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Dental caries constitutes one of the most ubiquitous diseases in Australia, with Indigenous children presenting a notably higher prevalence than their non‐Indigenous peers. This literature review aims to update the knowledge base developed by Christian and Blinkhorn in 2012, with a particular focus on the contemporary disparities in dental caries between Indigenous and non‐Indigenous children. Our research strategy involved a thorough exploration of the Medline, PubMed, and Scopus databases to identify pertinent studies published between 2009 and 2022. Supplementary resources included various government websites and citation searches. We prioritised studies that focused on children aged 5–6 or 12 years—reflecting the World Health Organization's index ages for oral health—and that reported dental caries prevalence and experience indicators. Our review methodology was guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) statement. The updated search, spanning 2009 to 2023, retrieved studies that reported caries estimates exclusively from 2009 to 2014. Within this period, the prevalence of dental caries in Indigenous children's primary teeth ranged between 52% and 77%, while the prevalence in permanent teeth varied from 36% to 60%. This updated review indicated that Indigenous children continue to experience caries at an approximately twice higher rate than non‐Indigenous children, sustaining the persisting disparity in caries estimates. The findings from this review show that no discernible improvement in dental caries rates among Australian Indigenous children has been observed in comparison to the previous review; and that Indigenous children continue to experience both higher prevalence and severity of dental caries compared to non‐Indigenous children. [ABSTRACT FROM AUTHOR]

Objectives: Malnutrition, particularly protein insufficiency, is common in institutionalised older adults and increases morbidity, mortality, and costs. We aimed to determine whether 12 months supplementation using high-protein foods (milk, cheese, yoghurt) prevents malnutrition in older adults. Design: Cluster randomised control study. Setting: Sixty Australian aged care facilities. Participants: Older adults living in aged care homes (n=654, mean age 86.7±7.2 years, 72% females). Intervention: Facilities randomly allocated to a high-protein (n=30 intervention) or regular (n=30 controls) menu. Measurements: Nutritional status assessed using the Mini Nutrition Assessment (MNA) tool and fasting morning blood samples (n=302) assayed for haemoglobin (Hb) and albumin. Food intake was monitored 3-monthly using visual plate waste assessment. Measurements at baseline and month 12 were analysed using random effects model accounting for clustering (facility), repeated measure and confounders. Results: Addition of 11g of protein as 1.5 servings of high-protein foods daily preserved nutritional status that deteriorated in controls [MNA screen (−0.68, 95%CI: −1.03, −0.32, p<0.001) and total (−0.90, 95%CI: −1.45, −0.35, p=0.001) scores], resulting in group differences in MNA screen (0.62, 95%CI: 0.17, 1.06, p=0.007) and total (0.81, 95%CI: 0.11, 1.51, p=0.023) scores and group difference in Hb (3.60g/L, 95%CI: 0.18, 7.03, p=0.039), the net result of preservation with intervention (0.19g/L, 95%CI: −2.04, 2.42, p=0.896) and a decline in controls (−3.41g/L, 95%CI: −6.01, −0.82, p=0.010). No group differences were observed for serum albumin. Conclusion: Consumption of high-protein foods is a pragmatic approach to maintaining nutritional status in older adults in aged-care. [ABSTRACT FROM AUTHOR]

Although seafood is considered to be an important part of a balanced diet, many national food consumption surveys suggest that seafood is not consumed in sufficient amounts. As consumers are moving to diversify their diet from animal-based protein, it is important to understand the factors influencing consumption of marine foods. This review aims to assess the characteristics of seafood consumers as well as the influences on seafood consumption in Europe, USA, Canada, Australia and New Zealand. Systematic search strategies were used to identify relevant journal articles from three electronic databases (PubMed, Web of Science and Embase). Three searches were carried out and identified 4405 unique publications from which 121 met the criteria for the review process. The reviewed studies revealed that seafood consumers were more likely to be older, more affluent and more physically active and were less likely to smoke compared with non-seafood consumers. Sex and BMI did not appear to have a directional association with seafood consumption. The most commonly reported barriers to seafood consumption were cost, followed by sensory or physical barriers, health and nutritional beliefs, habits, availability and cooking skills. The most commonly reported influences were beliefs about the contribution of seafood to health, environmental influences and personal preferences. Based on the findings of this review, future intervention strategies to increase seafood consumption may need to consider affordability and education in terms of health, nutrition and cooking skills. More research is needed to explore the effectiveness of specific interventions at increasing the consumption of seafood. [ABSTRACT FROM AUTHOR]

The exposures and risks of coastal built as well as natural assets to storm-tide inundation are expected to be more pronounced as a result of the reduced recurrence interval or the increased occurrence frequency of storm tides in Australia due to sea-level rise. This study investigates thedistributionsof direct damage losses and adaptation benefits for residential buildings considering uncertainties of storm tides under projected sea-level rises in South East Queensland, one of the fastest-growing regions in Australia in the last two decades. The study subsequently indicates that ‘deterministic decision-making’ based on an individual hazard or scenario could be fundamentally flawed for coastal planning and adaptation as a result of uncertain natures in coastal hazards under changing climate. The developed knowledge can eventually facilitate better decision-making processes for adapting coastal residential buildings to future climate change under considerable uncertainties. It is also found that constructing new buildings with higher floor heights is a relatively inexpensive but also a highly effective approach insensitive to uncertainties for reducing future damage losses of storm-tide inundation. [ABSTRACT FROM AUTHOR]

The probability of schedule overruns for construction and engineering projects can be ascertained using a 'best fit' probability distribution from an empirical distribution. The statistical characteristics of schedule overruns occurring in 276 Australian construction and engineering projects were analysed. Skewness and kurtosis values revealed that schedule overruns are non-Gaussian. Theoretical probability distributions were then fitted to the schedule overrun data; including the Kolmogorov-Smirnov, Anderson-Darling and Chi-Squared non-parametric tests to determine the 'Goodness of Fit'. A Four Parameter Burr probability function best described the behaviour of schedule overruns, provided the best overall distribution fit and was used to calculate the probability of a schedule overrun being experienced. The statistical characteristics of contract size and schedule overruns were also analysed, and the Wakeby (AU$101 m) models provided the best distribution fits and were used to calculate schedule overrun probabilities by contract size. [ABSTRACT FROM AUTHOR]

Hydraulic lift can be a desirable characteristic for cotton growing in areas that experience frequent drying of the topsoil. This study employed specialized soil columns to test if cotton can hydraulically lift water and whether this hydraulically lifted water can facilitate P acquisition from the dry topsoil of a clay and a sandy soil. The role of subsoil P placement on cotton growth was also tested. By using a Theta probe, hydraulic lift was detected in the clay soil for 7 days after water was withheld from the topsoil. However, in the sandy soil, a significant overnight increase in soil water was only detected for one day for the treatment with subsoil P application. Where P was applied to the topsoil, and water was withheld, cotton roots showed significant root P uptake from the sandy soil, but negligible P uptake from the clay soil. Irrespective of topsoil watering, the higher root length density in the subsoil of the clay soil accounted for the pronounced response to deep P placement. This study demonstrated that soil texture affects the amount and longevity of hydraulic lift from cotton roots. Hydraulic lift detected in the clay soil did not aid P acquisition from dry surface soil by cotton plants. [ABSTRACT FROM AUTHOR]

Abstract Rates of renal and cardiovascular disease are high among Aboriginal Australians living in remote communities. Nutritional problems, in particular low folate levels, are also common. This suggests that increased homocysteine concentrations might be widespread, and a possible contributor to the high rates of cardiovascular disease. To examine homocysteine concentrations, and their relationships to folate levels, and to markers of renal disease and cardiovascular disease in a remote Aboriginal Australian community As part of a cross-sectional survey among adults in one community, homocysteine concentrations, concentrations of the crucial determinants (red blood cell (RBC) folate, vitamin B12 and the C677T methylene tetrahydrofolate reductase polymorphism) and cardiovascular risk factors were examined. Among 221 people, geometric mean homocysteine concentration was 11.8 µmol/L (range: 11.1–12.5 µmol/L), with 57/221 (26%) values≥15.0 µmol/L. Higher concentrations were associated with older age, male gender, lower RBC folate and lower vitamin B12 concentrations and homozygosity for C677T. Homocysteine concentrations were not related to the presence of albuminuria, other than over the overt albuminuria range. Homocysteine concentrations were inversely correlated with calculated glomerular filtration rate (GFR). Carotid intima-media thickness, however, was not related to homocysteine concentration. In multivariate analyses, age, male gender, lower RBC folate concentrations, lower vitamin B12 concentrations, lower calculated GFR and the C677T polymorphism were all associated with homocysteine concentrations. : Homocysteine concentrations were consistent with previous limited reports in Aboriginal communities. Although superficially they are similar to reports from non-Aboriginal settings, the younger age of this cohort and the association of homocysteine concentrations with age suggest that age-specific concentrations are higher among Aboriginal Australians. In addition to dietary determinants, the high prevalence of apparently reduced renal function renal disease appears to be an important determinant of homocysteine concentrations in remote Aboriginal communities. The role of homocysteine concentrations as a potential mediator of the high rates of cardiovascular disease remains to be determined. (Intern Med J 2005; 35: 289–294) [ABSTRACT FROM AUTHOR]

