Rural Clinical School - Research Publications
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ItemEstimating global arthropod species richness: refining probabilistic models using probability bounds analysis(SPRINGER, 2013-02)A key challenge in the estimation of tropical arthropod species richness is the appropriate management of the large uncertainties associated with any model. Such uncertainties had largely been ignored until recently, when we attempted to account for uncertainty associated with model variables, using Monte Carlo analysis. This model is restricted by various assumptions. Here, we use a technique known as probability bounds analysis to assess the influence of assumptions about (1) distributional form and (2) dependencies between variables, and to construct probability bounds around the original model prediction distribution. The original Monte Carlo model yielded a median estimate of 6.1 million species, with a 90 % confidence interval of [3.6, 11.4]. Here we found that the probability bounds (p-bounds) surrounding this cumulative distribution were very broad, owing to uncertainties in distributional form and dependencies between variables. Replacing the implicit assumption of pure statistical independence between variables in the model with no dependency assumptions resulted in lower and upper p-bounds at 0.5 cumulative probability (i.e., at the median estimate) of 2.9-12.7 million. From here, replacing probability distributions with probability boxes, which represent classes of distributions, led to even wider bounds (2.4-20.0 million at 0.5 cumulative probability). Even the 100th percentile of the uppermost bound produced (i.e., the absolutely most conservative scenario) did not encompass the well-known hyper-estimate of 30 million species of tropical arthropods. This supports the lower estimates made by several authors over the last two decades.
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ItemIwao's patchiness regression through the origin: biological importance and efficiency of sampling applications(WILEY, 2014-04)Abstract Iwao's mean crowding‐mean density relation can be treated both as a linear function describing the biological characteristics of a species at a population level, or a regression model fitted to empirical data (Iwao's patchiness regression). In this latter form its parameters are commonly used to construct sampling plans for insect pests, which are characteristically patchily distributed or overdispersed. It is shown in this paper that modifying both the linear function and statistical model to force the intercept or lower functional limit through the origin results in more intuitive biological interpretation of parameters and better sampling economy. Firstly, forcing the function through the origin has the effect of ensuring that zero crowding occurs when zero individuals occupy a patch. Secondly, it ensures that negative values of the intercept, which do not yield an intuitive biological interpretation, will not arise. It is shown analytically that sequential sampling plans based on regression through the origin should be more efficient compared to plans based on conventional regression. For two overdispersed data sets, through‐origin based plans collected a significantly lower sample size during validation than plans based on conventional regression, but the improvement in sampling efficiency was not large enough to be of practical benefit. No difference in sample size was observed when through‐origin and conventional regression based plans were validated using underdispersed data. A field researcher wishing to adopt a through‐origin form of Iwao's regression for the biological reasons outlined above can therefore be confident that their sampling strategies will not be affected by doing so.
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ItemWaterbird use of artificial wetlands in an Australian urban landscape(SPRINGER, 2013-10)
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ItemAntibody therapy for histoplasmosis.(Frontiers Media SA, 2012)The endemic human pathogenic fungus Histoplasma capsulatum is a major fungal pathogen with a broad variety of clinical presentations, ranging from mild, focal pulmonary disease to life-threatening systemic infections. Although azoles, such as itraconazole and voriconazole, and amphotericin B have significant activity against H. capsulatum, about 1 in 10 patients hospitalized due to histoplasmosis die. Hence, new approaches for managing disease are being sought. Over the past 10 years, studies have demonstrated that monoclonal antibodies (mAbs) can modify the pathogenesis of histoplasmosis. Disease has been shown to be impacted by mAbs targeting either fungal cell surface proteins or host co-stimulatory molecules. This review will detail our current knowledge regarding the impact of antibody therapy on histoplasmosis.
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ItemTracking type specific prevalence of human Papillomavirus in cervical pre-cancer: a novel sampling strategy(BMC, 2012-06-14)BACKGROUND: Surveillance designed to detect changes in the type-specific distribution of HPV in cervical intraepithelial neoplasia grade 3 (CIN-3) is necessary to evaluate the effectiveness of the Australian vaccination programme on cancer causing HPV types. This paper develops a protocol that eliminates the need to calculate required sample size; sample size is difficult to calculate in advance because HPV's true type-specific prevalence is imperfectly known. METHOD: A truncated sequential sampling plan that collects a variable sample size was designed to detect changes in the type-specific distribution of HPV in CIN-3. Computer simulation to evaluate the accuracy of the plan at classifying the prevalence of an HPV type as low (< 5%), moderate (5-15%), or high (> 15%) and the average sample size collected was conducted and used to assess its appropriateness as a surveillance tool. RESULTS: The plan classified the proportion of CIN-3 lesions positive for an HPV type very accurately, with >90% of simulations correctly classifying a simulated data-set with known prevalence. Misclassifying an HPV type of high prevalence as being of low prevalence, arguably the most serious kind of potential error, occurred < 0.05 times per 100 simulations. A much lower sample size (21-22 versus 40-48) was required to classify samples of high rather than low or moderate prevalence. CONCLUSIONS: Truncated sequential sampling enables the proportion of CIN-3 due to an HPV type to be accurately classified using small sample sizes. Truncated sequential sampling should be used for type-specific HPV surveillance in the vaccination era.
