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Aim: To determine diabetic retinopathy prevalence and severity among remote Indigenous Australians. Methods: A cross-sectional diabetic retinopathy screening study of Indigenous adults with Type 2 diabetes was conducted by locally trained non-ophthalmic retinal imagers in a remote Aboriginal community-controlled primary healthcare clinic in Central Australia and certified non-ophthalmic graders in a retinal grading centre in Melbourne, Australia. The main outcome measure was prevalence of any diabetic retinopathy and sight-threatening diabetic retinopathy. Results: Among 301 participants (33% male), gradable image rates were 78.7% (n = 237) for diabetic retinopathy and 83.1% (n = 250) for diabetic macular oedema, and 77.7% (n = 234) were gradable for both diabetic retinopathy and diabetic macular oedema. For the gradable subset, the median (range) age was 48 (19-86) years and known diabetes duration 9.0 (0-24) years. The prevalence of diabetic retinopathy was 47% (n = 110) and for diabetic macular oedema it was 14.4% (n = 36). In the fully gradable imaging studies, sight-threatening diabetic retinopathy prevalence was 16.2% (n = 38): 14.1% (n = 33) for clinically significant macular oedema, 1.3% (n = 3) for proliferative diabetic retinopathy and 0.9% (n = 2) for both. Sight-threatening diabetic retinopathy had been treated in 78% of detected cases. Conclusions: A novel telemedicine diabetic retinopathy screening service detected a higher prevalence of 'any' diabetic retinopathy and sight-threatening diabetic retinopathy in a remote primary care setting than reported in earlier surveys among Indigenous and non-Indigenous populations. Whether the observed high prevalence of diabetic retinopathy was attributable to greater detection, increasing diabetic retinopathy prevalence, local factors, or a combination of these requires further investigation and, potentially, specific primary care guidelines for diabetic retinopathy management in remote Australia. Clinical Trials registration number: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN 12616000370404. Refereed/Peer-reviewed

Summary Background Indigenous populations have high rates of disease and premature mortality. Most Indigenous communities are young, and adolescence (age 10–24 years) provides great opportunities for population health gain. However, the absence of a comprehensive account of Indigenous adolescents' health has been a barrier to effective policy. We aimed to report a national health profile for Indigenous adolescents in Australia. Methods We undertook a systematic synthesis of population data to report the health and wellbeing of Indigenous adolescents in Australia. A reporting framework for Indigenous adolescent health in Australia was defined to measure health outcomes, health risks, and sociocultural determinants. Available data (primary data from national surveys and administrative datasets, and available published data) were mapped against the defined reporting framework, and the quality graded, with the highest quality data selected to report a health profile for Indigenous adolescents. Comparison with non-Indigenous adolescents was made where possible, and estimates (disaggregated by age, sex, and remoteness) were reported as relative risks. A national advisory group (six Indigenous young people, three Indigenous adult community members, three researchers, three policy makers, and two service providers, all aged ≥16 years) provided input about the reporting framework, interpretation of findings, and policy recommendations. Findings Data were available for 184 (79%) of 234 elements of the reporting framework. All-cause mortality for Indigenous adolescents (70 per 100 000) was more than twice that of non-Indigenous adolescents, with about 60% of deaths due to intentional self-harm and road traffic injury. 80% of all deaths among Indigenous adolescents were considered as potentially avoidable in the current health system. Communicable diseases (particularly sexually transmitted infections) were leading contributors to morbidity. Almost a third of Indigenous adolescents aged 18–24 years reported high levels of psychological distress (twice the non-Indigenous rate). There was an excess burden of mental disorders and substance use, alongside emerging type 2 diabetes and ischaemic heart disease. Additionally, there were excess intentional and unintentional injuries. Many aspects of this health profile differed markedly from that of non-Indigenous adolescents: rates of acute rheumatic fever, pneumococcal infection, gonorrhoea, and type 2 diabetes resulting in admission to hospital were ten times higher; rates of assault and childbirth in those aged 15–19 years were five times higher; whereas rates of eating disorders, melanoma and other skin cancers, and anaphylaxis were significantly lower. Risks for future ill-health were common; 43% of 15–24 year olds were current tobacco smokers and about 45% had high body mass (overweight or obese). Disadvantage across sociocultural health determinants also emerged, particularly around education. Interpretation Despite Australia's adolescents having one of the best health profiles globally, Indigenous adolescents have largely been left behind. Adequate responses will require intersectoral actions, including a health system responsive to the needs of Indigenous adolescents. Without a specific focus on adolescents, Australia will not redress Indigenous health inequalities. Funding Australia's National Health and Medical Research Council, Sidney Myer Foundation, and the Murdoch Children's Research Institute.

Background: Aboriginal Australians have poorer cancer survival than other Australians. Diagnoses at later stages and correlates of remote area living influence, but do not fully explain, these disparities. Little is known of the prevalence and influence of comorbid conditions experienced by Aboriginal people, including their effect on cancer survival. This study quantifies hospital recorded comorbidities using the Elixhauser Comorbidity Index (ECI), examines their influence on risk of cancer death, then considers effect variation by Aboriginality. Methods: Cancers diagnosed among Aboriginal South Australians in 1990–2010 (N = 777) were matched with randomly selected non-Aboriginal cases by birth year, diagnostic year, sex, and primary site, then linked to administrative hospital records to the time of diagnosis. Competing risk regression summarised associations of Aboriginal status, stage, geographic attributes and comorbidities with risk of cancer death. Results: A threshold of four or more ECI conditions was associated with increased risk of cancer death (sub-hazard ratio SHR 1.66, 95%CI 1.11-2.46). Alternatively, the presence of any one of a subset of ECI conditions was associated with similarly increased risk (SHR = 1.62, 95%CI 1.23-2.14). The observed effects did not differ between Aboriginal and matched non-Aboriginal cases. However, Aboriginal cases experienced three times higher exposure than non-Aboriginal to four or more ECI conditions (14.2% versus 4.5%) and greater exposure to the subset of ECI conditions (20.7% versus 8.0%). Conclusion: Comorbidities at diagnosis increased the risk of cancer death in addition to risks associated with Aboriginality, remoteness of residence and disease stage at diagnosis. The Aboriginal cohort experienced comparatively greater exposure to comorbidities which adds to disparities in cancer outcomes. Refereed/Peer-reviewed

