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.

Licensed to sell : product placement in the James Bond film series

As one of the longest running franchises in cinema history, and with its well-established use of product placements, the James Bond film series provides an ideal framework within which to measure and catalogue the number and types of products used within a particular timeframe. This case study will draw upon extensive content analysis of the James Bond film series in order to chart the evolution of product placement across the franchise's 50 year history.

A polymorphism in the HLA-DPB1 gene is associated with susceptibility to multiple sclerosis

We conducted an association study across the human leukocyte antigen (HLA) complex to identify loci associated with multiple sclerosis (MS). Comparing 1927 SNPs in 1618 MS cases and 3413 controls of European ancestry, we identified seven SNPs that were independently associated with MS conditional on the others (each ). All associations were significant in an independent replication cohort of 2212 cases and 2251 controls () and were highly significant in the combined dataset (). The associated SNPs included proxies for HLA-DRB1*15:01 and HLA-DRB1*03:01, and SNPs in moderate linkage disequilibrium (LD) with HLA-A*02:01, HLA-DRB1*04:01 and HLA-DRB1*13:03. We also found a strong association with rs9277535 in the class II gene HLA-DPB1 (discovery set , replication set , combined ). HLA-DPB1 is located centromeric of the more commonly typed class II genes HLA-DRB1, -DQA1 and -DQB1. It is separated from these genes by a recombination hotspot, and the association is not affected by conditioning on genotypes at DRB1, DQA1 and DQB1. Hence rs9277535 represents an independent MS-susceptibility locus of genome-wide significance. It is correlated with the HLA-DPB1*03:01 allele, which has been implicated previously in MS in smaller studies. Further genotyping in large datasets is required to confirm and resolve this association.

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).

Quantification of ebullitive and diffusive methane release to atmosphere from a water storage

Accurately quantifying total freshwater storage methane release to atmosphere requires the spatial–temporal measurement of both diffusive and ebullitive emissions. Existing floating chamber techniques provide localised assessment of methane flux, however, significant errors can arise when weighting and extrapolation to the entire storage, particularly when ebullition is significant. An improved technique has been developed that compliments traditional chamber based experiments to quantify the storage-scale release of methane gas to atmosphere through ebullition using the measurements from an Optical Methane Detector (OMD) and a robotic boat. This provides a conservative estimate of the methane emission rate from ebullition along with the bubble volume distribution. It also georeferences the area of ebullition activity across entire storages at short temporal scales. An assessment on Little Nerang Dam in Queensland, Australia, demonstrated whole storage methane release significantly differed spatially and throughout the day. Total methane emission estimates showed a potential 32-fold variation in whole-of-dam rates depending on the measurement and extrapolation method and time of day used. The combined chamber and OMD technique showed that 1.8–7.0% of the surface area of Little Nerang Dam is accounting for up to 97% of total methane release to atmosphere throughout the day. Additionally, over 95% of detectable ebullition occurred in depths less than 12 m during the day and 6 m at night. This difference in spatial and temporal methane release rate distribution highlights the need to monitor significant regions of, if not the entire, water storage in order to provide an accurate estimate of ebullition rates and their contribution to annual methane emissions.

Continuous monitoring of reservoir water quality: The Wivenhoe Project

The Lake Wivenhoe Integrated Wireless Sensor Network is conceptually similar to traditional SCADA monitoring and control approaches. However, it is applied in an open system using wireless devices to monitor processes that affect water quality at both a high spatial and temporal frequency. This monitoring assists scientists to better understand drivers of key processes that influence water quality and provide the operators with an early warning system if below standard water enters the reservoir. Both of these aspects improve the safety and efficient delivery of drinking water to the end users.

Industry school partnerships: Boundary crossing to enable school to work transitions

Industry-school partnerships (ISPs) are increasingly being recognised as a new way of providing vocational education opportunities. However, there is limited research investigating their impact on school to work transitions. This paper reports on a government-led ISP, the Gateway to Industry Schools Program, established in Queensland, Australia. Central to this initiative is the Queensland Minerals and Energy Academy (QMEA), a lead organisation for 28 schools and 17 multi-national sponsor companies. This research adopted a qualitative case study methodology and draws upon boundary crossing theory as means to understand a Minerals and Energy ISP. We distinguish four types of boundary crossing mechanisms, which align with principles for effectiveness in ISPs. The main findings were that boundary crossing mechanisms assist ISPs to develop industry-based contextualised curriculum and to prepare school students for employment.

Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma

We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1P29S) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1P29S showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration. These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit.

Identification of a serine protease inhibitor which causes inclusion vacuole reduction and is lethal to Chlamydia trachomatis

The mechanistic details of the pathogenesis of Chlamydia, an obligate intracellular pathogen of global importance, have eluded scientists due to the scarcity of traditional molecular genetic tools to investigate this organism. Here we report a chemical biology strategy that has uncovered the first essential protease for this organism. Identification and application of a unique CtHtrA inhibitor (JO146) to cultures of Chlamydia resulted in a complete loss of viable elementary body formation. JO146 treatment during the replicative phase of development resulted in a loss of Chlamydia cell morphology, diminishing inclusion size, and ultimate loss of inclusions from the host cells. This completely prevented the formation of viable Chlamydia elementary bodies. In addition to its effect on the human C. trachomatis strain, JO146 inhibited the viability of the mouse strain, Chlamydia muridarum, both in vitro and in vivo. Thus, we report a chemical biology approach to establish an essential role for Chlamydia CtHtrA. The function of CtHtrA for Chlamydia appears to be essential for maintenance of cell morphology during replicative the phase and these findings provide proof of concept that proteases can be targetted for anti-microbial therapy for intracellular pathogens.

Thorough assessment of DNA preservation from fossil bone and sediments excavated from a late Pleistocene–Holocene cave deposit on Kangaroo Island, South Australia

Fossils and sediments preserved in caves are an excellent source of information for investigating impacts of past environmental changes on biodiversity. Until recently studies have relied on morphology-based palaeontological approaches, but recent advances in molecular analytical methods offer excellent potential for extracting a greater array of biological information from these sites. This study presents a thorough assessment of DNA preservation from late Pleistocene–Holocene vertebrate fossils and sediments from Kelly Hill Cave Kangaroo Island, South Australia. Using a combination of extraction techniques and sequencing technologies, ancient DNA was characterised from over 70 bones and 20 sediment samples from 15 stratigraphic layers ranging in age from >20 ka to ∼6.8 ka. A combination of primers targeting marsupial and placental mammals, reptiles and two universal plant primers were used to reveal genetic biodiversity for comparison with the mainland and with the morphological fossil record for Kelly Hill Cave. We demonstrate that Kelly Hill Cave has excellent long-term DNA preservation, back to at least 20 ka. This contrasts with the majority of Australian cave sites thus far explored for ancient DNA preservation, and highlights the great promise Kangaroo Island caves hold for yielding the hitherto-elusive DNA of extinct Australian Pleistocene species.

Sampling designs on stream networks using the pseudo-Bayesian approach

Monitoring stream networks through time provides important ecological information. The sampling design problem is to choose locations where measurements are taken so as to maximise information gathered about physicochemical and biological variables on the stream network. This paper uses a pseudo-Bayesian approach, averaging a utility function over a prior distribution, in finding a design which maximizes the average utility. We use models for correlations of observations on the stream network that are based on stream network distances and described by moving average error models. Utility functions used reflect the needs of the experimenter, such as prediction of location values or estimation of parameters. We propose an algorithmic approach to design with the mean utility of a design estimated using Monte Carlo techniques and an exchange algorithm to search for optimal sampling designs. In particular we focus on the problem of finding an optimal design from a set of fixed designs and finding an optimal subset of a given set of sampling locations. As there are many different variables to measure, such as chemical, physical and biological measurements at each location, designs are derived from models based on different types of response variables: continuous, counts and proportions. We apply the methodology to a synthetic example and the Lake Eacham stream network on the Atherton Tablelands in Queensland, Australia. We show that the optimal designs depend very much on the choice of utility function, varying from space filling to clustered designs and mixtures of these, but given the utility function, designs are relatively robust to the type of response variable.

The effect of three different (-135°C) whole body cryotherapy exposure durations on elite rugby league players

Background: Whole body cryotherapy (WBC) is the therapeutic application of extreme cold air for a short duration. Minimal evidence is available for determining optimal exposure time. Purpose: To explore whether the length of WBC exposure induces differential changes in inflammatory markers, tissue oxygenation, skin and core temperature, thermal sensation and comfort. Method: This study was a randomised cross over design with participants acting as their own control. Fourteen male professional first team super league rugby players were exposed to 1, 2, and 3 minutes of WBC at -135°C. Testing took place the day after a competitive league fixture, each exposure separated by seven days. Results: No significant changes were found in the inflammatory cytokine interleukin six. Significant reductions (p<0.05) in deoxyhaemoglobin for gastrocnemius and vastus lateralis were found. In vastus lateralis significant reductions (p<0.05) in oxyhaemoglobin and tissue oxygenation index (p<0.05) were demonstrated. Significant reductions (p<0.05) in skin temperature were recorded. No significant changes were recorded in core temperature. Significant reductions (p<0.05) in thermal sensation and comfort were recorded. Conclusion: Three brief exposures to WBC separated by 1 week are not sufficient to induce physiological changes in IL-6 or core temperature. There are however significant changes in tissue oxyhaemoglobin, deoxyhaemoglobin, tissue oxygenation index, skin temperature and thermal sensation. We conclude that a 2 minute WBC exposure was the optimum exposure length at temperatures of -135°C and could be applied as the basis for future studies.

Benthic shift in a Solomon Islands' lagoon : corals to cyanobacteria

In June 2011 a large phytoplankton bloom resulted in a catastrophic mortality event that affected a large coastal embayment in the Solomon Islands. This consisted of an area in excess of 20 km2 of reef and soft sandy habitats in Marovo Lagoon, the largest double barrier lagoon in the world. This embayment is home to over 1200 people leading largely subsistence lifestyles depending on the impacted reefs for majority of their protein needs. A toxic diatom (Psuedo-nitzchia spp.) and toxic dinoflagellate (Pyrodinium bahamense var. compressum) reached concentrations of millions of cells per litre. The senescent phytoplankton bloom led to complete de-oxygenation of the water column that reportedly caused substantial mortality of marine animal life in the immediate area within a rapid timeframe (24 h). Groups affected included holothurians, crabs and reef and pelagic fish species. Dolphins, reptiles and birds were also found dead within the area, indicating algal toxin accumulation in the food chain. Deep reefs and sediments, whilst initially unaffected, have now been blanketed in large cyanobacterial mats which have negatively impacted live coral cover especially within the deep reef zone (> 6 m depth). Reef recovery within the deep zone has been extremely slow and may indicate an alternative state for the system.

An autonomous surface vehicle for water quality monitoring

This paper describes a novel Autonomous Surface Vehicle capable of navigating throughout complex inland water storages and measuring a range of water quality properties and greenhouse gas emissions. The 16 ft long solar powered catamaran can collect this information throughout the water column whilst the vehicle is moving. A unique feature of this ASV is its integration into a storage scale floating sensor network to allow remote mission uploads, data download and adaptive sampling strategies. This paper provides an overview of the vehicle design and operation including control, laser-based obstacle avoidance, and vision-based inspection capabilities. Experimental results are shown illustrating its ability to continuously collect key water quality parameters and compliment intensive manual monitoring campaigns.