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Circulating epigenomic biomarkers correspond with kidney disease susceptibility in high-risk populations with type 2 diabetes mellitus
(Elsevier BV, 2023) Khurana, Ishant; Howard, Natasha; Maxwell, Scott; Preez, Anelle Du; Kaipananickala, Harikrishnan; Breen, Jimmy; Buckberry , Sam; Okabe, Jun; Al-Hasani, Keith; Nakasatien, Soontaree; Himathongkam, AI Thep; Brown, Alex
Aims: To investigate epigenomic indices of diabetic kidney disease (DKD) susceptibility among high-risk populations with type 2 diabetes mellitus. Methods: KDIGO (Kidney Disease: Improving Global Outcomes) clinical guidelines were used to classify people living with or without DKD. Differential gene methylation of DKD was then assessed in a discovery Aboriginal Diabetes Study cohort (PROPHECY, 89 people) and an external independent study from Thailand (THEPTARIN, 128 people). Corresponding mRNA levels were also measured and linked to levels of albuminuria and eGFR. Results: Increased DKD risk was associated with reduced methylation and elevated gene expression in the PROPHECY discovery cohort of Aboriginal Australians and these findings were externally validated in the THEPTARIN diabetes registry of Thai people living with type 2 diabetes mellitus. Conclusions: Novel epigenomic scores can improve diagnostic performance over clinical modelling using albuminuria and GFR alone and can distinguish DKD susceptibility.
Hyperprogressive Disease (HPD) in Solid Tumours Receiving Immune Checkpoint Inhibitors in a Real-World Setting
(Adenine Press, 2023) Kanjanapan, Yada; Guduguntla, Geetha; Varikara, Ashwati Krishnan; Szajer, Jeremy; Yip, Desmond; Cockburn, John; Fadia, Mitali
Introduction: Hyperprogressive disease (HPD) is a state of accelerated tumor growth from cancer immunotherapy, associated with poor outcome. The reported incidence is 6% to 29% among studies using varying definitions of HPD, with no predictive biomarkers. Tumor infiltrating lymphocytes (TILs) are prognostic and predictive for immunotherapy benefit in various tumor types, but have only been tested for correlation with HPD in one study. Objectives: The objective of the study was to determine the prevalence of HPD in solid tumor patients treated with immune checkpoint inhibitor therapy in a real-world setting, and to assess clinicopathological features as potential biomarkers for HPD. Methods: We conducted a retrospective analysis of solid tumor patients treated with immune checkpoint inhibitors at a single institution. Imaging pre-immunotherapy and postimmunotherapy were assessed for HPD, and correlated against clinicopathological factors, including TILs and programmed death-ligand 1 (PD-L1) status through archival tumor assessment. HPD was defined per Matos et al as response evaluation criteria in solid tumors (RECIST) progressive disease, minimum increase in measurable lesions of 10 mm, plus increase of ≥40% in sum of target lesions compared with baseline and/or increase of ≥20% in sum of target lesions compared with baseline plus new lesions in at least 2 different organs. Results: HPD occurred in 11 of 87 patients (13%), and associated with inferior overall survival (median 5.5 months vs 18.3 months, P = .002). However, on multivariate analysis, only liver metastases (hazard ratio [HR] 4.66, 95% confidence interval [CI] 2.27-9.56, P < .001) and PD-L1 status (HR 0.53, 95% CI 0.30-0.95, P = .03) were significantly associated with survival. Presence of liver metastases correlated with occurence of HPD (P = .01). Age, sex, and monotherapy versus combination immunotherapy were not predictive for HPD. PD-L1 status and TILs were not associated with HPD. Conclusions: We found 13% HPD among solid tumor patients treated with immunotherapy, consistent with the range reported in prior series. Assessment for HPD is feasible outside of a clinical trials setting, using modified criteria that require comparison of 2 imaging studies. Liver metastases were associated with risk of HPD, while TILs and PD-L1 status were not predictive for HPD.
Australian academic libraries and the United Nations Sustainable Development Goals
(Sage, 2024-05-30) Missingham, Roxanne
The United Nations Sustainable Development Goals have created an opportunity for the library sector to reconceptualise the services delivered to their communities. They provide the opportunity for libraries to be involved in national policy discussions and for their work to be translated into national programs for economic and social development. This article uses Australia as a case study of academic libraries in a broader policy context. The academic library community has built on many decades of work supporting social justice to set the scene to enable a significant contribution to be made to address the Sustainable Development Goals. The contribution that libraries have made has the potential to be reflected in university-wide reporting. The emergence of international university rankings on sustainability is assessed to review potential areas of impact. It is found that the most effective work to date has been collaborative. Further collaboration can contribute to strategic national planning and reporting.
Unpacking and validating the "physiological adaptation" core concept of physiology
(American Physiological Society, 2023-10-09) Estaphan, Suzanne; Wadley, Glenn D; Todd, Gabrielle; Towstoless, Michelle; Hryciw, Deanne H; Lexis, Louise; Hayes, Alan; Tangalakis, Kathy
A national Task Force of 25 Australian physiology educators used the Delphi protocol to develop seven physiology core concepts that were agreed to nationally. The aim of the current study was to unpack the “physiological adaptation” core concept with the descriptor “organisms adjust and adapt to acute and chronic changes in the internal and external environments across the lifespan.” This core concept was unpacked by three Task Force members and a facilitator into four themes and nine subthemes that encompass the role of stressors and disturbed homeostasis in adaptation and the capacity for, and the nature of, the physiological adaptation. Twenty-two Task Force members then provided feedback and rated the themes and subthemes for level of importance and difficulty for students to learn via an online survey using a five-point Likert scale. Seventeen respondents completed all survey questions. For all themes/subthemes, importance was typically rated 1 (Essential) or 2 (Important) (n = 17, means ±SD ranged from 1.1 ± 0.3 to 2.2 ± 0.9), and difficulty was typically rated 3 (Moderately Difficult) (n = 17, means ranged from 2.9 ± 0.7 to 3.4 ± 0.9). Subtle differences in the proportion of importance scores (n = 17, Fisher’s exact: P = 0.004, ANOVA: F12,220 = 2.630, P = 0.003; n = 22, Fisher’s exact: P = 0.002, ANOVA: F12,281 = 2.743, P < 0.001), but not difficulty scores, were observed between themes/subthemes, and free-text feedback was minor. The results suggest successful unpacking of the physiological adaptation core concept. The themes and subthemes can inform the design of learning outcomes, assessment, and teaching and learning activities that have commonality and consistency across curricula.
