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.

Capturing gazelles : features of high potential firms and new venture growth

This paper investigates the characteristics of ventures which have the potential to reach high growth and compares this with ‘everyday’ new ventures. Findings of interest in this paper include: • HP firms are characterised by higher human capital, are more likely to have a team of founders, are more likely to be product based. • HP firms are more likely to achieve more extreme levels of growth (both positive and negative). • HP ventures that make a loss are more likely to do so early in the venture process. Those that do hold on show that there can higher levels of loss made later on in firm development. HP firms have higher resource needs, in terms of seeking external finance, but are no more likely to receive external finance than regular firms.

Association of a vitamin D receptor polymorphism with sporadic breast cancer development

Breast cancer is the leading cause of cancer death among Australian women and its incidence is annually increasing. Genetic factors are involved in the complex etiology of breast cancer. The seco-steroid hormone, 1.25 dihydroxy vitamin D3 can influence breast cancer cell growth in vitro. A number of studies have reported correlations between vitamin D receptor (VDR) gene polymorphisms and several diseases including prostate cancer and osteoporosis. In breast cancer, low vitamin D levels in serum are correlated with disease progression and bone metastases, a situation also noted in prostate cancer and suggesting the involvement of the VDR. In our study, 2 restriction fragment length polymorphisms (RFLP) in the 3' region (detected by Apa1 and Taq1) and an initiation codon variant in the 5' end of the VDR gene (detected by Fok1) were tested for association with breast cancer risk in 135 females with sporadic breast cancer and 110 cancer-free female controls. Allele frequencies of the 3' Apa1 polymorphism showed a significant association (p = 0.016; OR = 1.56, 95% CI = 1.09-2.24) while the Taq1 RFLP showed a similar trend (p = 0.053; OR = 1.45, 95% CI = 1.00-2.00). Allele frequencies of the Fok1 polymorphism were not significantly different (p = 0.97; OR = 0.99, 95% CI = 0.69-1.43) in the study population. Our results suggest that specific alleles of the VDR gene located near the 3' region may identify an increased risk for breast cancer and justify further investigation of the role of VDR in breast cancer.

Postdiagnosis personal growth in an Australian population of parents raising children with developmental disability

Background Parenting a child with a developmental disability presents a variety of long-term physical and emotional challenges. When exploring parent wellbeing, the disability field is dominated by a deficit model despite parents reportedly demonstrating coping and resilience. The current study is embedded in a salutogenic theory (Antonovsky, 1979) and explores the potential for parents of children diagnosed with a developmental disability to undergo positive changes. Method Participants were 6 fathers and 27 mothers who completed measures of distress and posttraumatic growth. Results Compared with a number of other Australian samples, participants reported significantly higher levels of posttraumatic growth. Reports of growth did not negate reports of distress. Results also indicated that constructs of distress and growth were independent. Conclusions The research has important implications for disability support services, reminding providers to be cognisant of the potential for growth, as well as distress, thereby permitting an atmosphere conducive to exploring such outcomes.

Phenotypic changes in artemisinin-resistant plasmodium falciparum lines in vitro: evidence for decreased sensitivity to dormancy and growth inhibition

The appearance of Plasmodium falciparum parasites with decreased in vivo sensitivity but no measurable in vitro resistance to artemisinin has raised the urgent need to characterize the artemisinin resistance phenotype. Changes in the temporary growth arrest (dormancy) profile of parasites may be one aspect of this phenotype. In this study, we investigated the link between dormancy and resistance, using artelinic acid (AL)-resistant parasites. Our results demonstrate that the AL resistance phenotype has (i) decreased sensitivity of mature-stage parasites, (ii) decreased sensitivity of the ring stage to the induction of dormancy, and (iii) a faster recovery from dormancy.

Entrepreneurial growth : the role of international knowledge acquisition as moderated by firm age

In line with repeated recent calls for research on specific forms of growth rather than on an undifferentiated notion of “total growth,” our study contributes to the understanding of entrepreneurial growth. By this we mean growth through expansion into new geographic markets and/or via the introduction of new products or services. Building on Penrose's theory of the growth of the firm and on the research streams she has in part inspired, we investigate the impact of knowledge acquisition from international markets on entrepreneurial growth both at home and abroad. We further suggest that the effects of international knowledge acquisition on entrepreneurial growth will vary with firm age. Utilizing longitudinal data on 138 small and medium-sized enterprises (SMEs), we find that the acquisition of knowledge from international markets fuels growth through market development, and that this effect is stronger for international expansion than domestic expansion. Our results also show that firm age negatively moderates the relationship between international knowledge acquisition and entrepreneurial growth via the introduction of new products or services. Specifically, international knowledge acquisition has a positive effect on growth via new products/services development in young firms, but a negative effect in mature firms. We assume this reflects changes over time in how international knowledge is managed.

