http://hdl.handle.net/11343/159 2021-12-02T19:10:09Z http://hdl.handle.net/11343/294112 Morrow, Simon 2021 Informal Music Events, a Subculture’s Claim to the City This thesis explores the role of informal music events, as a subcultural practice, in Melbourne, focusing on their potential to be recognised as an exercising of the right to the city through the theoretical lenses of place and social capital. This area of study was chosen in an attempt to shed light on potential inequalities within the production space of Melbourne. Qualitative semi-structured interviews were used to gauge the presence of place processes and social capital within informal music events and understand the experience of these events from the point of view of the event organisers. The six place processes were found to be present along with two social capital typologies, indicating that there is place-based social value to this subculture that would make it valuable for mediation with planners and policy makers. Informal music events were found to be an alternative to the competitive formal live music venues, but also served as a key creative starting point that allowed organisers to access these formal venues later. This competitive creative environment was perceived to be related to policy such as the late-night freeze and the urban redevelopment of Melbourne’s inner municipalities. If planners are to foster creative subcultures that create social value within the city, then there needs to be a mediation of claims to the city to ensure that less economically viable subcultures may access formal spaces to prevent urban conflicts around land usage. © 2021 Simon Morrow Masters Coursework thesis 2021-01-01T00:00:00Z http://hdl.handle.net/11343/294111 Castrejon Campos, O; Aye, L; Hui, K 2021-11-03 Dataset on effects of learning curve models on onshore wind and solar PV cost developments in the USA This dataset includes input data to estimate learning-by-deploying (LbD) and learning-by-researching (LbR) rates for onshore wind and solar PV in the United States of America (USA). Using different learning curve approaches the simulated technological-based cost developments are also presented. Coefficient of determination (R squared) and Root Mean Square Error (RMSE) were applied for quantification of the agreement between simulated and observed technological-based costs. Dataset 2021-11-03T00:00:00Z http://hdl.handle.net/11343/294110 Huq, Aamira Jabeen 2021 Clinical Whole Genome Sequencing in Early Onset Dementia and Genomic Modifiers of APOE e4/e4 Risk Background When a genetic cause is suspected in a person with dementia, it creates unique diagnostic and management challenges to the clinicians. Even in specialised neurogenetics clinics, these patients and their families face significant delays in diagnosis. The main cause for this delay is the incremental nature of the genetic tests performed in these clinics. This is due to the lack of a single, comprehensive genetic test that could identify the different types of genetic variants associated with dementia. Another problem in dementia genetics is the inability to predict the risk of Alzheimer disease (AD) in people with the APOE e4/e4 genotype, despite it being a well-known high-risk genotype. The diversity in cognition among APOE e4 homozygotes can range from early-onset AD to a lifetime with no symptoms. Identifying the modifiers of such variation will enable further refinement of risk prediction for people with this genotype. This thesis describes two main studies. First is a study that explores the clinical impact of whole genome sequencing (WGS) in patients with early onset dementia (EOD). The second study investigates the modifying effect of genomic factors, including a polygenic risk score (PRS), between APOE e4/e4 participants with EOD (onset <65 years) and elderly (aged >75 years) who have escaped AD despite their high-risk genotype and advanced age. Methods WGS analysis was performed in 50 patients with EOD, exploring point mutations, small insertions and deletions using a targeted panel of 117 genes, followed by a “Mendeliome” approach with a broad range of Mendelian disease genes, not included in the targeted panel. Structural variants (SV) as well as short tandem repeats (STR) were also analysed. A polygenic hazard score (PHS) was calculated in patients with AD. In order to examine the APOE e4/e4 genomic modifiers, first, a systematic review was conducted to search the literature for evidence of any genetic modifiers already published. As no clear answers could be deduced from the literature, a novel phenotypic extremes study was designed to examine the modifying effect of a PRS between cognitively healthy APOE e4 homozygotes aged >/=75 years (n=213) and early-onset APOE e4 homozygote AD cases aged </=65 years (n=223). Results Through the WGS study of EOD patients, clinically diagnostic pathogenic variants were identified in 7/50 (14%) of the patients, with a further eight patients (16%) found to have established risk factors which may have contributed to their EOD. All relevant variants were in the targeted set of genes with no additional findings through the Mendeliome approach. Two of the clinically diagnostic variants were identified through SV analysis. No pathogenic expanded STRs were found in this study cohort, but a blinded analysis with a positive control identified a C9orf72 expansion accurately. PHS results in AD patients indicated that ~47% (9/19) had a PHS equivalent to >90th percentile risk. Although fifteen studies met the inclusion criteria for the systematic review of APOE e4/e4 modifiers, only two SNPs (CASP7 rs10553596 and SERPINA3 rs4934-A/A) had sufficient evidence towards risk modification/resilience in APOE e4 homozygote participants. The CASP7 rs10553596 deletion variant was not captured in the genotyping platforms used in the phenotypic extremes participants and could not be imputed reliably and therefore was not analysed. The frequency of the SERPINA3 rs4934-A/A variant was not different between the extreme phenotypic cases and controls. The phenotypic extremes PRS study demonstrated that the PRS for AD was significantly higher in APOE e4 homozygote AD cases compared with older cognitively healthy APOE e4/e4 controls (OR 8.39; CI 2.0 to 35.2; p=0.003). Conclusions The clinical whole genome study showed that WGS can act as a single genetic test to identify different types of clinically relevant genetic variations in patients with EOD. WGS, if used as a first-line