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1.
  • Thomas, HS, et al. (författare)
  • 2019
  • swepub:Mat__t
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  • Hay, S. I., et al. (författare)
  • Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016 : A systematic analysis for the Global Burden of Disease Study 2016
  • 2017
  • Ingår i: The Lancet. - : Lancet Publishing Group. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1260-1344
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). Methods: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE difered from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. Findings: The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9-78·6) for females and 72·0 years (68·8-75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0-49·5]) and for males was in Lesotho (41·5 years [39·0-44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97-6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74-6·27) for males and 6·49 years (6·08-6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61-1·93) for males and 1·96 years (1·69-2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2·3% [-5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs ofset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the fve lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. Interpretation: At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs ofset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention eforts, and development assistance for health, including fnancial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. © The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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6.
  • Hibar, Derrek P., et al. (författare)
  • Novel genetic loci associated with hippocampal volume
  • 2017
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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  • Stanaway, Jeffrey D., et al. (författare)
  • 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
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
  • Tidskriftsartikel (refereegranskat)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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8.
  • Wang, Haidong, et al. (författare)
  • Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
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  • Kassebaum, Nicholas J., et al. (författare)
  • Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
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10.
  • Lozano, Rafael, et al. (författare)
  • 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
  • Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
  • Tidskriftsartikel (refereegranskat)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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  • Locke, Adam E, et al. (författare)
  • Genetic studies of body mass index yield new insights for obesity biology.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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  • Murray, Christopher J. L., et al. (författare)
  • 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
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
  • Tidskriftsartikel (refereegranskat)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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  • Satizabal, Claudia L., et al. (författare)
  • Genetic architecture of subcortical brain structures in 38,851 individuals
  • 2019
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
  • Tidskriftsartikel (refereegranskat)abstract
    • Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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14.
  • Patel, Riyaz S., et al. (författare)
  • Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
  • 2019
  • Ingår i: Circulation. - 2574-8300. ; 12:4
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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15.
  • Shungin, Dmitry, et al. (författare)
  • New genetic loci link adipose and insulin biology to body fat distribution.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
  • Tidskriftsartikel (refereegranskat)abstract
    • Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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16.
  • Patel, Riyaz S., et al. (författare)
  • Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
  • 2019
  • Ingår i: Circulation. - 2574-8300. ; 12:4
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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17.
  • Zamora, Juan Carlos, et al. (författare)
  • Considerations and consequences of allowing DNA sequence data as types of fungal taxa
  • 2018
  • Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
  • Tidskriftsartikel (refereegranskat)abstract
    • Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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18.
  • Cadrin-Tourigny, Julia, et al. (författare)
  • A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy
  • 2019
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 40:23, s. 1850-1858
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. METHODS AND RESULTS: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P < 0.001). CONCLUSION: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).
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19.
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20.
  • Ried, Janina S., et al. (författare)
  • A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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21.
  • Wang, Haidong, et al. (författare)
  • Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015 : the Global Burden of Disease Study 2015.
  • 2016
  • Ingår i: The lancet. HIV. - : Elsevier. - 2352-3018. ; 3:8, s. e361-e387
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.METHODS: For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification.FINDINGS: Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1-3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5-2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6-40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7-1·9 million) in 2005, to 1·2 million deaths (1·1-1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections.INTERPRETATION: Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030.
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22.
  • Abolfathi, Bela, et al. (författare)
  • The Fourteenth Data Release of the Sloan Digital Sky Survey : First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment
  • 2018
  • Ingår i: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
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23.
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24.
  • Ashar, Foram N., et al. (författare)
  • A comprehensive evaluation of the genetic architecture of sudden cardiac arrest
  • 2018
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 39:44, s. 3961-
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA.Methods and results: We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk.Conclusions: Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.
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25.
  • Blanton, Michael R., et al. (författare)
  • Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
  • 2017
  • Ingår i: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
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26.
  • Bowden, John A., et al. (författare)
  • Harmonizing lipidomics : NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma
  • 2017
  • Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 58:12, s. 2275-2288
  • Tidskriftsartikel (refereegranskat)abstract
    • As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra-and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium.jlr While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.
