Bone tissue engineering : reconstruction of critical sized segmental bone defects in the ovine tibia

Well-established therapies for bone defects are restricted to bone grafts which face significant disadvantages (limited availability, donor site morbidity, insufficient integration). Therefore, the objective was to develop an alternative approach investigating the regenerative potential of medical grade polycaprolactone-tricalcium phosphate (mPCL-TCP) and silk-hydroxyapatite (silk-HA) scaffolds. Critical sized ovine tibial defects were created and stabilized. Defects were left untreated, reconstructed with autologous bone grafts (ABG) and mPCL-TCP or silk-HA scaffolds. Animals were observed for 12 weeks. X-ray analysis, torsion testing and quantitative computed tomography (CT) analyses were performed. Radiological analysis confirmed the critical nature of the defects. Full defect bridging occurred in the autograft and partial bridging in the mPCL-TCP group. Only little bone formation was observed with silk-HA scaffolds. Biomechanical testing revealed a higher torsional moment/stiffness (p < 0.05) and CT analysis a significantly higher amount of bone formation for the ABG group when compared to the silk-HA group. No significant difference was determined between the ABG and mPCL-TCP groups. The results of this study suggest that mPCL-TCP scaffolds combined can serve as an alternative to autologous bone grafting in long bone defect regeneration. The combination of mPCL-TCP with osteogenic cells or growth factors represents an attractive means to further enhance bone formation.

Comments on the Australian Accounting Research Foundation's Legislation Policy Discussion Paper NO.4 (A framework for financial reporting by incorporated associations)

The Australian Accounting Research Foundation (AARF) recently issued Legislative Policy Discussion Paper No.4 which proposes a framework for financial reporting by Australian incorporated associations.This paper comments on both the merits and deficiencies of the proposal. In particular it notes that the proposal simply advocates that the application of differential reporting, accounting standards, and the conceptual framework be imposed on incorporated associations by amended statutes. It is noted that in light of long experience in the corporate sector, he espoused benefits of such a move may not eventuate. Further, concern is expressed that the proposal is a blank cheque one because of the inadequacy of existing relevant accounting standards and the proposal to introduce new relevant standards. Another major defect in the proposal is that it emanates from accountants who acknowledge in their conceptual framework, the need for external reports to report on performance through both financial and non-financial reporting methods. Despite that acknowledgment, the standard set of external reports prepared by accountants do not measure performance as defined in their own conceptual framework (SAC 2) and in their auditing pronouncements (AUP 33), and they have restricted their domain to financial reporting (SAC 2). Accordingly the proposal appears to be seriously deficient and it is suggested that it be rejected and a new proposal be prepared by a multi-party group free from vested interests.

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.

Studies on the surface properties of biodegradable polymer carriers in respiratory delivery of drug from Dry Powder Inhaler formulations