clinical diagnostic test, has the potential to increase the diagnostic yield and reduce time to diagnosis for EOD. The APOE e4/e4 extremes phenotyping study has identified a risk modifying PRS, comprised of common AD associated variants, that could explain the variability in clinical presentation in people with APOE e4/e4. Larger studies are needed to further validate both the WGS and modifying PRS results. Moreover, qualitative studies and cost-effectiveness analysis are needed to understand how these results would impact patients with dementia in the “real-world” setting. © 2021 Aamira Jabeen Huq PhD thesis 2021-01-01T00:00:00Z http://hdl.handle.net/11343/294109 Incerti, Paola 2021 Fitting and evaluating binaural hearing in adults using electric and acoustic stimulation Abstract Background. Advances in the design of the cochlear implant electrode arrays and improved surgical techniques have resulted in the successful preservation of residual hearing after implantation. The preservation of residual hearing following cochlear implantation provides the capacity for combining electrical and acoustic stimulation in the same ear to benefit the listener. The effectiveness of electric and acoustic stimulation in the implanted ear as compared with electrical and acoustic stimulation alone has been consistently demonstrated in the research literature. There is also accumulating research evidence that supports the provision of acoustic stimulation for residual hearing in the implanted ear together with the non-implanted ear of recipients of a unilateral cochlear implant. A variety of approaches have been used in research studies to fit devices that provide electric and acoustic stimulation in either the implanted ear or in opposite ears, however, there is no comprehensive study evaluating binaural fitting strategies in adult cochlear implant users with residual hearing in both ears. Investigation of a fitting procedure that could maximise hearing outcomes for adult recipients who use electric and acoustic stimulation in the implanted ear and acoustic stimulation in the non-implanted ear would be of benefit. Objective. The overarching goal of this thesis is to examine the fitting of devices that combine electric and acoustic stimulation for cochlear implant recipients with residual hearing in both ears. Aims 1. To systematically investigate how to adjust the hearing aid acoustic output in both ears, for adults who use electric and acoustic stimulation in the implanted ear together with acoustic stimulation in the non-implanted ear. 2. To investigate the effect of varying cross-over frequency settings for electric and acoustic stimulation in the implanted ear combined with acoustic stimulation in the non-implanted ear on speech perception in noise, localisation, functional performance in real life, and music perception. 3. To investigate the relationship between the measured cochlear dead region edge frequency in the implanted ear and the selection of the preferred cross-over frequency setting in devices that provide electric and acoustic stimulation. Methods Research design. A repeated-measures, within-subject research design, in which each participant acted as their own control was used. Participants. Eleven adults with bilateral sensorineural hearing loss, who had residual hearing in both ears, and who used a unilateral cochlear implant in one ear, and a hearing aid in the contralateral ear, participated in the study. Data collection and analysis. The thesis was structured in two distinct studies. Study 1. Participants were fitted with new hearing aids in both ears. A two-staged, systematic fine-tuning procedure was used to evaluate the hearing aid output requirements for the group of eleven adults who use a Nucleus cochlear implant system in one ear together with acoustic stimulation in both ears. Firstly, a paired comparisons technique was used to determine the participant’s preferred hearing aid gain for speech intelligibility in the implanted and the non-implanted ear. Secondly, the HA was systematically adjusted to determine the hearing aid gain requirements to achieve equal loudness between electric and acoustic stimulation in the implanted ear and then for equal loudness between ears. Study 2. Performance was compared with three different cross-over frequency settings set according to audiometric criteria, following a four-week period of familiarisation with each setting. Speech perception in noise, localisation, functional performance in real life, and music perception were evaluated. On completion of all trials, participants selected their preferred cross-over frequency setting. The cochlear dead region edge frequency values were then determined for each participant using a fast-psychophysical tuning curves test. Results. Study 1. On average, participants’ preferred hearing aid gain settings were within 5 dB of the NAL-NL2 fitting formula’s prescribed gain in the implanted ear and non-implanted ear. In addition, the hearing aid gain to achieve equal loudness between electric and acoustic stimulation was higher on average than participants’ preferred loudness in the implanted ear. However, for the non-implanted ear, there was no significant difference between the gain preferred by participants and the gain required to achieve equal loudness between ears on average. Study 2. On average, cross-over frequency settings did not have a significant effect on performance scores. However, higher ratings on device usage were associated with the preferred cross-over frequency settings. All adults for whom a dead region edge frequency value could be determined using the fast-psychophysical tuning curves test preferred electric stimulation in their chosen cross-over frequency setting to start after the cochlear dead region edge frequency value in the implanted ear. Conclusions Study 1. The findings of this research suggest that the NAL-NL2 prescription provides an appropriate starting point for fitting hearing aids in adults who use a cochlear implant system in one ear together with acoustic stimulation in both ears. Secondly, the study findings suggest that there may be no benefit to performing a loudness balancing procedure between electric and acoustic stimulation in the implanted ear or non-implanted ear in a clinical setting. Using an empirically validated hearing aid prescription and real-ear measurements to verify that target gains are matched as closely as possible may be an important first step when clinically fitting electric and acoustic stimulation. Study 2. Changes in cross-over frequency settings, set according to audiometric criteria, did not affect performance. Identification of the cochlear dead region edge frequency value may potentially be helpful in determining the cross-over frequency setting for the implanted ear in routine clinical settings. Selecting a cross-over frequency setting where electric stimulation begins after the individually measured cochlear dead region edge frequency value in the implanted ear could provide an individualised approach to best fitting practices for devices that provide electric and acoustic stimulation. The findings should be interpreted with caution due to the limited number of participants in the current study. There is published literature on the potential benefit from avoiding the amplification of frequencies that incorporate cochlear dead regions for listeners with severe-profound steeply-sloping. This is the first direct examination of the relationship between the cochlear dead region edge frequency value in the implanted ear and the preferred cross-over frequency setting in adults who use electric and acoustic stimulation. Further investigation into the implications of this finding in fitting electric and acoustic stimulation is warranted. The evidence base created by this research may contribute to the development of guidelines and recommendations for clinical fitting of devices that provide electric and acoustic stimulation and may potentially lead to individualised treatment for optimal benefits in recipients of a cochlear implant with residual hearing in both ears. © 2021 Paola Incerti PhD thesis 2021-01-01T00:00:00Z http://hdl.handle.net/11343/294108 Young, M 2021 Climate Change and Law: A Global Challenge for Legal Education Preprint 2021-01-01T00:00:00Z http://hdl.handle.net/11343/294107 Pym, A Cooperation, risk, trust Within the general approach known as translator ethics, complementary roles are played by the concepts of cooperation, risk, and trust. Cooperation, as a technical term, describes the attainment of mutual benefits as the desired outcome of an interaction, indeed as the foundation of social life. In translator ethics, the aim is more specifically to enhance long-term cooperation between cultures. The concept of risk is then used to think about the probabilities of that general aim not being obtained and what kinds of strategies and efforts can be employed to avert that outcome by increasing mutual benefits. Trust, finally, characterizes the relationship that translators must have with those around them in order for them to contribute to cooperation, such that the most critical risk they face is that of losing credibility. Together, these concepts are able to address some of the thornier issues in translator ethics and provide a frame for ongoing discussion and research. Journal Article http://hdl.handle.net/11343/294106 Gleeson, J; Leger, A; Prawer, YDJ; Lane, TA; Harrison, PJ; Haerty, W; Clark, MB Accurate expression quantification from nanopore direct RNA sequencing with NanoCount Abstract Accurately quantifying gene and isoform expression changes is essential to understanding cell functions, differentiation and disease. Sequencing full-length native RNAs using long-read direct RNA sequencing (DRS) has the potential to overcome many limitations of short and long-read sequencing methods that require RNA fragmentation, cDNA synthesis or PCR. However, there are a lack of tools specifically designed for DRS and its ability to identify differential expression in complex organisms is poorly characterised. We developed NanoCount for fast, accurate transcript isoform quantification in DRS and demonstrate it outperforms similar methods. Using synthetic controls and human SH-SY5Y cell differentiation into neuron-like cells, we show that DRS accurately quantifies RNA expression and identifies differential expression of genes and isoforms. Differential expression of 231 genes, 333 isoforms, plus 27 isoform switches were detected between undifferentiated and differentiated SH-SY5Y cells and samples clustered by differentiation state at the gene and isoform level. Genes upregulated in neuron-like cells were associated with neurogenesis. NanoCount quantification of thousands of novel isoforms discovered with DRS likewise enabled identification of their differential expression. Our results demonstrate enhanced DRS isoform quantification with NanoCount and establish the ability of DRS to identify biologically relevant differential expression of genes and isoforms. Journal Article http://hdl.handle.net/11343/294105 Dooley, K; Holz, C; Kartha, S; Klinsky, S; Roberts, JT; Shue, H; Winkler, H; Athanasiou, T; Caney, S; Cripps, E; Dubash, NK; Hall, G; Harris, PG; Lahn, B; Moellendorf, D; Mueller, B; Sagar, A; Singer, P 2021-04-01 Ethical choices behind quantifications of fair contributions under the Paris Agreement The Parties to the UNFCCC and Paris Agreement agreed to act on the basis of equity to protect the climate system. Equitable effort sharing is an irreducibly normative matter, yet some influential studies have sought to create quantitative indicators of equitable effort that claim to be value-neutral (despite evident biases). Many of these studies fail to clarify the ethical principles underlying their indicators, some mislabel approaches that favour wealthy nations as ‘equity approaches’ and some combine contradictory indicators into composites we call derivative benchmarks. This Perspective reviews influential climate effort-sharing assessments and presents guidelines for developing and adjudicating policy-relevant (but not ethically neutral) equity research. Journal Article 2021-04-01T00:00:00Z http://hdl.handle.net/11343/294104 Workman, M; Darch, G; Dooley, K; Lomax, G; Maltby, J; Pollitt, H 2021-06-01 Climate policy decision making in contexts of deep uncertainty-from optimisation to robustness Integrated assessment models are often used to evaluate the role of different technologies in meeting global climate goals. Such models have been criticised for failing to address the deep uncertainties and plurality of values that are fundamental to energy transitions. One consequence is that model scenarios overwhelmingly depend on large-scale carbon dioxide removal to hold warming to below 2 °C. Here we propose an alternative approach using Scenario-Focused Decision Analysis (SFDA) as methods that embrace decision making under deep uncertainty. SFDA can accommodate