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1.
  • Stanaway, Jeffrey D., et al. (author)
  • Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • In: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
  • Journal article (peer-reviewed)abstract
    • Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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3.
  • Lozano, Rafael, et al. (author)
  • Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • In: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
  • Journal article (peer-reviewed)abstract
    • Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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4.
  • Griswold, Max G., et al. (author)
  • Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016
  • 2018
  • In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 392:10152, s. 1015-1035
  • Journal article (peer-reviewed)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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5.
  • Mahajan, Anubha, et al. (author)
  • Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
  • 2022
  • In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
  • Journal article (peer-reviewed)abstract
    • We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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6.
  • Abele, H., et al. (author)
  • Particle physics at the European Spallation Source
  • 2023
  • In: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 1023, s. 1-84
  • Research review (peer-reviewed)abstract
    • Presently under construction in Lund, Sweden, the European Spallation Source (ESS) will be the world’s brightest neutron source. As such, it has the potential for a particle physics program with a unique reach and which is complementary to that available at other facilities. This paper describes proposed particle physics activities for the ESS. These encompass the exploitation of both the neutrons and neutrinos produced at the ESS for high precision (sensitivity) measurements (searches).
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7.
  • Artigas Soler, María, et al. (author)
  • Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
  • 2011
  • In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
  • Journal article (peer-reviewed)abstract
    • Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
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8.
  • Marouli, Eirini, et al. (author)
  • Rare and low-frequency coding variants alter human adult height
  • 2017
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
  • Journal article (peer-reviewed)abstract
    • Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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9.
  • Murray, Christopher J. L., et al. (author)
  • Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • In: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
  • Journal article (peer-reviewed)abstract
    • Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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10.
  • Blösch, Günter, et al. (author)
  • Twenty-three unsolved problems in hydrology (UPH) - a community perspective
  • 2019
  • In: Hydrological Sciences Journal. - : Informa UK Limited. - 0262-6667 .- 2150-3435. ; 64:10, s. 1141-1158
  • Journal article (peer-reviewed)abstract
    • This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.
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11.
  • Loth, Daan W, et al. (author)
  • Genome-wide association analysis identifies six new loci associated with forced vital capacity
  • 2014
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46, s. 669-677
  • Journal article (peer-reviewed)abstract
    • Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
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12.
  • Sakornsakolpat, Phuwanat, et al. (author)
  • Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
  • 2019
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 494-505
  • Journal article (peer-reviewed)abstract
    • Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 x 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
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13.
  • Feigin, Valery L., et al. (author)
  • Global, regional, and national burden of neurological disorders, 1990–2016 : a systematic analysis for the Global Burden of Disease Study 2016
  • 2019
  • In: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:5, s. 459-480
  • Journal article (peer-reviewed)abstract
    • Background: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.Methods: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach.Findings: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable).Interpretation: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies.Funding: Bill & Melinda Gates Foundation.
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14.
  • Feigin, Valery L., et al. (author)
  • Global, regional, and national burden of stroke and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019
  • 2021
  • In: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 20:10, s. 795-820
  • Journal article (peer-reviewed)abstract
    • Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12.2 million (95% UI 11.0-13.6) incident cases of stroke, 101 million (93.2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6.55 million (6.00-7.02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11.6% [10.8-12.2] of total deaths) and the third-leading cause of death and disability combined (5.7% [5.1-6.2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70.0% (67.0-73.0), prevalent strokes increased by 85.0% (83.0-88.0), deaths from stroke increased by 43.0% (31.0-55.0), and DALYs due to stroke increased by 32.0% (22.0-42.0). During the same period, age-standardised rates of stroke incidence decreased by 17.0% (15.0-18.0), mortality decreased by 36.0% (31.0-42.0), prevalence decreased by 6.0% (5.0-7.0), and DALYs decreased by 36.0% (31.0-42.0). However, among people younger than 70 years, prevalence rates increased by 22.0% (21.0-24.0) and incidence rates increased by 15.0% (12.0-18.0). In 2019, the age-standardised stroke-related mortality rate was 3.6 (3.5-3.8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3.7 (3.5-3.9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62.4% of all incident strokes in 2019 (7.63 million [6.57-8.96]), while intracerebral haemorrhage constituted 27.9% (3.41 million [2.97-3.91]) and subarachnoid haemorrhage constituted 9.7% (1.18 million [1.01-1.39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79.6 million [67.7-90.8] DALYs or 55.5% [48.2-62.0] of total stroke DALYs), high body-mass index (34.9 million [22.3-48.6] DALYs or 24.3% [15.7-33.2]), high fasting plasma glucose (28.9 million [19.8-41.5] DALYs or 20.2% [13.8-29.1]), ambient particulate matter pollution (28.7 million [23.4-33.4] DALYs or 20.1% [16.6-23.0]), and smoking (25.3 million [22.6-28.2] DALYs or 17.6% [16.4-19.0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.
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15.
  • Micah, Angela E., et al. (author)
  • Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
  • 2021
  • In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
  • Research review (peer-reviewed)abstract
    • Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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16.
  • Kim, Min Seo, et al. (author)
  • Global burden of peripheral artery disease and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019
  • 2023
  • In: The Lancet Global Health. - : Elsevier. - 2214-109X. ; 11:10, s. E1553-E1565
  • Journal article (peer-reviewed)abstract
    • Background: Peripheral artery disease is a growing public health problem. We aimed to estimate the global disease burden of peripheral artery disease, its risk factors, and temporospatial trends to inform policy and public measures.Methods: Data on peripheral artery disease were modelled using the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019 database. Prevalence, disability-adjusted life years (DALYs), and mortality estimates of peripheral artery disease were extracted from GBD 2019. Total DALYs and age-standardised DALY rate of peripheral artery disease attributed to modifiable risk factors were also assessed.Findings: In 2019, the number of people aged 40 years and older with peripheral artery disease was 113 million (95% uncertainty interval [UI] 99 center dot 2-128 center dot 4), with a global prevalence of 1 center dot 52% (95% UI 1 center dot 33-1 center dot 72), of which 42 center dot 6% was in countries with low to middle Socio-demographic Index (SDI). The global prevalence of peripheral artery disease was higher in older people, (14 center dot 91% [12 center dot 41-17 center dot 87] in those aged 80-84 years), and was generally higher in females than in males. Globally, the total number of DALYs attributable to modifiable risk factors in 2019 accounted for 69 center dot 4% (64 center dot 2-74 center dot 3) of total peripheral artery disease DALYs. The prevalence of peripheral artery disease was highest in countries with high SDI and lowest in countries with low SDI, whereas DALY and mortality rates showed U-shaped curves, with the highest burden in the high and low SDI quintiles.Interpretation: The total number of people with peripheral artery disease has increased globally from 1990 to 2019. Despite the lower prevalence of peripheral artery disease in males and low-income countries, these groups showed similar DALY rates to females and higher-income countries, highlighting disproportionate burden in these groups. Modifiable risk factors were responsible for around 70% of the global peripheral artery disease burden. Public measures could mitigate the burden of peripheral artery disease by modifying risk factors.
