Global burden of disease attributable to mental and substance use disorders : findings from the Global Burden of Disease Study 2010

Background We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the burden of disease attributable to mental and substance use disorders in terms of disability-adjusted life years (DALYs), years of life lost to premature mortality (YLLs), and years lived with disability (YLDs). Methods For each of the 20 mental and substance use disorders included in GBD 2010, we systematically reviewed epidemiological data and used a Bayesian meta-regression tool, DisMod-MR, to model prevalence by age, sex, country, region, and year. We obtained disability weights from representative community surveys and an internet-based survey to calculate YLDs. We calculated premature mortality as YLLs from cause of death estimates for 1980–2010 for 20 age groups, both sexes, and 187 countries. We derived DALYs from the sum of YLDs and YLLs. We adjusted burden estimates for comorbidity and present them with 95% uncertainty intervals. Findings In 2010, mental and substance use disorders accounted for 183·9 million DALYs (95% UI 153·5 million–216·7 million), or 7·4% (6·2–8·6) of all DALYs worldwide. Such disorders accounted for 8·6 million YLLs (6·5 million–12·1 million; 0·5% [0·4–0·7] of all YLLs) and 175·3 million YLDs (144·5 million–207·8 million; 22·9% [18·6–27·2] of all YLDs). Mental and substance use disorders were the leading cause of YLDs worldwide. Depressive disorders accounted for 40·5% (31·7–49·2) of DALYs caused by mental and substance use disorders, with anxiety disorders accounting for 14·6% (11·2–18·4), illicit drug use disorders for 10·9% (8·9–13·2), alcohol use disorders for 9·6% (7·7–11·8), schizophrenia for 7·4% (5·0–9·8), bipolar disorder for 7·0% (4·4–10·3), pervasive developmental disorders for 4·2% (3·2–5·3), childhood behavioural disorders for 3·4% (2·2–4·7), and eating disorders for 1·2% (0·9–1·5). DALYs varied by age and sex, with the highest proportion of total DALYs occurring in people aged 10–29 years. The burden of mental and substance use disorders increased by 37·6% between 1990 and 2010, which for most disorders was driven by population growth and ageing. Interpretation Despite the apparently small contribution of YLLs—with deaths in people with mental disorders coded to the physical cause of death and suicide coded to the category of injuries under self-harm—our findings show the striking and growing challenge that these disorders pose for health systems in developed and developing regions. In view of the magnitude of their contribution, improvement in population health is only possible if countries make the prevention and treatment of mental and substance use disorders a public health priority.

Global, regional, and national age–sex specifi c all-cause and cause-specifi c mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65·3 years (UI 65·0–65·6) in 1990, to 71·5 years (UI 71·0–71·9) in 2013, while the number of deaths increased from 47·5 million (UI 46·8–48·2) to 54·9 million (UI 53·6–56·3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased. For women aged 25–39 years and older than 75 years and for men aged 20–49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10·7%, from 4·3 million deaths in 1990 to 4·8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specific mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.

Conformational Spread in the Flagellar Motor Switch: A Model Study

The reliable response to weak biological signals requires that they be amplified with fidelity. In E. coli, the flagellar motors that control swimming can switch direction in response to very small changes in the concentration of the signaling protein CheY-P, but how this works is not well understood. A recently proposed allosteric model based on cooperative conformational spread in a ring of identical protomers seems promising as it is able to qualitatively reproduce switching, locked state behavior and Hill coefficient values measured for the rotary motor. In this paper we undertook a comprehensive simulation study to analyze the behavior of this model in detail and made predictions on three experimentally observable quantities: switch time distribution, locked state interval distribution, Hill coefficient of the switch response. We parameterized the model using experimental measurements, finding excellent agreement with published data on motor behavior. Analysis of the simulated switching dynamics revealed a mechanism for chemotactic ultrasensitivity, in which cooperativity is indispensable for realizing both coherent switching and effective amplification. These results showed how cells can combine elements of analog and digital control to produce switches that are simultaneously sensitive and reliable. © 2012 Ma et al.

Depressive symptoms and adverse outcomes from hospitalization in older adults : secondary outcomes of a trial of falls prevention education

Depression is common in older people and symptoms of depression are known to substantially increase during hospitalization. There is little known about predictors of depressive symptoms in older adults or impact of common interventions during hospitalization. This study aimed to describe the magnitude of depressive symptoms, shift of depressive symptoms and the impact of the symptoms of depression among older hospital patients during hospital admission and identify whether exposure to falls prevention education affected symptoms of depression. Participants (n = 1206) were older adults admitted within two Australian hospitals, the majority of participants completed the Geriatric Depression Scale – Short Form (GDS) at admission (n = 1168). Participants’ mean age was 74.7 (±SD 11) years and 47% (n = 551) were male. At admission 53% (619 out of 1168) of participants had symptoms of clinical depression and symptoms remained at the same level at discharge for 55% (543 out of 987). Those exposed to the low intensity education program had higher GDS scores at discharge than those in the control group (low intensity vs control n = 652, adjusted regression coefficient (95% CI) = 0.24 (0.02, 0.45), p = 0.03). The only factor other than admission level of depression that affected depressive symptoms change was if the participant was worried about falling. Older patients frequently present with symptoms of clinical depression on admission to hospital. Future research should consider these factors, whether these are modifiable and whether treatment may influence outcomes.

Indigenous health issues in Australia

This adaptation of Understanding Pathophysiology by Huether and McCance builds on the strengths of the US edition while tailoring it to the specific needs of Australia and New Zealand undergraduate nursing students.

Mitochondrial membrane potential in a small subset of artemisinin-induced dormant plasmodium falciparum parasites in vitro

Artemisinin induced dormancy is a proposed mechanism for failures of mono-therapy and is linked with artemisinin resistance in Plasmodium falciparum. The biological characterization and dynamics of dormant parasites are not well understood. Here we report that following dihydroartemisinin (DHA) treatment in vitro, a small subset of morphologically dormant parasites was stained with rhodamine 123 (RH), a mitochondrial membrane potential (MMP) marker, and persisted to recovery. FACS sorted RH-positive parasites resumed growth at 10,000/well while RH-negative parasites failed to recover at 5 million/well. Furthermore, transcriptional activity for mitochondrial enzymes was only detected in RH-positive dormant parasites. Importantly, after treating dormant parasites with different concentrations of atovaquone, a mitochondrial inhibitor, the recovery of dormant parasites was delayed or stopped. This demonstrates that mitochondrial activity is critical for survival and regrowth of dormant parasites and that RH staining provides a means of identifying these parasites. These findings provide novel paths for studying and eradicating this dormant stage.

Power law distributions in entrepreneurship : implications for theory and research

A long-held assumption in entrepreneurship research is that normal (i.e., Gaussian) distributions characterize variables of interest for both theory and practice. We challenge this assumption by examining more than 12,000 nascent, young, and hyper-growth firms. Results reveal that variables which play central roles in resource-, cognition-, action-, and environment-based entrepreneurship theories exhibit highly skewed power law distributions, where a few outliers account for a disproportionate amount of the distribution's total output. Our results call for the development of new theory to explain and predict the mechanisms that generate these distributions and the outliers therein. We offer a research agenda, including a description of non-traditional methodological approaches, to answer this call.

Attributing human uniqueness and human nature to cultural groups : distinct forms of subtle dehumanization

Research on subtle dehumanization has focused on the attribution of human uniqueness to groups (infrahumanization), but has not examined another sense of humanness, human nature. Additionally, research has not extended far beyond Western cultures to examine the universality of these forms of dehumanization. Hence, the attribution of both forms of humanness was examined in three cross-cultural studies. Anglo-Australian and ethnic Chinese attributed values and traits (Study 1, N = 200) and emotions (Study 2, N = 151) to Australian and Chinese groups, and rated these characteristics on human uniqueness and human nature. Both studies found evidence of complementary attributions of humanness for Australians, who denied Chinese human nature but attributed them with greater human uniqueness. Chinese denied Australians human uniqueness, but their attributions of human nature varied for traits, values, and emotions. Study 3 (N = 54) demonstrated similar forms of dehumanization using an implicit method. These results and their implications for dehumanization and prejudice suggest the need to broaden investigation and theory to encompass both forms of humanness, and examine the attribution of both lesser and greater humanness to outgroups.

Design thinking frameworks as transformative cross-disciplinary pedagogy

Final report for the Australian Government Office for Learning and Teaching. "This seed project ‘Design thinking frameworks as transformative cross-disciplinary pedagogy’ aimed to examine the way design thinking strategies are used across disciplines to scaffold the development of student attributes in the domain of problem solving and creativity in order to enhance the nation’s capacity for innovation. Generic graduate attributes associated with innovation, creativity and problem solving are considered to be amongst the most important of all targeted attributes (Bradley Review of Higher Education, 2009). The project also aimed to gather data on how academics across disciplines conceptualised design thinking methodologies and strategies. Insights into how design thinking strategies could be embedded at the subject level to improve student outcomes were of particular interest in this regard. A related aim was the investigation of how design thinking strategies could be used by academics when designing new and innovative subjects and courses." Case Study 3: QUT Community Engaged Learning Lab Design Thinking/Design Led Innovation Workshop by Natalie Wright Context "The author, from the discipline area of Interior Design in the QUT School of Design, Faculty of Creative Industries, is a contributing academic and tutor for The Community Engaged Learning Lab, which was initiated at Queensland University of Technology in 2012. The Lab facilitates university-wide service-learning experiences and engages students, academics, and key community organisations in interdisciplinary action research projects to support student learning and to explore complex and ongoing problems nominated by the community partners. In Week 3, Semester One 2013, with the assistance of co-lead Dr Cara Wrigley, Senior Lecturer in Design led Innovation, a Masters of Architecture research student and nine participating industry-embedded Masters of Research (Design led Innovation) facilitators, a Design Thinking/Design led Innovation workshop was conducted for the Community Engaged Learning Lab students, and action research outcomes published at 2013 Tsinghua International Design Management Symposium, December 2013 in Shenzhen, China (Morehen, Wright, & Wrigley, 2013)."