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Background and ObjectivesAboriginal Australians are disproportionately affected by dementia, with incidence in remote populations approximately double that of non-Indigenous populations. This study aimed to identify dementia incidence and risk factors in Aboriginal Australians residing in urban areas, which are currently unknown.MethodsA population-based cohort of Aboriginal Australians ≥60 years of age was assessed at baseline and 6-year follow-up. Life-course risk factors (baseline) were examined for incident dementia or mild cognitive impairment (MCI) through logistic regression analyses; adjustments were made for age. APOE genotyping was available for 86 people.ResultsData were included from 155 participants 60 to 86 years of age (mean 65.70 years, SD 5.65 years; 59 male). There were 16 incident dementia cases (age-standardized rate 35.97/1,000 person-years, 95% confidence interval [CI] 18.34–53.60) and 36 combined incident MCI and dementia cases. Older age (odds ratio [OR] 2.29, 95% CI 1.42–3.70), male sex (OR 4.14, 95% CI 1.60–10.77), unskilled work history (OR 5.09, 95% CI 1.95–13.26), polypharmacy (OR 3.11, 95% CI 1.17–8.28), and past smoking (OR 0.24, 95% CI 0.08–0.75) were associated with incident MCI/dementia in the final model. APOE ε4 allele frequency was 24%; heterozygous or homozygous ε4 was associated with incident MCI/dementia (bivariate OR 3.96, 95% CI 1.25–12.50).DiscussionThese findings provide evidence for higher dementia incidence in Aboriginal Australians from urban areas, where the majority of Aboriginal people reside. This study also sheds light on sociodemographic, health, and genetic factors associated with incident MCI/dementia at older ages in this population, which is critical for targeted prevention strategies.

An important aspect of the work that takes place in and across our Aboriginal Health and Ageing research group is about building partnerships between Aboriginal and Torres Strait Islander peoples and non-Indigenous people. Partnerships are created between colleagues and co-researchers as well as with community Elders, Aboriginal community-controlled organisations, community groups and associations and individuals.To fully realise this has required an introspective look at the way we function as a team of Aboriginal researchers and non-Indigenous researchers working together. It has challenged us to explore and determine our shared visions and shared outcomes and to develop strong, enduring and authentic partnerships by putting culture at the centre of everything we do.This wisdom-led approach has fostered the development of a shared narrative about research WITH Aboriginal and Torres Strait Islander communities and a shared language of research collaboration.This paper aims to provide an opportunity to reflect on the key elements of co-design which have underpinned our work together across cultures both within team and within community.This paper will provide lived examples of the co-design and co-creation process utilised by our team in working with community. It will further share a model which underpins these experiences. It provides a framework to refer to and reflect upon, which commits to working with shared respect, shared meaning, shared knowledge and an enriched experience of collaboratively working and walking and learning together.

Introduction/Background* The accelerated US Food and Drug Administration approval of pembrolizumab validated the efficacy of anti-PD-(L)1 therapy for patients with recurrent/metastatic cervical cancer; however, the objective response rate (ORR) with pembrolizumab was 14.3% in patients with PD-L1–expressing tumours. Human papillomavirus infection is implicated in >95% of cervical cancers and is linked to upregulation of TGF-β signalling. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β ‘trap’) fused to a human immunoglobulin G1 monoclonal antibody blocking PD-L1. We report pooled safety and efficacy in patients with pretreated, immune checkpoint inhibitor-naive, recurrent/metastatic cervical cancer treated with bintrafusp alfa in phase 1 (INTR@PID 001; NCT02517398) and phase 2 (study 012; NCT03427411) studies. Methodology Patients received bintrafusp alfa 0.3-30 mg/kg (phase 1 dose escalation) or 1200 mg every 2 weeks (phase 1 dose expansion and phase 2) until progressive disease, unacceptable toxicity, or withdrawal. Treatment past progression was allowed. Primary endpoints were safety (phase 1 dose escalation) and best overall response per RECIST 1.1 (phase 1 dose expansion and phase 2). Result(s)* As of May 15, 2020 (phase 1) and December 22, 2020 (phase 2), 39 patients had received bintrafusp alfa for a median duration of 2.8 months (range, 0.5-19.3). The median follow-up to data cutoff was 35.0 months and 24.1 months for the phase 1 and phase 2 studies, respectively. All patients had received prior anticancer therapy; 16 (41.0%) had received ≥3 regimens. Confirmed ORR was 28.2% (table 1); responses occurred irrespective of Moore criteria (phase 1), tumour histology, prior bevacizumab treatment, or radiation treatment. Median overall survival was 13.4 months. No new safety signals and no treatment-related deaths were observed; side effects were manageable. Conclusion* Bintrafusp alfa had a manageable safety profile and demonstrated clinical activity in patients with heavily pretreated, immune checkpoint inhibitor-naive recurrent/metastatic cervical cancer. © 2021 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2021 ASCO Annual Meeting. All rights reserved.