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17.
  • Nichols, Emma, et al. (author)
  • Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016
  • 2019
  • In: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:1, s. 88-106
  • Journal article (peer-reviewed)abstract
    • Background: The number of individuals living with dementia is increasing, negatively affecting families, communities, and health-care systems around the world. A successful response to these challenges requires an accurate understanding of the dementia disease burden. We aimed to present the first detailed analysis of the global prevalence, mortality, and overall burden of dementia as captured by the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, and highlight the most important messages for clinicians and neurologists.Methods: GBD 2016 obtained data on dementia from vital registration systems, published scientific literature and surveys, and data from health-service encounters on deaths, excess mortality, prevalence, and incidence from 195 countries and territories from 1990 to 2016, through systematic review and additional data-seeking efforts. To correct for differences in cause of death coding across time and locations, we modelled mortality due to dementia using prevalence data and estimates of excess mortality derived from countries that were most likely to code deaths to dementia relative to prevalence. Data were analysed by standardised methods to estimate deaths, prevalence, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs; computed as the sum of YLLs and YLDs), and the fractions of these metrics that were attributable to four risk factors that met GBD criteria for assessment (high body-mass index [BMI], high fasting plasma glucose, smoking, and a diet high in sugarsweetened beverages).Findings: In 2016, the global number of individuals who lived with dementia was 43.8 million (95% uncertainty interval [UI] 3 7. 8-51.0), increased from 20.2 million (17. 4-23 5) in 1990. This increase of 117% (95% UI 114-121) contrasted with a minor increase in age-standardised prevalence of 1.7% (1.0-2.4), from 701 cases (95% UI 602-815) per 100 000 population in 1990 to 712 cases (614-828) per 100 000 population in 2016. More women than men had dementia in 2016 (27.0 million, 95% UI 23 .3-31. 4, vs 16.8 million, 14.4-19.6), and dementia was the fifth leading cause of death globally, accounting for 2.4 million (95% UI 2.1-2.8) deaths. Overall, 28.8 million (95% UI 24. 5-34. 0) DALYs were attributed to dementia; 6.4 million (95% UI 3 .4-10. 5) of these could be attributed to the modifiable GBD risk factors of high BMI, high fasting plasma glucose, smoking, and a high intake of sugar-sweetened beverages.Interpretation: The global number of people living with dementia more than doubled from 1990 to 2016, mainly due to increases in population ageing and growth. Although differences in coding for causes of death and the heterogeneity in case-ascertainment methods constitute major challenges to the estimation of the burden of dementia, future analyses should improve on the methods for the correction of these biases. Until breakthroughs are made in prevention or curative treatment, dementia will constitute an increasing challenge to health-care systems worldwide.
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18.
  • Brandsma, Arianne M., et al. (author)
  • Potent Fc Receptor Signaling by IgA Leads to Superior Killing of Cancer Cells by Neutrophils Compared to IgG
  • 2019
  • In: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 10
  • Journal article (peer-reviewed)abstract
    • Antibody therapy of cancer is increasingly used in the clinic and has improved patient's life expectancy. Except for immune checkpoint inhibition, the mode of action of many antibodies is to recognize overexpressed or specific tumor antigens and initiate either direct F(ab')(2)-mediated tumor cell killing, or Fc-mediated effects such as complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity/phagocytosis (ADCC/P) after binding to activating Fc receptors. All antibodies used in the clinic are of the IgG isotype. The IgA isotype can, however, also elicit powerful anti-tumor responses through engagement of the activating Fc receptor for monomeric IgA (Fc alpha RI). In addition to monocytes, macrophages and eosinophils as Fc alpha RI expressing immune cells, neutrophils are especially vigorous in eliminating IgA opsonized tumor cells. However, with IgG as single agent it appears almost impossible to activate neutrophils efficiently, as we have visualized by live cell imaging of tumor cell killing. In this study, we investigated Fc receptor expression, binding and signaling to clarify why triggering of neutrophils by IgA is more efficient than by IgG. Fc alpha RI expression on neutrophils is similar to 2 times and similar to 20 times lower than that of Fc gamma receptors Fc gamma RIIa and Fc gamma RIIIb, but still, binding of neutrophils to IgA- or IgG-coated surfaces was similar. In addition, our data suggest that IgA- mediated binding of neutrophils is more stable compared to IgG. IgA engagement of neutrophils elicited stronger Fc receptor signaling than IgG as indicated by measuring the p-ERK signaling molecule. We propose that the higher stoichiometry of IgA to the Fc alpha R/FcR gamma-chain complex, activating four ITAMs (Immunoreceptor Tyrosine-based Activating Motifs) compared to a single ITAM for Fc gamma RIIa, combined with a possible decoy role of the highly expressed Fc gamma RIIIb, explains why IgA is much better than IgG at triggering tumor cell killing by neutrophils. We anticipate that harnessing the vast population of neutrophils by the use of IgA monoclonal antibodies can be a valuable addition to the growing arsenal of antibody-based therapeutics for cancer treatment.
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19.
  • Dai, Qile, et al. (author)
  • OTTERS: a powerful TWAS framework leveraging summary-level reference data
  • 2023
  • In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
  • Journal article (peer-reviewed)abstract
    • Most existing TWAS tools require individual-level eQTL reference data and thus are not applicable to summary-level reference eQTL datasets. The development of TWAS methods that can harness summary-level reference data is valuable to enable TWAS in broader settings and enhance power due to increased reference sample size. Thus, we develop a TWAS framework called OTTERS (Omnibus Transcriptome Test using Expression Reference Summary data) that adapts multiple polygenic risk score (PRS) methods to estimate eQTL weights from summary-level eQTL reference data and conducts an omnibus TWAS. We show that OTTERS is a practical and powerful TWAS tool by both simulations and application studies.
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20.
  • Hancock, Dana B, et al. (author)
  • Genome-Wide Joint Meta-Analysis of SNP and SNP-by-Smoking Interaction Identifies Novel Loci for Pulmonary Function
  • 2012
  • In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 8:12, s. e1003098-
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV1), and its ratio to forced vital capacity (FEV1/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV1 and FEV1/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest PJMA = 5.00×10−11), HLA-DQB1 and HLA-DQA2 (smallest PJMA = 4.35×10−9), and KCNJ2 and SOX9 (smallest PJMA = 1.28×10−8) were associated with FEV1/FVC or FEV1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.
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21.
