Multifocal urothelial cancers with the mutator phenotype are of monoclonal origin and require panurothelial treatment for tumor clearance

Purpose: UC is a disease of the entire urothelium, characterized by multiplicity and multifocality. The clonal relationship among multiple UCs has implications regarding adjuvant chemotherapy. It has been investigated in studies of chromosomal alteration and single gene mutation. However, these genetic changes can occur in unrelated tumors under similar carcinogenic selection pressures. Tumors with high MSI have numerous DNA mutations, of which many provide no selection benefit. While these tumors represent an ideal model for studying UC clonality, their low frequency has prevented their previous investigation. Materials and Methods: We investigated 32 upper and lower urinary tract UCs with high MSI and 4 nonUC primary cancers in 9 patients. We used the high frequency and specificity of individual DNA mutations in these tumors (MSI at 17 loci) and the early timing of epigenetic events (methylation of 7 gene promoters) to investigate tumor clonality. Results: Molecular alterations varied among tumors from different primary organs but they appeared related in the UCs of all 9 patients. While 7 patients had a high degree of concordance among UCs, in 2 the UCs shared only a few similar alterations. Genetic and epigenetic abnormalities were frequently found in normal urothelial samples. Conclusions: Multiple UCs in each patient appeared to arise from a single clone. The molecular order of tumor development varied from the timing of clinical presentation and suggested that residual malignant cells persist in the urinary tract despite apparent curative surgery. These cells lead to subsequent tumor relapse and new methods are required to detect and eradicate them.

Stigmergy within web modelling languages : positive feedback mechanisms

Stigmergy is a biological term originally used when discussing insect or swarm behaviour, and describes a model supporting environment-based communication separating artefacts from agents. This phenomenon is demonstrated in the behavior of ants and their food foraging supported by pheromone trails, or similarly termites and their termite nest building process. What is interesting with this mechanism is that highly organized societies are formed without an apparent central management function. We see design features in Web sites that mimic stigmergic mechanisms as part of the User Interface and we have created generalizations of these patterns. Software development and Web site development techniques have evolved significantly over the past 20 years. Recent progress in this area proposes languages to model web applications to facilitate the nuances specific to these developments. These modeling languages provide a suitable framework for building reusable components encapsulating our design patterns of stigmergy. We hypothesize that incorporating stigmergy as a separate feature of a site’s primary function will ultimately lead to enhanced user coordination.

A practical comparison of manual and autonomous methods for acoustic monitoring

1. Autonomous acoustic recorders are widely available and can provide a highly efficient method of species monitoring, especially when coupled with software to automate data processing. However, the adoption of these techniques is restricted by a lack of direct comparisons with existing manual field surveys. 2. We assessed the performance of autonomous methods by comparing manual and automated examination of acoustic recordings with a field-listening survey, using commercially available autonomous recorders and custom call detection and classification software. We compared the detection capability, time requirements, areal coverage and weather condition bias of these three methods using an established call monitoring programme for a nocturnal bird, the little spotted kiwi(Apteryx owenii). 3. The autonomous recorder methods had very high precision (>98%) and required <3% of the time needed for the field survey. They were less sensitive, with visual spectrogram inspection recovering 80% of the total calls detected and automated call detection 40%, although this recall increased with signal strength. The areal coverage of the spectrogram inspection and automatic detection methods were 85% and 42% of the field survey. The methods using autonomous recorders were more adversely affected by wind and did not show a positive association between ground moisture and call rates that was apparent from the field counts. However, all methods produced the same results for the most important conservation information from the survey: the annual change in calling activity. 4. Autonomous monitoring techniques incur different biases to manual surveys and so can yield different ecological conclusions if sampling is not adjusted accordingly. Nevertheless, the sensitivity, robustness and high accuracy of automated acoustic methods demonstrate that they offer a suitable and extremely efficient alternative to field observer point counts for species monitoring.

