Australian Sites Research Articles

(080) Psychological Outcomes and Sexual Satisfaction Rates in Males with Phimosis Following the Novoglan Foreskin Extender Treatment

Abstract Introduction Phimosis can be associated with sexual dysfunction since it often causes discomfort or pain on erection or during sexual intercourse. While circumcision is routinely advocated in patients with phimosis, many males would prefer conservative treatment and are keen to preserve their foreskins. Novoglan foreskin tissue expander is a non-surgical device that uses a balloon to produce gradual stretching of the phimotic foreskin. Objective To assess the impact of phimosis and Novoglan treatment on sexual health and psychological domains. Methods Following Institutional Ethics Board approval (HREC/2020/QMS/66682), 20 males with phimosis were recruited across two Australian sites. Inclusion criteria include male aged ≥ 18 years, who has phimosis and normal erectile function, while those with balanoposthitis and/or recurrent UTIs were excluded. All participants received informed consent and completed questionnaires before and after the Novoglan treatment. The questionnaires included questions on pain or discomfort during sexual activity and levels of anxiety or depression. Circumcision was offered to all patients at the start and end of the study period. Results Nineteen (95%) patients with phimosis recruited in the Novoglan trial reported pain or discomfort during sexual activity, with one (5%) participant reporting pain or discomfort as severe, while moderate or mild levels were reported by ten (50%) and eight (40%) participants, respectively. The level of pain or discomfort during sexual activity improved significantly after the Novoglan treatment with no patients reporting severe level of pain or discomfort, with most males reporting mild or no pain or discomfort (80%). While all participants documented mild to moderate levels of anxiety or depression prior to treatment, 17 participants (85%) reported no anxiety or depression and only three (15%) men reported a mild degree of psychological distress. None of the participants elected for circumcision. Conclusions The Novoglan foreskin tissue expander device significantly improves the psychological outcomes and sexual function in males with phimosis. All patients reported minimal or no pain or discomfort during sexual activity, had minimal or no anxiety or depression related to foreskin issues, and declined circumcision at the end of the study period. Disclosure Yes, this is sponsored by industry/sponsor: Novoglan device company. Clarification: Industry funding only - investigator initiated and executed study.

Medicine utilization studies in Australian individual-level dispensing data: A blinded, multi-center replicated analysis.

Medicine dispensing data require extensive preparation when used for research and decisions during this process may lead to results that do not replicate between independent studies. We conducted an experiment to examine the impact of these decisions on results of a study measuring discontinuation, intensification, and switching in a cohort of patients initiating metformin. Four Australian sites independently developed a HARmonized Protocol template to Enhance Reproducibility (HARPER) protocol and executed their analyses using the Australian Pharmaceutical Benefits Scheme 10% sample dataset. Each site calculated cohort size and demographics and measured treatment events including discontinuation, switch to another diabetes medicine, and intensification (addition of another diabetes medicine). Time to event and hazard ratios for associations between cohort characteristics and each event were also calculated. Concordance was assessed by measuring deviations from the calculated median of each value across the sites. Good agreement was found across sites for the number of initiators (median: 53 127, range: 51 848-55 273), gender (56.9% female, range: 56.8%-57.1%) and age group. Each site employed different methods for estimating days supply and used different operational definitions for the treatment events. Consequently, poor agreement was found for incidence of discontinuation (median 55%, range: 34%-67%), switching (median 3.5%, range: 1%-7%), intensification (median 8%, range: 5%-12%), time to event estimates and hazard ratios. Differences in analytical decisions when deriving exposure from dispensing data affect replicability. Detailed analytical protocols, such as HARPER, are critical for transparency of operational definitions and interpretations of key study parameters.

Cross-sectional associations between 24-hour time-use composition, grey matter volume and cognitive function in healthy older adults

BackgroundIncreasing physical activity (PA) is an effective strategy to slow reductions in cortical volume and maintain cognitive function in older adulthood. However, PA does not exist in isolation, but coexists with sleep and sedentary behaviour to make up the 24-hour day. We investigated how the balance of all three behaviours (24-hour time-use composition) is associated with grey matter volume in healthy older adults, and whether grey matter volume influences the relationship between 24-hour time-use composition and cognitive function.MethodsThis cross-sectional study included 378 older adults (65.6 ± 3.0 years old, 123 male) from the ACTIVate study across two Australian sites (Adelaide and Newcastle). Time-use composition was captured using 7-day accelerometry, and T1-weighted magnetic resonance imaging was used to measure grey matter volume both globally and across regions of interest (ROI: frontal lobe, temporal lobe, hippocampi, and lateral ventricles). Pairwise correlations were used to explore univariate associations between time-use variables, grey matter volumes and cognitive outcomes. Compositional data analysis linear regression models were used to quantify associations between ROI volumes and time-use composition, and explore potential associations between the interaction between ROI volumes and time-use composition with cognitive outcomes.ResultsAfter adjusting for covariates (age, sex, education), there were no significant associations between time-use composition and any volumetric outcomes. There were significant interactions between time-use composition and frontal lobe volume for long-term memory (p = 0.018) and executive function (p = 0.018), and between time-use composition and total grey matter volume for executive function (p = 0.028). Spending more time in moderate-vigorous PA was associated with better long-term memory scores, but only for those with smaller frontal lobe volume (below the sample mean). Conversely, spending more time in sleep and less time in sedentary behaviour was associated with better executive function in those with smaller total grey matter volume.ConclusionsAlthough 24-hour time use was not associated with total or regional grey matter independently, total grey matter and frontal lobe grey matter volume moderated the relationship between time-use composition and several cognitive outcomes. Future studies should investigate these relationships longitudinally to assess whether changes in time-use composition correspond to changes in grey matter volume and cognition.

