Genomic characterisation of clinically significant blood group variants in Aboriginal Australians.

BACKGROUND: Hematological disorders are often treated with blood transfusions. Many blood group antigens and variants are population-specific, and for patients with rare blood types, extensive donor screening is required to find suitable matches for transfusion. There is a scarcity of knowledge regarding blood group variants in Aboriginal Australian populations, despite a higher need for transfusion due to the higher prevalence of renal diseases and anaemia. MATERIALS AND METHODS: In this study, we applied next-generation sequencing and analysis to 245 samples obtained from Aboriginal Australians from South-East Queensland, to predict antigen phenotypes for 36 blood group systems. RESULTS: We report potential weak antigens in blood group systems RH, FY and JR that have potential clinical implications in transfusion and pregnancy settings. These include partial DIII type 4, weak D type 33, and Del RHD (IVS2-2delA). The rare Rh phenotypes D+ C+ E+ c- e+ and D+ C+ E+ c+ e- were also detected. DISCUSSION: The comprehensive analyses of blood group genetic variant profiles identified in this study will provide insight and an opportunity to improve Aboriginal health by aiding in the identification of appropriate blood products for population-specific transfusion needs.

2023 Australian guideline for assessing and managing cardiovascular disease risk.

INTRODUCTION: The 2023 Australian guideline for assessing and managing cardiovascular disease risk provides updated evidence-based recommendations for the clinical assessment and management of cardiovascular disease (CVD) risk for primary prevention. It includes the new Australian CVD risk calculator (Aus CVD Risk Calculator), based on an equation developed from a large New Zealand cohort study, customised and recalibrated for the Australian population. The new guideline replaces the 2012 guideline that recommended CVD risk assessment using the Framingham risk equation. MAIN RECOMMENDATIONS: The new guideline recommends CVD risk assessment in people without known CVD: all people aged 45-79 years, people with diabetes from 35 years, and First Nations people from 30 years. The new Aus CVD Risk Calculator should be used to estimate and categorise CVD risk into low (< 5% risk over five years), intermediate (5% to < 10% risk over five years) or high risk (≥ 10% over five years). The following reclassification factors may be applied to recategorise calculated risk to improve accuracy of risk prediction, particularly in individuals close to a risk threshold: Indigenous status/ethnicity, estimated glomerular filtration rate, urine albumin to creatinine ratio measurements, severe mental illness, coronary artery calcium score and family history of premature CVD. A variety of communication formats is available to communicate CVD risk to help enable shared decision making. Healthy lifestyle modification, including smoking cessation, nutrition, physical activity and limiting alcohol, is encouraged for all individuals. Blood pressure-lowering and lipid-modifying pharmacotherapies should be prescribed for high risk and considered for intermediate risk individuals, unless contraindicated or clinically inappropriate. Reassessment of CVD risk should be considered within five years for individuals at low risk and within two years for those with intermediate risk. Reassessment of CVD risk is not recommended for individuals at high risk. CHANGES IN ASSESSMENT AND MANAGEMENT AS A RESULT OF THE GUIDELINE: The updated guideline recommends assessment over a broader age range and uses the Aus CVD Risk Calculator, which replaces the previous Framingham-based equation. It incorporates new variables: social disadvantage, diabetes-specific risk markers, diagnosis of atrial fibrillation and use of blood pressure-lowering and lipid-modifying therapies. Reclassification factors are also a new addition. Updated risk categories and thresholds are based on the new Aus CVD Risk Calculator. The proportion of the population in the high risk category (≥ 10% over five years) is likely to be broadly comparable to more than 15% risk from the Framingham-based equation. The full guideline and Aus CVD Risk Calculator can be accessed at www.cvdcheck.org.au.

Priority setting: Development of the South Australian Aboriginal Chronic Disease Consortium RoadMap for Action.