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ItemA novel software program for detection of potential air emboli during cardiac surgery.(Springer Science and Business Media LLC, 2015-01-12)BACKGROUND: Risks associated with air emboli introduced during cardiac surgery have been highlighted by reports of postoperative neuropsychological dysfunction, myocardial dysfunction, and mortality. Presently, there are no standard effective methods for quantifying potential emboli in the bloodstream during cardiac surgery. Our objective was to develop software that can automatically detect and quantify air bubbles within the ascending aorta and/or cardiac chambers during cardiac surgery in real time. FINDINGS: We created a software algorithm ("Detection of Emboli using Transesophageal Echocardiography for Counting, Total volume, and Size estimation", or DETECTS™) to identify and measure potential emboli present during cardiac surgery using two-dimensional ultrasound. An in vitro experiment was used to validate the accuracy of DETECTS™ at identifying and measuring air emboli. An experimental rig was built to correlate the ultrasound images to high definition camera images of air bubbles created in water by an automatic bubbler system. There was a correlation between true bubble size and the size reported by DETECTS™ in our in vitro experiment (r = 0.76). We also tested DETECTS™ using TEE images obtained during cardiac surgery, and provide visualization of the software interface. CONCLUSIONS: While monitoring the heart during cardiac surgery using existing ultrasound technology and DETECTS™, the operative team can obtain real-time data on the number and volume of potential air emboli. This system will potentially allow de-airing techniques to be evaluated and improved upon. This could lead to reduced air in the cardiac chambers after cardiopulmonary bypass, possibly reducing the risk of neurological dysfunction following cardiac surgery.
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ItemBiological function and molecular mapping of M antigen in yeast phase of Histoplasma capsulatum.(Public Library of Science (PLoS), 2008)Histoplasmosis, due to the intracellular fungus Histoplasma capsulatum, can be diagnosed by demonstrating the presence of antibodies specific to the immunodominant M antigen. However, the role of this protein in the pathogenesis of histoplasmosis has not been elucidated. We sought to structurally and immunologically characterize the protein, determine yeast cell surface expression, and confirm catalase activity. A 3D-rendering of the M antigen by homology modeling revealed that the structures and domains closely resemble characterized fungal catalases. We generated monoclonal antibodies (mAbs) to the protein and determined that the M antigen is present on the yeast cell surface and in cell wall/cell membrane preparations. Similarly, we found that the majority of catalase activity was in extracts containing fungal surface antigens and that the M antigen is not significantly secreted by live yeast cells. The mAbs also identified unique epitopes on the M antigen. The localization of the M antigen to the cell surface of H. capsulatum yeast and the characterization of the protein's major epitopes have important implications since it demonstrates that although the protein may participate in protecting the fungus against oxidative stress it is also accessible to host immune cells and antibody.
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ItemCarbodiimide-mediated cross-linking of RNA to nylon membranes improves the detection of siRNA, miRNA and piRNA by northern blot.(Oxford University Press (OUP), 2007)The northern blot, or RNA gel blot, is a widely used method for the discovery, validation and expression analysis of small regulatory RNA such as small interfering RNA (siRNA), microRNA (miRNA) and piwi-interacting RNA (piRNA). Although it is straightforward and quantitative, the main disadvantage of a northern blot is that it detects such RNA less sensitively than most other approaches. We found that the standard dose of UV used in northern blots was not the most efficient at immobilizing small RNA of 20-40 nt on nylon membranes. However, increasing the dose of UV reduced the detection of miRNA by hybridization in northern blotting experiments. We discovered that using the soluble carbodiimide, EDC, to cross-link RNA to nylon membranes greatly improved the detection of small RNA by hybridization. Compared to standard UV cross-linking procedures, EDC cross-linking provided a 25-50-fold increase in the sensitivity of detection of siRNA from plants and miRNA or piRNA from mammalian cells. All types of hybridization probes tested benefited from the new cross-linking procedure. Cross-linking was dependent on a terminal phosphate and so, should be applicable to other related categories of small RNA.
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ItemSLAC: A tool for addressing chaos in the ecology classroom(TAYLOR & FRANCIS LTD, 2005)