A flexible Bayesian model for describing temporal variability of N2O emissions from an Australian pasture

Soil-based emissions of nitrous oxide (N2O), a well-known greenhouse gas, have been associated with changes in soil water-filled pore space (WFPS) and soil temperature in many previous studies. However, it is acknowledged that the environment-N2O relationship is complex and still relatively poorly unknown. In this article, we employed a Bayesian model selection approach (Reversible jump Markov chain Monte Carlo) to develop a data-informed model of the relationship between daily N2O emissions and daily WFPS and soil temperature measurements between March 2007 and February 2009 from a soil under pasture in Queensland, Australia, taking seasonal factors and time-lagged effects into account. The model indicates a very strong relationship between a hybrid seasonal structure and daily N2O emission, with the latter substantially increased in summer. Given the other variables in the model, daily soil WFPS, lagged by a week, had a negative influence on daily N2O; there was evidence of a nonlinear positive relationship between daily soil WFPS and daily N2O emission; and daily soil temperature tended to have a linear positive relationship with daily N2O emission when daily soil temperature was above a threshold of approximately 19°C. We suggest that this flexible Bayesian modeling approach could facilitate greater understanding of the shape of the covariate-N2O flux relation and detection of effect thresholds in the natural temporal variation of environmental variables on N2O emission.

The mechanics of microdamage and microfracture in trabecular bone

This thesis presents a study using mechanical testing techniques combined with advanced computational methods to examine the mechanics of bone. It contributes novel observations and analysis of how bones fail at the microscopic level, which will be valuable in furthering our understanding and the treatment of bone damage in health and disease, including osteoporosis.

Mining temporal and spatial travel regularities for transit planning

Smart Card data from Automated Fare Collection system has been considered as a promising source of information for transit planning. However, literature has been limited to mining travel patterns from transit users and suggesting the potential of using this information. This paper proposes a method for mining spatial regular origins-destinations and temporal habitual travelling time from transit users. These travel regularity are discussed as being useful for transit planning. After reconstructing the travel itineraries, three levels of Density-Based Spatial Clustering of Application with Noise (DBSCAN) have been utilised to retrieve travel regularity of each of each frequent transit users. Analyses of passenger classifications and personal travel time variability estimation are performed as the examples of using travel regularity in transit planning. The methodology introduced in this paper is of interest for transit authorities in planning and managements

Fabrication and in vitro characterisation of bioactive glass composite scaffolds for bone regeneration

Here we fabricate and characterise bioactive composite scaffolds for bone tissue engineering applications. 45S5 Bioglass® (45S5) or strontium-substituted bioactive glass (SrBG) were incorporated into polycaprolactone (PCL) and fabricated into 3D bioactive composite scaffolds utilising additive manufacturing technology. We show that composite scaffolds (PCL/45S5 and PCL/SrBG) can be reproducibly manufactured with a scaffold morphology highly resembling that of PCL scaffolds. Additionally, micro-CT analysis reveals BG particles were homogeneously distributed throughout the scaffolds. Mechanical data suggested that PCL/45S5 and PCL/SrBG composite scaffolds have higher compressive Young’s modulus compared to PCL scaffolds at similar porosity (~75%). After 1 day in accelerated degradation conditions using 5M NaOH, PCL/SrBG, PCL/45S5 and PCL lost 48.6 ±3.8%, 12.1 ±1% and 1.6 ±1% of its original mass, respectively. In vitro studies were conducted using MC3T3 cells under normal and osteogenic conditions. All scaffolds were shown to be non-cytotoxic, and supported cell attachment and proliferation. Our results also indicate that the inclusion of bioactive glass (BG) promotes precipitation of calcium phosphate on the scaffold surfaces which leads to earlier cell differentiation and matrix mineralisation when compared to PCL scaffolds. However, as indicated by ALP activity, no significant difference in osteoblast differentiation was found between PCL/45S5 and PCL/SrBG scaffolds. These results suggest that PCL/45S5 and PCL/SrBG composite scaffold shows potential as a next generation bone scaffold.

