T lymphocyte responses to equid herpesviruses 1 and 4 in horses

This thesis describes the development, optimisation and use of assays to measure equine herpes virus-specific proliferative and cytotoxic T lymphocyte (CTL) responses in the blood of horses. Equine T cell blast cells stimulated from peripheral blood mononuclear cells (PBMC) with pokeweed mitogen were found to perform best as targets for CTL in "Cr release assays. CTL induced in vitro with an abortigenic strain of EHV-1 (EHV-1/Ab4) were shown to be antigen specific, genetically restricted and predominantly of the CD4' CD8+ phenotype. Cross-reactive CTL were induced in vitro with live EHV-4 virus, which killed EHV-1 infected blast cells. A proportion of EHV-1 induced CTL were shown to be directed against the immediate early gene products. A proliferative LDA was used to determine whether the frequency of precursor T cells detected before challenge with EHV-1 correlated with immune status. The precursor frequency of antigen-specific T cells increased in 3 out of 4 horses after infection. However, there was no correlation between precursor frequency and outcome of infection. A LDA was developed and used to evaluate the precursor frequencies of EHV-1 and EHV-4 induced CTL after infection with these viruses. Pre-infection CTLp frequencies in susceptible animals were <1/150,000. CTLp frequencies in animals which were immune to EHV-1 were between 1/10,000 and 1/20,000. To my knowledge this is the first report of the use of LDA techniques in the horse. The development and use of CTL LDA assays have provided new information on CTL responses in horses after EHV-1 and EHV-4 infection

Exploring the efficacy of problem-based learning in diverse secondary school classrooms: Characteristics and goals of problem-based learning

Problem-based learning (PBL) is increasingly referenced in secondary education as a teaching strategy. This quasi-experimental, field-based study is unique in that it examined whether PBL was effective for all students, including identified groups of exceptional learners within 10 mainstream, Grade 8, Australian classrooms in two schools. Each class completed the same three-week PBL unit. Pre- and post-unit indicators of key capacities - topic knowledge, understanding of the problem-solving process, and self-regulatory skills essential to achieving PBL goals - were measured. Significant differences both in initial capacity and in pre-post-assessment changes across the cohort and between identified groups of learners were found. The implications of these findings are discussed

Estimating cohort health expectancies from cross-sectional surveys of disability

A life history can be regarded as a random process that evolves with age through various states of health before terminating with absorption into the state of death. Health expectancies are the occupation times of the non-absorbing states and their estimation is of interest. A continuing major problem has been the lack of satisfactory longitudinal data on which to base estimates and as a result standard inferential techniques may not be relevant. Supposing only cross-sectional data available, we propose a method that is generally applicable and first estimates a logistic parametrization of the probabilities of the various states. A large sample approximation is obtained for the distribution of age specific log (odds). Parameters are estimated by weighted least squares, and this in turn leads to estimates of cohort health expectancies. A result of Liang and Zeger is used to find standard errors. The method is illustrated by application to Australian data from the health surveys of 1981, 1988 and 1993

Non-invasive molecular imaging of inflammatory macrophages in allograft rejection.

BackgroundMacrophages represent a critical cell type in host defense, development and homeostasis. The ability to image non-invasively pro-inflammatory macrophage infiltrate into a transplanted organ may provide an additional tool for the monitoring of the immune response of the recipient against the donor graft. We therefore decided to image in vivo sialoadhesin (Sn, Siglec 1 or CD169) using anti-Sn mAb (SER-4) directly radiolabelled with (99m)Tc pertechnetate.MethodsWe used a heterotopic heart transplantation model where allogeneic or syngeneic heart grafts were transplanted into the abdomen of recipients. In vivo nanosingle-photon emission computed tomography (SPECT/CT) imaging was performed 7 days post transplantation followed by biodistribution and histology.ResultsIn wild-type mice, the majority of (99m)Tc-SER-4 monoclonal antibody cleared from the blood with a half-life of 167 min and was located predominantly on Sn(+) tissues in the spleen, liver and bone marrow. The biodistribution in the transplantation experiments confirmed data derived from the non-invasive SPECT/CT images, with significantly higher levels of (99m)Tc-SER-4 observed in allogeneic grafts (9.4 (±2.7) %ID/g) compared to syngeneic grafts (4.3 (±10.3) %ID/g) (p = 0.0022) or in mice which received allogeneic grafts injected with (99m)Tc-IgG isotype control (5.9 (±0.6) %ID/g) (p = 0.0185). The transplanted heart to blood ratio was also significantly higher in recipients with allogeneic grafts receiving (99m)Tc-SER-4 as compared to recipients with syngeneic grafts (p = 0.000004) or recipients with allogeneic grafts receiving (99m)Tc-IgG isotype (p = 0.000002).ConclusionsHere, we demonstrate that imaging of Sn(+) macrophages in inflammation may provide an important additional and non-invasive tool for the monitoring of the pathophysiology of cellular immunity in a transplant model