ISSUES ADDRESSED: Aboriginal and Torres Strait Islander (Aboriginal) people in South Australia are overburdened by cardiovascular disease, diabetes and cancer. The South Australian Aboriginal Chronic Disease Consortium (Consortium) was established in June 2017 as a collaborative partnership to lead the implementation of three state-wide chronic disease plans using a strategic approach to identifying key priority areas for action. METHODS: In 2017-2018, the Consortium Coordinating Centre facilitated a priority setting process, which involved extensive consultation, including a prioritisation survey and stakeholder workshops. The Consortium's Aboriginal Community Reference Group was instrumental in leading the identification of priorities for action. RESULTS: The Consortium RoadMap for Action identified seven across-plan priorities and six condition-specific priorities. It acknowledged that: strengthening social and emotional well-being is central to improving health outcomes; prevention and early detection, acute management and ongoing management are all components of the continuum of care; and improving access to services, strengthening the workforce, and monitoring and evaluation are required across the continuum of care. CONCLUSION: Widespread implementation failure in the past across the health system and health services implementation and research translation highlights the value of the Consortium approach and its commitment to implementing the state-wide chronic disease plans in a collaborative manner. The Consortium relies on and fosters cross-sectoral alignment, with all key players including all public, private and Aboriginal Community Controlled health services, to progress its priorities and aspirations to improve health outcomes for Aboriginal people using evidence-based strategies. SO WHAT?: Rigorous and transparent priority setting processes that bring together research, clinical practice, health services operations, policy and community perspectives can foster intersectoral collaboration and partnership and support the implementation of shared priorities.

Beyond Explored Functionals: A Computational Journey of Two-Photon Absorption.

We present a thorough investigation into the efficacy of 19 density functional theory (DFT) functionals, relative to RI-CC2 results, for computing two-photon absorption (2PA) cross sections (σ2PA) and key dipole moments (|µ00|, |µ11|, |Δµ|, |µ01|) for a series of coumarin dyes in the gas-phase. The functionals include different categories, including local density approximation (LDA), generalized gradient approximation (GGA), hybrid-GGA (H-GGA), range-separated hybrid-GGA (RSH-GGA), meta-GGA (M-GGA), and hybrid M-GGA (HM-GGA), with 14 of them being subjected to analysis for the first time with respect to predicting σ2PA values. Analysis reveals that functionals integrating both short-range (SR) and long-range (LR) corrections, particularly those within the RSH-GGA and HM-GGA classes, outperform the others. Furthermore, the range-separation approach was found more impactful compared to the varying percentages of Hartree-Fock exchange (HF Ex) within different functionals. The functionals traditionally recommended for 2PA do not appear among the top 9 in our study, which is particularly interesting, as these top-performing functionals have not been previously investigated in this context. This list is dominated by M11, QTP variants, ωB97X, ωB97X-V, and M06-2X, surpassing the performance of other functionals, including the commonly used CAM-B3LYP.

Workforce training needs to address social and emotional wellbeing in home-based Aboriginal and Torres Strait Islander aged care.

ObjectiveTo explore the training needs of the home care workforce in supporting the social and emotional wellbeing (SEWB) of Aboriginal and Torres Strait Islander peoples receiving aged care services through the Home Care Package (HCP) Program.MethodsA mixed-methods design including (1) a focus group and interview with coordinators of HCP Program services for Aboriginal and Torres Strait Islander peoples across metropolitan and rural South Australia in April and June 2022, and (2) a desktop review of training, professional development opportunities and resources for existing and pre-entry workforce addressing the SEWB of Aboriginal and Torres Strait Islander peoples in aged care across the Vocational Education Training and higher education sectors in South Australia, the Australian Indigenous HealthInfoNet, the Department of Health and Aged Care website and aged care email alerts between December 2021 and September 2022.ResultsFive themes representing workforce training needs were identified: cultural safety, trauma-informed care, case management, compliance with funding rules and preferred formats for training. The desktop review identified a paucity of formal training, professional development and resources within the context of addressing the SEWB of Aboriginal and Torres Strait Islander peoples in aged care.ConclusionsThese findings suggest that ongoing practice-based professional development learning opportunities are needed within organisations to enhance peer-learning and support. These need to be available together with dedicated formal training programs and practical resources on meeting Aboriginal and Torres Strait Islander peoples' SEWB in aged care.