a range of value sets and perspectives, and most importantly can integrate value-based decision-making in designing climate policy. We specifically consider Robust Decision Making (RDM) as an exemplar of SFDA for developing climate policy. We outline an iterative five-stage framework for RDM using the role of carbon dioxide removal in long-term mitigation pathways as an example. The five steps comprise (i) participatory definition of goals, values, potential policy options and uncertainties; (ii) modelling the performance of policy portfolios across a wide range of future scenarios; (iii) visualisation and identification of portfolio vulnerabilities; (iv) analysis of trade-offs; and (v) development of policy strategies. SFDA, and specifically RDM, provide untapped opportunities for diverse actors to explore alternative mitigation pathways and evaluate the robustness of climate policy choices through “deliberation with analysis”. In relation to carbon dioxide removal methods, RDM provides a framework for evaluating their potential for safely meeting climate goals in a societally acceptable manner. Journal Article 2021-06-01T00:00:00Z http://hdl.handle.net/11343/294103 Rodina, L; Dooley, K; McLeman, R; Rhiney, K; Neville, KJ; Malin, SA; Shi, L; Elder, S; Prys-Hansen, M 2021-10-22 Inequalities through the lens of science Journal Article 2021-10-22T00:00:00Z http://hdl.handle.net/11343/294101 Lau, Andrew 2021 The Epidemiology and Management of Rectal Chlamydia Thesis Summary Introduction Chlamydia trachomatis (“chlamydia”) is the most commonly reported sexually transmitted infection (STI) in the world. Untreated, chlamydia is associated with serious reproductive sequelae in women including infertility. Rectal chlamydia is an important public health problem in Australia with rates rising dramatically among men who have sex with men (MSM), increasing evidence to suggest it is also an issue for women, and ongoing concern about rectal chlamydia treatment failure. This PhD program of research aims to investigate the epidemiology of rectal chlamydia with particular focus on treatment. It includes the first double-blind randomised control trial to identify the most efficacious treatment (azithromycin vs doxycycline), a cross-sectional study to further our understanding about the management of rectal chlamydia infection in men who have sex with men, and a systematic review and meta-analysis of the factors associated with rectal chlamydia positivity in women. Chapter outline The objectives of this thesis were: 1) To determine whether azithromycin or doxycycline is the most efficacious treatment for rectal chlamydia infection; 2) To examine the factors associated with the resumption of sexual activity following treatment for rectal chlamydia among MSM; and 3) To investigate the factors associated with rectal chlamydia in women with concurrent infection at other sites, and to compare these with those observed for rectal gonorrohoea. This thesis is comprised of three major components: 1) the protocol, statistical analysis plan, and results of a double-blind randomised controlled trial (RCT) comparing the efficacy of 1g azithromycin with 7-day 100mg doxycycline (twice a day) for the treatment of rectal chlamydia; 2) a cross-sectional study examining factors associated with resuming sexual activity following treatment for rectal chlamydia among MSM; and, 3) a systematic review and meta-analysis on the factors associated with rectal chlamydia positivity in women. Chapter 1 is a comprehensive literature review on what we know about the chlamydia and in particular, rectal chlamydia. The review discusses the factors for rectal chlamydia, its management, and the treatment concerns to provide context and rationale for this thesis. The literature review demonstrates that rectal Chlamydia trachomatis infection remains an important public health concern with increasing prevalence in both men and women and ongoing uncertainty in the efficacy differences for the treatments used. Several gaps remain in the epidemiology and control of rectal chlamydia including: 1) uncertainty about the most efficacious treatment for rectal chlamydia - azithromycin 1g single dose versus 7-day of doxycycline 100mg (twice a day); 2) the risk of onward transmission or reinfection following treatment among men who have sex with men, and the risk of selection pressure and resistance with continued use of azithromycin; 3) the factors associated with rectal chlamydia among women, in particular with concomitant infection at other sites. Chapters 2 to 4 presents the protocol, statistical analysis plan, and results of the RCT to compare the efficacy of 1g azithromycin to 100mg doxycycline twice daily for seven days for the treatment of rectal chlamydia – the first such trial in the world. The trial observed a microbiologic cure of 281/290 (96.9%; 95CI% 94.9, 98.9) for doxycycline and 227/297 (76.4%; 95%CI 73.8, 79.1) for azithromycin, with an adjusted risk difference of 19.9% (95%CI 14.6, 25.3; p<0.001) in favour of doxycycline. The trial found that the treatment efficacy of 1g azithromycin was even lower than predicted by previous meta-analysis (82.9%; 95%CI 76.0, 89.8%) and confirm that the efficacy this regimen to be far below the World Health Organization efficacy threshold of 95% for STI treatments. The trial provided unequivocal evidence that 1g azithromycin should be removed from international STI management guidelines. Chapter 5 is a cross-sectional study that utilised data from the RCT to investigate factors associated with resuming sexual activity following treatment for rectal chlamydia as a marker for risk of reinfection. This chapter also highlights the possibility of selective pressure of antimicrobial resistance for STIs such as Neisseria gonorrhoeae (NG) or Mycoplasma genitalium through the continued use of azithromycin for the treatment of rectal chlamydia. The study found that 9.5% of men resumed condomless receptive anal intercourse within a week of commencing treatment for rectal chlamydia and that this was independently associated with PrEP use (aRR=3.4; 95%CI 2.5, 4.8) or a man living with HIV (aRR=3.2; 95%CI 1.0, 9.9), relative to an HIV-negative man who did not use PrEP, and reporting 9 or more partners in the last three months (aRR=2.9; 95%CI 1.6, 5.0), relative to reporting 3 or fewer. In addition, 40% of men resumed condomless anal sex within 3 weeks. The study also found that 75% of men resumed any sexual activity within 3 weeks of commencing