Vitronectin – master controller or micromanager?

The concept of the cellular glycoprotein vitronectin acts as a biological ‘glue’ and key controller of mammalian tissue repair and remodelling activity is emerging from nearly 50 years of experimental in vitro and in vivo data. Unexpectedly, the vitronectin-knock-out mouse was found to be viable and to have largely normal phenotype. However, diligent observation revealed that the VN-KO animal exhibits delayed coagulation and poor wound healing. This is interpreted to indicate that vitronectin occupies a role in the earliest events of thrombogenesis and tissue repair. That role is as a foundation upon which the thrombus grows in an organised structure. In addition to closing the wound, the thrombus also serves to protect the underlying tissue from oxidation, is a reservoir of mitogens and tissue repair mediators and provides a provisional scaffold for the repairing tissue. In the absence of vitronectin (e.g. VN-KO animal) this cascade is disrupted before it begins. Our data demonstrates that a wide variety of biologically active species associate with VN. While initial studies were focused on mitogens, other classes of bioactives (e.g. glycosaminoglycans, metalloproteinases) are now also known to specifically interact with VN. Many of these interactions are long-lived, often resulting in multi-protein complexes, while others are stable for prolonged periods. Multiprotein complexes provide several advantages: prolonging molecular interaction; sustaining local concentrations, facilitating co-stimulation of cell surface receptors and thereby enhancing cellular / biological responses. We contend that these, or equivalent, multi-protein complexes mediate vitronectin functionality in vivo. It is also likely that many of the species demonstrated to associate with vitronectin in vitro, also associate with vitronectin in vivo in similar multi-protein complexes. Thus the predominant biological function of vitronectin is that of a master controller of the extracellular environment; informing, and possibly instructing cells ‘where’ to behave, ‘when’ to behave, and ‘how’ to behave (i.e. appropriately for the current circumstance).

Universal access to ambulance does not increase overall demand for ambulance services in Queensland, Australia

Objective. To determine the impact of the introduction of universal access to ambulance services via the implementation of the Community Ambulance Cover (CAC) program in Queensland in 2003–04. Method. The study involved a 10-year (2000–01 to 2009–10) retrospective analysis of routinely collected data reported by the Queensland Ambulance Service (QAS) and by the Council of Ambulance Authorities. The data were analysed for the impact of policy changes that resulted in universal access to ambulance services in Queensland. Results. QASis a statewide, publically funded ambulance service. In Queensland, ambulance utilisation rate (AUR)per 1000 persons grew by 41% over the decade or 3.9% per annum (10-year mean = 149.8, 95% CI: 137.3–162.3). The AUR mean after CAC was significantly higher for urgent incidents than for non-urgent ones. However projection modelling demonstrates that URs after the introduction of CAC were significantly lower than the projected utilisation for the same period. Conclusions. The introduction of universal access under the Community Ambulance Cover program in Queensland has not had any significant independent long-term impact on demand overall. There has been a reduction in the long-term growth rate, which may have been contributed to by an ‘appropriate use’ public awareness program.

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.

Differences between provisionally licensed drivers who always display P plates and those who do not

Like most Australian states, the New South Wales Graduated Driver Licensing system requires all provisionally licensed drivers to display ‘P plates’ on their vehicle to indicate their licence status and facilitate enforcement. This paper examines whether the display of P plates increases compliance with driving laws in New South Wales. The driving behaviours of provisional drivers who reported always displaying their P plates were compared with those of drivers who sometimes drove without displaying their P plates. While no differences were found between the two groups on some behaviours, provisional drivers who did not always display their P plates indicated that they were less likely to obey the provisional speed limit and more likely to break the road rules if they knew they would not be caught. These results suggest that the requirement to display a P plate remains a priority to facilitate more general traffic law enforcement initiatives.

