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  • 2017
  • swepub:Mat__t
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  • Murari, A., et al. (författare)
  • A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
  • 2024
  • Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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  • Barber, R. M., et al. (författare)
  • Healthcare access and quality index based on mortality from causes amenable to personal health care in 195 countries and territories, 1990-2015 : A novel analysis from the global burden of disease study 2015
  • 2017
  • Ingår i: The Lancet. - : Lancet Publishing Group. - 0140-6736 .- 1474-547X. ; 390:10091, s. 231-266
  • Tidskriftsartikel (refereegranskat)abstract
    • Background National levels of personal health-care access and quality can be approximated by measuring mortality rates from causes that should not be fatal in the presence of effective medical care (ie, amenable mortality). Previous analyses of mortality amenable to health care only focused on high-income countries and faced several methodological challenges. In the present analysis, we use the highly standardised cause of death and risk factor estimates generated through the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to improve and expand the quantification of personal health-care access and quality for 195 countries and territories from 1990 to 2015. Methods We mapped the most widely used list of causes amenable to personal health care developed by Nolte and McKee to 32 GBD causes. We accounted for variations in cause of death certification and misclassifications through the extensive data standardisation processes and redistribution algorithms developed for GBD. To isolate the effects of personal health-care access and quality, we risk-standardised cause-specific mortality rates for each geography-year by removing the joint effects of local environmental and behavioural risks, and adding back the global levels of risk exposure as estimated for GBD 2015. We employed principal component analysis to create a single, interpretable summary measure-the Healthcare Quality and Access (HAQ) Index-on a scale of 0 to 100. The HAQ Index showed strong convergence validity as compared with other health-system indicators, including health expenditure per capita (r=0·88), an index of 11 universal health coverage interventions (r=0·83), and human resources for health per 1000 (r=0·77). We used free disposal hull analysis with bootstrapping to produce a frontier based on the relationship between the HAQ Index and the Socio-demographic Index (SDI), a measure of overall development consisting of income per capita, average years of education, and total fertility rates. This frontier allowed us to better quantify the maximum levels of personal health-care access and quality achieved across the development spectrum, and pinpoint geographies where gaps between observed and potential levels have narrowed or widened over time. Findings Between 1990 and 2015, nearly all countries and territories saw their HAQ Index values improve; nonetheless, the difference between the highest and lowest observed HAQ Index was larger in 2015 than in 1990, ranging from 28·6 to 94·6. Of 195 geographies, 167 had statistically significant increases in HAQ Index levels since 1990, with South Korea, Turkey, Peru, China, and the Maldives recording among the largest gains by 2015. Performance on the HAQ Index and individual causes showed distinct patterns by region and level of development, yet substantial heterogeneities emerged for several causes, including cancers in highest-SDI countries; chronic kidney disease, diabetes, diarrhoeal diseases, and lower respiratory infections among middle-SDI countries; and measles and tetanus among lowest-SDI countries. While the global HAQ Index average rose from 40·7 (95% uncertainty interval, 39·0-42·8) in 1990 to 53·7 (52·2-55·4) in 2015, far less progress occurred in narrowing the gap between observed HAQ Index values and maximum levels achieved; at the global level, the difference between the observed and frontier HAQ Index only decreased from 21·2 in 1990 to 20·1 in 2015. If every country and territory had achieved the highest observed HAQ Index by their corresponding level of SDI, the global average would have been 73·8 in 2015. Several countries, particularly in eastern and western sub-Saharan Africa, reached HAQ Index values similar to or beyond their development levels, whereas others, namely in southern sub-Saharan Africa, the Middle East, and south Asia, lagged behind what geographies of similar development attained between 1990 and 2015. Interpretation This novel extension of the GBD Study shows the untapped potential for personal health-care access and quality improvement across the development spectrum. Amid substantive advances in personal health care at the national level, heterogeneous patterns for individual causes in given countries or territories suggest that few places have consistently achieved optimal health-care access and quality across health-system functions and therapeutic areas. This is especially evident in middle-SDI countries, many of which have recently undergone or are currently experiencing epidemiological transitions. The HAQ Index, if paired with other measures of health-system characteristics such as intervention coverage, could provide a robust avenue for tracking progress on universal health coverage and identifying local priorities for strengthening personal health-care quality and access throughout the world. Copyright © The Author(s). Published by Elsevier Ltd.
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  • 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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  • 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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  • 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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  • 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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  • Axfors, Cathrine, et al. (författare)
  • Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
  • 2021
  • Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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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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  • Ademuyiwa, Adesoji O., et al. (författare)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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18.
  • Griswold, Max G., et al. (författare)
  • Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016
  • 2018
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 392:10152, s. 1015-1035
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older.Methods: Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health.Findings: Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week.Interpretation: Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.
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19.
  • Tiegs, Scott D., et al. (författare)
  • Global patterns and drivers of ecosystem functioning in rivers and riparian zones
  • 2019
  • Ingår i: Science Advances. - Washington : American Association of Advancement in Science. - 2375-2548. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth's biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented "next-generation biomonitoring" by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.
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20.
  • 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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21.
  • Beal, Jacob, et al. (författare)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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22.