Remote paediatric ear examination comparing video-otoscopy and still otoscopy clinician rated outcomes

ObjectiveTelemedicine, particularly real time video-otoscopy in rural and remote Australia holds great potential in assessing and managing otology conditions. There is good evidence of store and forward images for assessment, however limited evidence exists for the use of real-time video-otoscopy. The objective of this study was to assess the validity of using real time video-otoscopy, compared to standard store and forward still image otoscopy, in a paediatric population. MethodFifty-two paediatric tympanic membranes in 27 patients were examined and photographed by a telehealth facilitator with prior otoscope training. This occurred at two rural Western Australian health centre sites. These images were stored and forwarded to a tertiary paediatric hospital for otolaryngology department assessment on the day of real-time video-otoscopy consultation. During this consultation the same twenty-seven patients underwent real-time video-otoscopy assessment, which was recorded. Across six domains including, image quality, focus, light, cerumen amount, field of view and tympanic membrane landmarks, real-time video-otoscopy was compared against still image capture. The recording of each real-time video-otoscopy and still image tympanic membrane was assessed by two otology specialists for the ability to diagnose each as either normal or abnormal. An inter-rater reliability agreement was then calculated. ResultsThere was greater image adequacy across five of the six domains for real time video-otoscopy compared to standard store and forward otoscopy images. Substantial agreement in diagnosing each tympanic membrane as either normal or abnormal between each rater was evident. ConclusionThis study supports the use of real time video-otoscopy during telemedicine consultation. With greater image quality, focus, light, field of view and identification of tympanic membrane landmarks video-otoscopy compared to still images has broad clinical applications. This includes primary assessment of the tympanic membrane and post operative follow-up clinical settings. Video-otoscopy offers a promising new way to over-come barriers in delivering ear health care in rural populations.

Reversible strengthening behaviour of subsurface layers in sandy soils – understanding variable response to strategic deep tillage

Deep sandy soils cover more than 10 M ha of Australia's southern dryland cropping lands. Farming these soils is inherently challenging, and yield gaps are often wide due to multiple cropping constraints. Physical constraints that limit rooting depth are commonplace and often attributed to traffic-induced soil compaction. However, recent observations draw attention to a reversible hardsetting behaviour in response to soil water content. This hardsetting phenomenon is poorly understood and it may explain inconsistent crop responses to deep ripping in sandy soils. We examined the dynamic behaviour of soil strength under different soil water contents in deep ripped and unripped sands from four South Australian sites. We analyzed the elemental, mineralogical, chemical and physical compositions to differentiate the nature of hardened subsurface layers. Soil compaction and cementation were ruled out due to the soil's bulk density (<1.6 g cm−3) encountered and the rapid slaking that occurred when a hardened pan was submerged in water. The hardsetting behaviour was confirmed by the abrupt change in soil strength in response to the soil water content, measured using intact samples in a laboratory-based penetrometer. This significant increase in soil strength was also observed for soils collected from the ripped plots and for repacked soil samples, with penetration resistance ranging from 0.4 to 5.7 MPa depending on soil content. In contrast to our hypotheses, the hardsetting layer could not be distinguished from the layers above or below it by any analytical method. Given soil strength is typically measured on field moist soil, and standard chemical analysis did not differentiate hardsetting behaviour, alternative methods of diagnosis are needed to understand where deep tillage is likely to have the desired long-term effect. Identifying the nature of potential binding agents responsible for increased strength upon drying would be valuable. Our results confirmed reversible hardsetting in deep sandy soils is driven by small changes in soil water content, from 0.08 g g−1 to 0.05 g g−1 upon drying. Given that rapid re-consolidation of the soil matrix after expensive deep ripping interventions are reported, there is a strong imperative to improve diagnosis, and to identify if soil ameliorants could improve longevity by disrupting hardsetting behaviour.

Analysis of Violent Incidents at Five Regional and Remote Australian Emergency Departments: A Retrospective Descriptive Study.

Workplace violence is endemic, destructive, and escalating in frequency and severity in healthcare. There is a paucity of research on workplace violence in regional and remote hospital emergency departments (EDs). The aim of this study was to identify the perpetrator and situational characteristics associated with violent incidents in the ED across five regional and remote Australian sites. This study audited hospital summary data, incident reports, and medical records for a 12-month period in 2018 to examine the perpetrator and situational characteristics of workplace violence incidents in five regional and remote Australian EDs. Violent incidents were evenly spread throughout the week and across shifts. Most incidents were triaged as urgent, occurred within the first 4 hr, and had multidisciplinary involvement. Almost one in every six incidents resulted in an injury. Perpetrators of violence were predominantly young and middle-aged males and almost always patients, with most presenting with mental and behavioral disorders, or psychoactive substance use. Understanding the characteristics of perpetrators of violence can help in seeking to tailor interventions to reduce further violent behaviors. These findings carry implications for optimizing patient care, staff safety and resource management.