Melt-electrospun polycaprolactone-strontium substituted bioactive glass scaffolds for bone regeneration

Polycaprolactone (PCL) is a resorbable polymer used extensively in bone tissue engineering owing to good structural properties and processability. Strontium substituted bioactive glass (SrBG) has the ability to promote osteogenesis and may be incorporated into scaffolds intended for bone repair. Here we describe for the first time, the development of a PCL-SrBG composite scaffold incorporating 10% (weight) of SrBG particles into PCL bulk, produced by the technique of melt-electrospinning. We show that we are able to reproducibly manufacture composite scaffolds with an interconnected porous structure and, furthermore, these scaffolds were demonstrated to be non-cytotoxic in vitro. Ions present in the SrBG component were shown to dissolve into cell culture media and promoted precipitation of a calcium phosphate layer on the scaffold surface which in turn led to noticeably enhanced alkaline phosphatase activity in MC3T3-E1 cells compared to PLC-only scaffolds. These results suggest that melt-electrospun PCL-SrBG composite scaffolds show potential to become effective bone graft substitutes.

The effect of polystyrene sodium sulfonate grafting on polyethylene terephthalate artificial ligaments on in vitro mineralisation and in vivo bone tissue integration

This study investigates the impact of polystyrene sodium sulfonate (PolyNaSS) grafting onto the osseo-integration of a polyethylene terephthalate artificial ligament (Ligament Advanced Reinforcement System, LARS™) used for Anterior Cruciate Ligament (ACL). The performance of grafted and non-grafted ligaments was assessed in vitro by culturing human osteoblasts under osteogenic induction and this demonstrated that the surface modification was capable of up-regulating the secretion of ALP and induced higher level of mineralisation as measured 6 weeks post-seeding by Micro-Computed Tomography. Grafted and non-grafted LARS™ were subsequently implanted in an ovine model for ACL reconstruction and the ligament-to-bone interface was evaluated by histology and biomechanical testings 3 and 12 months post-implantation. The grafted ligaments exhibited more frequent direct ligament-to-bone contact and bone formation in the core of the ligament at the later time point than the non-grafted specimens, the grafting also significantly reduced the fibrous encapsulation of the ligament 12 months post-implantation. However, this improved osseo-integration was not translated into a significant increase in the biomechanical pull-out loads. These results provide evidences that PolyNaSS grafting improved the osseo-integration of the artificial ligament within the bone tunnels. This might positively influence the outcome of the surgical reconstructions, as higher ligament stability is believed to limit micro-movement and therefore permits earlier and enhanced healing.

Spatio-temporal modelling of ultrafine particle number concentration

This thesis developed semi-parametric regression models for estimating the spatio-temporal distribution of outdoor airborne ultrafine particle number concentration (PNC). The models developed incorporate multivariate penalised splines and random walks and autoregressive errors in order to estimate non-linear functions of space, time and other covariates. The models were applied to data from the "Ultrafine Particles from Traffic Emissions and Child" project in Brisbane, Australia, and to longitudinal measurements of air quality in Helsinki, Finland. The spline and random walk aspects of the models reveal how the daily trend in PNC changes over the year in Helsinki and the similarities and differences in the daily and weekly trends across multiple primary schools in Brisbane. Midday peaks in PNC in Brisbane locations are attributed to new particle formation events at the Port of Brisbane and Brisbane Airport.

Controlling whole blood activation and resultant clot properties on various material surfaces : a possible therapeutic approach for enhancing bone healing

