Identifying vertebral end plate lesions (schmorl's nodes) using a semi-automatic method

INTRODUCTION There is a large range in the reported prevalence of end plate lesions (EPLs), sometimes referred to as Schmorl's nodes in the general population (3.8-76%). One possible reason for this large range is the differences in definitions used by authors. Previous research has suggested that EPLs may potentially be a primary disturbance of growth plates that leads to the onset of scoliosis. The aim of this study was to develop a technique to measure the size, prevalence and location of EPLs on Computed Tomography (CT) images of scoliosis patients in a consistent manner. METHODS A detection algorithm was developed and applied to measure EPLs for five adolescent females with idiopathic scoliosis (average age 15.1 years, average major Cobb 60°). In this algorithm, the EPL definition was based on the lesion depth, the distance from the edge of the vertebral body and the gradient of the lesion edge. Existing low-dose, CT scans of the patients' spines were segmented semi-automatically to extract 3D vertebral endplate morphology. Manual sectioning of any attachments between posterior elements of adjacent vertebrae and, if necessary, endplates was carried out before the automatic algorithm was used to determine the presence and position of EPLs. RESULTS EPLs were identified in 15 of the 170 (8.8%) endplates analysed with an average depth of 3.1mm. 73% of the EPLs were seen in the lumbar spines (11/15). A sensitivity study demonstrated that the algorithm was most sensitive to changes in the minimum gradient required at the lesion edge. CONCLUSION An imaging analysis technique for consistent measurement of the prevalence, location and size of EPLs on CT images has been developed. Although the technique was tested on scoliosis patients, it can be used to analyse other populations without observer errors in EPL definitions.

Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis

Objective: To identify genetic associations with severity of radiographic damage in ankylosing spondylitis (AS). Method: We studied 1537 AS cases of European descent; all fulfilled the modified New York Criteria. Radiographic severity was assessed from digitised lateral radiographs of the cervical and lumbar spine using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A two-phase genotyping design was used. In phase 1, 498 single nucleotide polymorphisms (SNPs) were genotyped in 688 cases; these were selected to capture >90% of the common haplotypic variation in the exons, exon-intron boundaries, and 5 kb flanking DNA in the 5' and 3' UTR of 74 genes involved in anabolic or catabolic bone pathways. In phase 2, 15 SNPs exhibiting p<0.05 were genotyped in a further cohort of 830 AS cases; results were analysed both separately and in combination with the discovery phase data. Association was tested by contingency tables after separating the samples into 'mild' and 'severe' groups, defined as the bottom and top 40% by mSASSS, adjusted for gender and disease duration. Results: Experiment-wise association was observed with the SNP rs8092336 (combined OR 0.32, p=1.2×10-5), which lies within RANK (receptor activator of NF?B), a gene involved in osteoclastogenesis, and in the interaction between T cells and dendritic cells. Association was also found with the SNP rs1236913 in PTGS1 (prostaglandin-endoperoxide synthase 1, cyclooxygenase 1), giving an OR of 0.53 (p=2.6×10-3). There was no observed association between radiographic severity and HLA-B*27. Conclusions: These findings support roles for bone resorption and prostaglandins pathways in the osteoproliferative changes in AS.

Excessive bone formation in a mouse model of ankylosing spondylitis is associated with decreases in Wnt pathway inhibitors

Introduction: Ankylosing spondylitis (AS) is unique in its pathology where inflammation commences at the entheses before progressing to an osteoproliferative phenotype generating excessive bone formation that can result in joint fusion. The underlying mechanisms of this progression are poorly understood. Recent work has suggested that changes in Wnt signalling, a key bone regulatory pathway, may contribute to joint ankylosis in AS. Using the proteoglycan-induced spondylitis (PGISp) mouse model which displays spondylitis and eventual joint fusion following an initial inflammatory stimulus, we have characterised the structural and molecular changes that underlie disease progression. Methods: PGISp mice were characterised 12 weeks after initiation of inflammation using histology, immunohistochemistry (IHC) and expression profiling. Results: Inflammation initiated at the periphery of the intervertebral discs progressing to disc destruction followed by massively excessive cartilage and bone matrix formation, as demonstrated by toluidine blue staining and IHC for collagen type I and osteocalcin, leading to syndesmophyte formation. Expression levels of DKK1 and SOST, Wnt signalling inhibitors highly expressed in joints, were reduced by 49% and 63% respectively in the spine PGISp compared with control mice (P < 0.05) with SOST inhibition confirmed by IHC. Microarray profiling showed genes involved in inflammation and immune-regulation were altered. Further, a number of genes specifically involved in bone regulation including other members of the Wnt pathway were also dysregulated. Conclusions: This study implicates the Wnt pathway as a likely mediator of the mechanism by which inflammation induces bony ankylosis in spondyloarthritis, raising the potential that therapies targeting this pathway may be effective in preventing this process.