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27.
  • Esteban-Cornejo, Irene, et al. (författare)
  • Fitness, cortical thickness and surface area in overweight/obese children: The mediating role of body composition and relationship with intelligence
  • 2019
  • Ingår i: NeuroImage. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1053-8119 .- 1095-9572. ; 186, s. 771-781
  • Tidskriftsartikel (refereegranskat)abstract
    • Cortical thickness and surface area are thought to be genetically unrelated and shaped by independent neurobiological events suggesting that they should be considered separately in morphometric analyses. Although the developmental trajectories of cortical thickness and surface area may differ across brain regions and ages, there is no consensus regarding the relationships of physical fitness with cortical thickness and surface area as well as for its subsequent influence on intelligence. Thus, this study examines: (i) the associations of physical fitness components (i.e., cardiorespiratory fitness, speed-agility and muscular fitness) with overall and regional cortical thickness and surface area; (ii) whether body composition indicators (i.e., body mass index, fat-free mass index and fat mass index) mediate these associations; and (iii) the association of physical fitness and cortical thickness with intelligence in overweight/obese children. A total of 101 overweight/obese children aged 8-11 years were recruited in Granada, Spain. The physical fitness components were assessed following the ALPHA health-related fitness test battery. T1-weighted images were acquired with a 3.0 Tesla Siemens Magnetom Tim Trio system. We used FreeSurfer software version 5.3.0 to assess cortical thickness (mm) and surface area (mm(2)). The main results showed that cardiorespiratory fitness and speed-agility were related to overall cortical thickness (beta = 0.321 and beta = 0.302, respectively; both P amp;lt; 0.05), and in turn, cortical thickness was associated with higher intelligence (beta = 0.198, P amp;lt; 0.05). Muscular fitness was not related to overall cortical thickness. None of the three physical fitness components were related to surface area (p amp;gt; 0.05). The associations of cardiorespiratory fitness and speed-agility with overall cortical thickness were mediated by fat mass index (56.86% amp; 62.28%, respectively). In conclusion, cardiorespiratory fitness and speed-agility, but not muscular fitness, are associated with overall cortical thickness, and in turn, thicker brain cortex is associated with higher intelligence in overweight/obese children. Yet, none of the three physical fitness components were related to surface area. Importantly, adiposity may hinder the benefits of cardiorespiratory fitness and speed-agility on cortical thickness. Understanding individual differences in brain morphology may have important implications for educators and policy makers who aim to determine policies and interventions to maximize academic learning and occupational success later in life.
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28.
  • Lopes, Fernando, et al. (författare)
  • ER-stress mobilization of death-associated protein kinase-1-dependent xenophagy counteracts mitochondria stress-induced epithelial barrier dysfunction
  • 2018
  • Ingår i: Journal of Biological Chemistry. - : AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. - 0021-9258 .- 1083-351X. ; 293:9, s. 3073-3087
  • Tidskriftsartikel (refereegranskat)abstract
    • The gut microbiome contributes to inflammatory bowel disease (IBD), in which bacteria can be present within the epithelium. Epithelial barrier function is decreased in IBD, and dysfunctional epithelial mitochondria and endoplasmic reticulum (ER) stress have been individually associated with IBD. We therefore hypothesized that the combination of ER and mitochondrial stresses significantly disrupt epithelial barrier function. Here, we treated human colonic biopsies, epithelial colonoids, and epithelial cells with an uncoupler of oxidative phosphorylation, dinitrophenol (DNP), with or without the ER stressor tunicamycin and assessed epithelial barrier function by monitoring internalization and translocation of commensal bacteria. We also examined barrier function and colitis in mice exposed to dextran sodium sulfate (DSS) or DNP and co-treated with DAPK6, an inhibitor of death-associated protein kinase 1 (DAPK1). Contrary to our hypothesis, induction of ER stress (i.e. the unfolded protein response) protected against decreased barrier function caused by the disruption of mitochondrial function. ER stress did not prevent DNP-driven uptake of bacteria; rather, specific mobilization of the ATF6 arm of ER stress and recruitment of DAP K1 resulted in enhanced autophagic killing (xenophagy) of bacteria. Of note, epithelia with a Crohns disease susceptibility mutation in the autophagy gene ATG16L.1 exhibited less xenophagy. Systemic delivery of the DAPK1 inhibitor DAPK6 increased bacterial translocation in DSS- or DNP-treated mice. We conclude that promoting ER stress ATF6 DAPK1 signaling in transporting enterocytes counters the transcellular passage of bacteria evoked by dysfunctional mitochondria, thereby reducing the potential for metabolic stress to reactivate or perpetuate inflammation.