Injured bone initiates the healing process by forming a blood clot at the damaged site. However, in severe damage, synthetic bone implants are used to provide structural integrity and restore the healing process. The implant unavoidably comes into direct contact with whole blood, leading to a blood clot formation on its surface. Despite this, most research in bone tissue engineering virtually ignores the important role of a blood clot in supporting healing. Surface chemistry of a biomaterial is a crucial property in mediating blood-biomaterials interactions, and hence the formation of the resultant blood clot. Surfaces presenting mixtures of functional groups carboxyl (–COOH) and methyl (–CH3) have been shown to enhance platelet response and coagulation activation, leading to the formation of fibrin fibres. In addition, it has been shown that varying the compositions of these functional groups and the length of alkyl groups further modulate the immune complement response. In this study, we hypothesised that a biomaterial surface with mixture of –COOH/–CH3(methyl), –CH2CH3 (ethyl) or –(CH2)3CH3 (butyl) groups at different ratios would modulate blood coagulation and complement activation, and eventually tailor the structural and functional properties of the blood clot formed on the surface, which subsequently impacts new bone formation. Firstly, we synthesised a series of materials composed of acrylic acid (AA), and methyl (MMA), ethyl (EMA) or butyl methacrylates (BMA) at different ratios and coated on the inner surfaces of incubation vials. Our surface analysis showed that the amount of –COOH groups on the surface coatings was lower than the ratios of AA prepared in the materials even though the surface content of –COOH groups increased with increasing in AA ratios. It was indicated that the surface hydrophobicity increased with increasing alkyl chain length: –CH 3 > –CH2CH3 > –(CH2)3CH3, and decreased with increasing –COOH groups. No significant differences in surface hydrophobicity was found on surfaces with –CH3 and –CH2CH3 groups in the presence of –COOH groups. The material coating was as smooth as uncoated glass and without any major flaws. The average roughness of material-coated surface (3.99 ± 0.54 nm) was slightly higher than that of uncoated glass surface (2.22 ± 0.29 nm). However, no significant differences in surface average roughness was found among surfaces with the same functionalities at different –COOH ratios nor among surfaces with different alkyl groups but the same –COOH ratios. These suggested that the surface functional groups and their compositions had a combined effect on modulating surface hydrophobicity but not surface roughness. The second part of our study was to investigate the effect of surface functional groups and their compositions on blood cascade activation and structural properties of the formed clots. It was found that surfaces with –COOH/–(CH2)3CH3 induced a faster coagulation activation than those with –COOH/–CH3 and –CH2CH3, regardless of the –COOH ratios. An increase in –COOH ratios on –COOH/–CH3 and –CH2CH3 surfaces decreased the rate of activation. Moreover, all material-coated surfaces markedly reduced the complement activation compared to uncoated glass surfaces, and the pattern of complement activation was entirely similar to that of surface-induced coagulation, suggesting there is an interaction between two cascades. The clots formed on material-coated surfaces had thicker fibrin with a tighter network at the exterior when compared to uncoated glass surfaces. Compared to the clot exteriors, thicker fibrins with a loose network were found in clot interiors. Coated surfaces resulted in more rigid clots with a significantly slower fibrinolysis after 1 h of lysis when compared to uncoated glass surfaces. Significant differences in fibrinolysis after 1 h of lysis among clots on material-coated surfaces correlated well with the differences in fibrin thickness and density at clot exterior. In addition, more growth factors were released during clot formation than during clot lysis. From an intact clot, there was a correlation between the amount of PDGF-AB release and fibrin density. Highest amount of PDGF-AB was released from clots formed on surfaces with 40% –COOH/60% –CH 3 (i.e. 65MMA). During clot lysis, the release of PDGF-AB also correlated with the fibrinolytic rate while the release of TGF-â1 was influenced by the fibrin thickness. This suggested that different clot structures led to different release profiles of growth factors in clot intact and degrading stages. We further validated whether the clots formed on material-coatings provide the microenvironment for improved bone healing by using a rabbit femoral defect model. In this pilot study, the implantation of clots formed on 65MMA coatings significantly increased new bone formation with enhanced chondrogenesis, osteoblasts activity and vascularisation, but decreased inflammatory macrophage number at the defects after 4 weeks when compared to commercial bone grafts ChronOSTM â-TCP granules. Empty defects were observed when blood clot formation was inhibited. In summary, our study demonstrated that surface functional groups and their relative ratios on material coatings synergistically modulate activation of blood cascades, resultant fibrin architecture, rigidity, susceptibility to fibrinolysis as well as growth factor release of the formed clots, which ultimately alter the healing microenvironment of injured bones.

