Delineating breast cancer cell interactions with engineered bone microenvironments

The mechanisms leading to colonization of metastatic breast cancer cells (BCa) in the skeleton are still not fully understood. Here, we demonstrate that mineralized extracellular matrices secreted by primary human osteoblasts (hOBM) modulate cellular processes associated with BCa colonization of bone. A panel of four BCa cell lines of different bone-metastatic potential (T47D, SUM1315, MDA-MB-231, and the bone-seeking subline MDA-MB-231BO) was cultured on hOBM. After 3 days, the metastatic BCa cells had undergone morphological changes on hOBM and were aligned along the hOBM's collagen type I fibrils that were decorated with bone-specific proteins. In contrast, nonmetastatic BCa cells showed a random orientation on hOBM. Atomic force microscopy-based single-cell force spectroscopy revealed that the metastatic cell lines adhered more strongly to hOBM compared with nonmetastatic cells. Function-blocking experiments indicated that β1-integrins mediated cell adhesion to hOBM. In addition, metastatic BCa cells migrated directionally and invaded hOBM, which was accompanied by enhanced MMP-2 and -9 secretion. Furthermore, we observed gene expression changes associated with osteomimickry in BCa cultured on hOBM. As such, osteopontin mRNA levels were significantly increased in SUM1315 and MDA-MB-231BO cells in a β1-integrin-dependent manner after growing for 3 days on hOBM compared with tissue culture plastic. In conclusion, our results show that extracellular matrices derived from human osteoblasts represent a powerful experimental platform to dissect mechanisms underlying critical steps in the development of bone metastases.

It's just an old apron : aprons, artefacts and art - representations of personal and private 'her-stories', as public histories

This paper examines art and artefact in the representation and recollection of deeply personal WWII women’s experiences as POW’s under the Japanese. This kind of treatment of internees in the Tjideng Women and Children’s internment camp (and others) in Batavia under the Japanese in WWII, stands in stark and brutal contrast to the idyllic life lived by many families up to that time in what was then known as the Dutch East Indies (Indonesia). The deprivation and brutality of the Japanese incarceration of these women and children evoked responses - not military, but certainly militant, if muted. Representations of those responses – as both art and artefact - may be found in the most unlikely places and unexpected forms - and are still being unearthed to this day. However close we might personally be to these artists and artisans, can we, as observers from a distance, ever truly comprehend through spoken or written words alone, the day-today realities of those extraordinary times?

Nutrition prescription to achieve positive outcomes in Chronic Kidney Disease : a systematic review

In Chronic Kidney Disease (CKD), management of diet is important in prevention of disease progression and symptom management, however evidence on nutrition prescription is limited. Recent international CKD guidelines and literature was reviewed to address the following question “What is the appropriate nutrition prescription to achieve positive outcomes in adult patients with chronic kidney disease?” Databases included in the search were Medline and CINAHL using EBSCOhost search engine, Embase and the Cochrane Database of Systematic Reviews published from 2000 to 2009. International guidelines pertaining to nutrition prescription in CKD were also reviewed from 2000 to 2013. Three hundred and eleven papers and eight guidelines were reviewed by three reviewers. Evidence was graded as per the National Health and Medical Research Council of Australia criteria. The evidence from thirty six papers was tabulated under the following headings: protein, weight loss, enteral support, vitamin D, sodium, fat, fibre, oral nutrition supplements, nutrition counselling, including protein and phosphate, nutrients in peritoneal dialysis solution and intradialytic parenteral nutrition, and was compared to international guidelines. While more evidence based studies are warranted, the customary nutrition prescription remains satisfactory with the exception of Vitamin D and phosphate. In these two areas, additional research is urgently needed given the potential of adverse outcomes for the CKD patient.

