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1.	Klionsky, Daniel J, et al. (författare) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). 2016 Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 12:1, s. 1-222 Tidskriftsartikel (refereegranskat)
2.	Menkveld, Albert J., et al. (författare) Nonstandard Errors 2024 Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390 Tidskriftsartikel (refereegranskat)abstract In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
3.	Vos, Theo, et al. (författare) Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013 2015 Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 386:9995, s. 743-800 Tidskriftsartikel (refereegranskat)abstract Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2.4 billion and 1.6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537.6 million in 1990 to 764.8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114.87 per 1000 people to 110.31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21.1% in 1990 to 31.2% in 2013. Interpretation Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
4.	Naghavi, Mohsen, et al. (författare) Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013 2015 Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171 Tidskriftsartikel (refereegranskat)abstract Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
5.	Shungin, Dmitry, et al. (författare) New genetic loci link adipose and insulin biology to body fat distribution. 2015 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378 Tidskriftsartikel (refereegranskat)abstract Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
6.	Forouzanfar, Mohammad H, et al. (författare) Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013. 2015 Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
7.	Locke, Adam E, et al. (författare) Genetic studies of body mass index yield new insights for obesity biology. 2015 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401 Tidskriftsartikel (refereegranskat)abstract Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
8.	Nguyen, Thanh N, et al. (författare) Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up. 2023 Ingår i: Neurology. - 1526-632X. ; 100:4 Tidskriftsartikel (refereegranskat)abstract Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
9.	Berndt, Sonja I., et al. (författare) Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture 2013 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69 Tidskriftsartikel (refereegranskat)abstract Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
10.	de las Fuentes, