Search

To assess longitudinal, population-based data on the prevalence and impact of chronic pancreatitis in children.Administrative data linkage was used to ascertain an index cohort consisting of all individuals who had an initial diagnosis of chronic pancreatitis before age 19 years in the South Australian public hospital system between June 2000 and June 2019. Age- and sex-matched controls were drawn from the general population of South Australia, children with type 1 diabetes, and children with type 2 diabetes. Main outcomes and measures included hospital visits, days in hospital, emergency department (ED) visits, intensive care unit (ICU) admissions, education comparators, and incidence and prevalence estimates.A total of 73 incident cases were identified. The crude prevalence and incidence of pediatric chronic pancreatitis were estimated at 6.8/100 000 and 0.98/100 000 per year, respectively. Of the index cohort, 24 cases (32.8%) of pediatric chronic pancreatitis were identified as occurring in children of Aboriginal and/or Torres Strait Islander descent. Compared with matched general population controls, children with chronic pancreatitis averaged 11-fold more hospital visits, 5-fold more ED visits, and 9-fold more ICU admissions; spent 10-fold more days in the hospital; and had a 2-fold higher rate of absence from school (P .001 for all). Similarly, children with chronic pancreatitis used substantially more health resources than children with type 1 or 2 diabetes.Pediatric patients with chronic pancreatitis consume a high volume of public health services and are significantly impacted in their ability to engage in education.

Background There are major health disparities between Indigenous and non-Indigenous Australians. To address this, it is vital to understand the landscape of Indigenous trial activity. Methods We extracted data from all Australian trials registered between 2008-2018 on the Australian New Zealand Clinical Trials Registry or ClinicalTrials.gov. Indigenous-focused trials were identified by searching for relevant terms such as ‘Indigenous’ and ‘Aboriginal’. Indigenous versus non-Indigenous trials and Australian trials overall were compared by conditions studied, intervention type, study design and funding. Results Of the 9206 included trials, 139 (1.5%) focused on Indigenous health, and these were mostly in ‘Public Health’ (n = 69, 50%), ‘Mental Health’ (n = 35, 25%) and ‘Cardiovascular’ (n = 25, 18%) (Figure). Compared to other Australian trials, Indigenous trials more frequently studied ear conditions (OR 16.47, 95%CI=8.43-29.99) and public health (OR 4.87, 95%CI=3.65-6.41), and were more likely to focus on screening (OR 3.57, 95%CI=2.10-5.70) and prevention (OR 2.24, 95%CI=1.61-3.08) rather than treatment (OR 0.40, 95%CI =0.30-0.52). They were less likely to be blinded (OR 1.72, 95%CI=1.20-2.49), or have any industry involvement (OR 2.52, 95%CI=1.54-4.43). Conclusions Indigenous trials differed from other Australian trials in health conditions studied, intervention focus, blinding and industry involvement. Relative to population size and burden of disease, the number of trials focusing on Indigenous health is low. Key messages Trial registries can be used to explore whether research appropriately addresses diverse populations such as Indigenous Australians. This can inform future research prioritisation.

It is critical that health service evaluation frameworks include Aboriginal people and their cultural worldviews from design to implementation. During a large participatory action research study, Elders, service leaders and Aboriginal and non-Aboriginal researchers co-designed evaluation tools to test the efficacy of a previously co-designed engagement framework. Through a series of co-design workshops, tools were built using innovative collaborative processes that foregrounded Aboriginal worldviews. The workshops resulted in the development of a three-way survey that records the service experiences related to cultural safety from the perspective of Aboriginal clients, their carer/s, and the service staff with whom they work. The surveys centralise the role of relationships in client-service interactions, which strongly reflect their design from an Aboriginal worldview. This paper provides new insights into the reciprocal benefits of engaging community Elders and service leaders to work together to develop new and more meaningful ways of servicing Aboriginal families. Foregrounding relationships in service evaluations reinstates the value of human connection and people-centred engagement in service delivery which are central to rebuilding historically fractured relationships between mainstream services and Aboriginal communities. This benefits not only Aboriginal communities, but also other marginalised populations expanding the remit of mainstream services to be accessed by many. Refereed/Peer-reviewed

Solvent extraction is used widely for chemical separations and environmental remediation. Although the kinetics and efficiency of this process rely upon the formation of ion–extractant complexes, it has proven challenging to identify the location of ion–extractant complexation within the solution and its impact on the separation. Here, we use tensiometry and X-ray scattering to characterize the surface of aqueous solutions of lanthanide chlorides and the water-soluble extractant bis(2-ethylhexyl) phosphoric acid (HDEHP), in the absence of a coexisting organic solvent. These studies restrict ion–extractant interactions to the aqueous phase and its liquid–vapor interface, allowing us to explore the consequences that one or the other is the location of ion–extractant complexation. Unexpectedly, we find that light lanthanides preferentially occupy the liquid–vapor interface. This contradicts our expectation that heavy lanthanides should have a higher interfacial density since they are preferentially extracted by HDEHP in solvent extraction processes. These results reveal the antagonistic role played by ion–extractant complexation within the aqueous phase and clarify the advantages of complexation at the interface. Extractants in common use are often soluble in water, in addition to their organic phase solubility, and similar effects to those described here are expected to be relevant to a variety of separations processes., Observations of lanthanide ions and HDEHP extractants at the aqueous−vapor interface suggest an unexpected role for aqueous complexation and speciation in the process of liquid−liquid extraction.

To assess associations of hyperglycemia in pregnancy with the risk of postpartum hemorrhage (PPH) in a prospective cohort of Indigenous and non-Indigenous women, compared with normoglycemia.Data were from 1102 (48% Indigenous) women of the Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) Study. Age-adjusted associations of gestational diabetes mellitus (GDM) or pre-existing type 2 diabetes mellitus (T2DM), obstetric and demographic covariables with PPH (blood loss ≥500 ml) were assessed using logistic regression. Multivariable-adjusted models included Indigenous ethnicity, diabetes type and their interaction.A higher proportion of Indigenous women developed PPH than non-Indigenous women (32% versus 22%; P 0.001). Compared with non-Indigenous women with normoglycemia, risks of PPH for Indigenous women with GDM or T2DM were higher (odds ratio [OR] 1.83, 95% confidence intervals [CI] 1.11-3.02, and OR 1.72, 95% CI 0.99-3.00 after age adjustment, OR 1.84, 95% CI 1.06-3.19, and OR 1.33, 95% CI 0.70-2.54 after adjustment for school education and delivery mode, and OR 1.62, 95% CI 0.95-2.77, and OR 0.99, 95% CI 0.53-1.86 after adjustment for birth weight). Importantly, Indigenous women without hyperglycemia in pregnancy were not at increased risk of PPH.The significantly higher rates of PPH experienced by Indigenous women compared with non-Indigenous women may be explained by a greater effect of GDM among Indigenous women that was only partly accounted for by birth weight.

Background This study examines the claim that social inequality in health in European populations was absent prior to 1750. This claim is primarily based on comparisons of life expectancy at birth in England between general and ducal (elite aristocrat) social classes from the 1550s to the 1870s. Methods We examined historic childhood mortality trends among the English ducal class and the general population, based on previously published data. We compared mid-childhood to adolescent mortality (age 5–14) and early-childhood mortality (age 0–4) between the ducal class and the general population from the 17th to 19th centuries. Results Prior to 1750, ducal early-childhood mortality was higher than the general population. However, mid-childhood to adolescent mortality was lower among the ducal class than the general population in all observed periods for boys, and almost all periods for girls. Among the ducal class, but not the general population, there was a sharp decline in early-childhood mortality around the 1750s which may partly explain the divergent trends in overall life expectancy at birth. Conclusion Health inequality between the ducal class and general population was present in England from the 16th to mid-18th centuries, with disadvantages in mortality for ducal children in infancy and early childhood, but survival advantages in mid-childhood and adolescence. These opposing effects are obscured in life expectancy at birth data. Relatively high early-childhood mortality among ducal families before 1750 likely resulted from short birth intervals and harmful infant feeding practices during this time., Highlights • We re-examine the claim that social inequality in health was absent in Britain before 1750. • This claim is based on life expectancy at birth among ducal and general populations. • We found consistently “pro-ducal” mortality gaps from age 5 to 14. • “Anti-ducal” under-5 mortality before 1750 may relate to short ducal birth intervals and feeding practices. • Social inequality in health did exist before 1750, but varied by age group.

ObjectiveTo identify factors associated with sight-threatening diabetic macular oedema (STDM) in Indigenous Australians attending an Indigenous primary care clinic in remote Australia.Methods and analysisA cross-sectional study design of retinopathy screening data and routinely-collected clinical data among 236 adult Indigenous participants with type 2 diabetes (35.6% men) set in one Indigenous primary care clinic in remote Australia. The primary outcome variable was STDM assessed from retinal images.ResultsAge (median (range)) was 48 (21–86) years, and known diabetes duration (median (range)) was 8.0 (0–24) years. Prevalence of STDM was high (14.8%) and similar in men and women. STDM was associated with longer diabetes duration (11.7 vs 7.9 years, respectively; p300 mg/mmol) (20.6 vs 5.7%, respectively; p=0.014) and chronic kidney disease (25.7 vs 12.2%, respectively; p=0.035). Some clinical factors differed by sex: anaemia was more prevalent in women. A higher proportion of men were smokers, prescribed statins and had increased albuminuria. Men had higher blood pressure, but lower glycated Haemoglobin A1c (HbA1c) levels and body mass index, than women.ConclusionSTDM prevalence was high and similar in men and women. Markers of renal impairment and longer diabetes duration were associated with STDM in this Indigenous primary care population. Embedded teleretinal screening, known diabetes duration-based risk stratification and targeted interventions may lower the prevalence of STDM in remote Indigenous primary care services.Trial registration numberAustralia and New Zealand Clinical Trials Register: ACTRN 12616000370404.

IntroductionOpportunities for improved mental health and wellbeing of Aboriginal and Torres Strait Islander children and young people lie in improving the capability of primary healthcare services to identify mental healthcare needs and respond in timely and appropriate ways. The development of culturally appropriate mental health assessment tools and clinical pathways have been identified as opportunities for strengthening workforce capacity in this area. The Ngalaiya Boorai Gabara Budbut implementation project seeks to pursue these opportunities by developing and validating a psychosocial assessment tool, understanding what services need to better care for your people and developing resources that address those needs.Methods and analysisThe project will be governed by a research governance group comprising Aboriginal service providers, young people, and researchers. It will be implemented in an urban health service in Canberra, and regional services in Moree, Wollongong, and the Illawarra regions of New South Wales Australia. The validation study will follow an argument-based approach, assessing cultural appropriateness and ease of use; test–retest validity; internal consistency, construct validity and the quality of decisions made based on the assessment. Following piloting with a small group of young people and their caregivers (n=10), participants (n=200) will be young people and/or their caregivers, attending one of the partner services. The needs assessment will involve an in-depth exploration of service via an online survey (n=60) and in-depth interviews with service providers (n=16) and young people (n=16). These activities will run concurrently. Service providers, researchers and the governance group will codesign resources that respond to the needs identified and pilot them through the participating services.Ethics and disseminationThe Aboriginal Health and Medical Research Council of NSW Human Research Ethics committee (#1769/21) has approved this project. Informed consent will be obtained from all participants and/or their caregivers (with assent from those aged

Aboriginal and Torres Strait Islander holistic health represents the interconnection of social, emotional, spiritual and cultural factors on health and well-being. Social factors (education, employment, housing, transport, food and financial security) are internationally described and recognised as the social determinants of health. The social determinants of health are estimated to contribute to 34% of the overall burden of disease experienced by Aboriginal and Torres Strait Islander people. Primary health care services currently ‘do what it takes’ to address social and emotional well-being needs, including the social determinants of health, and require culturally relevant tools and processes for implementing coordinated and holistic responses. Drawing upon a research-setting pilot program, this manuscript outlines key elements encapsulating a strengths-based approach aimed at addressing Aboriginal and Torres Strait Islander holistic social and emotional well-being. The Cultural Pathways Program is a response to community identified needs, designed and led by Aboriginal and Torres Strait Islander people and informed by holistic views of health. The program aims to identify holistic needs of Aboriginal and Torres Strait Islander people as the starting point to act on the social determinants of health. Facilitators implement strengths-based practice to identify social and cultural needs (e.g. cultural and community connection, food and financial security, housing, mental health, transport), engage in a goal setting process and broker connections with social and health services. An integrated culturally appropriate clinical supervision model enhances delivery of the program through reflective practice and shared decision making. These embedded approaches enable continuous review and improvement from a program and participant perspective. A developmental evaluation underpins program implementation and the proposed culturally relevant elements could be further tailored for delivery within primary health care services as part of routine care to strengthen systematic identification and response to social and emotional well-being needs.

Background Aboriginal and Torres Strait Islander peoples (hereafter respectfully referred to as Indigenous Australians) represent about 3% of the total Australian population. Major health disparities exist between Indigenous and Non-Indigenous Australians. To address this, it is vital to understand key health priorities and knowledge gaps in the current landscape of clinical trial activity focusing on Indigenous health in Australia. Methods Australian-based clinical trials registered on the Australian New Zealand Clinical Trials Registry or ClinicalTrials.gov from 2008 to 2018 were analysed. Australian clinical trials with and without a focus on Indigenous health were compared in terms of total numbers, participant size, conditions studied, design, intervention type and funding source. Results Of the 9206 clinical trials included, 139 (1.5%) focused on Indigenous health, with no proportional increase in Indigenous trials over the decade (p = 0.30). Top conditions studied in Indigenous-focused trials were mental health (n = 35, 28%), cardiovascular disease (n = 20, 20%) and infection (n = 16, 16%). Compared to General Australian trials, Indigenous-focused trials more frequently studied ear conditions (OR 20.26, 95% CI 10.32–37.02, p p p p p = 0.021) and surgery (OR 0.17, 95% CI 0.01–0.73, p = 0.027). For intervention types, Indigenous trials focused more on prevention (n = 48, 36%) and screening (n = 18, 13%). They were far less involved in treatment (n = 72, 52%) as an intervention than General Australian trials (n = 6785, 75%), and were less likely to be blinded (n = 48, 35% vs n = 4273, 47%) or have industry funding (n = 9, 7% vs 1587, 17%). Conclusions Trials with an Indigenous focus differed from General Australian trials in the conditions studied, design and funding source. The presented findings may inform research prioritisation and alleviate the substantial burden of disease for Indigenous population.

The nuclear root-mean-square charge radius of ^{54}Ni was determined with collinear laser spectroscopy to be R(^{54}Ni)=3.737(3) fm. In conjunction with the known radius of the mirror nucleus ^{54}Fe, the difference of the charge radii was extracted as ΔR_{ch}=0.049(4) fm. Based on the correlation between ΔR_{ch} and the slope of the symmetry energy at nuclear saturation density (L), we deduced 21≤L≤88 MeV. The present result is consistent with the L from the binary neutron star merger GW170817, favoring a soft neutron matter EOS, and barely consistent with the PREX-2 result within 1σ error bands. Our result indicates the neutron-skin thickness of ^{48}Ca as 0.15-0.21 fm.

(1) Background: Genomic precision medicine (PM) utilises people’s genomic data to inform the delivery of preventive and therapeutic health care. PM has not been well-established for use with people of Aboriginal and Torres Strait Islander ancestry due to the paucity of genomic data from these communities. We report the development of a new protocol using co-design methods to enhance the potential use of PM for Aboriginal Australians. (2) Methods: This iterative qualitative study consists of five main phases. Phase-I will ensure appropriate governance of the project and establishment of a Project Advisory Committee. Following an initial consultation with the Aboriginal community, Phase-II will invite community members to participate in co-design workshops. In Phase-III, the Chief Investigators will participate in co-design workshops and document generated ideas. The notes shall be analysed thematically in Phase-IV with Aboriginal community representatives, and the summary will be disseminated to the communities. In Phase-V, we will evaluate the co-design process and adapt our protocol for the use in partnership with other communities. (3) Discussion: This study protocol represents a crucial first step to ensure that PM research is relevant and acceptable to Aboriginal Australians. Without fair access to PM, the gap in health outcome between Aboriginal and non-Aboriginal Australians will continue to widen.

