Development of a method to assess the quality of ankle joint reduction in 3D

This project developed a quantitative method for determining the quality of the surgical alignment of the bone fragments after an ankle fracture. The research examined the feasibility of utilising MRI-based bone models versus the gold standard CT-based bone models in order to reduce the amount of ionising radiation the patient is exposed to. In doing so, the thesis reports that there is potential for MRI to be used instead of CT depending on the scanning parameters used to obtain the medical images, the distance of the implant relative to the joint surface, and the implant material.

WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk

We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ~2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2×10-9). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3×10-12, and -0.16 SD per G allele, P = 1.2×10-15, respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3×10-9), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9×10-6 and rs2707466: OR = 1.22, P = 7.2×10-6). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16-/- mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5×10-13<P<5.9×10-4) at both femur and tibia, compared with their wild-type littermates. Natural variation in humans and targeted disruption in mice demonstrate that WNT16 is an important determinant of CBT, BMD, bone strength, and risk of fracture. © 2012 Zheng et al.

Legal translation

Legal translation theory brooks little interference with the source legal text. With few exceptions (Joseph 2005; Hammel 2008; Harvey 2002; Kahaner 2005; Kasirer 2001; Lawson 2006), lawyers and linguists tend to tether themselves to the pole of literalism. More a tight elastic band than an unyielding rope, this tether constrains — rather than prohibits — liberal legal translations. It can stretch to accommodate a degree of freedom by the legal translator however, should it go too far, it snaps back to the default position of linguistic fidelity. This ‘stretch and snap’ gives legal translation a unique place in general translation theory. In the general debate over the ‘degree of freedom’ the translator enjoys in conveying the meaning of the text, legal translation theory has reached its own settlement. Passivity is the default; creativity, the ‘qualified’ exception (Hammel 2008: 275).

Automated fit assessment of intramedullary nail designs during insertion

Modern intramedullary nails, which are utilised for the treatment of bone fractures, need to be designed to fit the anatomy of the patient population. Traditional and recent semi-automated approaches for quantifying the anatomical fit between bones and nail designs suffer from various drawbacks. This thesis proposed an automated comprehensive nail design validation method. The developed software tool was utilised to quantify the anatomical fit of four commercial nail designs. Furthermore, the thesis demonstrated the existence of a bone-nail specific nail entry point. The developed method is of great benefit for the implant manufacturing industry as a nail design validation tool.

Biofabrication of customized bone grafts by combination of additive manufacturing and bioreactor knowhow

This study reports on an original concept of additive manufacturing for the fabrication of tissue engineered constructs (TEC), offering the possibility of concomitantly manufacturing a customized scaffold and a bioreactor chamber to any size and shape. As a proof of concept towards the development of anatomically relevant TECs, this concept was utilized for the design and fabrication of a highly porous sheep tibia scaffold around which a bioreactor chamber of similar shape was simultaneously built. The morphology of the bioreactor/scaffold device was investigated by micro-computed tomography and scanning electron microscopy confirming the porous architecture of the sheep tibiae as opposed to the non-porous nature of the bioreactor chamber. Additionally, this study demonstrates that both the shape, as well as the inner architecture of the device can significantly impact the perfusion of fluid within the scaffold architecture. Indeed, fluid flow modelling revealed that this was of significant importance for controlling the nutrition flow pattern within the scaffold and the bioreactor chamber, avoiding the formation of stagnant flow regions detrimental for in vitro tissue development. The bioreactor/scaffold device was dynamically seeded with human primary osteoblasts and cultured under bi-directional perfusion for two and six weeks. Primary human osteoblasts were observed homogenously distributed throughout the scaffold, and were viable for the six week culture period. This work demonstrates a novel application for additive manufacturing in the development of scaffolds and bioreactors. Given the intrinsic flexibility of the additive manufacturing technology platform developed, more complex culture systems can be fabricated which would contribute to the advances in customized and patient-specific tissue engineering strategies for a wide range of applications.

