The getting of wisdom : the future of PM university education in Australia

The dynamic and complex nature of project management (PM) in Australia provides exciting opportunities for universities to that are willing to actively engage with their corporate partners and other key stakeholders to develop program and course offerings that simultaneously address the needs of students, employers, and other stakeholders and further the current body of PM knowledge and research. This article identifies key challenges and opportunities for the future direction of PM university education. This draws on descriptions of successful program models, examining teaching on PM skills on generic business and engineering degrees, dedicated graduate masters programs in PM, doctoral research programs in PM, and forms of effective collaboration between industry and academia.

Modeling the cumulative genetic risk for multiple sclerosis from genome-wide association data

Background: Multiple sclerosis (MS) is the most common cause of chronic neurologic disability beginning in early to middle adult life. Results from recent genome-wide association studies (GWAS) have substantially lengthened the list of disease loci and provide convincing evidence supporting a multifactorial and polygenic model of inheritance. Nevertheless, the knowledge of MS genetics remains incomplete, with many risk alleles still to be revealed. Methods: We used a discovery GWAS dataset (8,844 samples, 2,124 cases and 6,720 controls) and a multi-step logistic regression protocol to identify novel genetic associations. The emerging genetic profile included 350 independent markers and was used to calculate and estimate the cumulative genetic risk in an independent validation dataset (3,606 samples). Analysis of covariance (ANCOVA) was implemented to compare clinical characteristics of individuals with various degrees of genetic risk. Gene ontology and pathway enrichment analysis was done using the DAVID functional annotation tool, the GO Tree Machine, and the Pathway-Express profiling tool. Results: In the discovery dataset, the median cumulative genetic risk (P-Hat) was 0.903 and 0.007 in the case and control groups, respectively, together with 79.9% classification sensitivity and 95.8% specificity. The identified profile shows a significant enrichment of genes involved in the immune response, cell adhesion, cell communication/ signaling, nervous system development, and neuronal signaling, including ionotropic glutamate receptors, which have been implicated in the pathological mechanism driving neurodegeneration. In the validation dataset, the median cumulative genetic risk was 0.59 and 0.32 in the case and control groups, respectively, with classification sensitivity 62.3% and specificity 75.9%. No differences in disease progression or T2-lesion volumes were observed among four levels of predicted genetic risk groups (high, medium, low, misclassified). On the other hand, a significant difference (F = 2.75, P = 0.04) was detected for age of disease onset between the affected misclassified as controls (mean = 36 years) and the other three groups (high, 33.5 years; medium, 33.4 years; low, 33.1 years). Conclusions: The results are consistent with the polygenic model of inheritance. The cumulative genetic risk established using currently available genome-wide association data provides important insights into disease heterogeneity and completeness of current knowledge in MS genetics.

Lysine residues of IGF-I are substrates for transglutaminases and modulate downstream IGF-I signalling

Numerous studies have reported associations between IGF-I and other extra cellular matrix (ECM) proteins, including fibronectin (FN), integrins, IGF-binding proteins (IGFBPs) and through IGFBPs, with vitronectin (VN). Nevertheless, the precise nature and mechanisms of these interactions are still being characterised. In this paper, we discuss transglutaminases (TGases) as a constituent of the ECM and provide evidence for the first time that IGF-I is a lysine (K)-donor substrate to TGases. When IGF-I was incubated with an alpha-2 plasmin inhibitor-derived Q peptide in the presence of tissue transglutaminase (TG2), an IGF-I:Q peptide cross-linked species was detected using Western immunoblotting and confirmed by mass spectrometry. Similar findings were observed in the presence of Factor XIIIa (FXIIIa) TGase. To identify the precise location of this K-donor TGase site/s on IGF-I, all the three IGF-I K-sites, individually and collectively (K27, K65 and K68), were substituted to arginine (R) using site-directed mutagenesis. Incubation of these K→R IGF-I analogues with Q peptide in the presence of TG2 or FXIIIa resulted in the absence of cross-linking in IGF-I analogues bearing arginine substitution at site 68. This established that K68 within the IGF-I D-domain was the principal K-donor site to TGases. We further annotated the functional significance of these K→R IGF-I analogues on IGF-I mediated actions. IGF-I analogues with K→R substitution within the D-domain at K65 and K68 hindered migration of MCF-7 breast carcinoma cells and correspondingly reduced PI3-K/AKT activation. Therefore, this study also provides first insights into a possible functional role of the previously uncharacterised IGF-I D-domain.

