Evolutionary design of bone scaffolds with reference to material selection

The favourable scaffold for bone tissue engineering should have desired characteristic features, such as adequate mechanical strength and three-dimensional open porosity, which guarantee a suitable environment for tissue regeneration. In fact, the design of such complex structures like bone scaffolds is a challenge for investigators. One of the aims is to achieve the best possible mechanical strength-degradation rate ratio. In this paper we attempt to use numerical modelling to evaluate material properties for designing bone tissue engineering scaffold fabricated via the fused deposition modelling technique. For our studies the standard genetic algorithm was used, which is an efficient method of discrete optimization. For the fused deposition modelling scaffold, each individual strut is scrutinized for its role in the architecture and structural support it provides for the scaffold, and its contribution to the overall scaffold was studied. The goal of the study was to create a numerical tool that could help to acquire the desired behaviour of tissue engineered scaffolds and our results showed that this could be achieved efficiently by using different materials for individual struts. To represent a great number of ways in which scaffold mechanical function loss could proceed, the exemplary set of different desirable scaffold stiffness loss function was chosen. © 2012 John Wiley & Sons, Ltd.

Spatial and temporal clusters of Barmah Forest virus disease in Queensland, Australia

Objective To identify the spatial and temporal clusters of Barmah Forest virus (BFV) disease in Queensland in Australia, using geographical information systems (GIS) and spatial scan statistic (SaTScan). Methods We obtained BFV disease cases, population and statistical local areas boundary data from Queensland Health and Australian Bureau of Statistics respectively during 1992-2008 for Queensland. A retrospective Poisson-based analysis using SaTScan software and method was conducted in order to identify both purely spatial and space-time BFV disease high-rate clusters. A spatial cluster size of a proportion of the population and a 200km circle radius and varying time windows from 1 month to 12 months were chosen (for the space-time analysis). Results The spatial scan statistic detected a most likely significant purely spatial cluster (including 23 SLAs) and a most likely significant space-time cluster (including 24 SLAs) in approximately the same location. Significant secondary clusters were also identified from both the analyses in several locations. Conclusions This study provides evidence of the existence of statistically significant BFV disease clusters in Queensland, Australia. The study also demonstrated the relevance and applicability of SaTScan in analysing on-going surveillance data to identify clusters to facilitate the development of effective BFV disease prevention and control strategies in Queensland, Australia.

Phylogeography of Echinocladius martini Cranston (Diptera: Chironomidae) in closed forest streams of eastern Australia

The eastern Australian rainforests have experienced several cycles of range contraction and expansion since the late Miocene that are closely correlated with global glaciation events. Together with ongoing aridification of the continent, this has resulted in current distributions of native closed forest that are highly fragmented along the east coast. Several closed forest endemic taxa exhibit patterns of population genetic structure that are congruent with historical isolation of populations in discrete refugia and reflect evolutionary histories dramatically affected by vicariance. Currently, limited data are available regarding the impact of these past climatic fluctuations on freshwater invertebrate taxa. The non-biting midge species Echinocladius martini Cranston is distributed along the east coast and inhabits predominantly montane streams in closed forest habitat. Phylogeographic structure in E. martini was resolved here at a continental scale by incorporating data from a previous pilot study and expanding the sampling design to encompass populations in the Wet Tropics of north-eastern Queensland, south-east Queensland, New South Wales and Victoria. Patterns of phylogeographic structure revealed several deeply divergent mitochondrial lineages from central and south-eastern Australia that were previously unrecognised and were geographically endemic to closed forest refugia. Estimated divergence times were congruent with late Miocene onset of rainforest contractions across the east coast of Australia. This suggested that dispersal and gene flow among E. martini populations isolated in refugia has been highly restricted historically. Moreover, these data imply, in contrast to existing preconceptions about freshwater invertebrates, that this taxon may be acutely susceptible to habitat fragmentation.

Socio-environmental variability and Barmah Forest virus disease transmission : a review of epidemiological evidence and future prospects

Barmah Forest Virus (BFV) disease is the most rapidly emerging mosquito-borne disease in Australia. BFV transmission depends on factors such as climate, virus, vector and the human population. However, the impact of climatic and social factors on BFV remains to be determined. This paper provided an overview of current research and discusses the future research directions on the BFV transmission. These research findings could be regarded as an impetus towards BFV prevention and control strategies.

