Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Power management and control strategies for off-grid hybrid power systems with renewable energies and storage

This document is the Accepted Manuscript of the following article: Belkacem Belabbas, Tayeb Allaoui, Mohamed Tadjine, and Mouloud Denai, 'Power management and control strategies for off-grid hybrid power systems with renewable energies and storage', Energy Systems, September 2017. Under embargo. Embargo end date: 19 September 2018. The final publication is available at Springer via https://doi.org/10.1007/s12667-017-0251-y.This paper presents a simulation study of standalone hybrid Distributed Generation Systems (DGS) with Battery Energy Storage System (BESS). The DGS consists of Photovoltaic (PV) panels as Renewable Power Source (RPS), a Diesel Generator (DG) for power buck-up and a BESS to accommodate the surplus of energy, which may be employed in times of poor PV generation. While off-grid DGS represent an efficient and cost-effective energy supply solution particularly to rural and remote areas, fluctuations in voltage and frequency due to load variations, weather conditions (temperature, irradiation) and transmission line short-circuits are major challenges. The paper suggests a hierarchical Power Management (PM) and controller structure to improve the reliability and efficiency of the hybrid DGS. The first layer of the overall control scheme includes a Fuzzy Logic Controller (FLC) to adjust the voltage and frequency at the Point of Common Coupling (PCC) and a Clamping Bridge Circuit (CBC) which regulates the DC bus voltage. A maximum power point tracking (MPPT) controller based on FLC is designed to extract the optimum power from the PV. The second control layer coordinates among PV, DG and BESS to ensure reliable and efficient power supply to the load. MATLAB Simulink is used to implement the overall model of the off-grid DGS and to test the performance of the proposed control scheme which is evaluated in a series of simulations scenarios. The results demonstrated the good performance of the proposed control scheme and effective coordination between the DGS for all the simulation scenarios considered.Peer reviewedFinal Accepted Versio

Expression of αvβ6integrin in oral leukoplakia

The distribution of αvβ6integrin was examined in oral leukoplakia, lichen planus and squamous cell carcinomas using immunohistochemistry. Controls included oral mucosal wounds, chronically inflamed and normal oral mucosa. Integrins β1, β3, β4, β5, fibronectin and tenascin were also studied. The integrin αvβ6was highly expressed throughout the whole lesion of 90% of the squamous cell carcinomas but was not present in any of the normal specimens. αvβ6integrin was also expressed in 41% of the leukoplakia specimens, and 85% of the lichen planus samples, but in none of the tissues with inflammatory hyperplasia or chronic inflammation. The expression of β1 integrins was localized in the basal layer, and that of the β4at the cell surface facing the basement membrane of all specimens. The integrins β3and β5were absent from all normal and leukoplakia specimens. Fibronectin and tenascin were present in the connective tissue underneath the epithelium of all the sections, and their expression was similar in both αvβ6-positive and αvβ6-negative tissues. A group of 28 leukoplakia patients were followed 1–4 years after first diagnosis. In this group, initially αvβ6integrin-positive leukoplakia specimens had high tendency for disease progression while αvβ6-negative specimens did not progress. These results suggest that the expression of αvβ6integrin could be associated in the malignant transformation of oral leukoplakias. © 2000 Cancer Research Campaig

Burden of musculoskeletal disorders in the Eastern Mediterranean Region, 1990-2013: findings from the Global Burden of Disease Study 2013.

OBJECTIVES: We used findings from the Global Burden of Disease Study 2013 to report the burden of musculoskeletal disorders in the Eastern Mediterranean Region (EMR). METHODS: The burden of musculoskeletal disorders was calculated for the EMR's 22 countries between 1990 and 2013. A systematic analysis was performed on mortality and morbidity data to estimate prevalence, death, years of live lost, years lived with disability and disability-adjusted life years (DALYs). RESULTS: For musculoskeletal disorders, the crude DALYs rate per 100 000 increased from 1297.1 (95% uncertainty interval (UI) 924.3-1703.4) in 1990 to 1606.0 (95% UI 1141.2-2130.4) in 2013. During 1990-2013, the total DALYs of musculoskeletal disorders increased by 105.2% in the EMR compared with a 58.0% increase in the rest of the world. The burden of musculoskeletal disorders as a proportion of total DALYs increased from 2.4% (95% UI 1.7-3.0) in 1990 to 4.7% (95% UI 3.6-5.8) in 2013. The range of point prevalence (per 1000) among the EMR countries was 28.2-136.0 for low back pain, 27.3-49.7 for neck pain, 9.7-37.3 for osteoarthritis (OA), 0.6-2.2 for rheumatoid arthritis and 0.1-0.8 for gout. Low back pain and neck pain had the highest burden in EMR countries. CONCLUSIONS: This study shows a high burden of musculoskeletal disorders, with a faster increase in EMR compared with the rest of the world. The reasons for this faster increase need to be explored. Our findings call for incorporating prevention and control programmes that should include improving health data, addressing risk factors, providing evidence-based care and community programmes to increase awareness

Global, regional, and national burden of stroke, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Stroke is a leading cause of mortality and disability worldwide and the economic costs of treatment and post-stroke care are substantial. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic, comparable method of quantifying health loss by disease, age, sex, year, and location to provide information to health systems and policy makers on more than 300 causes of disease and injury, including stroke. The results presented here are the estimates of burden due to overall stroke and ischaemic and haemorrhagic stroke from GBD 2016. Methods: We report estimates and corresponding uncertainty intervals (UIs), from 1990 to 2016, for incidence, prevalence, deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs). DALYs were generated by summing YLLs and YLDs. Cause-specific mortality was estimated using an ensemble modelling process with vital registration and verbal autopsy data as inputs. Non-fatal estimates were generated using Bayesian meta-regression incorporating data from registries, scientific literature, administrative records, and surveys. The Socio-demographic Index (SDI), a summary indicator generated using educational attainment, lagged distributed income, and total fertility rate, was used to group countries into quintiles. Findings: In 2016, there were 5·5 million (95% UI 5·3 to 5·7) deaths and 116·4 million (111·4 to 121·4) DALYs due to stroke. The global age-standardised mortality rate decreased by 36·2% (−39·3 to −33·6) from 1990 to 2016, with decreases in all SDI quintiles. Over the same period, the global age-standardised DALY rate declined by 34·2% (−37·2 to −31·5), also with decreases in all SDI quintiles. There were 13·7 million (12·7 to 14·7) new stroke cases in 2016. Global age-standardised incidence declined by 8·1% (−10·7 to −5·5) from 1990 to 2016 and decreased in all SDI quintiles except the middle SDI group. There were 80·1 million (74·1 to 86·3) prevalent cases of stroke globally in 2016; 41·1 million (38·0 to 44·3) in women and 39·0 million (36·1 to 42·1) in men. Interpretation: Although age-standardised mortality rates have decreased sharply from 1990 to 2016, the decrease in age-standardised incidence has been less steep, indicating that the burden of stroke is likely to remain high. Planned updates to future GBD iterations include generating separate estimates for subarachnoid haemorrhage and intracerebral haemorrhage, generating estimates of transient ischaemic attack, and including atrial fibrillation as a risk factor. Funding: Bill & Melinda Gates Foundatio

Designing Bioactive Delivery Systems for Tissue Regeneration

The direct infusion of macromolecules into defect sites generally does not impart adequate physiological responses. Without the protection of delivery systems, inductive molecules may likely redistribute away from their desired locale and are vulnerable to degradation. In order to achieve efficacy, large doses supplied at interval time periods are necessary, often at great expense and ensuing detrimental side effects. The selection of a delivery system plays an important role in the rate of re-growth and functionality of regenerating tissue: not only do the release kinetics of inductive molecules and their consequent bioactivities need to be considered, but also how the delivery system interacts and integrates with its surrounding host environment. In the current review, we describe the means of release of macromolecules from hydrogels, polymeric microspheres, and porous scaffolds along with the selection and utilization of bioactive delivery systems in a variety of tissue-engineering strategies

Optical imaging in vivo with a focus on paediatric disease: technical progress, current preclinical and clinical applications and future perspectives

To obtain information on the occurrence and location of molecular events as well as to track target-specific probes such as antibodies or peptides, drugs or even cells non-invasively over time, optical imaging (OI) technologies are increasingly applied. Although OI strongly contributes to the advances made in preclinical research, it is so far, with the exception of optical coherence tomography (OCT), only very sparingly applied in clinical settings. Nevertheless, as OI technologies evolve and improve continuously and represent relatively inexpensive and harmful methods, their implementation as clinical tools for the assessment of children disease is increasing. This review focuses on the current preclinical and clinical applications as well as on the future potential of OI in the clinical routine. Herein, we summarize the development of different fluorescence and bioluminescence imaging techniques for microscopic and macroscopic visualization of microstructures and biological processes. In addition, we discuss advantages and limitations of optical probes with distinct mechanisms of target-detection as well as of different bioluminescent reporter systems. Particular attention has been given to the use of near-infrared (NIR) fluorescent probes enabling observation of molecular events in deeper tissue

Global and regional burden of chronic respiratory disease in 2016 arising from non-infectious airborne occupational exposures: a systematic analysis for the Global Burden of Disease Study 2016

OBJECTIVES: This paper presents detailed analysis of the global and regional burden of chronic respiratory disease arising from occupational airborne exposures, as estimated in the Global Burden of Disease 2016 study. METHODS: The burden of chronic obstructive pulmonary disease (COPD) due to occupational exposure to particulate matter, gases and fumes, and secondhand smoke, and the burden of asthma resulting from occupational exposure to asthmagens, was estimated using the population attributable fraction (PAF), calculated using exposure prevalence and relative risks from the literature. PAFs were applied to the number of deaths and disability-adjusted life years (DALYs) for COPD and asthma. Pneumoconioses were estimated directly from cause of death data. Age-standardised rates were based only on persons aged 15 years and above. RESULTS: The estimated PAFs (based on DALYs) were 17% (95% uncertainty interval (UI) 14%-20%) for COPD and 10% (95% UI 9%-11%) for asthma. There were estimated to be 519 000 (95% UI 441,000-609,000) deaths from chronic respiratory disease in 2016 due to occupational airborne risk factors (COPD: 460,100 [95% UI 382,000-551,000]; asthma: 37,600 [95% UI 28,400-47,900]; pneumoconioses: 21,500 [95% UI 17,900-25,400]. The equivalent overall burden estimate was 13.6 million (95% UI 11.9-15.5 million); DALYs (COPD: 10.7 [95% UI 9.0-12.5] million; asthma: 2.3 [95% UI 1.9-2.9] million; pneumoconioses: 0.58 [95% UI 0.46-0.67] million). Rates were highest in males; older persons and mainly in Oceania, Asia and sub-Saharan Africa; and decreased from 1990 to 2016. CONCLUSIONS: Workplace exposures resulting in COPD, asthma and pneumoconiosis continue to be important contributors to the burden of disease in all regions of the world. This should be reducible through improved prevention and control of relevant exposures