Aboriginal Australians are disproportionately affected by dementia, with incidence in remote populations approximately double that of non-Indigenous populations. This study aimed to identify dementia incidence and risk factors in Aboriginal Australians residing in urban areas, which are currently unknown.A population-based cohort of Aboriginal Australians ≥60 years of age was assessed at baseline and 6-year follow-up. Life-course risk factors (baseline) were examined for incident dementia or mild cognitive impairment (MCI) through logistic regression analyses; adjustments were made for age.Data were included from 155 participants 60 to 86 years of age (mean 65.70 years, SD 5.65 years; 59 male). There were 16 incident dementia cases (age-standardized rate 35.97/1,000 person-years, 95% confidence interval [CI] 18.34-53.60) and 36 combined incident MCI and dementia cases. Older age (odds ratio [OR] 2.29, 95% CI 1.42-3.70), male sex (OR 4.14, 95% CI 1.60-10.77), unskilled work history (OR 5.09, 95% CI 1.95-13.26), polypharmacy (OR 3.11, 95% CI 1.17-8.28), and past smoking (OR 0.24, 95% CI 0.08-0.75) were associated with incident MCI/dementia in the final model.These findings provide evidence for higher dementia incidence in Aboriginal Australians from urban areas, where the majority of Aboriginal people reside. This study also sheds light on sociodemographic, health, and genetic factors associated with incident MCI/dementia at older ages in this population, which is critical for targeted prevention strategies.

While there is strong evidence of the need for healthy ageing programs for older Aboriginal Australians, few are available. It is important to understand older Aboriginal Australians&rsquo, perspectives on healthy ageing in order to co-design culturally-appropriate programs, including views on technology use in this context. Semi-structured interviews were conducted with 34 Aboriginal Australians aged 50 years and older from regional and urban communities to explore participants&rsquo, health concerns, preferences for healthy ageing programs, and receptiveness to technology. Qualitative data were analyzed using a grounded theory approach. This study found that older Aboriginal Australians are concerned about chronic health conditions, social and emotional well-being, and difficulties accessing health services. A range of barriers and enablers to participation in current health programs were identified. From the perspective of older Aboriginal people, a successful healthy ageing program model includes physical and cognitive activities, social interaction, and health education. The program model also provides culturally safe care and transport for access as well as family, community, cultural identity, and empowerment regarding ageing well as central tenets. Technology could also be a viable approach for program delivery. These findings can be applied in the implementation and evaluation of culturally-appropriate, healthy ageing programs with older Aboriginal people.

Objectives To determine preferences for health and aged care services in Aboriginal and Torres Strait Islander Australians and explore related factors. Methods Mixed-method, cross-sectional study including 336 Aboriginal and Torres Strait Islander people aged 60 years and older from regional and urban areas. Results Exclusive preference for Aboriginal Community Controlled services was most common. This preference significantly increased when preferences for, and use of, aged care and disability services were considered. The likelihood of holding an exclusive preference for Aboriginal Community Controlled services was higher in regional settings compared to urban and in those reporting lower engagement in traditional activities during childhood. Conclusions These findings suggest that the majority of older Australian Aboriginal and Torres Strait Islander people prefer aged and disability care provided by Aboriginal services. Given the anticipated increase in service demand in this population, there is a growing need for culturally safe services, particularly in regional settings.

Biofilms provide physical, mechanical and chemical protection for microbes from their external environment, necessitating the use of harsh chemicals (such as sanitisers and antimicrobials) and abrasive cleaning (brushing or pigging) for their control. Biofilms have a broad impact upon the manufacturing of a wide range of fast-moving consumer goods, and biofilm contamination during their manufacture can lead to production interruption and significant economic costs to industry for cleaning and sanitisation. Biofilms formed by Pseudomonas aeruginosa (Ps. a.), a major contaminant of industrial processes, have yet to be studied in-depth with respect to the changes that occur in response to high-flow shear conditions from a combined physical and biological perspective. The central aims of this work were to understand and elucidate the biological response of Ps. a. biofilms when grown under different, industrially-relevant fluid flow conditions; to characterise the mechanisms through which Ps. a. produces phenotypic responses, and how these in turn affect biofilm architecture. Two strains of Ps. a., PA01 and PA14, were used, known to differentially produce two exopolysaccharides (Psl and Pel respectively), integral components in the biofilm’s protective extracellular matrix (Colvin et al. 2012). To investigate the effect of shear stress on biofilm formation, the CDC Bioreactor (CBR) was used to grow biofilms on polyethylene coupons under high or low shear conditions for 96 hours. At 24, 48, 72 and 96-hour timepoints, coupons containing biofilms were removed from the CBR and analysed by confocal laser scanning microscopy (CSLM) and biochemical assays. Exopolysaccharide (EPS) production was quantified by CSLM image analysis in Fiji. In order to determine how EPS organisation effects wider biofilm architecture and individual structures within a maturing biofilm, Psl and Pel localisation and distribution throughout biofilms was assessed. Under low and high shear conditions, the architecture of PA01 and PA14 biofilms was compared to further identify similarities and differences in their phenotypic responses to shear stress. We will present data that shows that Psl and Pel have distinct localisation patterns throughout PA01 and PA14 biofilms over our selected time course. PA01 and PA14 were shown to produce varying amounts of the exopolysaccharides Psl and Pel in mature biofilm structures (i.e. mushroom colonies) and throughout the entire biofilm population. Early adhesion, colony morphology and overall biofilm architecture was shown to be considerably affected by shear. Hydrodynamic conditions impose shear stress on Ps. a. biofilms, in turn affecting the structural components that make up their mature architecture. Reference: Colvin, K.M., Irie, Y., and Tart, C.S. et al. (2012). The Pel and Psl polysaccharides provide Pseudomonas aeruginosa structural redundancy within the biofilm matrix. Environmental Microbiology, 14(8):1913-28.