Spatio-temporal patterns of Barmah Forest virus disease in Queensland, Australia

Background Barmah Forest virus (BFV) disease is a common and wide-spread mosquito-borne disease in Australia. This study investigated the spatio-temporal patterns of BFV disease in Queensland, Australia using geographical information system (GIS) tools and geostatistical analysis. Methods/Principal Findings We calculated the incidence rates and standardised incidence rates of BFV disease. Moran's I statistic was used to assess the spatial autocorrelation of BFV incidences. Spatial dynamics of BFV disease was examined using semi-variogram analysis. Interpolation techniques were applied to visualise and display the spatial distribution of BFV disease in statistical local areas (SLAs) throughout Queensland. Mapping of BFV disease by SLAs reveals the presence of substantial spatio-temporal variation over time. Statistically significant differences in BFV incidence rates were identified among age groups (χ2 = 7587, df = 7327,p<0.01). There was a significant positive spatial autocorrelation of BFV incidence for all four periods, with the Moran's I statistic ranging from 0.1506 to 0.2901 (p<0.01). Semi-variogram analysis and smoothed maps created from interpolation techniques indicate that the pattern of spatial autocorrelation was not homogeneous across the state. Conclusions/Significance This is the first study to examine spatial and temporal variation in the incidence rates of BFV disease across Queensland using GIS and geostatistics. The BFV transmission varied with age and gender, which may be due to exposure rates or behavioural risk factors. There are differences in the spatio-temporal patterns of BFV disease which may be related to local socio-ecological and environmental factors. These research findings may have implications in the BFV disease control and prevention programs in Queensland.

Communications materials on methods of development of revenue and cost estimates to non-technical audiences

This CDROM includes PDFs of presentations on the following topics: "TXDOT Revenue and Expenditure Trends;" "Examine Highway Fund Diversions, & Benchmark Texas Vehicle Registration Fees;" "Evaluation of the JACK Model;" "Future highway construction cost trends;" "Fuel Efficiency Trends and Revenue Impact"

A tissue engineering solution for segmental defect regeneration in load-bearing long bones

The reconstruction of large defects (>10 mm) in humans usually relies on bone graft transplantation. Limiting factors include availability of graft material, comorbidity, and insufficient integration into the damaged bone. We compare the gold standard autograft with biodegradable composite scaffolds consisting of medical-grade polycaprolactone and tricalcium phosphate combined with autologous bone marrow-derived mesenchymal stem cells (MSCs) or recombinant human bone morphogenetic protein 7 (rhBMP-7). Critical-sized defects in sheep - a model closely resembling human bone formation and structure - were treated with autograft, rhBMP-7, or MSCs. Bridging was observed within 3 months for both the autograft and the rhBMP-7 treatment. After 12 months, biomechanical analysis and microcomputed tomography imaging showed significantly greater bone formation and superior strength for the biomaterial scaffolds loaded with rhBMP-7 compared to the autograft. Axial bone distribution was greater at the interfaces. With rhBMP-7, at 3 months, the radial bone distribution within the scaffolds was homogeneous. At 12 months, however, significantly more bone was found in the scaffold architecture, indicating bone remodeling. Scaffolds alone or with MSC inclusion did not induce levels of bone formation comparable to those of the autograft and rhBMP-7 groups. Applied clinically, this approach using rhBMP-7 could overcome autograft-associated limitations.

