Fine-mapping the HOXB region detects common variants tagging a rare coding allele : evidence for synthetic association in prostate cancer

The HOXB13 gene has been implicated in prostate cancer (PrCa) susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with PrCa risk, described by rs117576373 (OR 1.30, P = 2.62×10(-14)). Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene (G84E, rs138213197), which has been identified recently as a moderate penetrance PrCa susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility.

The adhesion molecule L1 regulates transendothelial migration and trafficking of dendritic cells

The adhesion molecule L1, which is extensively characterized in the nervous system, is also expressed in dendritic cells (DCs), but its function there has remained elusive. To address this issue, we ablated L1 expression in DCs of conditional knockout mice. L1-deficient DCs were impaired in adhesion to and transmigration through monolayers of either lymphatic or blood vessel endothelial cells, implicating L1 in transendothelial migration of DCs. In agreement with these findings, L1 was expressed in cutaneous DCs that migrated to draining lymph nodes, and its ablation reduced DC trafficking in vivo. Within the skin, L1 was found in Langerhans cells but not in dermal DCs, and L1 deficiency impaired Langerhans cell migration. Under inflammatory conditions, L1 also became expressed in vascular endothelium and enhanced transmigration of DCs, likely through L1 homophilic interactions. Our results implicate L1 in the regulation of DC trafficking and shed light on novel mechanisms underlying transendothelial migration of DCs. These observations might offer novel therapeutic perspectives for the treatment of certain immunological disorders.

A comparison of Australian and Canadian informatics competencies for undergraduate nurses

Health information technologies (HIT) have changed healthcare delivery. Yet, there are few opportunities for student nurses in their undergraduate studies to develop nursing informatics competencies. More importantly, many countries around the world have not fully specified nursing informatics competencies that will be expected of student nurses prior to their graduation from undergraduate nursing programs. In this paper the authors compare and contrast the undergraduate nursing informatics competencies that were developed by two countries: Australia and Canada. They also identify some of the challenges and future research directions in the area.

DIY media architecture: Open and participatory approaches to community engagement

Media architecture’s combination of the digital and the physical can trigger, enhance, and amplify urban experiences. In this paper, we examine how to bring about and foster more open and participatory approaches to engage communities through media architecture by identifying novel ways to put some of the creative process into the hands of laypeople. We review technical, spatial, and social aspects of DIY phenomena with a view to better understand maker cultures, communities, and practices. We synthesise our findings and ask if and how media architects as a community of practice can encourage the ‘open-sourcing’ of information and tools allowing laypeople to not only participate but become active instigators of change in their own right. We argue that enabling true DIY practices in media architecture may increase citizen control. Seeking design strategies that foster DIY approaches, we propose five areas for further work and investigation. The paper begs many questions indicating ample room for further research into DIY Media Architecture.

Recognising emotional expressions of complaining customers : A cross-cultural study

Purpose This study aims to test service providers’ ability to recognise non-verbal emotions in complaining customers of same and different cultures. Design/methodology/approach In a laboratory study, using a between-subjects experimental design (n = 153), we tested the accuracy of service providers’ perceptions of the emotional expressions of anger, fear, shame and happiness of customers from varying cultural backgrounds. After viewing video vignettes of customers complaining (with the audio removed), participants (in the role of service providers) assessed the emotional state of the customers portrayed in the video. Findings Service providers in culturally mismatched dyads were prone to misreading anger, happiness and shame expressed by dissatisfied customers. Happiness was misread in the displayed emotions of both dyads. Anger was recognisable in the Anglo customers but not Confucian Asian, while Anglo service providers misread both shame and happiness in Confucian Asian customers. Research limitations/implications The study was conducted in the laboratory and was based solely on participant’s perceptions of actors’ non-verbal facial expressions in a single encounter. Practical implications Given the level of ethnic differences in developed nations, a culturally sensitive workplace is needed to foster effective functioning of service employee teams. Ability to understand cultural display rules and to recognise and interpret emotions is an important skill for people working in direct contact with customers. Originality/value This research addresses the lack of empirical evidence for the recognition of customer emotions by service providers and the impact of cross-cultural differences.