Market Games In Finance Education

An electronic share market trading game was introduced to a large first year undergraduate finance course to allow students to experience share market trading. The response from students was positive.  We surveyed a sample of 51 of the students in this class who undertook a further one-hour trading session as part of a separate research experiment.  These students rate the game as a valuable learning experience.  They suggest that their use of the game increased their understanding of share market and the way that prices are set.  While the study results cannot be generalised to all students in the course, the results suggest that there are benefits to be gained from including an electronic share market trading game as part of the course

Forward simulation MCMC with applications to stochastic epidemic models

For many stochastic models, it is difficult to make inference about the model parameters because it is impossible to write down a tractable likelihood given the observed data. A common solution is data augmentation in a Markov chain Monte Carlo (MCMC) framework. However, there are statistical problems where this approach has proved infeasible but where simulation from the model is straightforward leading to the popularity of the approximate Bayesian computation algorithm. We introduce a forward simulation MCMC (fsMCMC) algorithm, which is primarily based upon simulation from the model. The fsMCMC algorithm formulates the simulation of the process explicitly as a data augmentation problem. By exploiting non-centred parameterizations, an efficient MCMC updating schema for the parameters and augmented data is introduced, whilst maintaining straightforward simulation from the model. The fsMCMC algorithm is successfully applied to two distinct epidemic models including a birth–death–mutation model that has only previously been analysed using approximate Bayesian computation methods

Imaging DNA Damage Repair In Vivo After 177Lu-DOTATATE Therapy

Molecular radiotherapy using 177Lu-DOTATATE is a most effective treatment for somatostatin receptor-expressing neuroendocrine tumors. Despite its frequent and successful use in the clinic, little or no radiobiologic considerations are made at the time of treatment planning or delivery. On positive uptake on octreotide-based PET/SPECT imaging, treatment is usually administered as a standard dose and number of cycles without adjustment for peptide uptake, dosimetry, or radiobiologic and DNA damage effects in the tumor. Here, we visualized and quantified the extent of DNA damage response after 177Lu-DOTATATE therapy using SPECT imaging with 111In-anti-γH2AX-TAT. This work was a proof-of-principle study of this in vivo noninvasive biodosimeter with β-emitting therapeutic radiopharmaceuticals. Methods: Six cell lines were exposed to external-beam radiotherapy (EBRT) or 177Lu-DOTATATE, after which the number of γH2AX foci and the clonogenic survival were measured. Mice bearing CA20948 somatostatin receptor-positive tumor xenografts were treated with 17

Mastectomy or breast conserving surgery? Factors affecting type of surgical treatment for breast cancer – a classification tree approach

BACKGROUND: A critical choice facing breast cancer patients is which surgical treatment – mastectomy or breast conserving surgery (BCS) – is most appropriate. Several studies have investigated factors that impact the type of surgery chosen, identifying features such as place of residence, age at diagnosis, tumor size, socio-economic and racial/ethnic elements as relevant. Such assessment of "propensity" is important in understanding issues such as a reported under-utilisation of BCS among women for whom such treatment was not contraindicated. Using Western Australian (WA) data, we further examine the factors associated with the type of surgical treatment for breast cancer using a classification tree approach. This approach deals naturally with complicated interactions between factors, and so allows flexible and interpretable models for treatment choice to be built that add to the current understanding of this complex decision process. METHODS: Data was extracted from the WA Cancer Registry on women diagnosed with breast cancer in WA from 1990 to 2000. Subjects' treatment preferences were predicted from covariates using both classification trees and logistic regression. RESULTS: Tumor size was the primary determinant of patient choice, subjects with tumors smaller than 20 mm in diameter preferring BCS. For subjects with tumors greater than 20 mm in diameter factors such as patient age, nodal status, and tumor histology become relevant as predictors of patient choice. CONCLUSION: Classification trees perform as well as logistic regression for predicting patient choice, but are much easier to interpret for clinical use. The selected tree can inform clinicians' advice to patients