Shear tests of hollow flange channel beams with stiffened web openings

LiteSteel beam (LSB) is a new cold-formed steel hollow flange channel section produced using a patented manufacturing process involving simultaneous cold-forming and dual electric resistance welding. The LSBs are commonly used as floor joists and bearers with web openings in residential, industrial and commercial buildings. Their shear strengths are considerably reduced when web openings are included for the purpose of locating building services. Shear tests of LSBs with web openings have shown that there is up to a 60% reduction in the shear capacity due to the inclusion of web openings. Hence there is a need to improve the shear capacity of LSBs with web openings. A cost effective way to eliminate the shear capacity reduction is to attach suitable stiffeners around the web openings. Hence experimental studies were undertaken to investigate the shear behaviour and strength of LSBs with stiffened web openings. In this research, various stiffening methods using plate and LSB stiffeners attached to LSBs using both welding and screw-fastening were attempted. Our test results showed that the stiffening arrangements recommended by past research for cold-formed steel channel beams are not adequate to restore the shear strengths of LSBs with web openings. Therefore new stiffener arrangements were proposed for LSBs with web openings. This paper presents the details of this experimental study and the results including the details of the optimum stiffener details for LiteSteel beams.

Quality and readability of information materials for people with brain tumours and their families

Written information is commonly used to inform patients about their disease and treatment, but must be evidence-based and understandable to be useful. This study assessed the quality of the content and the readability of information brochures for people affected by brain tumours. We randomly selected 18 publicly available brochures. Brochures were assessed by criteria to assess the quality of content using the DISCERN instrument. Readability was tested using three commonly used formulas, which yield the reading grade level required to comprehend the brochure (sixth grade level recommended). The mean overall DISCERN score was 3.17 out of a maximum of 5 (moderate quality); only one achieved a rating greater than 4 (high quality). Only one brochure met the sixth grade readability criteria. Although brochures may have accurate content, few satisfied all of the recommended criteria to evaluate their content. Existing brochures need to be critically reviewed and simplified, consumer-focused brochures produced.

Preparation, characterisation and in vivo osteogenesis of mesoporous bioactive glasses

Bone defects, especially large bone defects, remain a major challenge in orthopaedic surgery. Autologous bone transplantation is considered the most effective treatment, but insufficient donor tissue, coupled with concerns about donor site morbidity, has hindered this approach in large-scale applications. Alternative approaches include implanting biomaterials such as bioactive glass (BG), which has been widely used for bone defect healing, due to having generally good biocompatibility, and can be gradually biodegraded during the process of new bone formation. Mesoporous bioactive glass (MBG) is a newly developed bioactive glass which has been proven to have enhanced in-vitro bioactivity; however the in-vivo osteogenesis has not been studied. A critical problem in using the bone tissue engineering approach to restore large bone defects is that the nutrient supply and cell viability at the centre of the scaffold is severely hampered since the diffusion distance of nutrients and oxygen for cell survival is limited to 150-200µm. Cobalt ions has been shown to mimic hypoxia, which plays a pivotal role in coupling angiogenesis with osteogenesis in-vivo by activating hypoxia inducing factor-1α (HIF-1α) transcription factor, subsequently initiating the expression of genes associated with tissue regeneration. Therefore, one aim of this study is to investigate the in-vivo osteogenesis of MBG by comparison with BG and β-TCP, which are widely used clinically. The other aim is to explore hypoxia-mimicking biomaterials by incorporating Cobalt into MBG and β-TCP. MBG and β-TCP incorporated with 5% cobalt (5Co-MBG and 5CCP) have also been studied in-vivo to determine whether the hypoxic effect has a beneficial effect on the bone formation. The composition and microstructure of synthesised materials (BG, MBG, 5Co-MBG, 5CCP) were characterised, along with the mesopore properties of the MBG materials. Dissolution and cytotoxicity of the Co-containing materials were also investigated. Femoral samples with defects harvested at 4 and 8 weeks were scanned using micro-CT followed by processing for histology (H&E staining) to determine bone formation. Histology of MBG showed a slower rate of bone formation at 4 weeks than BG, however at 8 weeks it could be clearly seen that MBG had more bone formation. The in-vivo results show that the osteogenesis of MBG reciprocates the enhanced performance shown in-vitro compared to BG. Dissolution study showed that Co ions can be efficiently released from MBG and β-TCP in a controllable way. Low amounts of Co incorporated into the MBG and β-TCP showed no significant cytotoxicity and the Co-MBG powders maintained a mesopore structure although not as highly ordered as pure MBG. Preliminary study has shown that Co incorporated samples showed little to no bone formation, instead incurring high lymphocyte activity. Further studies need to be done on Co incorporated materials to determine the cause for high lymphocyte activity in-vivo, which appear to hinder bone formation. In conclusion, this study demonstrated the osteogenic activity of MBG and provided some valuable information of tissue reaction to Co-incorporated MBG and TCP materials.

