Contemporary Perspectives on the Development of Australia’s Animal Research Regulation

This thesis considers historical and current practices in Australian animal research. I address: (i) considerations in animal model choice; (ii) Australian regulatory structures in animal research; (iii) transparency in Australian animal research; and (iv) transnational comparisons of these themes. I review the literature on Australian animal research regulation from historical and contemporary perspectives and then situate my research questions within their global and historical context by reviewing the history of animal use in experimentation. In a case study considering animal model choice, I review research in psychology using Australian marsupials in the place of standard model organisms. The primary aim is to evaluate the nature of studies choosing to use marsupial species. I am interested in how animal model choice is influenced by different factors such as the research question, the suitability of the animal to a research environment, and how the animal is framed in broader society. This discussion demonstrates that there are useful experimental models amongst Australia’s marsupial species. I address changes in Australian regulatory structures around animal research through the framework of The Code1, which guides Australian legislation on animal research. Replacement as a construct is considered here as a vehicle of change, with regulation and practice moving away from traditional animal models and exploring alternatives, motivated by ethical concerns and the need for better translation to human clinical outcomes. I emphasise the importance of the Australian Government and public supporting the development of alternatives to animal models. I argue that transparency is a vital element of the scientific process, and this is particularly true for research that makes instrumental use of animals. I appraise the processes Animal Ethics Committees (AECs) undertake in reviewing and approving applications for animal research. I respond to a claim that these committees do not reject projects by conducting a quantitative analysis of application outcomes in a sample of Australian AECs. I conclude, based on this research, that changes relating to transparency should be implemented within the AEC process to ensure public trust. A transnational comparison of the themes that emerged through the discussion of historical and current practices in Australian animal research frames the discussion around how Australia may be different. I discuss the state of transparency in the US, the UK, Canada and Europe, comparing the extent to which this has been made a priority. I then evaluate and compare the processes and structures in place for the review and approval of animal research in these jurisdictions. Australia has fallen behind other countries in implementing transparency within the regulatory structures of animal research, and in supporting the development and validation of alternative non-animal models. I present concluding statements in relation to Australia’s current regulation of animal research and the state of animal research transparency. I also discuss the future of animal research in light of claims that the translation of animal research to human outcomes is poor; emerging non-animal research models become crucial from a practical standpoint, and there is a need for greater government investment.Thesis (Ph.D.) -- University of Adelaide, School of History, 202

Re-valuation of annual cytology using HPV self-sampling to upgrade prevention (REACH UP): A feasibility study in women living with HIV in the UK

Introduction: Current UK guidelines for cervical cancer screening are based on the assumption that most women living with HIV (WLWH) are also high-risk (HR) human papillomavirus (HPV)-positive. We aimed to provide data on prevalence of HR-HPV in WLWH in the UK and to assess feasibility and acceptability of HR-HPV self-sampling in this group. // Methods: Women living with HIV attending six HIV services in London/south of England, with no history of cervical cancer, were enrolled. Participants self-collected a vaginal swab for the detection of HR-HPV, completed a survey about sexual/gynaecological history, attitudes towards annual screening and perception of HR-HPV self-sampling, and were asked to have their annual cervical smear. // Results: In all, 67 women were included: 86.5% were of black ethnicity, the median (range) age was 47 (24–60) years, median CD4 T-cell count was 683 cells/µL [interquartile range (IQR): 527–910], and 95.4% had viral load ≤ 50 copies/mL. All performed the vaginal swab. Eighteen (27%) had no cervical smear results; none of these women attended HIV services where this was routinely offered. No cervical samples were positive for HR-HPV. Three-quarters (75.8%) of participants reported adherence to annual screening, with only one woman (1.5%) attending irregularly. On visual analogue scales (from 0 to 100), median (IQR) acceptability and necessity of smear tests were 100 (75–100) and 100 (85–100), respectively. // Conclusions: Our results suggest that the prevalence of HR-HPV in WLWH in the UK may be low. Self-sampling seems to be acceptable, suggesting, if validated, its potential role in supporting less frequent smear testing and improving screening uptake in WLW

Me, My Girls, and the Ideal Hotel: Segmenting Motivations of the Girlfriend Getaway Market Using Fuzzy C-Medoids for Fuzzy Data.