Reconstructing 3D x-ray CT images of polymer gel dosimeters using the zero-scan method

In this study x-ray CT has been used to produce a 3D image of an irradiated PAGAT gel sample, with noise-reduction achieved using the ‘zero-scan’ method. The gel was repeatedly CT scanned and a linear fit to the varying Hounsfield unit of each pixel in the 3D volume was evaluated across the repeated scans, allowing a zero-scan extrapolation of the image to be obtained. To minimise heating of the CT scanner’s x-ray tube, this study used a large slice thickness (1 cm), to provide image slices across the irradiated region of the gel, and a relatively small number of CT scans (63), to extrapolate the zero-scan image. The resulting set of transverse images shows reduced noise compared to images from the initial CT scan of the gel, without being degraded by the additional radiation dose delivered to the gel during the repeated scanning. The full, 3D image of the gel has a low spatial resolution in the longitudinal direction, due to the selected scan parameters. Nonetheless, important features of the dose distribution are apparent in the 3D x-ray CT scan of the gel. The results of this study demonstrate that the zero-scan extrapolation method can be applied to the reconstruction of multiple x-ray CT slices, to provide useful 2D and 3D images of irradiated dosimetry gels.

Going offline : An exploratory cultural artifact analysis of an internet dating site's development trajectories

In this study we develop a theorization of an Internet dating site as a cultural artifact. The site, Gaydar, is targeted at gay men. We argue that contemporary received representations of their sexuality figure heavily in the site’s focus by providing a cultural logic for the apparent ad hoc development trajectories of its varied commercial and non-­‐commercial services. More specifically, we suggest that the growing sets of services related to the website are heavily enmeshed within current social practices and meanings. These practices and meanings are, in turn, shaped by the interactions and preferences of a variety of diverse groups involved in what is routinely seen within the mainstream literature as a singularly specific sexuality and cultural project. Thus, we attend to two areas – the influence of the various social engagements associated with Gaydar together with the further extension of its trajectory ‘beyond the web’. Through the case of Gaydar, we contribute a study that recognizes the need for attention to sexuality in information systems research and one which illustrates sexuality as a pivotal aspect of culture. We also draw from anthropology to theorize ICTs as cultural artifacts and provide insights into the contemporary phenomena of ICT enabled social networking.

A study of the diffusion characteristics of normal, delipidized and relipidized articular cartilage using magnetic resonance imaging

This paper assesses the capacity to provide semipermeability of the synthetic layer of surface-active phospholipids created to replace the depleted surface amorphous layer of articular cartilage. The surfaces of articular cartilage specimens in normal, delipidized, and relipidized conditions following incubation in dipalmitoyl-phosphatidylcholine and palmitoyl-oleoyl-phosphatidylcholine components of the joint lipid mixture were characterized nanoscopically with the atomic force microscope and also imaged as deuterium oxide (D2O) diffused transiently through these surfaces in a magnetic resonance imaging enclosure. The MR images were then used to determine the apparent diffusion coefficients in a purpose-built MATLAB®-based algorithm. Our results revealed that all surfaces were permeable to D2O, but that there was a significant difference in the semipermeability of the surfaces under the different conditions, relative to the apparent diffusion coefficients. Based on the results and observations, it can be concluded that the synthetic lipid that is deposited to replace the depleted SAL of articular cartilage is capable of inducing some level of semipermeability.

Sun, sea, sex, sand and soap

A recent issue of Young People Now (November 1995) mentioned the new (UK) Channel 4 television soap opera Hollyoaks by Phil Redmond, which raises the issue of the role of ‘soaps’ in the daily lives of young people. Australian soaps are especially popular in Britain and of interest to those who work with young people, because they have a high proportion of youthful looking actors and actresses and frequently depict scenes involving young people and apparent ‘real’ teenage dilemmas.