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29.
  • Lubin, Jay H., et al. (författare)
  • Thyroid Cancer Following Childhood Low-Dose Radiation Exposure : A Pooled Analysis of Nine Cohorts
  • 2017
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 102:7, s. 2575-2583
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: The increased use of diagnostic and therapeutic procedures that involve radiation raises concerns about radiation effects, particularly in children and the radiosensitive thyroid gland.Objectives: Evaluation of relative risk (RR) trends for thyroid radiation doses <0.2 gray (Gy); evidence of a threshold dose; and possible modifiers of the dose-response, e.g., sex, age at exposure, time since exposure.Design and Setting: Pooled data from nine cohort studies of childhood external radiation exposure and thyroid cancer with individualized dose estimates, ≥1000 irradiated subjects or ≥10 thyroid cancer cases, with data limited to individuals receiving doses <0.2 Gy.Participants: Cohorts included the following: childhood cancer survivors (n = 2); children treated for benign diseases (n = 6); and children who survived the atomic bombings in Japan (n = 1). There were 252 cases and 2,588,559 person-years in irradiated individuals and 142 cases and 1,865,957 person-years in nonirradiated individuals.Intervention: There were no interventions.Main Outcome Measure: Incident thyroid cancers.Results: For both <0.2 and <0.1 Gy, RRs increased with thyroid dose (P < 0.01), without significant departure from linearity (P = 0.77 and P = 0.66, respectively). Estimates of threshold dose ranged from 0.0 to 0.03 Gy, with an upper 95% confidence bound of 0.04 Gy. The increasing dose–response trend persisted >45 years after exposure, was greater at younger age at exposure and younger attained age, and was similar by sex and number of treatments.Conclusions: Our analyses reaffirmed linearity of the dose response as the most plausible relationship for “as low as reasonably achievable” assessments for pediatric low-dose radiation-associated thyroid cancer risk.
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30.
  • Mooij, Wolf M., et al. (författare)
  • Modeling water quality in the Anthropocene : directions for the next-generation aquatic ecosystem models
  • 2019
  • Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 36, s. 85-95
  • Forskningsöversikt (refereegranskat)abstract
    • Everything changes and nothing stands still (Heraclitus). Here we review three major improvements to freshwater aquatic ecosystem models - and ecological models in general - as water quality scenario analysis tools towards a sustainable future. To tackle the rapid and deeply connected dynamics characteristic of the Anthropocene, we argue for the inclusion of eco-evolutionary, novel ecosystem and social-ecological dynamics. These dynamics arise from adaptive responses in organisms and ecosystems to global environmental change and act at different integration levels and different time scales. We provide reasons and means to incorporate each improvement into aquatic ecosystem models. Throughout this study we refer to Lake Victoria as a microcosm of the evolving novel social-ecological systems of the Anthropocene. The Lake Victoria case clearly shows how interlinked eco-evolutionary, novel ecosystem and social-ecological dynamics are, and demonstrates the need for transdisciplinary research approaches towards global sustainability.
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31.
  • Rader, Romina, et al. (författare)
  • Non-bee insects are important contributors to global crop pollination.
