Theory of change for addressing sex and gender bias, invisibility and exclusion in Australian health and medical research, policy and practice.

Sex and gender are inadequately considered in health and medical research, policy and practice, leading to preventable disparities in health and wellbeing. Several global institutions, journals, and funding bodies have developed policies and guidelines to improve the inclusion of diverse participants and consideration of sex and gender in research design and reporting and the delivery of clinical care. However, according to recent evaluations, these policies have had limited impact on the inclusion of diverse research participants, adequate reporting of sex and gender data and reducing preventable inequities in access to, and quality provision of, healthcare. In Australia, the Sex and Gender Policies in Medical Research (SGPMR) project aims to address sex and gender bias in health and medical research by (i) examining how sex and gender are currently considered in Australian research policy and practice; (ii) working with stakeholders to develop policy interventions; and (iii) understanding the wider impacts, including economic, of improved sex and gender consideration in Australian health and medical research. In this paper we describe the development of a theory of change (ToC) for the SGPMR project. The ToC evolved from a two-stage process consisting of key stakeholder interviews and a consultation event. The ToC aims to identify the pathways to impact from improved consideration of sex and gender in health and medical research, policy and practice, and highlight how key activities and policy levers can lead to improvements in clinical practice and health outcomes. In describing the development of the ToC, we present an entirely novel framework for outlining how sex and gender can be appropriately considered within the confines of health and medical research, policy and practice.

Sex and gender reporting in Australian health and medical research publications.

OBJECTIVE: This study aimed to determine how sex and gender are being incorporated into Australian medical research publications and if this is influenced by journals endorsing the International Committee of Medical Journal Editors (ICMJE) guidelines, which contain criteria for sex and gender reporting. METHODS: Analysis of original research articles published in Australia's top 10 medical journals in 2020. RESULTS: From the 10 leading journals, 1,136 articles were eligible for analysis, including 990 human participant populations. Sex and/or gender were reported for 873 (88.2%) human populations, with 480 using conflicting terminology. Only 14 (1.6%) described how sex and gender were determined. The primary outcome, or key aim, was stratified by sex and/or gender for 249 (29.2%) participant groups and the influence of sex and/or gender on the results was discussed for only 171 (17.3%). There was no significant association between endorsement of the ICMJE guidelines and adherence to any sex and gender criteria. CONCLUSIONS: Sex and gender are poorly incorporated into Australian medical research publications and was not improved by journals endorsing the ICMJE guidelines. IMPLICATIONS FOR PUBLIC HEALTH: Reporting and analysis of sex and gender data in health research in Australian medical journals requires improvement, for better health for all.

Elder Mediation Services Among Diverse Older Adult Communities in Australia: Practitioner Perspectives on Accessibility.

BACKGROUND AND OBJECTIVES: Elder abuse is a complex problem, and barriers to reporting and help-seeking include shame and fear of loss of relationships with key family members. Elder mediation has been identified as one promising method of alternative dispute resolution. This study aimed to investigate the accessibility of elder mediation services among diverse groups of older adults, from the perspective of practitioners in a large Australian jurisdiction. RESEARCH DESIGN AND METHODS: The study employed a sequential mixed-methods approach, comprising a thematic analysis of semistructured interviews (N = 17) and an online survey of practitioners (N = 49) involved in referral to, or provision of, elder mediation services. Accessibility was conceptualized using existing theoretical frameworks, spanning practical (logistics-related), and normative (justice- and culture-related) dimensions. RESULTS: Factors limiting accessibility of elder mediation services included lack of community and practitioner awareness of elder abuse and elder mediation, discomfort with the mediation process, financial costs, lack of services in regional and remote areas, and complex service systems for older people. Within the mediation process, difficulties in assessing and accommodating cognitive and other impairments, managing power imbalances, and determining the appropriateness of the dispute for mediation were influential. DISCUSSION AND IMPLICATIONS: This study showed that mediation can be a promising and effective approach to resolving disputes involving older people. The emergent perceptive dimension (community and practitioner awareness) emphasizes the importance of awareness-raising efforts surrounding both elder abuse and the potential of mediation as a viable pathway, the training of elder-mediators as well as resourcing elder mediation services, especially in rural and remote locations.

Markers of inflammation in men with small abdominal aortic aneurysm.

BACKGROUND: Markers of inflammation and fibrin turnover are elevated in individuals with a large (>55 mm) abdominal aortic aneurysm (AAA). Fibrin degradation generates D-dimer, known to possess multiple proinflammatory effects, and levels are elevated during early AAA development. This study characterized the plasma inflammatory response during early AAA pathogenesis to determine the effect of D-dimer levels. METHODS: The study compared 75 men with a small AAA (range, 30-54 mm) with 90 age-, sex-, and race-matched controls. Plasma interleukin-6 (IL-6), complement C3, high-sensitivity C-reactive protein (hsCRP), fibrinogen, and D-dimer levels were measured. RESULTS: Mean levels of fibrinogen (2.92 vs 2.59 g/L; P = .003), hsCRP (2.07 vs 1.29 ng/mL; P = .005), and D-dimer (346.7 vs 120.2 ng/mL; P < .001) were higher in men with a small AAA. These markers correlated with maximum aortic diameter determined by ultrasound imaging. On multivariate analysis, D-dimer levels were elevated in AAA individuals independent of smoking, cardiovascular disease (CVD), atherosclerotic risk factors, and inflammatory parameters. Fibrinogen and hsCRP levels remained elevated after adjustment for these covariates but lost significance when D-dimer was added to the model. CONCLUSION: C-reactive protein and D-dimer levels are elevated during early AAA development. D-dimer levels are most tightly associated with AAA status, however, and may mediate the observed elevation in acute-phase reactants.