Determining the Optimal Methodology for Identifying Incident Stroke Deaths Using Administrative Datasets Within Australia.

BACKGROUND AND AIM: Quantifying stroke incidence and mortality is crucial for disease surveillance and health system planning. Administrative data offer a cost-effective alternative to "gold standard" population-based studies. However, the optimal methodology for establishing stroke deaths from administrative data remains unclear. We aimed to determine the optimal method for identifying stroke-related deaths in administrative datasets as the fatal component of stroke incidence, comparing counts derived using underlying and all causes of death (CoD). METHOD: Using whole-population multijurisdictional person-level linked data from hospital and death datasets from South Australia, the Northern Territory, and Western Australia, we identified first-ever stroke events between 2012 and 2015, using underlying CoD and all CoD to identify fatal stroke counts. We determined the 28-day case fatality for both counts and compared results with gold standard Australian population-based stroke incidence studies. RESULTS: The total number of incident stroke events was 16,150 using underlying CoD and 18,074 using all CoD. Case fatality was 24.7% and 32.7% using underlying and all CoD, respectively. Case fatality using underlying CoD was similar to that observed in four Australian "gold standard" population-based studies (20%-24%). CONCLUSIONS: Underlying CoD generates fatal incident stroke estimates more consistent with population-based studies than estimates based on stroke deaths identified from all-cause fields in death registers.

Synthesis, Structure, and Properties of 2O-BaPtO3, a Phase Derived from Hexagonal Perovskite.

We have made the compound 2O-BaPtO3 by high-pressure, high-temperature synthesis, determined its structure, and tested its catalytic activity. Compounds of the same stoichiometry have been reported and tentatively identified as hexagonal perovskites, and although no structural model was ever established, 2O-BaPtO3 is clearly different and, to the best of our knowledge, unique. It features continuous chains of face-sharing PtO6 octahedra, like the well-known 2H hexagonal perovskite type, but with a staggered offset between the chains that breaks hexagonal symmetry and disrupts the close-packed array of A = Ba and X = O that is a defining characteristic of ABX3 perovskites. We investigated this structure and its stability vs the conventional 2H form using X-ray and neutron diffraction, X-ray absorption spectroscopy, and ab initio calculations. Catalytic testing of 2O-BaPtO3 showed that it is active for hydrogen evolution.

Codesigning enhanced models of care for Northern Australian Aboriginal and Torres Strait Islander youth with type 2 diabetes: study protocol.

INTRODUCTION: Premature onset of type 2 diabetes and excess mortality are critical issues internationally, particularly in Indigenous populations. There is an urgent need for developmentally appropriate and culturally safe models of care. We describe the methods for the codesign, implementation and evaluation of enhanced models of care with Aboriginal and Torres Strait Islander youth living with type 2 diabetes across Northern Australia. METHODS AND ANALYSIS: Our mixed-methods approach is informed by the principles of codesign. Across eight sites in four regions, the project brings together the lived experience of Aboriginal and Torres Strait Islander young people (aged 10-25) with type 2 diabetes, their families and communities, and health professionals providing diabetes care through a structured yet flexible codesign process. Participants will help identify and collaborate in the development of a range of multifaceted improvements to current models of care. These may include addressing needs identified in our formative work such as the development of screening and management guidelines, referral pathways, peer support networks, diabetes information resources and training for health professionals in youth type 2 diabetes management. The codesign process will adopt a range of methods including qualitative interviews, focus group discussions, art-based methods and healthcare systems assessments. A developmental evaluation approach will be used to create and refine the components and principles of enhanced models of care. We anticipate that this codesign study will produce new theoretical insights and practice frameworks, resources and approaches for age-appropriate, culturally safe models of care. ETHICS AND DISSEMINATION: The study design was developed in collaboration with Aboriginal and Torres Strait Islander and non-Indigenous researchers, health professionals and health service managers and has received ethical approval across all sites. A range of outputs will be produced to disseminate findings to participants, other stakeholders and the scholarly community using creative and traditional formats.