  • 2016
  • Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 113:1, s. 146-151
  • Tidskriftsartikel (refereegranskat)abstract
    • Wild and managed bees are well documented as effective pollinators of global crops of economic importance. However, the contributions by pollinators other than bees have been little explored despite their potential to contribute to crop production and stability in the face of environmental change. Non-bee pollinators include flies, beetles, moths, butterflies, wasps, ants, birds, and bats, among others. Here we focus on non-bee insects and synthesize 39 field studies from five continents that directly measured the crop pollination services provided by non-bees, honey bees, and other bees to compare the relative contributions of these taxa. Non-bees performed 25-50% of the total number of flower visits. Although non-bees were less effective pollinators than bees per flower visit, they made more visits; thus these two factors compensated for each other, resulting in pollination services rendered by non-bees that were similar to those provided by bees. In the subset of studies that measured fruit set, fruit set increased with non-bee insect visits independently of bee visitation rates, indicating that non-bee insects provide a unique benefit that is not provided by bees. We also show that non-bee insects are not as reliant as bees on the presence of remnant natural or seminatural habitat in the surrounding landscape. These results strongly suggest that non-bee insect pollinators play a significant role in global crop production and respond differently than bees to landscape structure, probably making their crop pollination services more robust to changes in land use. Non-bee insects provide a valuable service and provide potential insurance against bee population declines.
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32.
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33.
  • Turkington, RC, et al. (författare)
  • Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma
  • 2019
  • Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:11, s. 1918-1927
  • Tidskriftsartikel (refereegranskat)abstract
    • Current strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability of a DNA damage immune response (DDIR) assay to predict response following neoadjuvant chemotherapy in OAC.DesignTranscriptional profiling of 273 formalin-fixed paraffin-embedded prechemotherapy endoscopic OAC biopsies was performed. All patients were treated with platinum-based neoadjuvant chemotherapy and resection between 2003 and 2014 at four centres in the Oesophageal Cancer Clinical and Molecular Stratification consortium. CD8 and programmed death ligand 1 (PD-L1) immunohistochemical staining was assessed in matched resection specimens from 126 cases. Kaplan-Meier and Cox proportional hazards regression analysis were applied according to DDIR status for recurrence-free survival (RFS) and overall survival (OS).ResultsA total of 66 OAC samples (24%) were DDIR positive with the remaining 207 samples (76%) being DDIR negative. DDIR assay positivity was associated with improved RFS (HR: 0.61; 95% CI 0.38 to 0.98; p=0.042) and OS (HR: 0.52; 95% CI 0.31 to 0.88; p=0.015) following multivariate analysis. DDIR-positive patients had a higher pathological response rate (p=0.033), lower nodal burden (p=0.026) and reduced circumferential margin involvement (p=0.007). No difference in OS was observed according to DDIR status in an independent surgery-alone dataset.DDIR-positive OAC tumours were also associated with the presence of CD8+ lymphocytes (intratumoural: p<0.001; stromal: p=0.026) as well as PD-L1 expression (intratumoural: p=0.047; stromal: p=0.025).ConclusionThe DDIR assay is strongly predictive of benefit from DNA-damaging neoadjuvant chemotherapy followed by surgical resection and is associated with a proinflammatory microenvironment in OAC.
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34.
  • Veiga, Lene H. S., et al. (författare)
  • Thyroid Cancer after Childhood Exposure to External Radiation : An Updated Pooled Analysis of 12 Studies
  • 2016
  • Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 185:5, s. 473-484
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies have causally linked external thyroid radiation exposure in childhood with thyroid cancer. In 1995, investigators conducted relative risk analyses of pooled data from seven epidemiologic studies. Doses were mostly <10 Gy, although childhood cancer therapies can result in thyroid doses >50 Gy. We pooled data from 12 studies of thyroid cancer patients who were exposed to radiation in childhood (ages <20 years), more than doubling the data, including 1,070 (927 exposed) thyroid cancers and 5.3 million (3.4 million exposed) person-years. Relative risks increased supralinearly through 2-4 Gy, leveled off between 10-30 Gy and declined thereafter, remaining significantly elevated above 50 Gy. There was a significant relative risk trend for doses <0.10 Gy (P < 0.01), with no departure from linearity (P = 0.36). We observed radiogenic effects for both papillary and nonpapillary tumors. Estimates of excess relative risk per Gy (ERR/Gy) were homogeneous by sex (P = 0.35) and number of radiation treatments (P = 0.84) and increased with decreasing age at the time of exposure. The ERR/Gy estimate was significant within ten years of radiation exposure, 2.76 (95% CI, 0.94-4.98), based on 42 exposed cases, and remained elevated 50 years and more after exposure. Finally, exposure to chemotherapy was significantly associated with thyroid cancer, with results supporting a nonsynergistic (additive) association with radiation.
