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

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

An Analysis of the Effects of Globalization on Local Firm Competitiveness: A Case of Regent Automobile Valuers and Assessors Ltd

A Research Project Report proposed to the School of Business in Partial Fulfillment of the Requirement for the Degree Of Masters in Business Administration (MBA)The purpose of the study is to analyze the effects of globalization on local firm competitiveness, and thus to analyze strategies that aid local Kenyan firms to adapt to globalization. In recent years, the world has witnessed constant waves of globalization. These waves have impacted both local and international firms. A sample effect has been the entry of numerous foreign competitors into the Kenyan market. The study aims to come up with strategies by answering three research questions. First, what have been the effects of globalization on local firm competitiveness? Second, which strategies do local firms use to compete with foreign multinational corporations (which possess more resources) in an increasingly globalized local environment? Third, how do local firms enter international markets to gain competitive advantage? Tackling these three research questions will assist local Kenyan firms to better understand and respond to the effects of globalization, while planning for and beginning the process of internationalization. The study used a descriptive research method for its research design. This is used to describe characteristics of a population or phenomenon. The study’s population was picked from Regent Automobile Valuers and Assessors Ltd, a local Kenyan firm that specializes in the valuation of automobiles and machinery. The research utilized a population census. It dealt with primary data. Data was collected using questionnaires. To ensure a high degree of accuracy, the questionnaire was pretested. Once data was collected, it was cleaned and input into a computer. Data analysis was conducted using IBM SPSS Statistical Analysis software and Microsoft Excel Spreadsheet software. Data analysis was then carried out using descriptive statistics and inferential statistics. Descriptive statistics analyzed frequency distribution of responses, measures of central tendency, and reliability. Measures of central tendency included the mean, median, mode, standard deviation, variance, range, minimum values and maximum values. Reliability analysis utilized the Chronbach’s Alpha. Inferential Statistics undertook a correlation analysis using Pearson’s correlation coefficient. Statistical findings were presented in the form of frequency distribution tables, bar graphs and pie charts. The research discovered that globalization forces had a large impact on local firm competitiveness. Analysis discovered that firms that successfully adapted to globalization were likely to be highly successful in the local market, and were also likely to expand; or desire to expand into foreign markets. The research concluded that globalization has a great impact on both the competitiveness of local firms; and the business environments they operate in. Positive effects such as access to foreign technologies and foreign direct investments greatly benefit local firms; while negative effects, such as adverse competition, have the potential to drive companies that do not adapt into extinction. Local firms can successfully compete with foreign firms in the local business environment. They can also successfully enter international markets despite an increasingly hostile, competitive and volatile international business environment. The research recommended that local firms need to analyze the effects of globalization on both their competitiveness and their local business environments. Doing this will aid them to better position themselves to respond, adapt and exploit the effects of globalization to their advantage. The research also recommended that firms conduct thorough industry analyses to map out potential foreign threats, and position themselves in the industry. Local companies need to deeply analyze the special competitive advantages they possess by being local; and learn how to exploit them effectively. Firms that desire to expand into international markets should have an adequate global strategy

In Vitro Chemosensitization of Plasmodium falciparum to Antimalarials by Verapamil and Probenecid▿

We tested the effect of probenecid and verapamil in chemosensitizing Plasmodium falciparum to 14 antimalarials using the multidrug-resistant strain V1S and the drug-sensitive 3D7. Verapamil chemosensitizes V1S to quinine and chloroquine. Interestingly, probenecid profoundly chemosensitizes V1S to piperaquine. Thus, probenecid could be used to increase piperaquine efficacy in vivo

Adaptation and performance of rice genotypes in tropical and subtropical environments