A further example of a distinctive autosomal recessive syndrome comprising neonatal diabetes mellitus, intestinal atresias and gall bladder agenesis.

We report a patient born to consanguineous parents as a further example of a recently described phenotype comprising neonatal diabetes, intestinal atresias and gall bladder agenesis. Other reports have described cases with overlapping patterns including malrotation, biliary atresia and pancreatic hypoplasia (e.g. as described by Martínez-Frías). We propose that these cases may represent variations of the same syndrome. It is likely that this disorder is inherited as an autosomal recessive trait. Our case is the first to have neonatal diabetes without a demonstrable structural pancreatic abnormality, showing that a deficit in pancreatic function is involved. We sequenced genes with a recognized role in monogenic forms of diabetes, including KCNJ11, ABCC8, GCK, IPF1, HNF1beta, NeuroD1 and TCF7L2, as well as a novel candidate gene, HNF6, known to be involved in hepatobiliary and pancreatic development, but did not identify mutations.

Identification and characterization of small RNAs from the phloem of Brassica napus.

Systemic signalling is indispensable for the coordination of diverse physiological processes during development, defence and nutrient allocation. Indirect evidence suggests that plant small RNAs (smRNAs) could be involved in long-distance information transfer via the vasculature of the plant. Analyses of the smRNA complements of vascular exudates from oilseed rape (Brassica napus) showed that xylem sap is devoid of RNA, whereas phloem sap contained a large number of smRNAs. In addition to 32 annotated microRNAs (miRNAs) from 18 different families that could be identified and approved, a set of unknown smRNAs, predominantly of 21 and 24 nucleotides in length, was obtained, and selected candidates were found to be highly abundant in phloem sap. Moreover, we could demonstrate that the levels of three miRNAs known to respond to nutrient deprivation in non-vascular tissue, miR395 (sulphate), miR398 (copper) and miR399 (phosphate), were increased in phloem sap during the growth of plants under the respective starvation conditions. Interestingly, only mature miRNA molecules were found to be stress responsive, demonstrating that single-stranded sense miRNAs are most likely to represent the physiologically relevant molecules. The strong responses in the phloem suggest a role of miRNAs in systemic information transfer via this long-distance transport system.

Evaluation of a polymerase chain reaction-based heteroduplex assay for detecting the adulteration of processed orange juice with mandarin juice.

A polymerase chain reaction (PCR)-based heteroduplex assay was evaluated for the detection of mandarin juice in processed orange juice. PCR amplification of a fragment of the chloroplast trnT-trnL intergenic spacer derived from mixtures of DNA extracted from orange and mandarin juice resulted in heteroduplex formation. The heteroduplex resulted from the co-amplification of a fragment containing an 8 base-pair indel that distinguished mixtures of orange and mandarin juice from orange juice and mandarin juice alone. The heteroduplex assay was evaluated against authentic juices obtained from different citrus species and confirmed that the marker was homogeneous within Citrus. The data obtained demonstrated maternal inheritance of chloroplast type in Citrus sp. and allowed the identification and confirmation of the maternal parentage of unknown and known citrus hybrids. Analysis of the quantitative potential of the PCR and polyacrylamide gel electrophoresis (PAGE) analysis demonstrated good repeatability with a coefficient of variation of 7.5%. Greatest sources of variance in experimental results were attributable to species and varietal differences in the levels of the PCR target. Mandarin juice contained approximately 18% (w/v) less PCR target sequence than did orange juice. The assay was tested in a blind trial using processed juices and correctly identified 20/22 samples with no false-positive results.

Isolation and cloning of small RNAs from virus-infected plants.

RNA silencing is an evolutionarily conserved, RNA-mediated, regulatory system of eukaryotic organisms that also acts as an antiviral system in plants and animals. A defining feature of RNA silencing is the presence of 21- to 26-nucleotide small RNAs corresponding to the silencing target sequence, which in virus-infected plants are derived from the viral genome. The virus-derived small RNAs have a nonrandom distribution along the viral genome, suggesting hotspots for viral small-RNA generation. The isolated small RNAs can be used either as probes for hybridization studies or for directional cloning in order to get detailed information about their sizes, origins, and functions. This unit describes an isotope-free small-RNA cloning procedure that utilizes unmodified small RNAs and is routinely used to characterize small RNAs from various plant tissues.

Two classes of short interfering RNA in RNA silencing.

RNA silencing is a eukaryotic genome defence system that involves processing of double-stranded RNA (dsRNA) into 21-26 nt, short interfering RNA (siRNA). The siRNA mediates suppression of genes corresponding to the dsRNA through targeted RNA degradation. In some plant systems there are additional silencing processes, involving systemic spread of silencing and RNA-directed methylation/transcriptional suppression of homologous genomic DNA. We show here that siRNAs produced in plants from a green fluorescent protein (GFP) transgene are in short (21-22 nt) and long (24-26 nt) size classes, whereas those from endogenous retroelements are only in the long class. Viral suppressors of RNA silencing and mutations in Arabidopsis indicate that these classes of siRNA have different roles. The long siRNA is dispensable for sequence-specific mRNA degradation, but correlates with systemic silencing and methylation of homologous DNA. Conversely, the short siRNA class correlates with mRNA degradation but not with systemic signalling or methylation. These findings reveal an unexpected level of complexity in the RNA silencing pathway in plants that may also apply in animals.