Road safety knowledge exchange and capacity building between China and Australia

Road traffic injuries are one of the major public health burdens worldwide. The United Nations Decade of Action for Road Safety (2011-2020) implores all nations to work to reduce this burden. This decade represents a unique and historic period of time in the field of road safety. Information exchange and co-operation between nations is an important step in achieving the goal. The burden of road crashes, fatalities and injuries is not equally distributed. We know that low and middle-income countries experience the majority of the road trauma burden. Therefore it is imperative that these countries learn from the successes of others that have developed and implemented road safety laws, public education campaigns and countermeasures over many years and have achieved significant road trauma reductions as a result. China is one of the countries experiencing a large road trauma burden. Vulnerable road users such as pedestrians and cyclists make up a large proportion of fatalities and injuries in China. Speeding, impaired/drug driving, distracted driving, vehicle overloading, inadequate road infrastructure, limited use of safety restraints and helmets, and limited road safety training have all been identified as contributing to the problem. Some important steps have been taken to strengthen China’s approach, including increased penalties for drunk driving in May 2011 and increased attention to school bus safety in 2011/12. However, there is still a large amount of work needed to improve the current road safety position in China. This paper provides details of a program to assist with road safety knowledge exchange between China and Australia that was funded by the Australian Government which was undertaken in the latter part of 2012. The four month program provided the opportunity for the first author to work closely with key agencies in Australia that are responsible for policy development and implementation of a broad range of road safety initiatives. In doing so, an in-depth understanding was gained about key road safety strategies in Australia and processes for developing and implementing them. Insights were also gained into the mechanisms used for road safety policy development, implementation and evaluation in several Australian jurisdictions. Road traffic law and enforcement issues were explored with the relevant jurisdictional transport and police agencies to provide a greater understanding of how Chinese laws and practices could be enhanced. Working with agencies responsible for public education and awareness campaigns about road safety in Australia also provided relevant information about how to promote road safety at the broader community level in China. Finally, the program provided opportunities to work closely with several world-renowned Australian research centres and key expert researchers to enhance opportunities for ongoing road safety research in China. The overall program provided the opportunity for the first author to develop knowledge in key areas of road safety strategy development, implementation and management which are directly relevant to the current situation in China. This paper describes some main observations and findings from participation in the program.

Typing early Australian healthcare-associated MRSA : confirmation of major clones and emergence of ST1-MRSA-IV and novel ST2249-MRSA-III

AIMS: To investigate the evolutionary origins of Australian healthcare-associated (HCA) methicillin-resistant Staphylococcus aureus (MRSA) strains from a panel of historical isolates typed using current genotyping techniques. METHODS: Nineteen MRSA isolates from 1965 to 1981 were examined and antibiotic susceptibility profiles determined. Genetic characterisation included real-time (RT) polymerase chain reaction (PCR) assays to identify single nucleotide polymorhpism (SNP) clonal complexes (SNP CC) and sequence type (SNP ST), multi locus sequence typing (MLST) and staphylococcal chromosomal cassette mec typing. RESULTS: All SNP CC30 isolates belonged to a novel sequence type, ST2249. All SNP CC239 isolates were confirmed as ST239-MRSA-III, except for a new single locus variant of ST239, ST2275. A further new type, ST2276, was identified. CONCLUSIONS: The earliest MRSA examined from 1965 was confirmed as ST250-MRSA-I, consistent with archaic European types. Identification of ST1-MRSA-IV in 1981 is the earliest appearance of this clinically important lineage which manifested in Australia and the United States in the 1990s. A previously unknown multi-resistant clone, ST2249-MRSA-III, was identified from 1973. Gentamicin resistance first appeared in this novel strain from 1976 and not ST239 as previously suspected. Thus, ST2249 was present in the earliest phase of the HCA MRSA epidemic in eastern Australia and was perhaps related to the emergence of the globally epidemic strain ST239.

A conceptualization of knowledge governance in project-based organizations

This paper conceptualizes and defines knowledge governance (KG) in project-based organizations (PBOs). Two key contributions towards a multi-faceted view of KG and an understanding of KG in PBOs are advanced, as distinguished from knowledge management and organizational learning concepts. The conceptual framework addresses macro- and micro-level elements of KG and their interaction. Our definition of KG in PBOs highlights the contingent nature of KG processes in relation to their organizational context. These contributions provide a novel platform for understanding KG in PBOs.

Effect of ramipril on walking times and quality of life among patients with peripheral artery disease and intermittent claudication : a randomized controlled trial

Importance Approximately one-third of patients with peripheral artery disease experience intermittent claudication, with consequent loss of quality of life. Objective To determine the efficacy of ramipril for improving walking ability, patient-perceived walking performance, and quality of life in patients with claudication. Design, Setting, and Patients Randomized, double-blind, placebo-controlled trial conducted among 212 patients with peripheral artery disease (mean age, 65.5 [SD, 6.2] years), initiated in May 2008 and completed in August 2011 and conducted at 3 hospitals in Australia. Intervention Patients were randomized to receive 10 mg/d of ramipril (n = 106) or matching placebo (n = 106) for 24 weeks. Main Outcome Measures Maximum and pain-free walking times were recorded during a standard treadmill test. The Walking Impairment Questionnaire (WIQ) and Short-Form 36 Health Survey (SF-36) were used to assess walking ability and quality of life, respectively. Results At 6 months, relative to placebo, ramipril was associated with a 75-second (95% CI, 60-89 seconds) increase in mean pain-free walking time (P < .001) and a 255-second (95% CI, 215-295 seconds) increase in maximum walking time (P < .001). Relative to placebo, ramipril improved the WIQ median distance score by 13.8 (Hodges-Lehmann 95% CI, 12.2-15.5), speed score by 13.3 (95% CI, 11.9-15.2), and stair climbing score by 25.2 (95% CI, 25.1-29.4) (P < .001 for all). The overall SF-36 median Physical Component Summary score improved by 8.2 (Hodges-Lehmann 95% CI, 3.6-11.4; P = .02) in the ramipril group relative to placebo. Ramipril did not affect the overall SF-36 median Mental Component Summary score. Conclusions and Relevance Among patients with intermittent claudication, 24-week treatment with ramipril resulted in significant increases in pain-free and maximum treadmill walking times compared with placebo. This was associated with a significant increase in the physical functioning component of the SF-36 score. Trial Registration clinicaltrials.gov Identifier: NCT00681226