The sizing of water heating plants for outdoor community swimming pools conventionally relies on empirical methods and industry guidelines that seldom account for local climatic conditions. In the absence of a model that accounts for all modes of heat and mass transfer, the prediction of water temperature of an outdoor pool and hence the sizing of the heating plant can result in either significant over or under estimation which could impact on not only capital and operating costs but also on complying with environmental accountability and control strategy. The model developed herein accounts for numerous contributors to the thermal energy balance of pool water, notable among them being free and forced convection heat and mass transfer to/from pool and radiation cooling to the sky. Cloud and rain effects are also incorporated into the model. The role of solar and ambient weather conditions is emphasised. The first-principle and analytical model has been calibrated against data from an Olympic sized swimming pool in Perth, Australia. A comparison between various models in the literature shows that the present model is able to replicate experimental data much more closely than others, with 82% of the results being within ±0.5 °C of the actual measured pool temperatures and with 67% of the predicted heating capacities being within ±100 kW of the measured heating capacities. Image 1 • Free convection and evaporation is important to outdoor swimming pool performance. • Our study is benchmarked against 27 months of data from an Olympic swimming pool. • 82% of our model prediction is within ±0.5 °C of the actual pool temperature. • 67% of our model prediction is within ±100 kW of the actual pool heating capacity. [ABSTRACT FROM AUTHOR]

Differentially methylated CpG sites (dmCpGs) that distinguish prostate tumour from adjacent benign tissue could aid in the diagnosis and prognosis of prostate cancer. Previously, the identification of such dmCpGs has only been undertaken in radical prostatectomy (RP) samples and not primary diagnostic tumour samples (needle biopsy or transurethral resection of the prostate). We interrogated an Australian dataset comprising 125 tumour and 43 adjacent histologically benign diagnostic tissue samples, including 41 paired samples, using the Infinium Human Methylation450 BeadChip. Regression analyses of paired tumour and adjacent benign samples identified 2,386 significant dmCpGs (Bonferroni p < 0.01; delta-β ≥ 40%), with LASSO regression selecting 16 dmCpGs that distinguished tumour samples in the full Australian diagnostic dataset (AUC = 0.99). Results were validated in independent North American (n paired  = 19; AUC = 0.87) and The Cancer Genome Atlas (TCGA; n paired  = 50; AUC = 0.94) RP datasets. Two of the 16 dmCpGs were in genes that were significantly down-regulated in Australian tumour samples (Bonferroni p < 0.01; GSTM2 and PRKCB). Ten additional dmCpGs distinguished low (n = 34) and high Gleason (n = 88) score tumours in the diagnostic Australian dataset (AUC = 0.95), but these performed poorly when applied to the RP datasets (North American: AUC = 0.66; TCGA: AUC = 0.62). The DNA methylation marks identified here could augment and improve current diagnostic tests and/or form the basis of future prognostic tests., (© 2024. The Author(s).)

Background: Given the growing evidence on the health benefits associated with physical literacy (PL), it is necessary to develop sound measures to assess the levels of PL in children. The Physical Literacy in Children Questionnaire (PL-C Quest) is the first self-report pictorial-based scale to assess children's perceived PL. It has good validity and reliability in Australian children aged 7 to 12 years, but little is known in younger children and in other cultural contexts. The aim of this study was to examine the validity and reliability in an expanded age range., Methods: A total of 1,870 Chinese children (girls, n = 871; 46.6%), aged 4 to 12 years (M = 8.07 ± 2.42) participated in validity testing. Structural equation modeling with the Weighted Least Squares with Mean and Variance approach was used to assess construct validity. The hypothesized theoretical model used the 30 items and four hypothesized factors: physical, psychological, social and cognitive capabilities. Multigroup confirmatory factor analysis was used to assess sex and age group (4-6 years, 7-9 years and 10-12 years) measurement invariance. Internal consistency analyses were conducted using polychoric alpha. A random subsample (n = 262) was selected to determine test-retest reliability using Intra-Class Correlations (ICC)., Results: All items except one (moving with equipment-skateboarding) loaded on sub-domains with λ > 0.45. The hypothesized model had a good fit (CFI = 0.954, TLI = 0.950, RMSEA = 0.042), with measurement equivalence across sex and age groups separately. Internal consistency values were good to excellent (overall: α = 0.94; physical: α = 0.86; psychological: α = 0.83; social: α = 0.81; cognitive: α = 0.86). Test-retest reliability was adequate to excellent (overall: ICC = 0.90, physical: ICC = 0.86, psychological: ICC = 0.75, social: ICC = 0.71, cognitive: ICC = 0.72)., Conclusion: The Chinese version of the PL-C Quest is valid and reliable for testing the self-reported PL of Chinese children aged 4 to 12. This study provides the first evidence of validity for this tool in children aged 4-6 years and also evidence that the PL-C Quest would be a meaningful instrument to assess PL in Chinese children., (© 2024. The Author(s).)

Sydney estuary catchment supports the largest city in Australia and provides essential eco-social and environmental services; however, the region has been influenced by extensive anthropogenic modification. Soil metal concentrations in the catchment had been studied previously; however, the current investigation was designed to determine the risk posed by these contaminants to human health. Soil metal concentrations were higher than observed in most global capitals and increased substantially in the south and south-east of the catchment and close to the central business district. Road-side soils and road dust contained the highest concentration of metals in the catchment. Lead in catchment soils was closely related to traffic density and sourced from the historic use of Pb in petrol. A human health assessment indicated that soil Cd, Ni and Zn posed no non-carcinogenic risk (NCR), or carcinogenic risk (CR) for children, or adults in Sydney estuary catchment and that Cu and Cr may pose minor NCR for children. Vehicle-related Pb raised the greatest human health risk in catchment soils and may pose NCR at 32% and 4.3% of sites for children and adults, respectively. Inconsistent analytical techniques used in CR and NCR evaluations produce incomparable assessments and a consistent` methodology is suggested to improve interpretation. Human health risk may well be higher than commonly calculated due to pollutants present in urban soil not being included in assessments., (© 2024. The Author(s).)