Incidence of Stroke in Indigenous Populations of Countries With a Very High Human Development Index: A Systematic Review.

BACKGROUND AND OBJECTIVES: Cardiovascular disease contributes significantly to disease burden among many Indigenous populations. However, data on stroke incidence in Indigenous populations are sparse. We aimed to investigate what is known of stroke incidence in Indigenous populations of countries with a very high Human Development Index (HDI), locating the research in the broader context of Indigenous health. METHODS: We identified population-based stroke incidence studies published between 1990 and 2022 among Indigenous adult populations of developed countries using PubMed, Embase, and Global Health databases, without language restriction. We excluded non-peer-reviewed sources, studies with fewer than 10 Indigenous people, or not covering a 35- to 64-year minimum age range. Two reviewers independently screened titles, abstracts, and full-text articles and extracted data. We assessed quality using "gold standard" criteria for population-based stroke incidence studies, the Newcastle-Ottawa Scale for risk of bias, and CONSIDER criteria for reporting of Indigenous health research. An Indigenous Advisory Board provided oversight for the study. RESULTS: From 13,041 publications screened, 24 studies (19 full-text articles, 5 abstracts) from 7 countries met the inclusion criteria. Age-standardized stroke incidence rate ratios were greater in Aboriginal and Torres Strait Islander Australians (1.7-3.2), American Indians (1.2), Sámi of Sweden/Norway (1.08-2.14), and Singaporean Malay (1.7-1.9), compared with respective non-Indigenous populations. Studies had substantial heterogeneity in design and risk of bias. Attack rates, male-female rate ratios, and time trends are reported where available. Few investigators reported Indigenous stakeholder involvement, with few studies meeting any of the CONSIDER criteria for research among Indigenous populations. DISCUSSION: In countries with a very high HDI, there are notable, albeit varying, disparities in stroke incidence between Indigenous and non-Indigenous populations, although there are gaps in data availability and quality. A greater understanding of stroke incidence is imperative for informing effective societal responses to socioeconomic and health disparities in these populations. Future studies into stroke incidence in Indigenous populations should be designed and conducted with Indigenous oversight and governance to facilitate improved outcomes and capacity building. REGISTRATION INFORMATION: PROSPERO registration: CRD42021242367.

Strategies used for childhood chronic functional constipation: the SUCCESS evidence synthesis.