Writing embodied practice from the inside : outside the exegesis

The textual turn is a good friend of expert spectating, where it assumes the role of writing-productive apparatus, but no friend at all of expert practices or practitioners (Melrose, 2003). Introduction The challenge of time-based embodied performance when the artefact is unstable As a former full-time professional practitioner with an embodied dance practice as performer, choreographer and artistic director for three decades, I somewhat unexpectedly entered the world of academia in 2000 after completing a practice-based PhD, which was described by its examiners as ‘pioneering’. Like many artists my intention was to deepen and extend my practice through formal research into my work and its context (which was intercultural) and to privilege the artist’s voice in a research world where it was too often silent. Practice as research, practice-based research, and practice-led research were not yet fully named. It was in its infancy and my biggest challenge was to find a serviceable methodology which did not betray my intentions to keep practice at the centre of the research. Over the last 15 years, practice led doctoral research, where examinable creative work is placed alongside an accompanying (exegetical) written component, has come a long way. It has been extensively debated with a range of theories and models proposed (Barrett & Bolt, 2007, Pakes, 2003 & 2004, Piccini, 2005, Philips, Stock & Vincs 2009, Stock, 2009 & 2010, Riley & Hunter 2009, Haseman, 2006, Hecq, 2012). Much of this writing is based around epistemological concerns where the research methodologies proposed normally incorporate a contextualisation of the creative work in its field of practice, and more importantly validation and interrogation of the processes of the practice as the central ‘data gathering’ method. It is now widely accepted, at least in the Australian creative arts context, that knowledge claims in creative practice research arise from the material activities of the practice itself (Carter, 2004). The creative work explicated as the tangible outcome of that practice is sometimes referred to as the ‘artefact’. Although the making of the artefact, according to Colbert (2009, p. 7) is influenced by “personal, experiential and iterative processes”, mapping them through a research pathway is “difficult to predict [for] “the adjustments made to the artefact in the light of emerging knowledge and insights cannot be foreshadowed”. Linking the process and the practice outcome most often occurs through the textual intervention of an exegesis which builds, and/or builds on, theoretical concerns arising in and from the work. This linking produces what Barrett (2007) refers to as “situated knowledge… that operates in relation to established knowledge” (p. 145). But what if those material forms or ‘artefacts’ are not objects or code or digitised forms, but live within the bodies of artist/researchers where the nature of the practice itself is live, ephemeral and constantly transforming, as in dance and physical performance? Even more unsettling is when the ‘artefact’ is literally embedded and embodied in the work and in the maker/researcher; when subject and object are merged. To complicate matters, the performing arts are necessarily collaborative, relying not only on technical mastery and creative/interpretive processes, but on social and artistic relationships which collectively make up the ‘artefact’. This chapter explores issues surrounding live dance and physical performance when placed in a research setting, specifically the complexities of being required to translate embodied dance findings into textual form. Exploring how embodied knowledge can be shared in a research context for those with no experiential knowledge of communicating through and in dance, I draw on theories of “dance enaction” (Warburton, 2011) together with notions of “affective intensities” and “performance mastery” (Melrose, 2003), “intentional activity” (Pakes, 2004) and the place of memory. In seeking ways to capture in another form the knowledge residing in live dance practice, thus making implicit knowledge explicit, I further propose there is a process of triple translation as the performance (the living ‘artefact’) is documented in multi-facetted ways to produce something durable which can be re-visited. This translation becomes more complex if the embodied knowledge resides in culturally specific practices, formed by world views and processes quite different from accepted norms and conventions (even radical ones) of international doctoral research inquiry. But whatever the combination of cultural, virtual and genre-related dance practices being researched, embodiment is central to the process, outcome and findings, and the question remains of how we will use text and what forms that text might take.

Tendinopathy alters cumulative transverse strain in the patellar tendon postexercise.

Introduction This research evaluated the effect of tendinopathy on the cumulative transverse strain response of the patellar tendon to a bout of resistive quadriceps exercise. Methods Nine adults with unilateral patellar tendinopathy (age 18.2±0.7 years, height 1.92±0.06 m and weight 76.8±6.8 kg) and ten healthy adults free of knee pain (age 17.8±0.8 years, height 1.83±0.05 m and weight 73.2±7.6 kg) underwent standardised sagittal sonograms (7.2–14 MHz linear–array transducer) of both patellar tendons immediately prior and following 45 repetitions of a double–leg decline–squat exercise performed against a resistance of 145% bodyweight. Tendon thickness was determined 5–mm and 25–mm distal to the patellar pole. Transverse Hencky strain was calculated as the natural log of the ratio of post– to pre–exercise tendon thickness and expressed as a percentage. Measures of tendon echogenicity were calculated within the superficial and deep aspects of each tendon site from gray–scale profiles. Intratendinous microvessels were evaluated using power Doppler ultrasound. Results The cumulative transverse strain response to exercise in symptomatic tendinopathy was significantly lower than that of asymptomatic and healthy tendon (P<.05). There was also a significant reduction (57%) in the area of microvascularity immediately following exercise (P=.05), which was positively correlated (r=0.93, P<.05) with VISA-P score. Conclusions This study is the first to show that patellar tendinopathy is associated with an altered morphological and mechanical response of the tendon to exercise, which is manifest by a reduction in cumulative transverse strain and microvascularity, when present. Research directed toward identifying factors that influence the acute microvascular and transverse strain response of the patellar tendon to exercise in the various stages of tendinopathy is warranted.