Background: During the 2019 severe influenza season, New South Wales (NSW) experienced the highest number of cases in Australia. This study retrospectively investigated the genetic characteristics of influenza viruses circulating in NSW in 2019 and identified genetic markers related to antiviral resistance and potential virulence., Methods: The complete genomes of influenza A and B viruses were amplified using reverse transcription-polymerase chain reaction (PCR) and sequenced with an Illumina MiSeq platform., Results: When comparing the sequencing data with the vaccine strains and reference sequences, the phylogenetic analysis revealed that most NSW A/H3N2 viruses (n = 68; 94%) belonged to 3C.2a1b and a minority (n = 4; 6%) belonged to 3C.3a. These viruses all diverged from the vaccine strain A/Switzerland/8060/2017. All A/H1N1pdm09 viruses (n = 20) showed genetic dissimilarity from vaccine strain A/Michigan/45/2015, with subclades 6B.1A.5 and 6B.1A.2 identified. All B/Victoria-lineage viruses (n = 21) aligned with clade V1A.3, presenting triple amino acid deletions at positions 162-164 in the hemagglutinin protein, significantly diverging from the vaccine strain B/Colorado/06/2017. Multiple amino acid substitutions were also found in the internal proteins of influenza viruses, some of which have been previously reported in hospitalized influenza patients in Thailand. Notably, the oseltamivir-resistant marker H275Y was present in one immunocompromised patient infected with A/H1N1pdm09 and the resistance-related mutation I222V was detected in another A/H3N2-infected patient., Conclusions: Considering antigenic drift and the constant evolution of circulating A and B strains, we believe continuous monitoring of influenza viruses in NSW via the high-throughput sequencing approach provides timely and pivotal information for both public health surveillance and clinical treatment., (© 2024 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: People living with a cancer diagnosis often experience cancer-related fatigue (CRF). Between 9% and 45% of people report CRF as moderate to severe, negatively impacting their quality-of-life (QOL). The evidence-base for managing CRF recommends exercise-related therapies over pharmaceutical interventions. One such exercise-like therapy is Baduanjin mind-body exercise (MBE), which has additional benefits. A remotely delivered program may further benefit people with CRF. The primary objective of this pilot will test study feasibility of a remotely delivered Baduanjin MBE exercise program for people living with CRF., Methods: This is a randomized wait-list controlled pilot study and will take place in Sydney, Australia. Subject to informed consent, 40 adults with moderate CRF levels and receiving or previously received adjuvant chemotherapy, will undertake a home-based 8-week Baduanjin MBE program supported by online resources and instructors. The primary feasibility outcomes are recruitment, enrollment, retention, and adherence rates; and safety as measured by tolerance and adverse-event frequency. Clinical outcomes (eg, changes in CRF, QOL, and participant perceptions) are assessed at pre-intervention, week 1, week 4, week 8, and post-intervention. Analyses follows the Intent-to-Treat (all participants as per randomization) and per-protocol (participants adhering to the protocol). Missing data will be imputed from previous data entries and regression models may be tested to predict missing outcomes., Discussion: To our knowledge, this is the first study evaluating the feasibility and effects of Baduanjin MBE on CRF using a remote delivery method. These feasibility data will inform a fully powered future trial investigating evidence of effect on CRF and QOL. Trial registration : Australian and New Zealand Clinical Trials Registry (ANZCTR 12623000177651). Ringgold ID : 651498 Chinese Medicine Centre., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Older people in the nursing home environment are much less mobile and capable of taking care of themselves as they age, and most of them face the plight of loneliness, which seriously affects the quality of life of older people in their later years., Aims: A systematic review and synthesis of older people's experiences of loneliness in nursing homes., Design: Following ENTREQ, do a systematic evaluation and synthesis of qualitative investigations., Methods: A search of PubMed, Cochrane Library, Web of Science, Embase, the Chinese biomedical literature service system, the China National Knowledge Infrastructure, the Wanfang Database and the Wipu Database for qualitative studies of older people's experiences of loneliness in nursing homes was conducted with a search time frame of March 2023. Evaluation of the quality of the literature using the Joanna Briggs Institute's Australian Centre for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research, And the data were synthesised using Thomas and Harden's method of thematic and content analysis., Results: A total of 13 papers were included, and 36 research findings were distilled and integrated into three themes: causes of loneliness; feelings of loneliness; coping with loneliness; and seven sub-themes: aging and loss; environmental transformation; loneliness is a pain; loneliness is a choice; participation; strengthening social ties; and diverting attention., Conclusions: Older people in nursing homes face varying degrees of loneliness, which is a subjective feeling influenced by the interplay between personal awareness and the external environment, so future care interventions should be developed in a comprehensive manner, taking into account the characteristics of the older people themselves and their external environment., No Patient or Public Contribution: This study is a meta-synthesis and does not require relevant contributions from patients or the public., (© 2023 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Objective: Nurse home visiting (NHV) is designed to redress child and maternal health inequities. Of the previous trials to investigate NHV benefits beyond preschool, none were designed for populations with universal healthcare. To address this evidence gap, we investigated whether the Australian 'right@home' NHV programme improved child and maternal outcomes when children turned 6 and started school., Methods: A screening survey identified pregnant women experiencing adversity from antenatal clinics across two states (Victoria, Tasmania). 722 were randomised: 363 to the right@home programme (25 visits promoting parenting and home learning environment) and 359 to usual care. Child measures at 6 years (first school year): Strengths and Difficulties Questionnaire (SDQ), Social Skills Improvement System (SSIS), Childhood Executive Functioning Inventory (CHEXI) (maternal/teacher-reported); general health and paediatric quality of life (maternal-reported) and reading/school adaptation items (teacher-reported). Maternal measures: Personal Well-being Index (PWI), Depression Anxiety Stress Scales, warm/hostile parenting, Child-Parent Relationship Scale (CPRS), emotional abuse and health/efficacy items. Following best-practice methods for managing missing data, outcomes were compared between groups (intention-to-treat) using regression models adjusted for stratification factors, baseline variables and clustering (nurse/site level)., Results: Mothers reported on 338 (47%) children, and teachers on 327 (45%). Patterns of group differences favoured the programme arm, with small benefits (effect sizes ranging 0.15-0.26) evident for SDQ, SSIS, CHEXI, PWI, warm parenting and CPRS., Conclusions: Four years after completing the right@home programme, benefits were evident across home and school contexts. Embedding NHV in universal healthcare systems from pregnancy can offer long-term benefits for families experiencing adversity., Trial Registration Number: ISRCTN89962120., Competing Interests: Competing interests: The 'right@home' sustained nurse home visiting trial is a research collaboration between the Australian Research Alliance for Children and Youth (ARACY); the Translational Research and Social Innovation (TReSI) Group at Western Sydney University and the Centre for Community Child Health (CCCH), which is a department of The Royal Children’s Hospital and a research group of Murdoch Children’s Research Institute. Ownership of the right@home implementation and support license, which is purchased by Australian state governments for roll out for fidelity support, is shared between institutes., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Unequal access to cognitive assessments is a major barrier to timely diagnosis, especially for those living in rural or remote areas. 'One-stop' cognitive clinic models are a proposed solution, but few such clinics exist. We evaluate the implementation of a new one-stop State-wide clinic model in Tasmania, Australia, where 27% of people live in rural/remote areas., Methods: A novel single-visit protocol has been developed, comprising interdisciplinary medical and cognitive assessments, research participation, consensus diagnosis and management plan. A cross-sectional evaluation was undertaken using the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework and results benchmarked against the national Australian Dementia Network Registry., Results: Over the first 52 consecutive weekly clinics: Reach: 130 adults were assessed (mean age [SD] 70.12 years [10.31]; 59.2% female) with 40 (36.8%) from rural/remote areas., Effectiveness: 98.5% (128/130) received a same-day diagnosis: 30.1% (n = 40) Subjective Cognitive Decline, 35.4% (46) Mild Cognitive Impairment, 33.1% (43) dementia and one case inconclusive. Adoption: 22.9% (156) of General Practitioners referred patients., Implementation: Nearly all 'ideal' diagnostic clinical practices were met and >90% of surveyed patients reported 'good/very good' clinic experience. The wait from referral to diagnosis was 2 months shorter than other national Registry clinics (78 vs. 133 days)., Conclusions: This 'one-stop' model provides an interdisciplinary consensus cognitive diagnosis quickly and is well accepted; this may reduce health inequities especially for people living in rural/remote areas. This cognitive clinic model may be of relevance to other centres worldwide and also provides a rich data source for research studies., (© 2023 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Background: Though snoring is often regarded as a harmless condition that coincides with sound sleep, it is a sleep disorder that can be a potential indicator of more severe conditions such as sleep apnea syndrome. In the present study, we investigated the association between seasonal variations and snoring., Method: Search index for snoring (SIS) data were obtained from Google Trends and Baidu Index. SIS data were collected for the USA, India, Germany, Russia, Japan, Australia, China, and Brazil from 2011 to 2020, with the periodicity of the relationship between seasonal time series data and snoring evaluated using a time series decomposition model., Result: The highest average SIS growth rates from 2011 to 2020 were observed for Brazil, Japan, and Germany, with average SIS values of 94%, 68%, and 49%, respectively. The SIS of the USA, Russia, Japan, Brazil, Australia, Germany, and India increased by 22.3%, 12.4%, 11.9%, 35.4%, 12.3%, 28.0%, and 55.8%, respectively, in comparison with their SIS values in 2019, whereas for China, it decreased by 13.7%. Relative to countries in the southern hemisphere, those in the northern hemisphere showed comparable SIS trends, increasing from September to February and decreasing from March to August., Conclusion: The SIS data showed cyclical changes over the study period. The search index for snoring increased during the cold season or the heating season, suggesting that snoring is associated with seasonal changes., (© 2022. The Author(s).)

Background: Senaparib is a novel, selective poly(ADP-ribose) polymerase-1/2 inhibitor with strong antitumor activity in preclinical studies. This first-in-human, phase 1, dose-escalation study examined the safety and preliminary efficacy of senaparib in patients with advanced solid tumors., Methods: Patients with advanced solid tumors were enrolled from three centers in Australia, using a conventional 3 + 3 design. Dose-escalation cohorts continued until the maximum tolerated dose or a recommended phase 2 dose was determined. Patients received one dose of oral senaparib and, if no dose-limiting toxicity occurred within 7 days, they received senaparib once daily in 3-week cycles. The primary end points were safety and tolerability., Results: Thirty-nine patients were enrolled at 10 dose levels ranging from 2 to 150 mg. No dose-limiting toxicities were observed in any cohort. Most treatment-emergent adverse events were grade 1-2 (91%). Seven patients (17.9%) reported hematologic treatment-emergent adverse events. Treatment-related adverse events occurred in eight patients (20.5%), and the most frequent was nausea (7.7%). Two deaths were reported after the end of study treatment, one of which was considered a complication from senaparib-related bone marrow failure. Pharmacokinetic analysis indicated that senaparib the accumulation index was 1.06-1.67, and absorption saturation was 80-150 mg daily. In 22 patients with evaluable disease, the overall response rate was 13.6%, and the disease control rate was 81.8%. The overall response rate was 33.3% for the BRCA mutation-positive subgroup and 6.3% for the nonmutated subgroup., Conclusions: Senaparib was well tolerated in Australian patients with advanced solid tumors, with encouraging signals of antitumor activity. The recommended phase 2 dose for senaparib was determined to be 100 mg daily., Gov Id: NCT03507543., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Multiple sclerosis (MS) is a debilitating disease that requires prolonged treatment with often severe side effects. One experimental MS therapeutic currently under development is a single amino acid mutant of a plant peptide termed kalata B1, of the cyclotide family. Like all cyclotides, the therapeutic candidate [T20K]kB1 is highly stable as it contains a cyclic backbone that is cross-linked by three disulfide bonds in a knot-like structure. This stability is much sought after for peptide drugs, which despite exquisite selectivity for their targets, are prone to rapid degradation in human serum. In preliminary investigations, it was found that [T20K]kB1 retains oral activity in experimental autoimmune encephalomyelitis, a model of MS in mice, thus opening up opportunities for oral dosing of the peptide. Although [T20K]kB1 can be synthetically produced, a recombinant production system provides advantages, specifically for reduced scale-up costs and reductions in chemical waste. In this study, we demonstrate the capacity of the Australian native Nicotiana benthamiana plant to produce a structurally identical [T20K]kB1 to that of the synthetic peptide. By optimizing the co-expressed cyclizing enzyme, precursor peptide arrangements, and transgene regulatory regions, we demonstrate a [T20K]kB1 yield in crude peptide extracts of ~ 0.3 mg/g dry mass) in whole plants and close to 1.0 mg/g dry mass in isolated infiltrated leaves. With large-scale plant production facilities coming on-line across the world, the sustainable and cost-effective production of cyclotide-based therapeutics is now within reach., (© 2023. The Author(s).)

Glyphosate is the most used herbicide globally, but our understanding of human exposure and how different uses affect exposure is not well understood. The aim of this study was to obtain the first data on glyphosate and its primary degradation product aminomethylphosphonic acid (AMPA) concentrations in pooled and individual urine from the Australia and New Zealand region using a sensitive direct injection method and compare results with studies from elsewhere. Pooled urine samples from the Australian general population (n = 125 pools representing >1875 individuals) and individual urine samples (n = 27) from occupationally exposed New Zealand farmers were analysed by LC-MS/MS. Glyphosate was detected above the LOD (0.20-1.25 μg/L) in 8 % of the Australian population pooled urine samples with most detections in the 45-60 years age group. Furthermore, glyphosate (0.85 to 153 μg/L) and AMPA (0.50 to 3.35 μg/L) were detected in 96 % and 33 % of farmers, respectively. The maximum glyphosate urine concentration was 1.7 times above the recommended acceptable daily intake (ADI), when assuming a urinary excretion rate of 1 %. The pooled sampling and analysis approach proved effective for rapid large-scale screening of populations and could be used to determine where targeted and more specific individual sampling may be required., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: There is an unmet need for treatments for knee osteoarthritis (OA). Effusion-synovitis is a common inflammatory phenotype of knee OA and predicts knee pain and structural degradation. Anti-inflammatory therapies, such as diacerein, may be effective for this phenotype. While diacerein is recommended for alleviating pain in OA patients, evidence for its effectiveness is inconsistent, possibly because studies have not targeted patients with an inflammatory phenotype. Therefore, we will conduct a multi-centre, randomised, placebo-controlled double-blind trial to determine the effect of diacerein on changes in knee pain and effusion-synovitis over 24 weeks in patients with knee OA and magnetic resonance imaging (MRI)-defined effusion-synovitis., Methods: We will recruit 260 patients with clinical knee OA, significant knee pain, and MRI-detected effusion-synovitis in Hobart, Melbourne, Adelaide, and Perth, Australia. They will be randomly allocated to receive either diacerein (50mg twice daily) or identical placebo for 24 weeks. MRI of the study knee will be performed at screening and after 24 weeks of intervention. The primary outcome is improvement in knee pain at 24 weeks as assessed by a 100-mm visual analogue scale (VAS). Secondary outcomes include improvement in volumetric (ml) and semi-quantitative (Whole-Organ Magnetic Resonance Imaging Score, 0-3) measurements of effusion-synovitis using MRI over 24 weeks, and improvement in knee pain (VAS) at 4, 8, 12, 16, and 20 weeks. Intention-to-treat analyses of primary and secondary outcomes will be performed as the primary analyses. Per protocol analyses will be performed as the secondary analyses., Discussion: This study will provide high-quality evidence to determine whether diacerein improves pain, changes disease trajectory, and slows disease progression in OA patients with effusion-synovitis. If diacerein proves effective, this has the potential to significantly benefit the substantial proportion (up to 60%) of knee OA patients with an inflammatory phenotype., Trial Registration: Australian and New Zealand Clinical Trial Registry ACTRN12618001656224 . Registered on 08 October 2018., (© 2022. The Author(s).)

A semiquantitative high-resolution mass spectrometry method was developed and applied to assess the occurrence of bromo-/chloro paraffins (BCPs) and olefins (BCOs) in the environment. More than 400 possible BCPs and BCO congener groups were detected in dust, air, and sewage sludge samples collected from Australia. Median chain analytes with the number of halogen atoms <7 (C n H m Cl x Br y , 14 ≤ n ≤ 17, x + y < 7) prevailed in the dust and sludge samples, while short chain analytes (C n H m Cl x Br y , 10 ≤ n ≤ 13, x + y < 7) predominated the air samples. The estimated concentrations of ∑BCPs and ∑BCOs in dust and sludge were approximately 20% that of the chlorinated paraffins (CPs) present, with the median concentrations of 5.4 μg/g (dust) and 0.18 μg/g (sludge) for ∑BCPs and 22 μg/g (in dust) and 0.50 μg/g (sludge) for BCOs. In the air samples, the concentrations of BCPs (0.020 pg/m 3 ) and BCOs (0.032 pg/m 3 ) were 3-4 orders of magnitudes lower than the concentrations of CPs (790 pg/m 3 ). Significant correlations ( P < 0.001) were found between the concentration of CPs, BCPs, and BCOs in all the matrices.

Thinopyrum intermedium (JJJ s J s StSt, 2 n = 6 x = 42), a wild relative of common wheat, possesses many desirable agronomic genes for wheat improvement. The production of wheat- Thinopyrum intermedium introgression lines is a key step for transferring these beneficial genes into wheat. In this study, we characterized three wheat- Thinopyrum intermedium introgression lines TA3681, TA5566, and TA5567 using non-denaturing fluorescence in situ hybridization, genomic in situ hybridization, PCR-based landmark unique gene, and intron targeting markers. Our results showed that TA3681 is a wheat- Thinopyrum intermedium 1St disomic addition line, TA5566 is a wheat- Thinopyrum intermedium non-Robertsonian translocation line carrying two pairs of 3A-7J s translocation chromosomes, and that TA5567 is a wheat- Thinopyrum intermedium non-Robertsonian translocation line carrying a pair of 3A-7J s translocation chromosomes. We developed 13, 36, and 15 Thinopyrum intermedium chromosome-specific markers for detecting the introgressed Thinopyrum chromosomes in TA3681, TA5566, and TA5567, respectively. Stem rust assessment revealed that TA3681 exhibited a high level of seedling resistance to Chinese-prevalent Puccinia graminis f. sp. tritici pathotypes, and both TA5566 and TA5567 were highly resistant to Australian P . graminis f. sp. tritici pathotypes, indicating that Thinopyrum intermedium chromosomes 1St and 7J s might carry new stem rust resistance genes. Therefore, the new identified introgression lines may be useful for improving wheat stem rust resistance.

Objective: To explore the person-level predictors of adherence to a step count intervention following total knee replacement (TKR)., Design: Prospective cohort study, nested within the PATHway trial., Methods: Participants who had recently undergone TKR were recruited from 3 rehabilitation hospitals in Sydney, Australia, for the main trial. Only data from participants who were randomized to the TKR intervention group were analyzed. Participants in the intervention group (n = 51) received a wearable tracker to monitor the number of steps taken per day. Step count adherence was objectively measured at 3 months as the number of steps completed divided by the number prescribed and multiplied by 100 to express adherence as a percentage. Participants were classified into 4 groups: withdrawal, low adherence (0%-79%), adherent (80%-100%), and >100% adherent. Ordinal logistic regression was used to identify which factors predicted adherence to the prescribed step count., Results: Of the 51 participants enrolled, nine (18% of 51) withdrew from the study before 3 months. Half of participants were classified as >100% adherent (n = 24%, 47%). Ten were classified as low adherence (20%), and 8 participants were classified as adherent (16%). In the univariable model, lower age (OR 0.90; 95% CI 0.83-0.97), higher patient activation (OR 1.03; 95% CI 1.00-1.06), and higher technology self-efficacy (OR 1.03; 95% CI 1.00-1.06) were associated with higher adherence. After adjusting for age in the multivariable model, patient activation and technology self-efficacy were not significant., Conclusion: Younger age, higher patient activation, and higher technology self-efficacy were associated with higher adherence to a step count intervention following TKR in the univariable model. Patient activation and technology self-efficacy were not associated with higher adherence following adjustment for age. J Orthop Sports Phys Ther 2022;52(9):620-629. Epub: 9 July 2022. doi:10.2519/jospt.2022.11133 .

Cerebral palsy (CP) is a nonprogressive neurological disorder and the most common physical disability of childhood. There is no cure for CP, but stem cells have the potential to improve brain injury and hence function. This phase 1 clinical trial investigated the safety of the intravenous infusion of full-matched sibling cord blood cells for children with CP aged 1 to 16 years. Preliminary efficacy outcomes were also investigated. Twelve participants received 12/12 HLA-matched sibling cord blood cell infusions. One treatable serious adverse reaction to cryoprotectant was observed, and no adverse reactions occurred beyond 24 h after infusion. Gross motor function measure (GMFM-66) scores did not improve compared with baseline beyond what could be expected from developmental levels, and participants had varied changes in the Quality of Upper Extremity Skills Test (QUEST) and Vineland Adaptive Behavior Scales (VABS-II) scores. In conclusion, matched sibling cord blood cell infusion for children with CP is relatively safe when conducted in an appropriate facility. Australian and New Zealand Clinical Trials Registry (ACTRN12616000403437) and Clinicaltrials.gov (NCT03087110)., Competing Interests: Declaration of Competing Interest Cell Care Australia is a private cord blood bank with a representative on the Trial Steering Committee. There is, therefore, a potential conflict of interest which has been declared to HREC and Steering Committee and is well recognized. No one affiliated with Cell Care Australia was involved in data analysis or interpretation., (Copyright © 2022 International Society for Cell & Gene Therapy. All rights reserved.)