A discourse on the non-method

In spite of the activism of professional bodies and researchers, empirical evidence shows that project management still does not deliver the expected benefits and promises. Hence, many have questioned the validity of the hegemonic rationalist paradigm anchored in the Enlightenment and Natural Sciences tradition supporting project management research and practice for the last 60 years and the lack of relevance to practice of the current conceptual base of project management. In order to address these limitations many authors, taking a post-modernist stance in social sciences, build on ‘pre-modern’ philosophies such as the Aristotelian one, specially emphasizing the role of praxis (activity), and phronesis (practical wisdom, prudence). Indeed, ‘Praxis … is the central category of the philosophy which is not merely an interpretation of the world, but is also a guide to its transformation …’ (Vazquez, 1977:. 149). Therefore, praxis offers an important focus for practitioners and researchers in social sciences, one in which theory is integrated with practice at the point of intervention. Simply stated, praxis can serve as a common ground for those interested in basic and applied research by providing knowledge of the reality in which action, informed by theory, takes place. Consequently, I suggest a ‘praxeological’ style of reasoning (praxeology being defined as study or science of human actions and conduct, including praxis, practices and phronesis) and to go beyond the ‘Theory-Practice’ divide. Moreover, I argue that we need to move away from the current dichotomy between the two classes ‘scholars experts-researchers’ and ‘managers/workers-practitioners-participants’. Considering one single class of ‘PraXitioner’, becoming a phronimos, may contribute to create new perspectives and open up new ways of thinking and acting in project situations. Thus, I call for a Perestroika in researching and acting in project management situations. My intent is to suggest a balanced praxeological view of the apparent opposition between social and natural science approaches. I explore, in this chapter, three key questions, covering the ontological, epistemological and praxeological dimensions of project management in action. 1. Are the research approaches being currently used appropriate for generating contributions that matter to both theory and practice with regards to what a ‘project’ is or to what we do when we call a specific situation ‘a project’? 2. On the basis of which intellectual virtues is the knowledge generated and what is the impact for theory and practice? 3. Are the modes of action of the practitioners ‘prudent’ and are they differentiating or reconciling formal and abstract rationality from substantive rationality and situated reasoning with regards to the mode of action they adopt in particular project situations? The investigation of the above questions leads me to debate about ‘Project Management-as-Praxis’, and to suggest ‘A’ (not ‘THE’) ‘praxeological’ style of reasoning and mode of inquiry – acknowledging a non-paradigmatic, subjective and kaleidoscopic perspective – for ‘Knowing-as-Practicing’ in project management. In short, this is about making a ‘Projects Science’ that matters.

What is a good project manager? Reconceptualizing the “do” : an Aristotelian perspective