Dry Powder Inhaler (DPI) technology has a significant impact in the treatment of various respiratory disorders. DPI formulations consist of a micronized drug (<5ìm) blended with an inert coarse carrier, for which lactose is widely used to date. DPIs are one of the inhalation devices which are used to target the delivery of drugs to the lungs. Drug delivery via DPI formulations is influenced by the physico-chemical characteristics of lactose particles such as size, shape, surface roughness and adhesional forces. Commercially available DPI formulations, which utilise lactose as the carrier, are not efficient in delivering drug to the lungs. The reasons for this are the surface morphology, adhesional properties and surface roughness of lactose. Despite several attempts to modify lactose, the maximum efficient drug delivery to the lungs remains limited; hence, exploring suitable alternative carriers for DPIs is of paramount importance. Therefore, the objective of the project was to study the performance of spherical polymer microparticles as drug carriers and the factors controlling their performance. This study aimed to use biodegradable polymer microspheres as alternative carriers to lactose in DPIs for achieving efficient drug delivery into the lungs. This project focused on fabricating biodegradable polymer microparticles with reproducible surface morphology and particle shape. The surface characteristics of polymeric carriers and the adhesional forces between the drug and carrier particles were investigated in order to gain a better understanding of their influence on drug dispersion. For this purpose, two biodegradable polymers- polycaprolactone (PCL) and poly (DL-lactide-co-glycolide) (PLGA) were used as the carriers to deliver the anti-asthmatic drug - Salbutamol Sulphate (SS). The first study conducted for this dissertation was the aerosolization of SS from mixtures of SS and PCL or PLGA microparticles. The microparticles were fabricated using an emulsion technique and were characterized by laser diffraction for particle size analysis, Scanning Electron Microscopy (SEM) for surface morphology and X-ray Photoelectron Spectroscopy (XPS) to obtain surface elemental composition. The dispersion of the drug from the DPI formulations was determined by using a Twin Stage Impinger (TSI). The Fine particle Fraction (FPF) of SS from powder mixtures was analyzed by High Performance Liquid Chromatography (HPLC). It was found that the drug did not detach from the surface of PCL microspheres. To overcome this, the microspheres were coated with anti-adherent agents such as magnesium stearate and leucine to improve the dispersion of the drug from the carrier surfaces. It was found that coating the PCL microspheres helped in significantly improving the FPF of SS from the PCL surface. These results were in contrast to the PLGA microspheres which readily allowed detachment of the SS from their surface. However, coating PLGA microspheres with antiadherent agents did not further improve the detachment of the drug from the surface. Thus, the first part of the study demonstrated that the surface-coated PCL microspheres and PLGA microspheres can be potential alternatives to lactose as carriers in DPI formulations; however, there was no significant improvement in the FPF of the drug. The second part of the research studied the influence of the size of the microspheres on the FPF of the drug. For this purpose, four different sizes (25 ìm, 48 ìm, 100 ìm and 150 ìm) of the PCL and PLGA microspheres were fabricated and characterized. The dispersion of the drug from microspheres of different sizes was determined. It was found that as the size of the carrier increased there was a significant increase in the FPF of SS. This study suggested that the size of the carrier plays an important role in the dispersion of the drug from the carrier surface. Subsequent experiments in the third part of the dissertation studied the surface properties of the polymeric carrier. The adhesion forces existing between the drug particle and the polymer surfaces, and the surface roughness of the carriers were quantified using Atomic Force Microscopy (AFM). A direct correlation between adhesion forces and dispersion of the drug from the carrier surface was observed suggesting that adhesion forces play an important role in determining the detachment potential of the drug from the carrier surface. However, no direct relationship between the surface roughness of the PCL or PLGA carrier and the FPF of the drug was observed. In conclusion, the body of work presented in this dissertation demonstrated the potential of coated PCL microspheres and PLGA microspheres to be used in DPI formulations as an alternative carrier to sugar based carriers. The study also emphasized the role of the size of the carrier particles and the forces of interaction prevailing between the drug and the carrier particle surface on the aerosolization performances of the drug.

Waterfall : Nature and Culture

Many people take pleasure in visiting waterfalls and much has been written on the subject. Numerous accounts of Niagara Falls were published after Hennepin's late seventeenth-centure descriptions, particularly from the early nineteenth century, but is was only later that other waterfalls became the subject of books. George Holley's Niagara and Other Famous Cataracts of the World, published in 1883, and John Gibson's Great Waterfalls, Cataracts and Geysers, published in 1887, are early examples of global accounts of major falls. Most books about waterfalls are guides to the falls of a particular country, state or region. Apart from a few slim illustrated volumes, few books have been puslished on the world's waterfalls since Edward Rashleigh's Among the Waterfalls (1935). Most of these are slim pictorial volumes, some aimed at the children's market. Geologist Richard Maxwell Pearl published a series of waterfall articles in his journal Earth Science between 1973 and 1975, apparently with the intention of turning them into a book, but this never materialized. My book, the culmination of more than a decade of waterfalls research, is comprehensive in its approach, but is not intended to describe as many of the world's waterfalls as possible. This is far from my aim, and readers may be disappointed at my omission of falls they feel deserved mention. What I have attempted to do is celebrate the delights of these beautiful wonders of nature by considering them from many points of view, emphasizing the roles that they play in the human experience. To be as representative as possible, I draw on examples of waterfalls from all over the world, some famous, many not. North and South America, Europe, Africa, Asia and Oceania and, with recent global warming, the Earth's polar regions, all feature in the discussion. Even though there are already enough books and articles about Niagara Falls to fill a large library, it has been impossible to avoid making frequent reference to this great cataract, which has been so important in the history of travel and tourism, power generation, urban development and art. Amoung the issues that I consider is the human impact on waterfalls, particularly the effects of hydropower schemes and tourism development. Also considered are artificial waterfalls, which have long been features of the designed landscape. Their contemporay role is poignantly exemplified in the design of the National September 11 Memorial, in which the footprints of the Twin Towers are traced by walls of waterfalls. A geographer and urban and regional planner by training, I have ventured into many other fields of knowledge that are outside my areas of expertise. I apologize for any errors that I may have made in my book and invite correction.

