Expression profiling in spondyloarthropathy synovial biopsies highlights changes in expression of inflammatory genes in conjunction with tissue remodelling genes

Background: In the spondyloarthropathies, the underlying molecular and cellular pathways driving disease are poorly understood. By undertaking a study in knee synovial biopsies from spondyloarthropathy (SpA) and ankylosing spondylitis (AS) patients we aimed to elucidate dysregulated genes and pathways. Methods RNA was extracted from six SpA, two AS, three osteoarthritis (OA) and four normal control knee synovial biopsies. Whole genome expression profiling was undertaken using the Illumina DASL system, which assays 24000 cDNA probes. Differentially expressed candidate genes were then validated using quantitative PCR and immunohistochemistry. Results: Four hundred and sixteen differentially expressed genes were identified that clearly delineated between AS/SpA and control groups. Pathway analysis showed altered gene-expression in oxidoreductase activity, B-cell associated, matrix catabolic, and metabolic pathways. Altered «myogene» profiling was also identified. The inflammatory mediator, MMP3, was strongly upregulated (5-fold) in AS/SpA samples and the Wnt pathway inhibitors DKK3 (2.7-fold) and Kremen1 (1.5-fold) were downregulated. Conclusions: Altered expression profiling in SpA and AS samples demonstrates that disease pathogenesis is associated with both systemic inflammation as well as local tissue alterations that may underlie tissue damaging modelling and remodelling outcomes. This supports the hypothesis that initial systemic inflammation in spondyloarthropathies transfers to and persists in the local joint environment, and might subsequently mediate changes in genes directly involved in the destructive tissue remodelling.

Non-enzymatic glycosylation of skin collagen in patients with type 1 (insulin-dependent) diabetes mellitus and limited joint mobility

Forearm skin biopsies were obtained from diabetic subjects with and without limited joint mobility, and from non-diabetic control subjects. Collagen purified from these samples was assayed for non-enzymatic glycosylation. The level in all diabetic patients was significantly greater than that in control subjects (p less than 0.001), but those diabetic patients with limited joint mobility had a level of collagen glycosylation similar to that in those with normal joints (15.3 +/- 1.3 and 16.5 +/- 1.3 nmol fructose/10 mg protein, respectively; mean +/- SEM). Glycosylation of collagen in the diabetic patients correlated with glycosylated haemoglobin measured at the time of skin biopsy (r = 0.60). These results do not support the hypothesis that non-enzymatic glycosylation of collagen, as reflected by the ketoamine link, plays an important role in the development of limited joint mobility in diabetes.

Intra-tumoral budding in preoperative biopsy specimens predicts lymph node and distant metastasis in patients with colorectal cancer

Tumor budding, a histological hallmark of epithelial-mesenchymal transition in colorectal cancer, is a parameter of tumor progression and according to the International Union Against Cancer/American Joint Committee on Cancer an 'additional' prognostic factor. The current definition of tumor budding is reserved for the invasive tumor front of colorectal cancer (so called peri-tumoral budding), but tumor buds can also be observed in small preoperative biopsy specimens. Whereas the prognostic value of peri-tumoral budding assessed in resection specimens has found wide acceptance, the value of budding in preoperative biopsies, which normally do not encompass the invasive tumor margin and hence can be called intra-tumoral budding, has not been systematically investigated yet. Therefore, the aim of this study is to assess the predictive value of intra-tumoral budding for lymph node and distant metastasis in preoperative biopsies. Preoperative biopsy samples and consecutive resection specimens from 72 patients with pathological information on TNM stage, vascular, lymphatic and perineural invasion, and tumor border configuration were used to evaluate intra-tumoral budding and peri-tumoral budding. Both parameters were scored semiquantitatively as 'high' (detectable at low power magnification × 2.5) and 'low' (occasional budding at intermediate magnification × 10, difficult to find or absent). In biopsy samples high intra-tumoral budding was observed in 12/72 patients (17%) and associated with high peri-tumoral budding in the corresponding resection specimens (P=0.008). Additionally, there was a correlation between high intra-tumoral budding and lymph node metastasis (P=0.034), distant metastasis (P=0.007) and higher tumor grade (P=0.025). Peri-tumoral budding was associated with higher N stage (P=0.004), vascular (P=0.046) and lymphatic invasion (P=0.019) as well as with an infiltrating tumor border (P<0.001), reflecting the predictive power of peri-tumoral budding for tumor progression. High intra-tumoral budding in preoperative biopsy samples of colorectal cancer patients predicts high peri-tumoral budding at the invasive margin and lymph node metastasis in the corresponding resection specimens as well as distant metastasis.

Biomechanical force displacement analysis of strength of fixation of tracker holding devices to bone in computer aided joint replacement

Computer aided joint replacement surgery has become very popular during recent years and is being done in increasing numbers all over the world. The accuracy of the system depends to a major extent, on accurate registration and immobility of the tracker attachment devices to the bone. This study was designed to asses the forces needed to displace the tracker attachment devices in the bone simulators. Bone simulators were used to maintain the uniformity of the bone structure during the study. The fixation devices tested were 3mm diameter self drilling, self tapping threaded pin, 4mm diameter self tapping cortical threaded pin, 5mm diameter self tapping cancellous threaded pin and a triplanar fixation device ‘ortholock’ used with three 3mm pins. All the devices were tested for pull out, translational and rotational forces in unicortical and bicortical fixation modes. Also tested was the normal bang strength and forces generated by leaning on the devices. The forces required to produce translation increased with the increasing diameter of the pins. These were 105N, 185N, and 225N for the unicortical fixations and 130N, 200N, 225N for the bicortical fixations for 3mm, 4mm and 5mm diameter pins respectively. The forces required to pull out the pins were 1475N, 1650N, 2050N for the unicortical, 1020N, 3044N and 3042N for the bicortical fixated 3mm, 4mm and 5mm diameter pins. The ortholock translational and pull out strength was tested to 900N and 920N respectively and still it did not fail. Rotatory forces required to displace the tracker on pins was to the magnitude of 30N before failure. The ortholock device had rotational forces applied up to 135N and still did not fail. The manual leaning forces and the sudden bang forces generated were of the magnitude of 210N and 150N respectively. The strength of the fixation pins increases with increasing diameter from three to five mm for the translational forces. There is no significant difference in pull out forces of four mm and five mm diameter pins though it is more that the three mm diameter pins. This is because of the failure of material at that stage rather than the fixation device. The rotatory forces required to displace the tracker are very small and much less that that can be produced by the surgeon or assistants in single pins. Although the ortholock device was tested to 135N in rotation without failing, one has to be very careful not to put any forces during the operation on the tracker devices to ensure the accuracy of the procedure.

Joint venture behaviour in construction industry : an Australia case study

Joint ventures can take many forms and can be formed for different reasons, from sharing resources to creating future business opportunities. At the same time, there is increasing interest and discussion of alternative procurement methods, moving away from traditional procurement systems to relational approaches. Business systems and strategies need to be redefined and move from a short-term project to project culture to a more strategic, long-term perspective. Joint ventures of construction organisations, global and local, have become increasingly popular to deliver large-scale infrastructure construction projects. However, successful strategic collaborations require project organisations to formulate a fit between contractual and operational arrangements for each situation. This study reviews the movement from traditional procurement methods towards relational contracting approaches in Queensland, Australia. The study examines the organisational factors that facilitates sustainable relationship between project organisations and hence, lead to long-term business success. This paper reports on initial findings captured from a survey undertaken with construction contracting organisations in Australia, focusing on the supply chain relationships. Contractors’ perceptions of the relationship management process and the engagement of the supply chain are also presented.

The neuro-muscular and musculo-skeletal characterization of children with joint hypermobility