How to increase the accuracy of analysis and reduce the computational time in ANSYS in the case of deformation study of orthopedic bone plates

Currently, finite element analyses are usually done by means of commercial software tools. Accuracy of analysis and computational time are two important factors in efficiency of these tools. This paper studies the effective parameters in computational time and accuracy of finite element analyses performed by ANSYS and provides the guidelines for the users of this software whenever they us this software for study on deformation of orthopedic bone plates or study on similar cases. It is not a fundamental scientific study and only shares the findings of the authors about structural analysis by means of ANSYS workbench. It gives an idea to the readers about improving the performance of the software and avoiding the traps. The solutions provided in this paper are not the only possible solutions of the problems and in similar cases there are other solutions which are not given in this paper. The parameters of solution method, material model, geometric model, mesh configuration, number of the analysis steps, program controlled parameters and computer settings are discussed through thoroughly in this paper.

Mathematical modelling of soft callus formation in early murine bone repair

Fracture healing is a complicated coupling of many processes. Yet despite the apparent complexity, fracture repair is usually effective. There is, however, no comprehensive mathematical model addressing the multiple interactions of cells, cytokines and oxygen that includes extra-cellular matrix production and that results in the formation of the early stage soft callus. This thesis develops a one dimensional continuum transport model in the context of early fracture healing. Although fracture healing is a complex interplay of many local factors, critical components are identified and used to construct an hypothesis about regulation of the evolution of early callus formation. Multiple cell lines, cellular differentiation, oxygen levels and cytokine concentrations are examined as factors affecting this model of early bone repair. The model presumes diffusive and chemotactic cell migration mechanisms. It is proposed that the initial signalling regime and oxygen availability arising as consequences of bone fracture, are sufficient to determine the quantity and quality of early soft callus formation. Readily available software and purpose written algorithms have been used to obtain numerical solutions representative of various initial conditions. These numerical distributions of cellular populations reflect available histology obtained from murine osteotomies. The behaviour of the numerical system in response to differing initial conditions can be described by alternative in vivo healing pathways. An experimental basis, as illustrated in murine fracture histology, has been utilised to validate the mathematical model outcomes. The model developed in this thesis has potential for future extension, to incorporate processes leading to woven bone deposition, while maintaining the characteristics that regulate early callus formation.

Osteogenic differentiation of bone marrow MSCs by β-tricalcium phosphate stimulating macrophages via BMP2 signalling pathway

Immune reactions play important roles in determining the in vivo fate of bone substitute materials, either in new bone formation or inflammatory fibrous tissue encapsulation. The paradigm for the development of bone substitute materials has been shifted from inert to immunomodulatory materials, emphasizing the importance of immune cells in the material evaluation. Macrophages, the major effector cells in the immune reaction to implants, are indispensable for osteogenesis and their heterogeneity and plasticity render macrophages a primer target for immune system modulation. However, there are very few reports about the effects of macrophages on biomaterial-regulated osteogenesis. In this study, we used b-tricalcium phosphate (b-TCP) as a model biomaterial to investigate the role of macrophages on the material stimulated osteogenesis. The macrophage phenotype switched to M2 extreme in response to b-TCP extracts, which was related to the activation of calcium-sensing receptor (CaSR) pathway. Bone morphogenetic protein 2 (BMP2) was also significantly upregulated by the b-TCP stimulation, indicating that macrophage may participate in the b-TCP stimulated osteogenesis. Interestingly, when macrophageconditioned b-TCP extracts were applied to bone marrow mesenchymal stem cells (BMSCs), the osteogenic differentiation of BMSCs was significantly enhanced, indicating the important role of macrophages in biomaterial-induced osteogenesis. These findings provided valuable insights into the mechanism of material-stimulated osteogenesis, and a strategy to optimize the evaluation system for the in vitro osteogenesis capacity of bone substitute materials.