BackgroundGlioblastoma (GBM) is marked by cellular heterogeneity, including metabolic heterogeneity, that varies among cellular microenvironments in the same tumor. Altered cellular metabolism in cancer is well-established, but how lipid metabolism is altered to suit different microenvironmental conditions and cellular states within a tumor remains unexplored.MethodsWe assessed GBM organoid models that mimic the transition zone between nutrient-rich and nutrient-poor pseudopalisading/perinecrotic tumor zones and performed spatial RNA-sequencing of cells to interrogate lipid metabolism. Using targeted lipidomic analysis, we assessed differences in acutely enriched cancer stem cells (CSCs) and non-CSCs from multiple patient-derived models to explore the link between the stem cell state and lipid metabolism.ResultsSpatial analysis revealed a striking difference in lipid content between microenvironments, with lipid enrichment in the hypoxic organoid cores and the perinecrotic and pseudopalisading regions of primary patient tumors. This was accompanied by regionally restricted upregulation of hypoxia-inducible lipid droplet-associated (HILPDA) gene expression in organoid cores and in clinical GBM specimens, but not lower-grade brain tumors, that was specifically localized to pseudopalisading regions of patient tumors. CSCs have low lipid droplet accumulation compared to non-CSCs in organoid models and xenograft tumors, and prospectively sorted lipid-low GBM cells are functionally enriched for stem cell activity. Targeted lipidomic analysis revealed that CSCs had decreased levels of major classes of neutral lipids compared to non-CSCs but had significantly increased polyunsaturated fatty acid production due to high fatty acid desaturase (FADS1/2) expression.ConclusionsOur data demonstrate that lipid metabolism is differentially altered across GBM microenvironments and cellular hierarchies, providing guidance for targeting of these altered lipid metabolic pathways.Key pointsGBM cells in nutrient-poor tumor regions have increased accumulation of lipid droplets.CSCs have reduced lipid content compared to non-CSCs.GBM CSCs and non-CSCs have disparate lipid metabolisms that may be uniquely targetable.Importance of the StudyMetabolic targeting has long been advocated as a therapy against many tumors including GBM, and it remains an outstanding question whether cancer stem cells (CSCs) have altered lipid metabolism. We demonstrated striking differences in lipid metabolism between diverse cell populations from the same patient. These spatially and phenotypically distinct lipid phenotypes occur clinically in the majority of patients and can be recapitulated in laboratory models. Lipidomic analysis of multiple patient-derived models shows a significant shift in lipid metabolism between GBM CSCs and non-CSCs, suggesting that lipid levels may not be simply a product of the microenvironment but also may be a reflection of cellular state. Our results suggest that therapeutic targeting of GBM lipid metabolism must consider multiple separate tumor cell populations to be effective, and we provide a methodologic framework for studying these metabolically diverse cellular populations.

BACKGROUND: Diabetes is 3-4 times more prevalent in Indigenous Australians with blood glucose levels often above target range. Once weekly formulations of exenatide(exenatide-LAR) have demonstrated significantly greater improvements in glycaemic management with no increased risk of hypoglycaemia and with reductions in bodyweight but have not been studied in Indigenous Australians. AIMS: To assess the feasibility and metabolic effects of once weekly supervised injection of exenatide-LAR in addition to standard care in Indigenous Australians with type 2 diabetes. METHODS: Two communities in Central Australia with longstanding specialist clinical outreach services were allocated by random coin toss to receive once-weekly exenatide-LAR injection with weekly nurse review and adjustment of medication for 20 weeks (community with exenatide-LAR) or to weekly nurse review in addition to standard care over 20 weeks (community without exenatide-LAR). The primary outcome was the feasibility of an intensive diabetes management model of care with and without weekly supervised exenatide-LAR. Secondary outcomes included change in HbA1c. RESULTS: Thirteen participants from the community with exenatide-LAR and nine participants from the community without exenatide-LAR were analysed. Eighty-five percent of individuals in the community with exenatide-LAR and 67% in the community without exenatide-LAR attended more than half of clinic visits. Median difference in the change in HbA1c from baseline to final visit, adjusted for baseline HbA1c, between the community with exenatide-LAR and the community without exenatide-LAR was -3.1%, 95% CI (-5.80%, -0.38%; P = 0.03). CONCLUSIONS: Weekly exenatide-LAR combined with weekly nurse review demonstrated greater improvements in HbA1c, highlighting its potential for use in remote communities.

The Wittig reaction can be used for late stage functionalization of proteins and peptides to ligate glycans, pharmacophores, and many other functionalities. In this manuscript, we modified 160,000 N-terminal glyoxaldehyde peptides displayed on phage with the Wittig reaction by biotin labeled ylide under conditions that functionalize only 1% of the library population. Deep-sequencing of the biotinylated and input populations estimated the rate of conversion for each sequence. This “deep conversion” (DC) from deep sequencing correlates with rate constants measured by HPLC. Peptide sequences with fast and slow reactivity highlighted a critical role of primary backbone amides (N-H) in accelerating the rate of the aqueous Wittig reaction. Experimental measurement of reaction rates and density functional theory (DFT) computation of the transition state geometries corroborated this relationship. We also collected deep-sequencing data to build structure activity relationship (SAR) models that can predict DC value of the Wittig reaction. By using this data, we trained two classifier models based on Gradient Boosted trees. These classifiers achieved area under the ROC (Receiver Operating Characteristic) Curve (ROC AUC) of 81.2 ± 0.4 and 73.7 ± 0.8 (90–92% accuracy) in determining whether a sequence belonged to the top 5% or the bottom 5% in terms of its reactivity. We have deployed our learned models as a publicly available web app: http://44.226.164.95/ We anticipate that phage-displayed peptides and related mRNA or DNA-displayed substrates can be employed in a similar fashion to study the substrate scope and mechanisms of many other chemical reactions.

High prevalence of chronic and infectious diseases in Indigenous populations is a major public health concern both in global and Australian contexts. Limited research has examined the role of built environments in relation to Indigenous health in remote Australia. This study engaged stakeholders to understand their perceptions of the influence of built environmental factors on chronic and infectious diseases in remote Northern Territory (NT) communities. A preliminary set of 1120 built environmental indicators were systematically identified and classified using an Indigenous Indicator Classification System. The public and environmental health workforce was engaged to consolidate the classified indicators (n = 84), and then sort and rate the consolidated indicators based on their experience with living and working in remote NT communities. Sorting of the indicators resulted in a concept map with nine built environmental domains. Essential services and Facilities for health/safety were the highest ranked domains for both chronic and infectious diseases. Within these domains, adequate housing infrastructure, water supply, drainage system, reliable sewerage and power infrastructure, and access to health services were identified as the most important contributors to the development of these diseases. The findings highlight the features of community environments amenable to public health and social policy actions that could be targeted to help reduce prevalence of chronic and infectious diseases Refereed/Peer-reviewed

IntroductionMainstream Australian mental health services are failing Aboriginal young people. Despite investing resources, improvements in well-being have not materialised. Culturally and age appropriate ways of working are needed to improve service access and responsiveness. This Aboriginal-led study brings Aboriginal Elders, young people and youth mental health service staff together to build relationships to co-design service models and evaluation tools. Currently, three Western Australian youth mental health services in the Perth metropolitan area and two regional services are working with local Elders and young people to improve their capacity for culturally and age appropriate services. Further Western Australian sites will be engaged as part of research translation.Methods and analysisRelationships ground the study, which utilises Indigenous methodologies and participatory action research. This involves Elders, young people and service staff as co-researchers and the application of a decolonising, strengths-based framework to create the conditions for engagement. It foregrounds experiential learning and Aboriginal ways of working to establish relationships and deepen non-Aboriginal co-researchers’ knowledge and understanding of local, place-based cultural practices. Once relationships are developed, co-design workshops occur at each site directed by local Elders and young people. Co-designed evaluation tools will assess any changes to community perceptions of youth mental health services and the enablers and barriers to service engagement.Ethics and disseminationThe study has approval from the Kimberley Aboriginal Health Planning Forum Kimberley Research Subcommittee, the Western Australian Aboriginal Health Ethics Committee, and the Curtin University Human Research Ethics Committee. Transferability of the outcomes across the youth mental health sector will be directed by the co-researchers and is supported through Aboriginal and non-Aboriginal organisations including youth mental health services, peak mental health bodies and consumer groups. Community reports and events, peer-reviewed journal articles, conference presentations and social and mainstream media will aid dissemination.

The use of machine learning methods for the prediction of reaction yield is an emerging area. We demonstrate the applicability of support vector regression (SVR) for predicting reaction yields, using combinatorial data. Molecular descriptors used in regression tasks related to chemical reac?tivity have often been based on time-consuming, computationally demanding quantum chemical calculations, usually density functional theory. Structure-based descriptors (molecular fingerprints and molecular graphs) are quicker and easier to calculate, and are applicable to any molecule. In this study, SVR models built on structure-based descriptors were compared to models built on quantum chemical descriptors. The models were evaluated along the dimension of each reaction component in a set of Buchwald-Hartwig amination reactions. The structure-based SVR models out-performed the quantum chemical SVR models, along the dimension of each reaction compo?nent. The applicability of the models was assessed with respect to similarity to training. Prospec?tive predictions of unseen Buchwald-Hartwig reactions are presented for synthetic assessment, to validate the generalisability of the models, with particular interest along the aryl halide dimension.

BackgroundDelirium is a distressing, common and serious condition in older people in hospital. Evidence suggests that it could be prevented in about one-third of patients using multicomponent interventions targeting delirium risk factors, but these interventions are not yet routinely available in the NHS.ObjectiveThe objective was to improve delirium prevention for older people admitted to the NHS.DesignProject 1 comprised case studies employing qualitative methods (observation, interviews, workshops) in three NHS hospitals to develop the Prevention of Delirium system of care. Project 2 comprised case studies using mixed methods in five NHS hospitals to test the Prevention of Delirium implementation, feasibility and acceptability, and to modify the Prevention of Delirium system of care. Project 3 comprised a multicentre, cluster randomised, controlled, pragmatic feasibility study in eight hospitals, with embedded economic evaluation, to investigate the potential clinical effectiveness and cost-effectiveness of the Prevention of Delirium system of care, compared with standard care, among older patients admitted to hospital for emergency care. The primary objectives related to gathering information to design a definitive trial. Criteria for progression to a definitive trial were as follows: a minimum of six wards (75%) completing the Prevention of Delirium manual milestone checklist and an overall recruitment rate of at least 10% of the potential recruitment pool.SettingThis study was set in NHS general hospitals.ParticipantsIn project 1, participants were staff, volunteers, and patient and carer representatives. In project 2, participants were staff, volunteers, patients and carers. In project 3, participants were older patients admitted to elderly care and orthopaedic trauma wards.InterventionThe developed intervention (i.e. the Prevention of Delirium system of care).Main outcome measuresFor the feasibility study (project 3), the primary outcome measure was the Confusion Assessment Method. The secondary outcome measures were the Nottingham Extended Activities of Daily Living scale, the Clinical Anxiety Scale and the Geriatric Depression Scale Short Form.ResultsProject 1: understanding of delirium prevention was poor. Drawing on evidence, and working with ward teams, we developed the Prevention of Delirium system of care, which targeted 10 delirium risk factors. This multicomponent intervention incorporated systems and mechanisms to introduce and embed delirium prevention into routine ward practices. Project 2: five out of six wards implemented or partially implemented the Prevention of Delirium intervention. A prominent role for hospital volunteers was intended, but most wards were unable to recruit or sustain the numbers needed. We identified four conditions necessary to implement and deliver the Prevention of Delirium intervention: (1) commitment of senior nurse, (2) a named person to drive implementation forward, (3) dedicated time (1 day per week) of an experienced nurse to lead implementation and (4) adequate ward staffing levels. Overall, the intervention was acceptable to staff, volunteers, patients and carers, and did not increase nursing staff workload. In the light of these findings, the Prevention of Delirium system of care was modified for use in project 3. Project 3: 16 wards in eight hospitals (two wards per hospital) were recruited. Out of 4449 patients screened, 3274 (73.6%) were eligible and 713 were registered, resulting in a recruitment rate of 16.0%. Thirty-three (4.6%) participants withdrew. The screened and registered participants were similar, but some between-treatment group imbalances were noted among those registered to the trial. All eight wards allocated to the intervention group completed the Prevention of Delirium manual milestone checklist and delivered the Prevention of Delirium intervention (median time 18.6 weeks for implementation). Overall, fidelity to the intervention was assessed as being high in two wards, medium in five wards and low in one ward. Of the expected 5645 Confusion Assessment Method delirium assessments, 5065 (89.7%) were completed during the first 10 days of admission. The rates of return of the patient-reported questionnaire booklets were 98.0% at baseline, 81.8% at 30 days and 70.5% at 3 months. The return rate of the EuroQol-5 Dimensions questionnaire was 98.6% at baseline, 77.5% at 1 month and 65.3% at 3 months (94–98% fully completed). The completion rate of the resource use questionnaire was lower (48.7%). The number of people with new-onset delirium at 10 days was 24 (7.0%) in the Prevention of Delirium group and 33 (8.9%) in the control group. Multilevel logistic regression analysis showed that participants in the Prevention of Delirium group had non-significant lower odds of developing delirium (odds ratio 0.68, 95% confidence interval 0.37 to 1.26;p = 0.2225). The average cost of the Prevention of Delirium intervention was estimated as £10.98 per patient and the mean costs for the Prevention of Delirium and usual-care groups were £5332 and £4412, respectively, with negligible between-group differences in quality-adjusted life-years. There was conflicting evidence from the trial- and model-based analyses relating to the cost-effectiveness of the Prevention of Delirium intervention. Given this, and in view of issues with the data (e.g. high levels of missingness), the results from the economic evaluation are highly uncertain. The criteria for continuation to a future definitive randomised controlled trial were met. Such a trial would need to recruit 5200 patients in 26 hospital clusters (200 patients per cluster).ConclusionsThe Prevention of Delirium system of care was successfully developed, and a multicentre feasibility study showed that the intervention is capable of implementation and delivery in routine care, with acceptable intervention fidelity and preliminary estimate of effectiveness.LimitationsA prominent role for volunteers was originally intended in the Prevention of Delirium system of care, but only three of the eight wards allocated to the trial intervention group involved volunteers.Future workThe findings indicate that a definitive multicentre evaluation of the Prevention of Delirium system of care should be designed and conducted to obtain robust estimates of clinical effectiveness and cost-effectiveness.Trial registrationCurrent Controlled Trials ISRCTN28213290 (project 1), ISRCTN65924234 (project 2) and ISRCTN01187372 (project 3).FundingThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full inProgramme Grants for Applied Research; Vol. 9, No. 4. See the NIHR Journals Library website for further project information.

AIM: There is a wealth of data concerning the health behaviours of Indigenous Australians, but the health behaviours of Indigenous Australians with diabetes are not systematically documented. At the clinical level, understanding a person's health behaviours can help identify and address barriers to diabetes care and promote good clinical outcomes. METHODS: We used a novel survey tool to systematically collect health behaviour data on Smoking, Nutrition, Alcohol consumption, Physical activity and Emotional well-being (SNAPE) from Indigenous Australians with Type 2 diabetes in a remote primary care setting in Alice Springs. RESULTS: At least one of the five surveys in the SNAPE tool was completed by 210 participants: 30% male, mean age 52.6 years (range 22.9 - 87.4). Fifty per cent of men and 23% of women were current smokers (P

Editor’s PerspectiveWhat We Already Know about This TopicWhat This Article Tells Us That Is NewBackgroundPostoperative delirium and postoperative cognitive dysfunction share risk factors and may co-occur, but their relationship is not well established. The primary goals of this study were to describe the prevalence of postoperative cognitive dysfunction and to investigate its association with in-hospital delirium. The authors hypothesized that delirium would be a significant risk factor for postoperative cognitive dysfunction during follow-up.MethodsThis study used data from an observational study of cognitive outcomes after major noncardiac surgery, the Successful Aging after Elective Surgery study. Postoperative delirium was evaluated each hospital day with confusion assessment method–based interviews supplemented by chart reviews. Postoperative cognitive dysfunction was determined using methods adapted from the International Study of Postoperative Cognitive Dysfunction. Associations between delirium and postoperative cognitive dysfunction were examined at 1, 2, and 6 months.ResultsOne hundred thirty-four of 560 participants (24%) developed delirium during hospitalization. Slightly fewer than half (47%, 256 of 548) met the International Study of Postoperative Cognitive Dysfunction-defined threshold for postoperative cognitive dysfunction at 1 month, but this proportion decreased at 2 months (23%, 123 of 536) and 6 months (16%, 85 of 528). At each follow-up, the level of agreement between delirium and postoperative cognitive dysfunction was poor (kappa less than .08) and correlations were small (r less than .16). The relative risk of postoperative cognitive dysfunction was significantly elevated for patients with a history of postoperative delirium at 1 month (relative risk = 1.34; 95% CI, 1.07–1.67), but not 2 months (relative risk = 1.08; 95% CI, 0.72–1.64), or 6 months (relative risk = 1.21; 95% CI, 0.71–2.09).ConclusionsDelirium significantly increased the risk of postoperative cognitive dysfunction in the first postoperative month; this relationship did not hold in longer-term follow-up. At each evaluation, postoperative cognitive dysfunction was more common among patients without delirium. Postoperative delirium and postoperative cognitive dysfunction may be distinct manifestations of perioperative neurocognitive deficits.

