A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer

Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.

Changes in mood, depression and suicidal ideation after commencing pregabalin for neuropathic pain

Background Pregabalin is a treatment option for patients with persistent neuropathic pain. Its use has been associated with changes in mood and the development of depression and/or suicidal ideation. Objective Case presentations were reviewed of five patients reporting changes in mood, depression and suicidal ideation from the first 50 (approximately) patients commenced on pregabalin at the clinic. Discussion Although these patients had a history of depression, their mood had been stable before commencing pregabalin. Soon after commencement they reported changes in mood, and development of depression and/or suicidal ideation, which improved with dose reduction or cessation of pregabalin. Ultimately, all five patients ceased pregabalin treatment. Suicidal ideation is a recog-nised adverse effect of pregabalin. Patients should be warned of and monitored for deterioration in mood.

Guidelines for syringe driver management in palliative care

These guidelines are intended to provide clinicians and palliative care services with guidelines to inform practice, the development of policy and procedures, and associated training and education programs in relation to portable subcutaneous infusion device (syringe driver) management.

Developing guidelines for syringe driver management

The aim of this project was to develop clinical practice guidelines for the use and administration of pharmacological agents for symptom control via syringe drivers within Australia. By developing evidence-based clinical practice guidelines for the use of this common device, this project aimed to improve patient outcomes, reduce practice variation, minimize errors and encourage more efficient use of resources. A literature review identified current literature regarding syringe driver management and an expert panel was assembled to assist in the development of the guidelines. The development of these practice guidelines provides an example of how palliative care practitioners can use a framework of contemporary evidence to enhance clinical practice.

Community uses of co-creative media. Digital storytelling and Co-creative Media : The role of community arts and media in propagating and coordinating population-wide creative practice

This report describes a dynamic ‘Co-creative Media System’ that is emerging in the social space bounded by the following institutional pillars: • major cultural institutions (including screen culture agencies, libraries, museums, galleries and public service broadcasters) • the Community Arts and Cultural Development sector (historically supported through various programs of the Australia Council for the Arts) • the community broadcasting sector • the Indigenous media sector, and • the higher education sector. It illustrates how this system activates the immense creative potential of the Australian population through the ongoing development and application of participatory storytelling methods and media.

Application of fragment-based screening to the design of inhibitors of Escherichia coli DsbA

The thiol-disulfide oxidoreductase enzyme DsbA catalyzes the formation of disulfide bonds in the periplasm of Gram-negative bacteria. DsbA substrates include proteins involved in bacterial virulence. In the absence of DsbA, many of these proteins do not fold correctly, which renders the bacteria avirulent. Thus DsbA is a critical mediator of virulence and inhibitors may act as antivirulence agents. Biophysical screening has been employed to identify fragments that bind to DsbA from Escherichia coli. Elaboration of one of these fragments produced compounds that inhibit DsbA activity in vitro. In cell-based assays, the compounds inhibit bacterial motility, but have no effect on growth in liquid culture, which is consistent with selective inhibition of DsbA. Crystal structures of inhibitors bound to DsbA indicate that they bind adjacent to the active site. Together, the data suggest that DsbA may be amenable to the development of novel antibacterial compounds that act by inhibiting bacterial virulence.

Large variations in the Holocene marine radiocarbon reservoir effect reflect ocean circulation and climatic changes

Accurate radiocarbon dating of marine samples requires knowledge of the marine radiocarbon reservoir effect. This effect for a particular site/region is generally assumed constant through time when calibrating marine 14C ages. However, recent studies have shown large temporal variations of several hundred to a couple of thousand years in this effect for a number of regions during the late Quaternary and Holocene. Here we report marine radiocarbon reservoir correction (ΔRΔR) for Heron Reef and Moreton Bay in southwestern (SW) Pacific for the last 8 ka derived from 14C analysis of 230Th-dated corals. Most of our ΔRΔR for the last ∼5.4 ka agree well with their modern value, but large ΔRΔR variability of ∼410 yr (from trough to peak) with possible decadal/centennial fluctuations is evident for the period ∼5.4–8 ka. The latter time interval also has significant variations with similar features in previously published ΔRΔR values for other sites in the Pacific, including southern Peru–northern Chile in southeastern (SE) Pacific, the South China Sea, Vanuatu and Papua New Guinea, with the largest magnitude of ∼920 yr from SE Pacific. The mechanisms for these large ΔRΔR variations across the Pacific during the mid-Holocene are complex processes involving (1) changes in the quantity and 14C content of upwelled waters in tropical east Pacific (TEP) (frequency and intensity of ocean upwelling in the TEP, and contribution of Subantarctic Mode Water to the upwelled waters, which is influenced by the intensity and position of southern westerly winds), and (2) variations in ocean circulation associated with climate change (La Niña/El Niño conditions, intensity of easterly trade winds, positions of the Intertropical Convergence Zone and the South Pacific Convergence Zone), which control the spreading of the older upwelled surface waters in the TEP to the western sites. Our results imply the need for employing temporal changes in ΔRΔR values, instead of constant (modern) values, for age calibration of Holocene marine samples not only for the SW Pacific sites but also for other tropical and subtropical sites in the Pacific.

The Macroecology of Airborne Pollen in Australian and New Zealand Urban Areas

he composition and relative abundance of airborne pollen in urban areas of Australia and New Zealand are strongly influenced by geographical location, climate and land use. There is mounting evidence that the diversity and quality of airborne pollen is substantially modified by climate change and land-use yet there are insufficient data to project the future nature of these changes. Our study highlights the need for long-term aerobiological monitoring in Australian and New Zealand urban areas in a systematic, standardised, and sustained way, and provides a framework for targeting the most clinically significant taxa in terms of abundance, allergenic effects and public health burden.

Regional and seasonal variation in airborne grass pollen levels between cities of Australia and New Zealand

Although grass pollen is widely regarded as the major outdoor aeroallergen source in Australia and New Zealand (NZ), no assemblage of airborne pollen data for the region has been previously compiled. Grass pollen count data collected at 14 urban sites in Australia and NZ over periods ranging from 1 to 17 years were acquired, assembled and compared, revealing considerable spatiotemporal variability. Although direct comparison between these data is problematic due to methodological differences between monitoring sites, the following patterns are apparent. Grass pollen seasons tended to have more than one peak from tropics to latitudes of 37°S and single peaks at sites south of this latitude. A longer grass pollen season was therefore found at sites below 37°S, driven by later seasonal end dates for grass growth and flowering. Daily pollen counts increased with latitude; subtropical regions had seasons of both high intensity and long duration. At higher latitude sites, the single springtime grass pollen peak is potentially due to a cooler growing season and a predominance of pollen from C3 grasses. The multiple peaks at lower latitude sites may be due to a warmer season and the predominance of pollen from C4 grasses. Prevalence and duration of seasonal allergies may reflect the differing pollen seasons across Australia and NZ. It must be emphasized that these findings are tentative due to limitations in the available data, reinforcing the need to implement standardized pollen-monitoring methods across Australasia. Furthermore, spatiotemporal differences in grass pollen counts indicate that local, current, standardized pollen monitoring would assist with the management of pollen allergen exposure for patients at risk of allergic rhinitis and asthma. © 2015 Springer Science+Business Media Dordrecht

Total transcriptome, proteome, and allergome of Johnson grass pollen, which is important for allergic rhinitis in subtropical regions

Background Genomic data are lacking for many allergen sources. To circumvent this limitation, we implemented a strategy to reveal the repertoire of pollen allergens of a grass with clinical importance in subtropical regions, where an increasing proportion of the world's population resides. Objective We sought to identify and immunologically characterize the allergenic components of the Panicoideae Johnson grass pollen (JGP; Sorghum halepense). Methods The total pollen transcriptome, proteome, and allergome of JGP were documented. Serum IgE reactivities with pollen and purified allergens were assessed in 64 patients with grass pollen allergy from a subtropical region. Results Purified Sor h 1 and Sor h 13 were identified as clinically important allergen components of JGP with serum IgE reactivity in 49 (76%) and 28 (43.8%), respectively, of patients with grass pollen allergy. Within whole JGP, multiple cDNA transcripts and peptide spectra belonging to grass pollen allergen families 1, 2, 4, 7, 11, 12, 13, and 25 were identified. Pollen allergens restricted to subtropical grasses (groups 22-24) were also present within the JGP transcriptome and proteome. Mass spectrometry confirmed the IgE-reactive components of JGP included isoforms of Sor h 1, Sor h 2, Sor h 13, and Sor h 23. Conclusion Our integrated molecular approach revealed qualitative differences between the allergenic components of JGP and temperate grass pollens. Knowledge of these newly identified allergens has the potential to improve specific diagnosis and allergen immunotherapy treatment for patients with grass pollen allergy in subtropical regions and reduce the burden of allergic respiratory disease globally.

Differences in grass pollen allergen exposure across Australia

Objective Allergic rhinitis and allergic asthma are important chronic diseases posing serious public health issues in Australia with associated medical, economic, and societal burdens. Pollen are significant sources of clinically relevant outdoor aeroallergens, recognised as both a major trigger for, and cause of, allergic respiratory diseases. This study aimed to provide a national, and indeed international, perspective on the state of Australian pollen data using a large representative sample. Methods Atmospheric grass pollen concentration is examined over a number of years within the period 1995 to 2013 for Brisbane, Canberra, Darwin, Hobart, Melbourne, and Sydney, including determination of the clinical' grass pollen season and grass pollen peak. Results The results of this study describe, for the first time, a striking spatial and temporal variability in grass pollen seasons in Australia, with important implications for clinicians and public health professionals, and the Australian grass pollen-allergic community. Conclusions These results demonstrate that static pollen calendars are of limited utility and in some cases misleading. This study also highlights significant deficiencies and limitations in the existing Australian pollen monitoring and data. Implications: Establishment of an Australian national pollen monitoring network would help facilitate advances in the clinical and public health management of the millions of Australians with asthma and allergic rhinitis.

Facing the wave of change: Stakeholder perspectives on climate adaptation for Australian seafood supply chains

Climate change is one of the most important issues confronting the sustainable supply of seafood, with projections suggesting major effects on wild and farmed fisheries worldwide. While climate change has been a consideration for Australian fisheries and aquaculture management, emphasis in both research and adaptation effort has been at the production end of supply chains—impacts further along the chain have been overlooked to date. A holistic biophysical and socio-economic system view of seafood industries, as represented by end-to-end supply chains, may lead to an additional set of options in the face of climate change, thus maximizing opportunities for improved fishery profitability, while also reducing the potential for maladaptation. In this paper, we explore Australian seafood industry stakeholder perspectives on potential options for adaptation along seafood supply chains based on future potential scenarios. Stakeholders, representing wild capture and aquaculture industries, provided a range of actions targeting different stages of the supply chain. Overall, proposed strategies were predominantly related to the production end of the supply chain, suggesting that greater attention in developing adaptation options is needed at post-production stages. However, there are chain-wide adaptation strategies that can present win–win scenarios, where commercial objectives beyond adaptation can also be addressed alongside direct or indirect impacts of climate. Likewise, certain adaptation strategies in place at one stage of the chain may have varying implications on other stages of the chain. These findings represent an important step in understanding the role of supply chains in effective adaptation of fisheries and aquaculture industries to climate change.

A quantitative metric to identify critical elements within seafood supply networks

A theoretical basis is required for comparing key features and critical elements in wild fisheries and aquaculture supply chains under a changing climate. Here we develop a new quantitative metric that is analogous to indices used to analyse food-webs and identify key species. The Supply Chain Index (SCI) identifies critical elements as those elements with large throughput rates, as well as greater connectivity. The sum of the scores for a supply chain provides a single metric that roughly captures both the resilience and connectedness of a supply chain. Standardised scores can facilitate cross-comparisons both under current conditions as well as under a changing climate. Identification of key elements along the supply chain may assist in informing adaptation strategies to reduce anticipated future risks posed by climate change. The SCI also provides information on the relative stability of different supply chains based on whether there is a fairly even spread in the individual scores of the top few key elements, compared with a more critical dependence on a few key individual supply chain elements. We use as a case study the Australian southern rock lobster Jasus edwardsii fishery, which is challenged by a number of climate change drivers such as impacts on recruitment and growth due to changes in large-scale and local oceanographic features. The SCI identifies airports, processors and Chinese consumers as the key elements in the lobster supply chain that merit attention to enhance stability and potentially enable growth. We also apply the index to an additional four real-world Australian commercial fishery and two aquaculture industry supply chains to highlight the utility of a systematic method for describing supply chains. Overall, our simple methodological approach to empirically-based supply chain research provides an objective method for comparing the resilience of supply chains and highlighting components that may be critical.

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.