In Social Science (Organization Studies, Economics, Management Science, Strategy, International Relations, Political Science…) the quest for addressing the question “what is a good practitioner?” has been around for centuries, with the underlying assumptions that good practitioners should lead organizations to higher levels of performance. Hence to ask “what is a good “captain”?” is not a new question, we should add! (e.g. Tsoukas & Cummings, 1997, p. 670; Söderlund, 2004, p. 190). This interrogation leads to consider problems such as the relations between dichotomies Theory and Practice, rigor and relevance of research, ways of knowing and knowledge forms. On the one hand we face the “Enlightenment” assumptions underlying modern positivist Social science, grounded in “unity-of-science dream of transforming and reducing all kinds of knowledge to one basic form and level” and cause-effects relationships (Eikeland, 2012, p. 20), and on the other, the postmodern interpretivist proposal, and its “tendency to make all kinds of knowing equivalent” (Eikeland, 2012, p. 20). In the project management space, this aims at addressing one of the fundamental problems in the field: projects still do not deliver their expected benefits and promises and therefore the socio-economical good (Hodgson & Cicmil, 2007; Bredillet, 2010, Lalonde et al., 2012). The Cartesian tradition supporting projects research and practice for the last 60 years (Bredillet, 2010, p. 4) has led to the lack of relevance to practice of the current conceptual base of project management, despite the sum of research, development of standards, best & good practices and the related development of project management bodies of knowledge (Packendorff, 1995, p. 319-323; Cicmil & Hodgson, 2006, p. 2–6, Hodgson & Cicmil, 2007, p. 436–7; Winter et al., 2006, p. 638). Referring to both Hodgson (2002) and Giddens (1993), we could say that “those who expect a “social-scientific Newton” to revolutionize this young field “are not only waiting for a train that will not arrive, but are in the wrong station altogether” (Hodgson, 2002, p. 809; Giddens, 1993, p. 18). While, in the postmodern stream mainly rooted in the “practice turn” (e.g. Hällgren & Lindahl, 2012), the shift from methodological individualism to social viscosity and the advocated pluralism lead to reinforce the “functional stupidity” (Alvesson & Spicer, 2012, p. 1194) this postmodern stream aims at overcoming. We suggest here that addressing the question “what is a good PM?” requires a philosophy of practice perspective to complement the “usual” philosophy of science perspective. The questioning of the modern Cartesian tradition mirrors a similar one made within Social science (Say, 1964; Koontz, 1961, 1980; Menger, 1985; Warry, 1992; Rothbard, 1997a; Tsoukas & Cummings, 1997; Flyvbjerg, 2001; Boisot & McKelvey, 2010), calling for new thinking. In order to get outside the rationalist ‘box’, Toulmin (1990, p. 11), along with Tsoukas & Cummings (1997, p. 655), suggests a possible path, summarizing the thoughts of many authors: “It can cling to the discredited research program of the purely theoretical (i.e. “modern”) philosophy, which will end up by driving it out of business: it can look for new and less exclusively theoretical ways of working, and develop the methods needed for a more practical (“post-modern”) agenda; or it can return to its pre-17th century traditions, and try to recover the lost (“pre-modern”) topics that were side-tracked by Descartes, but can be usefully taken up for the future” (Toulmin, 1990, p. 11). Thus, paradoxically and interestingly, in their quest for the so-called post-modernism, many authors build on “pre-modern” philosophies such as the Aristotelian one (e.g. MacIntyre, 1985, 2007; Tsoukas & Cummings, 1997; Flyvbjerg, 2001; Blomquist et al., 2010; Lalonde et al., 2012). It is perhaps because the post-modern stream emphasizes a dialogic process restricted to reliance on voice and textual representation, it limits the meaning of communicative praxis, and weaking the practice because it turns away attention from more fundamental issues associated with problem-definition and knowledge-for-use in action (Tedlock, 1983, p. 332–4; Schrag, 1986, p. 30, 46–7; Warry, 1992, p. 157). Eikeland suggests that the Aristotelian “gnoseology allows for reconsidering and reintegrating ways of knowing: traditional, practical, tacit, emotional, experiential, intuitive, etc., marginalised and considered insufficient by modernist [and post-modernist] thinking” (Eikeland, 2012, p. 20—21). By contrast with the modernist one-dimensional thinking and relativist and pluralistic post-modernism, we suggest, in a turn to an Aristotelian pre-modern lens, to re-conceptualise (“re” involving here a “re”-turn to pre-modern thinking) the “do” and to shift the perspective from what a good PM is (philosophy of science lens) to what a good PM does (philosophy of practice lens) (Aristotle, 1926a). As Tsoukas & Cummings put it: “In the Aristotelian tradition to call something good is to make a factual statement. To ask, for example, ’what is a good captain’?’ is not to come up with a list of attributes that good captains share (as modem contingency theorists would have it), but to point out the things that those who are recognized as good captains do.” (Tsoukas & Cummings, 1997, p. 670) Thus, this conversation offers a dialogue and deliberation about a central question: What does a good project manager do? The conversation is organized around a critic of the underlying assumptions supporting the modern, post-modern and pre-modern relations to ways of knowing, forms of knowledge and “practice”.

