952 resultados para Judith Butler


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The international trend towards an increasingly standards-based approach to higher education and the resultant focus on the assurance of learning in tertiary programs have generated a strong emphasis on the assessment of outcomes across the higher education sector. In legal education, curriculum reform is highly prevalent internationally as a result of various reviews of legal education. As legal education focuses more on the attainment of a broader set of outcomes encompassing soft skills, capabilities and attributes, more authentic assessment will need to be developed appropriate to this new environment, meaning that modes of assessment with strong application in real-life settings should be preferred.

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Multiple sclerosis (MS) is a chronic relapsing-remitting inflammatory disease of the central nervous system characterized by oligodendrocyte damage, demyelination and neuronal death. Genetic association studies have shown a 2-fold or greater prevalence of the HLA-DRB1*1501 allele in the MS population compared with normal Caucasians. In discovery cohorts of Australasian patients with MS (total 2941 patients and 3008 controls), we examined the associations of 12 functional polymorphisms of P2X7, a microglial/macrophage receptor with proinflammatory effects when activated by extracellular adenosine triphosphate (ATP). In discovery cohorts, rs28360457, coding for Arg307Gln was associated with MS and combined analysis showed a 2-fold lower minor allele frequency compared with controls (1.11% for MS and 2.15% for controls, P = 0.0000071). Replication analysis of four independent European MS case–control cohorts (total 2140 cases and 2634 controls) confirmed this association [odds ratio (OR) = 0.69, P = 0.026]. A meta-analysis of all Australasian and European cohorts indicated that Arg307Gln confers a 1.8-fold protective effect on MS risk (OR = 0.57, P = 0.0000024). Fresh human monocytes heterozygous for Arg307Gln have >85% loss of ‘pore’ function of the P2X7 receptor measured by ATP-induced ethidium uptake. Analysis shows Arg307Gln always occurred with 270His suggesting a single 307Gln–270His haplotype that confers dominant negative effects on P2X7 function and protection against MS. Modeling based on the homologous zP2X4 receptor showed Arg307 is located in a region rich in basic residues located only 12 Å from the ligand binding site. Our data show the protective effect against MS of a rare genetic variant of P2RX7 with heterozygotes showing near absent proinflammatory ‘pore’ function.

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What is the future for public health in the twenty-first century? Can we glean an idea about the future of public health from its past? As Winston Churchill once said: ‘[T]he further backward you look, the further forward you can see.’ What can we see in the history of public health that gives us an idea of where public health might be headed in the future? (Gruszin et al. 2012). In the twentieth century there was substantial progress in public health in Australia. These improvements were brought about through a number of factors. In part, improvements were due to increasing knowledge about the natural history of disease and its treatment. Added to this knowledge was a shifting focus from legislative measures to protect health, to the emergence of improved promotion and prevention strategies, and a general improvement in social and economic conditions for people living in countries such as Australia. Gruszin et al. (2012) consider the range of social and economic reforms of the twentieth century as the most important determinants of the public’s health at the start of the twenty-first century (Gruszin et al. 2012 p 201). The same could not, however, be said for second or third world countries, many of whom have the most fundamental of sanitary and health protection issues still to deal with. For example, in sub-Saharan Africa and in Russia the decline in life expectancy can be said to be related to a range of interconnected factors. In Russia, issues such as alcoholism, violence, suicide, accidents and cardiovascular disease could be contributing to the falling life expectancy (McMichael & Butler 2007). In sub-Saharan Africa, a range of factors, such as HIV/AIDS, poverty, malaria, tuberculosis, undernutrition, totally inadequate infrastructure, gender inequality, conflict and violence, political taboos and a complete lack of political will, have all contributed to a dramatic drop in life expectancy (McMichael & Butler 2007).

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Current translational and basic prostate cancer research is limited by the number of cell lines that truly reflect the spectrum of disease progression, with most commonly used cell lines being derived from metastatic lesions. There are essentially no prostate cancer cell lines derived from primary tumours or localised disease in wide use.

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Understanding mechanisms associated with the emergence of castration resistant prostate cancer cells (CRPC) after androgen deprivation therapy (ADT) is essential to create new therapeutic agents to counteract this aggressive form of prostate cancer (PCa). Because proteases are involved in almost all cancer associated mechanisms such as cell proliferation, invasion and metastasis, we are interested in their modulation in PCa after ADT and their involvement in CRPC.

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Kallikrein-related peptidase 4 (KLK4) is a protease with elevated production in prostate cancer versus benign tissue. KLK4 expression is associated with prostate cancer risk, and its activity favours tumour progression through increasing cell motility and growth. Importantly, over-production of KLK4 in prostate glandular cells precedes tumour formation, positioning the enzyme to play a role in early remodelling of the tumour microenvironment, a process essential for tumour growth. We sought to identify the proteins and downstream signalling pathways targeted by KLK4 activity, to define its role in tumour microenvironment remodelling and evaluate the efficacy of KLK4 inhibition as a cancer therapy.

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In castrate-resistant prostate cancer (CRPC), the prevailing organ for metastasis is bone, where the survival of cancer cells is regulated by the permissive metastatic niche offered by the bone marrow. The tumour microenvironment and cellular interactions with the matrix and bone cells enable metastasis and lead to cancer cells becoming androgen resistant. Hence, 3D models that mimic CRPC in terms of an androgen deprivation state (ADS) are needed to identify the mechanisms for CPRC growth in bone and further develop therapeutic strategies.