A systematic review of mathematical models of mosquito-borne pathogen transmission: 1970-2010

Mathematical models of mosquito-borne pathogen transmission originated in the early twentieth century to provide insights into how to most effectively combat malaria. The foundations of the Ross–Macdonald theory were established by 1970. Since then, there has been a growing interest in reducing the public health burden of mosquito-borne pathogens and an expanding use of models to guide their control. To assess how theory has changed to confront evolving public health challenges, we compiled a bibliography of 325 publications from 1970 through 2010 that included at least one mathematical model of mosquito-borne pathogen transmission and then used a 79-part questionnaire to classify each of 388 associated models according to its biological assumptions. As a composite measure to interpret the multidimensional results of our survey, we assigned a numerical value to each model that measured its similarity to 15 core assumptions of the Ross–Macdonald model. Although the analysis illustrated a growing acknowledgement of geographical, ecological and epidemiological complexities in modelling transmission, most models during the past 40 years closely resemble the Ross–Macdonald model. Modern theory would benefit from an expansion around the concepts of heterogeneous mosquito biting, poorly mixed mosquito-host encounters, spatial heterogeneity and temporal variation in the transmission process.

Reimagining learning spaces : A research report for the Queensland Council for Social Science Innovation

The purpose of the Reimagining Learning Spaces project was to conduct an empirical study that would result in findings to inform the design and use of physical school facilities and examine the ways in which these constructions influence pedagogy. The study focused on newly-established school libraries in Queensland, many of which had been established with funding from the Federal Government’s Building the Education Revolution economic stimulus program. To explore the field, the study sought multiple perspectives that included those of school students as well as teacher-librarians and other key school staff, addressing the following focus question: - How does the physical environment of school libraries influence pedagogic practices and learning outcomes? Further research questions that guided the inquiry included: - What are the implications for teacher-librarians when transitioning into a new library learning space? - How do members of the school community (principals, teachers, teacher-librarians and students) experience the creation of a new school library learning space? - How do school students imagine the design and use of engaging library learning spaces? An extensive review explored Australian and international literature based on the research questions, focused on the following major areas: • School library renewal: trends in reimagining the place of libraries in virtual and real space • School libraries as learning spaces: the expanded role of school libraries in whole-school pedagogical support. • The role of teacher-librarians in new times • Built environments and the implications for learning • Learners and learning in newly established spaces • Learning space design: perspectives, research and principles • Pedagogical principles and voices of experience • Transitions to newly created learning spaces Approach Using an innovative qualitative research design, Reimagining Learning Spaces investigated learner and teacher perspectives across three intersecting domains exploring: - Imagined spaces: learners’ imaginative concepts of learning within engaging learning environments; - Emerging spaces: experiences of teacher-librarians in the transition into new spaces for learning, and - Established spaces: learners’ and teachers’ perceptions of ways in which the physical environment influences and shapes pedagogy. Seven schools that had recently benefitted from the BER program became the research sites at which data were collected from teacher-librarians, teachers, school leaders and students. With this range of participants, an appropriately diverse set of data collection tools was developed, including video interviews, drawings, and focus groups. Evocative narrative case studies (Simons 2009) were developed from the data, representing the voices of users of learning spaces. Key findings The study’s findings are presented in this report and complemented by an array of visual materials on the project web site http:// The report includes: • a set of seven cases studies that reveal nuanced experiences of designing and creating school libraries, based on the narrative of key stakeholders (teacher-librarians, teachers, students and principals) • thematic discussion of student imaginings of their ideal school library, based on drawings and narrative of students at the seven case study schools • critical analysis of the case study and student imaginings, focusing on implications for (re)designing school learning spaces and pedagogy, and responding to the study’s overarching research question - .17 recommendations to support: designing, transitioning and reimagining pedagogy; leadership; and policy development

GEF-H1-RhoA signaling pathway mediates LPS-induced NF-κB transactivation and IL-8 synthesis in endothelial cells