Tranexamic Acid to Prevent Bleeding in Patients with Hematologic Malignancies and Severe Thrombocytopenia (TREATT trial). a Randomized Placebo-Controlled Trial

Conclusions LJE &amp; ZM and EMW &amp; SJS contributed equally Patients undergoing treatment for hematologic malignancies continue to have a high burden of clinically significant bleeding (WHO grade 2 or above) despite receiving prophylactic platelet transfusions (43% in TOPPS trial, NEJM 2013). One potential approach to reduce the burden of bleeding is antifibrinolytic therapy, which has been shown to reduce bleeding and transfusion needs in patients undergoing surgery. The Trial to EvaluAte Tranexamic acid therapy in Thrombocytopenia (TREATT) is a double-blind randomized controlled trial evaluating the safety and efficacy of tranexamic acid (TXA) in patients with hematologic malignancies with severe thrombocytopenia (EudraCT number 2014-001513-35). We enrolled adults with hematologic malignancies having intensive chemotherapy or a hematopoietic stem cell transplant (HSCT) who were expected to have severe thrombocytopenia (platelet count ≤10x10 9/L for ≥5 days) at 16 UK and 11 Australian sites. We stratified randomization by site. We randomized participants to receive TXA (1g iv or 1.5g orally) or placebo (saline or capsule/tablet) 8-hourly from when platelet count ≤30x10 9/L or as soon as possible if the platelet count was already ≤ 30x10 9/L (no later than 72 hours after start of chemotherapy or HSCT). We stopped treatment if the unsupported platelet count reached ≥ 30x10 9/L, thrombosis occurred, or patient had received 30 days treatment. Patients received red cell and platelet transfusions according to national transfusion guidelines. Bleeding assessments were performed by trained research staff (inpatients) or via a patient diary, with significant bleeding reported to clinicians (outpatients), using validated tools. The primary outcome was the proportion of participants who died or had bleeding of WHO Grade 2 or above from study day 1 ([D1], first day of treatment) to D30. We used marginal Cox proportional hazards regression modelling (adjusted for site to account for clustering) to compare the two arms. Secondary outcomes included: safety outcomes (thrombotic events to D120) and use of blood components. Recruitment was affected by the COVID pandemic. We randomized 616 participants between June 2015 and February 2022 and included 597 in the modified intention to treat (mITT) analysis (platelet count ≤ 30x10 9/L for ≥ 1 day and no exclusion criteria). 16 participants were lost to follow-up prior to D120 (8 each arm); we included them in analyses if possible. Participant mean age was 55.6 years (SD12.2), 38.2% (236/616) were women, 42.9% (264/616) had AML, 35.1% (216/626) autograft and 25.4% (156/626) allograft. There was no evidence of a difference in the risk of death or ≥ Grade 2 bleeding between the TXA and placebo arms (HR 0.92; 95% CI: 0.67, 1.27; p-value 0.62). 29.0% (87/300) of participants in the TXA arm and 32.7% (97/297) in the placebo arm experienced ≥ Grade 2 bleeding, 66.0% (198/300) of participants in the TXA arm and 73.4% (218/297) in the placebo arm experienced ≥ Grade 1 bleeding. There was no evidence of a difference in the risk of death to D30 (HR 2.72; 95% CI 0.29, 25.36; p-value 0.38), however there were only 11 deaths overall. No patient died from bleeding (to D30) or thrombosis (to D120). The proportion of participants surviving to D30 without a platelet transfusion was 8.3% in TXA arm (95% CI: 5.4, 11.9), 6.4% placebo arm (95% CI 3.9, 9.7) (HR 0.92; 95% CI: 0.84, 1.02; p-value 0.10). The proportion of participants surviving to D30 without a red cell transfusion was 29.4% in TXA arm (95% CI: 24.1, 34.8), 20.5% placebo arm (95% CI 16.0, 25.4) (HR 0.82; 95% CI: 0.72, 0.93; p-value 0.003). 13 participants developed thrombosis to D120: 2 arterial events (1 each arm), and 11 venous (7 TXA arm, 4 placebo). 5 participants developed veno-occlusive disease (VOD) to D60 (3 TXA arm, 2 placebo). Additional secondary outcomes (Table 1). Prophylactic TXA had no effect on the incidence of WHO Grade ≥2 bleeding or death when given in addition to prophylactic platelet transfusions to severely thrombocytopenic patients undergoing therapy for hematologic malignancies. The results are consistent with those of a similar trial (A-TREAT, Blood 2022). These results indicate no role for TXA to prevent WHO ≥ Grade 2 bleeding in this patient population. There was no evidence that TXA increases the risk of venous or arterial thrombosis, or VOD, despite use for up to 30 days.