Fracture healing via periosteal callus formation requires macrophages for both initiation and progression of early endochondral ossification

The distribution, phenotype, and requirement of macrophages for fracture-associated inflammation and/or early anabolic progression during endochondral callus formation were investigated. A murine femoral fracture model [internally fixed using a flexible plate (MouseFix)] was used to facilitate reproducible fracture reduction. IHC demonstrated that inflammatory macrophages (F4/80+Mac-2+) were localized with initiating chondrification centers and persisted within granulation tissue at the expanding soft callus front. They were also associated with key events during soft-to-hard callus transition. Resident macrophages (F4/80+Mac-2neg), including osteal macrophages, predominated in the maturing hard callus. Macrophage Fas-induced apoptosis transgenic mice were used to induce macrophage depletion in vivo in the femoral fracture model. Callus formation was completely abolished when macrophage depletion was initiated at the time of surgery and was significantly reduced when depletion was delayed to coincide with initiation of early anabolic phase. Treatment initiating 5 days after fracture with the pro-macrophage cytokine colony stimulating factor-1 significantly enhanced soft callus formation. The data support that inflammatory macrophages were required for initiation of fracture repair, whereas both inflammatory and resident macrophages promoted anabolic mechanisms during endochondral callus formation. Overall, macrophages make substantive and prolonged contributions to fracture healing and can be targeted as a therapeutic approach for enhancing repair mechanisms. Thus, macrophages represent a viable target for the development of pro-anabolic fracture treatments with a potentially broad therapeutic window...

Predictive models for water sources with high susceptibility for bromine-containing disinfection by-product formation: Implications for water treatment

This study examines a matrix of synthetic water samples designed to include conditions that favour brominated disinfection by-product (Br-DBP) formation, in order to provide predictive models suitable for high Br-DBP forming waters such as salinity-impacted waters. Br-DBPs are known to be more toxic than their chlorinated analogues, in general, and their formation may be favoured by routine water treatment practices such as coagulation/flocculation under specific conditions; therefore, circumstances surrounding their formation must be understood. The chosen factors were bromide concentration, mineral alkalinity, bromide to dissolved organic carbon (Br/DOC) ratio and Suwannee River natural organic matter concentration. The relationships between these parameters and DBP formation were evaluated by response surface modelling of data generated using a face-centred central composite experimental design. Predictive models for ten brominated and/or chlorinated DBPs are presented, as well as models for total trihalomethanes (tTHMs) and total dihaloacetonitriles (tDHANs), and bromide substitution factors for the THMs and DHANs classes. The relationships described revealed that increasing alkalinity and increasing Br/DOC ratio were associated with increasing bromination of THMs and DHANs, suggesting that DOC lowering treatment methods that do not also remove bromide such as enhanced coagulation may create optimal conditions for Br-DBP formation in waters in which bromide is present.

Profiles of illicit drug use during annual key holiday and control periods in Australia: Wastewater analysis in an urban, a semi-rural and a vacation area