OBJECTIVE To examine the association between soluble tumor necrosis factor receptor 1 (sTNFR1) levels and kidney disease progression in Indigenous Australians at high risk of kidney disease. RESEARCH DESIGN AND METHODS This longitudinal observational study examined participants aged ≥18 years recruited from >20 sites across diabetes and/or kidney function strata. Baseline measures included sTNFR1, serum creatinine, urine albumin-to-creatinine ratio (uACR), HbA1c, C-reactive protein (CRP), waist-to-hip ratio, systolic blood pressure, and medical history. Linear regression was used to estimate annual change in estimated glomerular filtration rate (eGFR) for increasing sTNFR1, and Cox proportional hazards were used to estimate the hazard ratio (HR) and 95% CI for developing a combined renal outcome (first of a ≥30% decline in eGFR with a follow-up eGFR RESULTS Over a median of 3 years, participants with diabetes (n = 194) in the highest compared with the lowest quartile of sTNFR1 experienced significantly greater eGFR decline (−4.22 mL/min/1.73 m2/year [95% CI −7.06 to −1.38]; P = 0.004), independent of baseline age, sex, eGFR, and uACR. The adjusted HR (95% CI) for participants with diabetes per doubling of sTNFR1 for the combined renal outcome (n = 32) was 3.8 (1.1–12.8; P = 0.03). No association between sTNFR1 and either renal outcome was observed for those without diabetes (n = 259). CONCLUSIONS sTNFR1 is associated with greater kidney disease progression independent of albuminuria and eGFR in Indigenous Australians with diabetes. Further research is required to assess whether TNFR1 operates independently of other metabolic factors associated with kidney disease progression.

A well-defined Ir-allyl complex catalyzes the Z-selective cross-coupling of allyl carbonates with α-aryl diazo esters. The process overrides the large thermodynamic preference for E-products typically observed in metal-mediated coupling reactions to enable the synthesis of Z,E-dieneoates in good yield with selectivities consistently approaching or greater than 90 : 10. This transformation represents the first productive merger of Ir-carbene and Ir-allyl species, which are commonly encountered intermediates in allylation and cyclopropanation/E-H insertion catalysis. Potentially reactive functional groups (aryl halides, ketones, nitriles, olefins, amines) are tolerated owing to the mildness of reaction conditions. Kinetic analysis of the reaction suggests oxidative addition of the allyl carbonate to an Ir-species is rate-determining. Mechanistic studies uncovered a pathway for catalyst activation mediated by NEt3.

Gas density distributions for an underexpanded jet at several different pressure ratios were measured at ultrahigh speeds in this work using digital holographic interferometry (DHI). DHI measurements have generally been performed on the order of several Hz in the literature, although some recent groups report measurements at 10 and 100 kHz. We demonstrate 2D imaging of gas density distributions at imaging rates up to 5 MHz, which is an increase by a factor of 50 compared to the previous DHI literature. A narrow-linewidth, continuous-wave laser was used in a Mach–Zehnder configuration, and the holograms were recorded using one of two different CMOS cameras. The interferograms were analyzed using the Fourier method, and a phase unwrapping was performed. Axisymmetric flow was assumed for the region near the nozzle exit, and an Abel inversion was performed to generate a planar-slice gas density distribution from the line-of-sight unwrapped phase. The challenges and opportunities associated with performing DHI measurements at ultrahigh speeds are discussed.

Aims: To determine among First Nations and Europid pregnant women the cumulative incidence and predictors of postpartum type 2 diabetes and prediabetes and describe postpartum cardiovascular disease (CVD) risk profiles. Methods: PANDORA is a prospective longitudinal cohort of women recruited in pregnancy. Ethnic-specific rates of postpartum type 2 diabetes and prediabetes were reported for women with diabetes in pregnancy (DIP), gestational diabetes (GDM) or normoglycaemia in pregnancy over a short follow-up of 2.5 years (n = 325). Pregnancy characteristics and CVD risk profiles according to glycaemic status, and factors associated with postpartum diabetes/prediabetes were examined in First Nations women. Results: The cumulative incidence of postpartum type 2 diabetes among women with DIP or GDM were higher for First Nations women (48%, 13/27, women with DIP, 13%, 11/82, GDM), compared to Europid women (nil DIP or GDM p < 0.001). Characteristics associated with type 2 diabetes/prediabetes among First Nations women with GDM/DIP included, older age, multiparity, family history of diabetes, higher glucose values, insulin use and body mass index (BMI). Conclusions: First Nations women experience a high incidence of postpartum type 2 diabetes after GDM/DIP, highlighting the need for culturally responsive policies at an individual and systems level, to prevent diabetes and its complications. Refereed/Peer-reviewed

A series of donor–acceptor–donor (D-A-D) type small molecule (SM) donors containing Pechmann dye analogues (N, S, O) are designed and their geometrical, optoelectronic, charge transport, and photovoltaic properties are investigated using density functional theory (DFT). The structural modification of the donor backbone has been performed via additional sp2-nitrogen heteroatom incorporation in the Pechmann analogue acceptor cores. The N-heteroatom containing SM donors are found to be more air-stable due to having relatively deeper HOMO/LUMO levels than their unsubstituted counterparts. The maximum computed open-circuit voltage (Voc) is 1.53 V for the N-heteroatom substituted O-Pechmann core based donor. The designed donors are expected to harvest photon energy efficiently as their simulated absorption spectra lie in the visible region (575–724 nm). The N-heteroatom incorporation plays a significant role in lowering the charge recombination rate (KCR) and increasing the charge separation rate (KCS) at the SM donor/PC61BM interface. The ratio of interfacial KCS and KCR is found to be improved by 1 0 4 − 1 0 10 times after sp2-nitrogen substitution in the Pechmann analogue cores. The maximum predicted power conversion efficiencies (PCEs) using the Scharber diagram reach up to ∼ 9% for the S-analogue of the Pechmann dye core based donor. This study sheds light on promising SM donors based on Pechmann dye analogues with low interfacial charge recombination rates and high charge separation rates and also demonstrates the impact of structural modification of Pechmann dye analogue cores on air-stability and overall photovoltaic performance.