Background: The global increase in total hip or knee arthroplasty has led to concern about the provision of postoperative rehabilitation. Telerehabilitation may be a strategy to meet the patients' requirements for rehabilitation after arthroplasty. This study aims to investigate the effectiveness of a telerehabilitation programme delivered via the mobile application WeChat in patients after total hip or knee arthroplasty on the following outcomes: self-efficacy, physical function, pain, depression, anxiety and health-related quality of life., Methods: This is a single-centre, single-blinded, parallel-group, superiority randomised controlled trial conducted in Shanghai, China. Eighty-four eligible participants who undergo primary total hip or knee arthroplasty will be recruited preoperatively in a university teaching hospital and randomly assigned to the experimental or control group with their informed consent. Once discharged, the control group (n = 42) will receive the usual care provided by the hospital. The experimental group (n = 42) will receive usual care and a 6-week mobile application rehabilitation programme that consists of physical exercises and techniques for enhancing participants' self-efficacy for rehabilitation. Baseline assessments will be conducted on the day before hospital discharge, and outcome assessments will be conducted 6 and 10 weeks postoperatively. The primary outcomes are changes in self-efficacy and physical function 6 weeks postoperatively, and the secondary outcomes include pain, depression, anxiety and health-related quality of life. The approach of a generalised estimating equation will be used to analyse the effect of the intervention on outcomes at a significance level of 0.05., Discussion: This study is the first of its kind conducted in China to incorporate self-efficacy and learning theories as a framework to guide the development of a mobile application rehabilitation programme after arthroplasty. This study will contribute to the knowledge about the effectiveness of mobile application-based rehabilitation among patients after total hip or knee arthroplasty. If the findings are positive, they will support the implementation of mobile application-based rehabilitation in practice, which may potentially increase the accessibility of rehabilitation services as well as patient adherence to rehabilitation., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12621000867897 . Retrospectively registered on July 6, 2021., (© 2022. The Author(s).)

Background: Previous studies suggest that polygenic risk scores (PRSs) may improve melanoma risk stratification. However, there has been limited independent validation of PRS-based risk prediction, particularly assessment of calibration (comparing predicted to observed risks)., Objectives: To evaluate PRS-based melanoma risk prediction in prospective UK and Australian cohorts with European ancestry., Methods: We analysed invasive melanoma incidence in the UK Biobank (UKB; n = 395 647, 1651 cases) and a case-cohort nested within the Melbourne Collaborative Cohort Study (MCCS, Australia; n = 4765, 303 cases). Three PRSs were evaluated: 68 single-nucleotide polymorphisms (SNPs) at 54 loci from a 2020 meta-analysis (PRS68), 50 SNPs significant in the 2020 meta-analysis excluding UKB (PRS50) and 45 SNPs at 21 loci known in 2018 (PRS45). Ten-year melanoma risks were calculated from population-level cancer registry data by age group and sex, with and without PRS adjustment., Results: Predicted absolute melanoma risks based on age and sex alone underestimated melanoma incidence in the UKB [ratio of expected/observed cases: E/O = 0·65, 95% confidence interval (CI) 0·62-0·68] and MCCS (E/O = 0·63, 95% CI 0·56-0·72). For UKB, calibration was improved by PRS adjustment, with PRS50-adjusted risks E/O = 0·91, 95% CI 0·87-0·95. The discriminative ability for PRS68- and PRS50-adjusted absolute risks was higher than for risks based on age and sex alone (Δ area under the curve 0·07-0·10, P < 0·0001), and higher than for PRS45-adjusted risks (Δ area under the curve 0·02-0·04, P < 0·001)., Conclusions: A PRS derived from a larger, more diverse meta-analysis improves risk prediction compared with an earlier PRS, and might help tailor melanoma prevention and early detection strategies to different risk levels. Recalibration of absolute risks may be necessary for application to specific populations., (© 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Objective: To determine whether the combination of systemic corticosteroids and nebulized epinephrine, compared with standard care, reduces the duration of positive pressure support in children with bronchiolitis admitted to intensive care., Study Design: We performed a pragmatic, multicenter, open-label, randomized trial between July 2013 and November 2019 in children younger than 18 months old with a clinical diagnosis of bronchiolitis. The intervention group received the equivalent of 13 mg/kg prednisolone over 3 days, then 1 mg/kg daily for 3 days, plus 0.05 mL/kg of nebulized 1% epinephrine made up to 6 ml with 0.9% saline via jet nebulizer and mask using oxygen at 12 l/min every 30 minutes for 5 doses, then 1-4 hourly for 3 days, then as required for 3 days. The primary outcome was clinician-managed duration of positive pressure support in intensive care defined as high-flow nasal-prong oxygen, nasopharyngeal continuous positive airway pressure, or mechanical ventilation., Results: In total, 210 children received positive pressure support. In the corticosteroid-epinephrine group, 107 children received positive pressure support for a geometric mean of 26 (95% CI, 22-32) hours compared with 40 (95% CI 34-47) hours in 103 controls, adjusted ratio 0.66 (95% CI 0.51-0.84), P = .001. In the intervention group, 41 (38%) children experienced at least 1 adverse event, compared with 39 (38%) in the control group., Conclusions: In children with severe bronchiolitis, the duration of clinician-managed pressure support was reduced by regular treatment with systemic corticosteroids and inhaled epinephrine compared with standard care., Clinical Trial Registration: Australian Clinical Trials Research Network: ACTRN12613000316707., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Importance: More than 1 billion adults have hypertension globally, of whom 70% cannot achieve their hypertension control goal with monotherapy alone. Data are lacking on clinical use patterns of dual combination therapies prescribed to patients who escalate from monotherapy., Objective: To investigate the most common dual combinations prescribed for treatment escalation in different countries and how treatment use varies by age, sex, and history of cardiovascular disease., Design, Setting, and Participants: This cohort study used data from 11 electronic health record databases that cover 118 million patients across 8 countries and regions between January 2000 and December 2019. Included participants were adult patients (ages ≥18 years) who newly initiated antihypertensive dual combination therapy after escalating from monotherapy. There were 2 databases included for 3 countries: the Iqvia Longitudinal Patient Database (LPD) Australia and Electronic Practice-based Research Network 2019 linked data set from South Western Sydney Local Health District (ePBRN SWSLHD) from Australia, Ajou University School of Medicine (AUSOM) and Kyung Hee University Hospital (KHMC) databases from South Korea, and Khoo Teck Puat Hospital (KTPH) and National University Hospital (NUH) databases from Singapore. Data were analyzed from June 2020 through August 2021., Exposures: Treatment with dual combinations of the 4 most commonly used antihypertensive drug classes (angiotensin-converting enzyme inhibitor [ACEI] or angiotensin receptor blocker [ARB]; calcium channel blocker [CCB]; β-blocker; and thiazide or thiazide-like diuretic)., Main Outcomes and Measures: The proportion of patients receiving each dual combination regimen, overall and by country and demographic subgroup., Results: Among 970 335 patients with hypertension who newly initiated dual combination therapy included in the final analysis, there were 11 494 patients from Australia (including 9291 patients in Australia LPD and 2203 patients in ePBRN SWSLHD), 6980 patients from South Korea (including 6029 patients in Ajou University and 951 patients in KHMC), 2096 patients from Singapore (including 842 patients in KTPH and 1254 patients in NUH), 7008 patients from China, 8544 patients from Taiwan, 103 994 patients from France, 76 082 patients from Italy, and 754 137 patients from the US. The mean (SD) age ranged from 57.6 (14.8) years in China to 67.7 (15.9) years in the Singapore KTPH database, and the proportion of patients by sex ranged from 24 358 (36.9%) women in Italy to 408 964 (54.3%) women in the US. Among 12 dual combinations of antihypertensive drug classes commonly used, there were significant variations in use across country and patient subgroup. For example starting an ACEI or ARB monotherapy followed by a CCB (ie, ACEI or ARB + CCB) was the most commonly prescribed combination in Australia (698 patients in ePBRN SWSLHD [31.7%] and 3842 patients in Australia LPD [41.4%]) and Singapore (216 patients in KTPH [25.7%] and 439 patients in NUH [35.0%]), while in South Korea, CCB + ACEI or ARB (191 patients in KHMC [20.1%] and 1487 patients in Ajou University [24.7%]), CCB + β-blocker (814 patients in Ajou University [13.5%] and 217 patients in KHMC [22.8%]), and ACEI or ARB + CCB (147 patients in KHMC [15.5%] and 1216 patients in Ajou University [20.2%]) were the 3 most commonly prescribed combinations. The distribution of 12 dual combination therapies were significantly different by age and sex in almost all databases. For example, use of ACEI or ARB + CCB varied from 873 of 3737 patients ages 18 to 64 years (23.4%) to 343 of 2292 patients ages 65 years or older (15.0%) in South Korea's Ajou University database (P for database distribution by age < .001), while use of ACEI or ARB + CCB varied from 2121 of 4718 (44.8%) men to 1721 of 4549 (37.7%) women in Australian LPD (P for drug combination distributions by sex < .001)., Conclusions and Relevance: In this study, large variation in the transition between monotherapy and dual combination therapy for hypertension was observed across countries and by demographic group. These findings suggest that future research may be needed to investigate what dual combinations are associated with best outcomes for which patients.