AIMS: To examine changes in illicit drug consumption between peak holiday season (23 December-3 January) in Australia and a control period two months later in a coastal urban area, an inland semi-rural area and an island populated predominantly by vacationers during holidays. DESIGN: Analysis of representative daily composite wastewater samples collected from the inlet of the major wastewater treatment plant in each area. SETTING: Three wastewater treatment plants. PARTICIPANTS: Wastewater treatment plants serviced approximately 350, 000 persons in the urban area, 120,000 in the semi-rural area and 1100-2400 on the island. MEASUREMENTS: Drug residues were analysed using liquid chromatography coupled to a tandem mass spectrometer. Per capita drug consumption was estimated. Changes in drug use were quantified using Hedges' g. FINDINGS: During the holidays, cannabis consumption in the semi-rural area declined (g = -2.8) as did methamphetamine (-0.8), whereas cocaine (+1.5) and ecstasy (+1.6) use increased. In the urban area, consumption of all drugs increased during holidays (cannabis +1.6, cocaine +1.2, ecstasy +0.8 and methamphetamine +0.3). In the vacation area, methamphetamine (+0.7), ecstasy (+0.7) and cocaine (+1.1) use increased, but cannabis (-0.5) use decreased during holiday periods. CONCLUSIONS: While the peak holiday season in Australia is perceived as a period of increased drug use, this is not uniform across all drugs and areas. Substantial declines in drug use in the semi-rural area contrasted with substantial increases in urban and vacation areas. Per capita drug consumption in the vacation area was equivalent to that in the urban area, implying that these locations merit particular attention for drug use monitoring and harm minimisation measures.

Illicit drug use between an annual key holiday and a control period: Wastewater analysis in a semi-rural, an urban and a vacation area

Introduction and Aims: Holiday periods are potentially a time for increased substance use as social events and private parties are more common. Data on community illicit drug consumption during holiday periods are limited. Besides existing methods for determining drug use, such as population surveys, one emerging method is to measure illicit drugs and/or their metabolites in wastewater samples. This study examined the change in consumption of cannabis, methamphetamine, cocaine and 3,4- methylenedioxymethamphetamine in three different types of areas (an inland semi-rural area, a coastal urban area and a vacation island) with respect to holiday times. Design and Methods: Samples were collected at the inlet of the major wastewater treatment plant in each area during a key annual holiday (i.e. the summer holiday including Christmas and New Year) and control period. Illicit drug residues in the daily composited samples were measured by liquid chromatography coupled with tandem mass spectrometry. Results: Drug use varied substantially among the three areas within each monitoring period as well as between the holiday and control period within each area. Use consistently increased and peaked over New Year particularly for cocaine and 3,4-methylenedioxymethamphetamine whereas cannabis and methamphetamine were relatively less subjected to holiday times in all the areas. Discussion and Conclusions: Wastewater sampling and analysis provides higher spatio-temporal resolution than national surveys and supplements drug epidemiology studies originating primary in metropolitan locations. Such data is essential for policy makers to plan potential intervention strategies associated with these illicit substances in regional areas and other settings besides urban areas in the future.

Theorising the impacts of digitally mediated social interaction on diasporic identity formation: A case of Chinese diaspora in Australia

With the scope of Chinese diaspora in Australia, this paper theorises the impacts of digitally mediated social interaction on diasporic identity formation in the new media landscape. People’s identity is the outcome of their social interactions with other individuals. In the new media landscape, digital media technologies are changing the way in which people communicate with others. On one hand, space and time are unprecedentedly compressed by media technologies so people can maintain more frequent and instant connections with others than before. On the other hand, the digital media technologies have constructed a virtual social space that might withdraw people from their physical social interactions. As we witness today, our social interactions are increasing digitally mediated, in the forms of posts and comments in social network sites, as well as the messages in social apps. As to the diasporic groups, this new media landscape is presenting a challenge to their identity formation. They physically live in the host countries but still keep close social and cultural connections with their homelands. Facilitated by digital media technologies, they are facing two platforms in which they can practice different identity performances: one is the digitally mediated social network; the other is the physical social network. In the case of Chinese diaspora, the situation is more complex due to the language factor and media censorship in Mainland China, which will be articulated in the main text. This paper aims to fill a gap between media studies and diaspora research. Most of existing research on the relationship between diasporic identity and media primarily focuses on the development of ethnic media institutions, and the production and consumption of ethnic media in the pre-digital media context. However, the process of globalisation and digital media technologies are increasing the homogeneity and hybridity of media content worldwide. In this new context, attributing the formation of different identities to the consumption of media content is arguable to some extent. Therefore, the overlapped area of new media studies and diaspora research still has space deserves further investigation.