A new process was developed to recover high specific activity (no carrier added)

Phosphor thermometry has been successfully applied within several challenging environments. Typically, the thermographic phosphors are excited by an ultraviolet light source, and the temperature-dependent spectral or temporal response is measured. However, this is challenging or impossible in optically thick environments. In addition, emission from other sources (e.g., a flame) may interfere with the optical phosphor emission. A temperature dependent x-ray excitation/emission could alleviate these issues as x-rays could penetrate obscurants with no interference from flame luminosity. In addition, x-ray emission could allow for thermometry within solids while simultaneously x-ray imaging the structural evolution. In this study, select thermographic phosphors were excited via x-ray radiation, and their x-ray emission characteristics were measured at various temperatures. Several of the phosphors showed varying levels of temperature dependence with the strongest sensitivity occurring for YAG:Dy and ZnGa2O4:Mn. This approach opens a path for less intrusive temperature measurements, particularly in optically opaque multiphase and solid phase combustion environments.

PurposeOur aims are to: (1) estimate prevalence, incidence, clearance and persistence of oral human papillomavirus (HPV) infection among Indigenous Australians; (2) identify risk factors associated with oropharyngeal squamous cell carcinoma (OPSCC)-related HPV types (HPV 16 or 18); (3) develop HPV-related health state valuations and; (4) determine the impact on OPSCC and cervical cancers, and the cost-effectiveness of extending publicly-funded HPV vaccination among Indigenous Australians.ParticipantsParticipants were recruited from February 2018 to January 2019. Twelve-month follow-up occurred from March 2019 to March 2020. Participants provided socio-demographic characteristics, health-related behaviours including tobacco and alcohol use and sexual history. Health state preferences in regard to HPV vaccination, knowledge regarding HPV infection, OPSCC and cervical cancer were collected using a two-stage standard gamble approach. Participants provided saliva samples and DNA for microbial genotyping was extracted.Findings to dateOf the 910 participants who were positive for β-globin at baseline, 35% had any oral HPV infection. The most prevalent HPV types were 13 or 32 (Heck’s disease; 23%). The second most prevalent types were associated with OPSCC (HPV 16 or 18; 3.3%). Of the 645 participants who were positive for β-globin at 12-month follow-up, 43% had any HPV infection. Of these, 33% were HPV types 13 or 32 and 2.5% were HPV 16 or 18. Some 588 participants had β-globin positive oral samples at baseline and 12-month follow-up. The prevalence of any oral HPV infection increased from 34% at baseline to 44% at 12-month follow-up; due to increases in HPV types 13 or 32 (20% at baseline and 34% at 12-month follow-up).Future plansFurther funding will be sought to continue follow-up of this cohort, and to include (after a full medical history) a thorough clinical examination of the external head and neck; a complete oral examination and examination of the oropharynx. Blood tests for early stage OPSCC will also be undertaken.

Thermographic phosphors have been employed for temperature sensing in challenging environments, such as on surfaces or within solid samples exposed to dynamic heating, because of the high temporal and spatial resolution that can be achieved using this approach. Typically, UV light sources are employed to induce temperature-sensitive spectral responses from the phosphors. However, it would be beneficial to explore x-rays as an alternate excitation source to facilitate simultaneous x-ray imaging of material deformation and temperature of heated samples and to reduce UV absorption within solid samples being investigated. The phosphors BaMgAl10O17:Eu (BAM), Y2SiO5:Ce, YAG:Dy, La2O2S:Eu, ZnGa2O4:Mn, Mg3F2GeO4:Mn, Gd2O2S:Tb, and ZnO were excited in this study using incident synchrotron x-ray radiation. These materials were chosen to include conventional thermographic phosphors as well as x-ray scintillators (with crossover between these two categories). X-ray-induced thermographic behavior was explored through the measurement of visible spectral response with varying temperature. The incident x-rays were observed to excite the same electronic energy level transitions in these phosphors as UV excitation. Similar shifts in the spectral response of BAM, Y2SiO5:Ce, YAG:Dy, La2O2S:Eu, ZnGa2O4:Mn, Mg3F2GeO4:Mn, and Gd2O2S:Tb were observed when compared to their response to UV excitation found in literature. Some phosphors were observed to thermally quench in the temperature ranges tested here, while the response from others did not rise above background noise levels. This may be attributed to the increased probability of non-radiative energy release from these phosphors due to the high energy of the incident x-rays. These results indicate that x-rays can serve as a viable excitation source for phosphor thermometry.

The complexation of HDEHP, HEH[EHP], T2EHDGA, and TODGA and mixtures thereof in n-dodecane with Nd(III), Pm(III), and Am(III), extracted from pH 3 aqueous media, were analyzed by distribution analysis, IR, UV–vis, and X-ray spectroscopies. Appreciable ternary complex formation is seen among HDEHP with DGA components and to a lesser extent with HEH[EHP]. Ternary complex formation constants were determined by absorption spectroscopy and slope analysis. The effect of the adduct formation on the process performance and on the Ln/An selectivity is discussed. It has been shown that the ternary complexes have the tendency to extract larger trivalent cations as Am and Nd over Eu, thus diminishing the overall Ln/Am selectivity of the process. Also, previously unreported extraction constants were derived for HEH[EHP] with Am and Pm as well as coordination information for Nd-HEH[EHP] and Nd-T2EHDGA complexes.

Previous research in our group showed that tellurophenes with pinacolboronate (BPin) units at the 2- and/or 5-positions displayed efficient phosphorescence in the solid state, both in the presence of oxygen and water. In this current study, we show that luminescence from a tellurophene is possible when various aryl-based substituents are present, thus greatly expanding the family of known (and potentially accessible) Te-based phosphors. Moreover, for the green phosphorescent perborylated tellurium heterocycle, 2,3,4,5-TeC4BPin4 (4BTe), oxygen-mediated quenching of phosphorescence is an important contributor to the lack of emission in solution (when exposed to air); thus this system displays aggregation-enhanced emission (AEE). These discoveries should facilitate the future design of color tunable tellurium-based luminogens.