  •  
35.
  •  
36.
  • Ade, Peter, et al. (författare)
  • The Simons Observatory : science goals and forecasts
  • 2019
  • Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
  • Tidskriftsartikel (refereegranskat)abstract
    • The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
  •  
37.
  • Anderson, J. L., et al. (författare)
  • The Fishery Performance Indicators: A Management Tool for Triple Bottom Line Outcomes
  • 2015
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Pursuit of the triple bottom line of economic, community and ecological sustainability has increased the complexity of fishery management; fisheries assessments require new types of data and analysis to guide science-based policy in addition to traditional biological information and modeling. We introduce the Fishery Performance Indicators (FPIs), a broadly applicable and flexible tool for assessing performance in individual fisheries, and for establishing cross-sectional links between enabling conditions, management strategies and triple bottom line outcomes. Conceptually separating measures of performance, the FPIs use 68 individual outcome metrics-coded on a 1 to 5 scale based on expert assessment to facilitate application to data poor fisheries and sectors-that can be partitioned into sectorbased or triple-bottom-line sustainability-based interpretative indicators. Variation among outcomes is explained with 54 similarly structured metrics of inputs, management approaches and enabling conditions. Using 61 initial fishery case studies drawn from industrial and developing countries around the world, we demonstrate the inferential importance of tracking economic and community outcomes, in addition to resource status.
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38.
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39.
  • Arthur, R., et al. (författare)
  • Serum inflammatory markers in relation to prostate cancer severity and death in the Swedish AMORIS study
  • 2018
  • Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 142:11, s. 2254-2262
  • Tidskriftsartikel (refereegranskat)abstract
    • Inflammation is a well-documented driver of cancer development and progression. However, little is known about its role in prostate carcinogenesis. Thus, we examined the association of C-reactive protein (CRP), haptoglobin, albumin and white blood cells (WBC) with prostate cancer (PCa) severity (defined by PCa risk category and clinicopathological characteristics) and progression (defined by PCa death). We selected 8,471 Swedish men with newly diagnosed PCa who had exposure measurements taken approximately 14 years prior to diagnosis. We calculated odds ratio (OR) and 95% confidence interval (CI) for the associations between the inflammatory markers and PCa severity using logistic regression, while Cox proportional hazard regression was used for the associations with overall and PCa death. Serum CRP levels were associated with increased odds of high risk and metastatic PCa, and high PSA levels (20 mu g/L) (OR: 1.29; 95% CI: 1.06-1.56, 1.32; 1.05-1.65 and 1.51; 1.26-1.81, respectively). Similarly, higher haptoglobin levels were associated with increased odds of metastatic PCa, high PSA level and possibly high grade PCa (1.38; 1.10-1.74, 1.50; 1.17-1.93 and 1.25; 1.00-1.56, respectively). Albumin was positively associated with Gleason 4+3 tumour (1.38; 1.02-1.86) and overall death (HRunit increase in log: 1.60; 95% CI: 1.11-2.30), but inversely associated with high risk PCa and high PSA levels (20 mu g/L) (0.71; 0.56-0.89 and 0.72; 0.5 9-0.90). WBC was associated with increased odds of T3-T4 PCa. Except for albumin, none of these markers were associated with PCa death or overall death. Systemic inflammation as early as 14 years prior to diagnosis may influence prostate cancer severity. What's new? High levels of C-reactive protein can presage a particularly malignant prostate cancer, new results show. Cancers certainly arise in the wake of chronic inflammation, but it's not known exactly how markers of inflammation initiate prostate cancer. Here, the authors show that systemic inflammation can worsen the severity of the cancer, even if it occurred long before the cancer's onset. High levels of CRP and haptoglobin, they found, were associated with prostate cancer with high PSA and metastasis. The question remains whether inflammation pushes cancer cells into a more malignant mode, or selects for the more dangerous cells early on.