  • Stephens, Lucas, et al. (författare)
  • Archaeological assessment reveals Earth’s early transformation through land use
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 365:6456, s. 897-902
  • Tidskriftsartikel (refereegranskat)abstract
    • Humans began to leave lasting impacts on Earth’s surface starting 10,000 to 8000 years ago. Through a synthetic collaboration with archaeologists around the globe, Stephens et al. compiled a comprehensive picture of the trajectory of human land use worldwide during the Holocene (see the Perspective by Roberts). Hunter-gatherers, farmers, and pastoralists transformed the face of Earth earlier and to a greater extent than has been widely appreciated, a transformation that was essentially global by 3000 years before the present.Science, this issue p. 897; see also p. 865Environmentally transformative human use of land accelerated with the emergence of agriculture, but the extent, trajectory, and implications of these early changes are not well understood. An empirical global assessment of land use from 10,000 years before the present (yr B.P.) to 1850 CE reveals a planet largely transformed by hunter-gatherers, farmers, and pastoralists by 3000 years ago, considerably earlier than the dates in the land-use reconstructions commonly used by Earth scientists. Synthesis of knowledge contributed by more than 250 archaeologists highlighted gaps in archaeological expertise and data quality, which peaked for 2000 yr B.P. and in traditionally studied and wealthier regions. Archaeological reconstruction of global land-use history illuminates the deep roots of Earth’s transformation and challenges the emerging Anthropocene paradigm that large-scale anthropogenic global environmental change is mostly a recent phenomenon.
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23.
  • Mayes, Maureen D, et al. (författare)
  • Immunochip analysis identifies multiple susceptibility Loci for systemic sclerosis.
  • 2014
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 94:1, s. 47-61
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.
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24.
  • Arias, M. C., et al. (författare)
  • Permanent Genetic Resources added to Molecular Ecology Resources Database 1 February 2013-31 March 2013
  • 2013
  • Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 13:4, s. 760-762
  • Tidskriftsartikel (refereegranskat)abstract
    • This article documents the addition of 142 microsatellite marker loci to the Molecular Ecology Resources database. Loci were developed for the following species: Agriophyllum squarrosum, Amazilia cyanocephala, Batillaria attramentaria, Fungal strain CTeY1 (Ascomycota), Gadopsis marmoratus, Juniperus phoenicea subsp. turbinata, Liriomyza sativae, Lupinus polyphyllus, Metschnikowia reukaufii, Puccinia striiformis and Xylocopa grisescens. These loci were cross-tested on the following species: Amazilia beryllina, Amazilia candida, Amazilia rutila, Amazilia tzacatl, Amazilia violiceps, Amazilia yucatanensis, Campylopterus curvipennis, Cynanthus sordidus, Hylocharis leucotis, Juniperus brevifolia, Juniperus cedrus, Juniperus osteosperma, Juniperus oxycedrus, Juniperus thurifera, Liriomyza bryoniae, Liriomyza chinensis, Liriomyza huidobrensis and Liriomyza trifolii.
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25.
  • Bossini-Castillo, Lara, et al. (författare)
  • A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort
  • 2011
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:4, s. 638-641
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features. Methods A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers. Results A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively). Conclusions The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.
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26.
  • Muncke, Jane, et al. (författare)
  • Impacts of food contact chemicals on human health : a consensus statement
  • 2020
  • Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Food packaging is of high societal value because it conserves and protects food, makes food transportable and conveys information to consumers. It is also relevant for marketing, which is of economic significance. Other types of food contact articles, such as storage containers, processing equipment and filling lines, are also important for food production and food supply. Food contact articles are made up of one or multiple different food contact materials and consist of food contact chemicals. However, food contact chemicals transfer from all types of food contact materials and articles into food and, consequently, are taken up by humans. Here we highlight topics of concern based on scientific findings showing that food contact materials and articles are a relevant exposure pathway for known hazardous substances as well as for a plethora of toxicologically uncharacterized chemicals, both intentionally and non-intentionally added. We describe areas of certainty, like the fact that chemicals migrate from food contact articles into food, and uncertainty, for example unidentified chemicals migrating into food. Current safety assessment of food contact chemicals is ineffective at protecting human health. In addition, society is striving for waste reduction with a focus on food packaging. As a result, solutions are being developed toward reuse, recycling or alternative (non-plastic) materials. However, the critical aspect of chemical safety is often ignored. Developing solutions for improving the safety of food contact chemicals and for tackling the circular economy must include current scientific knowledge. This cannot be done in isolation but must include all relevant experts and stakeholders. Therefore, we provide an overview of areas of concern and related activities that will improve the safety of food contact articles and support a circular economy. Our aim is to initiate a broader discussion involving scientists with relevant expertise but not currently working on food contact materials, and decision makers and influencers addressing single-use food packaging due to environmental concerns. Ultimately, we aim to support science-based decision making in the interest of improving public health. Notably, reducing exposure to hazardous food contact chemicals contributes to the prevention of associated chronic diseases in the human population.
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27.
  • Acevedo, F., et al. (författare)
  • Degradation of polycyclic aromatic hydrocarbons by free and nanoclay-immobilized manganese peroxidase from Anthracophyllum discolor
  • 2010
  • Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 80:3, s. 271-278
  • Tidskriftsartikel (refereegranskat)abstract
    • Manganese peroxidase (MnP) produced by Anthracophyllum discolor, a Chilean white rot fungus, was immobilized on nanoclay obtained from volcanic soil and its ability to degrade polycyclic aromatic hydrocarbons (PAHs) compared with the free enzyme was evaluated. At the same time, nanoclay characterization was performed.Nanoclay characterization by transmission electronic microscopy showed a particle average size smaller than 100nm. The isoelectric points (IEP) of nanoclay and MnP from A. discolor were 7.0 and 3.7, respectively, as determined by micro electrophoresis migration and preparative isoelectric focusing. Results indicated that 75% of the enzyme was immobilized on the nanoclay through physical adsorption. As compared to the free enzyme, immobilized MnP from A. discolor achieved an improved stability to temperature and pH. The activation energy (Ea) value for immobilized MnP (51.9kJmol -1) was higher than that of the free MnP (34.4kJmol -1).The immobilized enzyme was able to degrade pyrene (>86%), anthracene (>65%), alone or in mixture, and to a less extent fluoranthene (<15.2%) and phenanthrene (<8.6%). Compared to free MnP from A. discolor, the enzyme immobilized on nanoclay enhanced the enzymatic transformation of anthracene in soil.Overall results indicate that nanoclay, a carrier of natural origin, is a suitable support material for MnP immobilization. In addition, immobilized MnP shows an increased stability to high temperature, pH and time storage, as well as an enhanced PAHs degradation efficiency in soil. All these characteristics may suggest the possible use of nanoclay-immobilized MnP from A. discolor as a valuable option for in situ bioremediation purposes. © 2010 Elsevier Ltd.
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28.
  • Bossini-Castillo, Lara, et al. (författare)
  • Confirmation of association of the macrophage migration inhibitory factor gene with systemic sclerosis in a large European population.
  • 2011
  • Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 50, s. 1976-1981
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives. The aim of this study was to confirm the implication of macrophage migration inhibitory factor (MIF) gene in SSc susceptibility or clinical phenotypes in a large European population.Methods. A total of 3800 SSc patients and 4282 healthy controls of white Caucasian ancestry from eight different European countries were included in the study. The MIF -173 single nucleotide polymorphism (SNP) was selected as genetic marker and genotyped using Taqman 5' allelic discrimination assay.Results. The MIF -173 SNP showed association with SSc [P = 0.04, odds ratio (OR) = 1.10, 95% CI 1.00, 1.19]. Analysis of the MIF -173 polymorphism according to SSc clinical phenotype revealed that the frequency of the -173*C allele was significantly higher in the dcSSc group compared with controls (P = 5.30E-03, OR = 1.21, 95% CI 1.07, 1.38). Conversely, the frequency of the MIF -173*C allele was significantly underrepresented in the lcSSc group compared with dcSSc patients, supporting previous findings [(P = 0.04, OR = 0.86, 95% CI 0.75, 0.99); meta-analysis including previous results (P = 0.005, OR = 0.83, 95% CI 0.73, 0.94)].Conclusion. Our results confirm the role of MIF -173 promoter polymorphism in SSc, and provide evidence of a strong association with the dcSSc subgroup of patients. Hence, the MIF -173 variant is confirmed as a promising clinical phenotype genetic marker.
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29.
  • Breznau, Nate, et al. (författare)
  • Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
  • Tidskriftsartikel (refereegranskat)abstract
    • This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
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30.
  • Castillo, Elio Rodrigo D., et al. (författare)
  • Karyotype evolution in Ronderosia grasshoppers (Orthoptera: Acrididae)
  • 2023
  • Ingår i: Zoological Journal of the Linnean Society. - : Oxford University Press. - 0024-4082 .- 1096-3642. ; 198:2, s. 351-367
  • Tidskriftsartikel (refereegranskat)abstract
    • Grasshoppers in the genus Ronderosia (divergence time < 5 Mya) provide a special opportunity to examine the impact of chromosome rearrangements (CRs) in evolution and speciation, because they exhibit extensively rearranged karyotypes involving autosome-autosome and autosome-X chromosomes, the latter leading to the formation of a neo-sex chromosome system (neo-SCS). Despite the potential role of CRs in speciation, the general patterns of karyotype changes resulting from CRs in Ronderosia are still unclear. Here we investigated karyotype evolution in eight Ronderosia species using cytogenetic and phylogenetic models of ancestral character reconstruction. The overall findings suggest a central role for CRs in generating variability in chromosome number and neo-SCS across Ronderosia grasshoppers. It also suggests that incipient species with little morphological change, such as those observed in Ronderosia species, could accumulate marked differences in their karyotypes contributing to post-zygotic reproductive isolation. Besides the evolution of chromosome number in the phylogeny of the genus, chromosome change due to centric fusion is coupled with the divergence pattern observed in the group. While a cladogenetic event could represent a case where karyotypic differences result in speciation, further in-depth genomic studies are needed to better understand how these dramatic restructurings of karyotypes may have occurred.
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31.