Molybdenum-99 is the parent isotope of the most widely used isotope, technetium-99m, in all diagnostic nuclear medicine procedures. Due to proliferation concerns associated with the use of highly enriched uranium (HEU), the preferred method of fission-based Mo-99 production uses low enriched uranium (LEU) targets. Using LEU versus HEU for Mo-99 production produces ∼30 times more Pu-239, due to neutron capture on U-238 to produce Np-239, which ultimately decays to Pu-239 (t1/2 = 24,110 yr). Argonne National Laboratory is supporting a potential US Mo-99 producer in their efforts to produce Mo-99 from an LEU solution. In order to mitigate the generation of large volumes of greater-than-class-C (GTCC) low level waste (Pu-239 concentrations greater than 1 nCi/g), we have focused our efforts on the separation chemistry of Pu and Mo with a titania sorbent in sulfate media. Results from batch and column experiments show that temperature and acid wash concentration can be used to control Pu behavior on titania.

Predation risk has a profound influence on the behavior of marine mammals, affecting grouping patterns and habitat use. Dolphins frequently bear evidence of shark bites, which can provide an indirect measure of predation pressure. Using photo-identification data, we investigated the prevalence of shark bites on three sympatric species of inshore dolphin, the Australian snubfin (Orcaella heinsohni), Australian humpback (Sousa sahulensis), and Indo-Pacific bottlenose dolphin (Tursiops aduncus), among four study sites in northwestern Australia. Bite prevalence varied markedly between species, with 72% of snubfin, 46% of humpback, and 18% of bottlenose dolphins exhibiting evidence of shark bites. Binomial logistic regression confirmed a high likelihood of bite presence on snubfin dolphins, and at one particular site for snubfin and bottlenose dolphins. The prevalence of tiger shark (Galeocerdo cuvier) bites on snubfin dolphins was high, and bites attributed to other carcharhinid sharks were observed on all species. While acknowledging methodological differences with other studies, the prevalence of shark bites on snubfin dolphins is among the highest reported for any dolphins, suggesting predation risk represents an important but varying influence thereon. This study provides a baseline for future investigations into the affect of predation risk on the behavioral ecology of these sympatric species.

Aims: Preconception care may decrease adverse pregnancy outcomes associated with pre-existing diabetes mellitus. Aboriginal Australians are at high risk of type 2 diabetes mellitus (T2DM), with earlier onset. We explored practitioner views on preconception care delivery for women with T2DM in the Northern Territory, where 31% of births are to Aboriginal women. Methods: Mixed-methods study including cross-sectional survey of 156 health practitioners and 11 semi-structured interviews. Results: Practitioners reported low attendance for preconception care however, 51% provided counselling on an opportunistic basis. Rural/remote practitioners were most likely to find counselling feasible. The majority (69%) utilised appropriate guidelines and addressed lifestyle modifications including smoking (81%), weight management (79%), and change medications appropriately such as ceasing ACE inhibitors (69%). Fewer (40%) prescribed the recommended dose of folate (5 mg) or felt comfortable recommending delaying pregnancy to achieve optimal preconception glucose control (42%). Themes identified as barriers to care included the complexity of care setting and infrequent preconception consultations. There was a focus on motivation of women to make informed choices about conception, including birth spacing, timing and contraception. Preconception care enablers included cross-cultural communication, a multi-disciplinary care team and strong client-based relationships. Conclusions: Health practitioners are keen to provide preconception counselling and reported knowledge of evidence-based guidelines. Improvements are needed in recommending high dose folate and optimising glucose control. Cross-cultural communication and team-based care were reported as fundamental to successful preconception care in women with T2DM. Continued education and policy changes are required to support practitioners in opportunities to enhance pregnancy planning. Refereed/Peer-reviewed

Determining the impact of lipid electrophile-mediated protein damage that occurs during oxidative stress requires a comprehensive analysis of electrophile targets adducted under pathophysiological conditions. Incorporation of ω-alkynyl linoleic acid into the phospholipids of macrophages prior to activation by Kdo2-lipid A, followed by protein extraction, click chemistry, and streptavidin affinity capture, enabled a systems-level survey of proteins adducted by lipid electrophiles generated endogenously during the inflammatory response. Results revealed a dramatic enrichment for membrane and mitochondrial proteins as targets for adduction. A marked decrease in adduction in the presence of MitoTEMPO demonstrated a primary role for mitochondrial superoxide in electrophile generation and indicated an important role for mitochondria as both a source and target of lipid electrophiles, a finding that has not been revealed by prior studies using exogenously provided electrophiles.

© 2017 The Author(s). Background: In spite of bearing a heavier burden of death, disease and disability, there is mixed evidence as to whether Indigenous Australians utilise more or less healthcare services than other Australians given their elevated risk level. This study analyses the Medicare expenditure and its predictors in a cohort of Indigenous and non-Indigenous Australians at high risk of cardiovascular disease. Methods: The healthcare expenditure of participants of the Kanyini Guidelines Adherence with the Polypill (GAP) pragmatic randomised controlled trial was modelled using linear regression methods. 535 adult (48% Indigenous) participants at high risk of cardiovascular disease (CVD) were recruited through 33 primary healthcare services (including 12 Aboriginal Medical Services) across Australia. Results: There was no significant difference in the expenditure of Indigenous and non-Indigenous participants in non-remote areas following adjustment for individual characteristics. Indigenous individuals living in remote areas had lower MBS expenditure (932 per year P < 0.001) than other individuals. MBS expenditure was found to increase with being aged over 65 years (128, p = 0.013), being female (472, p = 0.003), lower baseline reported quality of life (102 per 0.1 decrement of utility p = 0.004) and a history of diabetes (324, p = 0.001), gout (631, p = 0.022), chronic obstructive pulmonary disease (469, p = 0.019) and established CVD whether receiving guideline-recommended treatment prior to the trial (452, p = 0.005) or not (483, p = 0.04). When controlling for all other characteristics, morbidly obese patients had lower MBS expenditure than other individuals (-887, p = 0.002). Conclusion: The findings suggest that for the majority of participants, once individuals are engaged with a primary care provider, factors other than whether they are Indigenous determine the level of Medicare expenditure for each person. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN 126080005833347.