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40.
  • Benjamin, Daniel J., et al. (författare)
  • Redefine statistical significance
  • 2018
  • Ingår i: Nature Human Behaviour. - : Nature Research (part of Springer Nature). - 2397-3374. ; 2:1, s. 6-10
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
41.
  • Bhogal, P, et al. (författare)
  • Endosaccular flow disruption: where are we now?
  • 2019
  • Ingår i: Journal of neurointerventional surgery. - : BMJ. - 1759-8486 .- 1759-8478. ; 11:10, s. 1024-1035
  • Tidskriftsartikel (refereegranskat)abstract
    • Endosaccular flow disruption is an innovative method of treating wide-necked complex aneurysms. Currently four types of devices have obtained the CE mark for use within Europe. These are the Woven EndoBridge device (WEB), the Luna Aneurysm Embolization System, the Medina Embolic Device (Medtronic), and the Contour Neurovascular System. The aim of this article is to provide an overview of these devices and to summarize the evidence in the literature pertaining to the treatment of intracranial aneurysms with them.
  •  
42.
  • Boccaletti, Anthony, et al. (författare)
  • Fast-moving features in the debris disk around AU Microscopii
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7572, s. 230-
  • Tidskriftsartikel (refereegranskat)abstract
    • In the 1980s, excess infrared emission was discovered around main-sequence stars; subsequent direct-imaging observations revealed orbiting disks of cold dust to be the source(1). These 'debris disks' were thought to be by-products of planet formation because they often exhibited morphological and brightness asymmetries that may result from gravitational perturbation by planets. This was proved to be true for the beta Pictoris system, in which the known planet generates an observable warp in the disk(2-5). The nearby, young, unusually active late-type star AU Microscopii hosts a well-studied edge-on debris disk; earlier observations in the visible and near-infrared found asymmetric localized structures in the form of intensity variations along the midplane of the disk beyond a distance of 20 astronomical units(6-9). Here we report high-contrast imaging that reveals a series of five large-scale features in the southeast side of the disk, at projected separations of 10-60 astronomical units, persisting over intervals of 1-4 years. All these features appear to move away from the star at projected speeds of 4-10 kilometres per second, suggesting highly eccentric or unbound trajectories if they are associated with physical entities. The origin, localization, morphology and rapid evolution of these features are difficult to reconcile with current theories.
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43.
  • Dwaikat, Nidal Yousef, et al. (författare)
  • How does information sharing affect first-tier suppliers' flexibility? : Evidence from the automotive industry in Sweden
  • 2018
  • Ingår i: Production planning & control (Print). - : TAYLOR & FRANCIS LTD. - 0953-7287 .- 1366-5871. ; 29:4, s. 289-300
  • Tidskriftsartikel (refereegranskat)abstract
    • This study addresses the critical research issue of how supplier delivery performance can be enhanced by integrating information sharing into volume and delivery flexibility. This study developed a research model to relate information sharing on demand forecasts and inventory data between original equipment manufacturers (OEMs) and first-tier suppliers. Based on a sample of 52 suppliers from automotive industry in Sweden, partial least squares structural equations modelling (PLS-SEM) was used to assess the model. The results confirm that sharing demand forecasts is a key enabler of supplier volume and delivery flexibility while sharing inventory data is not. The study contributes to enlarging the knowledge about supply chain management from the suppliers' perspective. It also contributes to knowledge by validating the conceptual model and operationalisation of constructs. The study also has practical contribution in which management should focus on improving communication and collaboration practices with OEMs for effective sharing of demand forecasts.
  •  
44.