Stability of corneal topography and wavefront aberrations in young Singaporeans

Purpose To investigate the differences between and variations across time in corneal topography and ocular wavefront aberrations in young Singaporean myopes and emmetropes. Methods We used a videokeratoscope and wavefront sensor to measure the ocular surface topography and wavefront aberrations of the total eye optics in the morning, mid-day and late afternoon on two separate days. Topography data were used to derive the corneal surface wavefront aberrations. Both the corneal and total wavefronts were analysed up to the 4th radial order of the Zernike polynomial expansion, and were centred on the entrance pupil (5 mm). The participants included 12 young progressing myopes, 13 young stable myopes and 15 young age-matched emmetropes. Results For all subjects considered together there were significant changes in some of the aberrations terms across the day, such as spherical aberration ( ) and vertical coma ( ) (repeated measures ANOVA, p<0.05). The magnitude of positive spherical aberration ( ) was significantly lower in the progressing myope group than that of the stable myopes (p=0.04) and emmetrope group (p=0.02). There were also significant interactions between refractive group and time of day for with/against-the-rule astigmatism ( ). Significantly lower 4th order RMS of ocular wavefront aberrations were found in the progressing myope group compared with the stable myopes and emmetropes (p<0.01). Conclusions These differences and variations in the corneal and total aberrations may have significance for our understanding of refractive error development and for clinical applications requiring accurate wavefront measurements.

Re : Why optometry must work from urban and regional Aboriginal health services

We are writing to support the recent Viewpoint written by Anjou, Boudville and Taylor ‘Why optometry must work in Aboriginal Health Services in urban and regional Australia’.[1] We are a group of optometrists who provide optometric services within Aboriginal Health Services in urban and regional settings and we agree that access to optometry in Aboriginal Health Services should be supported and expanded in an effort to ‘close the gap’ for vision.

Study protocol : a randomised controlled trial of a theory-based online intervention to improve sun safety among Australian adults

Background The effects of exposure to ultraviolet radiation are a significant concern in Australia which has one of the highest incidences of skin cancer in the world. Despite most skin cancers being preventable by encouraging consistent adoption of sun-protective behaviours, incidence rates are not decreasing. There is a dearth of research examining the factors involved in engaging in sun-protective behaviours. Further, online multi-behavioural theory-based interventions have yet to be explored fully as a medium for improving sun-protective behaviour in adults. This paper presents the study protocol of a randomised controlled trial of an online intervention based on the Theory of Planned Behaviour (TPB) that aims to improve sun safety among Australian adults. Methods/Design Approximately 420 adults aged 18 and over and predominantly from Queensland, Australia, will be recruited and randomised to the intervention (n = 200), information only (n = 200) or the control group (n = 20). The intervention focuses on encouraging supportive attitudes and beliefs toward sun-protective behaviour, fostering perceptions of normative support for sun protection, and increasing perceptions of control/self-efficacy over sun protection. The intervention will be delivered online over a single session. Data will be collected immediately prior to the intervention (Time 1), immediately following the intervention (Time 1b), and one week (Time 2) and one month (Time 3) post-intervention. Primary outcomes are intentions to sun protect and sun-protective behaviour. Secondary outcomes are the participants’ attitudes toward sun protection, perceptions of normative support for sun protection (i.e. subjective norms, group norms, personal norms and image norms) and perceptions of control/self-efficacy toward sun protection. Discussion The study will contribute to an understanding of the effectiveness of a TPB-based online intervention to improve Australian adults’ sun-protective behaviour. Trials registry Australian and New Zealand Trials Registry number ACTRN12613000470796

Short term variability in urinary bisphenol A in Australian children

Used frequently in food contact materials, bisphenol A (BPA) has been studied extensively in recent years, and ubiquitous exposure in the general population has been demonstrated worldwide. Characterising within- and between-individual variability of BPA concentrations is important for characterising exposure in biomonitoring studies, and this has been investigated previously in adults, but not in children. The aim of this study was to characterise the short-term variability of BPA in spot urine samples in young children. Children aged ≥2-<4 years (n = 25) were recruited from an existing cohort in Queensland Australia, and donated four spot urine samples each over a two day period. Samples were analysed for total BPA using isotope dilution online solid phase extraction-liquid chromatography-tandem mass spectrometry, and concentrations ranged from 0.53–74.5 ng/ml, with geometric mean and standard deviation of 2.70 ng/ml and 2.94 ng/ml, respectively. Sex and time of sample collection were not significant predictors of BPA concentration. The between-individual variability was approximately equal to the within-individual variability (ICC = 0.51), and this ICC is somewhat higher than previously reported literature values. This may be the result of physiological or behavioural differences between children and adults or of the relatively short exposure window assessed. Using a bootstrapping methodology, a single sample resulted in correct tertile classification approximately 70% of the time. This study suggests that single spot samples obtained from young children provide a reliable characterization of absolute and relative exposure over the short time window studied, but this may not hold true over longer timeframes.

Proteomic and other analyses to determine the functional consequences of deregulated kallikrein-related peptidase (KLK) expression in prostate and ovarian cancer

Rapidly developing proteomic tools are improving detection of deregulated kallikrein-related peptidase (KLK) expression, at the protein level, in prostate and ovarian cancer, as well as facilitating the determination of functional consequences downstream. Mass spectrometry (MS)-driven proteomics uniquely allows for the detection, identification and quantification of thousands of proteins in a complex protein pool, and this has served to identify certain KLKs as biomarkers for these diseases. In this review we describe applications of this technology in KLK biomarker discovery, and elucidate MS-based techniques which have been used for unbiased, global screening of KLK substrates within complex protein pools. Although MS-based KLK degradomic studies are limited to date, they helped to discover an array of novel KLK substrates. Substrates identified by MS-based degradomics are reported with improved confidence over those determined by incubating a purified or recombinant substrate and protease of interest, in vitro. We propose that these novel proteomic approaches represent the way forward for KLK research, in order to correlate proteolysis of biological substrates with tissue-related consequences, toward clinical targeting of KLK expression and function for cancer diagnosis, prognosis and therapies.

Interactions between organizational culture, trustworthiness, and mechanisms for inter-project knowledge sharing

This research used a multiple-case study approach to empirically investigate the complex relationship between factors influencing inter-project knowledge sharing—trustworthiness, organizational culture, and knowledge-sharing mechanisms. Adopting a competing values framework, we found evidence of patterns existing between the type of culture, on the project management unit level, and project managers’ perceptions of valuing trustworthy behaviors and the way they share knowledge, on the individual level. We also found evidence for mutually reinforcing the effect of trust and clan culture, which shape tacit knowledge-sharing behaviors.

The Chemistry of Mycotoxins

Mycotoxins – from the Greek μύκης (mykes, mukos) “fungus” and the Latin (toxicum) “poison” – are a large and growing family of secondary metabolites and hence natural products produced by fungi, in particular by molds (1). It is estimated that well over 1,000 mycotoxins have been isolated and characterized so far, but this number will increase over the next few decades due the availability of more specialized analytical tools and the increasing number of fungi being isolated. However, the most important classes of fungi responsible for these compounds are Alternaria, Aspergillus (multiple forms), Penicillium, and Stachybotrys. The biological activity of mycotoxins ranges from weak and/or sometimes positive effects such as antibacterial activity (e.g. penicillin derivatives derived from Penicillium strains) to strong mutagenic (e.g. aflatoxins, patulin), carcinogenic (e.g. aflatoxins), teratogenic, neurotoxic (e.g. ochratoxins), nephrotoxic (e.g. fumonisins, citrinin), hepatotoxic, and immunotoxic (e.g. ochratoxins, diketopiperazines) activities (1, 2), which are discussed in detail in this volume.

Teachers in early childhood policy

This paper examines teacher accountability and authority in early childhood policy. It reports on data from a study that investigated the influences affecting early childhood teacher decision-making at the preschool level in Victoria, Australia. Using a question raised by Ball ‘Where are the teachers in all this [policy]?’ provided a starting point for the critical discourse analysis into how forms of control, teacher authority, obligation and constraint within policies potentially influenced teachers’ curriculum decisions. The study found that despite no government-mandated curriculum framework at the time, teachers were held accountable for their curricular practice. Yet as professionals, early childhood teachers were denied public acknowledgement of their expertise as they were almost invisible in policy. In the four policies analysed, proprietors of early childhood settings and preschool agencies held authority over curriculum. Subsequently, teachers’ authority as professionals with curricular knowledge was diminished.