Background The Getting it Right study determined the validity, sensitivity, specificity and acceptability of the culturally adapted 9-item Patient Health Questionnaire (aPHQ-9) as a screening tool for depression in Aboriginal and Torres Strait Islander (hereafter referred to as Indigenous) people. In this process evaluation we aimed to explore staff perceptions about whether Getting it Right was conducted per protocol, and if the aPHQ-9 was considered an acceptable and feasible screening tool for depression in primary healthcare. This process evaluation will provide information for clinicians and policy makers about the experiences of staff and patients with Getting it Right and what they thought about using the aPHQ-9. Methods Process evaluation using grounded theory approaches. Semi-structured interviews with primary healthcare staff from services participating in Getting it Right were triangulated with feedback (free-text and elicited) from participants collected during the validation study and field notes. Data were thematically analysed according to the Getting it Right study protocol to identify the acceptability and feasibility of the aPHQ-9. Results Primary healthcare staff (n = 36) and community members (n = 4) from nine of the ten participating Getting it Right services and Indigenous participants (n = 500) from the ten services that took part. Most staff reported that the research was conducted according to the study protocol. Staff from two services reported sometimes recruiting opportunistically (rather than recruiting consecutive patients attending the service as outlined in the main study protocol), when they spoke to patients who they knew from previous interactions, because they perceived their previous relationship may increase the likelihood of patients participating. All Getting it Right participants responded to at least six of the seven feedback questions and 20% provided free-text feedback. Most staff said they would use the aPHQ-9 and most participants said that the questions were easy to understand (87%), the response categories made sense (89%) and that they felt comfortable answering the questions (91%). Conclusion Getting it Right was predominantly conducted according to the study protocol. The aPHQ-9, the first culturally adapted, nationally validated, freely available depression screening tool for use by Indigenous people, appears to be acceptable and feasible to use. Trial registration Australian New Zealand Clinical Trial Registry ANZCTR12614000705684, 03/07/2014.

Expanded low-carbon baseload power production through the use of nuclear fission can be enabled by recycling long-lived actinide isotopes within the nuclear fuel cycle. This approach provides the benefits of (a) more completely utilizing the energy potential of mined uranium, (b) reducing the footprint of nuclear geological repositories, and (c) reducing the time required for the radiotoxicity of the disposed waste to decrease to the level of uranium ore from one hundred thousand years to a few hundred years. A key step in achieving this goal is the separation of long-lived isotopes of americium (Am) and curium (Cm) for recycle into fast reactors. To achieve this goal, a novel process was successfully demonstrated on a laboratory scale using a bank of 1.25-cm centrifugal contactors, fabricated by additive manufacturing, and a simulant containing the major fission product elements. Americium and Cm were separated from the lanthanides with over 99.9% completion. The sum of the impurities of the Am/Cm product stream using the simulated raffinate was found to be 3.2 × 10−3 g/L. The process performance was validated using a genuine high burnup used nuclear fuel raffinate in a batch regime. Separation factors of nearly 100 for 154Eu over 241Am were achieved. All these results indicate the process scalability to an engineering scale.

Objectives\ud \ud To determine the validity, sensitivity, specificity and acceptability of the culturally adapted nine‐item Patient Health Questionnaire (aPHQ‐9) as a screening tool for depression in Aboriginal and Torres Strait Islander people.\ud \ud Design\ud \ud Prospective observational validation study, 25 March 2015 – 2 November 2016.\ud \ud Setting, participants\ud \ud 500 adults (18 years or older) who identified as Aboriginal or Torres Strait Islander people and attended one of ten primary health care services or service events in urban, rural and remote Australia that predominantly serve Indigenous Australians, and were able to communicate sufficiently to respond to questionnaire and interview questions.\ud \ud \ud Main outcome measures\ud \ud Criterion validity of the aPHQ‐9, with the depression module of the Mini‐International Neuropsychiatric Interview (MINI) 6.0.0 as the criterion standard.\ud \ud \ud Results\ud \ud 108 of 500 participants (22%; 95% CI, 18–25%) had a current episode of major depression according to the MINI criterion. The sensitivity of the aPHQ‐9 algorithm for diagnosing a current major depressive episode was 54% (95% CI, 40–68%), its specificity was 91% (95% CI, 88–94%), with a positive predictive value of 64%. For screening for a current major depressive episode, the area under the receiver operator characteristic curve was 0.88 (95% CI, 0.85–0.92); with a cut‐point of 10 points its sensitivity was 84% (95% CI, 74–91%) and its specificity 77% (95% CI, 71–83%). The aPHQ‐9 was deemed acceptable by more than 80% of participants.\ud \ud \ud Conclusions\ud \ud Indigenous Australians found the aPHQ‐9 acceptable as a screening tool for depression. Applying a cut‐point of 10 points, the performance characteristics of the aPHQ were good.

Application of fluorescent proteins (FPs), e.g., as probes for biological imaging, has led to the goal of finding FPs with notable one- and two-photon absorption (OPA and TPA, respectively) features. The variables that affect the TPA cross section are many; e.g., structurally speaking, some studies have shown its magnitude is influenced by the presence of the protein backbone and the molecules of water surrounding the chromophore. However, the impact that the surroundings have on the TPA cross section has not been conclusively determined. One of the main problems that can be faced when trying to account for excited state properties is the cost associated with such computations. Among the methods chosen for this type of computations is time-dependent density functional theory (TD-DFT), commonly used on molecules with no more than 50 atoms due to its computational cost. A cheaper alternative to DFT and, moreover, to TD-DFT is the so-called time-dependent tight binding density functional theory (TD-DFTB), which within the second-order approximation is designated TD-DFTB2. In the present work, TD-DFTB2 was tested to determine whether or not it is an alternative method to TD-DFT for computing excited state properties beyond excitation energies and oscillator strengths such as TPA cross sections. Studies around the performance of TD-DFTB2 on the computation of excitation energies have been previously carried out, and the results show it is comparable to TD-DFT in terms of the computation of excitation energies and oscillator strengths. Despite the latter, what we found is that neither the magnitude nor the trend of the obtained TPA cross sections is preserved with respect to CAM-B3LYP and B3LYP TPA cross sections previously reported by other authors. The computation of TPA cross sections within the two-level model allowed us to determine that among the reasons behind such behavior is the overestimation of the excited state dipole moments. Based on the above, we conclude that TD-DFTB2 is not (yet) a viable route to obtain quantitatively TPA cross sections.

Summary Background Rapid demographic, epidemiological, and nutritional transitons have brought a pressing need to track progress in adolescent health. Here, we present country-level estimates of 12 headline indicators from the Lancet Commission on adolescent health and wellbeing, from 1990 to 2016. Methods Indicators included those of health outcomes (disability-adjusted life-years [DALYs] due to communicable, maternal, and nutritional diseases; injuries; and non-communicable diseases); health risks (tobacco smoking, binge drinking, overweight, and anaemia); and social determinants of health (adolescent fertility; completion of secondary education; not in education, employment, or training [NEET]; child marriage; and demand for contraception satisfied with modern methods). We drew data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016, International Labour Organisation, household surveys, and the Barro-Lee education dataset. Findings From 1990 to 2016, remarkable shifts in adolescent health occurred. A decrease in disease burden in many countries has been offset by population growth in countries with the poorest adolescent health profiles. Compared with 1990, an additional 250 million adolescents were living in multi-burden countries in 2016, where they face a heavy and complex burden of disease. The rapidity of nutritional transition is evident from the 324·1 million (18%) of 1·8 billion adolescents globally who were overweight or obese in 2016, an increase of 176·9 million compared with 1990, and the 430·7 million (24%) who had anaemia in 2016, an increase of 74·2 million compared with 1990. Child marriage remains common, with an estimated 66 million women aged 20–24 years married before age 18 years. Although gender-parity in secondary school completion exists globally, prevalence of NEET remains high for young women in multi-burden countries, suggesting few opportunities to enter the workforce in these settings. Interpretation Although disease burden has fallen in many settings, demographic shifts have heightened global inequalities. Global disease burden has changed little since 1990 and the prevalence of many adolescent health risks have increased. Health, education, and legal systems have not kept pace with shifting adolescent needs and demographic changes. Gender inequity remains a powerful driver of poor adolescent health in many countries. Funding Australian National Health and Medical Research Council, and the Bill & Melinda Gates Foundation.

