Do Indigenous Australians age prematurely? The implications of life expectancy and health conditions of older Indigenous people for health and aged care policy

Objective. To assess whether Indigenous Australians age prematurely compared with other Australians, as implied by Australian Government aged care policy, which uses age 50 years and over for population-based planning for Indigenous people compared with 70 years for non-indigenous people. Methods. Cross-sectional analysis of aged care assessment, hospital and health survey data comparing Indigenous and non-indigenous age-specific prevalence of health conditions. Analysis of life tables for Indigenous and non-indigenous populations comparing life expectancy at different ages. Results. At age 63 for women and age 65 for men, Indigenous people had the same life expectancy as non-indigenous people at age 70. There is no consistent pattern of a 20-year lead in age-specific prevalence of age-associated conditions for Indigenous compared with other Australians. There is high prevalence from middle-age onwards of some conditions, particularly diabetes (type unspecified), but there is little or no lead for others. Conclusion. The idea that Indigenous people age prematurely is not well supported by this study of a series of discrete conditions. The current focus and type of services provided by the aged care sector may not be the best way to respond to the excessive burden of chronic disease and disability of middle-aged Indigenous people

The Calan-Hertfordshire Extrasolar Planet Search

The detailed study of the exoplanetary systems HD189733 and HD209458 has given rise to a wealth of exciting information on the physics of exoplanetary atmospheres. To further our understanding of the make-up and processes within these atmospheres we require a larger sample of bright transiting planets. We have began a project to detect more bright transiting planets in the southern hemisphere by utilising precision radial-velocity measurements. We have observed a constrained sample of bright, inactive and metal-rich stars using the HARPS instrument and here we present the current status of this project, along with our first discoveries which include a brown dwarf/extreme-Jovian exoplanet found in the brown dwarf desert region around the star HD191760 and improved orbits for three other exoplanetary systems HD48265, HD143361 and HD154672. Finally, we briefly discuss the future of this project and the current prospects we have for discovering more bright transiting planets.Comment: 4 pages, 2 figures, to appear in the conference proceedings "New Technologies for Probing the Diversity of Brown Dwarfs and Exoplanets" Shanghai 200

Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.

Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (Emax ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes

The successes and challenges of harmonising juvenile idiopathic arthritis (JIA) datasets to create a large-scale JIA data resource

Background CLUSTER is a UK consortium focussed on precision medicine research in JIA/JIA-Uveitis. As part of this programme, a large-scale JIA data resource was created by harmonizing and pooling existing real-world studies. Here we present challenges and progress towards creation of this unique large JIA dataset. Methods Four real-world studies contributed data; two clinical datasets of JIA patients starting first-line methotrexate (MTX) or tumour necrosis factor inhibitors (TNFi) were created. Variables were selected based on a previously developed core dataset, and encrypted NHS numbers were used to identify children contributing similar data across multiple studies. Results Of 7013 records (from 5435 individuals), 2882 (1304 individuals) represented the same child across studies. The final datasets contain 2899 (MTX) and 2401 (TNFi) unique patients; 1018 are in both datasets. Missingness ranged from 10 to 60% and was not improved through harmonisation. Conclusions Combining data across studies has achieved dataset sizes rarely seen in JIA, invaluable to progressing research. Losing variable specificity and missingness, and their impact on future analyses requires further consideration

Exome array analysis identifies ETFB as a novel susceptibility gene for anthracycline-induced cardiotoxicity in cancer patients.

PURPOSE: Anthracyclines are widely used chemotherapeutic drugs that can cause progressive and irreversible cardiac damage and fatal heart failure. Several genetic variants associated with anthracycline-induced cardiotoxicity (AIC) have been identified, but they explain only a small proportion of the interindividual differences in AIC susceptibility. METHODS: In this study, we evaluated the association of low-frequency variants with risk of chronic AIC using the Illumina HumanExome BeadChip array in a discovery cohort of 61 anthracycline-treated breast cancer patients with replication in a second independent cohort of 83 anthracycline-treated pediatric cancer patients, using gene-based tests (SKAT-O). RESULTS: The most significant associated gene in the discovery cohort was ETFB (electron transfer flavoprotein beta subunit) involved in mitochondrial β-oxidation and ATP production (P = 4.16 × 10-4) and this association was replicated in an independent set of anthracycline-treated cancer patients (P = 2.81 × 10-3). Within ETFB, we found that the missense variant rs79338777 (p.Pro52Leu; c.155C > T) made the greatest contribution to the observed gene association and it was associated with increased risk of chronic AIC in the two cohorts separately and when combined (OR 9.00, P = 1.95 × 10-4, 95% CI 2.83-28.6). CONCLUSIONS: We identified and replicated a novel gene, ETFB, strongly associated with chronic AIC independently of age at tumor onset and related to anthracycline-mediated mitochondrial dysfunction. Although experimental verification and further studies in larger patient cohorts are required to confirm our finding, we demonstrated that exome array data analysis represents a valuable strategy to identify novel genes contributing to the susceptibility to chronic AIC

A haemagglutination test for rapid detection of antibodies to SARS-CoV-2

Serological detection of antibodies to SARS-CoV-2 is essential for establishing rates of seroconversion in populations, and for seeking evidence for a level of antibody that may be protective against COVID-19 disease. Several high-performance commercial tests have been described, but these require centralised laboratory facilities that are comparatively expensive, and therefore not available universally. Red cell agglutination tests do not require special equipment, are read by eye, have short development times, low cost and can be applied at the Point of Care. Here we describe a quantitative Haemagglutination test (HAT) for the detection of antibodies to the receptor binding domain of the SARS-CoV-2 spike protein. The HAT has a sensitivity of 90% and specificity of 99% for detection of antibodies after a PCR diagnosed infection. We will supply aliquots of the test reagent sufficient for ten thousand test wells free of charge to qualified research groups anywhere in the world