiwall carbon nanotube deformation caused by poly(3-hexylthiophene) adhesion

We show that when a soft polymer like Poly(3-hexyl-thiophene) wraps multiwall nanotubes by coiling around the main axis, a localized deformation of the nanotube structure is observed. High resolution transmission electron microscopy shows that radial compressions of about 4% can take place, and could possibly lead to larger interlayer distance between the nanotube inner walls and reduce the innermost nanotube radius. The mechanical stress due to the polymer presence was confirmed by Raman spectroscopic observation of a gradual upshift of the carbon nanotube G-band when the polymer content in the composites was progressively increased. Vibrational spectroscopy also indicates that charge transfer from the polymer to the nanotubes is responsible for a peak frequency relative downshift for high P3HT-content samples. Continuously acquired transmission electron microscopy images at rising temperature show the MWCNT elastic compression and relaxation due to polymer rearrangement on the nanotube surface.

Application of hyperbaric oxygen in bone tissue engineering : effect of hyperbaric oxygen treatment on bone marrow stem cells

and non-union of bony fractures has been proposed since 1966, little has been known about the effect of HBOT on bone marrow stem cells (BMSC). The aim of this study is to investigate the effect of HBO treatment on osteogenetic differentiation of BMSC and potential application in bone tissue engineering. Adhesive stromal cells harvested from bone marrow were characterized by mesenchymal differentiation potential, cell surface markers and their proliferation capacity. Mesenchymal stem cells, which demonstrated osteogenic, chondrogenic and adipogenic differentiation potential and expressed positively for CD 29, CD 44, CD 73, CD 90, CD 105, CD 166 and negatively for CD34 and CD 45, were selected and treated in a laboratory-scale HBO chamber using different oxygen pressures and exposure times. No obvious effect of HBO treatment on BMSC proliferation was noticed. However, cytotoxic effects of HBO were considerably less pronounced when cells were cultured in medium supplemented with 10% FBS in comparison to medium supplemented with 2% FCS, as was evaluated by WST-1 assay. Under HBO treatment, bone nodules were formed in three days, which was clearly revealed by Von Kossa staining. In contrasts, without HBO treatment, bone nodules were not detected until 9-12 days using the same inducing culture media. Calcium deposition was also significantly increased after three days of HBO treatments compared to no HBO treatment. In addition it was also found that oxygen played a direct role in the enhancement of BMSC osteogenic differentiation, which was independent of the effect of air pressure.

The patella morphology in trochlear dysplasia : a comparative MRI study

BACKGROUND: Trochlear dysplasia is suspected to have a genetic basis and causes recurrent patellar instability due to insufficient anatomical geometry. Numerous studies about trochlear morphology and the optimal surgical treatment have been carried out, but no attention has been paid to the corresponding patellar morphology.----- ----- PURPOSE: The aim of this study was the evaluation of the patellar morphology in normal and trochlear dysplastic knees. ----- ----- STUDY DESIGN: Biometric analysis. ----- ----- METHODS: Twenty two patellae with underlying trochlear dysplasia (study group--SG) were compared with 22 matched knees with normal trochlear shape (control group--CG) on transverse and sagittal MRI slices. We compared transverse diameter, cartilaginous thickness, Wiberg-index and -angle, length and radius of lateral and medial facet, patellar shape and angle, retropatellar length, and type of trochlear dysplasia. For statistical analysis we used the Wilcoxon signed ranks test. ----- ----- RESULTS: The transverse and sagittal diameter, mean length of medial patellar facet, and mean cartilaginous and subchondral Wiberg-index showed statistical differences between the two groups. ----- ----- CONCLUSIONS: Although the insufficient trochlear depth and decreased lateral trochlear slope are responsible for patellofemoral instability, the patella shows morphological changes in trochlear dysplastic knees. Its overall size and the medial facet are smaller. Although the femoral sulcus angle is larger, the Wiberg-angle and -index are equal to the control group. This may indicate that the patellar morphology may not be a result of missing medial patellofemoral pressure in trochlear dysplastic knees, but a decreased medial patellofemoral traction. This seems to be caused by hypotrophic medial patellofemoral restraints in combination with an increased lateral patellar tilt, both resulting in a decreased tension onto the medial patella facet. Whether there is a genetic component to the patellar morphology remains open.