Osteoclast formation from circulating precursors in osteoporosis

Objective: An imbalance between bone formation and bone resorption is thought to underlie the pathogenesis of reduced bone mass in osteoporosis. Bone resorption is carried out by osteoclasts, which are formed from marrow-derived cells that circulate in the monocyte fraction. Ihe aim of this study was to determine the role of osteoclast formation in the pathogenesis of bone loss in osteoporosis. Methods: The proportion of circulating osteoclast precursors and their relative sensitivity to the osteoclastogenic effects of M-CSF, 1,25(OH)2D3 and RANKL were assessed in primary osteoporosis patients and normal controls. Results: Although there was no difference in the number of circulating osteoclast precursors in osteoporosis patients and normal controls, osteoclasts formed from osteoporosis patients exhibited substantially increased resorptive activity relative to normal controls. Although no increased sensitivity to the osteoclastogenic effects of 1,25(OH)2D3 or M-CSF was noted, increased bone resorption was found in osteoporosis peripheral blood mononuclear cell (PBMC) cultures to which these factors were added. Conclusion: Our findings suggest that osteoclast functional activity rather than formation is increased in primary involutional osteoporosis and that dexamethasone acts to increase osteoclast formation.

Semi-supervised document clustering via loci

Document clustering is one of the prominent methods for mining important information from the vast amount of data available on the web. However, document clustering generally suffers from the curse of dimensionality. Providentially in high dimensional space, data points tend to be more concentrated in some areas of clusters. We take advantage of this phenomenon by introducing a novel concept of dynamic cluster representation named as loci. Clusters’ loci are efficiently calculated using documents’ ranking scores generated from a search engine. We propose a fast loci-based semi-supervised document clustering algorithm that uses clusters’ loci instead of conventional centroids for assigning documents to clusters. Empirical analysis on real-world datasets shows that the proposed method produces cluster solutions with promising quality and is substantially faster than several benchmarked centroid-based semi-supervised document clustering methods.

State-formation, teaching techniques, and globalization as aporia

Eleanor Smith [pseudonym], teacher : I was talking to the kids about MacDonalds*/I forget exactly what the context was*/I said ‘‘ah, the Americans call them French fries, and, you know, MacDonalds is an American chain and they call them French fries because the Americans call them French fries’’, and this little Australian kid in the front row, very Australian child, said to me, ‘‘I call them French fries!’’ . . . Um, a fourth grade boy whom I taught in 1993 at this school, the world basketball championships were on . . . Americans were playing their dream machine and the Boomers were up against them . . . and, ah, this boy was very interested in basketball . . . but it’s not in my blood, not in the way cricket is for example . . . Um, Um, and I said to this fellow, ‘‘um, well’’, I said, ‘‘Australia’s up against Dream Machine tomorrow’’. He [Jason, pseudonym] said, ‘‘Ah, you know, Boomers probably won’t win’’. . . . I said, ‘‘Well that’s sport, mate’’. I said, ‘‘You never know in sport. Australia might win’’. And he looked at me and he said, ‘‘I’m not going for Australia, I’m going for America’’. This is from an Australian boy! And I thought so strong is the hype, so strong is the, is the, power of the media, etc., that this boy is not [pause], I can’t tell you how outraged I was. Here’s me as an Australian and I don’t even support basketball, it’s not even my sport, um, but that he would respond like that because of the power of the American machine that’s converting kids’ minds, the way they think, where they’re putting their loyalties, etc. I was just appalled, but that’s where he was. And when I asked kids for their favourite place, he said Los Angeles.

Comparative proteomics of uropathogenic Escherichia coli during growth in human urine identify UCA-like (UCL) fimbriae as an adherence factor involved in biofilm formation and binding to uroepithelial cells

Uropathogenic Escherichia coli (UPEC) are the primary cause of urinary tract infection (UTI) in humans. For the successful colonisation of the human urinary tract, UPEC employ a diverse collection of secreted or surface-exposed virulence factors including toxins, iron acquisition systems and adhesins. In this study, a comparative proteomic approach was utilised to define the UPEC pan and core surface proteome following growth in pooled human urine. Identified proteins were investigated for subcellular origin, prevalence and homology to characterised virulence factors. Fourteen core surface proteins were identified, as well as eleven iron uptake receptor proteins and four distinct fimbrial types, including type 1, P, F1C/S and a previously uncharacterised fimbrial type, designated UCA-like (UCL) fimbriae in this study. These pathogenicity island (PAI)-associated fimbriae are related to UCA fimbriae of Proteus mirabilis, associated with UPEC and exclusively found in members of the E. coli B2 and D phylogroup. We further demonstrated that UCL fimbriae promote significant biofilm formation on abiotic surfaces and mediate specific attachment to exfoliated human uroepithelial cells. Combined, this study has defined the surface proteomic profiles and core surface proteome of UPEC during growth in human urine and identified a new type of fimbriae that may contribute to UTI.