  • Frykholm, Erik, 1985-, et al. (författare)
  • Test-retest reliability of three strategies to measure quadriceps muscle endurance in people with COPD
  • 2018
  • Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Despite its clinical relevance, there is no consensus on how to measure quadriceps muscle endurance in people with COPD. Moreover, the reliability of available measurement strategies are only partly known.Aim: To determine test-retest reliability and feasibility of isokinetic, isometric and isotonic protocols to assess quadriceps muscle endurance in people with COPD.Method: Fifty nine participants (FEV1 of predicted 55±18%, age 67±8 years) were included and tested in an interday multicentre test-retest design with test occasions separated by 5-9 days. Quadriceps muscle endurance was assessed using isokinetic, isometric and isotonic knee extension protocols controlled by a computerized dynamometer. Relative reliability was determined by intra-class correlation coefficient (ICC)( two-way mixed effects, absolute agreement, single measurement) and absolute reliability by standard error of measurement (SEM).Result: Isokinetic measurements demonstrated very high relative reliability (ICC: [95% confidence interval] 0.97 [0.94-0.99]), and isometric and isotonic demonstrated high relative reliability (0.89 [0.79-0.94], and 0.89 [0.82-0.94], respectively). Mean values across test-retest occasions were 2122 joules, 49 seconds, and 29 repetitions, for isokinetic, isometric and isotonic measurements, respectively. Corresponding SEM values were 150 joules, 7 seconds, and 5 repetitions. All three measurement strategies were feasible with an average time consumption of less than 10 minutes and no major adverse events.Conclusion: The results indicate that isokinetic, isotonic and isometric measurements of quadriceps muscle endurance are reliable and feasible in people with COPD.
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45.
  • Garcia-Larsen, Vanessa, et al. (författare)
  • Is fruit and vegetable intake associated with asthma or chronic rhino-sinusitis in European adults? : Results from the Global Allergy and Asthma Network of Excellence (GA(2)LEN) Survey
  • 2017
  • Ingår i: Clinical and Translational Allergy. - : BIOMED CENTRAL LTD. - 2045-7022. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Fruits and vegetables are rich in compounds with proposed antioxidant, anti-allergic and anti-inflammatory properties, which could contribute to reduce the prevalence of asthma and allergic diseases. Objective: We investigated the association between asthma, and chronic rhino-sinusitis (CRS) with intake of fruits and vegetables in European adults. Methods: A stratified random sample was drawn from the Global Allergy and Asthma Network of Excellence (GA(2)LEN) screening survey, in which 55,000 adults aged 15-75 answered a questionnaire on respiratory symptoms. Asthma score (derived from self-reported asthma symptoms) and CRS were the outcomes of interest. Dietary intake of 22 subgroups of fruits and vegetables was ascertained using the internationally validated GA(2)LEN Food Frequency Questionnaire. Adjusted associations were examined with negative binomial and multiple regressions. Simes procedure was used to control for multiple testing. Results: A total of 3206 individuals had valid data on asthma and dietary exposures of interest. 22.8% reported having at least 1 asthma symptom (asthma score >= 1), whilst 19.5% had CRS. After adjustment for potential confounders, asthma score was negatively associated with intake of dried fruits (beta-coefficient -2.34;95% confidence interval [CI] -4.09,-0.59), whilst CRS was statistically negatively associated with total intake of fruits (OR 0.73; 95% CI 0.55, 0.97). Conversely, a positive association was observed between asthma score and alliums vegetables (adjusted beta-coefficient 0.23; 95% CI 0.06, 0.40). None of these associations remained statistically significant after controlling for multiple testing. Conclusion and clinical relevance: There was no consistent evidence for an association of asthma or CRS with fruit and vegetable intake in this representative sample of European adults.
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46.
  • Haas, Jan, et al. (författare)
  • Atlas of the clinical genetics of human dilated cardiomyopathy
  • 2015
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 36:18, s. 1123-U43
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: We were able to show that targeted Next-Generation Sequencing is well suited to be applied in clinical routine diagnostics, substantiating the ongoing paradigm shift from low- to high-throughput genomics in medicine. By means of our atlas of the genetics of human DCM, we aspire to soon be able to apply our findings to the individual patient with cardiomyopathy in daily clinical practice. Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. Methods and results: In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. Conclusion: This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.
  •  
47.
