| 1. |
- Lozano, Rafael, et al.
(author)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
-
In: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Journal article (peer-reviewed)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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| 2. |
- Stanaway, Jeffrey D., et al.
(author)
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Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
- 2018
-
In: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
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Journal article (peer-reviewed)abstract
- Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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| 3. |
- Murray, Christopher J. L., et al.
(author)
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Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
-
In: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
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Journal article (peer-reviewed)abstract
- Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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| 4. |
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| 5. |
- Gregson, J., et al.
(author)
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Cardiovascular Risk Factors Associated With Venous Thromboembolism
- 2019
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In: JAMA Cardiology. - : American Medical Association (AMA). - 0965-2590 .- 2380-6583 .- 2380-6591. ; 4:2, s. 163-173
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Journal article (peer-reviewed)abstract
- IMPORTANCE It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). OBJECTIVE To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. DESIGN, SETTING, AND PARTICIPANTS This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CND], 25131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). RESULTS Of the 731728 participants from the ERFC. 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. CONCLUSIONS AND RELEVANCE Older age, smoking, and adiposity were consistently associated with higher VTE risk.
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| 6. |
- Clark, Andrew G., et al.
(author)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 7. |
- Kooner, Jaspal S, et al.
(author)
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Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.
- 2011
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:10
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Journal article (peer-reviewed)abstract
- We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 × 10(-8) to P = 1.9 × 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.
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| 8. |
- Reddy, B. K. Kishore, et al.
(author)
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Assessment of Mycobacterium tuberculosis Pantothenate Kinase Vulnerability through Target Knockdown and Mechanistically Diverse Inhibitors
- 2014
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In: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 58:6, s. 3312-3326
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Journal article (peer-reviewed)abstract
- Pantothenate kinase (PanK) catalyzes the phosphorylation of pantothenate, the first committed and rate-limiting step toward coenzyme A (CoA) biosynthesis. In our earlier reports, we had established that the type I isoform encoded by the coaA gene is an essential pantothenate kinase in Mycobacterium tuberculosis, and this vital information was then exploited to screen large libraries for identification of mechanistically different classes of PanK inhibitors. The present report summarizes the synthesis and expansion efforts to understand the structure-activity relationships leading to the optimization of enzyme inhibition along with antimycobacterial activity. Additionally, we report the progression of two distinct classes of inhibitors, the triazoles, which are ATP competitors, and the biaryl acetic acids, with a mixed mode of inhibition. Cocrystallization studies provided evidence of these inhibitors binding to the enzyme. This was further substantiated with the biaryl acids having MIC against the wild-type M. tuberculosis strain and the subsequent establishment of a target link with an upshift in MIC in a strain overexpressing PanK. On the other hand, the ATP competitors had cellular activity only in a M. tuberculosis knockdown strain with reduced PanK expression levels. Additionally, in vitro and in vivo survival kinetic studies performed with a M. tuberculosis PanK (MtPanK) knockdown strain indicated that the target levels have to be significantly reduced to bring in growth inhibition. The dual approaches employed here thus established the poor vulnerability of PanK in M. tuberculosis.
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| 9. |
- Abelev, Betty, et al.
(author)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Journal article (peer-reviewed)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 10. |
- Abelev, Betty, et al.
(author)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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In: Journal of High Energy Physics. - 1029-8479. ; :11
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Journal article (peer-reviewed)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 11. |
- Abelev, Betty, et al.
(author)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
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In: Journal of High Energy Physics. - 1029-8479. ; :7
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Journal article (peer-reviewed)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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| 12. |
- Gezelius, Henrik, 1977-, et al.
(author)
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Genetic Labeling of Nuclei-Specific Thalamocortical Neurons Reveals Putative Sensory-Modality Specific Genes.