Pleistocene raptors from cave deposits of South Australia, with a description of a new species of Dynatoaetus (Accipitridae: Aves): morphology, systematics and palaeoecological implications

The Pleistocene fossil record of Australian raptors (Accipitridae: eagles, hawks and Old World vultures) is very poorly understood with only three distinct extinct species confirmed until now. The small Necrastur alacer remains unstudied; however recent research has established Cryptogyps lacertosus as a valid species that, along with the very large Dynatoaetus gaffae, has potential affinities with the Aegypiinae–Circaetinae clade. These, along with a single large living inland raptor, the Wedge-tailed Eagle Aquila audax, suggest that Australia had an impoverished diversity of large raptors compared to other similar continental regions. However, fossil material similar in size to A. audax from multiple Pleistocene cave deposits raises the possibility of further taxa and is here assessed. A partial skeleton from Green Waterhole/Fossil Cave in the Tantanoola District of South Australia is referred to Cryptogyps lacertosus on the basis of similar size to bones of this species and that the associated coracoid is identical to that found with a tarsometatarsus that was previously referred to this species, coming from Leaena’s Breath Cave on the Nullarbor Plain, Western Australia. This partial skeleton allowed additional material from the Old Collections, Wellington Caves, and Walli Caves in New South Wales to be referred to this species. A second species, more robust than A. audax, is identified from material from Victoria Fossil Cave at Naracoorte. Phylogenetic analyses determined this species to be the sister taxon of the much larger Dynatoaetus gaffae recently described from several Australian sites, and so we name it as Dynatoaetus pachyosteus sp. nov. Further fragmentary remains attributable to either A. audax, C. lacertosus or D. pachyosteus are recorded from sites in the Wellington Caves complex, NSW. This study increases the known diversity of raptors in Pleistocene Australia, consistent with the presence of the more diverse megafaunal prey that existed at the time. Ellen K. Mather [ math0083@flinders.edu.au ], College of Science and Engineering, Flinders University, GPO 2100, Adelaide, SA 5001, Australia; Michael S. Y. Lee [ Mike.Lee@samuseum.sa.gov.au ], Earth Sciences Section, South Australian Museum, North Terrace, Adelaide 5000, Australia (College of Science and Engineering, Flinders University, GPO 2100, Adelaide, SA 5001, Australia); Diana A. Fusco [ diana.fusco@flinders.edu.au ], College of Science and Engineering, Flinders University, GPO 2100, Adelaide, SA 5001, Australia; John Hellstrom [ j.hellstrom@unimelb.edu.au ], Faculty of Science, School of Geography, Earth and Atmospheric Sciences, University of Melbourne, Grattan Street, Parkville, Melbourne, 3010, Australia; Trevor H. Worthy [ trevor.worthy@flinders.edu.au ], College of Science and Engineering, Flinders University, GPO 2100, Adelaide, SA 5001, Australia.

Multicenter prospective blinded melanoma detection study with a handheld elastic scattering spectroscopy device

BackgroundThe elastic scattering spectroscopy (ESS) device (DermaSensor Inc., Miami, FL) is a non-invasive, painless, adjunctive tool for skin cancer detection. ObjectivesTo investigate the performance of the ESS device in the detection of melanoma. MethodsA prospective, investigator-blinded, multicenter study was conducted at 8 United States (US) and 2 Australian sites. All eligible skin lesions were clinically concerning for melanoma, examined with the ESS device, subsequently biopsied according to dermatologists’ standard of care, and evaluated with histopathology. A total of 311 participants with 440 lesions were enrolled, including 44 melanomas (63.6% in situ and 36.4% invasive) and 44 severely dysplastic nevi. ResultsThe observed sensitivity of the ESS device for melanoma detection was 95.5% (95% CI, 84.5%-98.8%, 42 of 44 melanomas), and the observed specificity was 32.5% (95% CI, 27.2%-38.3%). The positive and negative predictive values were 16.0% and 98.1%, respectively. LimitationsThe device was tested in a high-risk population with lesions selected for biopsy based on clinical and dermoscopic assessments of board-certified dermatologists. Most enrolled lesions were pigmented. ConclusionThe ESS device’s high sensitivity and NPV for the detection of melanoma suggest the device may be a useful adjunctive, point-of-care tool for melanoma detection.

Phase 1 Pharmacodynamic and Pharmacokinetic Study of the Geranylgeranyltransferase I Inhibitor PTX-100 (GGTI-2418) in Patients with Advanced Malignancies