treatment for rectal chlamydia and that this was associated with reporting 4-8 (aRR=1.2; 95%CI 1.1, 1.5) or 9 or more sexual partners in the last three months (aRR=1.5; 95%CI 1.3, 1.7), relative to reporting 3 or fewer. This study illustrates the risk of induced antimicrobial resistance if azithromycin is continued to be used for rectal chlamydia in populations where reinfection is common and suggests that new health promotion messages may be required in some subgroups. Chapter 6 presents the findings of a systematic review and meta-analysis investigating the factors associated with anorectal chlamydia positivity in women. The review was novel in that it both: 1) quantified the relationship between anorectal chlamydia with concurrent chlamydia infection at the urogenital or oropharyngeal sites; and 2) compared to the same for anorectal gonorrhoea infection within the same study populations for a more comprehensive understanding. The review found that among the 25 studies eligible for inclusion, anorectal chlamydia positivity (summary estimate=8.0%; 95%CI 7.0, 9.1, I2=88.5%) was higher than anorectal gonorrhoea positivity (summary estimate=2.1%; 95%CI 1.6, 2.8, I2=92.7%). It found that urogenital chlamydia was strongly associated with rectal chlamydia (summary prevalence ratio [PR]=32.2; 95%CI 25.6, 40.7, I2=70.3%), but urogenital gonorrhoea was even more strongly associated with anorectal gonorrhoea (PR=89.3; 95%CI 53.1, 150.3, I2=80.1%). Similarly, the association between oropharyngeal and anorectal positivity was also stronger for gonorrhoea than chlamydia (PR=34.8; 95%CI 10.2, 118.2, I2=89.9% vs PR=8.8; 95%CI 6.8, 11.5, I2=58.1%). Finally, anal intercourse was associated with anorectal gonorrhoea (PR=4.3, 95%CI 2.2, 8.6, I2=0.0%) but not anorectal chlamydia (PR=1.0; 95%CI 0.7, 1.4; I2=0.0%). Conclusions This thesis found that azithromycin 1g was inferior to 7-day doxycycline in the treatment of anorectal chlamydia in men who have sex with men, providing unequivocal evidence that doxycycline must replace azithromycin as first line treatment for rectal chlamydia. It is essential that while azithromycin is still in use, there must be stronger health promotion messages following treatment encouraging condom use to minimize exposure to sub-inhibitory levels of the drug. Continued use of azithromycin 1g may contribute to selection pressure for antimicrobial resistance in other STIs that are highly prevalent in those diagnosed with rectal chlamydia. Finally, this thesis found that re-testing following treatment with azithromycin in women diagnosed with urogenital chlamydia is very important because of its strong association with concurrent rectal chlamydia and its potential to autoinoculate a subsequent urogenital infection if not effectively cured. © 2021 Andrew Lau PhD thesis 2021-01-01T00:00:00Z http://hdl.handle.net/11343/294100 Radke, B; Champion, DC; Gallagher, SJ; Wang, L; De Vleeschouwer, D; Kalinowski, A; Tenthorey, E; Urosevic, M; Feitz, A Geology, geochemistry and depositional history of the Port Campbell Limestone on the eastern flank of the Otway Basin, southeastern Australia Journal Article http://hdl.handle.net/11343/294099 Gamage, PJ; Seker, S; Orchard, J; Humphries, D; Fitzgerald, K; Fitzpatrick, J 2021-11 Insights into the complexity of presentation and management of patients: the Sport and Exercise Physician’s perspective Objectives Sport and Exercise Physicians represent a relatively new specialty focusing on exercise in complex diseases including musculoskeletal diseases. Our objective was to describe the characteristics, type and complexity of patient presentations, their management strategies and referral information in Australian practice. Methods A cross-sectional study including a cohort of 11 senior Sport and Exercise Physicians in Australia studied all new patient consultations within an 8-week period. Data were analysed relating to presentation, referral source, follow-up referrals, and patient management strategies. Results Data from 419 patients were recorded. The majority, 97% (n=406), had musculoskeletal conditions, 53% (n=222) had one or more associated comorbidities and 47% (n=195) had ongoing symptoms for &gt;12 months. Most patients, 82% (n=355), were referred by general practitioners. Prior consultations included physiotherapy 72% (n=301) and orthopaedic 20% (n=85). A multidisciplinary network of referrals from Sport and Exercise Physicians was observed, including 210 referrals to 9 allied health specialities and 61 referrals to 17 medical specialities. Over 74% (n=311) of patients received exercise-based intervention as part of the treatment plan, including 57% (n=240) physician managed exercise interventions. Conclusion Our work shines a light on the nature and complexity of the role of Sport and Exercise Physicians in an Australian practice context. Findings will assist in implementing measures to promote patient care at the community level in managing musculoskeletal conditions. Sport and exercise medicine stakeholders and government policy makers can use this information in developing appropriate programmes to support patients and create integrated sport and exercise medicine services for the community. Journal Article 2021-11-01T00:00:00Z http://hdl.handle.net/11343/294098 Thevathasan, A; Naylor, J; Churilov, L; Mitchell, PJ; Dowling, RJ; Yan, B; Kwan, P 2018-02-01 Association between hemorrhagic transformation after endovascular therapy and poststroke seizures OBJECTIVE: Endovascular therapy has recently become standard therapy for select patients with acute ischemic stroke. Infarcted brain tissue may undergo hemorrhagic transformation (HT) after endovascular therapy. We investigated the association between HT and occurrence of poststroke seizures in patients treated with endovascular therapy. METHODS: Consecutive patients treated with endovascular therapy for acute anterior circulation ischemic stroke were included. HT was assessed with computed tomography/magnetic resonance imaging (CT/MRI) at 24 h after stroke onset. Patients were followed for up to 2 years for seizure occurrence. RESULTS: A total of 205 (57.1% male) patients were analyzed. Median age was 69 years (interquartile range [IQR] 57-78). Among patients with HT, 17.9% (10/56) developed poststroke seizures compared with 4.0% (6/149) among those without HT (hazard ratio [HR] 5.52; 95% confidence interval [CI] 2.00-15.22; P = .001). The association remained significant after adjustment for cortical involvement, baseline