  • Sharifi, Sina, et al. (author)
  • Electron Beam Sterilization of Poly(Methyl Methacrylate)-Physicochemical and Biological Aspects
  • 2021
  • In: Macromolecular Bioscience. - : John Wiley & Sons. - 1616-5187 .- 1616-5195. ; 21:4
  • Journal article (peer-reviewed)abstract
    • Electron beam (E-beam) irradiation is an attractive and efficient method for sterilizing clinically implantable medical devices made of natural and/or synthetic materials such as poly(methyl methacrylate) (PMMA). As ionizing irradiation can affect the physicochemical properties of PMMA, understanding the consequences of E-beam sterilization on the intrinsic properties of PMMA is vital for clinical implementation. A detailed assessment of the chemical, optical, mechanical, morphological, and biological properties of medical-grade PMMA after E-beam sterilization at 25 and 50 kiloGray (kGy) is reported. Fourier transform infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry studies indicate that E-beam irradiation has minimal effect on the chemical properties of the PMMA at these doses. While 25 kGy irradiation does not alter the mechanical and optical properties of the PMMA, 50 kGy reduces the flexural strength and transparency by 10% and 2%, respectively. Atomic force microscopy demonstrates that E-beam irradiation reduces the surface roughness of PMMA in a dose dependent manner. Live-Dead, AlamarBlue, immunocytochemistry, and complement activation studies show that E-beam irradiation up to 50 kGy has no adverse effect on the biocompatibility of the PMMA. These findings suggest that E-beam irradiation at 25 kGy may be a safe and efficient alternative for PMMA sterilization.
  •  
22.
  • Sharifi, Sina, et al. (author)
  • Sputter Deposition of Titanium on Poly(Methyl Methacrylate) Enhances Corneal Biocompatibility
  • 2020
  • In: Translational Vision Science & Technology. - : Association for Research in Vision and Ophthalmology. - 2164-2591. ; 9:13, s. 1-14
  • Journal article (peer-reviewed)abstract
    • Purpose: To evaluate titanium (Ti) sputtering of the poly(methyl methacrylate) (PMMA) stem of the Boston Keratoprosthesis (BK) as a method to enhance interfacial adhesion between the PMMA and the recipient corneal tissue. Methods: PMMA specimens were plasma treated with Ar/O-2 and coated with Ti using a DC magnetron sputtering instrument. The topography and hydrophilicity of the surfaces were characterized using atomic force microscopy and a water contact angle instrument, respectively. Scratch hardness and adhesion of the Ti film were measured using a mechanical tester. Biocompatibility assessments were performed using cultured human corneal fibroblasts and whole blood ex vivo. The optical quality of the Ti sputtered BK was evaluated using a custom-made optical bench. Results: By contact angle studies, the Ti coating improved PMMA hydrophilicity to match that of medical-grade Ti (Ti-6Al-4V-ELI). Ti sputtering of contact surfaces resulted in a plate-like morphology with increased surface roughness, without impacting the transparency of the BK optical component. Scratch testing indicated that the mechanical behavior of the Ti coating was similar to that of casted Ti, and the coating was stable in pull-off adhesion testing. Sputtered Ti film was highly biocompatible based on tests of cell viability, adhesion, proliferation, differentiation, collagen deposition, and keratocan expression, the properties of which exceeded those of uncoated PMMA and did not induce increased complement activation. Conclusions: Titanium coating of the BK stem generated a mechanically and biologically favorable interface, which may help to enhance corneal stromal adhesion and biocompatibility. Translational Relevance: Improving the biocompatibility of the BK PMMA stem may improve long-term outcomes of implantation.
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23.
  • Sharifi, Sina, et al. (author)
  • Tuning gelatin-based hydrogel towards bioadhesive ocular tissue engineering applications
  • 2021
  • In: Bioactive Materials. - : Elsevier. - 2452-199X. ; 6:11, s. 3947-3961
  • Journal article (peer-reviewed)abstract
    • Gelatin based adhesives have been used in the last decades in different biomedical applications due to the excellent biocompatibility, easy processability, transparency, non-toxicity, and reasonable mechanical properties to mimic the extracellular matrix (ECM). Gelatin adhesives can be easily tuned to gain different viscoelastic and mechanical properties that facilitate its ocular application. We herein grafted glycidyl methacrylate on the gelatin backbone with a simple chemical modification of the precursor, utilizing epoxide ring-opening reactions and visible light-crosslinking. This chemical modification allows the obtaining of an elastic protein-based hydrogel (GELGYM) with excellent biomimetic properties, approaching those of the native tissue. GELGYM can be modulated to be stretched up to 4 times its initial length and withstand high tensile stresses up to 1.95 MPa with compressive strains as high as 80% compared to Gelatin-methacryloyl (GeIMA), the most studied derivative of gelatin used as a bioadhesive. GELGYM is also highly biocompatible and supports cellular adhesion, proliferation, and migration in both 2 and 3-dimensional cell-cultures. These characteristics along with its super adhesion to biological tissues such as cornea, aorta, heart, muscle, kidney, liver, and spleen suggest widespread applications of this hydrogel in many biomedical areas such as transplantation, tissue adhesive, wound dressing, bioprinting, and drug and cell delivery.
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24.
  • Van Loon, Anne F., et al. (author)
  • Review article: Drought as a continuum: memory effects in interlinked hydrological, ecological, and social systems
  • 2024
  • Other publication (other academic/artistic)abstract
    • Droughts are often long lasting phenomena, without a distinct start or end, and with impacts cascading across sectors and systems, creating long-term legacies. Nevertheless, our current perception and management of droughts and their impacts is often event-based, which can limit the effective assessment of drought risks and reduction of drought impacts. Here, we advocate for changing this perspective and viewing drought as a hydro-eco-social continuum. We take a systems theory perspective and focus on how “memory” causes feedback and interactions between parts of the interconnected systems at different time scales. We first discuss the characteristics of the drought continuum with a focus on the hydrological, ecological, and social systems separately; and then study the system of systems. Our analysis is based on a review of the literature and a study of five cases: Chile, the Colorado River Basin in the US, Northeast Brazil, Kenya, and the Rhine River Basin in Northwest Europe. We find that the memories of past dry and wet periods, carried by both bio-physical (e.g. groundwater, vegetation) and social systems (e.g. people, governance), influence how future drought risk manifests. We identify four archetypes of drought dynamics: Impact & recovery; Slow resilience-building; Gradual collapse; and High resilience, big shock. The interactions between the hydrological, ecological and social systems result in systems shifting between these types, which plays out differently in the five case studies. We call for more research on drought preconditions and recovery in different systems, on dynamics cascading between systems and triggering system changes, and on dynamic vulnerability and maladaptation. Additionally, we argue for more continuous monitoring of drought hazards and impacts, modelling tools that better incorporate memories and adaptation responses, and management strategies that increase social and institutional memory to better deal with the complex hydro-eco-social drought continuum and identify effective pathways to adaptation.
  •  
25.
  • van Setten, Jessica, et al. (author)
  • PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
  • 2018
  • In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
  • Journal article (peer-reviewed)abstract
    • Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are overrepresented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of similar to 105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
  •  
26.