First Nations 'survivors' are ageing in increasing numbers. Life-course stress and depression are of concern for older First Nations Australians, yet there are limited psychosocial interventions. This study aimed to co-design a culturally-grounded mindfulness-based program ('Ngarraanga Giinganay') and evaluate acceptability/feasibility with an Aboriginal community on Gumbaynggirr Country. An expert Working Group guided program development, with Aboriginal and non-Aboriginal clinicians/consultants. A workshop, collaborative yarning group with older Aboriginal people (n = 9), and further consultation contributed to the design/refinement of the 8-session group-based program, ensuring content aligned with therapeutic principles of mindfulness and cultural understandings of the Gumbaynggirr community. A single-group pilot study was conducted (n = 7, 62-81 years), co-facilitated by an Aboriginal clinician and Elder. Outcomes were qualitative (understandings of mindfulness, program acceptability, benefits to health/wellbeing). Pilot results demonstrated feasibility, acceptability and preliminary effectiveness. The program enhanced understandings of mindfulness and participants highlighted benefits such as helping anxiety, relaxation, focusing on the moment and connection to Country/land. Trends were seen for reducing depression, anxiety and stress symptoms, and blood pressure. This study provides insight into partnering with underrepresented populations through ageing research, highlighting the effectiveness of this co-design approach. Ngarraanga Giinganay has considerable potential for supporting health and wellbeing of First Nations peoples.

3022 Background: The phosphatidylinositol 3-kinase (PI3K) pathway is a promising target in cancer. CH5132799 is a novel PI3K inhibitor, selectively inhibiting class I PI3Ks (α, β, δ and γ) with no inhibition of class II and III or mTOR, and with potent antitumor activity in preclinical studies (Tanaka et al, Clin Cancer Res; 17; 3272-81, 2011). First-in-human study objectives were determination of maximum tolerated dose (MTD), safety/tolerability, PK/PD and clinical activity (RECIST). Methods: A 3+3 dose escalation design was used. The initial dosing schedule of CH5132799(schedule A) was once a day (QD). Due to a relatively short half-life, a twice a day (BID) schedule (schedule B) was introduced. PK profiles were studied over 72 hours. PD analyses included quantification of various phosphoproteins in platelet rich plasma (PRP). Tumor assessments were performed at baseline and cycle 3 day 1 (C3D1) and FDG-PET scans at baseline, C1D8 and C3D1. Results: 29 patients (pts) with a variety of solid tumors have been treated (A 23 pts, B 6 pts, the most common tumors were breast, oesophageal, colorectal and ovarian). The starting doses were 2 mg (A) and 48 mg (B). The current doses being explored are 96 mg (A) and 72 mg (B). The most frequently reported drug-related AEs were Grade 1/2 diarrhea, nausea, fatigue, anorexia and anemia. 1 DLT (Grade 3 elevated LFT) was observed in a hepatocellular carcinoma pt at 48 mg BID. MTD has not yet been determined. The preliminary mean ±SD Cmax and AUC at 96 mg QD were 202±129 ng/ml and 1407±935 ng·hr/ml respectively, which is consistent with an efficacious exposure based on preclinical models. Some patients achieved the expected exposure at over 32 mg. From single dose of 48mg there was a reduction of phosphorylation of AKT in PRP after treatment, consistent with pathway modulation. A patient with clear cell ovarian cancer and a PIK3CA mutation treated at 48 mg BID showed >50% decrease in SUV on a PET scan at C1D8 and a 75% decrease in CA-125 at C2D1. 5 pts exhibited SD (>8 weeks). Conclusions: CH5132799 is well tolerated either QD ≤96 mg or BID ≤48 mg. Dose-escalation continues and updated safety/efficacy/PK/PD data will be presented.