Force-deformation properties of the human heel pad during barefoot walking

Introduction: The plantar heel pad is a specialized fibroadipose tissue that attenuates and, in part, dissipates the impact energy associated with heel strike. Although near maximal deformation of the heel pad has been shown during running, in vivo measurement of the deformation and structural properties of the heel pad during walking remains largely unexplored. This study employed a fluoroscope, synchronized with a pressure platform, to obtain force–deformation data for the heel pad during walking. Methods: Dynamic lateral foot radiographs were acquired from 6 male and 10 female adults (age, 45 ± 10 yrs; height, 1.66 ± 0.10 m; and weight, 80.7 ± 10.8 kg), while walking barefoot at preferred speeds. The inferior aspect of the calcaneus was digitized and the sagittal thickness and deformation of the heel pad relative to the support surface calculated. Simultaneous measurement of the peak force beneath the heel was used to estimate the principal structural properties of the heel pad. Results: Transient loading profiles associated with walking induced rapidly changing deformation rates in the heel pad and resulted in irregular load–deformation curves. The initial stiffness (32 ± 11 N.mm-1) of the heel pad was an order of magnitude lower than its final stiffness (212 ± 125 N.mm-1) and on average, only 1.0 J of energy was dissipated by the heel pad with each step during walking. Peak deformation (10.3 mm) approached that predicted for the limit of pain tolerance (10.7 mm). Conclusion: These findings suggest the heel pad operates close to its pain threshold even at speeds encountered during barefoot walking and provides insight as to why barefoot runners may adopt ‘forefoot’ strike patterns that minimize heel loading.

Running shoes increase Achilles tendon load in walking : an acoustic propagation study

Background: Footwear remains a prime candidate for the prevention and rehabilitation of Achilles tendinopathy as it is thought to decrease tension in the tendon through elevation of the heel. However, evidence for this effect is equivocal. Purpose: This study used an acoustic transmission technique to investigate the effect of running shoes on Achilles tendon loading during barefoot and shod walking. Methods: Acoustic velocity was measured in the Achilles tendon of twelve recreationally–active males (age, 31±9 years; height, 1.78±0.06 m; weight, 81.0±16.9 kg) during barefoot and shod walking at matched self–selected speed (3.4±0.7 km/h). Standard running shoes incorporating a 10– mm heel offset were used. Vertical ground reaction force and spatiotemporal parameters were determined with an instrumented treadmill. Axial acoustic velocity in the Achilles tendon was measured using a custom built ultrasonic device. All data were acquired at a rate of 100 Hz during 10s of steady–state walking. Statistical comparisons between barefoot and shod conditions were made using paired t–tests and repeated measure ANOVAs. Results: Acoustic velocity in the Achilles tendon was highly reproducible and was typified by two maxima (P1, P2) and minima (M1, M2) during walking. Footwear resulted in a significant increase in step length, stance duration and peak vertical ground reaction force compared to barefoot walking. Peak acoustic velocity in the Achilles tendon (P1, P2) was significantly higher with running shoes. Conclusions: Peak acoustic velocity in the Achilles tendon was higher with footwear, suggesting that standard running shoes with a 10–mm heel offset increase tensile load in the Achilles tendon. Although further research is required, these findings question the therapeutic role of standard running shoes in Achilles tendinopathy.

History of Work Health and Safety Laws

This definitive guide (formerly the Australian Master OHS & Environment Guide) is a first point of reference for work health and safety best practice and strategy. Written by WHS and legal experts, the guide provides key information on the challenges that professionals and organisations face in relation to WHS. It includes valuable information on legal obligations and risk management, and covers the latest changes brought about by the Work Health and Safety Act.

Overview of New Work Health and Safety Laws

This definitive guide (formerly the Australian Master OHS & Environment Guide) is a first point of reference for work health and safety best practice and strategy. Written by WHS and legal experts, the guide provides key information on the challenges that professionals and organisations face in relation to WHS. It includes valuable information on legal obligations and risk management, and covers the latest changes brought about by the Work Health and Safety Act.