In children, joint hypermobility (typified by structural instability of joints) manifests clinically as neuro-muscular and musculo-skeletal conditions and conditions associated with development and organization of control of posture and gait (Finkelstein, 1916; Jahss, 1919; Sobel, 1926; Larsson, Mudholkar, Baum and Srivastava, 1995; Murray and Woo, 2001; Hakim and Grahame, 2003; Adib, Davies, Grahame, Woo and Murray, 2005:). The process of control of the relative proportions of joint mobility and stability, whilst maintaining equilibrium in standing posture and gait, is dependent upon the complex interrelationship between skeletal, muscular and neurological function (Massion, 1998; Gurfinkel, Ivanenko, Levik and Babakova, 1995; Shumway-Cook and Woollacott, 1995). The efficiency of this relies upon the integrity of neuro-muscular and musculo-skeletal components (ligaments, muscles, nerves), and the Central Nervous System’s capacity to interpret, process and integrate sensory information from visual, vestibular and proprioceptive sources (Crotts, Thompson, Nahom, Ryan and Newton, 1996; Riemann, Guskiewicz and Shields, 1999; Schmitz and Arnold, 1998) and development and incorporation of this into a representational scheme (postural reference frame) of body orientation with respect to internal and external environments (Gurfinkel et al., 1995; Roll and Roll, 1988). Sensory information from the base of support (feet) makes significant contribution to the development of reference frameworks (Kavounoudias, Roll and Roll, 1998). Problems with the structure and/ or function of any one, or combination of these components or systems, may result in partial loss of equilibrium and, therefore ineffectiveness or significant reduction in the capacity to interact with the environment, which may result in disability and/ or injury (Crotts et al., 1996; Rozzi, Lephart, Sterner and Kuligowski, 1999b). Whilst literature focusing upon clinical associations between joint hypermobility and conditions requiring therapeutic intervention has been abundant (Crego and Ford, 1952; Powell and Cantab, 1983; Dockery, in Jay, 1999; Grahame, 1971; Childs, 1986; Barton, Bird, Lindsay, Newton and Wright, 1995a; Rozzi, et al., 1999b; Kerr, Macmillan, Uttley and Luqmani, 2000; Grahame, 2001), there has been a deficit in controlled studies in which the neuro-muscular and musculo-skeletal characteristics of children with joint hypermobility have been quantified and considered within the context of organization of postural control in standing balance and gait. This was the aim of this project, undertaken as three studies. The major study (Study One) compared the fundamental neuro-muscular and musculo-skeletal characteristics of 15 children with joint hypermobility, and 15 age (8 and 9 years), gender, height and weight matched non-hypermobile controls. Significant differences were identified between previously undiagnosed hypermobile (n=15) and non-hypermobile children (n=15) in passive joint ranges of motion of the lower limbs and lumbar spine, muscle tone of the lower leg and foot, barefoot CoP displacement and in parameters of barefoot gait. Clinically relevant differences were also noted in barefoot single leg balance time. There were no differences between groups in isometric muscle strength in ankle dorsiflexion, knee flexion or extension. The second comparative study investigated foot morphology in non-weight bearing and weight bearing load conditions of the same children with and without joint hypermobility using three dimensional images (plaster casts) of their feet. The preliminary phase of this study evaluated the casting technique against direct measures of foot length, forefoot width, RCSP and forefoot to rearfoot angle. Results indicated accurate representation of elementary foot morphology within the plaster images. The comparative study examined the between and within group differences in measures of foot length and width, and in measures above the support surface (heel inclination angle, forefoot to rearfoot angle, normalized arch height, height of the widest point of the heel) in the two load conditions. Results of measures from plaster images identified that hypermobile children have different barefoot weight bearing foot morphology above the support surface than non-hypermobile children, despite no differences in measures of foot length or width. Based upon the differences in components of control of posture and gait in the hypermobile group, identified in Study One and Study Two, the final study (Study Three), using the same subjects, tested the immediate effect of specifically designed custom-made foot orthoses upon balance and gait of hypermobile children. The design of the orthoses was evaluated against the direct measures and the measures from plaster images of the feet. This ascertained the differences in morphology of the modified casts used to mould the orthoses and the original image of the foot. The orthoses were fitted into standardized running shoes. The effect of the shoe alone was tested upon the non-hypermobile children as the non-therapeutic equivalent condition. Immediate improvement in balance was noted in single leg stance and CoP displacement in the hypermobile group together with significant immediate improvement in the percentage of gait phases and in the percentage of the gait cycle at which maximum plantar flexion of the ankle occurred in gait. The neuro-muscular and musculo-skeletal characteristics of children with joint hypermobility are different from those of non-hypermobile children. The Beighton, Solomon and Soskolne (1973) screening criteria successfully classified joint hypermobility in children. As a result of this study joint hypermobility has been identified as a variable which must be controlled in studies of foot morphology and function in children. The outcomes of this study provide a basis upon which to further explore the association between joint hypermobility and neuro-muscular and musculo-skeletal conditions, and, have relevance for the physical education of children with joint hypermobility, for footwear and orthotic design processes, and, in particular, for clinical identification and treatment of children with joint hypermobility.

Curriculum development of joint degrees courses with international institutions

With globalisation and severe budget constraints in the education sector in Australia and around the world it has become necessary for higher education institutions to be more outward looking and seek funding from non traditional sources to supplement the financial shortfalls. One way to overcome this problem is to work cooperatively with other institutions to share facilities and courses, at the same time generating valuable income to maintain the operation of the university. This paper describes the development of joint curricula in built environment and engineering courses in QUT. It outlines the stages of development starting from seeking international partners, developing memorandum of understanding, making visit to partner institution to inspect the facilities, curriculum development to meet the academic requirements of the institutions and professional bodies and finally the implementation process.