- 2017
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In: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 27:11, s. 5054-5069
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Journal article (peer-reviewed)abstract
- The thalamus is a central brain structure with topographically ordered long-range axonal projections that convey sensory information to the cortex via distinct nuclei. Although there is an increasing knowledge about genes important for thalamocortical (TC) development, the identification of genetic landmarks of the distinct thalamic nuclei during the embryonic development has not been addressed systematically. Indeed, a more comprehensive understanding of how the axons from the individual nuclei find their way and connect to their corresponding cortical area is called for. Here, we used a genetic dual labeling strategy in mice to purify distinct principal sensory thalamic neurons. Subsequent genome-wide transcriptome profiling revealed genes specifically expressed in each nucleus during embryonic development. Analysis of regulatory regions of the identified genes revealed key transcription factors and networks that likely underlie the specification of individual sensory-modality TC connections. Finally, the importance of correct axon targeting for the specific sensory-modality population transcriptome was evidenced in a Sema6A mutant, in which visual TC axons are derailed at embryonic life. In sum, our data determined the developmental transcriptional profile of the TC neurons that will eventually support sensory processing.
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| 13. |
- Harding, Jessica L., et al.
(author)
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All-cause cancer mortality over 15 years in multi-ethnic Mauritius : The impact of diabetes and intermediate forms of glucose tolerance
- 2012
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 131:10, s. 2385-2393
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Journal article (peer-reviewed)abstract
- There are accumulating data describing the association between diabetes and cancer mortality from Westernised populations. There are no data describing the relationship between diabetes and cancer mortality in African or South Asian populations from developing countries. We explored the relationship of abnormal glucose tolerance and diabetes on cancer mortality risk in a large, multi-ethnic cohort from the developing nation of Mauritius. Population-based surveys were undertaken in 1987, 1992 and 1998. The 9559 participants comprised 66% of South Asian (Indian), 27% of African (Creole), and 7% of Chinese descent. Cox's proportional hazards model with time varying covariates was used to obtain hazard ratios (HRs) and 95% confidence intervals (95% CI) for risk of cancer mortality, after adjustment for confounding factors. In men, but not women, cancer mortality risk increased with rising 2h-PG levels with HR for the top versus bottom quintile of 2.77 (95%CI: 1.28 to 5.98). South Asian men with known diabetes had a significantly greater risk of cancer mortality than those with normal glucose tolerance (NGT) HR: 2.74 (95%CI: 1.00-7.56). Overall, impaired glucose tolerance was associated with an elevated risk of cancer mortality compared to NGT (HR: 1.47, 95% CI: 0.982.19), though this was not significant. We have shown that the association between abnormal glucose tolerance and cancer extends to those of African and South Asian descent. These results highlight the importance of understanding this relationship in a global context to direct future health policy given the rapid increase in type 2 diabetes, especially in developing nations.
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| 14. |
- Hare, Matthew JL, et al.
(author)
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Glucose-independent ethnic differences in HbA(1c), in people without known diabetes
- 2013
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 36:6, s. 1534-1540
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Journal article (peer-reviewed)abstract
- OBJECTIVE To determine whether glucose-independent differences in HbA(1c) exist between people of African, South Asian, and Chinese ethnicities.RESEARCH DESIGN AND METHODS Data from 6,701 people aged 19-78 years, without known diabetes, from Mauritius, and participating in the population-based Non-Communicable Disease Surveys of the main island and the island of Rodrigues were included. Participants were African (n = 1,219 from main island, n = 1,505 from Rodrigues), South Asian (n = 3,820), and Chinese (n = 157). Survey data included HbA(1c), plasma glucose during oral glucose tolerance testing (OGTT), anthropometry, demographics, and medical and lifestyle history.RESULTS Mean HbA(1c), after adjustment for fasting and 2-h plasma glucose and other factors known to influence HbA(1c), was higher in Africans from Rodrigues (6.1%) than in South Asians (5.7%, P < 0.001), Chinese (5.7%, P < 0.001), or Africans from the main island of Mauritius (5.7%, P < 0.001). The age-standardized prevalence of diabetes among Africans from Rodrigues differed substantially depending on the diagnostic criteria used [OGTT 7.9% (95% CI 5.8-10.0); HbA(1c) 17.3% (15.3-19.2)]. Changing diagnostic criteria resulted in no significant change in the prevalence of diabetes within the other ethnic groups.CONCLUSIONS People of African ethnicity from Rodrigues have higher HbA(1c) than those of South Asian or African ethnicity from the main island of Mauritius for reasons not explained by plasma glucose during an OGTT or traditional factors known to affect glycemia. Further research should be directed at determining the mechanism behind this disparity and its relevance to clinical outcomes.
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| 15. |
- Lindahl, Johanna, et al.
(author)
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The Extent and Structure of Peri-urban Smallholder Dairy Farming in Five Cities in India
- 2020
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In: Frontiers in Veterinary Science. - : Frontiers Media SA. - 2297-1769. ; 7
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Journal article (peer-reviewed)abstract
- Livestock keeping is common in many cities in India, driven by the demand for animal-source foods, particularly perishable milk. We selected five cities from different regions of the country and conducted a census in 34 randomly selected peri-urban villages to identify and describe all smallholder dairy farms. In total 1,690 smallholder dairy farms were identified, keeping on average 2.2 milking cows and 0.7 milking buffaloes. In Bhubaneswar, the proportion of cows milking was only 50%, but in other cities it was 63-73%. In two of the five cities, more than 90% of the farmers stated that dairy production was their main source of income, while <50% in the other cities reported this. In one of the cities, only 36% of the households kept milk for themselves. Market channels varied considerably; in one city about 90% of farms sold milk to traders, in another, 90% sold to the dairy cooperative, and in another around 90% sold directly to consumers. In conclusion, peri-urban dairy systems in India are important but also varying between different cities, with only one city, Bengaluru, having a well-developed cooperative system, and the northeastern poorer region being more dependent on traders. Further studies may be needed to elucidate the importance and to design appropriate developmental interventions.
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| 16. |
- Magliano, Dianna J, et al.
(author)
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Explaining the increase of diabetes prevalence and plasma glucose in Mauritius
- 2012
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 35:1, s. 87-91
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Journal article (peer-reviewed)abstract
- OBJECTIVE Secular trends in the epidemiology of diabetes are best described by studying the same population over time, but few such studies exist. Using surveys from Mauritius in 1987 and 2009, we examined 1) the change in the prevalence of diabetes, 2) the extent to which changes in traditional diabetes risk factors explained the increase, and 3) the change in the distribution of plasma glucose levels over time.RESEARCH DESIGN AND METHODS Independent population-based surveys were undertaken in Mauritius in 1987 and 2009 using similar methodology in adults aged 20-74 years. Physical measurements and fasting blood samples were taken, and an oral glucose tolerance test was performed at both surveys.RESULTS The age-standardized prevalence of diabetes in 2009 was 22.3% (95% CI 20.0-24.6) among men and 20.2% (18.3-22.3) among women, representing an increase since 1987 of 64 and 62% among men and women, respectively. Concurrent changes in the distribution of age, ethnicity, waist circumference, BMI, physical activity, smoking, family history of diabetes, and hypertension explained more of the increase in the prevalence of diabetes in men than in women. Increases in plasma glucose (especially fasting glucose) were seen across the population but were greater at the upper levels.CONCLUSIONS In Mauritius, there has been a marked increase in diabetes prevalence over 22 years. This mainly results from changes in traditional risk factors, leading to population-wide increases in plasma glucose levels. Interventions to control this escalation of diabetes should focus on population-wide strategies.
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| 17. |
- Magliano, Dianna J, et al.