Introduction: The RAS superfamily of small GTPases mediate hallmarks of cancer cell proliferation, viability, migration, invasion and metastasis. Several GTPases such as RAL, RHO and RAC are required for RAS to induce malignant transformation. RAS post-translational modification (PTM) by farnesyltransferase (FT) as well as RAL, RHO and RAC PTM by geranylgeranyltransferase 1 (GGT-1) are critical for the membrane localization and oncogenicity of these GTPases. Mutations in HRAS, NRAS, KRAS and RHOA are prevalent in solid tumors as well as T-cell lymphomas (TCL) such as peripheral T-cell lymphoma (PTCL), angioimmunoblastic T-cell lymphoma (AITL), PTCL-not otherwise specified and cutaneous T-cell lymphoma (CTCL). PTX-100 is a small molecule inhibitor of GGT-1 that disrupts the oncogenic activity by inhibiting RAL, RHO and RAC PTM. Methods: This ongoing phase 1 study (NCT03900442) in 2 Australian sites, consists of a 3+3 dose escalation with an expansion phase. The aim is to evaluate the pharmacodynamic (PD), pharmacokinetics (PK), preliminary efficacy and safety of 500, 1000 and 2000 mg/m 2 PTX-100 in patients (pts) with advanced malignancies. PTX-100 is administered by IV infusion over 60 minutes days 1 to 5 of a 14 day cycle for 4 cycles. Disease response is assessed via CT, MRI or PET-CT or per SOC after 4 cycles. Pts with a complete response (CR), partial response (PR) or stable disease (SD) may be eligible for continued treatment with PTX 100, dosed in 21 day cycles with response assessment every 3 months. Results: The first pt was enrolled in October 2019 and enrollment is nearly completed in the expansion cohort. The data cutoff was 10 th July 2023. Ten pts were enrolled into Part 1 with 3 dosed at 500 mg/m 2, 3 at 1000 mg/m 2 and 4 at 2000 mg/m 2. The expansion cohort at 2000 mg/m 2 began in May 2022 and there have been 10/15 enrolled to date. Positive long-term responses (32 and 13.8 months) were observed for 2 TCL pts in Part 1 so the decision was made to enroll TCL pts into the expansion cohort. The median age was 67 years (44 to 81), the median number of prior lines was 3 (1-6). The TCL subtypes were PCTL NOS (n=6), AITL (n=3), and CTCL (n=5). Of the 14 enrolled TCL pts, 10 pts had response assessments after 4 cycles, with an overall response rate (ORR) of 40% (4pts), including 10% (1 pt) CR, 30% (3pts) PR. Two CTCL pts (20%) had durable SD &amp;gt;6 months, contributing to a 60% Disease Control Rate. The median Progression Free Survival (PFS) for all TCL pts was 5.3 mos, CTCL pts 13.6 mos and PTCL pts 2.5 mos. No responses were observed in the 5 solid tumor pts. There were 23 Grade ≥3 adverse events in 8 pts including laboratory neutropenia in 2 pts with 1 deemed possibly related. Neutrophil count decreased in 2 pts with 1 deemed possibly related and the platelet count decreased in 2 pts with 1 deemed possibly related. Grade 1-2 adverse events deemed possibly related included, nausea reported in 4 pts and diarrhea in 3 pts. For the PD studies, we determined the effects of PTX-100 on the geranylgeranylation (GG) of the small GTPase RAP1 in peripheral blood monocytes (PBMCs) isolated from pts on cycle 1, day 1 (prior to treatment) and subsequently on days 2, 3, 4, 5, and 8. PTX-100 inhibited GG of RAP1A as early as 1 day after treatment, and with the majority of the pts, the inhibition of RAP1A GG persisted three days after the last dose of PTX-100. Inhibition of RAP1 GG was observed with all doses including the lowest dose of 500 mg/m 2. PK analysis is underway at the time of abstract preparation and the PK parameters will be presented at the meeting. Conclusions: Preliminary data from this phase 1 dose escalation study of PTX-100 indicates promising safety profile in this difficult to treat pt population. PTX-100 demonstrated clinical activity in TCL with an ORR of 40%, and a median PFS for all TCL pts of 5.3 months. PD studies demonstrated that the GGT-1 target was engaged with sustained inhibition of RAP1 GG.

Obinutuzumab, Lenalidomide and Venetoclax in Patients with Treatment-Naïve Advanced-Stage Follicular Lymphoma: First Results of the Investigator-Initiated Phase Ib/II, Multicenter Leverage Study

Background Follicular lymphoma (FL) is the most common indolent lymphoma. The most widely used initial treatment is chemo-immunotherapy, however conventional cytotoxic agents may result in acute and late toxicities which can be problematic. There is a need for active novel treatment approaches with more favorable safety profiles. Methods We designed a phase Ib/II study of obinutuzumab, lenalidomide and venetoclax in patients with treatment-naïve follicular lymphoma. Key inclusion criteria included non-contiguous or bulky stage II-IV disease, meeting GELF criteria for treatment, adequate organ function and performance status. Treatment was divided into 2 phases, induction (6 x 28-day cycles) and maintenance (12 x 56-day cycles). During induction, patients received fixed doses of obinutuzumab (1000mg D1, 8, 15 cycle 1; D1 of C2-6) and lenalidomide 20mg days 1-21 from C2-6. Venetoclax was given from C1-6 and the dose was escalated, according to a 3+3 design with 4 dose levels (DL) tested: DL 1: 400mg daily D1-10, DL 2: 800mg D1-10, DL 3: 400mg D1-28 and DL 4: 800mg D1-28. After 6 cycles, patients who attained complete response (CR) received obinutuzumab maintenance (1000mg every 8 weeks for 2 years). Patients who attained partial response received a further 6 cycles of lenalidomide (10mg D1-28) and venetoclax (at the same dose given in induction) in addition to the obinutuzumab maintenance. Patients who experienced SD discontinued study in favour of alternate therapy. The primary endpoint of phase Ib was recommended phase II dose (RP2D). The primary endpoint of phase II was intention to treat CR rate by investigator assessment at end of induction by Lugano 2014. Key secondary endpoints included safety, objective response rate (ORR), progression free survival (PFS), overall survival and quality of life. This interim analysis focuses on the RP2D, safety and preliminary efficacy data. Results As of 13 Mar 2023, 36 patients have been enrolled of whom 26 completed end of induction phase and are included in this interim analysis. Eighteen patients were treated in dose escalation (3, 6, 3 and 6 at dose levels 1-4, respectively) and 18 in expansion phase. The baseline characteristics are summarized in Table 1. The median relative dose intensity was &amp;gt;90% for all 3 agents. One dose limiting toxicity (DLT) occurred (grade 3 ALT elevation possibly related to venetoclax on C1D1, which resolved within 48 hours) and no maximum tolerated dose was reached. Dose level 4 (venetoclax 800mg daily D1-28) was the RP2D. The only grade≥3 AEs to occur in more than two patients were neutropenia (65%), without febrile neutropenia. The most common any grade AEs were nausea (50%), diarrhea (46%), maculopapular rash (31%), thrombocytopenia (27%), fatigue (23%) and constipation (23%). One patient developed biochemical TLS. 7 patients prematurely discontinued study treatment due to progressive disease (PD) in 2, and 1 case of each DLT, COVID-19, grade≥3 cytopenias lasting &amp;gt;28 days, upper respiratory infection and development of a second malignancy requiring systemic therapy. At the end of induction, the CR and ORR were 81% and 92%, respectively. The 2 PD events were both found at the end of induction restaging, and biopsy revealed histologic transformation to diffuse large B-cell lymphoma. Updated data (including PFS) will be presented at the meeting. Conclusion The combination of obinutuzumab, lenalidomide and venetoclax is a highly active and safe combination in patients with treatment-naïve high tumor burden FL. No unexpected safety signals were identified. Enrolment to phase II is ongoing at 4 Australian sites. This trial is registered at clinicaltrials.gov (NCT03980171)

