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.

A qualitative study of the spouse's experience following coronary artery bypass surgery: Implications for Nursing Practice

Findings from numerous quantitative studies suggest that spouses of patients undergoing Coronary Artery Bypass (CAB) surgery experience both physical and emotional stress before and after their partner's surgery. Such studies have contributed to our understanding of the spouses' experiences, however they have largely failed to capture the qualitative experience of what it is like to be a spouse of a partner who has undergone CAB surgery. The objective of this study was to describe the experience of spouses of patients who had recently undergone CAB surgery. This study was guided by Husserl's phenomenological approach to qualitative research. In accordance with the nature of phenomenological research the number of participants necessarily needs to be small because phenomenology values the unique experience of individuals. Therefore this study gathered data from four participants utilising open ended indepth interviews. The method of analysis was adapted from Amedeo Giorgi's five step empirical phenomenological process which brackets preconceived notions, reducing participants' accounts to the essential essence or meanings. Numerous themes common to each of the spouses emerged. These included: seeking information; the necessity for rapid decision making; playing guardian; a desire to debrief with their partner and lastly, uncertainty of their future role. This study has attempted to understand the phenomena of the spouse's experience and in doing so, believe that we now have a better understanding and insight into the needs of spouses of CAB surgery patients. This has added another dimension to our existing body of knowledge and further facilitates holistic patient care.

The cross-talk of LDL-cholesterol with cell migration: Insights from the Niemann Pick Type C1 mutation

Cholesterol is considered indispensible for the recruitment and functioning of integrins in focal adhesions for cell migration. However, the physiological cholesterol pools that control integrin trafficking and focal adhesion assembly remain unclear. Using Niemann Pick Type C1 (NPC) mutant cells, which accumulate Low Density lipoprotein (LDL)-derived cholesterol in late endosomes (LE), several recent studies indicate that LDL-cholesterol has multiple roles in regulating focal adhesion dynamics. Firstly, targeting of endocytosed LDL-cholesterol from LE to focal adhesions controls their formation at the leading edge of migrating cells. Other newly emerging literature suggests that this may be coupled to vesicular transport of integrins, Src kinase and metalloproteases from the LE compartment to focal adhesions. Secondly, our recent work identified LDL-cholesterol as a key factor that determines the distribution and ability of several Soluble NSF Attachment Protein (SNAP) Receptor (SNARE) proteins, key players in vesicle transport, to control integrin trafficking to the cell surface and extracellular matrix (ECM) secretion. Collectively, dietary, genetic and pathological changes in cholesterol metabolism may link with efficiency and speed of integrin and ECM cell surface delivery in metastatic cancer cells. This commentary will summarize how direct and indirect pathways enable LDL-cholesterol to modulate cell motility.

Australia

Crisis management in the banking sector is a topical issue in Australia. This is not because financial institutions are facing a financial crisis. Indeed, in 2012, the International Monetary Fund (IMF) noted that ‘Australia has a history of few bank failures, even fewer financial crises, and its banking sector emerged from the global financial crisis relatively well.’ Rather, crisis management of banks is topical because there has been the first full review of Australia’s banking and financial system in nearly 20 years, which has examined and raised issues about the resilience and capacity of the Australian regime in this post GFC world. At the time of writing, the Report’s recommendations, including for Australian banks to meet capital standards in line with emerging international practice, are the subject of industry debate in advance of the Australian government’s decision.

Shared common variants in prostate cancer and blood lipids

Background Epidemiological and clinical studies suggest comorbidity between prostate cancer (PCA) and cardiovascular disease (CVD) risk factors. However, the relationship between these two phenotypes is still not well understood. Here we sought to identify shared genetic loci between PCA and CVD risk factors. Methods We applied a genetic epidemiology method based on conjunction false discovery rate (FDR) that combines summary statistics from different genome-wide association studies (GWAS), and allows identification of genetic overlap between two phenotypes. We evaluated summary statistics from large, multi-centre GWA studies of PCA (n = 50 000) and CVD risk factors (n = 200 000) [triglycerides (TG), low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, systolic blood pressure, body mass index, waist-hip ratio and type 2 diabetes (T2D)]. Enrichment of single nucleotide polymorphisms (SNPs) associated with PCA and CVD risk factors was assessed with conditional quantile-quantile plots and the Anderson-Darling test. Moreover, we pinpointed shared loci using conjunction FDR. Results We found the strongest enrichment of P-values in PCA was conditional on LDL and conditional on TG. In contrast, we found only weak enrichment conditional on HDL or conditional on the other traits investigated. Conjunction FDR identified altogether 17 loci; 10 loci were associated with PCA and LDL, 3 loci were associated with PCA and TG and additionally 4 loci were associated with PCA, LDL and TG jointly (conjunction FDR < 0.01). For T2D, we detected one locus adjacent to HNF1B. Conclusions We found polygenic overlap between PCA predisposition and blood lipids, in particular LDL and TG, and identified 17 pleiotropic gene loci between PCA and LDL, and PCA and TG, respectively. These findings provide novel pathobiological insights and may have implications for trials using targeting lipid-lowering agents in a prevention or cancer setting.

Introducing a new limit states design concept to railway concrete sleepers: An Australian experience

Over 50 years, a large number of research and development projects with respect to the use of cementitious and concrete materials for manufacturing railway sleepers have been significantly progressed in Australia, Europe, and Japan (Wang, 1996; Murray and Cai, 1998; Wakui and Okuda, 1999; Esveld, 2001; Freudenstein and Haban, 2006; Remennikov and Kaewunruen, 2008). Traditional sleeper materials are timber, steel, and concrete. Cost-efficiency, superior durability, and improved track stability are the main factors toward significant adoption of concrete materials for railway sleepers. The sleepers in a track system, as shown in Figure 1, are subjected to harsh and aggressive external forces and natural environments across a distance. Many systemic problems and technical issues associated with concrete sleepers have been tackled over decades. These include pre-mature failures of sleepers, concrete cancer or ettringite, abrasion of railseats and soffits, impact damages by rail machinery, bond-slip damage, longitudinal and lateral instability of track system, dimensional instability of sleepers, nuisance noise and vibration, and so on (Pfeil, 1997; Gustavson, 2002; Kaewunruen and Remennikov, 2008a,b, 2013). These issues are, however, becoming an emerging risk for many countries (in North and South Americas, Asia, and the Middle East) that have recently installed large volumes of concrete sleepers in their railway networks (Federal Railroad Administration, 2013). As a result, it is vital to researchers and practitioners to critically review and learn from previous experience and lessons around the world.

Rail fatigue and the role of impact forces

Fatigue of the steel in rails continues to be of major concern to heavy haul track owners despite careful selection and maintenance of rails. The persistence of fatigue is due in part to the erroneous assumption that the maximum loads on, and stresses in, the rails are predictable. Recent analysis of extensive wheel impact detector data from a number of heavy haul tracks has shown that the most damaging forces are in fact randomly distributed with time and location and can be much greater than generally expected. Large- scale Monte-Carlo simulations have been used to identify rail stresses caused by actual, measured distributions of wheel-rail forces on heavy haul tracks. The simulations show that fatigue failure of the rail foot can occur in situations which would be overlooked by traditional analyses. The most serious of these situations are those where track is accessed by multiple operators and in situations where there is a mix of heavy haul, general freight and/or passenger traffic. The least serious are those where the track is carrying single-operator-owned heavy haul unit trains. The paper shows how using the nominal maximum axle load of passing traffic, which is the key issue in traditional analyses, is insufficient and must be augmented with consideration of important operational factors. Ignoring such factors can be costly.

Heavy haul sleeper design: A rational cost-saving method

Heavy haul railway lines are important and expensive items of infrastructure operating in an environment which is increasingly focussed on risk-based management and constrained profit margins. It is vital that costs are minimised but also that infrastructure satisfies failure criteria and standards of reliability which account for the random nature of wheel-rail forces and of the properties of the materials in the track. In Australia and the USA, concrete railway sleepers/ties are still designed using methods which the rest of the civil engineering world discarded decades ago in favour of the more rational, more economical and probabilistically based, limit states design (LSD) concept. This paper describes a LSD method for concrete sleepers which is based on (a) billions of measurements over many years of the real, random wheel-rail forces on heavy haul lines, and (b) the true capacity of sleepers. The essential principles on which the new method is based are similar to current, widely used LSD-based standards for concrete structures. The paper proposes and describes four limit states which a sleeper must satisfy, namely: strength; operations; serviceability; and fatigue. The method has been applied commercially to two new major heavy haul lines in Australia, where it has saved clients millions of dollars in capital expenditure.

Inland Salt

This work, a small single room installation, was my contribution to the 2015 Palimpsest Biennale in Mildura, and was shown at the ADFA building in the town's centre. On an initial research trip in July, 2015, I stopped at a dried out salt lake near Wentworth. Beach-like, the lake left a tidal line along a curving shore. The vegetation looked like ocean flora; there was the glimmering saltiness of everything, and saltbush everywhere. It brought to mind Sturt's hankering for an inland sea, and his wishful voyage along the Murray, that led him out, not in. This work puts these observations together: a drawing, made from the sanded emboss of saltbush leaves, runs, riverlike, across the space. A looped film of clouds reflected in a shallow saltlake, recalls the dream of an inland sea, supported by the sound of ocean.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated approximately 2,000, approximately 3,700 and approximately 9,500 SNPs explained approximately 21%, approximately 24% and approximately 29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 x 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-kappaB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

The global burden of injury: Incidence, mortality, disability-adjusted life years and time trends from the Global Burden of Disease study 2013

Background The Global Burden of Diseases (GBD), Injuries, and Risk Factors study used the disability-adjusted life year (DALY) to quantify the burden of diseases, injuries, and risk factors. This paper provides an overview of injury estimates from the 2013 update of GBD, with detailed information on incidence, mortality, DALYs and rates of change from 1990 to 2013 for 26 causes of injury, globally, by region and by country. Methods Injury mortality was estimated using the extensive GBD mortality database, corrections for ill-defined cause of death and the cause of death ensemble modelling tool. Morbidity estimation was based on inpatient and outpatient data sets, 26 cause-of-injury and 47 nature-of-injury categories, and seven follow-up studies with patient-reported long-term outcome measures. Results In 2013, 973 million (uncertainty interval (UI) 942 to 993) people sustained injuries that warranted some type of healthcare and 4.8 million (UI 4.5 to 5.1) people died from injuries. Between 1990 and 2013 the global age-standardised injury DALY rate decreased by 31% (UI 26% to 35%). The rate of decline in DALY rates was significant for 22 cause-of-injury categories, including all the major injuries. Conclusions Injuries continue to be an important cause of morbidity and mortality in the developed and developing world. The decline in rates for almost all injuries is so prominent that it warrants a general statement that the world is becoming a safer place to live in. However, the patterns vary widely by cause, age, sex, region and time and there are still large improvements that need to be made.

A multi-centre open-label randomised non-inferiority trial comparing watchful waiting to antibiotic treatment for acute otitis media without perforation in low-risk urban Aboriginal and Torres Strait Islander children (the WATCH trial): study protocol for a randomised controlled trial

Background Treatment guidelines recommend watchful waiting for children older than 2 years with acute otitis media (AOM) without perforation, unless they are at high risk of complications. The high prevalence of chronic suppurative otitis media (CSOM) in remote Aboriginal and Torres Strait Islander communities leads these children to be classified as high risk. Urban Aboriginal and Torres Strait Islander children are at lower risk of complications, but evidence to support the subsequent recommendation for watchful waiting in this population is lacking. Methods/Design This non-inferiority multi-centre randomised controlled trial will determine whether watchful waiting is non-inferior to immediate antibiotics for urban Aboriginal and Torres Strait Islander children with AOM without perforation. Children aged 2 − 16 years with AOM who are considered at low risk for complications will be recruited from six participating urban primary health care services across Australia. We will obtain informed consent from each participant or their guardian. The primary outcome is clinical resolution on day 7 (no pain, no fever of at least 38 °C, no bulging eardrum and no complications of AOM such as perforation or mastoiditis) as assessed by general practitioners or nurse practitioners. Participants and outcome assessors will not be blinded to treatment. With a sample size of 198 children in each arm, we have 80 % power to detect a non-inferiority margin of up to 10 % at a significance level of 5 %, assuming clinical improvement of at least 80 % in both groups. Allowing for a 20 % dropout rate, we aim to recruit 495 children. We will analyse both by intention-to-treat and per protocol. We will assess the cost- effectiveness of watchful waiting compared to immediate antibiotic prescription. We will also report on the implementation of the trial from the perspectives of parents/carers, health professionals and researchers. Discussion The trial will provide evidence for the safety and effectiveness of watchful waiting for the management of AOM in Aboriginal and Torres Strait Islander children living in urban settings who are considered to be at low risk of complications.

Low-impact Use: A New Standard

Once the ugly duckling of the lighting world, the fluorescent bulb recently has become something of an eco-darling thanks to its energy efficiency. Whereas a standard off-the-shelf incandescent bulb devotes only about five percent of its total electrical consumption to produce visible light (the remainder is released in heat), fluorescent lighting employs an entirely different process (it radiates rather than burns) that is four to six times more efficient. Fluorescents are indisputably superior in ­performance, but up to 5 milligrams of mercury, a hazardous trace metal, is included in the manufacture of each lamp