  • Adaldo, Antonio, et al. (author)
  • Cooperative coverage for surveillance of 3D structures
  • 2017
  • In: IEEE International Conference on Intelligent Robots and Systems. - Piscataway, NJ : Institute of Electrical and Electronics Engineers (IEEE). - 9781538626825 ; , s. 1838-1845
  • Conference paper (peer-reviewed)abstract
    • In this article, we propose a planning algorithm for coverage of complex structures with a network of robotic sensing agents, with multi-robot surveillance missions as our main motivating application. The sensors are deployed to monitor the external surface of a 3D structure. The algorithm controls the motion of each sensor so that a measure of the collective coverage attained by the network is nondecreasing, while the sensors converge to an equilibrium configuration. A modified version of the algorithm is also provided to introduce collision avoidance properties. The effectiveness of the algorithm is demonstrated in a simulation and validated experimentally by executing the planned paths on an aerial robot.
  •  
27.
  • Adl, Sina M., et al. (author)
  • Revisions to the Classification, Nomenclature, and Diversity of Eukaryotes
  • 2019
  • In: Journal of Eukaryotic Microbiology. - : WILEY. - 1066-5234 .- 1550-7408. ; 66:1, s. 4-119
  • Journal article (peer-reviewed)abstract
    • This revision of the classification of eukaryotes follows that of Adl et al., 2012 [J. Euk. Microbiol. 59(5)] and retains an emphasis on protists. Changes since have improved the resolution of many nodes in phylogenetic analyses. For some clades even families are being clearly resolved. As we had predicted, environmental sampling in the intervening years has massively increased the genetic information at hand. Consequently, we have discovered novel clades, exciting new genera and uncovered a massive species level diversity beyond the morphological species descriptions. Several clades known from environmental samples only have now found their home. Sampling soils, deeper marine waters and the deep sea will continue to fill us with surprises. The main changes in this revision are the confirmation that eukaryotes form at least two domains, the loss of monophyly in the Excavata, robust support for the Haptista and Cryptista. We provide suggested primer sets for DNA sequences from environmental samples that are effective for each clade. We have provided a guide to trophic functional guilds in an appendix, to facilitate the interpretation of environmental samples, and a standardized taxonomic guide for East Asian users.
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28.
  • Angelovska, Marina, et al. (author)
  • Siamese Neural Networks for Detecting Complementary Products
  • 2021
  • In: Proceedings of the 16th Conference of the European Chapter of the Association for Computational Linguistics. - : Association for Computational Linguistics. ; , s. 65-70
  • Conference paper (peer-reviewed)abstract
    • Recommender systems play an important role in e-commerce websites as they improve the customer journey by helping the users find what they want at the right moment. In this paper, we focus on identifying a complementary relationship between the products of an e-commerce company. We propose a content-based recommender system for detecting complementary products, using Siamese Neural Networks (SNN). To this end, we implement and compare two different models: Siamese Convolutional Neural Network (CNN) and Siamese Long Short-Term Memory (LSTM). Moreover, we propose an extension of the SNN approach to handling millions of products in a matter of seconds, and we reduce the training time complexity by half. In the experiments, we show that Siamese LSTM can predict complementary products with an accuracy of ~85% using only the product titles.
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29.
  • Arheimer, Berit, et al. (author)
  • The IAHS Science for Solutions decade, with Hydrology Engaging Local People IN a Global world (HELPING)
  • 2024
  • In: Hydrological Sciences Journal. - 0262-6667 .- 2150-3435.
  • Journal article (peer-reviewed)abstract
    • The new scientific decade (2023-2032) of the International Association of Hydrological Sciences (IAHS) aims at searching for sustainable solutions to undesired water conditions - may it be too little, too much or too polluted. Many of the current issues originate from global change, while solutions to problems must embrace local understanding and context. The decade will explore the current water crises by searching for actionable knowledge within three themes: global and local interactions, sustainable solutions and innovative cross-cutting methods. We capitalise on previous IAHS Scientific Decades shaping a trilogy; from Hydrological Predictions (PUB) to Change and Interdisciplinarity (Panta Rhei) to Solutions (HELPING). The vision is to solve fundamental water-related environmental and societal problems by engaging with other disciplines and local stakeholders. The decade endorses mutual learning and co-creation to progress towards UN sustainable development goals. Hence, HELPING is a vehicle for putting science in action, driven by scientists working on local hydrology in coordination with local, regional, and global processes.
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30.
  • Aschard, Hugues, et al. (author)
  • Evidence for large-scale gene-by-smoking interaction effects on pulmonary function
  • 2017
  • In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 46:3, s. 894-904
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV1 (forced expiratory volume in 1 second) or FEV1/FVC (FEV1/forced vital capacity). Although the main effects of smoking and genetic loci are well established, the question of potential gene-by-smoking interaction effect remains unanswered. The aim of the present study was to assess, using a genetic risk score approach, whether the effect of these 26 loci on pulmonary function is influenced by smoking.METHODS: We evaluated the interaction between smoking exposure, considered as either ever vs never or pack-years, and a 26-single nucleotide polymorphisms (SNPs) genetic risk score in relation to FEV1 or FEV1/FVC in 50 047 participants of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and SpiroMeta consortia.RESULTS: We identified an interaction (βint = -0.036, 95% confidence interval, -0.040 to -0.032, P = 0.00057) between an unweighted 26 SNP genetic risk score and smoking status (ever/never) on the FEV1/FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling below the FEV 1: /FVC threshold used to diagnose chronic obstructive pulmonary disease is higher among ever smokers than among never smokers. A replication analysis in two independent datasets, although not statistically significant, showed a similar trend in the interaction effect.CONCLUSIONS: This study highlights the benefit of using genetic risk scores for identifying interactions missed when studying individual SNPs and shows, for the first time, that persons with the highest genetic risk for low FEV1/FVC may be more susceptible to the deleterious effects of smoking.
  •  
31.
  • Bondza, Sina, et al. (author)
  • Bivalent binding on cells varies between anti-CD20 antibodies and is dose-dependent
  • 2020
  • In: mAbs. - : TAYLOR & FRANCIS INC. - 1942-0862 .- 1942-0870. ; 12:1
  • Journal article (peer-reviewed)abstract
    • Based on their mechanism of action, two types of anti-CD20 antibodies are distinguished: Type I, which efficiently mediate complement-dependent cytotoxicity, and Type II, which instead are more efficient in inducing direct cell death. Several molecular characteristics of these antibodies have been suggested to underlie these different biological functions, one of these being the manner of binding to CD20 expressed on malignant B cells. However, the exact binding model on cells is unclear. In this study, the binding mechanism of the Type I therapeutic antibodies rituximab (RTX) and ofatumumab (OFA) and the Type II antibody obinutuzumab (OBI) were established by real-time interaction analysis on live cells. It was found that the degree of bivalent stabilization differed for the antibodies: OFA was stabilized the most, followed by RTX and then OBI, which had the least amount of bivalent stabilization. Bivalency inversely correlated with binding dynamics for the antibodies, with OBI displaying the most dynamic binding pattern, followed by RTX and OFA. For RTX and OBI, bivalency and binding dynamics were concentration dependent; at higher concentrations the interactions were more dynamic, whereas the percentage of antibodies that bound bivalent was less, resulting in concentration-dependent apparent affinities. This was barely noticeable for OFA, as almost all molecules bound bivalently at the tested concentrations. We conclude that the degree of bivalent binding positively correlates with the complement recruiting capacity of the investigated CD20 antibodies.