Queer criminology, critique, and the "art of not being governed"

This article builds on previous work that argues that a useful path for a ‘‘queer/ed criminology’’ to follow is one that takes ‘‘queer’’ to denote a position. It suggests that one way of developing such an approach is to adopt a particular understanding of critique—specifically one that draws from Michel Foucault’s view of critique as ‘‘the art of not being governed.’’ It then charts some of the possible directions for such a ‘‘queer/ed criminology.’’ While such an approach to critique has previously been discussed within critical criminologies, this article suggests that it is useful for queer criminologists to explore the opportunities that it affords, particularly in order to better appreciate how ‘‘queer/ed criminology’’ might connect to, draw from, or push against other currents among critical criminologies, and help to delineate the unique contribution that this kind of ‘‘queer/ed criminology’’ might make.

Not all dimensions of work self-efficacy are equal : understanding the role of tertiary work placements in the development of the elements of work self-efficacy

This paper examines the relationship between a final year tertiary work placement for criminology students at Griffith University in Brisbane and the development of their work self-efficacy. Using a work self-efficacy instrument developed by Professor Joe Raelin at Northeastern University in Boston, a pilot phase in 2006 and a larger study in 2007 investigated the students’ responses across seven self-efficacy factors of learning, problem-solving, teamwork, sensitivity, politics, pressure, and role expectations. Both studies utilised a pre- and post-test and comparisons between these indicated that they believed their abilities to participate constructively in their professional work contexts significantly improved as a result of their placement experience except in the areas of learning, teamwork and sensitivity. This finding will allow us to continue to refine the processes of work placements in order to ensure the integrity of this method for student learning.

Assessing exposures to emerging environmental contaminants in children

The period of developmental vulnerability to toxicants begins at conception and extends through gestation, parturition, infanthood and childhood to adolescence. The concern is that children: (1) may experience quantitatively and qualitatively different exposures, and (2) may have different sensitivity to chemical pollutants. Traditional toxicological studies are inappropriate for assessing the results of chronic exposure at very low levels during critical periods of development. This paper will discuss (1) the health effects associated with exposure to selected emerging organic pollutants, including brominated flame retardants, perfluorinated compounds, organophosphate pesticides and bisphenol A; (2) difficulties in monitoring these substances in children, and (3) suggest techniques and strategies for overcoming these difficulties. Such biomonitoring data can be used to identify where policies should be directed in order to reduce exposure, and to document policies that have successfully reduced exposure.

The IL-6 response to Chlamydia from primary reproductive epithelial cells is highly variable and may be involved in differential susceptibility to the immunopathological consequences of chlamydial infection

Background Chlamydia trachomatis infection results in reproductive damage in some women. The process and factors involved in this immunopathology are not well understood. This study aimed to investigate the role of primary human cellular responses to chlamydial stress response proteases and chlamydial infection to further identify the immune processes involved in serious disease sequelae. Results Laboratory cell cultures and primary human reproductive epithelial cultures produced IL-6 in response to chlamydial stress response proteases (CtHtrA and CtTsp), UV inactivated Chlamydia, and live Chlamydia. The magnitude of the IL-6 response varied considerably (up to 1000 pg ml-1) across different primary human reproductive cultures. Thus different levels of IL-6 production by reproductive epithelia may be a determinant in disease outcome. Interestingly, co-culture models with either THP-1 cells or autologous primary human PBMC generally resulted in increased levels of IL-6, except in the case of live Chlamydia where the level of IL-6 was decreased compared to the epithelial cell culture only, suggesting this pathway may be able to be modulated by live Chlamydia. PBMC responses to the stress response proteases (CtTsp and CtHtrA) did not significantly vary for the different participant cohorts. Therefore, these proteases may possess conserved innate PAMPs. MAP kinases appeared to be involved in this IL-6 induction from human cells. Finally, we also demonstrated that IL-6 was induced by these proteins and Chlamydia from mouse primary reproductive cell cultures (BALB/C mice) and mouse laboratory cell models. Conclusions We have demonstrated that IL-6 may be a key factor for the chlamydial disease outcome in humans, given that primary human reproductive epithelial cell culture showed considerable variation in IL-6 response to Chlamydia or chlamydial proteins, and that the presence of live Chlamydia (but not UV killed) during co-culture resulted in a reduced IL-6 response suggesting this response may be moderated by the presence of the organism.