Secretion of proinflammatory cytokines by LPS activated endothelial cells contributes substantially to the pathogenesis of sepsis. However, the mechanism involved in this process is not well understood. In the present study, we determined the roles of GEF-H1 (Guanine-nucleotide exchange factor-H1)-RhoA signalling in LPS-induced interleukin-8 (IL-8, CXCL8) production in endothelial cells. First, we observed that GEF-H1 expression was upregulated in a dose- and time-dependent manner as consistent with TLR4 (Toll-like receptor 4) expression after LPS stimulation. Afterwards, Clostridium difficile toxin B-10463 (TcdB-10463), an inhibitor of Rho activities, reduced LPS-induced NF-κB phosphorylation. Inhibition of GEF-H1 and RhoA expression reduced LPS-induced NF-κB and p38 phosphorylation. TLR4 knockout blocked LPS-induced activity of RhoA, however, MyD88 knockout did not impair the LPS-induced activity of RhoA. Nevertheless, TLR4 and MyD88 knockout both significantly inhibited transactivation of NF-κB. GEF-H1-RhoA and MyD88 both induced significant changes in NF-κB transactivation and IL-8 synthesis. Co-inhibition of GEF-H1-RhoA and p38 expression produced similar inhibitory effects on LPS-induced NF-κB transactivation and IL-8 synthesis as inhibition of p38 expression alone, thus confirming that activation of p38 was essential for the GEF-H1-RhoA signalling pathway to induce NF-κB transactivation and IL-8 synthesis. Taken together, these results demonstrate that LPS-induced NF-κB activation and IL-8 synthesis in endothelial cells are regulated by the MyD88 pathway and GEF-H1-RhoA pathway.

Paper, prices and politics : an evaluation of the Swedish support to the Bai Bang project in Vietnam : a Sida evaluation report

Sweden’s protest against the Vietnam War was given tangible form in 1969 through the decision to give economic aid to the Government of North Vietnam. The main outcome was an integrated pulp and paper mill in the Vinh Phu Province north-west of Hanoi. Known as Bai Bang after its location, the mill became the most costly, one of the longest lasting and the most controversial project in the history of Swedish development cooperation. In 1996 Bai Bang produced at its full capacity. Today the mill is exclusively managed and staffed by the Vietnamese and there are plans for future expansion. At the same time a substantial amount of money has been spent to reach these achievements. Looking back at the cumbersome history of the project the results are against many’s expectations. To learn more about the conditions for sustainable development Sida commissioned two studies of the Bai Bang project. Together they touch upon several important issues in development cooperation over a period of almost 30 years: the change of aid paradigms over time, the role of foreign policy in development cooperation, cultural obstacles, recipient responsibility versus donor led development etc. The two studies were commissioned by Sida’s Department for Evaluation and Internal Audit which is an independent department reporting directly to Sida’s Board of Directors. One study assesses the financial and economic viability of the pulp and paper mill and the broader development impact of the project in Vietnam. It has been carried out by the Centre for International Economics, an Australian private economic research agency. The other study analyses the decision-making processes that created and shaped the project over a period of two decades, and reflects on lessons from the project for development cooperation in general. This study has been carried out by the Chr. Michelsen Institute, a Norweigan independent research institution.

Identification of TFG (TRK-fused gene) as a putative metastatic melanoma tumor suppressor gene

High density SNP arrays can be used to identify DNA copy number changes in tumors such as homozygous deletions of tumor suppressor genes and focal amplifications of oncogenes. Illumina Human CNV370 Bead chip arrays were used to assess the genome for unbalanced chromosomal events occurring in 39 cell lines derived from stage III metastatic melanomas. A number of genes previously recognized to have an important role in the development and progression of melanoma were identified including homozygous deletions of CDKN2A (13 of 39 samples), CDKN2B (10 of 39), PTEN (3 of 39), PTPRD (3 of 39), TP53 (1 of 39), and amplifications of CCND1 (2 of 39), MITF (2 of 39), MDM2 (1 of 39), and NRAS (1 of 39). In addition, a number of focal homozygous deletions potentially targeting novel melanoma tumor suppressor genes were identified. Because of their likely functional significance for melanoma progression, FAS, CH25H, BMPR1A, ACTA2, and TFG were investigated in a larger cohort of melanomas through sequencing. Nonsynonymous mutations were identified in BMPR1A (1 of 43), ACTA2 (3 of 43), and TFG (5 of 103). A number of potentially important mutation events occurred in TFG including the identification of a mini mutation ‘‘hotspot’’ at amino acid residue 380 (P380S and P380L) and the presence of multiple mutations in two melanomas. Mutations in TFG may have important clinical relevance for current therapeutic strategies to treat metastatic melanoma.