  • López-Isac, Elena, et al. (författare)
  • Brief Report : IRF4 Newly Identified as a Common Susceptibility Locus for Systemic Sclerosis and Rheumatoid Arthritis in a Cross-Disease Meta-Analysis of Genome-Wide Association Studies
  • 2016
  • Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 68:9, s. 2338-2344
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc–RA genetic loci have been identified independently. The aim of the current study was to systematically search for new common SSc–RA loci through an interdisease meta–genome-wide association (meta-GWAS) strategy. Methods: The study was designed as a meta-analysis combining GWAS data sets of patients with SSc and patients with RA, using a strategy that allowed identification of loci with both same-direction and opposite-direction allelic effects. The top single-nucleotide polymorphisms were followed up in independent SSc and RA case–control cohorts. This allowed an increase in the sample size to a total of 8,830 patients with SSc, 16,870 patients with RA, and 43,393 healthy controls. Results: This cross-disease meta-analysis of the GWAS data sets identified several loci with nominal association signals (P < 5 × 10−6) that also showed evidence of association in the disease-specific GWAS scans. These loci included several genomic regions not previously reported as shared loci, as well as several risk factors that were previously found to be associated with both diseases. Follow-up analyses of the putatively new SSc–RA loci identified IRF4 as a shared risk factor for these 2 diseases (Pcombined = 3.29 × 10−12). Analysis of the biologic relevance of the known SSc–RA shared loci identified the type I interferon and interleukin-12 signaling pathways as the main common etiologic factors. Conclusion: This study identified a novel shared locus, IRF4, for the risk of SSc and RA, and highlighted the usefulness of a cross-disease GWAS meta-analysis strategy in the identification of common risk loci.
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32.
  • Saeed, Kordo, et al. (författare)
  • The early identification of disease progression in patients with suspected infection presenting to the emergency department : A multi-centre derivation and validation study
  • 2019
  • Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is a lack of validated tools to assess potential disease progression and hospitalisation decisions in patients presenting to the emergency department (ED) with a suspected infection. This study aimed to identify suitable blood biomarkers (MR-proADM, PCT, lactate and CRP) or clinical scores (SIRS, SOFA, qSOFA, NEWS and CRB-65) to fulfil this unmet clinical need. Methods: An observational derivation patient cohort validated by an independent secondary analysis across nine EDs. Logistic and Cox regression, area under the receiver operating characteristic (AUROC) and Kaplan-Meier curves were used to assess performance. Disease progression was identified using a composite endpoint of 28-day mortality, ICU admission and hospitalisation > 10 days. Results: One thousand one hundred seventy-five derivation and 896 validation patients were analysed with respective 28-day mortality rates of 7.1% and 5.0%, and hospitalisation rates of 77.9% and 76.2%. MR-proADM showed greatest accuracy in predicting 28-day mortality and hospitalisation requirement across both cohorts. Patient subgroups with high MR-proADM concentrations (≥ 1.54 nmol/L) and low biomarker (PCT < 0.25 ng/mL, lactate < 2.0 mmol/L or CRP < 67 mg/L) or clinical score (SOFA < 2 points, qSOFA < 2 points, NEWS < 4 points or CRB-65 < 2 points) values were characterised by a significantly longer length of hospitalisation (p < 0.001), rate of ICU admission (p < 0.001), elevated mortality risk (e.g. SOFA, qSOFA and NEWS HR [95%CI], 45.5 [10.0-207.6], 23.4 [11.1-49.3] and 32.6 [9.4-113.6], respectively) and a greater number of disease progression events (p < 0.001), compared to similar subgroups with low MR-proADM concentrations (< 1.54 nmol/L). Increased out-patient treatment across both cohorts could be facilitated using a derivation-derived MR-proADM cut-off of < 0.87 nmol/L (15.0% and 16.6%), with decreased readmission rates and no mortalities. Conclusions: In patients presenting to the ED with a suspected infection, the blood biomarker MR-proADM could most accurately identify the likelihood of further disease progression. Incorporation into an early sepsis management protocol may therefore aid rapid decision-making in order to either initiate, escalate or intensify early treatment strategies, or identify patients suitable for safe out-patient treatment.
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33.
  • Thorell, Kaisa, 1983, et al. (författare)
  • The Helicobacter pylori Genome Project: insights into H. pylori population structure from analysis of a worldwide collection of complete genomes
  • 2023
  • Ingår i: Nature Communications. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics.
  •  
34.
  • Urrutia, C., et al. (författare)
  • Influence of the rhizosphere in a biopurification system on the dissipation of a pesticide mixture
  • 2015
  • Ingår i: Journal of Soil Science and Plant Nutrition. - : Sociedad Chilena de la Ciencia del Suelo. - 0718-9508 .- 0718-9516. ; 15:4, s. 914-927
  • Tidskriftsartikel (refereegranskat)abstract
    • In a biopurification system such as a biobed, the rhizosphere of the grass layer may be a significant factor for promoting pesticide dissipation in the biomixture. The rhizosphere effect of a Lolium perenne, Festuca arundinacea and Trifolium repens mixture on the dissipation of a pesticide combination that was composed of atrazine, chlorpyrifos and isoproturon was studied. The assay was performed using glass pots divided into two separate compartments (root surface and root-free), each filled with an organic biomixture (oat husk, top soil and peat) and contaminated with the pesticide mixture at 5 mg kg-1. Non-planted and noncontaminated pots were also used as controls. The results indicated that there were high atrazine, chlorpyrifos and isoproturon dissipation in the planted pots compared with the unplanted pots. An inverse correlation was found throughout the assay between phenoloxidase activity and residual pesticide (r=0.684 to 0.952). Indeed, fungal biomass was positively correlated with phenoloxidase activity on day 1 (r =0.825) and day 30 (r =0.855). Besides, exudation of oxalic and malic acid in contaminated pots was higher than in the control without pesticides, associated with oxidation of the pesticide mixture in the biomixture of a bioded system. Therefore, the grass layer enhances pesticide removal in biobeds
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35.