In Australia's Northern Territory, Indigenous mothers account for 33% of births and have high rates of hyperglycemia in pregnancy. The prevalence of type 2 diabetes (T2D) in pregnancy is up to 10-fold higher in Indigenous than non-Indigenous Australian mothers, and the use of metformin is common. We assessed birth outcomes in relation to metformin use during pregnancy from a clinical register.The study included women with gestational diabetes (GDM), newly diagnosed diabetes in pregnancy (DIP), or pre-existing T2D from 2012 to 2016. Data were analyzed for metformin use in the third trimester. Regression models were adjusted for maternal age, body mass index, parity, and insulin use.Of 1649 pregnancies, 814 (49.4%) were to Indigenous women, of whom 234 (28.7%) had T2D (vs 4.6% non-Indigenous women; P 0.001). Metformin use was high in Indigenous women (84%-90% T2D, 42%-48% GDM/DIP) and increased over time in non-Indigenous women (43%-100% T2D, 14%-35% GDM/DIP). Among Indigenous women with GDM/DIP, there were no significant differences between groups with and without metformin in cesarean section (51% vs 39%; adjusted odds ratio [aOR] 1.25, 95% confidence interval [CI] 0.87-1.81), large for gestational age (24% vs 13%; aOR 1.5, 95% CI 0.9-2.5), or serious neonatal adverse events (9.4% vs 5.9%; aOR 1.32, 95% CI 0.68-2.57). Metformin use was independently associated with earlier gestational age (37.7 vs 38.5 weeks), but the risk did not remain independently higher after exclusion of women managed with medical nutrition therapy alone, and the increase in births37 weeks was not significant on multivariate analysis.We found no clear evidence of any adverse outcomes related to the use of metformin for the treatment of hyperglycemia in pregnancy.摘要: 背景 在澳大利亚北部地区, 原住民母亲的婴儿出生率占33%, 她们妊娠期间出现高血糖的风险很高。原住民母亲在妊娠期间的2型糖尿病(T2D)患病率与非原住民澳大利亚母亲相比较要高10倍, 并且经常使用二甲双胍治疗。我们利用临床登记表数据评估了妊娠期间使用二甲双胍治疗与出生结果之间的关系。 方法 这项研究从2012至2016年纳入了妊娠糖尿病(gestational diabetes, GDM)、妊娠期新诊断糖尿病(newly diagnosed diabetes in pregnancy, DIP)以及既往已经存在T2D的妇女。对妊娠晚期使用二甲双胍的数据进行了分析。根据母亲年龄、体重指数、产次以及胰岛素使用情况校正了回归模型。 结果 在1649名孕妇中有814名(49.4%)为原住民妇女, 其中234名(28.7%)为T2D(非原住民妇女T2D比例为4.6%；P 0.001)。原住民妇女的二甲双胍使用率更高(在T2D中为84%-90%, 在GDM/DIP中为42%-48%), 并且在非原住民妇女中随着时间的推移使用率在上升(在T2D中为43%-100%, 在GDM/DIP中为14%-35%)。在合并GDM/DIP的原住民妇女中, 使用二甲双胍治疗组与不使用二甲双胍治疗组之间的剖宫产率(分别为51%与39%; 校正后的odds ratio [aOR]为1.25, 95%置信区间[CI]为0.87-1.81)、出现大胎龄率(分别为24%与13%；aOR为1.5, 95% CI为0.9-2.5)、新生儿出现严重不良事件率(分别为9.4%与5.9%；aOR为1.32, 95% CI为0.68-2.57)都没有显著性差异。使用二甲双胍治疗与胎龄更小(分别为37.7与38.5周)独立相关, 但是将单独接受药物营养治疗的妇女排除之后, 这种风险没有独立地处于较高的水平, 并且多变量分析显示37周的出生率并没有显著地升高。 结论 我们没有发现任何与妊娠期间高血糖妇女使用二甲双胍治疗出现不良结果相关的明确证据。.

The artwork “placed on display” by my environment was the architectural container, as its own material structure; at the same time it was designed to be a display container for the viewers inside (...

Despite advancements in prevention and treatment, sudden cardiac death (SCD) remains a leading cause of mortality and is responsible for approximately half of all deaths from cardiovascular disease. Outcomes continue to remain poor following a sudden cardiac arrest, with most individuals not surviving. Although coronary heart disease remains the dominant underlying condition, our understanding of SCD is improving through greater knowledge of clinical risk factors, cardiomyopathies, and primary arrhythmic disorders. However, despite a growing wealth of information from studies in North America, Europe, and Japan, data from other global regions (and particularly from low-and middle-income countries) remains scarce. Refereed/Peer-reviewed

A semi-automatic sampling and fitting procedure for generating sum-of-product (Born–Oppenheimer) potential energy surfaces based on a high-dimensional model representation is presented. The adaptive sampling procedure and subsequent fitting rely on energies only and can be used for re-fitting existing analytic potential energy surfaces in the sum-of-product form or for direct fits from ab initio computations. The method is tested by fitting ground electronic state potential energy surfaces for small to medium sized semi-rigid molecules, i.e., HFCO, HONO, and HCOOH, based on ab initio computations at the coupled-cluster single double and perturbative triples-F12/cc-pVTZ-F12 or MP2/aug-cc-pVTZ levels of theory. Vibrational eigenstates are computed using block improved relaxation in the Heidelberg multi-configurational time dependent Hartree package and compared to available experimental and theoretical data. The new potential energy surfaces are compared to the best ones currently available for these molecules in terms of accuracy, including resulting vibrational states, required number of sampling points, and number of fitting parameters. The present procedure leads to compact expansions and scales well with the number of dimensions for simple potentials such as single or double wells.

This letter describes the on-going SAR efforts to develop PLD1, PLD2 and dual PLD1/2 inhibitors with improved physiochemical and disposition properties as well as securing intellectual property position. Previous PLD inhibitors, based on a triazaspiro[4.5]decanone core proved to be highly selective PLD2 inhibitors, but with low plasma free fraction (rat, human fu 65 mL/min/kg) and very short half-lives in vivo (t1/2 3 h), and led to the first issued US patent claiming composition of matter for small molecule PLD inhibitors.

The synthesis of the first bismuth-containing macromolecules that exhibit phosphorescence in the solid state and in the presence of oxygen is reported. These red emissive high molecular weight polymers (>300 kDa) feature benzobismoles appended to a hydrocarbon scaffold, and were built via an efficient ring-opening metathesis (ROMP) protocol. Moreover, our general procedure readily allows for the formation of cross-linked networks and block copolymers. Attaining stable red phosphorescence with non-toxic elements remains a challenge and, thus, our new class of soluble (processable) polymeric phosphor is of great interest. Furthermore, the formation of bismuth-rich cores within organic-inorganic block copolymer spherical micelles is possible, leading to patterned arrays of bismuth in the film state.