Mussel-inspired bioceramics with self-assembled Ca-P/polydopamine composite nanolayer : preparation, formation mechanism, improved cellular bioactivity and osteogenic differentiation of bone marrow stromal cells

The nanostructured surface of biomaterials plays an important role in improving their in vitro cellular bioactivity as well as stimulating in vivo tissue regeneration. Inspired by the mussel’s adhesive versatility, which is thought to be due to the plaque–substrate interface being rich in 3,4-dihydroxy-L-phenylalamine (DOPA) and lysine amino acids, in this study we developed a self-assembly method to prepare a uniform calcium phosphate (Ca-P)/polydopamine composite nanolayer on the surface of b-tricalcium phosphate (b-TCP) bioceramics by soaking b-TCP bioceramics in Tris–dopamine solution. It was found that the addition of dopamine, reaction temperature and reaction time are three key factors inducing the formation of a uniform Ca-P/polydopamine composite nanolayer. The formation mechanism of a Ca-P/polydopamine composite nanolayer involved two important steps: (i) the addition of dopamine to Tris–HCl solution decreases the pH value and accelerates Ca and P ionic dissolution from the crystal boundaries of b-TCP ceramics; (ii) dopamine is polymerized to form self-assembled polydopamine film and, at the same time, nanosized Ca-P particles are mineralized with the assistance of polydopamine, in which the formation of polydopamine occurs simultaneously with Ca-P mineralization (formation of nanosized microparticles composed of calcium phosphate-based materials), and finally a self-assembled Ca-P/polydopamine composite nanolayer forms on the surface of the b-TCP ceramics. Furthermore, the formed self-assembled Ca-P/polydopamine composite nanolayer significantly enhances the surface roughness and hydrophilicity of b-TCP ceramics, and stimulates the attachment, proliferation, alkaline phosphate (ALP) activity and bone-related gene expression (ALP, OCN, COL1 and Runx2) of human bone marrow stromal cells. Our results suggest that the preparation of self-assembled Ca-P/polydopamine composite nanolayers is a viable method to modify the surface of biomaterials by significantly improving their surface physicochemical properties and cellular bioactivity for bone regeneration application.

Impact of extracellular matrix derived from osteoarthritis subchondral bone osteoblasts on osteocytes : role of integrinβ1 and focal adhesion kinase signaling cues

INTRODUCTION: Our recent study indicated that subchondral bone pathogenesis in osteoarthritis (OA) is associated with osteocyte morphology and phenotypic abnormalities. However, the mechanism underlying this abnormality needs to be identified. In this study we investigated the effect of extracellular matrix (ECM) produced from normal and OA bone on osteocytic cells function. METHODS: De-cellularized matrices, resembling the bone provisional ECM secreted from primary human subchondral bone osteoblasts (SBOs) of normal and OA patients were used as a model to study the effect on osteocytic cells. Osteocytic cells (MLOY4 osteocyte cell line) cultured on normal and OA derived ECMs were analyzed by confocal microscopy, scanning electron microscopy (SEM), cell attachment assays, zymography, apoptosis assays, qRT-PCR and western blotting. The role of integrinβ1 and focal adhesion kinase (FAK) signaling pathways during these interactions were monitored using appropriate blocking antibodies. RESULTS: The ECM produced by OA SBOs contained less mineral content, showed altered organization of matrix proteins and matrix structure compared with the matrices produced by normal SBOs. Culture of osteocytic cells on these defective OA ECM resulted in a decrease of integrinβ1 expression and the de-activation of FAK cell signaling pathway, which subsequently affected the initial osteocytic cell's attachment and functions including morphological abnormalities of cytoskeletal structures, focal adhesions, increased apoptosis, altered osteocyte specific gene expression and increased Matrix metalloproteinases (MMP-2) and -9 expression. CONCLUSION: This study provides new insights in understanding how altered OA bone matrix can lead to the abnormal osteocyte phenotypic changes, which is typical in OA pathogenesis.