Effect of caffeine on adenosine-induced reversible perfusion defects assessed by automated analysis

Objectives This prospective study investigated the effects of caffeine ingestion on the extent of adenosine-induced perfusion abnormalities during myocardial perfusion imaging (MPI). Methods Thirty patients with inducible perfusion abnormalities on standard (caffeine-abstinent) adenosine MPI underwent repeat testing with supplementary coffee intake. Baseline and test MPIs were assessed for stress percent defect, rest percent defect, and percent defect reversibility. Plasma levels of caffeine and metabolites were assessed on both occasions and correlated with MPI findings. Results Despite significant increases in caffeine [mean difference 3,106 μg/L (95% CI 2,460 to 3,752 μg/L; P < .001)] and metabolite concentrations over a wide range, there was no statistically significant change in stress percent defect and percent defect reversibility between the baseline and test scans. The increase in caffeine concentration between the baseline and the test phases did not affect percent defect reversibility (average change −0.003 for every 100 μg/L increase; 95% CI −0.17 to 0.16; P = .97). Conclusion There was no significant relationship between the extent of adenosine-induced coronary flow heterogeneity and the serum concentration of caffeine or its principal metabolites. Hence, the stringent requirements for prolonged abstinence from caffeine before adenosine MPI—based on limited studies—appear ill-founded.

Experimental study on mechanical properties of pumpkin tissue

Purpose: The purpose of this study was to calculate mechanical properties of tough skinned vegetables as a part of Finite Element Modelling (FEM) and simulation of tissue damage during mechanical peeling of tough skinned vegetables. Design/methodology: There are some previous studies on mechanical properties of fruits and vegetables however, behaviour of tissue under different processing operations will be different. In this study indentation test was performed on Peel, Flesh and Unpeeled samples of pumpkin as a tough skinned vegetable. Additionally, the test performed in three different loading rates for peel: 1.25, 10, 20 mm/min and 20 mm/min for flesh and unpeeled samples respectively. The spherical end indenter with 8mm diameter used for the experimental tests. Samples prepare from defect free and ripped pumpkin purchased from local shops in Brisbane, Australia. Humidity and temperature were 20-55% and 20-250C respectively. Findings: Consequently, force deformation and stress and strain of samples were calculated and shown in presented figures. Relative contribution (%) of skin to different mechanical properties is computed and compared with data available from literature. According the results, peel samples had the highest value of rupture force (291N) and as well as highest value of firmness (1411Nm-1). Research limitations/implications: The proposed study focused on one type of tough skinned vegetables and one variety of pumpkin however, more tests will give better understandings of behaviours of tissue. Additionally, the behaviours of peel, unpeeled and flesh samples in different speed of loading will provide more details of tissue damages during mechanical loading. Originality/value: Mechanical properties of pumpkin tissue calculated using the results of indentation test, specifically the behaviours of peel, flesh and unpeeled samples were explored which is a new approach in Finite Element Modelling (FEM) of food processes. Keywords: Finite Element Modelling (FEM), relative contribution, firmness, toughness and rupture force.

Researching doctoral pedagogy close up : design and action in two doctoral programs

With growing international interest in diversifying sites for pedagogical work within the doctorate, doctoral programs of different kinds are being developed in different disciplinary, institutional and national settings. However, little is known about how the pedagogical work of these programs is designed and enacted, and with what effects. In this paper, we present two cases of doctoral pedagogical work being undertaken within different disciplinary and institutional settings to describe how learning opportunities were designed and to theorise what it means to be engaged in doing doctoral pedagogy. Starting from the position that working from a design model supports systematic and rigorous documentation and development of pedagogy, we employ the twin concepts of design and action, drawing broadly on rhetorical and ethnomethodological understandings of pedagogy as social action. Of particular interest within the concept of design itself is the concept of enactment, the translation of designs into the practices of doctoral work. Together, the two cases become a resource for ‘slowing down’ and making visible the practices of doctoral pedagogy that often go unrecognised because they appear so ordinary and everyday. This call for examining close-up existing doctoral education practices and relationships is attending to the ‘next challenge for doctoral education’ (Green, 2009).