(author)
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Mortality, all-cause and cardiovascular disease, over 15 years in multiethnic mauritius : impact of diabetes and intermediate forms of glucose tolerance
- 2010
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 33:9, s. 1983-1989
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Journal article (peer-reviewed)abstract
- This is the first study in a developing country of the impact of glucose intolerance on mortality in an African population, and one of the first studies of a South Asian population. It shows that the impact on mortality in these populations in Mauritius is comparable to that seen in developed countries. These results are important in a global context for future health policy in light of the impact of the rapid increase in prevalence of diabetes, especially in developing nations.
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| 18. |
- Tabesh, Maryam, et al.
(author)
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Association between type 2 diabetes mellitus and disability : what is the contribution of diabetes risk factors and diabetes complications?
- 2018
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In: Journal of Diabetes. - : John Wiley & Sons. - 1753-0393 .- 1753-0407. ; 10:9, s. 744-752
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Journal article (peer-reviewed)abstract
- Background: The aim of this study was to evaluate the association between type 2 diabetes and disability in Mauritius and to assess the extent to which the effect of diabetes is explained by diabetes risk factors and concomitant complications.Methods: Data from a national survey in the multiethnic nation of Mauritius, which comprises South Asians and African Creoles, were analyzed. Disability was measured using the Katz activities of daily living questionnaire in participants aged >50years.Results: Among 3692 participants, 487 (13.2%) had some level of disability. Diabetes was associated with significantly higher risk of disability (odds ratio [OR] 1.67; 95% confidence interval [CI] 1.34-2.08). After adjusting for demographic, behavioral, and metabolic factors, as well as comorbidities, disability was significantly associated with diabetes among African Creoles (OR 2.03; 95% CI 1.16-3.56), but not South Asians (OR 1.27; 95% CI 0.98-1.66). Obesity explained much of the association between diabetes and disability (excess percentage of risk: 26.3% in South Asians and 12.1% in African Creoles). Obesity, history of cardiovascular disease (CVD), asthma-like symptoms, and depression together explained 46.5% and 29.0% of the excess risk in South Asians and African Creoles, respectively.Conclusions: Diabetes is associated with a 67% increased risk of disability. Diabetes risk factors and comorbidities explain more of the association between diabetes and disability among South Asians than Africans. Obesity and history of CVD explained the largest percentage of the relationship between diabetes and disability, indicating that weight and CVD management may be helpful in controlling disability related to diabetes.
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| 19. |
- Tanamas, Stephanie K., et al.
(author)
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The performance of diabetes risk prediction models in new populations : the role of ethnicity of the development cohort
- 2015
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In: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 52:1, s. 91-101
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Journal article (peer-reviewed)abstract
- It is believed that diabetes risk scores need to be ethnic specific. However, this prerequisite has not been tested. We examined the performance of several risk models, developed in various populations, in a Europid and a South Asian population. The performance of 14 published risk prediction models were tested in two prospective studies: the Australian Diabetes, Obesity and Lifestyle (AusDiab) study and the Mauritius non-communicable diseases survey. Eight models were developed in Europid populations; the remainder in various non-Europid populations. Model performance was assessed using area under the receiver operating characteristic curves (discrimination), Hosmer-Lemeshow tests (goodness-of-fit) and Brier scores (accuracy). In both AusDiab and Mauritius, discrimination was highest for a model developed in a mixed population (non-Hispanic white and African American) and lowest for a model developed in a Europid population. Discrimination for all scores was higher in AusDiab than in Mauritius. For almost all models, goodness-of-fit was poor irrespective of the ethnicity of the development cohort, and accuracy was higher in AusDiab compared to Mauritius. Our results suggest that similarity of ethnicity or similarity of diabetes risk may not be the best way of identifying models that will perform well in another population. Differences in study methodology likely account for much of the difference in the performance. Thus, identifying models which use measurements that are clearly described and easily reproducible for both research and clinical settings may be more important.
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| 20. |
- Tattikota, Sudhir G, et al.
(author)
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Argonaute2 Mediates Compensatory Expansion of the Pancreatic β Cell.