Evidence for the adsorption of molecules at special sites located at copper/zinc oxide interfaces: Part 1. -- A Fourier-transform infrared study of formic acid and formaldehyde adsorption on reduced and oxidised Cu/ZnO/SiO2 catalysts

Fourier-transform infrared (FTIR) spectra are reported of formic acid and formaldehyde on ZnO/SiO2, reduced Cu/ZnO/SiO2 and reoxidised Cu/ZnO/SiO2 catalyst. Formic acid adsorption on ZnO/SiO2 produced mainly bidentate zinc formate species with a lesser quantity of unidentate zinc formate. Formic acid on reduced Cu/ZnO/SiO2 catalyst resulted not only in the formation of bridging copper formate structures but also in an enhanced amount of formate relative to that for ZnO/SiO2 catalyst. Formic acid on reoxidised Cu/ZnO/SiO2 gave unidentate formate species on copper in addition to zinc formate moieties. The interaction of formaldehyde with ZnO/SiO2 catalyst resulted in the formation of zinc formate species. The same reaction on reduced Cu/ZnO/SiO2 catalyst gave bridging formate on copper and a remarkable increase in the quantity of formate species associated with the zinc oxide. Adsorption of formaldehyde on a reoxidised Cu/ZnO/SiO2 catalyst produced bridging copper formate and again an apparent increase in the concentration of zinc formate species. An explanation in terms of the adsorption of molecules at special sites located at the interface between copper and zinc oxide is given.

In situ imaging of catalytic etching on silver during methanol oxidation conditions by environmental scanning electron microscopy

Polycrystalline silver is used to catalytically oxidise methanol to formaldehyde. This paper reports the results of extensive investigations involving the use of environmental scanning electron microscopy (ESEM) to monitor structural changes in silver during simulated industrial reaction conditions. The interaction of oxygen, nitrogen, and water, either singly or in combination, with a silver catalyst at temperatures up to 973 K resulted in the appearance of a reconstructed silver surface. More spectacular was the effect an oxygen/methanol mixture had on the silver morphology. At a temperature of ca. 713 K pinholes were created in the vicinity of defects as a consequence of subsurface explosions. These holes gradually increased in size and large platelet features were created. Elevation of the catalyst temperature to 843 K facilitated the wholescale oxygen induced restructuring of the entire silver surface. Methanol reacted with subsurface oxygen to produce subsurface hydroxyl species which ultimately formed water in the subsurface layers of silver. The resultant hydrostatic pressure forced the silver surface to adopt a "hill and valley" conformation in order to minimise the surface free energy. Upon approaching typical industrial operating conditions widespread explosions occurred on the catalyst and it was also apparent that the silver surface was extremely mobile under the applied conditions. The interaction of methanol alone with silver resulted in the initial formation of pinholes primarily in the vicinity of defects, due to reaction with oxygen species incorporated in the catalyst during electrochemical synthesis. However, dramatic reduction in the hole concentration with time occurred as all the available oxygen became consumed. A remarkable correlation between formaldehyde production and hole concentration was found.

trans-Polyacetylene on sodium and cesium mordenites: a resonance Raman spectroscopic study

Sodium and cesium mordenite (denoted NaM and CsM, respectively) were investigated as potential catalysts for the synthesis of polyacetylene ((CH) x). Both were successful in initiating polymerization of purified gaseous acetylene at room temperature as evidenced by Raman spectroscopic studies. The polyacetylene synthesised in this way exhibited resonance enhancement of the polyene skeletal vibrations. trans-Polyacetylene, but no cis-(CH) x, was detected. As no apparent coloration of the NaM and CsM substrates accompanied the formation of trans-(CH) x it was concluded that only small quantities of the polymer were present. The number of conjugated double bonds was estimated from the frequencies of the Raman active C-C and C=C stretching vibrations, and it was shown that the trans-(CH) x formed on CsM has a distribution of conjugation lengths ranging from less than 6 to at least 30 double bonds. The polyacetylene formed on NaM was significantly shorter and was produced in lower yields than that synthesized on CsM. "Sliced" resonance excitation profiles of polyacetylene formed on CsM were obtained using nearly 40 different excitation wavelengths and these confirmed that the adsorbed trans-(CH) x was composed of segments having a distribution of conjugated lengths. The architecture of the mordenite pore system permitted only a single polymer molecule per channel, thereby preventing cross-linking. Raman spectroscopic studies of the effects of exposure to air revealed that progressive oxidative degradation occurred with a reduction in the number of conjugated double bond

Gelatin-methacrylamide hydrogels as potential biomaterials for fabrication of tissue-engineered cartilage constructs

Gelatin-methacrylamide (gelMA) hydrogels are shown to support chondrocyte viability and differentiation and give wide ranging mechanical properties depending on several cross-linking parameters. Polymer concentration, UV exposure time, and thermal gelation prior to UV exposure allow for control over hydrogel stiffness and swelling properties. GelMA solutions have a low viscosity at 37 °C, which is incompatible with most biofabrication approaches. However, incorporation of hyaluronic acid (HA) and/or co-deposition with thermoplastics allows gelMA to be used in biofabrication processes. These attributes may allow engineered constructs to match the natural functional variations in cartilage mechanical and geometrical properties.

Producing and maintaining professional identities in early childhood

This study is an inquiry into early childhood teacher professional identities. In Australia, workforce reforms in early childhood include major shifts in qualification requirements that call for a university four-year degree-qualified teacher to be employed in child care. This marks a shift in the early years workforce, where previously there was no such requirement. At the same time as these reforms to quality measures are being implemented, and requiring a substantive up skilling of the workforce, there is a growing body of evidence through recent studies that suggests these same four-year degree-qualified early childhood teachers have an aversion to working in child care. Their preferred employment option is to work in the early years of more formal schooling, not in before-school contexts. This collision of agendas warrants investigation. This inquiry is designed to investigate the site at which advocacy for higher qualification requirements meets early childhood teachers who are reluctant to choose child care as a possible career pathway. The key research question for this study is: How are early childhood teachers’ professional identities currently produced? The work of this thesis is to problematise the early childhood teacher in child care through a particular method of discourse analysis. There are two sets of data. The first was a key early childhood political document that read as a "moment of arising" (Foucault, 1984a, p. 83). It is a political document which was selected for its current influence on the early childhood field, and in particular, workforce reforms that call for four-year degree-qualified teachers to work in before-school contexts, including child care. The second data set was generated through four focus group discussions conducted with preservice early childhood teachers. The document and transcripts of the focus groups were both analysed as text, as conceptualised by Foucault (1981). Foucault’s work spans a number of years and a range of philosophical matters. This thesis draws particularly on Foucault’s writings on discourse, power/knowledge, regimes of truth and resistance. In order to consider the production of early childhood teachers’ professional identities, the study is also informed by identity theorists, who have worked on gender, performativity and investment (Davies, 2004/2006; McNay, 1992; Osgood, 2012; Walkerdine, 1990; Weedon, 1997). The ways in which discourses intersect, compete and collide produce the subject (Foucault, 1981) and, in the case of this inquiry, there are a number of competing discourses at play, which produce the early childhood teacher. These particular theories turn particular lenses on the question of professional identities in early childhood, and such a study calls for the application of particular methodologies. Discourse analysis was used as the methodological framework, and the analysis was informed by Foucauldian concepts of discourse. While Foucault did not prescribe a form of discourse analysis as a method, his writings nonetheless provide a valuable framework for illuminating discursive practices and, in turn, how people are affected, through the shifts and distribution of power (Foucault, 1980a). The treatment used with both data sets involved redescription. For the policy document, a technique for reading document-as-text applied a genealogical approach (Foucault, 1984a). For the focus groups, the process of redescription (Rorty, 1989) involved reading talk-as-text. As a method, redescription involves describing "lots and lots of things in new ways until you have created a pattern of linguistic behaviour which will tempt the new generation to adopt it" (Rorty, 1989, p. 9). The development and application of categories (Davies, 2004/2006) built on a poststructuralist theoretical framework and the literature review informed the data analysis method of discourse analysis. Irony provided a rhetorical and playful tool (Haraway, 1991; Rorty, 1989), to look to how seemingly opposing discourses are held together. This opens a space to collapse binary thinking and consider seemingly contradictory terms in a way in which both terms are possible and both are true. Irony resists the choice of one or the other being right, and holds the opposites together in tension. The thesis concludes with proposals for new, ironic categories, which work to bring together seemingly opposing terms, located at sites in the field of early childhood where discourses compete, collide and intersect to produce and maintain early childhood teacher professional identities. The process of mapping these discourses goes some way to investigating the complexities about identities and career choices of early childhood teachers. The category of "the cost of loving" captures the collision between care/love, inherent in child care, and new discourses of investment/economics. Investment/economics has not completely replaced care/love, and these apparent opposites were not read as a binary because both are necessary and both are true (Haraway, 1991). They are held together in tension to produce early childhood teacher professional identities. The policy document under scrutiny was New Directions, released in 2007 by the then opposition ALP leader, Kevin Rudd. The claim was made strongly that the "economic prosperity" of Australia relies on investment in early childhood. The arguments to invest are compelling and the neuroscience/brain research/child development together with economic/investment discourses demand that early childhood is funding is increased. The intersection of these discourses produces professional identities of early childhood teachers as a necessary part of the country’s economy, and thus, worthy of high status. The child care sector and work in child care settings are necessary, with children and the early childhood teacher playing key roles in the economy of the nation. Through New Directions it becomes sayable (Foucault, 1972/1989) that the work the early childhood teacher performs is legitimated and valued. The children are produced as "economic units". A focus on what children are able to contribute to the future economy of the nation re-positions children and produces these "smart productive citizens", making future economic contribution. The early childhood teacher is produced through this image of a child and "the cost of loving" is emphasised. A number of these categories were produced through the readings of the document-as text and the talk-as-text. Two ironic categories were read in the analysis of the transcripts of the focus group discussions, when treated as talk-as-text data: the early childhood teacher as a "heroic victim"; and the early childhood teacher as a "glorified babysitter". This thesis raises new questions about professional identities in early childhood. These new questions might go some way to prompt re-thinking of some government policy, as well as some aspects of early childhood teacher education course design. The images of children and images of child care provide provocations to consider preservice teacher education course design. In particular, how child care, as one of the early childhood contexts, is located, conceptualised and spoken throughout the course. Consideration by course designers and teacher educators of what discourses are privileged in course content —what discourses are diminished or silenced—would go some way to reconceptualising child care within preservice teacher education and challenging dominant ways of speaking child care, and work in child care. This inquiry into early childhood teachers’ professional identities has gone some way to exploring the complexities around the early childhood teacher in child care. It is anticipated that the significance of this study will thus have immediate applicably and relevance for the Australian early childhood policy landscape. The early childhood field is in a state of rapid change, and this inquiry has examined some of the disconnects between policy and practice. Awareness of the discourses that are in play in the field will continue to allow space for conversations that challenge dominant assumptions about child care, work in child care and ways of being an early childhood teacher in child care.