  • Harrison, John A., et al. (författare)
  • Modeling phosphorus in rivers at the global scale: recent successes, remaining challenges, and near-term opportunities
  • 2019
  • Ingår i: Current Opinion in Environmental Sustainability. - : ELSEVIER SCI LTD. - 1877-3435 .- 1877-3443. ; 36, s. 68-77
  • Forskningsöversikt (refereegranskat)abstract
    • Understanding and mitigating the effects of phosphorus (P) overenrichment of waters globally, including the evaluation of the global Sustainability Development Goals, requires the use of global models. Such models quantitatively link land use, global population growth and climate to aquatic nutrient loading and biogeochemical cycling. Here we describe, compare, and contrast the existing global models capable of predicting P transport by rivers at a global scale. We highlight important insights gained from the development and application of these models, and identify important near-term opportunities for model improvements as well as additional insight to be gained through new model analysis.
  •  
48.
  • Howick, Virginia M., et al. (författare)
  • The Malaria Cell Atlas : Single parasite transcriptomes across the complete Plasmodium life cycle
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 365:6455
  • Tidskriftsartikel (refereegranskat)abstract
    • Malaria parasites adopt a remarkable variety of morphological life stages as they transition through multiple mammalian host and mosquito vector environments. We profiled the single-cell transcriptomes of thousands of individual parasites, deriving the first high-resolution transcriptional atlas of the entire Plasmodium berghei life cycle. We then used our atlas to precisely define developmental stages of single cells from three different human malaria parasite species, including parasites isolated directly from infected individuals. The Malaria Cell Atlas provides both a comprehensive view of gene usage in a eukaryotic parasite and an open-access reference dataset for the study of malaria parasites.
  •  
49.
  • Janssen, Annette B. G., et al. (författare)
  • Exploring, exploiting and evolving diversity of aquatic ecosystem models : a community perspective
  • 2015
  • Ingår i: Aquatic Ecology. - : Springer Science and Business Media LLC. - 1386-2588 .- 1573-5125. ; 49:4, s. 513-548
  • Tidskriftsartikel (refereegranskat)abstract
    • Here, we present a community perspective on how to explore, exploit and evolve the diversity in aquatic ecosystem models. These models play an important role in understanding the functioning of aquatic ecosystems, filling in observation gaps and developing effective strategies for water quality management. In this spirit, numerous models have been developed since the 1970s. We set off to explore model diversity by making an inventory among 42 aquatic ecosystem modellers, by categorizing the resulting set of models and by analysing them for diversity. We then focus on how to exploit model diversity by comparing and combining different aspects of existing models. Finally, we discuss how model diversity came about in the past and could evolve in the future. Throughout our study, we use analogies from biodiversity research to analyse and interpret model diversity. We recommend to make models publicly available through open-source policies, to standardize documentation and technical implementation of models, and to compare models through ensemble modelling and interdisciplinary approaches. We end with our perspective on how the field of aquatic ecosystem modelling might develop in the next 5-10 years. To strive for clarity and to improve readability for non-modellers, we include a glossary.
  •  
50.
  • Jonsson, Stefan, et al. (författare)
  • Identification of sequence variants influencing immunoglobulin levels
  • 2017
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 49:8, s. 1182-1191
  • Tidskriftsartikel (refereegranskat)abstract
    • Immunoglobulins are the effector molecules of the adaptive humoral immune system. In a genome-wide association study of 19,219 individuals, we found 38 new variants and replicated 5 known variants associating with IgA, IgG or IgM levels or with composite immunoglobulin traits, accounted for by 32 loci. Variants at these loci also affect the risk of autoimmune diseases and blood malignancies and influence blood cell development. Notable associations include a rare variant at RUNX3 decreasing IgA levels by shifting isoform proportions (rs188468174[C>T]: P = 8.3 × 10(-55), β = -0.90 s.d.), a rare in-frame deletion in FCGR2B abolishing IgG binding to the encoded receptor (p.Asn106del: P = 4.2 × 10(-8), β = 1.03 s.d.), four IGH locus variants influencing class switching, and ten new associations with the HLA region. Our results provide new insight into the regulation of humoral immunity.
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