Background: Up to 30% of children have constipation at some stage in their life. Although often short-lived, in one-third of children it progresses to chronic functional constipation, potentially with overflow incontinence. Optimal management strategies remain unclear. Objective: To determine the most effective interventions, and combinations and sequences of interventions, for childhood chronic functional constipation, and understand how they can best be implemented. Methods: Key stakeholders, comprising two parents of children with chronic functional constipation, two adults who experienced childhood chronic functional constipation and four health professional/continence experts, contributed throughout the research. We conducted pragmatic mixed-method reviews. For all reviews, included studies focused on any interventions/strategies, delivered in any setting, to improve any outcomes in children (0-18 years) with a clinical diagnosis of chronic functional constipation (excluding studies of diagnosis/assessment) included. Dual reviewers applied inclusion criteria and assessed risk of bias. One reviewer extracted data, checked by a second reviewer. Scoping review: We systematically searched electronic databases (including Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature) (January 2011 to March 2020) and grey literature, including studies (any design) reporting any intervention/strategy. Data were coded, tabulated and mapped. Research quality was not evaluated. Systematic reviews of the evidence of effectiveness: For each different intervention, we included existing systematic reviews judged to be low risk of bias (using the Risk of Bias Assessment Tool for Systematic Reviews), updating any meta-analyses with new randomised controlled trials. Where there was no existing low risk of bias systematic reviews, we included randomised controlled trials and other primary studies. The risk of bias was judged using design-specific tools. Evidence was synthesised narratively, and a process of considered judgement was used to judge certainty in the evidence as high, moderate, low, very low or insufficient evidence. Economic synthesis: Included studies (any design, English-language) detailed intervention-related costs. Studies were categorised as cost-consequence, cost-effectiveness, cost-utility or cost-benefit, and reporting quality evaluated using the consensus health economic criteria checklist. Systematic review of implementation factors: Included studies reported data relating to implementation barriers or facilitators. Using a best-fit framework synthesis approach, factors were synthesised around the consolidated framework for implementation research domains. Results: Stakeholders prioritised outcomes, developed a model which informed evidence synthesis and identified evidence gaps. Scoping review: 651 studies, including 190 randomised controlled trials and 236 primary studies, conservatively reported 48 interventions/intervention combinations. Effectiveness systematic reviews: studies explored service delivery models (n = 15); interventions delivered by families/carers (n = 32), wider children's workforce (n = 21), continence teams (n = 31) and specialist consultant-led teams (n = 42); complementary therapies (n = 15); and psychosocial interventions (n = 4). One intervention (probiotics) had moderate-quality evidence; all others had low to very-low-quality evidence. Thirty-one studies reported evidence relating to cost or resource use; data were insufficient to support generalisable conclusions. One hundred and six studies described implementation barriers and facilitators. Conclusions: Management of childhood chronic functional constipation is complex. The available evidence remains limited, with small, poorly conducted and reported studies. Many evidence gaps were identified. Treatment recommendations within current clinical guidelines remain largely unchanged, but there is a need for research to move away from considering effectiveness of single interventions. Clinical care and future studies must consider the individual characteristics of children. Study registration: This study is registered as PROSPERO CRD42019159008. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 128470) and is published in full in Health Technology Assessment; Vol. 28, No. 5. See the NIHR Funding and Awards website for further award information.

Between 5% and 30% of children experience constipation at some stage. In one-third of these children, this progresses to chronic functional constipation. Chronic functional constipation affects more children with additional needs. We aimed to find and bring together published information about treatments for chronic functional constipation, to help establish best treatments and treatment combinations. We did not cover assessment or diagnosis of chronic functional constipation. This project was guided by a 'stakeholder group', including parents of children with constipation, people who experienced constipation as children, and healthcare professionals/continence experts. We carried out a 'scoping review' and a series of 'systematic reviews'. Our 'scoping review' provides an overall picture of research about treatments, with 651 studies describing 48 treatments. This helps identify important evidence gaps. 'Systematic reviews' are robust methods of bringing together and interpreting research evidence. Our stakeholder group decided to structure our systematic reviews to reflect who delivered the interventions. We brought together evidence about how well treatments worked when delivered by families/carers (32 studies), the wider children's workforce (e.g. general practitioner, health visitor) (21 studies), continence teams (31 studies) or specialist consultant-led teams (42 studies). We also considered complementary therapies (15 studies) and behavioural strategies (4 studies). Care is affected by what is done and how it is done. We brought together evidence about different models of delivering care (15 studies), barriers and facilitators to implementation of treatments (106 studies) and costs (31 studies). Quality of evidence was mainly low to very low. Despite numerous studies, there was often insufficient information to support generalisable conclusions. Our findings generally agreed with current clinical guidelines. Management of childhood chronic functional constipation should be child-centred, multifaceted and adapted according to the individual child, their needs, the situation in which they live and the health-care setting in which they are looked after. Research is needed to address our identified evidence gaps.

Low baseline ribosome-related gene expression and resistance training-induced declines in ribosome-related gene expression are associated with skeletal muscle hypertrophy in young men and women.