National Institutes of Health Stroke Scale score, age and use of intravenous tissue plasminogen activator and clot retrieval (HR 4.85; 95% CI 1.60-14.76; P = .005). In patients who developed seizures within the follow-up period, median time to first seizure was 111 days (IQR 28-369) in patients with HT and 36 days (IQR 0.5-183) in patients without HT. SIGNIFICANCE: A patient who develops HT following endovascular therapy for acute ischemic stroke had a nearly 5 times higher rate of developing poststroke seizures within 2 years. HT may be used as an imaging biomarker for poststroke seizures. Journal Article 2018-02-01T00:00:00Z http://hdl.handle.net/11343/294097 Thuy, D; Tan, R; Bennett, M; Medvedovic, M; Grom, AA; Shen, N; Thornton, S; Schulert, GS 2018-01-01 MicroRNA networks associated with active systemic juvenile idiopathic arthritis regulate CD163 expression and anti-inflammatory functions in macrophages through two distinct mechanisms Systemic juvenile idiopathic arthritis (SJIA) is a severe childhood arthropathy with features of autoinflammation. Monocytes and macrophages in SJIA have a complex phenotype with both pro- and anti-inflammatory properties that combine features of several well characterized in vitro conditions used to activate macrophages. An important anti-inflammatory phenotype is expression of CD163, a scavenger receptor that sequesters toxic pro-inflammatory complexes that is highly expressed in both active SJIA and macrophage activation syndrome (MAS). CD163 is most strongly up-regulated by IL-10 (M(IL-10)), and not by other conditions that reflect features seen in SJIA monocytes such as M(LPS+IC). MicroRNA plays key roles in integrating cellular signals such as those in macrophage polarization, and as such we hypothesize microRNAs regulate macrophage functional responses in SJIA including CD163 expression. We find that 2 microRNAs previously found to be elevated in active SJIA, miR-125a-5p and miR-181c, significantly reduced macrophage CD163 expression through 2 distinct mechanisms. Neither microRNA was elevated in M(IL-10) with robust CD163 expression, but were instead induced in M(LPS+IC) where they restricted CD163 mRNA expression. Mir-181 species directly targeted CD163 mRNA for degradation. In contrast, miR-125a-5p functions indirectly, as transcriptome analysis of miR-125a-5p overexpression identified "cytokine-cytokine receptor interactions" as the most significantly repressed gene pathway, including decreased IL10RA, required for IL-10-mediated CD163 expression. Finally, overexpression of miR-181c inhibited CD163 anti-inflammatory responses to hemoglobin or high mobility group box 1 (HMGB1) complexes. Together, these data show that microRNA utilizes multiple mechanisms to integrate well-characterized polarization phenotypes and regulate macrophage functional properties seen in SJIA. Journal Article 2018-01-01T00:00:00Z http://hdl.handle.net/11343/294096 Conyers, R; Devaraja, S; Elliott, D 2018-04 Systematic review of pharmacogenomics and adverse drug reactions in paediatric oncology patients. Many paediatric patients with cancer experience significant chemotherapy side effects. Predisposition to drug reactions is governed by single nucleotide polymorphisms (SNPs). We performed a systematic review of the literature from 2006 through 2016. Outcomes of interest included patient characteristics, cancer type drug of interest, genes investigated, toxicity identified and genetic polymorphisms implicated. The primary toxicities studied were neurotoxicity cardiotoxicity, osteonecrosis, and thromboembolism and hypersensitivity reactions. The retrieved studies were grouped according to toxicity reported and SNP associations. This review highlights the discoveries to date in pharmacogenomics and paediatric oncology along with highlighting some of the important limitations in the area. Journal Article 2018-04-01T00:00:00Z http://hdl.handle.net/11343/294095 Assis, J; Tyberghein, L; Bosch, S; Verbruggen, H; Serrao, EA; De Clerck, O 2018-03-01 Bio-ORACLE v2.0: Extending marine data layers for bioclimatic modelling Journal Article 2018-03-01T00:00:00Z http://hdl.handle.net/11343/294094 Hanson, AL; Cuddihy, T; Haynes, K; Loo, D; Morton, CJ; Oppermann, U; Leo, P; Thomas, GP; Kim-Anh, LC; Kenna, TJ; Brown, MA 2018-02-01 Genetic Variants in ERAP1 and ERAP2 Associated With Immune-Mediated Diseases Influence Protein Expression and the Isoform Profile OBJECTIVE: Endoplasmic reticulum aminopeptidase 1 (ERAP-1) and ERAP-2, encoded on chromosome 5q15, trim endogenous peptides for HLA-mediated presentation to the immune system. Polymorphisms in ERAP1 and/or ERAP2 are strongly associated with several immune-mediated diseases with specific HLA backgrounds, implicating altered peptide handling and presentation as prerequisites for autoreactivity against an arthritogenic peptide. Given the thorough characterization of disease risk-associated polymorphisms that alter ERAP activity, this study aimed instead to interrogate the expression effect of chromosome 5q15 polymorphisms to determine their effect on ERAP isoform and protein expression. METHODS: RNA sequencing and genotyping across chromosome 5q15 were performed to detect genetic variants in ERAP1 and ERAP2 associated with altered total gene and isoform-specific expression. The functional implication of a putative messenger RNA splice-altering variant on ERAP-1 protein levels was validated using mass spectrometry. RESULTS: Polymorphisms associated with ankylosing spondylitis (AS) significantly influenced the transcript and protein expression of ERAP-1 and ERAP-2. Disease risk-associated polymorphisms in and around both genes were also associated with increased gene expression. Furthermore, key risk-associated ERAP1 variants were associated with altered transcript splicing, leading to allele-dependent alternate expression of 2 distinct isoforms and significant differences in the type of ERAP-1 protein produced. CONCLUSION: In accordance with studies demonstrating that polymorphisms that increase aminopeptidase activity predispose to immune disease, the increased risk also attributed to increased expression of ERAP1 and ERAP2 supports the notion of using aminopeptidase inhibition to treat AS and other ERAP-associated conditions. Journal Article 2018-02-01T00:00:00Z http://hdl.handle.net/11343/294093 Liu, DY; Cader, FN; Abduo, J; Palamara, J 2019-02-01 Accuracy of Different Implant Impression Techniques: Evaluation of New Tray Design Concept PURPOSE: To