Trial in Progress: Treatment of Newly-Diagnosed Follicular Lymphoma with Celmod BMS-986369, Rituximab +/- Nivolumab: An Umbrella Phase II Investigator-Initiated Study

Background: Follicular lymphoma (FL) outcomes are influenced by tumour microenvironment composition and manipulation. As patients (pts) with FL are predominantely aged over 65 and may require treatment multiple times over their disease course, novel regimens which maintain or enhance efficacy and minimise toxicity are highly desirable. We have previously reported favourable efficacy and safety of nivolumab plus rituximab as a 1 st line treatment in advanced-stage, grade 1-3A treatment naïve FL, (ORR 92%; CR 54%; toxicity grade 3 or higher in 41%) in an investigator-led trial. 1-3 Oral cereblon-modulating (CELMoD) compounds have shown substantial efficacy alone or in combination with rituximab in both treatment naive and relapsed/refractory FL. 4,5 CELMoDs co-opt cereblon to promote degradation of key transcription factors in cell development and homeostasis, including Ikaros and Aiolos, which are upregulated in FL. 6 Additionally, they act as immunomodulatory agents and augment immune host response. The novel CELMoD, BMS-986369 (golcadomide), demonstrated enhanced antiproliferative and apoptotic activity in pre-clinical studies, with ORR of up to 75% following monotherapy doses of 0.4mg or higher in heavily pre-treated FL pts. 7-10 Our follow-on study (‘TOP-FLOR’; NCT05788081) builds on these findings and potential immunomodulatory synergy to explore the efficacy and safety of BMS-986369 with rituximab +/-nivolumab in treatment-naïve advanced stage FL pts. Study Design and methods: This is an open label multicentre umbrella Bayesian Optimal randomised Phase II trial. The study will randomise up to 40 eligible pts 1:1 to receive rituximab, BMS986369 +/- nivolumab (20 per arm) from 5 Australian sites. Eligibility includes pts aged &amp;gt;18 years, with previously-untreated, stage II-IV, grade 1-3A FL with performance status of 0-1 who require systemic therapy. Treatment consists of 8 cycles (28 days each) of BMS-986369 0.4 mg po daily on days 1- 14 plus rituximab 375 mg/m2 IV day 1 in Arm A; BMS-986369, rituximab as above plus nivolumab 480mg IV day 1 in Arm B. All pts in partial or complete response at end of induction receive 12-weekly rituximab maintenance (8 doses). The primary endpoint will be CR rate in the absence of prohibitive toxicity in accordance with CTCAE V5.0 after eight cycles of rituximab, BMS-986369 +/-nivolumab. Secondary endpoints include: Overall toxicity, response rate (according to modified Lugano criteria), time to treatment failure, progression-free survival and overall survival. Exploratory endpoints include: pt reported outcomes as measured by EORTC-QLQ-c30 and FACT-Lym, PET radiomics and tissue, blood and stool immune and genomic biomarkers. Study assessments include: PET/CT, biomarker blood collection and pt reported outcome measures performed at baseline, post cycle 2, 5 and 8, then 6 monthly on maintenance therapy. Response assessment according to modified Lugano criteria. Safety assessments prior to each cycle until 28 days after the final study drug is administered using CTCAEv5.0. Interim assessment of the primary endpoint will be conducted for 11 pts in each arm, arms will be closed for futility if fewer than 7 pts achieve the primary endpoint. Treatment arms will not be formally compared. Survival probabilities will be reported using Kaplan-Meier analysis. Status: This trial received IRB approval on 14 July 2023 (HREC/88597/Austin-2023) at Austin Health, Heidelberg, Australia. Funding: This trial is supported by an investigator-sponsored research grant from Bristol-Myers Squibb. Nivolumab and BMS 989369 supplied by Bristol-Myers Squibb.

