Renal and genitourinary emergencies

Genitourinary (GU) problems are a common complaint in the community and to the emergency department (ED). Urinary tract infections (UTIs) are the second most common bacterial disease. UTIs rank as the sixteenth most frequently reported problem to general practitioners in Australia1 and between 10% and 20% of women will experience at least one UTI in their lifetime. Over 1,000,000 Australians are currently suffering with nephrolithiasis (renal calculi) and it is hy-pothesised that Australia’s hot, dry climate causes more stone formation than many other coun-tries in the world. Acute kidney injury (AKI) is a common complication of any trauma. Hypovol-aemia results in severe hypotension and this precipitates the development of acute tubular necrosis and subsequent AKI. The incidence of chronic kidney disease (CKD) is rising across the world. CKD is classified into five stages with those in stage 5 being classified as being in end stage kidney disease (ESKD). It is estimated that there are over 1.5 million people in Australia with CKD and there were over 16,000 Australians and over 2900 individuals in New Zealand with ESKD.2 Indigenous populations from both countries (Aboriginals, Torres Strait Islanders, Maoris, and Pacific Islanders) are over-represented in the number of people with all stages of CKD in both countries. Patients with compromised renal function often require the assistance of paramedics and will arrive at the ED with life-threatening fluid and electrolyte imbalances. Spe-cific GU emergencies discussed in this chapter are acute renal failure, rhabdomyolysis, chronic kidney disease, UTIs, acute urinary retention, urinary calculi, testicular torsion, epididymitis, and priapism. Refer to Chapter 31 for discussion of sexually transmitted infections (STIs) in women and to Chapter X for discussion of genitourinary trauma.

p53-independent NOXA induction overcomes apoptotic resistance of malignant melanomas

Once melanoma metastasizes, no effective treatment modalities prolong survival in most patients. This notorious refractoriness to therapy challenges investigators to identify agents that overcome melanoma resistance to apoptosis. Whereas many survival pathways contribute to the death-defying phenotype in melanoma, a defect in apoptotic machinery previously highlighted inactivation of Apaf-1, an apoptosome component engaged after mitochondrial damage. During studies involving Notch signaling in melanoma, we observed a gamma-secretase tripeptide inhibitor (GSI; z-Leu-Leu-Nle-CHO), selected from a group of compounds originally used in Alzheimer's disease, induced apoptosis in nine of nine melanoma lines. GSI only induced G2-M growth arrest (but not killing) in five of five normal melanocyte cultures tested. Effective killing of melanoma cells by GSI involved new protein synthesis and a mitochondrial-based pathway mediated by up-regulation of BH3-only members (Bim and NOXA). p53 activation was not necessary for up-regulation of NOXA in melanoma cells. Blocking GSI-induced NOXA using an antisense (but not control) oligonucleotide significantly reduced the apoptotic response. GSI also killed melanoma cell lines with low Apaf-1 levels. We conclude that GSI is highly effective in killing melanoma cells while sparing normal melanocytes. Direct enhancement of BH3-only proteins executes an apoptotic program overcoming resistance of this lethal tumor. Identification of a p53-independent apoptotic pathway in melanoma cells, including cells with low Apaf-1, bypasses an impediment to current cytotoxic therapy and provides new targets for future therapeutic trials involving chemoresistant tumors.

Continuous and pedagogically sound assessment : A new economy of power relations in Australian Law schools

In recent decades, assessment practices within Australian law schools have moved from the overwhelming use of end-of-year closed-book examinations to an increase in the use of a wider range of techniques. This shift is often characterised as providing a ‘better’ learning environment for students, contributing more positively to their own ‘personal development’ within higher education, or, considered along the lines of critical legal thought, as ‘liberating’ them from the ‘conservatising’ and ‘indoctrinating’ effects of the power relations that operate in law schools. This paper seeks to render problematic such liberal-progressive narratives about these changes to law school assessment practices. It will do so by utilising the work of French historian and philosopher Michel Foucault on power, arguing that the current range of assessment techniques demonstrates a shift in the ‘economy’ of power relations within the law school. Rather than ‘liberating’ students from relations of power, these practices actually extend the power relations through which students are governed. This analysis is intended to inform legal education research and assessment practice by providing a far more nuanced conceptual framework than one that seeks to ‘free’ law students from these ‘repressive’ practices, or hopes to ‘objectively’ contribute to their ‘personal development’.