Objective: To evaluate the cost-effectiveness of tapentadol immediate-release (IR) versus oxycodone IR for post-operative pain after a major hip surgery., Methods: This study has been conducted using an Australian societal perspective, focusing on adult patients after a major hip surgery. A cost-effectiveness analysis was conducted using a decision-analytic model. The model incorporated drug and other resource costs, the probability of opioid-related adverse events, and quality-adjusted life months (QALM) in each treatment arm. A willingness to pay (WTP) threshold of AU$2500 was used per QALM gained. A probabilistic sensitivity analysis was conducted to examine the uncertainty of the assumptions. The primary outcome was the incremental cost-effectiveness ratio (ICER) of tapentadol IR versus oxycodone IR, expressed as Australian dollars (AU$) per QALM gained., Results: Tapentadol IR dominated oxycodone IR, with a cost savings of AU$201 and an increase in QALM by 0.014. The ICER was -13,946 AU$/QALM (negative value attributed to numerator). In the probabilistic sensitivity analysis, 84.2% of the simulations were in favour of tapentadol IR at the WTP threshold., Conclusions: Tapentadol IR may be more cost-effective than oxycodone IR for the treatment of acute postoperative pain after major hip surgeries.

Introduction: Knee osteoarthritis (KOA) is a highly prevalent disabling joint disease. Intra-articular stem cell therapy is increasingly being used for treating KOA with little high-quality evidence to support its use. The aim of this study is to investigate the efficacy, safety and cost-effectiveness of allogeneic mesenchymal stem cells (Cymerus MSCs) for treating symptomatic tibiofemoral KOA and improving knee structure over 24 months., Methods and Analysis: The Stem Cell injections for symptomatic relief and strUctural improvement in people with Tibiofemoral knee OsteoaRthritis study is a phase III, multi-centre, parallel, superiority, randomised, double-blind, placebo-controlled trial, which will be conducted in Sydney and Hobart, Australia. 440 participants (220 per arm) aged over 40 years with painful KOA and mild to moderate structural change on X-ray (Kellgren and Lawrence grade 2 or 3) with medial minimum joint space width between 1 and 4 mm in the study knee will be recruited from the community and randomly allocated to receive either intra-articular MSCs or saline at baseline, week 3 and week 52. The coprimary outcomes will be the proportion of participants achieving patient-acceptable symptom state for knee pain at 24 months and quantitative central medial femorotibial compartment cartilage thickness change from baseline to 24 months. Main secondary outcomes include change in knee pain, Patient Global Assessment, physical function, quality of life and other structural changes. Additional data for cost-effectiveness analysis will also be recorded. Adverse events will be monitored throughout the study. The primary analysis will be conducted using modified intention-to-treat., Ethics and Dissemination: This protocol has been approved by The University of Sydney (USYD) Human Research Ethics Committee (HREC) #: 2020/119 and The University of Tasmania (UTAS) HREC #: H0021868. All participants will be required to provide informed consent. Dissemination will occur through conferences, social media, and scientific publications., Trial Registration Numbers: Australian New Zealand Clinical Trials Registry (ACTRN12620000870954); U1111-1234-4897., Competing Interests: Competing interests: DJH is supported by an NHMRC Investigator Grant and provides consulting advice for Merck Serono, TLC Bio, Tissuegene and Pfizer. CL has provided consulting advice for Merck Serono and Galapagos Pharmaceuticals, and receives research funding from numerous pharmaceutical companies through specific services/testing contract research agreements between and managed by The University of Sydney or the NSLHD. SL provides consulting advice for Arthro Therapeutics, Pfizer and Synartro. LAD has received partial reimbursement of a conference registration by Pfizer. FE is CEO/CMO and co-owner of Chondrometrics GmbH, and he has provided consulting services to Merck KGaA, Abbvie, Samumed, Kolon-Tissuegene, Servier, Galapagos, Roche, Novartis, ICM and HealthLink. WW is co-owner of Chondrometrics GmbH, and has provided consulting services to Galapagos., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The concentrations of dissolved yttrium and rare earth elements (REY) in sediment pore water provide important geochemical information. However, due to the low REY concentration, complex matrix, and limited sample volume (often only a few milliliters), analysis of the REY in pore water often is highly challenging. In this study, a method was established to determine the dissolved REY in pore water of marine sediments using an offline preconcentration step with the ethylenediaminetriacetate chelating resin, followed by inductively coupled plasma-mass spectrometry. In addition, using a commercially available automated trace-element preconcentration system, the preconcentration step can be fully automated, saving labor and providing a better control of the final elution volume. The experimental conditions (pH, elution volume, elution acid concentration, and organic complexation effect) were assessed, and the optimal conditions were chosen. In particular, the organic complexation effect was found to be negligible. The procedure blank and limit of detection were satisfactory for studying REY in pore water of marine sediments, and the method also yielded satisfactory recoveries for the REY elements (83-110%). The method was then applied to analyze the dissolved REY concentrations of pore water samples collected in a sediment core (~ 30 cm) in the central Indian Ocean. The vertical distribution, dissolved REY concentration, and the average Post Archean Australian Shale-normalized pattern of the REY showed similarities to the previously published pore water REY data. This method provides an accurate yet facile approach for the analysis of all 15 REY in marine pore water samples using the sample volume of only ~ 5 mL., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Objective: To assess the antifracture efficacy and safety of a nutritional intervention in institutionalised older adults replete in vitamin D but with mean intakes of 600 mg/day calcium and <1 g/kg body weight protein/day., Design: Two year cluster randomised controlled trial., Setting: 60 accredited residential aged care facilities in Australia housing predominantly ambulant residents., Participants: 7195 permanent residents (4920 (68%) female; mean age 86.0 (SD 8.2) years)., Intervention: Facilities were stratified by location and organisation, with 30 facilities randomised to provide residents with additional milk, yoghurt, and cheese that contained 562 (166) mg/day calcium and 12 (6) g/day protein achieving a total intake of 1142 (353) mg calcium/day and 69 (15) g/day protein (1.1 g/kg body weight). The 30 control facilities maintained their usual menus, with residents consuming 700 (247) mg/day calcium and 58 (14) g/day protein (0.9 g/kg body weight)., Main Outcome Measures: Group differences in incidence of fractures, falls, and all cause mortality., Results: Data from 27 intervention facilities and 29 control facilities were analysed. A total of 324 fractures (135 hip fractures), 4302 falls, and 1974 deaths were observed. The intervention was associated with risk reductions of 33% for all fractures (121 v 203; hazard ratio 0.67, 95% confidence interval 0.48 to 0.93; P=0.02), 46% for hip fractures (42 v 93; 0.54, 0.35 to 0.83; P=0.005), and 11% for falls (1879 v 2423; 0.89, 0.78 to 0.98; P=0.04). The risk reduction for hip fractures and falls achieved significance at five months (P=0.02) and three months (P=0.004), respectively. Mortality was unchanged (900 v 1074; hazard ratio 1.01, 0.43 to 3.08)., Conclusions: Improving calcium and protein intakes by using dairy foods is a readily accessible intervention that reduces the risk of falls and fractures commonly occurring in aged care residents., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12613000228785., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: funding support from the organisations listed above; SI has received lecture fees from Abbott; TVN has received research support and lecture fees from Amgen, MSD, and Novartis; ES has received research support from Amgen and MSD and lecture fees from Amgen, Eli Lilly, and Allergan; ES is a scientific consultant for StraxCorp and shareholder; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Microplastics (1 - 5000 µm) are pervasive in every compartment of our environment. However, little is understood regarding the concentration and size distribution of microplastics in road dust, and how they change in relation to human activity. Within road dust, microplastics move through the environment via atmospheric transportation and stormwater run-off into waterways. Human exposure pathways to road dust include dermal contact, inhalation and ingestion. In this study, road dust along an urban to rural transect within South-East Queensland, Australia was analysed using Accelerated Solvent Extraction followed by pyrolysis Gas Chromatography-Mass Spectrometry (Pyr-GC/MS). Polypropylene, polystyrene, polyethylene terephthalate, polyvinyl chloride, poly (methyl methacrylate) and polyethylene were quantified. Microplastic concentrations ranged from ~0.5 mg/g (rural site) to 6 mg/g (Brisbane city), consisting primarily of polyvinyl chloride (29%) and polyethylene terephthalate (29%). Size fractionation (< 250 µm, 250-500 µm, 500-1000 µm, 1000-2000 µm and 2000-5000 µm) established that the < 250 µm size fraction contained the majority of microplastics by mass (mg/g). Microplastic concentrations in road dust demonstrated a significant relationship with the volume of vehicles (r 2 = 0.63), suggesting traffic, as a proxy for human movement, is associated with increased microplastic concentrations in the built environment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study investigated mass concentrations of selected plastics in store-bought rice, the staple of more than half the world's population. Polyethylene, polyethylene terephthalate, poly-(methyl methacrylate), polypropylene, polystyrene and polyvinyl chloride were quantified using pressurized liquid extraction coupled to double-shot pyrolysis gas chromatography/mass spectrometry. Polyethylene, polypropylene and polyethylene terephthalate were quantifiable in the rice samples with polyethylene the most frequently detected (95%). There was no statistical difference between total plastic concentration in paper and plastic packaged rice. Shaking the rice in its packaging had no significant difference on the concentration of plastics. Washing the rice with water significantly reduced plastic contamination. Instant (pre-cooked) rice contained fourfold higher levels of plastics, suggesting that industrial processing potentially increases contamination. A preliminary estimate of the intake of plastic through rice consumption for Australians established 3.7 mg per serve (100 g) if not washed and 2.8 mg if washed. Annual consumption was estimated around 1 g/person., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Tezacaftor-ivacaftor is an approved cystic fibrosis transmembrane conductance regulator (CFTR) modulator shown to be efficacious and generally safe and well tolerated over 8-24 weeks in phase 3 clinical studies in participants aged 12 years or older with cystic fibrosis homozygous for the Phe508del CFTR mutation (F/F; study 661-106 [EVOLVE]) or heterozygous for the Phe508del CFTR mutation and a residual function mutation (F/RF; study 661-108 [EXPAND]). Longer-term (>24 weeks) safety and efficacy of tezacaftor-ivacaftor has not been assessed in clinical studies. Here, we present results of study 661-110 (EXTEND), a 96-week open-label extension study that assessed long-term safety, tolerability, and efficacy of tezacaftor-ivacaftor in participants aged 12 years or older with cystic fibrosis who were homozygous or heterozygous for the Phe508del CFTR mutation., Methods: Study 661-110 was a 96-week, phase 3, multicentre, open-label study at 170 clinical research sites in Australia, Europe, Israel, and North America. Participants were aged 12 years or older, had cystic fibrosis, were homozygous or heterozygous for Phe508del CFTR, and completed one of six parent studies of tezacaftor-ivacaftor: studies 661-103, 661-106, 661-107, 661-108, 661-109, and 661-111. Participants received oral tezacaftor 100 mg once daily and oral ivacaftor 150 mg once every 12 h for up to 96 weeks. The primary endpoint was safety and tolerability. Secondary endpoints were changes in lung function, nutritional parameters, and respiratory symptom scores; pulmonary exacerbations; and pharmacokinetic parameters. A post-hoc analysis assessed the rate of lung function decline in F/F participants who received up to 120 weeks of tezacaftor-ivacaftor in studies 661-106 (F/F) and/or 661-110 compared with a matched cohort of CFTR modulator-untreated historical F/F controls from the Cystic Fibrosis Foundation Patient Registry. Primary safety analyses were done in all participants from all six parent studies who received at least one dose of study drug during this study. This study was registered at ClinicalTrials.gov (NCT02565914)., Findings: Between Aug 31, 2015, to May 31, 2019, 1044 participants were enrolled in study 661-110 from the six parent studies of whom 1042 participants received at least one dose of study drug and were included in the safety set. 995 (95%) participants had at least one TEAE; 22 (2%) had TEAEs leading to discontinuation; and 351 (34%) had serious TEAEs. No deaths occurred during the treatment-emergent period; after the treatment-emergent period, two deaths occurred, which were both deemed unrelated to study drug. F/F (106/110; n=459) and F/RF (108/110; n=226) participants beginning tezacaftor-ivacaftor in study 661-110 had improvements in efficacy endpoints consistent with parent studies; improvements in lung function and nutritional parameters and reductions in pulmonary exacerbations observed in the tezacaftor-ivacaftor groups in the parent studies were generally maintained in study 661-110 for an additional 96 weeks. Pharmacokinetic parameters were also similar to those in the parent studies. The annualised rate of lung function decline was 61·5% (95% CI 35·8 to 86·1) lower in tezacaftor-ivacaftor-treated F/F participants versus untreated matched historical controls., Interpretation: Tezacaftor-ivacaftor was generally safe, well tolerated, and efficacious for up to 120 weeks, and the safety profile of tezacaftor-ivacaftor in study 661-110 was consistent with cystic fibrosis manifestations and with the safety profiles of the parent studies. The rate of lung function decline was significantly reduced in F/F participants, consistent with cystic fibrosis disease modification. Our results support the clinical benefit of long-term tezacaftor-ivacaftor treatment for people aged 12 years or older with cystic fibrosis with F/F or F/RF genotypes., Funding: Vertex Pharmaceuticals Incorporated., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The most prominent problem in the current citrus industry worldwide is the epidemic of citrus Huanglongbing (HLB), also known as greening disease. Huang et al. identified a stable peptide, which has antimicrobial activities and induces systemic immune response against HLB, from Australian finger lime. This peptide effectively suppresses disease symptoms in citrus and protects healthy trees against this disease., Competing Interests: Declaration of Interests The authors declare no conflicts of interest., (Published by Elsevier Ltd.)