Several promising pathways exist for the production of 99Mo/99mTc using enriched 98Mo or 100Mo. Use of Mo targets requires a major change in current generator technology, and the necessity for an e...

This white paper informs the nuclear astrophysics community and funding agencies about the scientific directions and priorities of the field and provides input from this community for the 2015 Nuclear Science Long Range Plan. It summarizes the outcome of the nuclear astrophysics town meeting that was held on August 21–23, 2014 in College Station at the campus of Texas A&M University in preparation of the NSAC Nuclear Science Long Range Plan. It also reflects the outcome of an earlier town meeting of the nuclear astrophysics community organized by the Joint Institute for Nuclear Astrophysics (JINA) on October 9–10, 2012 Detroit, Michigan, with the purpose of developing a vision for nuclear astrophysics in light of the recent NRC decadal surveys in nuclear physics (NP2010) and astronomy (ASTRO2010). The white paper is furthermore informed by the town meeting of the Association of Research at University Nuclear Accelerators (ARUNA) that took place at the University of Notre Dame on June 12–13, 2014. In summary we find that nuclear astrophysics is a modern and vibrant field addressing fundamental science questions at the intersection of nuclear physics and astrophysics. These questions relate to the origin of the elements, the nuclear engines that drive life and death of stars, and the properties of dense matter. A broad range of nuclear accelerator facilities, astronomical observatories, theory efforts, and computational capabilities are needed. With the developments outlined in this white paper, answers to long standing key questions are well within reach in the coming decade.

While statins have formed the cornerstone of strategies for cardiovascular prevention, the residual risk related to low-density lipoprotein cholesterol (LDL-C) and other lipoprotein factors provides a landscape for development of new therapies. However, a number of lipid-modifying therapies have failed to reduce cardiovascular event rates in contemporary clinical trials of statin-treated patients. The factors considered in outcome measure selection for clinical trials of novel lipid-lowering therapies are reviewed. Evaluation of lipid-modifying drugs in clinical trials spans a spectrum from their effects on conventional circulating lipid parameters through to their impact on atherosclerotic plaque and ultimately clinical outcomes. The design of these trials has an important impact on the result and ultimate interpretation of these studies.

The clinical reality of residual risk despite statin (HMG-CoA reductase inhibitor) therapy and emergence of statin intolerance support the need to develop additional lipid-lowering strategies. Proprotein convertase subtilisin kexin type 9 (PCSK9) has received considerable attention by virtue of genetic and clinical studies that have revealed its pivotal role in the regulation of cholesterol homeostasis. Monoclonal antibodies have been developed targeting PCSK9, which have been demonstrated to produce profound low-density lipoprotein cholesterol (LDL-C) lowering when provided as monotherapy or in combination with statins. With the reports that the PCSK9 inhibitor evolocumab has a favorable impact on both plaque progression and cardiovascular outcomes, these findings begin to translate the benefits of PCSK9 inhibition from lipids to the vessel wall and ultimately to clinical outcomes. The clinical implications for the use of these agents are reviewed in this article.

Lipid second messengers have essential roles in cellular function and contribute to the molecular mechanisms that underlie inflammation, malignant transformation, invasiveness, neurodegenerative disorders, and infectious and other pathophysiological processes. The phospholipase D (PLD) isoenzymes PLD1 and PLD2 are one of the major sources of signal-activated phosphatidic acid (PtdOH) generation downstream of a variety of cell-surface receptors, including G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs) and integrins. Recent advances in the development of isoenzyme-selective PLD inhibitors and in molecular genetics have suggested that PLD isoenzymes in mammalian cells and pathogenic organisms may be valuable targets for the treatment of several human diseases. Isoenzyme-selective inhibitors have revealed complex inter-relationships between PtdOH biosynthetic pathways and the role of PtdOH in pathophysiology. PLD enzymes were once thought to be undruggable owing to the ubiquitous nature of PtdOH in cell signalling and concerns that inhibitors would be too toxic for use in humans. However, recent promising discoveries suggest that small-molecule isoenzyme-selective inhibitors may provide novel compounds for a unique approach to the treatment of cancers, neurodegenerative disorders and other afflictions of the central nervous system, and potentially serve as broad-spectrum antiviral and antimicrobial therapeutics.

The effects of explicit hydrogen bonding with H2O on the resonance Raman spectra of uracil and thymine are examined computationally. The three bonding sites in uracil and thymine that form the lowest energy uracil-H2O and thymine-H2O complexes, as well as a more limited number of low-lying ones containing two waters, are considered. The ground state structures are optimized at the PBE0/aug-cc-pVTZ level of theory in H2O (C-PCM), and the gradients of the bright excited state ( S 1 ) are computed at the TD-CAM-B3LYP/aug-cc-pVTZ level of theory in H2O (C-PCM). As the resonance Raman spectrum is governed by the ground state normal modes and the excited state Cartesian gradient (within the Herzberg-Teller formalism), the differences between spectra of uracil- and thymine-(H2O)n, n = 1 or 2, are compared in terms of these two factors. Explicit hydrogen bonding to water is found to cause changes in both relative peak positions and intensities for the resonance Raman spectra of uracil and thymine when compared to the isolated molecules. The effect of hydrogen bonding is primarily on the ground state normal mode character, especially for the high frequency modes (>1600 cm−1), rather than on the excited state Cartesian gradients. Different hydrogen bonding sites are found to have different contributions to the resulting resonance Raman spectra, and inclusion of explicit hydrogen bonding on the carbonyl bond opposite to the ring nitrogen is necessary to obtain good agreement between the simulated and experimental resonance Raman spectra for uracil and thymine.

The scoping review project will identify and describe the existing research on health promotion programs and activities focusing on modifying risk factors (specifically to reduce smoking and alcohol consumption, increase physical activity and improve nutrition and social and emotional wellbeing) and/or improving the management of chronic diseases (specifically obesity, type 2 diabetes, chronic kidney disease and cardiovascular disease) for Aboriginal and Torres Strait Islander peoples across a diverse range of health and community settings.