Pathways to employment for migrants and refugees? The case of social enterprise

This paper examines the use of social enterprise – that is, not for personal profit businesses that have a strong social purpose- to support training and employment pathways for migrants and refugees facing multiple forms of exclusion. Drawing on an evaluation of a program that supports seven social enterprises in the Australian state of Victoria, the study finds that social enterprise affords unique local opportunities for economic and social participation for the program’s participants. Nevertheless, there are limits to the impacts of programs that mediate transitions within an increasingly flexible labour market without redressing the broader social determinants of labour market segmentation.

Long term exposure to asbestos satisfies test for causation

Background In Booth v Amaca Pty Ltd and Amaba Pty Ltd,1 the New South Wales Dust Diseases Tribunal awarded a retired motor mechanic $326 640 in damages for his malignant pleural mesothelioma allegedly caused by exposure to asbestos through working with the brake linings manufactured by the defendants. The evidence before the Tribunal was that the plaintiff had been exposed to asbestos prior to working as a mechanic from home renovations when he was a child and loading a truck as a youth. However, as a mechanic he had been exposed to asbestos in brake linings on which he worked from 1953 to 1983. Curtis DCJ held at [172] that the asbestos from the brake linings ‘materially contributed to [the plaintiff’s] contraction of mesothelioma’. This decision was based upon acceptance that the effect of exposure to asbestos on the development of mesothelioma was cumulative and rejection of theory that a single fibre of asbestos can cause the disease...

The heart of quality teaching : a values-based pedagogy for pre-service teacher education

In an ever changing world the adults of the future will be faced with many challenges. To cope with these challenges it seems apparent that values education will need to become paramount within a child.s education. A considerable number of research studies have indicated that values education is a critical component within education (Lovat & Toomey, 2007b). Building on this research Lovat (2006) claimed that values education was the missing link in quality teaching The concept of quality teaching had risen to the fore within educational research literature in the late 20th century with the claim that it is the teacher who makes the difference in schooling (Hattie, 2004). Thus, if teachers make such a difference to student learning, achievement and well-being, then it must hold true that pre-service teacher education programmes are vital in ensuring the development of quality teachers for our schools. The gap that this current research programme addressed was to link the fields of values education, quality teaching and pre-service teacher education. This research programme aimed to determine the impact of a values-based pedagogy on the development of quality teaching dimensions within pre-service teacher education. The values-based pedagogy that was investigated in this research programme was Philosophy in the Classroom. The research programme adopted a nested case study design based on the constructivist-interpretative paradigm in examining a unit within a pre-service teacher education programme at a Queensland university. The methodology utilised was qualitative where the main source of data was via interviews. In total, 43 pre-service teachers participated in three studies in order to determine if their involvement in a unit where the focus was on introducing pre-service teachers to an explicit values-based pedagogy impacted on their knowledge, skills and confidence in terms of quality teaching dimensions. The research programme was divided into three separate studies in order to address the two research questions: 1. In what ways do pre-service teachers perceive they are being prepared to become quality teachers? 2. Is there a connection between an explicit values-based pedagogy in pre-service teacher education and the development of pre-service teachers. understanding of quality teaching? Study One provided insight into 21 pre-service teachers. understandings of quality teaching. These 21 participants had not engaged in an explicit values-based pedagogy. Study Two involved the interviewing of 22 pre-service teachers at two separate points in time . prior to exposure to a unit that employed a values-explicit pedagogy and post this subject.s lecture content delivery. Study Three reported on and analysed individual case studies of five pre-service teachers who had participated in Study Two Time 1 and Time 2, as well as a third time following their field experience where they had practice in teaching the values explicit pedagogy. The results of the research demonstrate that an explicit values-based pedagogy introduced into a teacher education programme has a positive impact on the development of pre-service teachers. understanding of quality teaching skills and knowledge. The teaching and practice of a values-based pedagogy positively impacted on pre-service teachers with increases of knowledge, skills and confidence demonstrated on the quality teaching dimensions of intellectual quality, a supportive classroom environment, recognition of difference, connectedness and values. These findings were reinforced through the comparison of pre-service teachers who had participated in the explicit values-based pedagogical approach, with a sample of pre-service teachers who had not engaged in this same values-based pedagogical approach. A solid values-based pedagogy and practice can and does enhance pre-service teachers. understanding of quality teaching. These findings surrounding the use of a values-based pedagogy in pre-service teacher education to enhance quality teaching knowledge and skills has contributed theoretically to the field of educational research, as well having practical implications for teacher education institutions and teacher educators.

Flight guardian: a common avionics architecture for collision avoidance and safe emergency landing for unmanned aerial systems

This paper presents an approach to derive requirements for an avionics architecture that provides onboard sense-and-avoid and autonomous emergency forced landing capabilities to a UAS. The approach is based on two design paradigms that (1) derive requirements analyzing the common functionality between these two functions to then derive requirements for sensors, computing capability, interfaces, etc. (2) consider the risk and safety mitigation associated with these functions to derive certification requirements for the system design. We propose to use the Aircraft Certification Matrix (ACM) approach to tailor the system Development Assurance Levels (DAL) and architecture requirements in accordance with acceptable risk criteria. This architecture is developed under the name “Flight Guardian”. Flight Guardian is an avionics architecture that integrates common sensory elements that are essential components of any UAS that is required to be dependable. The Flight Guardian concept is also applicable to conventionally piloted aircraft, where it will serve to reduce cockpit workload.

"Are there any right or wrong answers in teaching philosophy": ethics, epistemology, and philosophy in the classroom

This article assesses undergraduate teaching students’ assertion that there are no right and wrong answers in teaching philosophy. When asked questions about their experiences of philosophy in the classroom for primary children, their unanimous declaration that teaching philosophy has ‘no right and wrong answers’ is critically examined across the three sub-disciplinary areas to which they were generally referring, namely, pedagogy, ethics, and epistemology. From a pedagogical point of view, it is argued that some teaching approaches may indeed be more effective than others, and some pupils’ opinions less defensible, but pedagogically, in terms of managing the power relations in the classroom, it is counter-productive to continually insist on notions of truth and falsity at every point. From an ethical point of view, it is contended that anti-realist approaches to meta-ethics may represent a viable intellectual position, but from the point of view of normative ethics, notions of right and wrong still retain significant currency. From an epistemological point of view, it is argued using Karl Poppers’ work that while it may be difficult to determine what constitutes a right answer, determining a wrong one is far more straightforward. In conclusion, it is clear that prospective teachers engaging in philosophy in the classroom, and also future teachers in general, require a far more nuanced philosophical understanding of the notions of right and wrong and truth and falsity. In view of this situation, it we wish to promote the effective teaching of philosophical thinking to children, or produce educators who can understand the conceptual limits of the claims they make and their very real and often serious practical and social consequences, it is recommended that philosophy be reinstated to a fundamental, foundational place within the pre-service teaching curriculum.

Investigation of the [−/A]8 and C1236T genetic variations within the human toll-like receptor 3 gene for association with multiple sclerosis

Multiple sclerosis (MS) is a serious cause of neurological disability among young adults. The clinical course remains difficult to predict, and the pathogenesis of the disease is still modestly understood. Autoimmunity is thought to be a key aspect of the disease, with autoreactive T cells thought to mediate central nervous system (CNS) inflammation to some extent. Toll-like receptors are known to mediate cellular recognition of pathogens by way of patterns of molecular presentation. Toll-like receptor 3 is coded by the gene TLR3 and is recognized as an important factor in virus recognition and is known to be involved in the expression of neuroprotective mediators. We set out to investigate two variations within the TLR3 gene, an 8 bp insertion-deletion \[-/A](8) and a single base-pair variation C1236T, in subjects with MS and matched healthy controls to determine whether significant differences exist in these markers in an Australian population. We used capillary gel electrophoresis and TaqMan genotyping assay techniques to resolve genotypes for each marker, respectively. Our work found no significant difference between frequencies for TLR3 \[-/A](8) by genotype (chi(2)=1.03, p=0.60) or allele (chi(2)=1.09, p=0.30). Similarly, we found no evidence for the association of TLR3 C1236T by genotype (chi(2)=0.35, p=0.84) or allele frequency (chi(2)=0.31, p=0.58). This work reveals no evidence to suggest that these markers are associated with MS in the tested population. Although the role of TLR3 and the wider toll-like receptor family remain significant in neurological and CNS inflammatory disorders, our current work does not support a role for the two tested variants in this gene with regard to MS susceptibility.

