Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010 : a systematic analysis for the Global Burden of Disease Study 2010

Background Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). Methods Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. Findings Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350 000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient −0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. Interpretation Rates of YLDs per 100 000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. Funding Bill & Melinda Gates Foundation.

The largest eruptions in Earth's history

Large igneous provinces (LIPs) host the most frequently recurring, largest volume basaltic & silicic eruptions on Earth. The largest volume (>1000 km^3 DRE) and magnitude (>M8) eruptions produce areally extensive (10^4-10^5 km^2) basaltic flow fields and sills, and silicic ignimbrites that are the main LIP building blocks. Basaltic and silicic eruptions have comparable magnitudes, but silicic ignimbrite volumes may be significantly underestimated due to unrecognized and correlated, but voluminous co-ignimbrite ash deposits. Magma composition is no barrier to individual eruption volume. Despite similar magnitudes, flood basaltic and silicic eruptions are very different in eruption mechanism, duration, intensity, vent configuration, and emplacement style. Flood basalts are dominantly effusive Hawaiian-Strombolian, with magma discharge rates of ~10^7-10^8 kg s^-1, and produce dominantly compound pahoehoe flow fields over eruption durations most likely >10 yrs. Most silicic eruptions are moderately to highly explosive, producing cocurrent pyroclastic fountains (rarely Plinian) and suggested to be of short-duration (hours to days) and high intensity (~10^11 kg s^-1). Eruption frequencies are elevated for largemagnitude eruptions of both magma types during LIP formation. In basalt-dominated provinces, large magnitude (>M8) eruptions have much shorter recurrence intervals (10^3-10^4 years) than similar magnitude silicic eruptions (~10^5 years). The huge volumes of magma erupted rapidly in LIPs raises several unresolved issues in terms of locus of magma generation and storage (if any) in the crust prior to eruption, the paths and rates of ascent from magma reservoirs to the surface, and relative aerosol contributions to the stratosphere from the flood basaltic and rhyolitic eruptions.

Retinal and choroidal thickness in myopic anisometropia

Purpose: To compare the retinal thickness (RT) and choroidal thickness (ChT) between the fellow eyes of non-amblyopic myopic anisometropes. Methods: The eyes of 22 non-amblyopic myopic anisometropes (1 D spherical equivalent refraction [SER] anisometropia) were examined using spectral domain optical coherence tomography (SD-OCT). Customised software was used to register, align and average multiple foveal OCT B-Scan images from each subject in order to enhance image quality. Two independent masked observers manually determined the RT and ChT from each SD-OCT image up to 2.5 mm nasal and temporal to the fovea. Axial length (AXL) was measured using optical low coherence biometry during relaxed accommodation. Results: The mean SER anisometropia was 1.74 ± 0.95 D and the mean interocular AXL difference was 0.58 ± 0.41 mm. There was no significant difference in foveal RT between the fellow eyes (P > 0.05). Mean subfoveal ChT was significantly thinner in the more myopic eye (252 ± 46 μm compared to the fellow, less myopic eye (286 ± 58 μm) (P < 0.001). There was a moderate correlation between the interocular difference in subfoveal ChT and the interocular difference in AXL (r = -0.50, P < 0.01). Asian anisometropes displayed more regionally symmetrical (nasal-temporal)interocular differences in ChT profile compared to Caucasians. Conclusions: RT was similar between the fellow eyes of myopic anisometropes; however, the subfoveal choroid was significantly thinner in the more myopic (longer) eye of this anisometropic cohort. The interocular asymmetry in ChT correlated with the interocular difference in AXL.

Bubble extinction in Hele-Shaw flow with surface tension and kinetic undercooling regularisation

We perform an analytic and numerical study of an inviscid contracting bubble in a two-dimensional Hele-Shaw cell, where the effects of both surface tension and kinetic undercooling on the moving bubble boundary are not neglected. In contrast to expanding bubbles, in which both boundary effects regularise the ill-posedness arising from the viscous (Saffman-Taylor) instability, we show that in contracting bubbles the two boundary effects are in competition, with surface tension stabilising the boundary, and kinetic undercooling destabilising it. This competition leads to interesting bifurcation behaviour in the asymptotic shape of the bubble in the limit it approaches extinction. In this limit, the boundary may tend to become either circular, or approach a line or "slit" of zero thickness, depending on the initial condition and the value of a nondimensional surface tension parameter. We show that over a critical range of surface tension values, both these asymptotic shapes are stable. In this regime there exists a third, unstable branch of limiting self-similar bubble shapes, with an asymptotic aspect ratio (dependent on the surface tension) between zero and one. We support our asymptotic analysis with a numerical scheme that utilises the applicability of complex variable theory to Hele-Shaw flow.

An accurate numerical scheme for the contraction of a bubble in a Hele-Shaw cell

We report on an accurate numerical scheme for the evolution of an inviscid bubble in radial Hele-Shaw flow, where the nonlinear boundary effects of surface tension and kinetic undercooling are included on the bubble-fluid interface. As well as demonstrating the onset of the Saffman-Taylor instability for growing bubbles, the numerical method is used to show the effect of the boundary conditions on the separation (pinch-off) of a contracting bubble into multiple bubbles, and the existence of multiple possible asymptotic bubble shapes in the extinction limit. The numerical scheme also allows for the accurate computation of bubbles which pinch off very close to the theoretical extinction time, raising the possibility of computing solutions for the evolution of bubbles with non-generic extinction behaviour.

Integrated genomic characterization of endometrial carcinoma

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

Book review: "Qualitative Health Psychology. Theories and Methods" Michael Murray and Kerry Chamberlain (Eds.)

Qualitative Health Psychology aims to contribute to the debate about the nature of psychology and of science through ‘an examination of the role of qualitative research within health psychology’ (p. 3). The editors, in bringing together contributors from the UK, Ireland, Canada, Brazil, New Zealand and Australia, have compiled a text that reflects different uses of qualitative health research in diverse social and cultural contexts. Structured into three parts, the book encompasses key theoretical and methodological issues in qualitative research in its attempt to encourage broad epistemological debate within health psychology.

Analysing the Sri Lankan conflict using Michael Mann's four-dimensional model of social power

This thesis provides an overview of the Sri Lankan civil war with a view to identifying some of the factors that contributed to the dispute between the Sri Lankan government and the Liberation Tigers of Tamil Eelam. It adopts a multi-causal explanation of the conflict by reference to the theories of social power developed by Michael Mann. The conflict has been variously described as an ethnic or political conflict, or has been characterised as a determined by a number of interacting factors (including colonialism, ethnicity, religion, economy, politics and globalisation). Mann’s four-dimensional model of social power is deployed to analyse the causal relationships, together with their inter-connections, which clarify the origins of the dispute. It argues that Mann’s theoretical framework helps to highlight some of the interconnected elements that contributed to the conflict.

Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20

To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13-14 (rs703842, P = 5.4 x 10(-11); rs10876994, P = 2.7 x 10(-10); rs12368653, P = 1.0 x 10(-7)) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 x 10(-7); rs1569723, P = 2.9 x 10(-7)). Both loci are also associated with other autoimmune diseases. We also replicated several known MS associations (HLA-DR15, P = 7.0 x 10(-184); CD58, P = 9.6 x 10(-8); EVI5-RPL5, P = 2.5 x 10(-6); IL2RA, P = 7.4 x 10(-6); CLEC16A, P = 1.1 x 10(-4); IL7R, P = 1.3 x 10(-3); TYK2, P = 3.5 x 10(-3)) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).

Mutations in cardiac T-Box Factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy

The T-box family transcription factor gene TBX20 acts in a conserved regulatory network, guiding heart formation and patterning in diverse species. Mouse Tbx20 is expressed in cardiac progenitor cells, differentiating cardiomyocytes, and developing valvular tissue, and its deletion or RNA interference-mediated knockdown is catastrophic for heart development. TBX20 interacts physically, functionally, and genetically with other cardiac transcription factors, including NKX2-5, GATA4, and TBX5, mutations of which cause congenital heart disease (CHD). Here, we report nonsense (Q195X) and missense (I152M) germline mutations within the T-box DNA-binding domain of human TBX20 that were associated with a family history of CHD and a complex spectrum of developmental anomalies, including defects in septation, chamber growth, and valvulogenesis. Biophysical characterization of wild-type and mutant proteins indicated how the missense mutation disrupts the structure and function of the TBX20 T-box. Dilated cardiomyopathy was a feature of the TBX20 mutant phenotype in humans and mice, suggesting that mutations in developmental transcription factors can provide a sensitized template for adult-onset heart disease. Our findings are the first to link TBX20 mutations to human pathology. They provide insights into how mutation of different genes in an interactive regulatory circuit lead to diverse clinical phenotypes, with implications for diagnosis, genetic screening, and patient follow-up.

A systematic review of mathematical models of mosquito-borne pathogen transmission: 1970-2010

Mathematical models of mosquito-borne pathogen transmission originated in the early twentieth century to provide insights into how to most effectively combat malaria. The foundations of the Ross–Macdonald theory were established by 1970. Since then, there has been a growing interest in reducing the public health burden of mosquito-borne pathogens and an expanding use of models to guide their control. To assess how theory has changed to confront evolving public health challenges, we compiled a bibliography of 325 publications from 1970 through 2010 that included at least one mathematical model of mosquito-borne pathogen transmission and then used a 79-part questionnaire to classify each of 388 associated models according to its biological assumptions. As a composite measure to interpret the multidimensional results of our survey, we assigned a numerical value to each model that measured its similarity to 15 core assumptions of the Ross–Macdonald model. Although the analysis illustrated a growing acknowledgement of geographical, ecological and epidemiological complexities in modelling transmission, most models during the past 40 years closely resemble the Ross–Macdonald model. Modern theory would benefit from an expansion around the concepts of heterogeneous mosquito biting, poorly mixed mosquito-host encounters, spatial heterogeneity and temporal variation in the transmission process.

Parallel ABM for electricity distribution grids : a case study

This paper introduces a parallel implementation of an agent-based model applied to electricity distribution grids. A fine-grained shared memory parallel implementation is presented, detailing the way the agents are grouped and executed on a multi-threaded machine, as well as the way the model is built (in a composable manner) which is an aid to the parallelisation. Current results show a medium level speedup of 2.6, but improvements are expected by incor-porating newer distributed or parallel ABM schedulers into this implementa-tion. While domain-specific, this parallel algorithm can be applied to similarly structured ABMs (directed acyclic graphs).

Choroidal thickness in childhood

Purpose To examine choroidal thickness (ChT) and its spatial distribution across the posterior pole in pediatric subjects with normal ocular health and minimal refractive error. Methods ChT was assessed using spectral domain optical coherence tomography (OCT) in 194 children aged between 4-12 years, with spherical equivalent refractive errors between +1.25 and -0.50 DS. A series of OCT scans were collected, imaging the choroid along 4 radial scan lines centered on the fovea (each separated by 45°). Frame averaging was used to reduce noise and enhance chorio-scleral junction visibility. The transverse scale of each scan was corrected to account for magnification effects associated with axial length. Two independent masked observers manually segmented the OCT images to determine ChT at foveal centre, and averaged across a series of perifoveal zones over the central 5 mm. Results The average subfoveal ChT was 330 ± 65 µm (range 189-538 µm), and was significantly influenced by age (p=0.04). The ChT of the 4 to 6 year old age group (312 ± 62 µm) was significantly thinner compared to the 7 to 9 year olds (337 ± 65 µm, p<0.05) and bordered on significance compared to the 10 to 12 year olds (341 ± 61 µm, p=0.08). ChT also exhibited significant variation across the posterior pole, being thicker in more central regions. The choroid was thinner nasally and inferiorly compared to temporally and superiorly. Multiple regression analysis revealed age, axial length and anterior chamber depth were significantly associated with subfoveal ChT (p<0.001). Conclusions ChT increases significantly from early childhood to adolescence. This appears to be a normal feature of childhood eye growth.

Hyperopic defocus and diurnal changes in human choroid and axial length

Purpose To investigate the influence of monocular hyperopic defocus on the normal diurnal rhythms in axial length and choroidal thickness of young adults. Methods A series of axial length and choroidal thickness measurements (collected at ~3 hourly intervals, with the first measurement at ~9 am and the final measurement at ~9 pm) were obtained for 15 emmetropic young adults over three consecutive days. The natural diurnal rhythms (Day 1, no defocus), diurnal rhythms with monocular hyperopic defocus (Day 2, – 2.00 DS spectacle lens over the right eye), and the recovery from any defocus induced changes (Day 3, no defocus) in diurnal rhythms were examined. Results Both axial length and choroidal thickness underwent significant diurnal changes on each of the three measurement days (p<0.0001). The introduction of monocular hyperopic defocus resulted in significant changes in the diurnal variations observed in both parameters (p<0.05). A significant (p<0.001) increase in the mean amplitude (peak to trough) of change in axial length (mean increase, 0.016 ± 0.005 mm) and choroidal thickness (mean increase, 0.011 ± 0.003 mm) was observed on day 2 with hyperopic defocus compared to the two ‘no defocus’ days (days 1 and 3). At the second measurement (mean time 12:10 pm) on the day with hyperopic defocus, the eye was significantly longer by 0.012 ± 0.002 mm compared to the other two days (p<0.05). No significant difference was observed in the average timing of the daily peaks in axial length (mean peak time 12:12 pm) and choroidal thickness (21:02 pm) over the three days. Conclusions The introduction of monocular hyperopic defocus resulted in a significant increase in the amplitude of the diurnal change in axial length and choroidal thickness that returned to normal the following day after removal of the blur stimulus.