Segmenting the motivation of travelers using the push and pull framework remains ubiquitous in tourism. This study segments the girlfriend getaway (GGA) market on motivation (push) and accommodation (pull) attributes and identifies relationships between these factors. Using a relatively novel clustering algorithm, the Fuzzy C-Medoids clustering for fuzzy data (FCM-FD), on a sample of 749 women travelers, three segments (Socializers, Enjoyers, and Rejoicers) are uncovered. The results of a multinomial fractional model show relationships between the clusters of motivation and accommodation attributes as well as sociodemographic characteristics. The research highlights the importance of using a gendered perspective in applying well established motivation models such as the push and pull framework. The findings have implications for both destination and accommodation management

Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis

Background: Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs). Methods: We estimated the incidence of infections with 16 antibiotic resistance–bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011–12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature. Findings: From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval [UI] 583 148–763 966) infections with antibiotic-resistant bacteria, of which 63·5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480–38 430) attributable deaths and 874 541 (768 837–989 068) DALYs. The burden for the EU and EEA was highest in infants (aged <1 year) and people aged 65 years or older, had increased since 2007, and was highest in Italy and Greece. Interpretation: Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases

Comprehensive quality assessment for aphasia rehabilitation after stroke: Protocol for a multicentre, mixed-methods study

INTRODUCTION: People with aphasia following stroke experience disproportionally poor outcomes, yet there is no comprehensive approach to measuring the quality of aphasia services. The Meaningful Evaluation of Aphasia SeRvicES (MEASuRES) minimum dataset was developed in partnership with people with lived experience of aphasia, clinicians and researchers to address this gap. It comprises sociodemographic characteristics, quality indicators, treatment descriptors and outcome measurement instruments. We present a protocol to pilot the MEASuRES minimum dataset in clinical practice, describe the factors that hinder or support implementation and determine meaningful thresholds of clinical change for core outcome measurement instruments. METHODS AND ANALYSIS: This research aims to deliver a comprehensive quality assessment toolkit for poststroke aphasia services in four studies. A multicentre pilot study (study 1) will test the administration of the MEASuRES minimum dataset within five Australian health services. An embedded mixed-methods process evaluation (study 2) will evaluate the performance of the minimum dataset and explore its clinical applicability. A consensus study (study 3) will establish consumer-informed thresholds of meaningful change on core aphasia outcome constructs, which will then be used to establish minimal important change values for corresponding core outcome measurement instruments (study 4). ETHICS AND DISSEMINATION: Studies 1 and 2 have been registered with the Australian and New Zealand Clinical Trial Registry (ACTRN12623001313628). Ethics approval has been obtained from the Royal Brisbane and Women\u27s Hospital (HREC/2023/MNHB/95293) and The University of Queensland (2022/HE001946 and 2023/HE001175). Study findings will be disseminated through peer-reviewed publications, conference presentations and engagement with relevant stakeholders including healthcare providers, policy-makers, stroke and rehabilitation audit and clinical quality registry custodians, consumer support organisations, and individuals with aphasia and their families

Comparative Study of rK39 Leishmania Antigen for Serodiagnosis of Visceral Leishmaniasis: Systematic Review with Meta-Analysis

Visceral Leishmaniasis (VL) is a neglected tropical disease for which serodiagnostic tests are available, but not yet widely implemented in rural areas. The rK39 recombinant protein is derived from a kinesin-like protein of parasites belonging to the Leishmania donovani complex, and has been used in the last two decades for the serodiagnosis of VL. We present here a systematic review and meta-analysis of studies evaluating serologic assays (rK39 strip-test, rK39 ELISA, Direct Agglutination Test [DAT], Indirect Immunofluorescence test [IFAT] and ELISA with a promastigote antigen preparation [p-ELISA]) to diagnose VL to determine the accuracy of rK39 antigen in comparison to the use of other antigen preparations. Fourteen papers fulfilled the inclusion and exclusion selection criteria. The summarized sensitivity for the rK39-ELISA was 92% followed by IFAT 88% and p-ELISA 87%. The summarized specificity for the three diagnostic tests was 81%, 90%, and 77%. Studies comparing the rK39 strip test with DAT found a similar sensitivity (94%) and specificity (89%). However, the rK39 strip test was more specific than the IFAT and p-ELISA. In conclusion, we found the rK39 protein used either in a strip test or in an ELISA is a good choice for the serodiagnosis of VL