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32.
  • Falcone, Paolo, 1977, et al. (author)
  • Regenerative Braking and Yaw Dynamics Optimal Control in Hybrid Vehicles
  • 2009
  • In: 21st International Symposium on Dynamics of Vehicles on Roads and Tracks, 17-21 August 2009, Stockholm, Sweden.
  • Conference paper (peer-reviewed)abstract
    • In hybrid vehicles, regenerative braking is used in order to recover energy when vehiclebrakes. Energy is recovered by converting the vehicle kinetic energy into electric energy tobe stored in electricity buffers, i.e., batteries or capacitors. The recovered energy can then beused for powering the vehicle and thus reduce the fuel consumption. In particular, in order togenerate a braking force, the wheels can be connected to the electric motor, thus providingmotion energy to the generator and charging the electric buffer. When regenerative brakingis applied, the connection of the wheels to the generator results in a load torque (i.e., a braketorque), slowing the vehicle down, and at the same time enables energy recovery.In this paper, we consider hybrid drivelines where the electric motor is connected to therear axle, i.e., the regenerative braking takes place by braking the rear wheels, and focus onthe implications of the regenerative braking on the vehicle dynamics.The scenario considered in this paper (i.e., regenerative braking at the rear axle) is challengingfrom both the brake force delivery and distribution and the vehicle stabilizationperspectives [1]. In fact, we first observe that the maximum force the regenerative brakingcan deliver is limited and, in general, less than the friction braking. In particular, a brakingforce request from the driver might not be delivered entirely through regenerative brakingand a combination of friction and regenerative braking might be necessary. Secondly, werecall that an “optimum” brake proportioning between front and rear axles exists, such thatthe braking performance is maximized and the vehicle stability is preserved (see [2] for adetailed explanation). Clearly, maximizing the braking at one axle might conflict with a brakeforce distribution determined according to some “optimum” brake proportioning. Moreover,preserving the vehicle stability and comfort on slippery surfaces while maximizing the energyrecovering is a significant challenge as well. In particular, on low friction surfaces, the braketorque from regenerative braking might be large enough to lock-up the rear wheel. This wouldinduce an oversteering behavior and might even lead to instability, i.e., vehicle spinning [1].Even though instability does not occur, the driver might perceive a reduction of comfort asconsequence of braking at the rear wheels. In particular, on low friction surfaces, where thevehicle can easily operate at the limit of tire force capabilities, a sudden reduction of lateralforce might be experienced as consequence of braking.In this paper, we consider testing scenarios where the driver demands a braking force whilethe vehicle is performing a cornering manoeuvres on slippery surfaces, i.e., snow or ice. Thecontrol objective is to maximize the energy recovery (i.e., the regenerative braking), while (i)delivering the requested braking force by introducing front and rear friction braking as well,if necessary, (ii) preserving the vehicle stability and (iii) limit the lateral force reduction. Weshow how this problem can be effectively formulated as a Model Predictive Control (MPC)problem. In particular, we design a cost function in order to achieve our control objectives.Every time step, based on measurements of the demanded brake force, the vehicle yaw turningrate and longitudinal and lateral velocities, we repeatedly solve an optimization problem inorder to find the braking policy minimizing the cost function while fulfilling design and systemconstraints. As shown in [3], such control approach can be high computational demandingand even prevent real-time implementation. In order to implement our MPC algorithms inreal-time, we resort to the low complexity MPC formulation used in [4], [5], [6] to solveautonomous path following problems.REFERENCES[1] M. Hancock and F. Assadian. Impact of regenerative braking on vehicle stability. IET The Institution of Engineeringand Technology, Hybrid Vehicle Conference, 2006.[2] T. Gillespie. Fundamentals of Vehicle Dynamics, chapter 3, pages 60–67. Society of Automotive Engineers (SAE),1992.[3] F. Borrelli, P. Falcone, T. Keviczky, J. Asgari, and D. Hrovat. MPC-based approach to active steering for autonomousvehicle systems. Int. J. Vehicle Autonomous Systems, 3(2/3/4):265–291, 2005.[4] P. Falcone, F. Borrelli, J. Asgari, H. E. Tseng, and D. Hrovat. Predictive active steering control for autonomous vehiclesystems. IEEE Trans. on Control System Technology, 15(3), 2007.[5] P. Falcone, F. Borrelli, J. Asgari, H. E. Tseng, and D. Hrovat. Linear time varying model predictive control and itsapplication to active steering systems: Stability analisys and experimental validation. International Journal of Robustand Nonlinear Control., 18:862–875, 2008.[6] P. Falcone. Nonlinear Model Predictive Control for Autonomous Vehicles. PhD thesis, Universit`a del Sannio,Dipartimento di Ingegneria, Piazza Roma 21, 82100, Benevento, Italy, June 2007.
  •  
33.
  • Hansson, Anita C., et al. (author)
  • Oxytocin Reduces Alcohol Cue-Reactivity in Alcohol-Dependent Rats and Humans
  • 2018
  • In: Neuropsychopharmacology. - : NATURE PUBLISHING GROUP. - 0893-133X .- 1740-634X. ; 43:6, s. 1235-1246
  • Journal article (peer-reviewed)abstract
    • Approved pharmacological treatments for alcohol use disorder are limited in their effectiveness, and new drugs that can easily be translated into the clinic are warranted. One of those candidates is oxytocin because of its interaction with several alcohol-induced effects. Alcoholdependent rats as well as post-mortem brains of human alcoholics and controls were analyzed for the expression of the oxytocin system by qRT-PCR, in situ hybridizaton, receptor autoradiography ([(125)l]OVTA binding), and immunohistochemistry. Alcohol self administration and cue-induced reinstatement behavior was measured after intracerebroventicular injection of 10 nM oxytocin in dependent rats. Here we show a pronounced upregulation of oxytocin receptors in brain tissues of alcohol dependent rats and deceased alcoholics, primarily in frontal and striatal areas. This upregulation stems most likely from reduced oxytocin expression in hypothalamic nuclei. Pharmacological validaton showed that oxytocin reduced cue-induced reinstatement response in dependent rats-an effect that was not observed in nondependent rats. Finally, a clinical pilot study (German clinical trial number DRKS00009253) using functional magnetic resonance imaging in heavy social male drinkers showed that intranasal oxytocin (24 IU) decreased neural cue-reactivity in brain networks similar to those detected in dependent rats and humans with increased oxytocin receptor expression. These studies suggest that oxytocin might be used as an anticraving medication and thus may positvely affect treatment outcomes in alcoholics.