Unique X-linked familial FSGS with co-segregating heart block disorder is associated with a mutation in the NXF5 gene

Focal segmental glomerulosclerosis (FSGS) is the consequence of a disease process that attacks the kidney's filtering system, causing serious scarring. More than half of FSGS patients develop chronic kidney failure within 10 years, ultimately requiring dialysis or renal transplantation. There are currently several genes known to cause the hereditary forms of FSGS (ACTN4, TRPC6, CD2AP, INF2, MYO1E and NPHS2). This study involves a large, unique, multigenerational Australian pedigree in which FSGS co-segregates with progressive heart block with apparent X-linked recessive inheritance. Through a classical combined approach of linkage and haplotype analysis, we identified a 21.19 cM interval implicated on the X chromosome. We then used a whole exome sequencing approach to identify two mutated genes, NXF5 and ALG13, which are located within this linkage interval. The two mutations NXF5-R113W and ALG13-T141L segregated perfectly with the disease phenotype in the pedigree and were not found in a large healthy control cohort. Analysis using bioinformatics tools predicted the R113W mutation in the NXF5 gene to be deleterious and cellular studies support a role in the stability and localization of the protein suggesting a causative role of this mutation in these co-morbid disorders. Further studies are now required to determine the functional consequence of these novel mutations to development of FSGS and heart block in this pedigree and to determine whether these mutations have implications for more common forms of these diseases in the general population.