Surgical accountability in the 1880s: the death of Susan Nixon

Susan Nixon died in 1881 following a surgical error. Her surgeon, Dr W. E. Warren, excised a normal 7-month gravid uterus under the misapprehension that he was removing a tubular pregnancy. It is believed that Mrs Nixon was the first woman in Australia to have an abdominal hysterectomy and the second to have a live Caesarean section. The surgical misadventure that resulted in Mrs Nixon's death became a public scandal, which gained currency through both parliamentary debate and the popular press.

The purpose of referring to this case is to explore the mechanisms of accountability that surgeons faced in the 1880s − a decade of rapid change in the practice of surgery. The response of late nineteenth century society to surgical error and the resultant reaction of the medical profession have resonances that are relevant to surgeons practising today.

U18666A-mediated apoptosis in cultured murine cortical neurons : role of caspases, calpains and kinases

Studies have suggested that cholesterol imbalance in the brain might be related to the development of neurological disorders such as Alzheimer's disease and Niemann–Pick disease type C. Previously, we have reported that U18666A, a cholesterol transport-inhibiting agent, leads to apoptosis and intracellular cholesterol accumulation in primary cortical neurons. In this study, we examined the effects of U18666A-mediated neuronal apoptosis, and found that chronic exposure to U18666A led to the activation of caspases and calpains and hyperphosphorylation of tau. Tau hyperphosphorylation is regulated by several kinases that phosphorylate specific sites of tau in vitro. Surprisingly, the kinase activity of cyclin-dependent kinase 5 decreased in U18666A-treated cortical neurons whereas its protein level remained unchanged. The amount of glycogen synthase kinase 3 and mitogen-activated protein kinases were found to decrease in their phosphorylated states by Western blot analysis. Gene transcription was further studied using microarray analysis. Genes encoding for kinases and phosphatases were differentially expressed with most up-regulated and some down-regulated in expression upon U18666A treatment. The activation of cysteine proteases and cholesterol accumulation with tauopathies may provide clues to the cellular mechanism of the inhibition of cholesterol transport-mediated cell death in neurodegenerative diseases.

Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1, a novel neuronal protein that regulates energy balance

To identify genes involved in the central regulation of energy balance, we compared hypothalamic mRNA from lean and obese Psammomys obesus, a polygenic model of obesity, using differential display PCR. One mRNA transcript was observed to be elevated in obese, and obese diabetic, P. obesus compared with lean animals and was subsequently found to be increased 4-fold in the hypothalamus of lethal yellow agouti (Ay/a) mice, a murine model of obesity and diabetes. Intracerebroventricular infusion of antisense oligonucleotide targeted to this transcript selectively suppressed its hypothalamic mRNA levels and resulted in loss of body weight in both P. obesus and Sprague Dawley rats. Reductions in body weight were mediated by profoundly reduced food intake without a concomitant reduction in metabolic rate. Yeast two-hybrid screening, and confirmation in mammalian cells by bioluminescence resonance energy transfer analysis, demonstrated that the protein it encodes interacts with endophilins, mediators of synaptic vesicle recycling and receptor endocytosis in the brain. We therefore named this transcript Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1 (SGIP1). SGIP1 encodes a large proline-rich protein that is expressed predominantly in the brain and is highly conserved between species. Together these data suggest that SGIP1 is an important and novel member of the group of neuronal molecules required for the regulation of energy homeostasis.

High stakes principalship - sleepless nights, heart attacks and sudden death accountabilities: reading media representations of the US principal shortage

The possible shortage of applicants for principal positions is news in both Australia and abroad. We subject a corpus of predominantly US news article to deconstructive narrative analysis and find that the dominant media representation of principals' work is one of long hours, low salary, high stress and sudden death from high stakes accountabilities. However reported US policy interventions focus predominantly on professional development for aspirants. We note that this will be insufficient to reverse the lack of applications, and suggest that the dominant media picture of completely unattractive principals' work, meant to leverage a policy solution will perhaps paradoxically perpetuate the problem. This picture is also curiously at odds with research that reports high job satisfaction among principals. We suggest that there is a dominant binary of victim and saviour principal in both media and policy which prevents some strategic re-thinking about how the principalship might be different.