An investigation of the C77G and C772T variations within the human protein tyrosine phosphatase receptor type C gene for association with multiple sclerosis in an Australian population

Multiple sclerosis (MS) is a common cause of neurological disability in young adults. The disease generally manifests in early to middle adulthood and causes various neurological deficits. Autoreactive T lymphocytes and their associated antigens have long been presumed important features of MS pathogenesis. The Protein tyrosine phosphatase receptor type C gene (PTPRC) encodes the T-cell receptor CD45. Variations within PTPRC have been previously associated with diseases of autoimmune origin such as type 1 diabetes mellitus and Graves' disease. We set out to investigate two variants within the PTPRC gene, C77G and C772T in subjects with MS and matched healthy controls to determine whether significant differences exist in these markers in an Australian population. We employed high resolution melt analysis (HRM) and restriction length polymorphism (RFLP) techniques to determine genotypic and allelic frequencies. Our study found no significant difference between frequencies for PTPRC C77G by either genotype (Χ2 = 0.65, P = 0.72) or allele (Χ2 = 0.48, P = 0.49). Similarly, we did not find evidence to suggest an association between PTPRC C772T by genotype (Χ2 = 1.06, P = 0.59) or allele (Χ2 = 0.20, P = 0.66). Linkage disequilibrium (LD) analysis showed strong linkage disequilibrium between the two tested markers (D' = 0.9970, SD = 0.0385). This study reveals no evidence to suggest that these markers are associated with MS in the tested Australian Caucasian population. Although the PTPRC gene has a significant role in regulating CD4+ and CD8+ autoreactive T-cells, interferon-beta responsiveness, and potentially other important processes, our study does not support a role for the two tested variants of this gene in MS susceptibility in the Australian population.

Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20

To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13-14 (rs703842, P = 5.4 x 10(-11); rs10876994, P = 2.7 x 10(-10); rs12368653, P = 1.0 x 10(-7)) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 x 10(-7); rs1569723, P = 2.9 x 10(-7)). Both loci are also associated with other autoimmune diseases. We also replicated several known MS associations (HLA-DR15, P = 7.0 x 10(-184); CD58, P = 9.6 x 10(-8); EVI5-RPL5, P = 2.5 x 10(-6); IL2RA, P = 7.4 x 10(-6); CLEC16A, P = 1.1 x 10(-4); IL7R, P = 1.3 x 10(-3); TYK2, P = 3.5 x 10(-3)) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).

Study of leukemia inhibitory factor polymorphism within an Australian multiple sclerosis population

OBJECTIVE: To examine a polymorphism within the 3' untranslated region of the leukemia inhibitory factor gene for an association with multiple sclerosis within an Australian case-control population. METHODS: A test group of 121 unrelated multiple sclerosis patients, of Caucasian origin, and 121 controls, matched for ethnicity, sex and age (+/-5 years) were included in the study. The LIF 3' UTR StuI polymorphism was genotyped by restriction fragment length polymorphism analysis. Statistical analysis of genotype and allele frequencies included Hardy-Weinberg law and conventional contingency table analysis incorporating the standard chi-squared test for independence. RESULTS: Allelic and genotype frequencies did not demonstrate a significant association between the case and control groups for the tested LIF 3' UTR StuI polymorphism. CONCLUSION: The results indicate that the LIF 3' UTR StuI polymorphism is not associated with multiple sclerosis, however we cannot exclude the hypothesis that other polymorphic alleles of LIF could be implicated in MS susceptibility.

The epidemiology of invasive group A streptococcal disease in Victoria, Australia

Objective To estimate the incidence and severity of invasive group A streptococcal infection in Victoria, Australia. Design Prospective active surveillance study. Setting Public and private laboratories, hospitals and general practitioners throughout Victoria. Patients eople in Victoria diagnosed with group A streptococcal disease notified to the surveillance system between 1 March 2002 and 31 August 2004. Main outcome measure Confirmed invasive group A streptococcal disease. Results We identified 333 confirmed cases: an average annualised incidence rate of 2.7 (95% CI, 2.3-3.2) per 100000 population per year. Rates were highest in people aged 65 years and older and those younger than 5 years. The case-fatality rate was 7.8%. Streptococcal toxic shock syndrome occurred in 48 patients (14.4%), with a case-fatality rate of 23%. Thirty cases of necrotising fasciitis were reported; five (17%) of these patients died. Type 1 (23%) was the most frequently identified emm sequence type in all, age groups. All tested isolates were susceptible to penicillin and clindamycin. Two isolates (4%) were resistant to erythromycin. Conclusion The incidence of invasive group A streptococcal disease in temperate Australia is greater than previously appreciated and warrants greater public health attention, including its designation as a notifiable disease.