Truth-telling, Ancestral Remains and the Establishment of a National Resting Place in Australia

ABSTRACT∞ This article explores the potential for truth-telling and healing created by the recently announced National Resting Place for Indigenous Ancestral Remains in Australia. The return of Indigenous Ancestral Remains provides the opportunity to make redress for past wrongs, and to reflect on the attitudes which informed the dehumanizing practices of their past collection and display. Indigenous Ancestral Remains are critical to truth-telling in Australia as by their very existence and materiality they disrupt colonial narratives about terra nullius. However, human remains are also a powerful reminder of the limits of human rights processes. We consider the potential of the National Resting Place as a new Australian site of truth and memory to disrupt the traditional ‘museum’ model and to restore the dignity and respect owing to previously objectified human remains.

A Grave Situation: Burial Practices among the Chinese Diaspora in Queensland, Australia (ca.1870–1930)

AbstractMany nineteenth-century Chinese migrants to Pacific Rim countries died far from their home villages. Diverse approaches were adopted to mark graves, possibly anticipating the subsequent, culturally important, repatriation of their bones. This paper evaluates the morphology of grave markers from eight northeast Australian sites and considers reasons for the variations. Physical appraisal of each site was undertaken and, where they exist, cemetery records and allied documentation examined. In an unusual departure from the norm the inscriptions on most identified grave markers rarely indicate date of death. The seemingly meticulous attention to grave identification in some areas contrasts with others where markers are absent. This study indicates divergent approaches to identification and recording of individual graves over time and place. Rather than indicating full-fledged ethnogenesis, wherein Australian Chinese developed new cultural practices, these behaviors suggest that ca.1870–1930 was a transitional period, during which extant cultural processes were adapted to meet immediate needs.

Vocalizations of two conspecific damselfish (Pomacentridae) at two Australian World Heritage sites: The Ningaloo Coast and the Great Barrier Reef

Novel methods to use Ocean Sound to address ecological questions are increasingly being developed but require optimization and validation to ensure their reliability. Source validation, increasing the number of known soniferous species of marine fauna, and characterizing their acoustic repertoires are important components of this effort. Coral reefs are remarkably complex, diverse, and noisy environments, inhabited by many soniferous species, hindering the association of vocalizations with the emitting species. Damselfish (Pomacentridae) are common and conspicuous reef fishes that have been relatively well-studied due to their abundance, territorial behaviors, and sound production. Most fish sound studies support that fish vocalizations are species-specific, often showing niche acoustic partitioning to avoid competition across frequency and time. It is imperative to record fish vocalizations in the field to avoid distortion in their acoustic attributes, which then can be used for further analyses such as automated detections. Here, we characterize the vocalizations of Dascyllus aruanus and Dascyllus reticulatus using field-experimental settings for in situ recordings from the Ningaloo Coast and the Great Barrier Reef. [Work supported by the BHP-AIMS Australian Coral Reef Resilience Initiative. JCAS was supported by Curtin University and BHP-AIMS in the form of a Curtin Strategic Scholarship and Top-up Scholarship.]

Best Practice in Post-Stroke Aphasia Services According to People with Lived Experience. A Modified Nominal Group Technique Study

ABSTRACT Background Clinical practice guidelines and best practice statements aim to optimise patient outcomes through recommended processes of care. The Aphasia United Best Practice Recommendations were developed to provide multi-national best-practice guidance for post-stroke aphasia services. The recommendations were developed through a multi-stage process which synthesised research evidence and the expert opinions of clinicians and researchers. To date, however, people with lived experience of aphasia have not contributed their expertise to these recommendations. Aims To explore the relevance, comprehensibility, and comprehensiveness of the Aphasia United Best Practice Recommendations, from the perspective of people with aphasia and their significant others. Conducted during the COVID-19 pandemic, a secondary aim was to evaluate participants’ satisfaction with videoconferencing for research. Methods & Procedures People with aphasia and their significant others participated in separate focus groups via videoconferencing. Participants were recruited at five Australian sites (representing major cities and regional locations). Participants rated the relevance and comprehensibility (clarity) of the recommendations and suggested improvements. Using the nominal group technique, participants assessed the comprehensiveness of the existing recommendations, and generated and prioritised new items for inclusion. These recommendations were synthesised across groups using qualitative content analysis. Participants rated their satisfaction with videoconferencing for research through a bespoke questionnaire. Outcomes & Results People with aphasia (n=13) and their significant others (n=10) participated in one of eight focus groups in Australia. Most participants rated the existing recommendations as highly relevant, however improvements to comprehensibility and comprehensiveness were suggested. Fifty-one new recommendations were prioritised and synthesised into seven themes for people with aphasia and six themes for significant others. The most highly ranked theme for people with aphasia was, Increased awareness about: what aphasia is, the impacts of aphasia, and how to communicate with a person with aphasia. The theme ranked most highly by significant others was, Aphasia services should be person and family centred. All participants reported being satisfied or highly satisfied with the use of Zoom videoconferencing for research. Conclusions People with aphasia and their significant others in Australia identified new important best practice recommendations for aphasia services. The results of this study suggest that revisions to existing recommendations may improve their relevance, comprehensibility, and comprehensiveness. Participants were satisfied with the use of videoconferencing for research. The results of this research will inform a future consensus process to finalise the revised recommendations and to pair them with measurable quality indicators for post-stroke aphasia services.