evaluate implant impression accuracy with a new tray design concept in comparison to nonsplinted and splinted impression techniques for a 2-implant situation. MATERIALS AND METHODS: A reference bar titanium framework was fabricated to fit on 2 parallel implants. The framework was used to generate a resin master model with 2 implants that fit precisely against the framework. Three impression techniques were evaluated: (1) nonsplinted, (2) splinted, and (3) nonsplinted with modified tray impressions. All the trays were fabricated from light-cured acrylic resin material with openings that corresponded to the implant impression copings. Ten impressions were taken for each technique using poly(vinyl siloxane) impression material. The impressions were poured with type IV dental stone to generate the test casts. A rosette strain gauge was bonded to the middle of the framework. As the framework retaining screws were tightened on each test cast, the developed strains were recorded until the completion of the tightening to 35 Ncm. The generated strains of the rosette strain gauge were used to calculate the maximum principal strain. RESULTS: A statistically significant difference was observed among the different impression techniques. The modified tray design impression technique was associated with the least framework strains, which indicates greater accuracy compared with the other techniques. There was no significant difference between the splinted and the nonsplinted impression techniques. CONCLUSIONS: The new tray design concept appeared to produce more accurate implant impressions than the other techniques. Despite the statistical difference among the impression techniques, the clinical significance of this difference is yet to be determined. Journal Article 2019-02-01T00:00:00Z http://hdl.handle.net/11343/294092 Haskali, MB; Roselt, PD; Hicks, RJ; Hutton, CA 2018-02-01 Automated preparation of 2-[F-18]fluoropropionate labeled peptides using a flexible, multi-stage synthesis platform (iPHASE Flexlab) Radiolabelled peptides are vital tools used in positron emission tomography imaging for the diagnosis of disease, drug discovery, and biomedical research. Peptides are typically labeled through conjugation to a radiolabelled prosthetic group, which usually necessitates complex, multi-step procedures, especially for fluorine-18 labeled peptides. Herein, we describe the automated synthesis and formulation of 2-[18 F]fluoropropionate labeled RGD-peptides through use of the iPHASE Flexlab as an effective dual-stage radiochemical synthesis module. The fully automated preparation of the monomeric RGD-peptides, [18 F]FP-GalactoRGD and [18 F]FP-c(RGDy(SO3 )K), was accomplished in under 90 minutes with n.d.c. radiochemical yields ca. 7% from fluoride. Similarly, the automated preparation of the dimeric RGD-peptides, [18 F]F-PRGD2 and [18 F]FP-E(RGDy(SO3 )K)2 , was accomplished in under 105 minutes with n.d.c. yields ca. 4% from fluoride. Journal Article 2018-02-01T00:00:00Z http://hdl.handle.net/11343/294091 Adler, NR; Kelly, JW; Haydon, A; McLean, CA; Mar, VJ 2018-01-01 Clinicopathological characteristics and prognosis of patients with multiple primary melanomas Journal Article 2018-01-01T00:00:00Z http://hdl.handle.net/11343/294090 Lawford, BJ; Bennell, KL; Kasza, J; Hinman, RS 2018-03-01 Physical Therapists' Perceptions of Telephone- and Internet Video-Mediated Service Models for Exercise Management of People With Osteoarthritis OBJECTIVE: To investigate physical therapists' perceptions of, and willingness to use, telephone- and internet-mediated service models for exercise therapy for people with knee and/or hip osteoarthritis. METHODS: This study used an internet-based survey of Australian physical therapists, comprising 3 sections: 1 on demographic information and 2 with 16 positively framed perception statements about delivering exercise via telephone and video over the internet, for people with hip and/or knee osteoarthritis. Levels of agreement with each statement were evaluated. Logistic regression models were used to determine therapist characteristics influencing interest in delivering telerehabilitation. RESULTS: A total of 217 therapists spanning metropolitan, regional, rural, and remote Australia completed the survey. For telephone-delivered care, there was consensus agreement that it would not violate patient privacy (81% agreed/strongly agreed) and would save patient's time (76%), but there was less than majority agreement for 10 statements. There was consensus agreement that video-delivered care would save a patient's time (82%), be convenient for patients (80%), and not violate patient privacy (75%). Most agreed with all other perception statements about video-delivered care, except for liking no physical contact (14%). Low confidence using internet video technologies, and inexperience with telerehabilitation, were significantly associated with reduced interest in delivering telephone and/or video-based services. CONCLUSION: Physical therapists agree that telerehabilitation offers time-saving and privacy advantages for people with osteoarthritis and perceive video-delivered care more favorably than telephone-delivered services. However, most do not like the lack of physical contact with either service model. These findings may inform the implementation of telerehabilitation osteoarthritis services and the training needs of clinicians involved in delivering care. Journal Article 2018-03-01T00:00:00Z http://hdl.handle.net/11343/294089 Seah, D; Choy, MC; Gorelik, A; Connell, WR; Sparrow, MP; Van Langenberg, D; Hebbard, G; Moore, G; De Cruz, P 2018-01-01 Examining maintenance care following infliximab salvage therapy for acute severe ulcerative colitis Abstract 2018-01-01T00:00:00Z http://hdl.handle.net/11343/294088 Taylor, S; McLean, B; Blair, E; Carey, LM; Valentine, J; Girdler, S; Elliott, C 2018-04-01 Clinical acceptability of the sense_assess (c) kids: Children and youth perspectives Journal Article 2018-04-01T00:00:00Z http://hdl.handle.net/11343/294087 Mack, HG; Fagan, X; Symons, RCA 2018-07-01 Functional screening devices for diabetic retinopathy Journal Article 2018-07-01T00:00:00Z http://hdl.handle.net/11343/294086 Deane, AM; Lamontagne, F; Dukes, GE; Neil, D; Vasist, L; Barton, ME; Hacquoil, K; Ou, X; Richards, D; Stelfox, HT; Mehta, S; Day, AG; Chapman, MJ; Heyland, DK 2018-07-01 Nutrition Adequacy Therapeutic Enhancement in the Critically Ill: A Randomized Double-Blind, Placebo-Controlled Trial of the