- 2014
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In: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 19:1, s. 122-134
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Journal article (peer-reviewed)abstract
- Pancreatic β cells adapt to compensate for increased metabolic demand during insulin resistance. Although the microRNA pathway has an essential role in β cell proliferation, the extent of its contribution is unclear. Here, we report that miR-184 is silenced in the pancreatic islets of insulin-resistant mouse models and type 2 diabetic human subjects. Reduction of miR-184 promotes the expression of its target Argonaute2 (Ago2), a component of the microRNA-induced silencing complex. Moreover, restoration of miR-184 in leptin-deficient ob/ob mice decreased Ago2 and prevented compensatory β cell expansion. Loss of Ago2 during insulin resistance blocked β cell growth and relieved the regulation of miR-375-targeted genes, including the growth suppressor Cadm1. Lastly, administration of a ketogenic diet to ob/ob mice rescued insulin sensitivity and miR-184 expression and restored Ago2 and β cell mass. This study identifies the targeting of Ago2 by miR-184 as an essential component of the compensatory response to regulate proliferation according to insulin sensitivity.
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| 21. |
- Tattikota, Sudhir G, et al.
(author)
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MiR-184 regulates pancreatic β-cell function according to glucose metabolism.
- 2015
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In: Journal of Biological Chemistry. - 1083-351X. ; 290:33, s. 20284-20294
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Journal article (peer-reviewed)abstract
- In response to fasting or hyperglycemia, the pancreatic β-cell alters its output of secreted insulin; however the pathways governing this adaptive response are not entirely established. While the precise role of microRNAs (miRNAs) is also unclear, a recurring theme emphasizes their function in cellular stress responses. We recently showed that miR-184, an abundant miRNA in the β-cell, regulates compensatory proliferation and secretion during insulin resistance. Consistent with previous studies showing miR-184 suppresses insulin release, expression of this miRNA was increased in islets after fasting, demonstrating an active role in the β-cell as glucose levels lower and the insulin demand ceases. Additionally, miR-184 was negatively regulated upon administration of a sucrose-rich diet in Drosophila demonstrating strong conservation of this pathway through evolution. Furthermore, miR-184 and its target Argonaute2 (Ago2) remained inversely correlated as concentrations of extracellular glucose increased, underlining a functional relationship between this miRNA and its targets. Lastly, restoration of Ago2 in the presence of miR-184 rescued suppression of miR-375-targeted genes suggesting these genes act in a coordinated manner during changes in the metabolic context. Together, these results highlight the adaptive role of miR-184 according to glucose metabolism and suggest the regulatory role of this miRNA in energy homeostasis is highly conserved.
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| 22. |
- White, Paul J, et al.
(author)
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Identifying the core concepts of pharmacology education: A global initiative.
- 2022
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In: British journal of pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 180:9, s. 1197-1209
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Journal article (peer-reviewed)abstract
- In recent decades, a focus on the most critical and fundamental concepts has proven highly advantageous to students and educators in many science disciplines. Pharmacology, unlike microbiology, biochemistry, or physiology, lacks a consensus list of such core concepts.We sought to develop a research-based, globally relevant list of core concepts that all students completing a foundational pharmacology course should master. This two-part project consisted of exploratory and refinement phases. The exploratory phase involved empirical data mining of the introductory sections of five key textbooks, in parallel with an online survey of over 200 pharmacology educators from 17 countries across six continents. The refinement phase involved three Delphi rounds involving 24 experts from 15 countries across six continents.The exploratory phase resulted in a consolidated list of 74 candidate core concepts. In the refinement phase, the expert group produced a consensus list of 25 core concepts of pharmacology.This list will allow pharmacology educators everywhere to focus their efforts on the conceptual knowledge perceived to matter most by experts within the discipline. Next steps for this project include defining and unpacking each core concept and developing resources to help pharmacology educators globally teach and assess these concepts within their educational contexts.
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