Background: The postpartum period is a critical time to improve health outcomes for Aboriginal women, particularly for those who have chronic conditions. Aims: To assess enhanced support methods (for women following diabetes in pregnancy (DIP)) to improve completion rates of recommended postpartum health checks. Materials and Methods: Fifty-three Aboriginal women in the Northern Territory (NT) were contacted in the postpartum period to encourage medical check-ups.Messages were delivered through phone (call or text messages) or other methods (Facebook or email). The primary outcome was postpartum blood glucose testing (oral glucose tolerance testing (OGTT), random or fasting glucose and HbA1c). Results: Establishing contact with women was difficult. Of 137 messages sent to52 women, 22 responded (42%). Phone was the most common contact method with successful contact made from 16 of 119 (13%) attempts. Rates of postpartum OGTT completion were higher in the group successfully contacted (32% vs 7%). However, for any postpartum glucose testing (including OGTT and HbA1c) rates were 25 of 42 (60%) and neither success in making contact nor the contact method was associated with higher rates. Conclusions: The small sample size limits our conclusions; however, results highlight that engaging remote women postpartum is difficult. While rates of postpartum OGTT completion differed according to successful contacts, rates of any postpartum blood glucose testing did not. Further research is needed to explore feasible intervention methods to improve postpartum screening after a pregnancy complicated by diabetes. Refereed/Peer-reviewed

Targeted radionuclide therapy generally relies on the chelation of select short-lived isotopes such as 177Lu and 67Cu. The majority of Lu(III) and Cu(II) chelate structural information is derived from solid state diffraction data. Herein, the complexes Lu(DOTA)−, Cu(NOTA)− were examined in solution using EXAFS for the first time. Both ligands were fully deprotonated and coordinated to the metal with four and three carboxylic sites for Lu(DOTA)− and Cu(NOTA)−, respectively. Near-neighbor correlations from nitrogen atoms on the macrocyclic cages were also visible in the spectra in addition to the adjacent carbon backbones. Coordination numbers, bond distances, and Debye-Waller factors are reported and discussed alongside differences with known crystal structures.

The high prevalence of preventable infectious and chronic diseases in Australian Indigenous populations is a major public health concern. Existing research has rarely examined the role of built and socio-political environmental factors relating to remote Indigenous health and wellbeing. This research identified built and socio-political environmental indicators from publicly available grey literature documents locally-relevant to remote Indigenous communities in the Northern Territory (NT), Australia. Existing planning documents with evidence of community input were used to reduce the response burden on Indigenous communities. A scoping review of community-focused planning documents resulted in the identification of 1120 built and 2215 socio-political environmental indicators. Indicators were systematically classified using an Indigenous indicator classification system (IICS). Applying the IICS yielded indicators prominently featuring the “community infrastructure” domain within the built environment, and the “community capacity” domain within the socio-political environment. This research demonstrates the utility of utilizing existing planning documents and a culturally appropriate systematic classification system to consolidate environmental determinants that influence health and disease occurrence. The findings also support understanding of which features of community-level built and socio-political environments amenable to public health and social policy actions might be targeted to help reduce the prevalence of infectious and chronic diseases in Indigenous communities Refereed/Peer-reviewed

Vacancy-ordered double perovskites Cs2SnX6 (X = Cl, Br, I) have emerged as promising lead-free and ambient-stable materials for photovoltaic and optoelectronic applications. To advance these promising materials, it is crucial to determine the correlations between physical properties and their local structure and dynamics. Solid-state NMR spectroscopy of multiple NMR-active nuclei (133Cs, 119Sn and 35Cl) in these cesium tin(IV) halides has been used to decode the structure, which plays a key role in the materials’ optical properties. The 119Sn NMR chemical shifts span approximately 4000 ppm and the 119Sn spin-lattice relaxation times span three orders of magnitude when the halogen goes from chlorine to iodine in these diamagnetic compounds. Moreover, ultrawideline 35Cl NMR spectroscopy for Cs2SnCl6 indicates an axially symmetric chlorine electric field gradient tensor with a large quadrupolar coupling constant of ca. 32 MHz, suggesting a chlorine that is directly attached to Sn(IV) ions. Variable temperature 119Sn spin lattice relaxation time measurements uncover the presence of hidden dynamics of octahedral SnI6 units in Cs2SnI6 with a low activation energy barrier of 12.45 kJ/mol (0.129 eV). We further show that complete mixed-halide solid solutions of Cs2SnClxBr6−x and Cs2SnBrxI6−x (0 ≤ x ≤ 6) form at any halogen compositional ratio. 119Sn and 133Cs NMR spectroscopy resolve the unique local SnClnBr6−nand SnBrnI6−n (n = 0−6) octahedral and CsBrmI12−m (m = 0−12) cuboctahedral environments in the mixed-halide samples. The experimentally observed 119Sn NMR results are consistent with magnetic shielding parameters obtained by density functional theory computations to verify random halogen distribution in mixed-halide analogues. Finally, we demonstrate the difference in the local structures and optical absorption properties of Cs2SnI6 samples prepared by solvent-assisted and solvent-free synthesis routes.

Vacancy-ordered double perovskites Cs2SnX6 (X = Cl, Br, I) have emerged as promising lead-free and ambient-stable materials for photovoltaic and optoelectronic applications. To advance these promising materials, it is crucial to determine the correlations between physical properties and their local structure and dynamics. Solid-state NMR spectroscopy of multiple NMR-active nuclei (133Cs, 119Sn and 35Cl) in these cesium tin(IV) halides has been used to decode the structure, which plays a key role in the materials’ optical properties. The 119Sn NMR chemical shifts span approximately 4000 ppm and the 119Sn spin-lattice relaxation times span three orders of magnitude when the halogen goes from chlorine to iodine in these diamagnetic compounds. Moreover, ultrawideline 35Cl NMR spectroscopy for Cs2SnCl6 indicates an axially symmetric chlorine electric field gradient tensor with a large quadrupolar coupling constant of ca. 32 MHz, suggesting a chlorine that is directly attached to Sn(IV) ions. Variable temperature 119Sn spin lattice relaxation time measurements uncover the presence of hidden dynamics of octahedral SnI6 units in Cs2SnI6 with a low activation energy barrier of 12.45 kJ/mol (0.129 eV). We further show that complete mixed-halide solid solutions of Cs2SnClxBr6−x and Cs2SnBrxI6−x (0 ≤ x ≤ 6) form at any halogen compositional ratio. 119Sn and 133Cs NMR spectroscopy resolve the unique local SnClnBr6−nand SnBrnI6−n (n = 0−6) octahedral and CsBrmI12−m (m = 0−12) cuboctahedral environments in the mixed-halide samples. The experimentally observed 119Sn NMR results are consistent with magnetic shielding parameters obtained by density functional theory computations to verify random halogen distribution in mixed-halide analogues. Finally, we demonstrate the difference in the local structures and optical absorption properties of Cs2SnI6 samples prepared by solvent-assisted and solvent-free synthesis routes.

Congenital heart disease is the most common type of birth defect, accounting for one-third of all congenital anomalies. Using whole-exome sequencing of 2718 patients with congenital heart disease and a search in GeneMatcher, we identified 30 patients from 21 unrelated families of different ancestries with biallelic phospholipase D1 (PLD1) variants who presented predominantly with congenital cardiac valve defects. We also associated recessive PLD1 variants with isolated neonatal cardiomyopathy. Furthermore, we established that p.1668F is a founder variant among Ashkenazi Jews (allele frequency of -.2%) and describe the phenotypic spectrum of PLD1-associated congenital heart defects. PLD1 missense variants were overrepresented in regions of the protein critical for catalytic activity, and, correspondingly, we observed a strong reduction in enzymatic activity for most of the mutant proteins in an enzymatic assay. Finally, we demonstrate that PLD1 inhibition decreased endothelial-mesenchymal transition, an established pivotal early step in valvulogenesis. In conclusion, our study provides a more detailed understanding of disease mechanisms and phenotypic expression associated with PLD1 loss of function.