Cisplatin and gemcitabine in the management of metastatic penile cancer

Penile cancer is rare and receives little public attention. There are few treatment options for advanced disease. The most active regimen to date is a combination of bleomycin, methotrexate, and cisplatin. However the treatment-related mortality is 11% and hence this combination has not been adapted as a standard of care. We report two cases of advanced penile cancer where a sustained palliative response was observed with combination chemotherapy using cisplatin and gemcitabine. Our experience demonstrates that this is a well tolerated regimen active in this setting. © 2009 Elsevier Inc. All rights reserved.

Reimagining school libraries : children's perspectives and new opportunities

The Federal Government’s recent Building the Education Revolution program resulted in, among other features, the creation of over 600 new school libraries in Queensland alone. This paper reports on a component of a research project carried out with students in six primary schools and one secondary school that benefitted from the program, investigating the influences of these new physical environments on learning and teaching. In particular, this paper discusses one missing voice from the design process - that of the students who would be key users of the newly-created spaces in those schools. While opportunities for real involvement in design were minimal for most potential users of the new spaces, students’ imagined possibilities for school libraries, as submitted to the research project, suggest that students could have contributed different perspectives to enhance learning engagement through imaginative design elements. The findings of the project have relevance for teachers and teacher librarians in reconsidering the ways in which the new learning spaces are used as well as informing school designers in planning engaging school facilities. The findings may be extrapolated to the design and planning of general classrooms and other learning environments.

Characterisation of a human skin equivalent model to study the effects of ultraviolet B radiation on keratinocytes

The incidences of skin cancers resulting from chronic ultraviolet radiation (UVR) exposure are on the incline both in Australia and globally. Hence, the cellular and molecular pathways associated with UVR-induced photocarcinogenesis urgently need to be elucidated, in order to develop more robust preventative and treatment strategies against skin cancers. In vitro investigations into the effects of UVR (in particular the highly-mutagenic UVB wavelength) have, to date, mainly involved the use of cell culture and animal models. However, these models possess biological disparities to native skin, which to some extent have limited their relevance to the in vivo situation. To address this, we characterised a 3-dimensional, tissue-engineered human skin equivalent (HSE) model (consisting of primary human keratinocytes cultured on a dermal-derived scaffold) as a representation of a more physiologically-relevant platform to study keratinocyte responses to UVB. Significantly, we demonstrate that this model retains several important epidermal properties of native skin. Moreover, UVB-irradiation of the HSE constructs was shown to induce key markers of photodamage in the HSE keratinocytes, including the formation of cyclobutane pyrimidine dimers, the activation of apoptotic pathways, the accumulation of p53 and the secretion of inflammatory cytokines. Importantly, we also demonstrate that the UVB-exposed HSE constructs retain the capacity for epidermal repair and regeneration following photodamage. Together, our results demonstrate the potential of this skin equivalent model as a tool to study various aspects of the acute responses of human keratinocytes to UVB radiation damage.

A pre-clinical functional assessment of an acellular scaffold intended for the treatment of hard-to-heal wounds

Dermal wound healing is a biochemical and cellular process critical to life. While the majority of the population will only ever experience successful wound healing outcomes, some 1-3 % of those aged over 65 years will experience wound healing delay or perpetuation. These hard-to-heal wounds are comprised of degraded and dysfunctional extracellular matrix, yet the integrity of this structure is critical in the processes of normal wound healing. As such, extracellular matrix replacements have been devised that can replace dysfunctional extracellular matrix in hard-to-heal wounds with the aim of restoring normal wound healing processes. Here we evaluated a novel synthetic matrix protein for its ability to act as an acellular scaffold that can replace dysfunctional extracellular matrix. In this regard the synthetic protein demonstrated an ability to rapidly adsorb to the dermal surface, permit cell attachment and facilitate the cellular functions essential to wound healing. When applied to deep partial thickness wounds in a porcine animal model the matrix protein also demonstrated the ability to reduce wound duration. These data provide evidence that the synthetic matrix protein has the ability to function as an acellular scaffold for wound healing purposes.