  • Wain, Louise V, et al. (författare)
  • Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.
  • 2017
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:3, s. 416-425
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10(-49)), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.
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36.
  • Acevedo, F., et al. (författare)
  • A practical culture technique for enhanced production of manganese peroxidase by Anthracophyllum discolor Sp4
  • 2011
  • Ingår i: Brazilian archives of biology and technology. - 1516-8913 .- 1678-4324. ; 54:6, s. 1175-1186
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, different growth conditions of Anthracophyllum discolor Sp4 including the effect of agitation, additions of lignocellulosic support, inducer and surfactant were evaluated on the MnP production in Kirk medium using a culture system made up of the tubes containing the glass bead. The highest MnP production (1,354 U/L on day 13) was obtained when the medium was supplemented with wheat grain and 0.25 mM MnSO 4 as inducer, under static conditions at 30°C. Two isoenzymes were purified (35 and 38 kDa respectively). MnP presented a maximal activity in the pH range between 4.5 and 5.5, a relatively high temperature tolerance (50°C) and a high catalytic activity for 2,6-dimethoxyphenol and hydrogen peroxide.
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37.
  • Luo, Jiao, et al. (författare)
  • Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease
  • 2023
  • Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 6:5
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia.OBJECTIVE To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention.DESIGN, SETTING, AND PARTICIPANTS This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022.EXPOSURES Genetically determined modifiable risk factors. MAIN OUTCOMES AND MEASURES Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors.RESULTS The EADB-diagnosed cohort included 39106 participants with clinically diagnosed AD and 401577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK Biobank was excluded from the EADB consortium; odds for AD were similar for HDL cholesterol (OR per 1-SD unit increase, 1.08 [95% CI, 1.02-1.15]) and systolic blood pressure after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.23 [95% CI, 1.01-1.50]).CONCLUSIONS AND RELEVANCE This genetic association study found novel genetic associations between high HDL cholesterol concentrations and high systolic blood pressure with higher risk of AD. These findings may inspire new drug targeting and improved prevention implementation.
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38.
  • Oparina, Nina Y., et al. (författare)
  • PXK locus in systemic lupus erythematosus : fine mapping and functional analysis reveals novel susceptibility gene ABHD6
  • 2015
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 74:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To perform fine mapping of the PXK locus associated with systemic lupus erythematosus (SLE) and study functional effects that lead to susceptibility to the disease. Methods Linkage disequilibrium (LD) mapping was conducted by using 1251 SNPs (single nucleotide polymorphism) covering a 862 kb genomic region on 3p14.3 comprising the PXK locus in 1467 SLE patients and 2377 controls of European origin. Tag SNPs and genotypes imputed with IMPUTE2 were tested for association by using SNPTEST and PLINK. The expression QTLs data included three independent datasets for lymphoblastoid cells of European donors: HapMap3, MuTHER and the cross-platform eQTL catalogue. Correlation analysis of eQTLs was performed using Vassarstats. Alternative splicing for the PXK gene was analysed on mRNA from PBMCs. Results Fine mapping revealed long-range LD (>200 kb) extended over the ABHD6, RPP14, PXK, and PDHB genes on 3p14.3. The highly correlated variants tagged an SLE-associated haplotype that was less frequent in the patients compared with the controls (OR=0.89, p=0.00684). A robust correlation between the association with SLE and enhanced expression of ABHD6 gene was revealed, while neither expression, nor splicing alterations associated with SLE susceptibility were detected for PXK. The SNP allele frequencies as well as eQTL pattern analysed in the CEU and CHB HapMap3 populations indicate that the SLE association and the effect on ABHD6 expression are specific to Europeans. Conclusions These results confirm the genetic association of the locus 3p14.3 with SLE in Europeans and point to the ABHD6 and not PXK, as the major susceptibility gene in the region. We suggest a pathogenic mechanism mediated by the upregulation of ABHD6 in individuals carrying the SLE-risk variants.
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39.