Laser capture microdissection and multiplex-tandem PCR analysis of proximal tubular epithelial cell signaling in human kidney disease

Interstitial fibrosis, a histological process common to many kidney diseases, is the precursor state to end stage kidney disease, a devastating and costly outcome for the patient and the health system. Fibrosis is historically associated with chronic kidney disease (CKD) but emerging evidence is now linking many forms of acute kidney disease (AKD) with the development of CKD. Indeed, we and others have observed at least some degree of fibrosis in up to 50% of clinically defined cases of AKD. Epithelial cells of the proximal tubule (PTEC) are central in the development of kidney interstitial fibrosis. We combine the novel techniques of laser capture microdissection and multiplex-tandem PCR to identify and quantitate “real time” gene transcription profiles of purified PTEC isolated from human kidney biopsies that describe signaling pathways associated with this pathological fibrotic process. Our results: (i) confirm previous in-vitro and animal model studies; kidney injury molecule-1 is up-regulated in patients with acute tubular injury, inflammation, neutrophil infiltration and a range of chronic disease diagnoses, (ii) provide data to inform treatment; complement component 3 expression correlates with inflammation and acute tubular injury, (iii) identify potential new biomarkers; proline 4-hydroxylase transcription is down-regulated and vimentin is up-regulated across kidney diseases, (iv) describe previously unrecognized feedback mechanisms within PTEC; Smad-3 is down-regulated in many kidney diseases suggesting a possible negative feedback loop for TGF-β in the disease state, whilst tight junction protein-1 is up-regulated in many kidney diseases, suggesting feedback interactions with vimentin expression. These data demonstrate that the combined techniques of laser capture microdissection and multiplex-tandem PCR have the power to study molecular signaling within single cell populations derived from clinically sourced tissue.

Transcutaneous bone-anchoring prosthesis with knee replacement: A novel treatment for amputees

Background Over the last two decades, Transcutaneous Bone-Anchored Prosthesis (TCBAP) has proven to be an effective alternative for prosthetic attachment for amputees, particularly for individuals unable to wear a socket. [1-17] However, the load transmitted through a typical TCBAP to the residual tibia and knee joint can be unbearable for transtibial amputees with knee arthritis. Aim A. To describe the surgical procedure combining TKR with TCBAP for the first time; and B. To present preliminary data on potential risks and benefits with assessment of clinical and functional outcomes at follow up Method We used a TCBAP connected to the tibial base plate of a Total Knee Replacement (TKR) prosthesis enabling the tibial residuum and the knee joint to act as weight sharing structures by transferring the load directly to the femur. We performed a standard hinged TKR connected to a custom made TCBAP at the first stage followed by creating a skin implant interface as a second stage. We retrospectively reviewed four cases of trans-tibial amputations presenting with knee joint arthritis. Patients were assessed clinically and functionally including standard measures of health-related quality of life, amputee mobility predictor tool, ambulation tests and actual activity level. Progress was monitored for 6-24 months. Results Clinical outcomes including adverse events show no major complications but one case of superficial infection. Functional outcomes improved for all participants as early as 6 months follow up. Discussion & Conclusion TKR and TCBAP were combined for the first time in this proof-of-concept case series. The preliminary outcomes indicated that this procedure is potentially a safe and effective alternative for this patient group despite the theoretical increase in risk of ascending infection through the skin-implant interface to the external environment. We suggest larger comparative series to further validate these results.

The multiple sclerosis whole blood mRNA transcriptome and genetic associations indicate dysregulation of specific T cell pathways in pathogenesis

Multiple sclerosis (MS) is an autoimmune disease with a genetic component, caused at least in part by aberrant lymphocyte activity. The whole blood mRNA transcriptome was measured for 99 untreated MS patients: 43 primary progressive MS, 20 secondary progressive MS, 36 relapsing remitting MS and 45 age-matched healthy controls. The ANZgene Multiple Sclerosis Genetics Consortium genotyped more than 300 000 SNPs for 115 of these samples. Transcription from genes on translational regulation, oxidative phosphorylation, immune synapse and antigen presentation pathways was markedly increased in all forms of MS. Expression of genes tagging T cells was also upregulated (P < 10-12) in MS. A T cell gene signature predicts disease state with a concordance index of 0.79 with age and gender as co-variables, but the signature is not associated with clinical course or disability. The ANZgene genome wide association screen identified two novel regions with genome wide significance: one encoding the T cell co-stimulatory molecule, CD40; the other a region on chromosome 12q13-14. The CD40 haplotype associated with increased MS susceptibility has decreased gene expression in MS (P < 0.0007). The second MS susceptibility region includes 17 genes on 12q13-14 in tight linkage disequilibrium. Of these, only 13 are expressed in leukocytes, and of these the expression of one, FAM119B, is much lower in the susceptibility haplotype (P tdthomlt; 10-14). Overall, these data indicate dysregulation of T cells can be detected in the whole blood of untreated MS patients, and supports targeting of activated T cells in therapy for all forms of MS.