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.

Molecular genetic analyses of RFLPs for PCR-amplified growth hormone gene, renal kallikrein gene and atrial natriuretic factor gene in essential hypertension

The present study examined polymorphisms of genes that might be involved in the onset of essential hypertension (HT). These included the (i) growth hormone gene (GH1), whose locus has recently been linked to elevated blood pressure (BP) in the stroke-prone SHR, although recent sib-pair analysis of a polymorphism near the human chorionic somatomammotropin gene (a member of the GH cluster) was unable to show linkage with HT; (ii) renal kallikrein gene (KLK1); and (iii) atrial natriuretic factor gene (ANF), where a primary defect in production or activity of kallikrein or ANF could cause NaCl retention and vasoconstriction. Association analyses were conducted to compare restriction fragment length polymorphisms (RFLPs) of each gene in 85 HT and 95 normotensive (NT) Caucasian subjects whose parents had a similar BP status at age ≥50 years. The frequency of the minor allele of (i) a RsaI RFLP in the promoter of GH1, amplified from leukocyte DNA by the polymerase chain reaction, was 0.15 in the HT group and 0.14 in the NT group (χ1=0.34, P=0.55); (ii) a TaqI RFLP for KLK1 was 0.035 in the HT group and 0.015 in the NT group (χ2=1.5, P=0.21); and (iii) a XhoI RFLP for ANF was 0.50 in HTs and 0.46 in NTs (χ2=0.20, P=0.65). Studies of HT pedigrees found one family in which the ANF locus and HT were not linked, owing to an obligate recombinant. The present data thus provide no evidence for involvement of the growth hormone, renal kallikrein, nor ANF gene in the causation of essential hypertension.

Effects of hyperbaric oxygen and inducible nitric oxide synthase inhibitor treatment on femoral head osteonecrosis in a rat model

Introduction: Apoptosis is the final destiny of many cells in the body, though this process has been observed in some pathological processes. One of these pathological processes is femoral head non-traumatic osteonecrosis. Among many pro/anti-apoptotic factors, nitric oxide has recently been an area of further interest. Osteocyte apoptosis and its relation to pro-apoptotic action invite further research, and the inducible form of nitric oxide synthase (iNOS)—which produces a high concentration of nitric oxide—has been flagged. The aim of this study was to investigate the effect of hyperbaric oxygen (HBO) and inducible NOS suppressor (Aminoguanidine) in prevention of femoral head osteonecrosis in an experimental model of osteonecrosis in spontaneous hypertensive rats (SHRs). Methods: After animal ethic approval 34 SHR rats were divided into four groups. Ten rats were allocated to the control group without any treatment, and eight rats were allocated to three treatment groups namely: HBO, Aminoguanidine (AMG), and the combination of HBO and AMG treatments (HBO+AMG). The HBO group received 250 kPa of oxygen via hyperbaric chamber for 30 days started at their 5th week of life; the AMG group received 1mg/ml of AMG in drinking water from the fifth week till the 17th week of life; and the last group received a combination of these treatments. Rats were sacrificed at the end of the 17th week of life and both femurs were analysed for evidence of osteonecrosis using Micro CT scan and H&E staining. Also, osteocyte apoptosis and the presence of two different forms of NOS (inducible (iNOS) and endothelial (eNOS)) were analysed by immunostaining and apoptosis staining (Hoechst and TUNEL). Results: Bone morphology of metaphyseal and epiphyseal area of all rats were investigated and analysed. Micro CT findings revealed significantly higher mean fractional trabecular bone volume (FBV) of metaphyseal area in untreated SHRs compared with all other treatments (HBO, P<0.05, HBO+AMG, P<0.005, and AMG P<0.001). Bone surface to volume ratio also significantly increased with HBO+AMG and AMG treatments when compared with the control group (18.7 Vs 20.8, P<0.05, and 18.7 Vs 21.1, P<0.05). Epiphyseal mean FBV did not change significantly among groups. In the metaphyseal area, trabecular thickness and numbers significantly decreased with AMG treatment, while trabecular separation significantly increased with both AMG and HBO+AMG treatment. Histological ratio of no ossification and osteonecrosis was 37.5%, 43.7%, 18.7% and 6.2% of control, HBO, HBO+AMG and AMG groups respectively with only significant difference observed between HBO and AMG treatment (P<0.01). High concentration of iNOS was observed in the region of osteonecrosis while there was no evidence of eNOS activity around that region. In comparison with the control group, the ratio of osteocyte apoptosis significantly reduced in AMG treatment (P<0.005). We also observed significantly fewer apoptotic osteocytes in AMG group comparing with HBO treatment (P<0.05). Conclusion: None of our treatments prevents osteonecrosis at the histological or micro CT scan level. High concentration of iNOS in the region of osteonecrosis and significant reduction of osteocyte apoptosis with AMG treatment were supportive of iNOS modulating osteocyte apoptosis in SHRs.