Assessment of an environmentally friendly, semi-pelagic fish trawl

Minimising catches of non-target animals in a trawl fishery reduces the impact on a marine community and may help to sustain the fishery resource in the long term. Hence the desirability for trawls that minimise impacts on non-target species while maintaining catches of target species. This study resulted from a need to further develop easily handled, semi-pelagic style trawls for Australia's Northern Fish Trawl Fishery. In November 1993 we compared catches from three differently rigged versions of a demersal wing trawl: one fished in a standard demersal configuration with its footrope on the sea bed, and two fished semi-pelagically, with their footropes raised to either 0.4-0.5 or 0.8-0.9 m above the sea bed. At two sites in the northeast Gulf of Carpentaria, each trawl type was used on the same combination of sites, grids within sites and times of day. Catches of the main target species (Lutjanus malabaricus and Lutjanus erythropterus) by the three trawl types were not significantly different. However, the mean catches of both these species and of other commercially important snappers, were highest in the semi-pelagic trawl raised 0.4-0.5 m above the sea bed. This increase could be due to a larger trawl spread or to the whole rig fishing higher in the water column. Of the 107 species of fishes analysed, 61 were caught in greater abundance in the demersal trawl. Seven species were caught more effectively in the semi-pelagic trawl with the footrope 0.4-0.5 m above the substrate; none was caught most effectively with the footrope set at 0.8-0.9 m. Epibenthic byproduct species (squid and Thenus orientalis), fish bycatch, sponges and other epibenthic invertebrates were also caught in lower numbers in the semi-pelagic trawls. The semi-pelagic trawls convincingly caught less (in both numbers and biomass) of the unwanted species which are normally discarded. Semi-pelagic fish trawls of the types tested would be suitable for Australia's Northern Fish Trawl Fishery and probably other demersal trawl fisheries that would benefit from the conservation of non-target epibenthic communities.

Ultrafast and reversible multiblock formation by the SET-Nitroxide radical coupling reaction

The single electron transfer-nitroxide radical coupling (SET-NRC) reaction has been used to produce multiblock polymers with high molecular weights in under 3 min at 50◦C by coupling a difunctional telechelic polystyrene (Br-PSTY-Br)with a dinitroxide. The well known combination of dimethyl sulfoxide as solvent and Me6TREN as ligand facilitated the in situ disproportionation of CuIBr to the highly active nascent Cu0 species. This SET reaction allowed polymeric radicals to be rapidly formed from their corresponding halide end-groups. Trapping of these carbon-centred radicals at close to diffusion controlled rates by dinitroxides resulted in high-molecular-weight multiblock polymers. Our results showed that the disproportionation of CuI was critical in obtaining these ultrafast reactions, and confirmed that activation was primarily through Cu0. We took advantage of the reversibility of the NRC reaction at elevated temperatures to decouple the multiblock back to the original PSTY building block through capping the chain-ends with mono-functional nitroxides. These alkoxyamine end-groups were further exchanged with an alkyne mono-functional nitroxide (TEMPO–≡) and ‘clicked’ by a CuI-catalyzed azide/alkyne cycloaddition (CuAAC) reaction with N3–PSTY–N3 to reform the multiblocks. This final ‘click’ reaction, even after the consecutive decoupling and nitroxide-exchange reactions, still produced high molecular-weight multiblocks efficiently. These SET-NRC reactions would have ideal applications in re-usable plastics and possibly as self-healing materials.

Depositional model for the early Miocene turbidite sequence, the Whakataki Formation, NZ

This research examined the influence of tectonic activity on submarine sedimentation processes, through a deposit-based analysis of turbidites in outcrop. A comprehensive field study of the Miocene Whakataki Formation yielded significant data that was analysed using methods of process-sedimentology, stratigraphy, and ichnology. Signatures of the tectonically active depositional environment were identifiable at very high resolution, from grain composition and texture to trace-fossil assemblages, as well as on a broader-scale in stratigraphic stacking patterns and structural deformation. From these results and environmental interpretations, an original facies characterisation and conceptual depositional model have been established.