Effectiveness of an acellular synthetic matrix in the treatment of hard-to-heal leg ulcers

Hard-to-heal leg ulcers are a major cause of morbidity in the elderly population. Despite improvements in wound care, some wounds will not heal and they present a significant challenge for patients and health care providers. A multi-centre cohort study was conducted to evaluate the effectiveness and safety of a synthetic, extracellular matrix protein as an adjunct to standard care in the treatment of hard-to-heal venous or mixed leg ulcers. Primary effectiveness criteria were (i) reduction in wound size evaluated by percentage change in wound area and (ii) healing assessed by number of patients healed by end of the 12 week study. Pain reduction was assessed as a secondary effectiveness criteria using VAS. A total of 45 patients completed the study and no difference was observed between cohorts for treatment frequency. Healing was achieved in 35·6% and wound size decreased in 93·3% of patients. Median wound area percentage reduction was 70·8%. Over 50% of patients reported pain on first visit and 87·0% of these reported no pain at the end of the study. Median time to first reporting of no pain was 14 days after treatment initiation. The authors consider the extracellular synthetic matrix protein an effective and safe adjunct to standard care in the treatment of hard-to-heal leg ulcers.

Reimagining school libraries : emerging teacher pedagogic practices

Agile learning spaces have the potential to afford flexible and innovative pedagogic practice. However there is little known about the experiences of teachers and learners in newly designed learning spaces, and whether the potential for reimagined pedagogies is being realised. This paper uses data from a recent study into the experiences of teacher-librarians, teachers, students and leaders of seven Queensland school libraries built with Building the Education Revolution (BER) funding, to explore the question, “how does the physical environment of school libraries influence pedagogic practices?” This paper proposes that teachers explored new pedagogies within the spaces when there was opportunity for flexibility and experimentation and the spaces sufficiently supported their beliefs about student learning. The perspectives of a range of library users were gathered through an innovative research design incorporating student drawings, videoed library tours and reflections, and interviews. The research team collected qualitative data from school libraries throughout 2012. The libraries represented a variety of geographic locations, socioeconomic conditions and both primary and secondary campuses. The use of multiple data sources, and also the perspectives of the multiple researchers who visited the sites and then coded the data, enabled complementary insights and synergies to emerge. Principles of effective teacher learning that can underpin school wide learning about the potential for agile learning spaces to enhance student learning, are identified. The paper concludes that widespread innovative use of the new library spaces was significantly enhanced when the school leadership fostered whole school discussions about the type of learning the spaces might provoke. This research has the potential to inform school designers, teachers and teacher-librarians to make the most of the transformative potential of next generation learning spaces.

Did you see that? Dissociating advanced visual information and ball flight constrains perception and action processes during one-handed catching

The integration of separate, yet complimentary, cortical pathways appears to play a role in visual perception and action when intercepting objects. The ventral system is responsible for object recognition and identification, while the dorsal system facilitates continuous regulation of action. This dual-system model implies that empirically manipulating different visual information sources during performance of an interceptive action might lead to the emergence of distinct gaze and movement pattern profiles. To test this idea, we recorded hand kinematics and eye movements of participants as they attempted to catch balls projected from a novel apparatus that synchronised or de-synchronised accompanying video images of a throwing action and ball trajectory. Results revealed that ball catching performance was less successful when patterns of hand movements and gaze behaviours were constrained by the absence of advanced perceptual information from the thrower's actions. Under these task constraints, participants began tracking the ball later, followed less of its trajectory, and adapted their actions by initiating movements later and moving the hand faster. There were no performance differences when the throwing action image and ball speed were synchronised or de-synchronised since hand movements were closely linked to information from ball trajectory. Results are interpreted relative to the two-visual system hypothesis, demonstrating that accurate interception requires integration of advanced visual information from kinematics of the throwing action and from ball flight trajectory.