The trend toward pre-graduation professional work experience for Australian young planners: Essential experience or essentially exploitation

This paper explores the changing employment expectations that frame the early professional work experiences of young planners in Australia. In particular, it considers the rising popularity of pre-graduation professional work experience as a precursor to formal entry into the workforce as a practising planner. This shift is being driven in part by employer expectations that graduates will already have ‘real world’ and relevant work experience. However, an equally significant driver appears to be a growing desire for early career and graduate planners to find ways to distinguish themselves from their peers in an increasingly tight labour market. Using data from an ongoing research project into the formative work experiences of young people this paper describes the three main types of pre-graduation professional work experience undertaken by young planners. It highlights the potential challenges and benefits of pre-graduation work experience from a legal, social and ethical perspective as well as from the perspective of young planners themselves. The paper concludes by reflecting on the role of the planning profession – employers, peak bodies and planning educators – in managing the tensions between producing ‘work ready’ graduates and safeguarding the employment conditions of early career planning professionals.

Osseointegrated total knee replacement connected to a lower limb prosthesis: 4 cases

Background and purpose — Osseointegrated implants are an alternative for prosthetic attachment in individuals with amputation who are unable to wear a socket. However, the load transmitted through the osseointegrated fixation to the residual tibia and knee joint can be unbearable for those with transtibial amputation and knee arthritis. We report on the feasibility of combining total knee replacement (TKR) with an osseointegrated implant for prosthetic attachment. Patients and methods — We retrospectively reviewed all 4 cases (aged 38–77 years) of transtibial amputations managed with osseointegration and TKR in 2012–2014. The below-the-knee prosthesis was connected to the tibial base plate of a TKR, enabling the tibial residuum and knee joint to act as weight-sharing structures. A 2-stage procedure involved connecting a standard hinged TKR to custom-made implants and creation of a skin-implant interface. Clinical outcomes were assessed at baseline and after 1–3 years of follow-up using standard measures of health-related quality of life, ambulation, and activity level including the questionnaire for transfemoral amputees (Q-TFA) and the 6-minute walk test. Results — There were no major complications, and there was 1 case of superficial infection. All patients showed improved clinical outcomes, with a Q-TFA improvement range of 29–52 and a 6-minute walk test improvement range of 37–84 meters. Interpretation — It is possible to combine TKR with osseointegrated implants.

Can we safely deform a plate to fit every bone? Population-based fit assessment and finite element deformation of a distal tibial plate

Anatomically precontoured plates are commonly used to treat periarticular fractures. A well-fitting plate can be used as a tool for anatomical reduction of the fractured bone. Recent studies highlighted that some plates fit poorly for many patients due to considerable shape variations between bones of the same anatomical site. While it is impossible to design one shape that fits all, it is also burdensome for the manufacturers and hospitals to produce, store and manage multiple plate shapes without the certainty of utilization by a patient population. In this study, we investigated the number of shapes required for maximum fit within a given dataset, and if they could be obtained by manually deforming the original plate. A distal medial tibial plate was automatically positioned on 45 individual tibiae, and the optimal deformation was determined iteratively using finite element analysis simulation. Within the studied dataset, we found that: (i) 89% fit could be achieved with four shapes, (ii) 100% fit was impossible through mechanical deformation, and (iii) the deformations required to obtain the four plate shapes were safe for the stainless steel plate for further clinical use. The proposed framework is easily transferable to other orthopaedic plates.

A bottom-up integration of vision and actions to create cognitive humanoids

In recent years more and more complex humanoid robots have been developed. On the other hand programming these systems has become more difficult. There is a clear need for such robots to be able to adapt and perform certain tasks autonomously, or even learn by themselves how to act. An important issue to tackle is the closing of the sensorimotor loop. Especially when talking about humanoids the tight integration of perception with actions will allow for improved behaviours, embedding adaptation on the lower-level of the system.