Ribosomes are essential cellular machinery for protein synthesis. It is hypothesised that ribosome content supports muscle growth and that individuals with more ribosomes have greater increases in muscle size following resistance training (RT). Aerobic conditioning (AC) also elicits distinct physiological adaptations; however, no measures of ribosome content following AC have been conducted. We used ribosome-related gene expression as a proxy measure for ribosome content and hypothesised that AC and RT would increase ribosome-related gene expression. Fourteen young men and women performed 6 weeks of single-legged AC followed by 10 weeks of double-legged RT. Muscle biopsies were taken following AC and following RT in the aerobically conditioned (AC+RT) and unconditioned (RT) legs. No differences in regulatory genes (Ubf, Cyclin D1, Tif-1a and Polr-1b) involved in ribosomal biogenesis or ribosomal RNA (45S, 5.8S, 18S and 28S rRNAs) expression were observed following AC and RT, except for c-Myc (RT > AC+RT) and 5S rRNA (RT < AC+RT at pre-RT) with 18S external transcribed spacer and 5.8S internal transcribed spacer expression decreasing from pre-RT to post-RT in the RT leg only. When divided for change in leg-lean soft tissue mass (ΔLLSTM) following RT, legs with the greatest ΔLLSTM had lower expression in 11/13 measured ribosome-related genes before RT and decreased expression in 9/13 genes following RT. These results indicate that AC and RT did not increase ribosome-related gene expression. Contrary to previous research, the greatest increase in muscle mass was associated with lower changes in ribosome-related gene expression over the course of the 10-week training programme. This may point to the importance of translational efficiency rather than translational capacity (i.e. ribosome content) in mediating long-term exercise-induced adaptations in skeletal muscle.

Development of Better Aptamers: Structured Library Approaches, Selection Methods, and Chemical Modifications.

Systematic evolution of ligands by exponential enrichment (SELEX) has been used to discover thousands of aptamers since its development in 1990. Aptamers are short single-stranded oligonucleotides capable of binding to targets with high specificity and selectivity through structural recognition. While aptamers offer advantages over other molecular recognition elements such as their ease of production, smaller size, extended shelf-life, and lower immunogenicity, they have yet to show significant success in real-world applications. By analyzing the importance of structured library designs, reviewing different SELEX methodologies, and the effects of chemical modifications, we provide a comprehensive overview on the production of aptamers for applications in drug delivery systems, therapeutics, diagnostics, and molecular imaging.

Microvascular flow ultrasound imaging for retinoblastoma.

PURPOSE: To present the results of a pilot study of microvascular flow imaging (MFI) in characterizing tumor vasculature of retinoblastoma. METHODS: The medical records of consecutive patients with retinoblastoma presenting at our institution between July 2019 and June 2022 that were imaged using MFI were reviewed retroactively. Each patient underwent diagnostic evaluation according to standard of care by examination under anesthesia with fluorescein angiography and ocular ultrasound imaging, including color Doppler and MFI. RESULTS: Thirteen eyes of 10 patients with retinoblastoma were included. MFI showed a prominent feeder vessel in 8 eyes, basket vasculature in 6 eyes and tumor bed vascularity in 10 eyes. MFI showed a more extensive vascular branching pattern that was not visible on color Doppler and fluorescein angiography in all eyes. CONCLUSIONS: MFI of retinoblastoma patients could add information about tumor vascularity not detectable by color Doppler or fluorescein angiography. Further study is needed to determine whether this information could be used to predict prognosis for ocular salvage and tumor response to treatment.

A fast ceramic mixed OH-/H+ ionic conductor for low temperature fuel cells.