  •  
34.
  • Jackson, Victoria E, et al. (author)
  • Meta-analysis of exome array data identifies six novel genetic loci for lung function.
  • 2018
  • In: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 3
  • Journal article (peer-reviewed)abstract
    • Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10 -7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs ( SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
  •  
35.
  • Jang, Seon-Kyeong, et al. (author)
  • Rare genetic variants explain missing heritability in smoking.
  • 2022
  • In: Nature human behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 6:11, s. 1577-1586
  • Journal article (peer-reviewed)abstract
    • Common genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this 'missing heritability'. We investigated the contribution of rare genetic variants to tobacco use with whole-genome sequences from up to 26,257 unrelated individuals of European ancestries and 11,743 individuals of African ancestries. Across four smoking traits, single-nucleotide-polymorphism-based heritability ([Formula: see text]) was estimated from 0.13 to 0.28 (s.e., 0.10-0.13) in European ancestries, with 35-74% of it attributable to rare variants with minor allele frequencies between 0.01% and 1%. These heritability estimates are 1.5-4 times higher than past estimates based on common variants alone and accounted for 60% to 100% of our pedigree-based estimates of narrow-sense heritability ([Formula: see text], 0.18-0.34). In the African ancestry samples, [Formula: see text] was estimated from 0.03 to 0.33 (s.e., 0.09-0.14) across the four smoking traits. These results suggest that rare variants are important contributors to the heritability of smoking.
  •  
36.
  • Jensen, Benjamin A H, et al. (author)
  • Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+ Tregs and improve metabolism
  • 2021
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Journal article (peer-reviewed)abstract
    • Interactions between host and gut microbial communities are modulated by diets and play pivotal roles in immunological homeostasis and health. We show that exchanging the protein source in a high fat, high sugar, westernized diet from casein to whole-cell lysates of the non-commensal bacterium Methylococcus capsulatus Bath is sufficient to reverse western diet-induced changes in the gut microbiota to a state resembling that of lean, low fat diet-fed mice, both under mild thermal stress (T22 °C) and at thermoneutrality (T30 °C). Concomitant with microbiota changes, mice fed the Methylococcus-based western diet exhibit improved glucose regulation, reduced body and liver fat, and diminished hepatic immune infiltration. Intake of the Methylococcu-based diet markedly boosts Parabacteroides abundances in a manner depending on adaptive immunity, and upregulates triple positive (Foxp3+RORγt+IL-17+) regulatory T cells in the small and large intestine. Collectively, these data point to the potential for leveraging the use of McB lysates to improve immunometabolic homeostasis.
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37.
  • McDonagh, Birgitte H, et al. (author)
  • Controlling the self-assembly and optical properties of gold nanoclusters and gold nanoparticles biomineralized with bovine serum albumin
  • 2015
  • In: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 5:122, s. 101101-101109
  • Journal article (peer-reviewed)abstract
    • While the size-dependent optical properties of BSA-stabilized gold nanoclusters are well known, the timedependent growth mechanism remains to be described. Herein, we systematically compare two synthesis methods with and without ascorbic acid, and show that tuning of BSA-stabilized gold nanoclusters (AuNCs) of different sizes can be performed without the aid of an extrinsic reducing agent and with good reproducibility. We also show that adding ascorbic acid yields larger BSA-stabilized gold nanoparticles (AuNPs), and that AuNPs can only form above a threshold gold precursor concentration. Using computed tomography, we describe how these biomineralized AuNPs show size-dependent X-ray attenuation. Growth of BSA-stabilized AuNCs and AuNPs, over a range of gold precursor concentrations, was followed with steady-state fluorescence and UV-vis spectroscopy for one week, constituting the first study of its kind. Based on our results, we propose a mechanism for BSA-stabilization of AuNCs and AuNPs that can further aid in selective growth of discrete AuNCs and AuNPs.
  •  
38.
  • McDonagh, Birgitte H., et al. (author)
  • Self-assembly and characterization of transferrin-gold nanoconstructs and their interaction with bio-interfaces
  • 2015
  • In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 7:17, s. 8062-8070
  • Journal article (peer-reviewed)abstract
    • Transferrin (Tf) conjugated to gold nanoparticles and clusters combine the protein's site-specific receptor targeting capabilities with the optical properties imparted by the nano-sized gold. We have described two different synthesis protocols, one yielding fluorescent Tf-stabilized gold nanoclusters (AuNCs) and one yielding Tf-stabilized gold nanoparticles that exhibit localized surface plasmon resonance. We demonstrate that the synthetic route employed has a large influence both on the gold nanostructure formed, and also on the structural integrity of the protein. A slight protein unfolding allows stronger interaction with lipids, and was found to significantly perturb lipid monolayers. Interactions between the protein-gold nanostructures and three different cell types were also assessed, indicating that the enhanced membrane affinity may be attributed to intercellular membrane differences.
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39.
  • Meister, Moritz, et al. (author)
  • Maggy : Scalable Asynchronous Parallel Hyperparameter Search
  • 2020
  • In: Proceedings of the 1st Workshop on Distributed Machine Learning. - New York, NY, USA : Association for Computing Machinery. ; , s. 28-33
  • Conference paper (peer-reviewed)abstract
    • Running extensive experiments is essential for building Machine Learning (ML) models. Such experiments usually require iterative execution of many trials with varying run times. In recent years, Apache Spark has become the de-facto standard for parallel data processing in the industry, in which iterative processes are implemented within the bulk-synchronous parallel (BSP) execution model. The BSP approach is also being used to parallelize ML trials in Spark. However, the BSP task synchronization barriers prevent asynchronous execution of trials, which leads to a reduced number of trials that can be run on a given computational budget. In this paper, we introduce Maggy, an open-source framework based on Spark, to execute ML trials asynchronously in parallel, with the ability to early stop poorly performing trials. In the experiments, we compare Maggy with the BSP execution of parallel trials in Spark and show that on random hyperparameter search on a convolutional neural network for the Fashion-MNIST dataset Maggy reduces the required time to execute a fixed number of trials by 33% to 58%, without any loss in the final model accuracy.
  •  
40.
  • Moeller, Sina, et al. (author)
  • Lack of association between autism and anti-GM1 ganglioside antibody
  • 2013
  • In: Neurology. - 0028-3878 .- 1526-632X. ; 81:18, s. 1640-1641
  • Journal article (other academic/artistic)abstract
    • Forty of 54 children with autism were reported to have an elevated antibody response to GM1 ganglioside that correlated with disease severity.1 Antiganglioside autoantibodies, especially those directed at GM1, are known to be associated with and play a pathogenic role in some immune-mediated peripheral neuropathies.2,3 The presumed link between autism and anti-GM1 antibodies, therefore, implies that testing may identify a sizable subset of patients who would benefit from immunomodulatory therapy. To evaluate the proposed association between autism and anti-GM1 antibodies, serum samples from children diagnosed with autism by strict clinical criteria and those without autism were analyzed using a standard, validated immunoassay protocol.