Standardized field experiments were carried out to study the performance of five rice genotypes derived from different germplasm in terms of yield, harvest index (HI) and grain quality at eight agro-ecological sites of the tropics and subtropics across Asia during 2001 and 2002. Considering that indica and javanica genotypes adapt to warm climatic conditions, and japonica genotypes to cool agro-climatic conditions, it is hypothesized that indica × japonica hybrids may combine high yields and good quality traits under a wide range of agro-climatic conditions. Grain yield, HI, protein content and amylose content varied considerably among genotypes and environments. Mean rice yields of genotypes ranged from 1.5 to 11 t ha-1 across the eight sites; on average yields were 7.2 t ha-1 under subtropical and 2.7 t ha-1 under tropical conditions. The much lower yields in tropical environments resulted from a low biomass as well as a low HI. Among the genotypes, the indica × japonica hybrid showed the highest yield under subtropical conditions, and a higher yield than the japonica genotypes and the indica × javanica hybrid but lower than the indica genotype under tropical conditions. Phenology of genotypes varied strongly across environments. Low yields at tropical locations were associated with a low light capture due to short growth duration. Post-anthesis light-use efficiencies and the photothermal quotient explained much of the variation in yield. Protein content varied among genotypes depending on location and year. Variation in amylose content of rice grains was mainly associated with genotypic differences and much less with environmental conditions, but contents decreased with higher post-anthesis ambient temperatures. The indica × japonica hybrid combined high yields with a favourable amylose content and showed a better ability to adapt to cool and to warm agro-climatic conditions than the indica or japonica genotypes. Our study showed the magnitude of yield penalties associated with growing rice genotypes in environments to which they are not adapted. The consequences of these findings for improved adaptation of rice are discusse

Declining Responsiveness of Plasmodium falciparum Infections to Artemisinin-Based Combination Treatments on the Kenyan Coast

BACKGROUND: The emergence of artemisinin-resistant P. falciparum malaria in South-East Asia highlights the need for continued global surveillance of the efficacy of artemisinin-based combination therapies. METHODS: On the Kenyan coast we studied the treatment responses in 474 children 6–59 months old with uncomplicated P. falciparum malaria in a randomized controlled trial of dihydroartemisinin-piperaquine vs. artemether-lumefantrine from 2005 to 2008. (ISRCTN88705995) RESULTS: The proportion of patients with residual parasitemia on day 1 rose from 55% in 2005–2006 to 87% in 2007–2008 (odds ratio, 5.4, 95%CI, 2.7–11.1; P<0.001) and from 81% to 95% (OR, 4.1, 95%CI, 1.7–9.9; P = 0.002) in the DHA-PPQ and AM-LM groups, respectively. In parallel, Kaplan-Meier estimated risks of apparent recrudescent infection by day 84 increased from 7% to 14% (P = 0.1) and from 6% to 15% (P = 0.05) with DHA-PPQ and AM-LM, respectively. Coinciding with decreasing transmission in the study area, clinical tolerance to parasitemia (defined as absence of fever) declined between 2005–2006 and 2007–2008 (OR body temperature >37.5°C, 2.8, 1.9–4.1; P<0.001). Neither in vitro sensitivity of parasites to DHA nor levels of antibodies against parasite extract accounted for parasite clearance rates or changes thereof. CONCLUSIONS: The significant, albeit small, decline through time of parasitological response rates to treatment with ACTs may be due to the emergence of parasites with reduced drug sensitivity, to the coincident reduction in population-level clinical immunity, or both. Maintaining the efficacy of artemisinin-based therapy in Africa would benefit from a better understanding of the mechanisms underlying reduced parasite clearance rates. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN8870599

Correlation coefficients of log2 fold changes (FC) by RT-qPCR and microarray analysis.

<p>The linear regression is indicated on the plot, with an r² = 0.7389.</p

Chromosomes 2 (A) and 10 (B) show over-expression of contiguous probes covering 21 and 22 CDS, respectively.

<p>Amplification of the signals for the left arms of chromosomes 2 (<b>A</b>) and 10 (<b>B</b>) are enlarged for each time point as indicated. Every single coloured dot corresponds to a 25-mer probe: red is for 0 h, blue for 12 h, green for 24 h and yellow for 36 h. Underneath every enlarged chromosomal arm are pink bars indicating 100% robustness of signal amplification at <i>p</i><0.01 (using SnoopCGH program with Smith–Waterman algorithm implementation). A normal distribution of the log ratios (y-axis) around the zero horizontal line is expected if the expression levels are the same along the chromosome (indicated as kilo base pair [kbp]). The CDS (represented under each chromosome by blue rectangles) contained within each amplified region are indicated on the right with their appropriate annotation (<a href="http://www.genedb.org" target="_blank">www.genedb.org</a>). The genes marked with an * have been found significant at B>0 in the pairwise comparisons of the microarray data in at least one time point, while the underlined genes have been double checked by qRT-PCR.</p