Why Not the Best Schools?

Why Not the Best Schools is drawn from a major research project undertaken by Brain Caldwell and Jessica Harris involving studies of successful schools in six countries (Finland, Wales, Australia, USA, China, England). It compares a total of 30 schools and examines the conditions necessary for schools anywhere to improve and attain high standards for students.

Why not the best schools? The Australia Report

"The Australia Report is part of a set of six country reports that support Why not the best schools? It contains seven case studies of successful schools in Australia and examines the reasons for their success. Through interviews with principals, other school leaders and analysis of school reports, the reports examine how these schools achieved transformation and success by actively developing and building strength in four kinds of capital: intellectual, social, financial and spiritual ? and aligning them to their mission through outstanding governance. Why Not the Best Schools?: The Australia Report is part of a set of six country reports that support Why Not the Best Schools? by Brian Caldwell and Jessica Harris (ACER Press 2008). Why Not the Best Schools? draws on the findings of the International Project to Frame the Transformation of Schools conducted in Australia, China, England, Finland."--Libraries Australia

Why not the best schools? [The series]

"Expectations have been raised in Australia and comparable countries for an 'education revolution' that will secure success for all students in all settings. Such a revolution must ensure the alignment of educational outcomes, the skills required for a strong economy, and the needs of a harmonious society. Why not the Best Schools? offers a ten-point, ten-year plan for an education revolution that will result in the transformation of Australia's schools. Why not the Best Schools? goes beyond system characteristics to provide an in-depth account of how transformation occurs in schools. Fifty indicators are provided to help shape strategies for policy makers and practitioners in schools and school systems. Guidelines for leadership and governance ensure a future-focus for those who are determined to ensure that all students will succeed in the twentieth-first century. This book draws on a five-year study culminating in the International Project to Frame the Transformation of Schools conducted in Australia, China, England, Finland, the United States and Wales. The findings are consistent with the McKinsey & Company report on the world's best performing school systems and those arising from OECD's PISA."--publisher website

Functional independence following subacute inpatient rehabilitation was not affected by age among older patients recovering from cardiac-related hospital admissions

Introduction Older people recovering from cardiac events requiring an acute hospital admission may experience a decline in physical function limiting their ability to return home to their previous accommodation. Subacute inpatient rehabilitation therapies have potential to assist recovery of physical functioning. However, it is unknown whether age influences the length of stay or physical functioning at discharge from subacute inpatient rehabilitation for this population. Objectives This study examined the outcomes of a cohort of older patients recovering from a cardiac event requiring hospitalisation to investigate the association between age and physical function at discharge, as well as age and length of rehabilitation stay. Methods Participants included 145 consecutive inpatient admissions to a subacute geriatric assessment and rehabilitation unit with a cardiac condition as their primary reason for hospital admission. Participants were required to complete a multi-disciplinary physical functioning assessment within 72 hours of admission to the unit, and again within 72 hours prior to discharge from the unit. The primary outcome measure was the Functional Independence Measure motor score. Demographic and clinical information, including length of stay and discharge destination, were also recorded. Results A total n=126 (87%) participants, with a mean (standard deviation) age of 79 (10) years, had both assessments completed and were included in analyses. Participants who had passed away (n=4, 3%), or did not have both assessments completed per protocol were excluded from analyses. Discharge destinations included home (n=101, 80%), residential aged care (n=17, 13%) and another hospital (n=8, 6%). The (median, interquartile range) Functional Independence Measure motor score was higher at discharge (79, 71 to 84) than admission (61, 48 to 71); z=7.75 p<0.001. Age was not associated with Functional Independence Measure motor score at discharge (t= -0.18, p=0.86), or length of stay in the rehabilitation unit (t= -0.52, 0.60). Conclusion Any perception that age may be associated with longer lengths of stay and reduced physical function outcomes among patients with cardiac conditions admitted for subacute inpatient rehabilitation for older adults is not supported data from this investigation. Older age should not be considered a disincentive when considering the suitability of patients with cardiac diagnoses for this type of inpatient rehabilitation or their potential physical functioning outcome.