  • Tortella, G.R., et al. (författare)
  • Chlorpyrifos degradation in a biomixture of biobed at different maturity stages
  • 2012
  • Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 88:2, s. 224-228
  • Tidskriftsartikel (refereegranskat)abstract
    • The biomixture is a principal element controlling the degradation efficacy of the biobed. The maturity of the biomixture used in the biobed affects its overall performance of the biobed, but this is not well studied yet. The aim of this research was to evaluate the effect of using a typical composition of Swedish biomixture at different maturity stages on the degradation of chlorpyrifos. Tests were made using biomixture at three maturity stages: 0d (BC0), 15d (BC15) and 30d (BC30); chlorpyrifos was added to the biobeds at final concentration of 200, 320 and 480mgkg -1. Chlorpyrifos degradation in the biomixture was monitored over time. Formation of TCP (3,5,6-trichloro-2-pyrinidol) was also quantified, and hydrolytic and phenoloxidase activities measured. The biomixture efficiently degraded chlorpyrifos (degradation efficiency >50%) in all the evaluated maturity stages. However, chlorpyrifos degradation decreased with increasing concentrations of the pesticide. TCP formation occurred in all biomixtures, but a major accumulation was observed in BC30. Significant differences were found in both phenoloxidase and hydrolytic activities in the three maturity stages of biomixture evaluated. Also, these two biological activities were affected by the increase in pesticide concentration. In conclusion, our results demonstrated that chlorpyrifos can be degraded efficiently in all the evaluated maturity stages. © 2012 Elsevier Ltd.
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40.
  • Acevedo, F., et al. (författare)
  • Degradation of polycyclic aromatic hydrocarbons by the Chilean white-rot fungus Anthracophyllum discolor
  • 2011
  • Ingår i: Journal of Hazardous Materials. - : Elsevier BV. - 0304-3894 .- 1873-3336. ; 185:1, s. 212-219
  • Tidskriftsartikel (refereegranskat)abstract
    • The degradation of three- and four-ring polycyclic aromatic hydrocarbons (PAHs) in Kirk medium by Anthracophyllum discolor, a white-rot fungus isolated from the forest of southern Chile, was evaluated. In addition, the removal efficiency of three-, four- and five-ring PAHs in contaminated soil bioaugmented with A. discolor in the absence and presence of indigenous soil microorganisms was investigated. Production of lignin-degrading enzymes and PAH mineralization in the soil were also determined. A. discolor was able to degrade PAHs in Kirk medium with the highest removal occurring in a PAH mixture, suggesting synergistic effects between PAHs or possible cometabolism. A high removal capability for phenanthrene (62%), anthracene (73%), fluoranthene (54%), pyrene (60%) and benzo(a)pyrene (75%) was observed in autoclaved soil inoculated with A. discolor in the absence of indigenous microorganisms, associated with the production of manganese peroxidase (MnP). The metabolites found in the PAH degradation were anthraquinone, phthalic acid, 4-hydroxy-9-fluorenone, 9-fluorenone and 4,5-dihydropyrene. A. discolor was able to mineralize 9% of the phenanthrene. In non-autoclaved soil, the inoculation with A. discolor did not improve the removal efficiency of PAHs. Suitable conditions must be found to promote a successful fungal bioaugmentation in non-autoclaved soils. © 2010 Elsevier B.V.
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41.
  • Aitken, Leanne M., et al. (författare)
  • What is the relationship between elements of ICU treatment and memories after discharge in adult ICU survivors?
  • 2016
  • Ingår i: Australian Critical Care. - : Elsevier BV. - 1036-7314 .- 1878-1721. ; 29:1, s. 5-14
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesPatients admitted to an intensive care unit (ICU) often experience distressing memories during recovery that have been associated with poor psychological and cognitive outcomes. The aim of this literature review was to synthesise the literature reporting on relationships between elements of ICU treatment and memories after discharge in adult ICU survivors.Review method usedIntegrative review methods were used to systematically search, select, extract, appraise and summarise current knowledge from the available research and identify gaps in the literature.Data sourcesThe following electronic databases were systematically searched: PubMed, Ovid EMBASE, EBSCOhost CINAHL, PsycINFO and Cochrane Central Register of Controlled Trials. Additional studies were identified through searches of bibliographies. Original quantitative research articles written in English that were published in peer-review journals were included.Review methodsData extracted from studies included authors, study aims, population, sample size and characteristics, methods, ICU treatments, ICU memory definitions, data collection strategies and findings. Study quality assessment was based on elements of the Critical Appraisal Skills Programme using the checklists developed for randomised controlled trials and cohort studies.ResultsFourteen articles containing data from 13 studies met the inclusion criteria and were included in the final analysis. The relatively limited evidence about the association between elements of ICU treatment and memories after ICU discharge suggest that deep sedation, corticoids and administration of glucose 50% due to hypoglycaemia contribute to the development of delusional memories and amnesia of ICU stay.ConclusionsThe body of literature on the relationship between elements of ICU treatment and memories after ICU discharge is small and at its early stages. Larger studies using rigorous study design are needed in order to evaluate the effects of different elements of ICU treatment on the development of memories of the ICU during recovery.
  •  
42.
  • Bossini-Castillo, Lara, et al. (författare)
  • KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor
  • 2012
  • Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 14:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort. Methods: The 2,343 SSc cases (179 PAH positive, confirmed by right-heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single-nucleotide polymorphism (SNP) was genotyped by using a TaqMan SNP genotyping assay. Results: Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (for example, limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH-positive group. The comparison of PAH-positive patients with PAH-negative patients showed no significant differences among patients. Conclusions: Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients.
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43.