The effect of friction on indenter force and pile-up in numerical simulations of bone nanoindentation

Nanoindentation is a useful technique for probing the mechanical properties of bone, and finite element (FE) modeling of the indentation allows inverse determination of elasto-plastic constitutive properties. However, all but one FE study to date have assumed frictionless contact between indenter and bone. The aim of this study was to explore the effect of friction in simulations of bone nanoindentation. Two dimensional axisymmetric FE simulations were performed using a spheroconical indenter of tip radius 0.6 m and angle 90°. The coefficient of friction between indenter and bone was varied between 0.0 (frictionless) and 0.3. Isotropic linear elasticity was used in all simulations, with bone elastic modulus E=13.56GPa and Poisson‟s ratio f 0.3. Plasticity was incorporated using both Drucker-Prager and von Mises yield surfaces. Friction had a modest effect on the predicted force-indentation curve for both von Mises and Drucker-Prager plasticity, reducing maximum indenter displacement by 10% and 20% respectively as friction coefficient was increased from zero to 0.3 (at a maximum indenter force of 5mN). However, friction has a much greater effect on predicted pile-up after indentation, reducing predicted pile-up from 0.27 to 0.11 m with a von Mises model, and from 0.09 to 0.02 m with Drucker-Prager plasticity. We conclude that it is potentially important to include friction in nanoindentation simulations of bone if pile-up is used to compare simulation results with experiment.

Is there a difference between narrowing of the spinal canal and neurological deficits comparing Denis and Magerl classifications?

We have read with great interest the retrospective study by Caffaro and Avanzi1 evaluating the relation between narrowing of the spinal canal and neurological deficits in patients with burst-type fractures of the spine. The authors are to be commended for obtaining detailed neurological and radiological data in a large cohort of 227 patients. The authors conclude: “The percentage of narrowing of the spinal canal proved to be a pre-disposing factor for the severity of the neurological status in thoracolumbar and lumbar burst-type fractures according to the classifications of Denis and Magerl.” Although this conclusion is mainly in accordance with previous findings, we would like to comment on the methodological approach applied in the current study.

Application of an optimisation algorithm to configure an internal fixation device

Fractures of long bones are sometimes treated using various types of fracture fixation devices including internal plate fixators. These are specialised plates which are used to bridge the fracture gap(s) whilst anatomically aligning the bone fragments. The plate is secured in position by screws. The aim of such a device is to support and promote the natural healing of the bone. When using an internal fixation device, it is necessary for the clinician to decide upon many parameters, for example, the type of plate and where to position it; how many and where to position the screws. While there have been a number of experimental and computational studies conducted regarding the configuration of screws in the literature, there is still inadequate information available concerning the influence of screw configuration on fracture healing. Because screw configuration influences the amount of flexibility at the area of fracture, it has a direct influence on the fracture healing process. Therefore, it is important that the chosen screw configuration does not inhibit the healing process. In addition to the impact on the fracture healing process, screw configuration plays an important role in the distribution of stresses in the plate due to the applied loads. A plate that experiences high stresses is prone to early failure. Hence, the screw configuration used should not encourage the occurrence of high stresses. This project develops a computational program in Fortran programming language to perform mathematical optimisation to determine the screw configuration of an internal fixation device within constraints of interfragmentary movement by minimising the corresponding stress in the plate. Thus, the optimal solution suggests the positioning and number of screws which satisfies the predefined constraints of interfragmentary movements. For a set of screw configurations the interfragmentary displacement and the stress occurring in the plate were calculated by the Finite Element Method. The screw configurations were iteratively changed and each time the corresponding interfragmentary displacements were compared with predefined constraints. Additionally, the corresponding stress was compared with the previously calculated stress value to determine if there was a reduction. These processes were continued until an optimal solution was achieved. The optimisation program has been shown to successfully predict the optimal screw configuration in two cases. The first case was a simplified bone construct whereby the screw configuration solution was comparable with those recommended in biomechanical literature. The second case was a femoral construct, of which the resultant screw configuration was shown to be similar to those used in clinical cases. The optimisation method and programming developed in this study has shown that it has potential to be used for further investigations with the improvement of optimisation criteria and the efficiency of the program.

