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Feminist bioethics and Indigenous research reform in Australia : is an alliance across gender, racial, and cultural borders a useful strategy for promoting change?
Long term effects of weight loss with a very low carbohydrate and low fat diet on vascular function in over weight and obese patients
Abstract. Wycherley TP, Brinkworth GD, Keogh JB, Noakes M, Buckley JD, Clifton PM. (Commonwealth Scientific and Industrial Research Organization, Food and Nutritional Sciences; School of Molecular and Biomedical Science, University of Adelaide; and Nutritional Physiology Research Centre and Australian Technology Network Centre for Metabolic Fitness, Sansom Institute for Health Research, University of South Australia). Long-term effects of weight loss with a very low carbohydrate and low fat diet on vascular function in overweight and obese patients. J InternMed2010; 267: 452–461.
Tracing multiscale mechanisms of drug disposition in normal and diseased livers
Hepatic drug disposition is different in normal and diseased livers. Different disease types alter disposition differently. What are the responsible micromechanistic changes and how do they influence drug movement within the liver? We provide plausible, concrete answers for two compounds, diltiazem and sucrose, in normal livers and two different types of cirrhotic rat livers: chronic pretreatment of rats with carbon tetrachloride (CCl4) and alcohol caused different types of cirrhosis. We started with simulated disposition data from normal, multilevel, physiologically based, object-oriented, discrete event in silico livers (normal ISLs) that validated against diltiazem and sucrose disposition data from normal livers. We searched the parameter space of the mechanism and found three parameter vectors that enabled matching the three wet-lab data sets. They specified micromechanistic transformations that enabled converting the normal ISL into two different types of diseased ISLs. Disease caused lobular changes at three of six levels. The latter provided in silico disposition data that achieved a prespecified degree of validation against wet-lab data. The in silico transformations from normal to diseased ISLs stand as concrete theories for disease progression from the disposition perspective. We also developed and implemented methods to trace objects representing diltiazem and sucrose during disposition experiments. This allowed valuable insight into plausible disposition details in normal and diseased livers. We posit that changes in ISL micromechanistic details may have disease-causing counterparts.
Mind mapping research methods
The mind maps represent the authors’ concept of research methods at this time. Themajor aspects, rather than a complete picture, of research methods are illustrated in seven distinct areas: research problem, research design, sampling techniques, ethical matters, data collection, data analysis, and report findings. Brief descriptions explain the mind maps and why items were placed in certain areas where as traditionally they may have been placed else where. The mind maps show that although decisions made in one area of research methods may affect decisions made in another, there is no pre-determined connection between each area and the research design chosen. The mind maps can be used to as a guide to teach, supervise, and chart a way though the concepts of research methods and may help to produce more robust research.
Modelling dermal drug distribution after topical application in human
Purpose: To model and interpret drug distribution in the dermis and underlying tissues after topical application which is relevant to the treatment of local conditions. Methods: We created a new physiological pharmacokinetic model to describe the effect of blood flow, blood protein binding and dermal binding on the rate and depth of penetration of topical drugs into the underlying skin. We used this model to interpret literature in vivo human biopsy data on dermal drug concentration at various depths in the dermis after topical application of six substances. This interpretation was facilitated by our in vitro human dermal penetration studies in which dermal diffusion coefficient and binding were estimated. Results: The model shows that dermal diffusion alone cannot explain the in vivo data, and blood and/or lymphatic transport to deep tissues must be present for almost all of the drugs tested. Conclusion: Topical drug delivery systems for deeper tissue delivery should recognise that blood/lymphatic transport may dominate over dermal diffusion for certain compounds.
The effect of sampling methods on the apparent constituents of ink from the squid Sepioteuthis australis
Results of experiments conducted on ink recovered from the squid Sepioteuthis australis indicate that there is no epinephrine or protein naturally present in the ink as it would be ejected in vivo. Protein content was effectively zero when ink was syringed from the duct end of the ink sac of freshly killed animals. By contrast, there were proteins in samples collected from dead specimens where ink was collected by a stripping method. From these samples, a single large molecular weight protein was identified as having tyrosinase activity. Digestion of syringed ink did not yield signs of melanin-bound proteins. Analysis of supernatants after centrifugation of squid ink consistently revealed the presence of DOPA, dopamine, and taurine, whereas epinephrine and nor-epinephrine were recorded from what was believed to be contaminated ink. Histological investigations of the ink sac revealed a compartmentalised glandular structure distal to the duct end. Closer observation of the glandular tissue showed that compartments increased in size as they matured and moved further into the lumen. It was concluded that the presence of epinephrine and tyrosinase (or a related protein) in the ink of S. australis could be attributed to rupturing of basal glandular compartments or contamination from other sources during the extraction process.
First-dose and steady-state population pharmacokinetics and pharmacodynamics of piperacillin by continuous or intermittent dosing in critically ill patients with sepsis
The objectives of this study were (i) to compare the plasma concentration–time profiles for first-dose and steady-state piperacillin administered by intermittent or continuous dosing to critically ill patients with sepsis and (ii) to use population pharmacokinetics to perform Monte Carlo dosing simulations in order to assess the probability of target attainment (PTA) by minimum inhibitory concentration (MIC) for different piperacillin dosing regimens against bacterial pathogens commonly encountered in critical care units. Plasma samples were collected on Days 1 and 2 of therapy in 16 critically ill patients, with 8 patients receiving intermittent bolus dosing and 8 patients receiving continuous infusion of piperacillin (administered with tazobactam). A population pharmacokinetic model was developed using NONMEM®, which found that a two-compartment population pharmacokinetic model best described the data. Total body weight was found to be correlated with drug clearance and was included in the final model. In addition, 2000 critically ill patients were simulated for pharmacodynamic evaluation of PTA by MIC [free (unbound) concentration maintained above the MIC for 50% of the dosing interval (50% fT>MIC)] and it was found that continuous infusion maintained superior free piperacillin concentrations compared with bolus administration across the dosing interval. Dosing simulations showed that administration of 16 g/day by continuous infusion vs. bolus dosing (4 g every 6 h) provided superior achievement of the pharmacodynamic endpoint (PTA by MIC) at 93% and 53%, respectively. These data suggest that administration of piperacillin by continuous infusion, with a loading dose, both for first dose and for subsequent dosing achieves superior pharmacodynamic targets compared with conventional bolus dosing.
Enhancing student learning experience using an audience response system
Contemporary learning environments require adaptive learning tools which actively engage students with the course material and with each other. Audience response systems or 'clickers', as they are commonly called, offer a management tool for engaging students in the classroom. An innovative pilot program, undertaken at the University of South Australia in 2008 for first year nursing students, has led to a modified application of this technology with enhanced student learning experience and student satisfaction in bioscience courses. In 2009 the program will be expanded to include other health science programs within the university.