  • Cornejo-Castillo, Francisco M., et al. (författare)
  • UCYN-A3, a newly characterized open ocean sublineage of the symbiotic N2-fixing cyanobacterium Candidatus Atelocyanobacterium thalassa
  • 2019
  • Ingår i: Environmental Microbiology. - : Wiley-Blackwell. - 1462-2912 .- 1462-2920. ; 21:1, s. 111-124
  • Tidskriftsartikel (refereegranskat)abstract
    • The symbiotic unicellular cyanobacterium Candidatus Atelocyanobacterium thalassa (UCYN-A) is one of the most abundant and widespread nitrogen (N-2)-fixing cyanobacteria in the ocean. Although it remains uncultivated, multiple sublineages have been detected based on partial nitrogenase (nifH) gene sequences, including the four most commonly detected sublineages UCYN-A1, UCYN-A2, UCYN-A3 and UCYN-A4. However, very little is known about UCYN-A3 beyond the nifH sequences from nifH gene diversity surveys. In this study, single cell sorting, DNA sequencing, qPCR and CARD-FISH assays revealed discrepancies involving the identification of sublineages, which led to new information on the diversity of the UCYN-A symbiosis. 16S rRNA and nifH gene sequencing on single sorted cells allowed us to identify the 16S rRNA gene of the uncharacterized UCYN-A3 sublineage. We designed new CARD-FISH probes that allowed us to distinguish and observe UCYN-A2 in a coastal location (SIO Pier; San Diego) and UCYN-A3 in an open ocean location (Station ALOHA; Hawaii). Moreover, we reconstructed about 13% of the UCYN-A3 genome from Tara Oceans metagenomic data. Finally, our findings unveil the UCYN-A3 symbiosis in open ocean waters suggesting that the different UCYN-A sublineages are distributed along different size fractions of the plankton defined by the cell-size ranges of their prymnesiophyte hosts.
  •  
44.
  • Diez, Cristina M., et al. (författare)
  • Influence of novel lignocellulosic residues in a biobed biopurification system on the degradation of pesticides applied in repeatedly high doses
  • 2013
  • Ingår i: Electronic Journal of Biotechnology. - : Elsevier BV. - 0717-3458. ; 16:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The biobed is a simple biopurification system used to prevent the point-source pesticide contamination that occurs at farm level. The typical composition of the biomixture used in this system is soil, peat and straw in volumetric proportions of 1:1:2. The principal component is straw due to its positive effects on biological activity and thus pesticide degradation. However, access to straw can be limited in some regions, so it must be replaced by other more readily available lignocellulosic residues. Results: Therefore, two alternate lignocellulosic materials (barley husks and pine sawdust) were evaluated as partial substitutes for straw. The degradation of a repeatedly applied mixture of six pesticides by these alternates was assessed. The microbial respiration and fluorescein diacetate (FDA) hydrolysis activity were also assessed. The results showed that the highest degradation efficiency was found in mixtures containing straw and barley husks. Each biomixtures tested achieved a high degradation (50 to 90%) of all the pesticides used except iprodione. Repeated applications of pesticides resulted in a slowing of the degradation rate of all pesticide types in all biomixtures. FDA activity and microbial respiration were higher in the biomixtures containing barley husks and straw compared to the mixture with pine sawdust, a result consistent with the pesticide degradations observed. Conclusions: This paper demonstrates that the straw in the traditional biomixture can be partially replaced by other lignocellulosic materials to efficiently degrade a mixture of pesticides, even when the pesticides are added in successive applications and high concentrations.
  •  
45.
  • Frede, Annika, et al. (författare)
  • B cell expansion hinders the stroma-epithelium regenerative cross talk during mucosal healing
  • 2022
  • Ingår i: Immunity. - : Elsevier BV. - 1074-7613 .- 1097-4180. ; 55:12, s. 2336-
  • Tidskriftsartikel (refereegranskat)abstract
    • Therapeutic promotion of intestinal regeneration holds great promise, but defining the cellular mechanisms that influence tissue regeneration remains an unmet challenge. To gain insight into the process of mucosal healing, we longitudinally examined the immune cell composition during intestinal damage and regeneration. B cells were the dominant cell type in the healing colon, and single-cell RNA sequencing (scRNA-seq) re-vealed expansion of an IFN-induced B cell subset during experimental mucosal healing that predominantly located in damaged areas and associated with colitis severity. B cell depletion accelerated recovery upon injury, decreased epithelial ulceration, and enhanced gene expression programs associated with tissue re-modeling. scRNA-seq from the epithelial and stromal compartments combined with spatial transcriptomics and multiplex immunostaining showed that B cells decreased interactions between stromal and epithelial cells during mucosal healing. Activated B cells disrupted the epithelial-stromal cross talk required for orga-noid survival. Thus, B cell expansion during injury impairs epithelial-stromal cell interactions required for mucosal healing, with implications for the treatment of IBD.
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46.
  •  
47.