Background: Physical activity (PA) is important to general health and knee osteoarthritis (OA). Excessive workplace PA is an established risk factor for knee OA however, appropriate methods of measurement are unclear. There is a need to examine and assess the utility of new methods of measuring workplace PA and estimating knee load prior to application to large-scale, knee OA cohorts. Our aims, therefore, were to monitor workplace PA and estimate lower-limb loading across different occupations in health participants., Methods: Twenty-four healthy adults, currently working full-time in a single occupation (≥ 35 h/week) and free of musculoskeletal disease, comorbidity and had no history of lower-limb injury/surgery (past 12-months) were recruited across New South Wales (Australia). A convenience sample was recruited with occupations assigned to levels of workload; sedentary, light manual and heavy manual. Metrics of workplace PA including tasks performed (i.e., sitting), step-count and lower-limb loading were monitored over 10 working days using a daily survey, smartwatch, and a smartphone., Results: Participants of light manual occupations had the greatest between-person variations in mean lower-limb load (from 2 to 59 kg*m/s3). Lower-limb load for most participants of the light manual group was similar to a single participant in heavy manual work (30 kg*m/s3) and was at least three times greater than the sedentary group (2 kg*m/s3). The trends of workplace PA over working hours were largely consistent, per individual, but rare events of extreme loads were observed across all participants (up to 760 kg*m/s3)., Conclusions: There are large interpersonal variations in metrics of workplace PA, particularly among light and heavy manual occupations. Our estimates of lower-limb loading were largely consistent with pre-conceived levels of physical demand. We present a new approach to monitoring PA and estimating lower-limb loading, which could be applied to future occupational studies of knee OA.