  •  
41.
  • Mortazavi, Sina, et al. (author)
  • Mapping inclusive innovation : A bibliometric study and literature review
  • 2021
  • In: Journal of Business Research. - : Elsevier. - 0148-2963 .- 1873-7978. ; 122, s. 736-750
  • Journal article (peer-reviewed)abstract
    • Inclusive innovation is a type of innovation that targets not only affordability but also localization of underdeveloped countries, with the aim of reducing poverty. Despite the increasing attention paid to inclusive innovation, there is no common understanding of how the inclusive innovation notion is formed among researchers and experts. This study adopts a novel approach by combining bibliometric methods of co-citation analysis and text codifying of 293 core and relevant journal articles on inclusive innovation. The results reveal that the notion of inclusive innovation has evolved in five clusters: (1) innovation as a tool for affordability, (2) innovation as a tool for inclusion, (3) building of capabilities and innovation, (4) innovation constraints associated with social empowerment, and (5) innovation as an inclusive system. Furthermore, this study proposes a conceptual model based on these clusters, and discusses the nature of how these clusters lead to the possibility for further studies on inclusive innovation. 
  •  
42.
  •  
43.
  • Mostaghel, Sina, et al. (author)
  • Integrated recycling at Boliden's Rönnskär Smelter; formation of slag products
  • 2012
  • In: International Smelting Technology Symposium. - : Wiley-TMS. - 9781118291160 ; , s. 117-124
  • Conference paper (peer-reviewed)abstract
    • Rönnskär Smelter of Boliden Mineral AB, Sweden, is a large end-processor of secondary raw materials and waste, including electronic scrap. Electronic scrap may introduce various impurities to the smelter's flow-sheet, among which alumina is a common and significant one. This article summarizes the results of an ongoing research at Luleå University of Technology, Sweden, to study the influences of alumina on different properties of slag from the zinc filming process at Rönnskär smelter. A combination of different experimental techniques and thermodynamic calculations have been used to investigate properties such as density, surface tension, effective thermal diffusivity, viscosity, and melting/leaching behaviors. Results show that the addition of alumina to this slag increases the degree of polymerization of the melt, and physical properties vary correspondingly. Mineralogy of the semi-rapidly solidified samples is also changed due to alumina addition. A correlation between mineralogy and leaching behavior can be observed.
  •  
44.
  • Pavliuk, Mariia V., et al. (author)
  • Polymer Dots as Photoactive Membrane Vesicles for [FeFe]-Hydrogenase Self-Assembly and Solar-Driven Hydrogen Evolution
  • 2022
  • In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 144:30, s. 13600-13611
  • Journal article (peer-reviewed)abstract
    • A semiartificial photosynthesis approach that utilizes enzymes for solar fuel production relies on efficient photosensitizers that should match the enzyme activity and enable long-term stability. Polymer dots (Pdots) are biocompatible photosensitizers that are stable at pH 7 and have a readily modifiable surface morphology. Therefore, Pdots can be considered potential photosensitizers to drive such enzyme-based systems for solar fuel formation. This work introduces and unveils in detail the interaction within the biohybrid assembly composed of binary Pdots and the HydA1 [FeFe]-hydrogenase from Chlamydomonas reinhardtii. The direct attachment of hydrogenase on the surface of toroid-shaped Pdots was confirmed by agarose gel electrophoresis, cryogenic transmission electron microscopy (Cryo-TEM), and cryogenic electron tomography (Cryo-ET). Ultrafast transient spectroscopic techniques were used to characterize photoinduced excitation and dissociation into charges within Pdots. The study reveals that implementation of a donor–acceptor architecture for heterojunction Pdots leads to efficient subpicosecond charge separation and thus enhances hydrogen evolution (88 460 μmolH2·gH2ase–1·h–1). Adsorption of [FeFe]-hydrogenase onto Pdots resulted in a stable biohybrid assembly, where hydrogen production persisted for days, reaching a TON of 37 500 ± 1290 in the presence of a redox mediator. This work represents an example of a homogeneous biohybrid system combining polymer nanoparticles and an enzyme. Detailed spectroscopic studies provide a mechanistic understanding of light harvesting, charge separation, and transport studied, which is essential for building semiartificial photosynthetic systems with efficiencies beyond natural and artificial systems. 
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45.
  •  
46.
  • Popp, Andrea L., et al. (author)
  • A Global Survey on the Perceptions and Impacts of Gender Inequality in the Earth and Space Sciences
  • 2019
  • In: Earth and Space Science. - : American Geophysical Union (AGU). - 2333-5084. ; 6:8, s. 1460-1468
  • Journal article (peer-reviewed)abstract
    • The leaky pipeline phenomenon refers to the disproportionate decline of female scientists at higher academic career levels and is a major problem in the natural sciences. Identifying the underlying causes is challenging, and thus, solving the problem remains difficult. To better understand the reasons for the leaky pipeline, we assess the perceptions and impacts of gender bias and imbalance—two major drivers of the leakage—at different academic career levels with an anonymous survey in geoscience academia (n=1,220). The survey results show that both genders view male geoscientists as substantially more gender biased than female scientists. Moreover, female geoscientists are more than twice as likely to experience negative gender bias at their workplaces and scientific organizations compared to male geoscientists. There are also pronounced gender differences regarding (i) the relevance of role models, (ii) family-friendly working conditions, and (iii) the approval of gender quotas for academic positions. Given the male dominance in senior career levels, our results emphasize that those feeling less impacted by the negative consequences of gender bias and imbalance are the ones in position to tackle the problem. We thus call for actions to better address gender biases and to ensure a balanced gender representation at decision-making levels to ultimately retain more women in geoscience academia.
  •  
47.
  • Senges, Christoph H.R., et al. (author)
  • Comparison of proteomic responses as global approach to antibiotic mechanism of action elucidation
  • 2021
  • In: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 65:1
  • Journal article (peer-reviewed)abstract
    • This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. New antibiotics are urgently needed to address the mounting resistance challenge. In early drug discovery, one of the bottlenecks is the elucidation of targets and mechanisms. To accelerate antibiotic research, we provide a proteomic approach for the rapid classification of compounds into those with precedented and unprecedented modes of action. We established a proteomic response library of Bacillus subtilis covering 91 antibiotics and comparator compounds, and a mathematical approach was developed to aid data analysis. Comparison of proteomic responses (CoPR) allows the rapid identification of antibiotics with dual mechanisms of action as shown for atypical tetracyclines. It also aids in generating hypotheses on mechanisms of action as presented for salvarsan (arsphenamine) and the antirheumatic agent auranofin, which is under consideration for repurposing. Proteomic profiling also provides insights into the impact of antibiotics on bacterial physiology through analysis of marker proteins indicative of the impairment of cellular processes and structures. As demonstrated for trans-translation, a promising target not yet exploited clinically, proteomic profiling supports chemical biology approaches to investigating bacterial physiology.
