Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: A systematic analysis for the Global Burden of Disease Study 2010

BACKGROUND Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. METHODS We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights. FINDINGS Global DALYs remained stable from 1990 (2·503 billion) to 2010 (2·490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. INTERPRETATION Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results.

The effect of using different regions of interest on local and mean skin temperature

The dynamic nature of tissue temperature and the subcutaneous properties, such as blood flow, fatness, and metabolic rate, leads to variation in local skin temperature. Therefore, we investigated the effects of using multiple regions of interest when calculating weighted mean skin temperature from four local sites. Twenty-six healthy males completed a single trial in a thermonetural laboratory (mean ± SD): 24.0 (1.2) °C; 56 (8%) relative humidity; < 0.1 m/s air speed). Mean skin temperature was calculated from four local sites (neck, scapula, hand and shin) in accordance with International Standards using digital infrared thermography. A 50 x 50 mm square, defined by strips of aluminium tape, created six unique regions of interest, top left quadrant, top right quadrant, bottom left quadrant, bottom right quadrant, centre quadrant and the entire region of interest, at each of the local sites. The largest potential error in weighted mean skin temperature was calculated using a combination of a) the coolest and b) the warmest regions of interest at each of the local sites. Significant differences between the six regions interest were observed at the neck (P < 0.01), scapula (P < 0.001) and shin (P < 0.05); but not at the hand (P = 0.482). The largest difference (± SEM) at each site was as follows: neck 0.2 (0.1) °C; scapula 0.2 (0.0) °C; shin 0.1 (0.0) °C and hand 0.1 (0.1) °C. The largest potential error (mean ± SD) in weighted mean skin temperature was 0.4 (0.1) °C (P < 0.001) and the associated 95% limits of agreement for these differences was 0.2 to 0.5 °C. Although we observed differences in local and mean skin temperature based on the region of interest employed, these differences were minimal and are not considered physiologically meaningful.

Child and youth sport in rurally remote regions of Australia: the views of a north Queensland community

This study addresses the under-researched area of community sport in rurally isolated contexts. Data were gathered using semi-structured interviews with teachers, children, parents, and local community members from a small township in an isolated North Queensland region. The data indicate that community sport for young people is circumstantially difficult in some regional centres, but is none-the-less viewed differently by different sectors of the community. There is much value ascribed to sport as part of the social and cultural capital of the area however, it appears that community opinion is divided on the quality of sport experiences available with the young people of the community being particularly critical of the facilities, equipment, and the level of service from sports organisations in larger towns and cities.

Airborne viable fungi in school environments in different climatic regions – A review

Elevated levels of fungi in indoor environments have been linked with mould/moisture damage in building structures. However, there is a lack of information about “normal” concentrations and flora as well as guidelines of viable fungi in the school environment in different climatic conditions. We have reviewed existing guidelines for indoor fungi and the current knowledge of the concentrations and flora of viable fungi in different climatic areas, the impact of the local factors on concentrations and flora of viable fungi in school environments. Meta-regression was performed to estimate the average behaviour for each analysis of interest, showing wide variation in the mean concentrations in outdoor and indoor school environments (range: 101-103 cfu/m3). These concentrations were significantly higher for both outdoors and indoors in the moderate than in the continental climatic area, showing that the climatic condition was a determinant for the concentrations of airborne viable fungi. The most common fungal species both in the moderate and continental area were Cladosporium spp. and Penicillium spp. The suggested few quantitative guidelines for indoor air viable fungi for school buildings are much lower than for residential areas. This review provides a synthesis, which can be used to guide the interpretation of the fungi measurements results and help to find indications of mould/moisture in school building structures.

Emerging water treatment technologies for decentralised systems : an overview of selected systems suited for application in towns and settlements in remote and very remote regions of Australia and vulnerable and lagging rural regions in Sri Lanka

The primary purpose of this paper is to overview a selection of advanced water treatment technology systems that are suited for application in towns and settlements in remote and very remote regions of Australia and vulnerable and lagging rural regions in Sri Lanka. This recognises that sanitation and water treatment are inextricably linked and both are needed to reduce risks to environment and population health from contaminated water sources. For both Australia and Sri Lanka only a small fraction of the settlements in rural and remote regions are connected to water treatment facilities and town water supplies. In Australia’s remote/very remote regions raw water is drawn from underground sources and rainwater capture. Most settlements in rural Sri Lanka rely on rivers, reservoirs, wells, springs or carted water. Furthermore, Sri Lanka has more than 25,000 hand pumped tube wells which saved the communities during recent droughts. Decentralised water supply systems offer the opportunity to provide safe drinking water to these remote/very remote and rural regions where centralised systems are not feasible due to socio-cultural, economic, political, technological reasons. These systems reduce health risks from contaminated water supplies. In remote areas centralized systems fail due to low population density and less affordability. Globally, a new generation of advanced water treatment technologies are positioned to make a major impact on the provision of safe potable water in remote/very remote regions in Australia and rural regions in Sri Lanka. Some of these systems were developed for higher income countries. However, with careful selection and further research they can be tailored to match local socio-economic conditions and technical capacity. As such, they can equally be used to provide decentralised water supply in communities in developed and developing countries such as Australia and Sri Lanka.

A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: A systematic analysis for the Global Burden of Disease Study 2010

BACKGROUND Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. METHODS We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. FINDINGS In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2-7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5-7·0]), and alcohol use (5·5% [5·0-5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8-9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6-8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4-6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2-10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0·9% (0·4-1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. INTERPRETATION Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children.

Can social resilience inform SA/SIA for adaptive planning for climate change in vulnerable regions?

This book represents a landmark effort to probe and analyze the theory and empirics of designing water disaster management policies. It consists of seven chapters that examine, in-depth and comprehensively, issues that are central to crafting effective policies for water disaster management. The authors use historical surveys, institutional analysis, econometric investigations, empirical case studies, and conceptual-theoretical discussions to clarify and illuminate the complex policy process. The specific topics studied in this book include a review and analysis of key policy areas and research priority areas associated with water disaster management, community participation in disaster risk reduction, the economics and politics of ‘green’ flood control, probabilistic flood forecasting for flood risk management, polycentric governance and flood risk management, drought management with the aid of dynamic inter-generational preferences, and how social resilience can inform SA/SIA for adaptive planning for climate change in vulnerable areas. A unique feature of this book is its analysis of the causes and consequences of water disasters and efforts to address them successfully through policy-rich, cross-disciplinary and transnational papers. This book is designed to help enrich the sparse discourse on water disaster management policies and galvanize water professionals to craft creative solutions to tackle water disasters efficiently, equitably, and sustainably. This book should also be of considerable use to disaster management professionals, in general, and natural resource policy analysts.

BRCA1 deficiency exacerbates estrogen-induced DNA damage and genomic instability

Germline mutations in BRCA1 predispose carriers to a high incidence of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through critical roles in DNA repair, cell cycle arrest and transcriptional control. A major question has been why BRCA1 loss or mutation leads to tumors mainly in estrogen-regulated tissues, given that BRCA1 has essential functions in all cell types. Here we report that estrogen and estrogen metabolites can cause DNA double strand breaks (DSB) in estrogen receptor-α negative breast cells and that BRCA1 is required to repair these DSBs to prevent metabolite-induced genomic instability. We found that BRCA1 also regulates estrogen metabolism and metabolite-mediated DNA damage by repressing the transcription of estrogen-metabolising enzymes, such as CYP1A1, in breast cells. Lastly, we used a knock-in human cell model with a heterozygous BRCA1 pathogenic mutation to show how BRCA1 haploinsufficiency affects these processes. Our findings provide pivotal new insights into why BRCA1 mutation drives the formation of tumours in estrogen-regulated tissues, despite the general role of BRCA1 in DNA repair in all cell types.

Identification of a BRCA1-mRNA splicing complex required for efficient DNA repair and maintenance of genomic stability

Mutations within BRCA1 predispose carriers to a high risk of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through the assembly of multiple protein complexes involved in DNA repair, cell-cycle arrest, and transcriptional regulation. Here, we report the identification of a DNA damage-induced BRCA1 protein complex containing BCLAF1 and other key components of the mRNA-splicing machinery. In response to DNA damage, this complex regulates pre-mRNA splicing of a number of genes involved in DNA damage signaling and repair, thereby promoting the stability of these transcripts/proteins. Further, we show that abrogation of this complex results in sensitivity to DNA damage, defective DNA repair, and genomic instability. Interestingly, mutations in a number of proteins found within this complex have been identified in numerous cancer types. These data suggest that regulation of splicing by the BRCA1-mRNA splicing complex plays an important role in the cellular response to DNA damage.

Someone else's boom but always our bust: Australia as a derivative economy, implications for regions

This paper examines the socio-economic impact of mineral and agricultural resource extraction on local communities and explores policy options for addressing them. An emphasis on the marketisation of services together with tight fiscal control has reinforced decline in many country communities in Australia and elsewhere. However, the introduction by the European Union of Regional Policy which emphasises ‘smart specialisation’ can enhance greatly the capacity of local people to generate decent livelihoods. For this to have real effect, the innovative state has to enable partnerships between communities, researchers and industry. For countries like Australia, this would be a substantive policy shift.

Cerebral regions associated with verbal response initiation, suppression and strategy use

Cerebral activation associated with performance on a novel task involving two conditions was investigated with functional magnetic resonance imaging (fMRI). In the response initiation condition, subjects nominated the general superordinate category to which each of a series of exemplars (concrete nouns) belonged. In the response suppression condition, subjects were required to nominate a general superordinate category to which each exemplar did not belong, with the instruction that they were not to nominate the same category response twice in a row. Both conditions produced distinct patterns of activation relative to an articulation control condition employing identical stimuli. When initiation and suppression conditions were directly compared, response suppression produced activation in the right frontal pole, orbital frontal cortex and anterior cingulate, left dorsolateral prefrontal cortex and posterior cingulate, and bilaterally in the precuneus, visual association cortex and cerebellum. Response latencies were significantly longer in the suppression condition. Two broadly-defined strategies associated with the correct production of words during the suppression condition were a self-ordered selection from among the superordinate categories identified during the first section of the task and the generation of novel category responses. The neuroanatomical correlates of response initiation, suppression and strategy use are discussed, as are the respective roles of response suppression and strategy generation.

Genetic architecture of subcortical brain regions: Common and region-specific genetic contributions

Understanding the aetiology of patterns of variation within and covariation across brain regions is key to advancing our understanding of the functional, anatomical and developmental networks of the brain. Here we applied multivariate twin modelling and principal component analysis (PCA) to investigate the genetic architecture of the size of seven subcortical regions (caudate nucleus, thalamus, putamen, pallidum, hippocampus, amygdala and nucleus accumbens) in a genetically informative sample of adolescents and young adults (N=1038; mean age=21.6±3.2years; including 148 monozygotic and 202 dizygotic twin pairs) from the Queensland Twin IMaging (QTIM) study. Our multivariate twin modelling identified a common genetic factor that accounts for all the heritability of intracranial volume (0.88) and a substantial proportion of the heritability of all subcortical structures, particularly those of the thalamus (0.71 out of 0.88), pallidum (0.52 out of 0.75) and putamen (0.43 out of 0.89). In addition, we also found substantial region-specific genetic contributions to the heritability of the hippocampus (0.39 out of 0.79), caudate nucleus (0.46 out of 0.78), amygdala (0.25 out of 0.45) and nucleus accumbens (0.28 out of 0.52). This provides further insight into the extent and organization of subcortical genetic architecture, which includes developmental and general growth pathways, as well as the functional specialization and maturation trajectories that influence each subcortical region. This multivariate twin study identifies a common genetic factor that accounts for all the heritability of intracranial volume (0.88) and a substantial proportion of the heritability of all subcortical structures, particularly those of the thalamus (0.71 out of 0.88), pallidum (0.52 out of 0.75) and putamen (0.43 out of 0.89). In parallel, it also describes substantial region-specific genetic contributions to the heritability of the hippocampus (0.39 out of 0.79), caudate nucleus (0.46 out of 0.78), amygdala (0.25 out of 0.45) and nucleus accumbens (0.28 out of 0.52).

A candidate gene association study for growth performance in an improved Giant Freshwater Prawn (Macrobrachium rosenbergii) culture line

A candidate gene approach using type I single nucleotide polymorphism (SNP) markers can provide an effective method for detecting genes and gene regions that underlie phenotypic variation in adaptively significant traits. In the absence of available genomic data resources, transcriptomes were recently generated in Macrobrachium rosenbergii to identify candidate genes and markers potentially associated with growth. The characterisation of 47 candidate loci by ABI re-sequencing of four cultured and eight wild samples revealed 342 putative SNPs. Among these, 28 SNPs were selected in 23 growth-related candidate genes to genotype in 200 animals selected for improved growth performance in an experimental GFP culture line in Vietnam. The associations between SNP markers and individual growth performance were then examined. For additive and dominant effects, a total of three exonic SNPs in glycogen phosphorylase (additive), heat shock protein 90 (additive and dominant) and peroxidasin (additive), and a total of six intronic SNPs in ankyrin repeats-like protein (additive and dominant), rolling pebbles (dominant), transforming growth factor-β induced precursor (dominant), and UTP-glucose-1-phosphate uridylyltransferase 2 (dominant) genes showed significant associations with the estimated breeding values in the experimental animals (P =0.001−0.031). Individually, they explained 2.6−4.8 % of the genetic variance (R2=0.026−0.048). This is the first large set of SNP markers reported for M. rosenbergii and will be useful for confirmation of associations in other samples or culture lines as well as having applications in marker-assisted selection in future breeding programs.

Characterization of novel microsatellite markers derived from Korean rose bitterling (Rhodeus uyekii) genomic library

Korean rose bitterling (Rhodeus uyekii) is a freshwater fish endemic to Korea. Natural populations of this species have experienced severe declines as a result of habitat fragmentation and water pollution. To conserve and restore R. uyekii, the genetic diversity of this species needs to be assessed at the population level. Eighteen novel polymorphic microsatellite loci for R. uyekii were developed using an enriched partial genomic library. Polymorphisms at these loci were studied in 150 individuals collected from three populations. The number of alleles at each locus ranged from 3 to 47 (mean = 17.1). Within the populations, the observed heterozygosity ranged from 0.032 to 1.000, expected heterozygosity from 0.082 to 0.967, and polymorphism information content from 0.078 to 0.950. Six loci showed significant deviation from Hardy-Weinberg equilibrium after Bonferroni’s correction, and no significant linkage disequilibrium was detected between most locus pairs, except in three cases. These highly informative microsatellite markers should be useful for genetic population structure analyses of R. uyekii.

Optimizing de novo transcriptome assembly and extending genomic resources for striped catfish (Pangasianodon hypophthalmus)

Striped catfish (Pangasianodon hypophthalmus) is a commercially important freshwater fish used in inland aquaculture in the Mekong Delta, Vietnam. The culture industry is facing a significant challenge however from saltwater intrusion into many low topographical coastal provinces across the Mekong Delta as a result of predicted climate change impacts. Developing genomic resources for this species can facilitate the production of improved culture lines that can withstand raised salinity conditions, and so we have applied high-throughput Ion Torrent sequencing of transcriptome libraries from six target osmoregulatory organs from striped catfish as a genomic resource for use in future selection strategies. We obtained 12,177,770 reads after trimming and processing with an average length of 97 bp. De novo assemblies were generated using CLC Genomic Workbench, Trinity and Velvet/Oases with the best overall contig performance resulting from the CLC assembly. De novo assembly using CLC yielded 66,451 contigs with an average length of 478 bp and N50 length of 506 bp. A total of 37,969 contigs (57%) possessed significant similarity with proteins in the non-redundant database. Comparative analyses revealed that a significant number of contigs matched sequences reported in other teleost fishes, ranging in similarity from 45.2% with Atlantic cod to 52% with zebrafish. In addition, 28,879 simple sequence repeats (SSRs) and 55,721 single nucleotide polymorphisms (SNPs) were detected in the striped catfish transcriptome. The sequence collection generated in the current study represents the most comprehensive genomic resource for P. hypophthalmus available to date. Our results illustrate the utility of next-generation sequencing as an efficient tool for constructing a large genomic database for marker development in non-model species.