Firefighters are exposed to a wide variety of chemicals including polycyclic aromatic hydrocarbons (PAHs) while attending fire scenes. The objective of this study was to understand the exposure of firefighters to PAHs when attending simulated compartment fires that consisted of either a diesel pan or particleboard fire. Firefighters remained in the compartment fires for 15 min while using standard gear including self contained breathing apparatus (SCBA). Firefighters were able to remove firefighting clothing and shower within 10 min of leaving the burn. Air samples were collected from inside the compartment during the fire. Twenty-six (26) firefighters participated in the study providing urine and skin wipe samples collected from the wrist and neck before and after either one of the burn types. The concentrations of PAHs were measured in skin wipes and air samples, while concentrations of monohydroxy metabolites of PAHs (OH-PAHs) were measured in urine. The concentrations of all PAHs were significantly higher (p < 0.05) in the smoke layer of particleboard fires than in diesel pan fires. Correspondingly, the level of PAHs deposited on the wrists and necks of participants attending the particleboard fires was higher than those attending diesel pan fires. Urine samples from participants who attended diesel pan fires showed no significant difference (p > 0.05) in the concentration of all OH-PAHs between pre-burn and post-burn. Samples from participants who attended particleboard fires, showed no significant difference (p > 0.05) between 1-hydroxypyrene (1-OH-PYR) concentrations in urine pre- and post-burn. However, median concentrations of hydroxynaphthalenes (OH-NAPs), hydroxyfluorenes (OH-FLUs) and hydroxyphenanthrenes (OH-PHEs) increased significantly from 5.2, 0.44 and 0.88 μg g -1 creatinine pre-burn to 12, 1.4 and 1.2 μg g -1 creatinine post-burn, respectively. This suggests that in compartment burns with high concentrations of PAHs in the smoke layer, such as those created by the particleboard fires, exposure to PAHs can be observed though urinary OH-PAH metabolites. Overall, concentrations of urinary OH-PAHs were relatively low considering the potential exposure in these burns. This suggests protective equipment in combination with rapid removal of firefighting ensembles and showering are relatively effective in controlling exposure., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Background and Purpose: As outcomes for acute ischemic stroke (AIS) vary according to clinical profile and management approaches, we aimed to determine disparities in clinical outcomes between Asian and non-Asian participants of the international, Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED)., Methods: ENCHANTED was a multicenter, prospective, partial-factorial, randomized, open trial of low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) alteplase, and intensive (target systolic blood pressure [SBP] 130-140 mm Hg) or guideline-recommended (<180 mm Hg) BP management, in thrombolysis-eligible AIS patients. Logistic regression models were used to examine the associations with outcomes of death or disability (modified Rankin scale [mRS] scores 2-6), major disability (mRS 3-5), death, and intracranial hemorrhage (ICH), with adjustment prognostic factors, alteplase dose, and mean SBP over 1-24 h., Results: Among 4,551 thrombolyzed AIS patients (mean age 66.7 years, 37.8% female), there were 65.4% Asians who were younger, fewer female, and with less atrial fibrillation, hypercholesterolemia, premorbid symptoms, and concomitant antihypertensive, antithrombotic and statin treatment, and more prior stroke, compared to non-Asians. Frequencies of hypertension, coronary artery disease, and diabetes mellitus were comparable between groups. Asian patients were less likely to be admitted to an acute stroke unit and receive early mobilization by a therapist or rehabilitation but more likely to receive intensive care. There were no significant differences between Asians and non-Asians in functional outcome (defined by mRS scores 2-6 or 3-5; adjusted odds ratio [OR] 1.00, 95% confidence interval [CI] 0.85-1.19 [p = 0.958] and OR 0.95, 95% CI 0.80-1.13 [p = 0.572], respectively), or death (OR 1.25, 95% CI 0.95-1.65; p = 0.116), despite Asians having greater odds of ICH (OR 1.51, 95% CI 1.23-1.86; p = 0.0001) and neurological deterioration within 24 h (OR 1.58, 95% CI 1.18-2.12; p = 0.002)., Conclusions: Within the context of an international clinical trial of thrombolyzed AIS patients, demography, risk factors, management, and odds of early neurological deterioration and ICH, all differ between Asian and non-Asian participants. However, patterns of functional recovery are similar between these major regional groups., (© 2021 S. Karger AG, Basel.)

Objective: Access to acute stroke unit (ASU) care is known to vary worldwide. We aimed to quantify regional variations in the various components of ASU care., Method: Secondary analysis of the Head Positioning in acute Stroke Trial (HeadPoST), an international, multicentre, cluster crossover trial of head-up versus head-down positioning in 11,093 acute stroke patients at 114 hospitals in 9 countries. Patients characteristics and 11 standard components of processes of care were described according to ASU admission within and across four economically-defined regional groups (Australia/UK, China [includes Taiwan], India/Sri Lanka, and South America [Brazil/Chile/Colombia]). Variations in process of ASU care estimates were obtained in hierarchical mixed models, with adjustment for study design and potential patient- and hospital-level confounders., Results: Of 11,086 patients included in analyses, 59.7% (n = 6620) had an ASU admission. In China, India/Sri Lanka and South America, ASU patients were older, had greater neurological severity and more premorbid conditions than non-ASU patients. ASU patients were more likely to receive reperfusion therapy and multidisciplinary care within regions, but the components of care varied across regions. With Australia/UK as reference, patients in other regions had a lower probability of receiving reperfusion therapy, especially in India/Sri Lanka (adjusted odds ratio [aOR] 0.27, 95% confidence interval [CI] 0.12-0.63) and multidisciplinary care (mainly in formal dysphagia assessment, physiotherapy and occupational therapy)., Conclusion: There is significant variation in the components of stroke care across economically-defined regions of the world. Ongoing efforts are required to reduce disparities and optimise health outcomes, especially in resource poor areas., Clinical Trial Registration: HeadPoST is registered at ClinicalTrials.gov (NCT02162017)., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Plastics are contaminants of emerging concern that can enter the environment from multiple sources, including via land application of treated sewage sludge (biosolids). Biosolids samples collected from 82 wastewater treatment plants (WWTPs) across Australia and covering 34% of the population during census week in 2016 were quantitatively analyzed to estimate the release of seven common plastics. Quantitative analysis was performed by pressurized liquid extraction followed by double-shot microfurnace pyrolysis coupled to gas chromatography mass spectrometry. Ninety nine percent of the samples contained plastics (Σ 6 plastics) at concentrations of between 0.4 and 23.5 mg/g dry weight (median; 10.4 mg/g dry weight), while polycarbonate was not detected in any sample. Per-capita mass loads of plastics (Σ 6 plastics) released were between 8 and 877 g/person/year across all investigated WWTPs. Polyethylene was the predominant plastic detected, contributing to 69% of Σ 6 plastics. Based on the concentrations measured, it was projected that around 4700 metric tons (Mt) of plastics are released into the Australian environment through biosolids end-use each year, equating to approximately 200 g/person/year, which represents 0.13% of total plastics use in Australia. Of this, 3700 Mt of plastics are released to agricultural lands and 140 Mt to landscape topsoil. Our results provide a first quantitative per-capita mass loads and emission estimate of plastic types through biosolids end-use.

Large-scale extraction of the leaves of the Australian rainforest tree Maytenus bilocularis followed by extensive purification studies afforded the targeted and abundant dihydro-β-agarofuran, bilocularin A, in sufficient quantities (>500 mg) for detailed semi-synthetic chemistry. Eight bilocularin A carbamate analogues were synthesised using a series of commercially available isocyanate reagents in high purity (>95%) and variable yields (9-91%). All previously undescribed analogues were spectroscopically characterised using NMR, UV, IR and MS data. One compound afforded crystalline material and subsequent single crystal X-ray analysis (Cu-Kα) confirmed the chemical structure along with the absolute configuration. All compounds were evaluated for anti-proliferative activity against the human prostate cancer cell line LNCaP; none of the compounds showed significant (>50%) growth inhibition at 20 μM. Compounds were also tested for their ability to inhibit leucine transport in LNCaP cells, and two analogues showed moderate activity with IC 50 values of 8.9 and 8.5 μM. This is the first reported synthesis of dihydro-β-agarofuran carbamate derivatives., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Key Message: We detected 213 lodging QTLs and demonstrated that drought-induced stem lodging in grain sorghum is substantially associated with stay-green and plant height suggesting a critical role of carbon remobilisation. Sorghum is generally grown in water limited conditions and often lodges under post-anthesis drought, which reduces yield and quality. Due to its complexity, our understanding on the genetic control of lodging is very limited. We dissected the genetic architecture of lodging in grain sorghum through genome-wide association study (GWAS) on 2308 unique hybrids grown in 17 Australian sorghum trials over 3 years. The GWAS detected 213 QTLs, the majority of which showed a significant association with leaf senescence and plant height (72% and 71%, respectively). Only 16 lodging QTLs were not associated with either leaf senescence or plant height. The high incidence of multi-trait association for the lodging QTLs indicates that lodging in grain sorghum is mainly associated with plant height and traits linked to carbohydrate remobilisation. This result supported the selection for stay-green (delayed leaf senescence) to reduce lodging susceptibility, rather than selection for short stature and lodging resistance per se, which likely reduces yield. Additionally, our data suggested a protective effect of stay-green on weakening the association between lodging susceptibility and plant height. Our study also showed that lodging resistance might be improved by selection for stem composition but was unlikely to be improved by selection for classical resistance to stalk rots.

The global monsoon is characterised by transitions between pronounced dry and wet seasons, affecting food security for two-thirds of the world's population. Rising atmospheric CO 2 influences the terrestrial hydrological cycle through climate-radiative and vegetation-physiological forcings. How these two forcings affect the seasonal intensity and characteristics of monsoonal precipitation and runoff is poorly understood. Here we use four Earth System Models to show that in a CO 2 -enriched climate, radiative forcing changes drive annual precipitation increases for most monsoon regions. Further, vegetation feedbacks substantially affect annual precipitation in North and South America and Australia monsoon regions. In the dry season, runoff increases over most monsoon regions, due to stomatal closure-driven evapotranspiration reductions and associated atmospheric circulation change. Our results imply that flood risks may amplify in the wet season. However, the lengthening of the monsoon rainfall season and reduced evapotranspiration will shorten the water resources scarcity period for most monsoon regions.

Coronavirus disease 19 (COVID-19) has become a pandemic around the world. With the explosive growth of confirmed cases, emergency medical supplies are facing global shortage, which restricts the treatment of seriously ill patients and protection of medical staff. Taking China, the United States, Australia, and Canada as examples, this study compares and analyzes the reserve and supply systems of emergency medical supplies and problems exposed in response to the COVID-19 epidemic. Some common problems were found, such as insufficient types and quantities of emergency medical supplies in reserve, insufficient emergency production capacity, and imperfect command mechanism for emergency supplies deployment and transportation. A sound reserve system of emergency medical supplies is the basis and guarantee for dealing with public health emergencies such as major outbreaks. Based on the comparison of systems and practical experience, countries around the world should further improve the reserve and supply system of emergency medical supplies, and improve the coordination and cooperation mechanism for emergency supplies for international public health emergencies, so as to cope with increasingly severe public health emergencies in the context of globalization.