Prospective association between physical activity and falls in community-dwelling older women

Abstract Objective: To explore associations between physical activity and risk of falls and broken or fractured bones in community-dwelling older women. Design, setting and participants: This was a prospective observational survey with 3- and 6-year follow-ups. The sample included 8562 healthy, community-dwelling women, aged 70-75 years in 1996, who completed surveys as participants in the Australian Longitudinal Study on Women’s Health. Outcomes were reports of a fall to the ground, injury from a fall, and broken or fractured bones in 1999 and 2002. The main predictor variable was physical activity level in 1996, categorized based on weekly frequency as none/very low, low, moderate, high, and very high. Covariates were demographic and health-related variables. Logistic regression models were computed separately for each outcome in 1999 and 2002. Main results: In multivariable models, very high physical activity was associated with decreased risk of a fall in 1999 (odds ratio 0.67, 95% CI 0.48 to 0.93) and in 2002 (odds ratio 0.62, 95% CI 0.42 to 0.92). High/very high physical activity was associated with decreased risk of broken or fractured bones in 2002 (odds ratio 0.64, 95% CI 0.42 to 0.96). No significant association was found between physical activity and injury from a fall. Conclusions: The results suggest that at least daily moderate to vigorous physical activity is required for the primary prevention of falls to the ground and broken or fractured bones in women aged 70-75 years.

Pattern recognition using invariants defined from higher order spectra : 2-D image inputs

A new algorithm for extracting features from images for object recognition is described. The algorithm uses higher order spectra to provide desirable invariance properties, to provide noise immunity, and to incorporate nonlinearity into the feature extraction procedure thereby allowing the use of simple classifiers. An image can be reduced to a set of 1D functions via the Radon transform, or alternatively, the Fourier transform of each 1D projection can be obtained from a radial slice of the 2D Fourier transform of the image according to the Fourier slice theorem. A triple product of Fourier coefficients, referred to as the deterministic bispectrum, is computed for each 1D function and is integrated along radial lines in bifrequency space. Phases of the integrated bispectra are shown to be translation- and scale-invariant. Rotation invariance is achieved by a regrouping of these invariants at a constant radius followed by a second stage of invariant extraction. Rotation invariance is thus converted to translation invariance in the second step. Results using synthetic and actual images show that isolated, compact clusters are formed in feature space. These clusters are linearly separable, indicating that the nonlinearity required in the mapping from the input space to the classification space is incorporated well into the feature extraction stage. The use of higher order spectra results in good noise immunity, as verified with synthetic and real images. Classification of images using the higher order spectra-based algorithm compares favorably to classification using the method of moment invariants

Influence of internal fixator stiffness on murine fracture healing : two types of fracture healing lead to two distinct cellular events and FGF-2 expressions

This study aimed to clarify the relationship between the mechanical environment at the fracture site and endogenous fibroblast growth factor-2 (FGF-2). We compared two types of fracture healing with different callus formations and cellular events using MouseFix(TM) plate fixation systems for murine fracture models. Left femoral fractures were induced in 72 ten-week-old mice and then fixed with a flexible (Group F) or rigid (Group R) Mouse Fix(TM) plate. Mice were sacrificed on days 3, 5, 7, 10, 14, and 21. The callus volumes were measured by 3D micro-CT and tissues were histologically stained with hematoxylin & eosin or safranin-O. Sections from days 3, 5, and 7 were immunostained for FGF-2 and Proliferating Cell Nuclear Antigen (PCNA). The callus in Group F was significantly larger than that in Group R. The rigid plate allowed bone union without a marked external callus or chondrogenesis. The flexible plate formed a large external callus as a result of endochondral ossification. Fibroblastic cells in the granulation tissue on days 5 and 7 in Group F showed marked FGF-2 expression compared with Group R. Fibroblastic cells showed ongoing proliferation in granulation tissue in group F, as indicated by PCNA expression, which explained the relative granulation tissue increase in group F. There were major differences in early phase endogenous FGF-2 expression between these two fracture healing processes, due to different mechanical environments.