Background Atrial fibrillation (AF) is the most common preoperative arrhythmia in heart valve surgery patients and its prevalence is rising. This study aims to investigate the impact of AF on valve surgery early complications and survival and on valve disease of different aetiologies and populations with particular reference to Indigenous Australians with rheumatic heart disease (RHD). Methods The Australian and New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database was analysed to determine the association between preoperative AF and valve surgery outcome. Its association with demographics, co-morbidities, preoperative status and short and long term outcome was assessed. Results Outcome of 1594 RHD and 19,029 non-RHD-related surgical procedures was analysed. Patients with preoperative AF were more likely to be older, female, Indigenous, to have RHD and to bear a greater burden of comorbidities. Patients with RHD and preoperative AF had a longer hospital stay and were more likely to require reoperation. Adjusted short (OR 1.4, 95% CI 1.2–1.7) and long term (HR 1.5, 95% CI 1.3–1.7) survival was inferior for patients with non-RHD preoperative AF but was no different for Indigenous and non-Indigenous Australians with RHD. Conclusions In this prospective Australian study, patients with valve disease and preoperative AF had inferior short and long term survival. This was particularly the case for patients with non-RHD valve disease. Earlier intervention or more aggressive AF management should be investigated as mechanisms for enhancing postoperative outcomes. This may influence treatment choice and the need for ongoing anticoagulation. Refereed/Peer-reviewed

For most patients, life continues beyond the intensive care unit,and this is where action is needed.

We have constructed a (semi)-global six-dimensional potential energy surface (PES) for HFCO, incorporating the equilibrium, cis- and trans- isomers (HOCF) as well as the transition states connecting them. The PES is based on a fit to 15000 CCSD(T)-F12/cc-pVTZ-F12 ab initio energies. The sum-of-products PES, obtained using neural network exponential fitting functions, was used to compute vibrational state frequencies using block improved relaxation with the multiconfiguration time dependent Hartree (MCTDH) approach. The PES is accurate (RMSE = 130 cm −1 ) up to 40,000 cm −1 above the minimum energy. The equilibrium region of the PES was fit very well based on a comparison of the vibrational frequencies with those from a recent local HFCO PES (Pradhan and Brown, 2016) and experimental measurements (RMSE = 10.9 cm −1 compared to experiment). The vibrational frequencies for the trans- and cis-isomers are computed from the PES and compared to anharmonic MP2/aug-cc-pVTZ and CCSD(T)/aug-cc-pVTZ results; the trans- and cis-isomers have yet to be detected experimentally. Based on the accuracy of the vibrational energies at equilibrium, the present results for the cis- and trans-isomers could facilitate the identification of these species. The PES will also enable the study of intramolecular vibrational energy redistribution and its control leading to the elusive equilibrium HFCO to trans-HOCF conversion.

Objective: Given the high prevalence of chronic disease, it is of concern that access to and sustained engagement with primary healthcare services by Aboriginal and Torres Strait Islander Australians is often far lower than would be expected. This study sought to explore ways in which relationships can support sustained engagement with healthcare services. Methods: Semi-structured interviews were conducted with 126 Aboriginal and Torres Strait Islander participants with and without chronic disease and 97 Aboriginal and Torres Strait Islander and non-Indigenous healthcare providers, healthcare service managers or administrative staff. Results: Our findings indicate that when faced with acute health issues, Aboriginal and Torres Strait Islander participants did prioritise care, provided that the service was both physically and emotionally welcoming. Trustworthiness of healthcare providers and strong relationships with patients were the most important factors for encouraging sustained engagement overtime. Conclusions: Responsibility for sustaining relationships does not rest solely with Aboriginal and Torres Strait Islander patients. Rather, healthcare providers need to commit to the process of building and maintaining relationships. Implications: First and foremost healthcare providers should take time to establish and then maintain relationships. Healthcare services can also contribute by ensuring facilities are welcoming for Aboriginal and Torres Strait Islander peoples.

Summary Lysophosphatidate acyltransferase (LPAAT) catalyses the second step of the Kennedy pathway for triacylglycerol (TAG) synthesis. In this study we expressed Trapaeolum majus LPAAT in Brassica napus (B. napus) cv 12075 to evaluate the effects on lipid synthesis and estimate the flux control coefficient for LPAAT.We estimated the flux control coefficient of LPAAT in a whole plant context by deriving a relationship between it and overall lipid accumulation, given that this process is a exponential.Increasing LPAAT activity resulted in greater TAG accumulation in seeds of between 25% and 29%; altered fatty acid distributions in seed lipids (particularly those of the Kennedy pathway); and a redistribution of label from 14C‐glycerol between phosphoglycerides.Greater LPAAT activity in seeds led to an increase in TAG content despite its low intrinsic flux control coefficient on account of the exponential nature of lipid accumulation that amplifies the effect of the small flux increment achieved by increasing its activity. We have also developed a novel application of metabolic control analysis likely to have broad application as it determines the in planta flux control that a single component has upon accumulation of storage products.

Type 2 diabetes mellitus (T2DM) poses significant challenges to individuals and broader society, much of which is borne by disadvantaged and marginalised population groups including Indigenous people. The increasing prevalence of T2DM among Indigenous people has meant that rates of diabetes-related complications such as blindness from end-stage diabetic retinopathy (DR) continue to be important health concerns. Australia, a high-income and resource-rich country, continues to struggle to adequately respond to the health needs of its Indigenous people living with T2DM. Trends among Indigenous Australians highlight that the prevalence of DR has almost doubled over two decades, and the prevalence of diabetes-related vision impairment is consistently reported to be higher among Indigenous Australians (5.2%–26.5%) compared to non-Indigenous Australians (1.7%). While Australia has collated reliable estimates of the eye health burden owing to T2DM in its Indigenous population, there is fragmentation of existing data and limited knowledge on the underlying risk factors. Taking a systems approach that investigates the social, environmental, clinical, biological and genetic risk factors, and—importantly—integrates these data, may give valuable insights into the most important determinants contributing to the development of diabetes-related blindness. This knowledge is a crucial initial step to reducing the human and societal impacts of blindness on Indigenous Australians, other priority populations and society at large.

Background: Australian Indigenous women experience high rates of social disadvantage and type 2 diabetes (T2D) in pregnancy, but it is not known how social factors and maternal behaviours impact neonatal adiposity in offspring of women with hyperglycaemia in pregnancy.Methods: Participants were Indigenous (n = 404) and Europid (n = 240) women with gestational diabetes mellitus (GDM) or T2D in pregnancy and their offspring in the Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) study. Social, economic factors, and maternal behaviours were measured in pregnancy and six neonatal anthropometric outcomes were examined after birth.Results: On univariate analysis, maternal education < 12 years (p = 0.03), unemployment(p = 0.001), welfare income vs no welfare income (p = 0.001), lower area based socioeconomic score (p < 0.001), and fast food intake > 2 times/week (p = 0.002) were associated with increased sum of skinfolds (SSF) in offspring. Smoking was significantly associated witha reduction in anthropometric measures, except SSF. In multivariable models adjusted for ethnicity, BMI and hyperglycaemia, social and economic factors were no longer significant predictors of neonatal outcomes. Smoking was independently associated with a reduction inlength, head circumference and fat free mass. Frequent fast food intake remained independently associated with SSF (b-coefficient 1.08 mm, p = 0.02).Conclusion: In women with hyperglycaemia in pregnancy, social factors were associated with neonatal adiposity, particularly skinfold measures. Promoting smoking cessation and limited intake of energy-dense, nutrient-poor foods in pregnancy are important to improve neonatal adiposity and lean mass outcomes. Addressing inequities in social and economic factors are likely to be important, particularly for Indigenous women or women experiencing social disadvantage. Refereed/Peer-reviewed

Traditional languages are a key element of Indigenous peoples&rsquo, identity, cultural expression, autonomy, spiritual and intellectual sovereignty, and wellbeing. While the links between Indigenous language loss and poor mental health have been demonstrated in several settings, little research has sought to identify the potential psychological benefits that may derive from language reclamation. The revival of the Barngarla language on the Eyre Peninsula, South Australia, offers a unique opportunity to examine whether improvements in mental health and social and emotional wellbeing can occur during and following the language reclamation process. This paper presents findings from 16 semi-structured interviews conducted with Barngarla community members describing their own experienced or observed mental health and wellbeing impacts of language reclamation activities. Aligning with a social and emotional wellbeing framework from an Aboriginal and Torres Strait Islander perspective, key themes included connection to spirituality and ancestors, connection to Country, connection to culture, connection to community, connection to family and kinship, connection to mind and emotions, and impacts upon identity and cultural pride at an individual level. These themes will form the foundation of assessment of the impacts of language reclamation in future stages of the project.

Aboriginal and Torres Strait Islander Australians are more likely to be admitted to acute care hospitals than non-Indigenous Australians.1While this is widely recognised, the over- representation of Indigenous patients in Australian intensive care units (ICUs) has been highlighted only recently.2,3 The headline finding that Indigenous Australians have an ICU admission rate that is 1.2 times the expected rate considering population representation is concerning, although not surprising, given higher Indigenous hospitalisation rates.1–3 It is reassuring that Indigenous patients appear to have similar in-ICU and in-hospital mortality.2,3 Intensivists should be justifiably proud of this mortality equivalence, but deeper analysis conveys some inconvenient truths. Refereed/Peer-reviewed

To provide a contemporary description of the demographics, characteristics and outcomes of critically ill Indigenous patients in Australia.Retrospective database review using the Australian and New Zealand Intensive Care Society Adult Patient Database for intensive care unit (ICU) admissions in 2017-18. Characteristics of critically ill Indigenous patients were compared with non-Indigenous patients.Primary outcome was hospital mortality. Secondary outcomes examined demographics and resource use.Per capita, Indigenous Australians were overrepresented in the intensive care. They were younger (51Indigenous patients, especially young Indigenous patients, were disproportionately represented in Australian ICUs, particularly for sepsis. The high level of acute illness and high proportion of emergency admissions could be interpreted as representing delayed presentation, which, with a higher re-admission rate, suggest access barriers to health care may exist. Nevertheless, there was no mortality gap between Indigenous and non-Indigenous Australians during a hospital admission for critical illness.

ObjectiveTo assess the performance of cardiovascular disease (CVD) risk equations in Indigenous Australians.MethodsWe conducted an individual participant meta-analysis using longitudinal data of 3618 Indigenous Australians (55% women) aged 30–74 years without CVD from population-based cohorts of the Cardiovascular Risk in IndigenouS People(CRISP) consortium. Predicted risk was calculated using: 1991 and 2008 Framingham Heart Study (FHS), the Pooled Cohorts (PC), GloboRisk and the Central Australian Rural Practitioners Association (CARPA) modification of the FHS equation. Calibration, discrimination and diagnostic accuracy were evaluated. Risks were calculated with and without the use of clinical criteria to identify high-risk individuals.ResultsWhen applied without clinical criteria, all equations, except the CARPA-adjusted FHS, underestimated CVD risk (range of percentage difference between observed and predicted CVD risks: −55% to −14%), with underestimation greater in women (−63% to −13%) than men (−47% to −18%) and in younger age groups. Discrimination ranged from 0.66 to 0.72. The CARPA-adjusted FHS equation showed good calibration but overestimated risk in younger people, those without diabetes and those not at high clinical risk. When clinical criteria were used with risk equations, the CARPA-adjusted FHS algorithm scored 64% of those who had CVD events as high risk; corresponding figures for the 1991-FHS were 58% and were 87% for the PC equation for non-Hispanic whites. However, specificity fell.ConclusionThe CARPA-adjusted FHS CVD risk equation and clinical criteria performed the best, achieving higher combined sensitivity and specificity than other equations. However, future research should investigate whether modifications to this algorithm combination might lead to improved risk prediction.

Transition into inpatient care represents a moment of increased metabolic vulnerability for patients with diabetes. There is scant information on diabetes therapeutic inertia during patient acute care transition. We examined the prevalence of therapeutic inertia among internal medicine (IM) residents admitting adults with diabetes on insulin to the hospital, and hypothesized that lack of change in insulin prescribing behavior was associated with decreased knowledge and perceived self-efficacy and that it could be modified by a provider-based multimodal diabetes education intervention (PB-DM-EDI). Methods: IM inpatient residents were surveyed on perceived self-efficacy and evaluated on insulin therapy knowledge. A PB-DM-EDI including group sessions and on-site one-to-one patient-based teaching addressing knowledge, skills and electronic diabetes order sets and tools (DMOST) use was implemented over 4-months. Insulin regimens were reviewed during a 3-month period prior to and after PB-DM-EDI to screen for therapeutic inertia on admission, defined by the lack of change of pre-admission insulin orders. Results: We analyzed 51 surveys and 325 patient insulin regimens; 28 surveys and 148 patients prior to PB-DM-EDI and 23 surveys and 177 patients post PB-DM-EDI. Therapeutic inertia was identified in 49.3% and 35.6% of patients before and after PB-DM-EDI, respectively. Surveys revealed low self-efficacy and knowledge relating to insulin therapy; frequent DMOST use was only reported by 50% of residents. PB-DM-EDI increased perceived self-efficacy by 20%, basic knowledge by 5-18%; and self-reported frequent use of DMOST by 15%. Conclusion: Therapeutic inertia is high among providers caring for patients with diabetes transitioning to the acute care setting and is associated with decreased knowledge and self-efficacy with insulin management. Education interventions that incorporate EMR DMOST may decrease therapeutic inertia, but need to be combined with other strategies to increase their effectiveness. Disclosure A. Brown: None. L. Belalcazar: None.

Diabetes is a major burden on Australia’s Indigenous population, with high rates of disease and vascular complications. Diabetic vascular complications are associated with impaired ischemia-driven angiogenesis. MicroRNAs (miRNAs) are known to regulate angiogenesis. We have recently identified a novel anti-angiogenic role for miR-181c. High-density lipoproteins (HDL) are associated with reduced rates of diabetic complications and serve as carriers of miRNAs in the circulation. HDL miRNA profiles differ in disease states. We sought to determine if circulating miR-181c levels reflect the severity of diabetic complications in Australian Aboriginal people. HDL was isolated from plasma samples of Australian Aboriginal participants with or without diabetes and associated complications living in regional South Australia; and a cohort of non-Indigenous participants without diabetes. We found that HDL miR-181c levels were strikingly elevated in the group of Aboriginal people with diabetic complications. However, plasma miR-181c levels were overall lower in Australian Aboriginal participants compared to the non-Indigenous group. Angiogenic capacity of isolated HDL was assessed in vitro using the Matrigel tubulogenesis assay. Under high glucose (25 mM) conditions, cells treated with HDL from the group of Aboriginal people with diabetic complications had a reduced capacity to form tubules and had lower mRNA levels of the hypoxia angiogenic transcription factor HIF-1α compared to all other groups. This attenuation of pro-angiogenic capacity may be attributed to the concurrent increase in cellular miR-181c levels. In conclusion, HDL from Aboriginal people with diabetic complications had reduced angiogenic capacity, highlighting its impaired function in the diabetic state and is potentially linked to the increased levels of the anti-angiogenic miRNA miR-181c. HDL miR-181c may be a novel biomarker for the extent of diabetic complications in Australian Aboriginal people. Disclosure K.R. Morrison: None. C. Bursill: None. E. Solly: None. T. Shemesh: None. S. Nicholls: Consultant; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Cerenis, CSL Behring, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Omthera, Pfizer Inc., Resverlogix Corp., Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; Amgen Inc., AstraZeneca, Athernova, Cerenis, Eli Lilly and Company, InfraReDx, Novartis Pharmaceuticals Corporation, Resverlogix Corp., Sanofi. A.D. Brown: None. J.T.M. Tan: None.

The nuclear quadrupole moment of aluminum (27Al) has been re-evaluated by determining the electric field gradients at this nucleus for AlF and AlCl using the coupled cluster method with single, double, and perturbative triple excitations [CCSD(T)]/aug-cc-pwCVXZ (X = T and Q) accounting for both vibrational averaging and core-core/core-valence electron correlation and then comparing to the experimentally measured nuclear quadrupole coupling constants (NQCCs). The new recommended value is Q(27Al) = 148.2 ± 0.5 mb, which can be compared to the previous value of 146.6 ± 1 mb. Using the new value of the nuclear quadrupole moment, the accuracy is assessed for several computational approaches [i.e., Hartree-Fock, Moller-Plesset perturbation theory to the second order, quadratic configuration interaction with single and double excitations, CCSD, CCSD(T), and density functional theory (DFT) with the B3LYP, PBE0, and M06-2X functionals] and basis sets (the aug-cc-pVXZ and aug-cc-pwCVXZ families) for determining the nuclear quadruple coupling constants for AlCN, AlNC, AlSH, AlOH, and AlCCH, where experimental measurements are available. From the results at equilibrium geometries of the polyatomic molecules, it has been determined that (i) the CCSD(T)/aug-cc-pwCVXZ approach is needed to obtain results within 4% of the experimental measurements, (ii) typical DFT values are only within 10%-15% of the experimental measurements, and (iii) the aug-cc-pVXZ family of basis sets is not recommended for computing the electric field gradients at aluminum. The present results also suggest that the NQCC for AlOH should be remeasured. Using the recommended CCSD(T)/aug-cc-pwCVXZ approach, the equilibrium geometries and corresponding NQCCs for AlCH3 and AlCCCN were determined, and the NQCCs are in excellent agreement with previously reported experimental values.

In fact, as early as 1875, Cayley had begun to notice the concept of chemical space and made many attempts to describe the chemical space. With the development of science and technology and the vigorous development of drug research in recent decades, many domestic and foreign scientists have done very important work in expanding chemical space and increasing the diversity of drug molecules. Martin D. Burke and other researchers are advocates of “Diversity-Oriented Synthesis”, which is clearly stated in the article “A Planning Strategy for Diversity-Oriented Synthesis”, and the method of diversity-directed synthesis can be elaborated to more deeply expand the drug-like molecules more efficiently. Covering more chemical space will bring more possibilities for drug-forming molecules. However, how to rapidly synthesize more types of small molecule compounds and screen for drug activity will become a greater challenge. Then DNA coding compound library comes to rescue, which can help solve the above problems well. In 1992, Brenner, S. and Lerner, R. A., two scientists propose the concept of DNA coded library for the first time in the “Encoded combinatorial chemistry”, as well as other elements like the theoretical basis and experimental methods from the establishment of DNA coded library to the final compound screening.