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.

Diurnal rhythm and effects of feeding, exercise and recombinant equine growth hormone on serum insulin concentrations in the horse

Reasons for performing the study As growth hormone increases lean body mass, it could be a therapy for obese horses. However, growth hormone use induces hyperinsulinaemia in some species, so further investigation is warranted. Objectives To investigate the effects of feeding, exercise and growth hormone therapy on basal insulin concentrations in healthy horses. Study design In vivo experimental study. Methods Blood samples were obtained every 30 min from 12 geldings over 24 h, to establish basal serum insulin concentrations, before they underwent a 3-week exercise programme. Horses were allocated into 2 groups and exercised for another 4 weeks. Group A received daily i.m. injections of recombinant equine growth hormone; 5 mg/day for 5 days, then 12.5 mg/day for 16 days. Blood samples were taken daily before feeding. Insulin vs. time area under curve of Groups A and B were compared using a Student's unpaired t test. Results Horses demonstrated insulin peaks within 2 h of feeding of 577 ± 108.3 pmol/l at 09.30 h and 342.4 ± 75.7 pmol/l at 17.30 h, despite receiving the same meal. The nadir was between midnight and 07.30 h. Exercise had no effect on basal insulin concentrations prior to equine growth hormone administrations. The equine growth hormone injections increased serum insulin concentrations (P = 0.01) within Group A, from 44.4 ± 15.3 pmol/l initially to 320.9 ± 238.2 pmol/l by Day 12. Exogenous growth hormone caused variable hyperinsulinaemia, which was alleviated once equine growth hormone administration ceased. Conclusions Single serum samples taken prior to the morning meal provide basal insulin concentrations. Exercise did not change basal insulin concentrations. However, equine growth hormone injections increased basal insulin concentrations, which were not ameliorated by exercise. Potential relevance This therapy is not recommended to address obesity in insulin-resistant equids.

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.

A meta-analytic clarification of the relationship between posttraumatic growth and symptoms of posttraumatic distress disorder

Traumatic experiences can have a powerful impact on individuals and communities but the relationship between perceptions of beneficial and pathological outcomes are not known. Therefore, this meta-analysis examined both the strength and the linearity of the relationship between symptoms of posttraumatic stress disorder (PTSD) and perceptions of posttraumatic growth (PTG) as well as identifying the potential moderating roles of trauma type and age. Literature searches of all languages were conducted using the ProQuest, Wiley Interscience, ScienceDirect, Informaworld and Web of Science databases. Linear and quadratic (curvilinear) rs as well as βs were analysed. Forty-two studies (N=11, 469) that examined both PTG and symptoms of PTSD were included in meta-analytic calculations. The combined studies yielded a significant linear relationship between PTG and PTSD symptoms (r=.315, CI = 0.299, 0.331), but also a significantly stronger (as tested by Fisher’s transformation) curvilinear relationship (r=.372, CI = 0.353, 0.391). The strength and linearity of these relationships differed according to trauma type and age. The results remind those working with traumatised people that positive and negative post-trauma outcomes can co-occur. A focus only on PTSD symptoms only may limit or slow recovery and mask the potential for growth.