Influence of pre-exsiting surface defects on the vibrational properties of Ag nanowires

Large-scale molecular dynamics simulations are performed to characterize the effects of pre-existing surface defects on the vibrational properties of Ag nanowires. It is found that the first order natural frequency of the nanowire appears insensitive to different surface defects, indicating a defect insensitivity property of the nanowire’s Young’s modulus. In the meanwhile, an increase of the quality (Q)-factor is observed due to the presence of defects. Particular, a beat phenomenon is observed for the nanowire with the presence of a surface edge defect, which is driven by a single actuation. It is concluded that different surface defects could act as an effective mean to tune the vibrational properties of nanowires. This study sheds lights on the better understanding of nanowire’s mechanical performance when surface defects are presented, which would benefit the development of nanowire-based devices.

A practical signal processing approach for condition monitoring of low speed machinery using Peak-Hold-Down-Sample algorithm

A simple and effective down-sample algorithm, Peak-Hold-Down-Sample (PHDS) algorithm is developed in this paper to enable a rapid and efficient data transfer in remote condition monitoring applications. The algorithm is particularly useful for high frequency Condition Monitoring (CM) techniques, and for low speed machine applications since the combination of the high sampling frequency and low rotating speed will generally lead to large unwieldy data size. The effectiveness of the algorithm was evaluated and tested on four sets of data in the study. One set of the data was extracted from the condition monitoring signal of a practical industry application. Another set of data was acquired from a low speed machine test rig in the laboratory. The other two sets of data were computer simulated bearing defect signals having either a single or multiple bearing defects. The results disclose that the PHDS algorithm can substantially reduce the size of data while preserving the critical bearing defect information for all the data sets used in this work even when a large down-sample ratio was used (i.e., 500 times down-sampled). In contrast, the down-sample process using existing normal down-sample technique in signal processing eliminates the useful and critical information such as bearing defect frequencies in a signal when the same down-sample ratio was employed. Noise and artificial frequency components were also induced by the normal down-sample technique, thus limits its usefulness for machine condition monitoring applications.

Kaolinite-NMF intercalates

Bulk and size-fractionated kaolinites from seven localities in Australia as well as the Clay Minerals Society Source Clays Georgia KGa-1 and KGa-2 have been studied by X-ray diffraction (XRD), laser scattering, and electron microscopy in order to understand the variation of particle characteristics across a range of environments and to correlate specific particle characteristics with intercalation behavior. All kaolinites have been intercalated with N-methyl (NMF) after pretreatment with hydrazine hydrate, and the relative efficiency of intercalation has been determined using XRD. Intercalate yields of kaolinite: NMF are consistently low for bulk samples that have a high proportion of small-sized particles (i.e., <0.5 µm) and for biphased kaolinites with a high percentage (>60%) of low-defect phase. In general, particle size appears to be a more significant controlling factor than defect distribution in determining the relative yield of kaolinite: NMF intercalate.

Krüppel-associated box (KRAB)-associated co-repressor (KAP-1) Ser-473 phosphorylation regulates heterochromatin protein 1 (HP1- ) mobilization and DNA repair in heterochromatin

The DNA damage response encompasses a complex series of signaling pathways that function to regulate and facilitate the repair of damaged DNA. Recent studies have shown that the repair of transcriptionally inactive chromatin, named heterochromatin, is dependent upon the phosphorylation of the co-repressor, Krüppel-associated box (KRAB) domain-associated protein (KAP-1), by the ataxia telangiectasia-mutated (ATM) kinase. Co-repressors, such as KAP-1, function to regulate the rigid structure of heterochromatin by recruiting histone-modifying enzymes, such HDAC1/2, SETDB1, and nucleosome-remodeling complexes such as CHD3. Here, we have characterized a phosphorylation site in the HP1-binding domain of KAP-1, Ser-473, which is phosphorylated by the cell cycle checkpoint kinase Chk2. Expression of a nonphosphorylatable S473A mutant conferred cellular sensitivity to DNA-damaging agents and led to defective repair of DNA double-strand breaks in heterochromatin. In addition, cells expressing S473A also displayed defective mobilization of the HP1-β chromodomain protein. The DNA repair defect observed in cells expressing S473A was alleviated by depletion of HP1-β, suggesting that phosphorylation of KAP-1 on Ser-473 promotes the mobilization of HP1-β from heterochromatin and subsequent DNA repair. These results suggest a novel mechanism of KAP-1-mediated chromatin restructuring via Chk2-regulated HP1-β exchange from heterochromatin, promoting DNA repair.