  •  
48.
  • Sepanlou, Sadaf G., et al. (author)
  • The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017 : a systematic analysis for the Global Burden of Disease Study 2017
  • 2020
  • In: The Lancet Gastroenterology & Hepatology. - 2468-1253. ; 5:3, s. 245-266
  • Journal article (peer-reviewed)abstract
    • Background Cirrhosis and other chronic liver diseases (collectively referred to as cirrhosis in this paper) are a major cause of morbidity and mortality globally, although the burden and underlying causes differ across locations and demographic groups. We report on results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 on the burden of cirrhosis and its trends since 1990, by cause, sex, and age, for 195 countries and territories. Methods We used data from vital registrations, vital registration samples, and verbal autopsies to estimate mortality. We modelled prevalence of total, compensated, and decompensated cirrhosis on the basis of hospital and claims data. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost due to premature death and years lived with disability. Estimates are presented as numbers and age-standardised or age-specific rates per 100 000 population, with 95% uncertainty intervals (UIs). All estimates are presented for five causes of cirrhosis: hepatitis B, hepatitis C, alcohol-related liver disease, non-alcoholic steatohepatitis (NASH), and other causes. We compared mortality, prevalence, and DALY estimates with those expected according to the Socio-demographic Index (SDI) as a proxy for the development status of regions and countries. Findings In 2017, cirrhosis caused more than 1.32 million (95% UI 1.27-1.45) deaths (440000 [416 000-518 000; 33.3%] in females and 883 000 [838 000-967 000; 66.7%] in males) globally, compared with less than 899 000 (829 000-948 000) deaths in 1990. Deaths due to cirrhosis constituted 2.4% (2.3-2.6) of total deaths globally in 2017 compared with 1.9% (1.8-2.0) in 1990. Despite an increase in the number of deaths, the age-standardised death rate decreased from 21.0 (19.2-22.3) per 100 000 population in 1990 to 16.5 (15.8-18-1) per 100 000 population in 2017. Sub-Saharan Africa had the highest age-standardised death rate among GBD super-regions for all years of the study period (32.2 [25.8-38.6] deaths per 100 000 population in 2017), and the high-income super-region had the lowest (10.1 [9.8-10-5] deaths per 100 000 population in 2017). The age-standardised death rate decreased or remained constant from 1990 to 2017 in all GBD regions except eastern Europe and central Asia, where the age-standardised death rate increased, primarily due to increases in alcohol-related liver disease prevalence. At the national level, the age-standardised death rate of cirrhosis was lowest in Singapore in 2017 (3.7 [3.3-4.0] per 100 000 in 2017) and highest in Egypt in all years since 1990 (103.3 [64.4-133.4] per 100 000 in 2017). There were 10.6 million (10.3-10.9) prevalent cases of decompensated cirrhosis and 112 million (107-119) prevalent cases of compensated cirrhosis globally in 2017. There was a significant increase in age-standardised prevalence rate of decompensated cirrhosis between 1990 and 2017. Cirrhosis caused by NASH had a steady age-standardised death rate throughout the study period, whereas the other four causes showed declines in age-standardised death rate. The age-standardised prevalence of compensated and decompensated cirrhosis due to NASH increased more than for any other cause of cirrhosis (by 33.2% for compensated cirrhosis and 54.8% for decompensated cirrhosis) over the study period. From 1990 to 2017, the number of prevalent cases snore than doubled for compensated cirrhosis due to NASH and more than tripled for decompensated cirrhosis due to NASH. In 2017, age-standardised death and DALY rates were lower among countries and territories with higher SDI. Interpretation Cirrhosis imposes a substantial health burden on many countries and this burden has increased at the global level since 1990, partly due to population growth and ageing. Although the age-standardised death and DALY rates of cirrhosis decreased from 1990 to 2017, numbers of deaths and DALYs and the proportion of all global deaths due to cirrhosis increased. Despite the availability of effective interventions for the prevention and treatment of hepatitis B and C, they were still the main causes of cirrhosis burden worldwide, particularly in low-income countries. The impact of hepatitis B and C is expected to be attenuated and overtaken by that of NASH in the near future. Cost-effective interventions are required to continue the prevention and treatment of viral hepatitis, and to achieve early diagnosis and prevention of cirrhosis due to alcohol-related liver disease and NASH.
  •  
49.
  • Sheikholeslami, Sina, 1993-, et al. (author)
  • AutoAblation: Automated Parallel Ablation Studies for Deep Learning
  • 2021
  • In: EuroMLSys '21: Proceedings of the 1st Workshop on Machine Learning and Systems. - New York, NY, USA : Association for Computing Machinery. ; , s. 55-61
  • Conference paper (peer-reviewed)abstract
    • Ablation studies provide insights into the relative contribution of different architectural and regularization components to machine learning models' performance. In this paper, we introduce AutoAblation, a new framework for the design and parallel execution of ablation experiments. AutoAblation provides a declarative approach to defining ablation experiments on model architectures and training datasets, and enables the parallel execution of ablation trials. This reduces the execution time and allows more comprehensive experiments by exploiting larger amounts of computational resources. We show that AutoAblation can provide near-linear scalability by performing an ablation study on the modules of the Inception-v3 network trained on the TenGeoPSAR dataset.  
  •  
50.
  • Sheikholeslami, Sina, 1993-, et al. (author)
  • The Impact of Importance-Aware Dataset Partitioning on Data-Parallel Training of Deep Neural Networks
  • 2023
  • In: Distributed Applications and Interoperable Systems - 23rd IFIP WG 6.1 International Conference, DAIS 2023, Held as Part of the 18th International Federated Conference on Distributed Computing Techniques, DisCoTec 2023, Proceedings. - : Springer Nature. ; , s. 74-89
  • Conference paper (peer-reviewed)abstract
    • Deep neural networks used for computer vision tasks are typically trained on datasets consisting of thousands of images, called examples. Recent studies have shown that examples in a dataset are not of equal importance for model training and can be categorized based on quantifiable measures reflecting a notion of “hardness” or “importance”. In this work, we conduct an empirical study of the impact of importance-aware partitioning of the dataset examples across workers on the performance of data-parallel training of deep neural networks. Our experiments with CIFAR-10 and CIFAR-100 image datasets show that data-parallel training with importance-aware partitioning can perform better than vanilla data-parallel training, which is oblivious to the importance of examples. More specifically, the proper choice of the importance measure, partitioning heuristic, and the number of intervals for dataset repartitioning can improve the best accuracy of the model trained for a fixed number of epochs. We conclude that the parameters related to importance-aware data-parallel training, including the importance measure, number of warmup training epochs, and others defined in the paper, may be considered as hyperparameters of data-parallel model training.
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