Preparation, characterization and in vitro angiogenic capacity of cobalt substituted β-tricalcium phosphate ceramics

Divalent cobalt ions (Co2+) have been shown to possess the capacity to induce angiogenesis by activating hypoxia inducible factor-1α (HIF-1α) and subsequently inducing the production of vascular endothelial growth factor (VEGF). However, there are few reports about Co-containing biomaterials for inducing in vitro angiogenesis. The aim of the present work was to prepare Co-containing β-tricalcium phosphate (Co-TCP) ceramics with different contents of calcium substituted by cobalt (0, 2, 5 mol%) and to investigate the effect of Co substitution on their physicochemical and biological properties. Co-TCP powders were synthesized by a chemistry precipitation method and Co-TCP ceramics were prepared by sintering the powder compacts. The effect of Co substitution on phase transition and the sintering property of the β-TCP ceramics was investigated. The proliferation and VEGF expression of human bone marrow mesenchymal stem cells (HBMSCs) cultured with both powder extracts and ceramic discs of Co-TCP was further evaluated. The in vitro angiogenesis was evaluated by the tube-like structure formation of human umbilical vein endothelial cells (HUVECs) cultured on ECMatrix™ in the presence of powder extracts. The results showed that Co substitution suppressed the phase transition from β- to α-TCP. Both the powder extracts and ceramic discs of Co-TCP had generally good cytocompatibility to support HBMSC growth. Importantly, the incorporation of Co into β-TCP greatly stimulated VEGF expression of HBMSCs and Co-TCP showed a significant enhancement of network structure formation of HUVECs compared with pure TCP. Our results suggested that the incorporation of Co into bioceramics is a potential viable way to enhance angiogenic properties of biomaterials. Co-TCP bioceramics may be used for bone tissue regeneration with improved angiogenic capacity.

Leucocytes, cytokines and satellite cells : what role do they play in muscle damage and regeneration following eccentric exercise?

Exercise-induced muscle damage is an important topic in exercise physiology. However several aspects of our understanding of how muscles respond to highly stressful exercise remain unclear In the first section of this review we address the evidence that exercise can cause muscle damage and inflammation in otherwise healthy human skeletal muscles. We approach this concept by comparing changes in muscle function (i.e., the force-generating capacity) with the degree of leucocyte accumulation in muscle following exercise. In the second section, we explore the cytokine response to 'muscle-damaging exercise', primarily eccentric exercise. We review the evidence for the notion that the degree of muscle damage is related to the magnitude of the cytokine response. In the third and final section, we look at the satellite cell response to a single bout of eccentric exercise, as well as the role of the cyclooxygenase enzymes (COX1 and 2). In summary, we propose that muscle damage as evaluated by changes in muscle function is related to leucocyte accumulation in the exercised muscles. 'Extreme' exercise protocols, encompassing unaccustomed maximal eccentric exercise across a large range of motion, generally inflict severe muscle damage, inflammation and prolonged recovery (> 1 week). By contrast, exercise resembling regular athletic training (resistance exercise and downhill running) typically causes mild muscle damage (myofibrillar disruptions) and full recovery normally occurs within a few days. Large variation in individual responses to a given exercise should, however be expected. The link between cytokine and satellite cell responses and exercise-induced muscle damage is not so clear The systemic cytokine response may be linked more closely to the metabolic demands of exercise rather than muscle damage. With the exception of IL-6, the sources of systemic cytokines following exercise remain unclear The satellite cell response to severe muscle damage is related to regeneration, whereas the biological significance of satellite cell proliferation after mild damage or non-damaging exercise remains uncertain. The COX enzymes regulate satellite cell activity, as demonstrated in animal models; however the roles of the COX enzymes in human skeletal muscle need further investigation. We suggest using the term 'muscle damage' with care. Comparisons between studies and individuals must consider changes in and recovery of muscle force-generating capacity.