A Bayesian network approach to modelling temporal behaviour of Lyngbya majuscula bloom initiation

Lyngbya majuscula is a cyanobacterium (blue-green algae) occurring naturally in tropical and subtropical coastal areas worldwide. Deception Bay, in Northern Moreton Bay, Queensland, has a history of Lyngbya blooms, and forms a case study for this investigation. The South East Queensland (SEQ) Healthy Waterways Partnership, collaboration between government, industry, research and the community, was formed to address issues affecting the health of the river catchments and waterways of South East Queensland. The Partnership coordinated the Lyngbya Research and Management Program (2005-2007) which culminated in a Coastal Algal Blooms (CAB) Action Plan for harmful and nuisance algal blooms, such as Lyngbya majuscula. This first phase of the project was predominantly of a scientific nature and also facilitated the collection of additional data to better understand Lyngbya blooms. The second phase of this project, SEQ Healthy Waterways Strategy 2007-2012, is now underway to implement the CAB Action Plan and as such is more management focussed. As part of the first phase of the project, a Science model for the initiation of a Lyngbya bloom was built using Bayesian Networks (BN). The structure of the Science Bayesian Network was built by the Lyngbya Science Working Group (LSWG) which was drawn from diverse disciplines. The BN was then quantified with annual data and expert knowledge. Scenario testing confirmed the expected temporal nature of bloom initiation and it was recommended that the next version of the BN be extended to take this into account. Elicitation for this BN thus occurred at three levels: design, quantification and verification. The first level involved construction of the conceptual model itself, definition of the nodes within the model and identification of sources of information to quantify the nodes. The second level included elicitation of expert opinion and representation of this information in a form suitable for inclusion in the BN. The third and final level concerned the specification of scenarios used to verify the model. The second phase of the project provides the opportunity to update the network with the newly collected detailed data obtained during the previous phase of the project. Specifically the temporal nature of Lyngbya blooms is of interest. Management efforts need to be directed to the most vulnerable periods to bloom initiation in the Bay. To model the temporal aspects of Lyngbya we are using Object Oriented Bayesian networks (OOBN) to create ‘time slices’ for each of the periods of interest during the summer. OOBNs provide a framework to simplify knowledge representation and facilitate reuse of nodes and network fragments. An OOBN is more hierarchical than a traditional BN with any sub-network able to contain other sub-networks. Connectivity between OOBNs is an important feature and allows information flow between the time slices. This study demonstrates more sophisticated use of expert information within Bayesian networks, which combine expert knowledge with data (categorized using expert-defined thresholds) within an expert-defined model structure. Based on the results from the verification process the experts are able to target areas requiring greater precision and those exhibiting temporal behaviour. The time slices incorporate the data for that time period for each of the temporal nodes (instead of using the annual data from the previous static Science BN) and include lag effects to allow the effect from one time slice to flow to the next time slice. We demonstrate a concurrent steady increase in the probability of initiation of a Lyngbya bloom and conclude that the inclusion of temporal aspects in the BN model is consistent with the perceptions of Lyngbya behaviour held by the stakeholders. This extended model provides a more accurate representation of the increased risk of algal blooms in the summer months and show that the opinions elicited to inform a static BN can be readily extended to a dynamic OOBN, providing more comprehensive information for decision makers.

Bone matters in lung cancer

Background: Bone metastases are a significant and undertreated clinical problem in patients with advanced lung cancer. Design: We reviewed the incidence of bone metastases and skeletal-related events (SREs) in patients with lung cancer and examined the burden on patients' lives and on health care systems. Available therapies to improve survival and lessen the impact of SREs on quality of life (QoL) were also investigated. Results: Bone metastases are common in lung cancer; however, owing to short survival times, data on the incidences of SREs are limited. As with other cancers, the costs associated with treating SREs in lung cancer are substantial. Bisphosphonates reduce the frequency of SREs and improve measures of pain and QoL in patients with lung cancer; however, nephrotoxicity is a common complication of therapy. Denosumab, a recently approved bone-targeted therapy, is superior to zoledronic acid in increasing the time to first on-study SRE in patients with solid tumours, including lung cancer. Additional roles of bone-targeted therapies beyond the prevention of SREs are under investigation. Conclusions: With increasing awareness of the consequences of SREs, bone-targeted therapies may play a greater role in the management of patients with lung cancer, with the aim of delaying disease progression and preserving QoL. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology.