Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Theoretical study of spermatozoa sorting by dielectrophoresis or magnetophoresis with supervised learning

Assisted reproduction currently accounts for over one in every hundred births in developed countries. The chances of successful conception are closely related to the morphology of sperm used. Despite well-established microfluidic sorting techniques, and reliable mathematical models to quantify the swimming of microorganisms, research on sperm sorting via dielectrophoresis or magnetophoresis lacks theoretical and statistical support. In this thesis, the kinematics of sperm subjected to an external electric or magnetic field is investigated to provide a theoretical framework for computing the resultant velocity. The flagellum waveform is prescribed analytically, and subsequently solved from force and moment balance. The hydrodynamic force acting on the sperm is computed using Resistive Force Theory as well as Slender Body Theory, and the resulting velocity is compared qualitatively and quantitatively. As normal and abnormal sperm cells have different morphological parameters, their velocities under the influence of dielectrophoresis or magnetophoresis are altered to varying extents. This effect is more prominent in a viscoelastic Oldroyd-B fluid than in a Newtonian fluid medium. To account for the natural variations in sperm morphology and beating characteristics, pseudo-random data are generated from a normal distribution. The crosssection of the microchannel is assumed to be much larger than the sperm, such that boundary effects can be ignored. A large number of velocity computations is performed to obtain statistically meaningful results. The difference in velocity distribution between normal and abnormal sperm cells can be widened using an external field to double the proportion of normal ones, with at least half the number of normal spermatozoa in the original sample retained. This sorting has potential to improve the probability of success for intrauterine insemination, given that pregnancy rates are similar as long as the percentage of normal cells exceed a minimum threshold, even if the initial motile sperm count is under a million. Supervised learning is proposed to reduce the computational costs by making predictions after a subset of the data is computed and used for training. By fitting the model to a tenth of the sample size required for statistical convergence, predicted results are precise and accurate to a handful of percentage points. This framework can be adopted to shortlist feasible designs of microfluidic devices before fabrication, as well as assess a wider variety of scenarios in preliminary hypotheses.Doctor of Philosoph

Supervised Learning to Predict Sperm Sorting by Magnetophoresis

Machine learning is gaining popularity in the commercial world, but its benefits are yet to be well-utilised by many in the microfluidics community. There is immense potential in bridging the gap between applied engineering and artificial intelligence as well as statistics. We illustrate this by a case study investigating the sorting of sperm cells for assisted reproduction. Slender body theory (SBT) is applied to compute the behavior of sperm subjected to magnetophoresis, with due consideration given to statistical variations. By performing computations on a small subset of the generated data, we train an ensemble of four supervised learning algorithms and use it to make predictions on the velocity of each sperm. Our results suggest that magnetophoresis can magnify the difference between normal and abnormal cells, such that a sorted sample has over twice the proportion of desirable cells. In addition, we demonstrated that the predictions from machine learning gave comparable results with significantly lower computational costs

A Circulating miRNA Signature for Stratification of Breast Lesions among Women with Abnormal Screening Mammograms

Although mammography is the gold standard for breast cancer screening, the high rates of false-positive mammograms remain a concern. Thus, there is an unmet clinical need for a non-invasive and reliable test to differentiate between malignant and benign breast lesions in order to avoid subjecting patients with abnormal mammograms to unnecessary follow-up diagnostic procedures. Serum samples from 116 malignant breast lesions and 64 benign breast lesions were comprehensively profiled for 2,083 microRNAs (miRNAs) using next-generation sequencing. Of the 180 samples profiled, three outliers were removed based on the principal component analysis (PCA), and the remaining samples were divided into training (n = 125) and test (n = 52) sets at a 70:30 ratio for further analysis. In the training set, significantly differentially expressed miRNAs (adjusted p < 0.01) were identified after correcting for multiple testing using a false discovery rate. Subsequently, a predictive classification model using an eight-miRNA signature and a Bayesian logistic regression algorithm was developed. Based on the receiver operating characteristic (ROC) curve analysis in the test set, the model could achieve an area under the curve (AUC) of 0.9542. Together, this study demonstrates the potential use of circulating miRNAs as an adjunct test to stratify breast lesions in patients with abnormal screening mammograms

Integrative microbiomics in bronchiectasis exacerbations

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this recordData availability: All of the sequence data described in this study have been uploaded to the NCBI SRA under project accession PRJNA590225. Publicly available taxonomic and functional databases are referenced by short-read sequence classification tools used in this study as further described in the Nature Research Reporting Summary. Other associated data, including bacterial, fungal and viral profiles for all of the patients, as well as patient clinical attributes, are available at https://github.com/translational-respiratory-lab/The_Interactome/tree/master/Data.Code availability: All code required for generation of the presented results, with accompanying documentation, are available at the study’s online code repository (https://github.com/translational-respiratory-lab/The_Interactome).Bronchiectasis, a progressive chronic airway disease, is characterized by microbial colonization and infection. We present an approach to the multi-biome that integrates bacterial, viral and fungal communities in bronchiectasis through weighted similarity network fusion (https://integrative-microbiomics.ntu.edu.sg). Patients at greatest risk of exacerbation have less complex microbial co-occurrence networks, reduced diversity and a higher degree of antagonistic interactions in their airway microbiome. Furthermore, longitudinal interactome dynamics reveals microbial antagonism during exacerbation, which resolves following treatment in an otherwise stable multi-biome. Assessment of the Pseudomonas interactome shows that interaction networks, rather than abundance alone, are associated with exacerbation risk, and that incorporation of microbial interaction data improves clinical prediction models. Shotgun metagenomic sequencing of an independent cohort validated the multi-biome interactions detected in targeted analysis and confirmed the association with exacerbation. Integrative microbiomics captures microbial interactions to determine exacerbation risk, which cannot be appreciated by the study of a single microbial group. Antibiotic strategies probably target the interaction networks rather than individual microbes, providing a fresh approach to the understanding of respiratory infection.Singapore Ministry of Health National Medical Research CouncilClinician-Scientist Individual Research GrantBiological and Environmental Life Sciences (NIMBELS)British Lung FoundationScottish Government Chief Scientist OfficeEngineering and Physical Sciences Research Council (EPSRC