Surviving the educational landscape: a case study of leadership, policy tensions and marketisation

Within a neoliberal educational policy context, we are increasingly witness to educational leaders compelled to become strategic operators to ensure the survival of their schools. Drawing on the tenets of institutional ethnography (IE), this article traces the everyday work and experience of a school leader in one Australian private school site that was in ‘survival mode’ after experiencing an unprecedented decline in enrolment numbers. By tracing the power of global and local market forces informing the work of one educational leader, our intention is to capture how a school leader’s subjectivity was influenced by market demands and how he invested his time in strategizing to ensure his school would survive. The article makes two main contributions; first, the case study complements research exploring the impact of neoliberal reform on schooling and, second, we highlight the role of IE in furthering our understanding of the pressures schools face and the lived experience of school leaders.

P05.02.A PRELIMINARY FINDINGS FROM THE MRI QUALITY ASSURANCE PROGRAMME FOR THE PROSPECTIVE MULTI-SITE AUSTRALIAN FIG ([FET-PET IN GLIOBLASTOMA) TROG 18.06 STUDY

Abstract BACKGROUND The O-(2-[18F]-fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) in Glioblastoma (FIG) study is a prospective study evaluating the management impact of FET-PET imaging in up to 210 newly diagnosed adult glioblastoma patients across 10 Australian sites. Patients undergo contrast MRI and FET-PET at 3 timepoints: pre-chemoradiotherapy (CRT), one-month post-CRT and at suspected progression. MRI QA programme components, approach and integrated workflows are described here. MATERIAL AND METHODS The FIG MRI protocol comprised 3D-T1, 3D-FLAIR, Axial 2D DWI (including derived ADC map), DCE (including T1 mapping), DSC, Axial T2 and 3D T1-post-contrast (T1C) sequences, with SWI and 3D DIR sequences optional. QA components included data acquisition quality and completeness (standard and advanced), motion artefact, low contrast to noise or signal to noise, series description and susceptibility artifacts. Suitability of T1/T1C using modified RANO (mRANO) criteria was assessed. An optimised workflow involved site upload from local PACS systems to centralised database via TROG Central Quality Management System (CQMS) platform and collation into a central imaging database utilising MIM software. The MRI QA workflow encompassed automated anonymisation of DICOM data, data completeness and reconstruction evaluation, then review by two expert neuroimaging analysts. Sites received feedback with request for resubmission where required. RESULTS Between December 2021 and February 2023, MRI data in 74 patients across 9 sites with median of 6 patients (range 2-17) per site was submitted. A total of 141 MRI datasets across all timepoints were collected (per site range:4-35, median:13), with 43 imaging time-points selected for QA (per site range:3-12, median: 4). Importantly, 41/43 (95%) of initial datasets were deemed suitable for mRANO assessment, but only 13/43 (30%) were suitable for advanced MRI analysis. Very few datasets had motion or susceptibility artifacts, low contrast to noise or signal to noise, or incorrect series description. Technical issues identified included incomplete data (DCE - missing T1 maps, DWI - missing ADC maps), incorrect sequence reconstruction (DCE split series and Axial/Sagittal/Coronal reformats for 3D images) and lack of non-mandatory SWI sequences. Feedback to sites resulted in improvements in DCE sequence acquisition from split series in 11/45 (24%) to preferred single series in 18/24 (75%) and similar increases in T1 maps completeness from 7/19 (37%) to 7/7 (100%). CONCLUSION Despite challenges in multisite workflow and substantial multi-modality site and central data management, a robust MRI QA program has confirmed 95% compliance for mRANO assessment. Site specific feedback resulted in increased compliance with advanced MRI sequences to enable detailed future analysis.

ACEMID cohort study: protocol of a prospective cohort study using 3D total body photography for melanoma imaging and diagnosis

IntroductionThree-dimensional (3D) total body photography may improve early detection of melanoma and facilitate surveillance, leading to better prognosis and lower healthcare costs. The Australian Centre of Excellence in Melanoma Imaging...

Stochastic soiling loss models for heliostats in Concentrating Solar Power plants

Reflectance losses on solar mirrors due to soiling are a significant challenge for Concentrating Solar Power (CSP) plants. Soiling losses can vary significantly from site to site — with (absolute) reflectance losses varying from fractions of a percentage point up to several percentage points per day (pp/day), a fact that has motivated several studies in soiling predictive modelling. Yet, existing studies have so far neglected the characterization of statistical uncertainty in their parameters and predictions. In this paper, two reflectance loss models are proposed that model uncertainty: an extension of a previously developed physical model and a simplified model. A novel uncertainty characterization enables Maximum Likelihood Estimation techniques for parameter estimation for both models, and permits the estimation of parameter (and prediction) confidence intervals.The models are applied to data from ten soiling campaigns conducted at three Australian sites (Brisbane, Mount Isa, Wodonga). The simplified model produces high-quality predictions of soiling losses on novel data, while the semi-physical model performance is mixed. The statistical distributions of daily losses were estimated for different dust loadings. Under median conditions, the daily soiling losses for Brisbane, Mount Isa, and Wodonga are estimated as 0.53±0.66, 0.08±0.08, and 0.58±0.15 pp/day, respectively. Yet, higher observed dust loadings can drive average losses as high as 2 pp/day.Overall, the results suggest a relatively simple approach characterizing the statistical distributions of soiling losses using airborne dust measurements and short reflectance monitoring campaigns.