Low temperature ionic conducting materials such as OH- and H+ ionic conductors are important electrolytes for electrochemical devices. Here we show the discovery of mixed OH-/H+ conduction in ceramic materials. SrZr0.8Y0.2O3-δ exhibits a high ionic conductivity of approximately 0.01 S cm-1 at 90 °C in both water and wet air, which has been demonstrated by direct ammonia fuel cells. Neutron diffraction confirms the presence of OD bonds in the lattice of deuterated SrZr0.8Y0.2O3-δ. The OH- ionic conduction of CaZr0.8Y0.2O3-δ in water was demonstrated by electrolysis of both H218O and D2O. The ionic conductivity of CaZr0.8Y0.2O3-δ in 6 M KOH solution is around 0.1 S cm-1 at 90 °C, 100 times higher than that in pure water, indicating increased OH- ionic conductivity with a higher concentration of feed OH- ions. Density functional theory calculations suggest the diffusion of OH- ions relies on oxygen vacancies and temporarily formed hydrogen bonds. This opens a window to discovering new ceramic ionic conducting materials for near ambient temperature fuel cells, electrolysers and other electrochemical devices.

Three-Dimensional Ultrasound Imaging of Retinoblastoma and Its Correlation With Pathology.

BACKGROUND AND OBJECTIVE: Monitoring the response of retinoblastoma to globe-salvaging therapies is based on subjective assessments of changes determined by fundoscopy, ultrasound, and optical coherence tomography. Advances in organ-preserving therapies have increased the need for objective, quantitative estimates of tumor response to treatment. Primary tumor volume is a metric that can be objectively determined as a surrogate measure of treatment response. PATIENTS AND METHODS: We evaluated the correlation of objective, quantitative estimates of tumor volume made with two-dimensional (2D) and three-dimensional (3D) ultrasound with gold standard pathological tumor volumes derived by analysis of enucleation specimens. RESULTS: Twelve eyes in 12 patients undergoing primary enucleation were evaluated by 2D and 3D ultrasound during ophthalmic examination under anesthesia prior to enucleation. 2D- and 3D-ultra-sound measurements of tumor volume were both strongly correlated with pathological estimates of tumor volume (r = 0.69, P = 0.018; and r = 0.66, P = 0.027, respectively). CONCLUSIONS: 2D- and 3D-ultrasound measurements of retinoblastoma primary tumor volume are highly correlated with pathological estimates. 3D measurements are easy to perform with volumetric probes and consider the irregular morphology of the tumor. Further study should be undertaken to evaluate the performance of these metrics as surrogate markers of tumor response to treatment. [Ophthalmic Surg Lasers Imaging Retina 2024;55:136-140.].

A density functional theory benchmark on antioxidant-related properties of polyphenols.

In this work, we present a density functional theory benchmark on antioxidant-related properties for a series of six polyphenols that are well-known antioxidants: caffeic acid, cyanidin, ellagic acid, gallic acid, myricetin, and phloretin. Computations on the 24 O-H bond dissociation enthalpies (BDEs) and 6 ionization potentials (IPs) were performed using twenty-three exchange-correlation functionals combined with four different basis sets in the gas-phase, water, and methanol; calibration against the Domain-based Local Pair Natural Orbital CCSD(T) (DLPNO-CCSD(T)) approach was employed. Mean absolute deviation (MAD) as well as linear fitting results suggested the LC-PBE approach as the most suitable for O-H BDEs in the gas-phase. The LC-PBE, M06-2X, and M05-2X results presented the smallest MADs for O-H BDEs when compared to the reference, in water. The LC-PBE results had the smallest MADs for IPs in the gas-phase while M05-2X, M06-2X, LC-PBE, and LC-ωPBE exhibited the best results for MAD in water. We expect the outcomes from the present work will serve as general guidance for researchers working in the field.

The influence of bias in randomized controlled trials on rehabilitation intervention effect estimates: what we have learned from meta-epidemiological studies.

This study aimed to synthesize evidence from studies that addressed the influence of bias domains in randomized controlled trials on rehabilitation intervention effect estimates and discuss how these findings can maximize the trustworthiness of an RCT in rehabilitation. We screened studies about the influence of bias on rehabilitation intervention effect estimates published until June 2023. The characteristics and results of the included studies were categorized based on methodological characteristics and summarized narratively. We included seven studies with data on 227,806 RCT participants. Our findings showed that rehabilitation intervention effect estimates are likely exaggerated in trials with inadequate/unclear sequence generation and allocation concealment when using continuous outcomes. The influence of blinding was inconsistent and different from the rest of medical science, as meta-epidemiological studies showed overestimation, underestimation, or neutral associations for different types of blinding on rehabilitation treatment effect estimates. Still, it showed a more consistent pattern when looking at patient-reported outcomes. The impact of attrition bias and intention to treat has been analyzed only in two studies with inconsistent results. The risk of reporting bias seems to be associated with overestimation of treatment effects. Bias domains can influence rehabilitation treatment effects in different directions. The evidence is mixed and inconclusive due to the poor methodological quality of RCTs and the limited number and quality of studies looking at the influence of bias and treatment effects in rehabilitation. Further studies about the influence of bias in RCTs on rehabilitation intervention effect estimates are needed.

The landscape of genomic structural variation in Indigenous Australians.

Indigenous Australians harbour rich and unique genomic diversity. However, Aboriginal and Torres Strait Islander ancestries are historically under-represented in genomics research and almost completely missing from reference datasets1-3. Addressing this representation gap is critical, both to advance our understanding of global human genomic diversity and as a prerequisite for ensuring equitable outcomes in genomic medicine. Here we apply population-scale whole-genome long-read sequencing4 to profile genomic structural variation across four remote Indigenous communities. We uncover an abundance of large insertion-deletion variants (20-49 bp; n = 136,797), structural variants (50 b-50 kb; n = 159,912) and regions of variable copy number (>50 kb; n = 156). The majority of variants are composed of tandem repeat or interspersed mobile element sequences (up to 90%) and have not been previously annotated (up to 62%). A large fraction of structural variants appear to be exclusive to Indigenous Australians (12% lower-bound estimate) and most of these are found in only a single community, underscoring the need for broad and deep sampling to achieve a comprehensive catalogue of genomic structural variation across the Australian continent. Finally, we explore short tandem repeats throughout the genome to characterize allelic diversity at 50 known disease loci5, uncover hundreds of novel repeat expansion sites within protein-coding genes, and identify unique patterns of diversity and constraint among short tandem repeat sequences. Our study sheds new light on the dimensions and dynamics of genomic structural variation within and beyond Australia.

Feasibility and acceptability of the use of flash glucose monitoring encountered by Indigenous Australians with type 2 diabetes mellitus: initial experiences from a pilot study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is highly prevalent within the Indigenous Australian community. Novel glucose monitoring technology offers an accurate approach to glycaemic management, providing real-time information on glucose levels and trends. The acceptability and feasibilility of this technology in Indigenous Australians with T2DM has not been investigated. OBJECTIVE: This feasibility phenomenological study aims to understand the experiences of Indigenous Australians with T2DM using flash glucose monitoring (FGM). METHODS: Indigenous Australians with T2DM receiving injectable therapy (n = 8) who used FGM (Abbott Freestyle Libre) for 6-months, as part of a clinical trial, participated in semi-structured interviews. Thematic analysis of the interviews was performed using NVivo12 Plus qualitative data analysis software (QSR International). RESULTS: Six major themes emerged: 1) FGM was highly acceptable to the individual; 2) FGM's convenience was its biggest benefit; 3) data from FGM was a tool to modify lifestyle choices; 4) FGM needed to be complemented with health professional support; 5) FGM can be a tool to engage communities in diabetes management; and 6) cost of the device is a barrier to future use. CONCLUSIONS: Indigenous Australians with T2DM had positive experiences with FGM. This study highlights future steps to ensure likelihood of FGM is acceptable and effective within the wider Indigenous Australian community.