Dry powder inhaler formulations : effect of carrier size on the drug dispersion

Background: The size of the carrier influences drug aerosolization from a dry powder inhaler (DPI) formulation. Lactose particles with irregular shape and rough surface in a variety of sizes are additionally used as carriers; however, contradictory reports exist regarding the effect of carrier size on the dispersion of drug. We examined the influence of the spherical particle size of the biodegradable polylactide-co-glycolide (PLGA) carrier on the aerosolization of a model drug, salbutamol sulphate (SS). Methods: Four different sizes (20-150 µm) of polymer carriers were fabricated using solvent evaporation technique and the dispersion of SS from these carriers was measured by a Twin Stage Impinger (TSI). The size and morphological properties of polymer carriers were determined by laser diffraction and SEM, respectively. Results: The FPF was found to increase from 5.6% to 21.3% with increasing carrier sizeup to150 µm. Conclusions: The aerosolization of drug increased linearly with the size of polymer carriers. For a fixed mass of drug particles in a formulation, the mass of drug particles per unit area of carriers is higher in formulations containing the larger carriers, which leads to an increase in the dispersion of drug due to the increased mechanical forces occurred between the carriers and the device walls.

The role of randomly mixed-layered chlorite/smectite in the transformation of smectite to chlorite

Vesicular and groundmass phyllosilicates in a hydrothermally altered basalt from the Point Sal ophiolite, California, have been studied using transmission electron microscopy (TEM). Pore-filling phyllosilicates are texturally characterized as having coherent, relatively thick and defect-free crystals of chlorite (14 Å) with occasional 24-Å periodicities. Groundmass phyllosilicates are texturally characterized as 1) randomly oriented crystals up to 200 Å in width and 2) larger, more coherent crystals up to 1000 Å in width. Small crystallites contain predominantly 14-Å layers with some 24-Å units. Large crystals show randomly interlayered chlorite/smectite (C/S), with approximately 50% chlorite on average. Adjacent smectite-like layers are not uncommon in the groundmass phyllosilicates. Electron microprobe analyses show that Fe/Mg ratios of both groundmass and vesicular phyllosilicates are fairly constant. Termination of brucite-like interlayers has been identified in some of the TEM images. The transformation mechanisms represented by these layer terminations are 1) growth of a brucite-like interlayer within smectite interlayer regions and 2) the dissolution and reprecipitation of elements to form chlorite layers. Both mechanisms require an increase in volume as smectite transforms to chlorite. The data, combined with that from previously published reports, suggest that randomly interlayered C/S is a metastable phase formed in microenvironments with low water/rock ratios. Chlorite forms in microenvironments in the same sample dominated by higher water/rock ratios. The relatively constant number of Mg's in the structure (Mg#) of both structures indicates that in both microenvironments the bulk rock composition has influence over the composition of phyllosilicates.

Kaolinite - NMF intercalates

Bulk and size-fractionated kaolinites from seven localities in Australia as well as the Clay Minerals Society Source Clays Georgia KGa-1 and KGa-2 have been studied by X-ray diffraction (XRD), laser scattering, and electron microscopy in order to understand the variation of particle characteristics across a range of environments and to correlate specific particle characteristics with intercalation behavior. All kaolinites have been intercalated with N-methyl formamide (NMF) after pretreatment with hydrazine hydrate, and the relative efficiency of intercalation has been determined using XRD. Intercalate yields of kaolinite: NMF are consistently low for bulk samples that have a high proportion of small-sized particles (i.e., <0.5 µm) and for biphased kaolinites with a high percentage (>60%) of low-defect phase. In general, particle size appears to be a more significant controlling factor than defect distribution in determining the relative yield of kaolinite: NMF intercalate.