Background Associations between kidney disease and periodontal disease are not well documented among Aboriginal people of Australia. The purpose of this investigation was to report and compare demographic, oral health, anthropometric and systemic health status of Aboriginal Australians with kidney disease and to compare against relevant Aboriginal Australians and Australian population estimates. This provides much needed evidence to inform dental health service provision policies for Aboriginal Australians with kidney disease. Methods Sample frequencies and means were assessed in adults represented in six datasets including: (1) 102 Aboriginal Australians with kidney disease residing in Central Australia who participated in a detailed oral health assessment; (2) 312 Aboriginal participants of the Northern Territory’s PerioCardio study; (3) weighted estimates from 4775 participants from Australia’s National Survey of Adult Oral Health (NSAOH); (4) Australian 2016 Census (all Australians); (5) National Health Survey 2017–2018 (all Australians) and; (6) Australian Health Survey: Biomedical Results for Chronic Diseases, 2011–2012 (all Australians). Oral health status was described by periodontal disease and experience of dental caries (tooth decay). Statistically significant differences were determined via non-overlapping 95% confidence intervals. Results Aboriginal Australians with kidney disease were significantly older, less likely to have a tertiary qualification or be employed compared with both PerioCardio study counterparts and NSAOH participants. Severe periodontitis was found in 54.3% of Aboriginal Australians with kidney disease, almost 20 times the 2.8% reported in NSAOH. A higher proportion of Aboriginal Australians with kidney disease had teeth with untreated caries and fewer dental restorations when compared to NSAOH participants. The extent of periodontal attachment loss and periodontal pocketing among Aboriginal Australians with kidney disease (51.0%, 21.4% respectively) was several magnitudes greater than PerioCardio study (22.0%, 12.3% respectively) and NSAOH (5.4%, 1.3% respectively) estimates. Conclusions Aboriginal Australians with kidney disease exhibited more indicators of poorer oral health than both the general Australian population and a general Aboriginal population from Australia’s Northern Territory. It is imperative that management of oral health among Aboriginal Australians with kidney disease be included as part of their ongoing medical care.

The strong interactions among nucleons have an approximate spin-isospin exchange symmetry that arises from the properties of quantum chromodynamics in the limit of many colors, $N_c$. However this large-$N_c$ symmetry is well hidden and reveals itself only when averaging over intrinsic spin orientations. Furthermore, the symmetry is obscured unless the momentum resolution scale is close to an optimal scale that we call $\Lambda_{{\rm large-}N_c}$. We show that the large-$N_c$ derivation requires a momentum resolution scale of $\Lambda_{{\rm large-}N_c} \sim 500$ MeV. We derive a set of spin-isospin exchange sum rules and discuss implications for the spectrum of $^{30}$P and applications to nuclear forces, nuclear structure calculations, and three-nucleon interactions., Comment: 5 pages (main) + 3 pages (supplemental materials), 1 figure (main) + 4 figures (supplemental materials), final version to appear in Phys. Rev. Lett

Māori and Pacific women in New Zealand and Aboriginal and Torres Strait Islander women in Australia are recognised as nurturers and leaders within their families and communities. However, women’s wellbeing, and that of their communities, are affected by a high burden of cardiovascular disease experienced at a younger age than women from other ethnic groups. There has been little focus on the cardiovascular outcomes and strategies to address heart health inequities among Māori, Pacific, Aboriginal and Torres Strait Islander women. The factors contributing to these inequities are complex and interrelated but include differences in exposure to risk and protective factors, rates of multi-morbidity, and substantial gaps within the health system, which include barriers to culturally responsive, timely and appropriate cardiovascular care. Evidence demonstrates critical treatment gaps across the continuum of risk and disease, including assessment and management of cardiovascular risk in young women and time-critical access to and receipt of acute services. Cardiovascular disease in women impacts not only the individual, but their family and community, and the burden of living with disease limits women’s capacity to fulfil their roles and responsibilities which support and sustain families and communities. Our response must draw on the strengths of Māori, Pacific, Aboriginal and Torres Strait Islander women, acknowledge health and wellbeing holistically, address the health and social needs of individuals, families and communities, and recognise that Indigenous women in New Zealand, Australia and across the Pacific must be involved in the design, development and implementation of solutions affecting their own health. Refereed/Peer-reviewed

Background: Aboriginal and Torres Strait Islander (hereinafter respectfully termed Aboriginal)people have a greater incidence of stroke at a younger age than non-Indigenous people in Australia. The needs and preferences of Aboriginal people for rehabilitation and longer-term support remain largely unknown. Objectives: To identify the long-term rehabilitation needs of Aboriginal people who have a stroke, from the perspectives of Aboriginal persons with stroke and health care providers. Methods: Aboriginal people who had experienced stroke in the previous three years were interviewed to obtain their experiences of rehabilitation care. Health professionals who provided care in each of six designated hospitals and nearby community health sites were involved in focus groups and individual interviews. Information obtained was thematically analyzed separately for Aboriginal people with stroke and health professionals, and compared using Nvivo. Results: Among six Aboriginal people with stroke and 78 healthcare providers, four main themes emerged: the importance of family; variable access to services; the impact of stroke on Aboriginal peoples’ lives; and making positive choices. Communication and involvement of family was highlighted as essential for a shared understanding, particularly when making decisions about participating in short and long-term rehabilitation. Co–morbidities, conflicting priorities, and inadequate or inflexible services and transport compounded issues with changing life roles. Stories of resilience were also shared. Conclusions: Aboriginal people report making positive lifestyle changes, but experience significant unmet rehabilitation needs. Addressing issues of communication, advocacy and flexible delivery should improve some of the shortfalls in service provision, particularly in regional and remote areas. Refereed/Peer-reviewed

Background: Aboriginal and Torres Strait Islander peoples’ perspectives of health and cultural wellbeing encapsulate the spiritual, social and environmental health of individuals, their communities and country. Strategies designed to reduce the cardiovascular burden of Aboriginal and Torres Strait Islander people often fail to consider their unique knowledge and worldview. Methods: This adapted, grounded theory study sought to explore Aboriginal women’s views of cardiovascular protective and risk factors. Results: Twenty-eight (28) women from five women’s groups across Central and South Australia participated. Women distinguished the heart as core to their spiritual and physical wellbeing. Women identified six attributes that keep a woman’s heart strong, four that can make the heart sick, and eight socio-ecological factors which affect a woman’s capacity to care for their heart. Women described having a healthy heart when able to identify as Aboriginal women, being connected to family and community, having a healthy life and body, and being engaged in their health and health care. Conclusions: There are gaps in the provision of cardiovascular risk assessment and management, gaps in the cultural safety of primary health care services, and gaps in the communication of the sex-specific warning signs of a heart attack, all of which must be addressed. Refereed/Peer-reviewed

Aim: To identify: 1) best practice aged care principles and practices for Aboriginal and Torres Strait Islander older peoples, and 2) actions to integrate aged care services with Aboriginal community-controlled primary health care. Background: There is a growing number of older Aboriginal and Torres Strait Islander peoples and an unmet demand for accessible, culturally safe aged care services. The principles and features of aged care service delivery designed to meet the unique needs of Aboriginal and Torres Strait Islander peoples have not been extensively explored and must be understood to inform aged care policy and primary health care planning into the future. Methods: The research was governed by leaders from across the Aboriginal community-controlled primary health care sector who identified exemplar services to explore best practice in culturally aligned aged care. In-depth case studies were undertaken with two metropolitan Aboriginal community-controlled services. We conducted semi-structured interviews and yarning circles with 46 staff members to explore key principles, ways of working, enablers and challenges for aged care service provision. A framework approach to thematic analysis was undertaken with emergent findings reviewed and refined by participating services and the governance panel to incorporate national perspectives. Findings: A range of principles guided Aboriginal community-controlled aged care service delivery, such as supporting Aboriginal and Torres Strait Islander identity, connection with elders and communities and respect for self-determination. Strong governance, effective leadership and partnerships, Aboriginal and Torres Strait Islander workforce and culturally safe non-Indigenous workforce were among the identified enablers of aged care. Nine implementation actions guided the integration of aged care with primary health care service delivery. Funding limitations, workforce shortages, change management processes and difficulties with navigating the aged care system were among the reported challenges. These findings contribute to an evidence base regarding accessible, integrated, culturally safe aged care services tailored to the needs of Aboriginal and Torres Strait Islander peoples.

This paper argues for the importance of transnational memories in framing Australian anti-nuclear activism after the Fukushima disaster. Japan has loomed large in the transnational nuclear imaginary in Australia. Commemorating Hiroshima as the site of the first wartime use of nuclear weapons has been a long-standing practice in the Australian anti-nuclear movement and the day has been linked to a variety of issues including weapons and uranium mining. As Australia began exporting uranium to Japan in the 1970s, Australia-Japan relations took on a new meaning for the Indigenous traditional owners from whose land uranium was extracted. After Fukushima, these complex transnational memories formed the basis for an orientation towards Japan by Indigenous land rights activists and for the anti-nuclear movement as a whole. This paper argues that despite the tenuousness of direct organisational links between the two countries, transnational memories drove Australian anti-nuclear activists to seek connections with Japan after the Fukushima disaster. The mobilisation of these collective memories helps us to understand how transnational social movements evolve and how they construct globalisation from below in the Asia-Pacific region.