Journeys with friends

Journeys with Friends Truna aka J. Turner, Giselle Rosman and Matt Ditton Panel Session description: We are no longer an industry (alone) we are a sector. Where the model once consisted of industry making games, we now see the rise of a cultural sector playing in the game space – industry, indies (for whatever that distinction implies) artists (another odd distinction), individuals and well … everyone and their mums. This evolution has an affect – on audiences and who they are, what they expect and want, and how they understand the purpose and language of these “digital game forms’; how we talk about our worlds and the kinds of issues that are raised; on what we create and how we create it and on our communities and who we are. This evolution has an affect on how these works are understood within the wider social context and how we present this understanding to the next generation of makers and players. We can see the potential of this evolution from industry to sector in the rise of the Australian indie. We can see the potential fractures created by this evolution in the new voices that ask questions about diversity and social justice. And yet, we still see a ‘solution’ type reaction to the current changing state of our sector which announces the monolithic, Fordist model as desirable (albeit in smaller form) – with the subsequent ramifications for ‘training’ and production of local talent. Experts talk about a mismatch of graduate skills and industry needs, insufficient linkages between industry and education providers and the need to explore opportunity for the now passing model in new spaces such as adver-games and serious games. Head counts of Australian industry don’t recognise trans media producers as being part of their purview or opportunity, they don’t count the rise of the cultural playful game inspired creative works as one of thier team. Such perspectives are indeed relevant to the Australian Games Industry, but what about the emerging Australian Games Sector? How do we enable a future in such a space? This emerging sector is perhaps best represented by Melbourne’s Freeplay audience: a heady mix of indie developers, players, artists, critical thinkers and industry. Such audiences are no longer content with an ‘industry’ alone; they are the community who already see themselves as an important, vibrant cultural sector. Part of the discussion presented here seeks to identify and understand the resources, primarily in the context of community and educational opportunities, available to the evolving sector now relying more on the creative processes. This creative process and community building is already visibly growing within the context of smaller development studios, often involving more multiskilling production methodologies where the definition of ‘game’ clearly evolves beyond the traditional one.

MRI study of the changes in crystalline lens shape with accommodation and ageing in humans

Magnetic Resonance Imaging was used to study changes in the crystalline lens and ciliary body with accommodation and aging. Monocular images were obtained in 15 young (19-29 years) and 15 older (60-70 years) emmetropes when viewing at far (6m) and at individual near points (14.5 to 20.9 cm) in the younger group. With accommodation, lens thickness increased (mean±95% CI: 0.33±0.06mm) by a similar magnitude to the decrease in anterior chamber depth (0.31±0.07mm) and equatorial diameter (0.32±0.04mm) with a decrease in the radius of curvature of the posterior lens surface (0.58±0.30mm). Anterior lens surface shape could not be determined due to the overlapping region with the iris. Ciliary ring diameter decreased (0.44±0.17mm) with no decrease in circumlental space or forward ciliary body movement. With aging, lens thickness increased (mean±95% CI: 0.97±0.24mm) similar in magnitude to the sum of the decrease in anterior chamber depth (0.45±0.21mm) and increase in anterior segment depth (0.52±0.23mm). Equatorial lens diameter increased (0.28±0.23mm) with no change in the posterior lens surface radius of curvature. Ciliary ring diameter decreased (0.57±0.41mm) with reduced circumlental space (0.43±0.15mm) and no forward ciliary body movement. Accommodative changes support the Helmholtz theory of accommodation including an increase in posterior lens surface curvature. Certain aspects of aging changes mimic accommodation.

Can the Cardiac ARIA Index Improve Cardiac Care for Australia's Indigenous Population?

Background: Timely access to appropriate cardiac care is critical for optimising outcomes. Our aim was to derive an objective, comparable, geographic measure reflecting access to cardiac services for Australia's 20,387 population locations. Methods: An expert panel defined a single patient care pathway. Using geographic information systems (GIS) the numeric/alpha index was modelled in two phases. The acute phase index (numeric) ranged from 1 (access to tertiary centre with PCI ≤1 h) to 8 (no ambulance service, >3 h to medical facility, air transport required). The aftercare index was modelled into 5 alphabetic categories; A (Access to general practitioner, pharmacy, cardiac rehabilitation, pathology ≤1 h) to E (no services available within 1 h). Results: Approximately 70% or 13.9 million people lived within a CardiacARIAindex category 1A location. Disparity continues in access to category 1A cardiac services for 5.8 million (30%) of all Australians, 60% of Aboriginal and Torres Strait Islander people and 32% of people over 65 years of age. In a cardiac emergency only 40% of the Indigenous population reside within one hour of category 1 hospital. Approximately 30% (81,491 Indigenous persons) are more than one to three hours from basic cardiac services. Conclusion: Geographically, the majority of Australian's have timely access for survival of a cardiac event. The CardiacARIAindex objectively demonstrates that the healthcare system may not be providing for the needs of 60% of Indigenous people residing outside the 1A geographic radius. Innovative clinical practice maybe required to address these disparities.