Crime Justice and Social Democracy: Proceedings of the 3rd International Conference, 9-10 July 2015

We are pleased to present these selected papers from the proceedings of the 3rd Crime, Justice and Social Democracy International Conference, held in July 2015 in Brisbane, Australia. Over 350 delegates attended the conference from 19 countries. The papers collected here reflect the diversity of topics and themes that were explored over three days. The Crime, Justice and Social Democracy International Conference aims to strengthen the intellectual and policy debates concerning links between justice, social democracy, and the reduction of harm and crime, through building more just and inclusive societies and proposing innovative justice responses. In 2015, attendees discussed these issues as they related to ideas of green criminology; indigenous justice; gender, sex and justice; punishment and society; and the emerging notion of ‘Southern criminology’. The need to build global connections to address these challenges is more evident than ever and the conference and these proceedings reflect a growing attention to interdisciplinary, novel, and interconnected responses to contemporary global challenges. Authors in these conference proceedings engaged with issues of online fraud, queer criminology and law, Indigenous incarceration, youth justice, incarceration in Brazil, and policing in Victoria, Australia, among others. The topics explored speak to the themes of the conference and demonstrate the range of challenges facing researchers of crime, harm, social democracy and social justice and the spaces of possibility that such research opens. Our thanks to the conference convenor, Dr Kelly Richards, for organising such a successful conference, and to all those presenters who subsequently submitted such excellent papers for review here. We would also particularly like to thank Jess Rodgers for their tireless editorial assistance, as well as the panel of international scholars who participated in the review process, often within tight timelines.

HR-MAS NMR spectroscopy shows regional metabolite variation in bovine articular cartilage

Mechanical stress is an important external factor effecting the development and maintenance of articular cartilage. The metabolite profile of diseased cartilage has been well studied but there is limited information about the variation in metabolite profile of healthy cartilage. With the importance of load in maintaining healthy cartilage, regional differences in metabolite profile associated with differences in load may provide information on how load contributes to the maintenance of healthy cartilage. HR-MAS NMR spectroscopy allows the assessment of tissue samples without modification and was used for assessing the difference in metabolic profile between the load bearing and non-load bearing regions of the bovine articular cartilage. In this preliminary study, we examined cartilage from tibia and femur of four knee joints. Sixteen pairs of 1D-NOESY spectra were acquired. Principle component analysis (PCA) identified chemical shifts responsible for variance. SBASE (AMIX) and the Human Metabolome Database were used in conjunction with previous reported cartilage data for identifying metabolites associated with the PCA results. The major contributors to load-related differences in metabolite profile were N-acetyl groups, lactate and phosphocholine peaks. Integrals of these regions were further analysed using a Student's t-test. In load bearing cartilage regions. N-acetyl groups and phosphocholine were found at significantly higher concentration (p < 0.05 and p < 0.005, respectively) in both femur and tibia, while lactate was reduced in load bearing cartilage (p < 0.005). The results of this pilot HR-MAS NMR study demonstrate its ability to provide useful metabolite information for healthy cartilage.

Association of FOXE1 Polyalanine Repeat Region with Papillary Thyroid Cancer

CONTEXT: Polyalanine tract variations in transcription factors have been identified for a wide spectrum of developmental disorders. The thyroid transcription factor forkhead factor E1 (FOXE1) contains a polymorphic polyalanine tract with 12-22 alanines. Single-nucleotide polymorphisms (SNP) close to this locus are associated with papillary thyroid cancer (PTC), and a strong linkage disequilibrium block extends across this region. OBJECTIVE: The objective of the study was to assess whether the FOXE1 polyalanine repeat region was associated with PTC and to assess the effect of polyalanine repeat region variants on protein expression, DNA binding, and transcriptional function on FOXE1-responsive promoters. DESIGN: This was a case-control study. SETTING: The study was conducted at a tertiary referral hospital. PATIENTS AND METHODS: The FOXE1 polyalanine repeat region and tag SNP were genotyped in 70 PTC, with a replication in a further 92 PTC, and compared with genotypes in 5767 healthy controls (including 5667 samples from the Wellcome Trust Case Control Consortium). In vitro studies were performed to examine the protein expression, DNA binding, and transcriptional function for FOXE1 variants of different polyalanine tract lengths. RESULTS: All the genotyped SNP were in tight linkage disequilibrium, including the FOXE1 polyalanine repeat region. We confirmed the strong association of rs1867277 with PTC (overall P = 1 × 10(-7), odds ratio 1.84, confidence interval 1.31-2.57). rs1867277 was in tight linkage disequilibrium with the FOXE1 polyalanine repeat region (r(2) = 0.95). FOXE1(16Ala) was associated with PTC with an odds ratio of 2.23 (confidence interval 1.42-3.50; P = 0.0005). Functional studies in vitro showed that FOXE1(16Ala) was transcriptionally impaired compared with FOXE1(14Ala), which was not due to differences in protein expression or DNA binding. CONCLUSIONS: We have confirmed the previous association of FOXE1 with PTC. Our data suggest that the coding polyalanine expansion in FOXE1 may be responsible for the observed association between FOXE1 and PTC.