Motilin Receptor Agonist Camicinal (GSK962040): The NUTRIATE Study BACKGROUND: Camicinal is a novel, nonmacrolide, motilin receptor agonist that accelerates gastric emptying in critically ill patients with established feed intolerance. The primary question was whether the preemptive administration of camicinal increased the provision of enteral nutrition (EN) to critically ill patients with risk factors that predisposed to feed intolerance. METHODS: This was an international, multicenter, parallel-group, blinded, randomized controlled trial. Patients at risk for feed intolerance, defined as receiving moderate to high doses of vasopressors or opiates, or admitted because of multiple traumatic injuries or with brain injury, received either enteral camicinal 50 mg or placebo daily for a maximum of 7 days, along with EN administered according to a standardized feeding protocol. The primary outcome was the daily adequacy of enteral feed delivered, as assessed by percentage of goal volume (delivered/prescribed × 100) before development of intolerance. RESULTS: Eighty-four patients participated. The administration of camicinal did not result in a statistically significant clinical difference in the daily average percentage goal volume delivered (camicinal vs placebo: 77% [95% confidence interval: 71, 83] vs 68% (58, 78); mean difference 9% [-5, 23]; P = 0.21). Similarly, there were no differences in the percentage goal calories (76% [65, 88] vs 68% [60, 77]) and protein (76% [66, 86] vs 70% [61, 80]) administered, or the incidence of feed intolerance (15% vs 14%). CONCLUSION: The incidence of feed intolerance was low in both groups. In this cohort the preemptive administration of enteral camicinal did not significantly augment the provision of goal EN. Journal Article 2018-07-01T00:00:00Z http://hdl.handle.net/11343/294085 Chen, L; Li, Y; Fan, D 2018-08-01 How do emerging multinationals configure political connections across institutional contexts? Research Summary Forming informal ties with political agents is viewed as a viable strategy for multinational enterprises seeking to enter emerging countries. Less is known about the conditions under which political connection is most helpful for firms dealing with cross‐border institutional distance. We discuss the distinctive mechanisms through which emerging multinationals may benefit from both home and host political connections. Based on the strategy tripod perspective, we postulate that the importance of different types of connections depends on the overall configurations of a firm’s resources and industry characteristics, and these may change with institutional distance. Our analysis of a sample of Chinese high‐tech manufacturing firms yields new insights into political connections, institutional distance, and the strategy tripod perspective. Managerial Summary Political connections play an important role in firms’ international expansion. In this study, we consider the importance of home political connections and host political connections in overcoming institutional barriers to foreign entry. We show that this importance varies, depending on firms’ resource bases and industry dynamics, and it may switch from a useful asset to a dispensable one under certain circumstances. We reach our conclusion from an analysis of Chinese high‐tech manufacturing firms’ foreign direct investment. Journal Article 2018-08-01T00:00:00Z http://hdl.handle.net/11343/294084 Selwood, KE; McGeoch, MA; Clarke, RH; Mac Nally, R 2018-03-01 High-productivity vegetation is important for lessening bird declines during prolonged drought Journal Article 2018-03-01T00:00:00Z http://hdl.handle.net/11343/294083 Walmsley, C; Taylor, S; Parkins, T; Carey, L; Girdler, S; Elliott, C 2018-04-01 What is the current practice of therapists in the measurement of somatosensation in children with cerebral palsy and other neurological disorders? BACKGROUND/AIM: Somatosensation is the ability to detect and recognise body sensations such as touch, vibration, pressure, pain, temperature and proprioception. Cerebral palsy is a neurological disorder that is often accompanied by impairments in somatosensation. Current somatosensory assessments have limited psychometrics established for use with these children. The aim of this study was to identify therapists' current practice and perspectives related to the assessment of somatosensation in children with neurological disorders. METHODS: A cross-sectional questionnaire was used to identify the somatosensory assessments currently used in clinical practice, time allocated to assessment, and therapists' satisfaction and confidence using the available assessments of somatosensation. The questionnaire was adapted from a previously utilised questionnaire that identified therapists' use of somatosensory assessments with adults post-stroke. RESULTS: A total of 135 therapists responded to the questionnaire. Seventy-nine (92%) occupational therapists and 44 (89.7%) physiotherapists indicated that they currently assessed or treated children with somatosensory deficits. Sixty-four (82.1%) occupational therapists and 38 (86.3%) physiotherapists regarded assessment of somatosensation in children with neurological disorders as important to very important. However, only seven (8.8%) occupational therapists and seven (15.9%) physiotherapists reported confidence in their ability to do so. The methods with which therapists detect and measure somatosensory impairment in children with neurological disorders are variable, with non-standardised and/or informal assessments most frequently used. CONCLUSION: Despite there being recommendations of best practice for the assessment of specific domains of somatosensation in children with cerebral palsy, current practice does not yet mirror these recommendations. Additionally, therapists have low satisfaction and confidence with what they are currently using, highlighting the need for a comprehensive and standardised assessment of somatosensation for use in children with neurological disorders. Journal Article 2018-04-01T00:00:00Z http://hdl.handle.net/11343/294082 Kim, J; Geyer, FC; Martelotto, LG; Ng, CKY; Lim, RS; Selenica, P; Li, A; Pareja, F; Fusco, N; Edelweiss, M; Kumar, R; Gularte-Merida, R; Forbes, AN; Khurana, E; Mariani, O; Badve, S; Vincent-Salomon, A; Norton, L; Reis-Filho, JS; Weigelt, B 2018-02-01 MYBL1 rearrangements and MYB amplification in breast adenoid cystic carcinomas lacking the MYB-NFIB fusion gene Journal Article 2018-02-01T00:00:00Z