  • Kabir, Maryam M, et al. (författare)
  • Effect of the N-methylmorpholine-N-oxide (NMMO) pretreatment on anaerobic digestion of forest residues
  • 2013
  • Ingår i: BioResources. - : North Carolina State University: College of Natural Resources. - 1930-2126. ; 8:4, s. 5409-5423
  • Tidskriftsartikel (refereegranskat)abstract
    • Pretreatment of forest residues using N - methylmorpholine - N - oxide (NMMO or NMO) prior to anaer obic digestion was investigated , where the effects of particle size, NMMO concentration , and pretreatment time were the primary focus. The pretreatments were carried out on forest residues; with different particle size s of 2, 4 and 8 mm , at 120 °C for 3, 7 , and 15 h in two different modes of NMMO - treatment : dissolution by 85% NMMO and swelling without dissolution using 75% NMMO solution in water . The pretreatment process led to minor changes in the composition of the forest residues . The best improvement in methane yield of the forest residues was achieved by pretreatment using 85% NMMO for 15 h at 120 °C. This treatment resulted in 0.1 7 Nm 3 /kg VS methane yield , which corresponds to 83 % of the expected theoretical yield of carbohydrates present in the material. Additionally, the accumulated methane yield and the rate of the methane production were highly affected by the amounts of remaining NMMO when it was not well separated during the washing and filtration step s after the treatment. The p resence o f concentrations even as low as 0.008 % NMMO resulted in a decrease in the final methan e yield by 45% , while the presence of 1% of this solvent in the digester completely terminated the anaerobic digestion process.
  •  
48.
  • Kabir, Maryam M., et al. (författare)
  • Effect of the N-methylmorpholine-N-oxide (NMMO) pretreatment on anaerobic digestion of forest residues
  • 2013
  • Ingår i: BioResources. - : BioResources. - 1930-2126. ; 8:4, s. 5409-5423
  • Tidskriftsartikel (refereegranskat)abstract
    • Pretreatment of forest residues using N-methylmorpholine-N-oxide (NMMO or NMO) prior to anaerobic digestion was investigated, where the effects of particle size, NMMO concentration, and pretreatment time were the primary focus. The pretreatments were carried out on forest residues; with different particle sizes of 2, 4 and 8 mm, at 120 °C for 3, 7, and 15 h in two different modes of NMMO-treatment: dissolution by 85% NMMO and swelling without dissolution using 75% NMMO solution in water. The pretreatment process led to minor changes in the composition of the forest residues. The best improvement in methane yield of the forest residues was achieved by pretreatment using 85% NMMO for 15 h at 120 °C. This treatment resulted in 0.17 Nm3/kg VS methane yield, which corresponds to 83% of the expected theoretical yield of carbohydrates present in the material. Additionally, the accumulated methane yield and the rate of the methane production were highly affected by the amounts of remaining NMMO when it was not well separated during the washing and filtration steps after the treatment. The presence of concentrations even as low as 0.008% NMMO resulted in a decrease in the final methane yield by 45%, while the presence of 1% of this solvent in the digester completely terminated the anaerobic digestion process.
  •  
49.
  • Karah, Nabil, et al. (författare)
  • The acinetobacter baumannii website (ab-web) : a multidisciplinary knowledge hub, communication platform, and workspace
  • 2023
  • Ingår i: FEMS Microbes. - : Oxford University Press. - 2633-6685. ; 4
  • Forskningsöversikt (refereegranskat)abstract
    • Acinetobacter baumannii is a Gram-negative bacterium increasingly implicated in hospital-acquired infections and outbreaks. Effective prevention and control of such infections are commonly challenged by the frequent emergence of multidrug-resistant strains. Here we introduce Ab-web (https://www.acinetobacterbaumannii.no), the first online platform for sharing expertise on A. baumannii. Abweb is a species-centric knowledge hub, initially with 10 articles organized into two main sections, 'Overview' and 'Topics', and three themes, 'epidemiology', 'antibiotic resistance', and 'virulence'. The 'workspace' section provides a spot for colleagues to collaborate, build, and manage joint projects. Ab-web is a community-driven initiative amenable to constructive feedback and new ideas.
  •  
50.
  • Lescano, M R, et al. (författare)
  • Glyphosate and aminomethylphosphonic acid degradation in biomixtures based on alfalfa straw, wheat stubble and river waste.
  • 2018
  • Ingår i: Journal of Environmental Management. - : Elsevier BV. - 0301-4797 .- 1095-8630. ; 228, s. 451-457
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the work was to evaluate novel biomixtures for their use on biopurification systems (BPS) in Argentina also called biobeds. Glyphosate and aminomethylphosphonic acid (AMPA) degradation was evaluated on biomixtures containing local materials: alfalfa straw (As), wheat stubble (Ws), river waste (Rw) and soil. Glyphosate, AMPA concentrations and biological activity were followed with time. Soil was used as control. Glyphosate initial concentration was 1000 mg kg-1. Glyphosate disappeared almost completely after 63 days in all tested biomixtures. For Ws, WsRw and AsRw glyphosate degradation was around 99% and for As 85%. The biomixture Ws showed the highest glyphosate degradation rate. In all cases AMPA was formed and degraded to concentrations between 60 and 100 mg kg-1. In the control with only soil, glyphosate was degraded 53% and AMPA concentration at the end of the test was 438 mg kg-1. We conclude that alfalfa straw, wheat stubble and river waste are local materials that can be used in the preparation of biomixtures since they showed higher glyphosate degradation capacity and less AMPA accumulation compared to the soil alone. Also, the presence of river waste did enhance the water retention capacity.
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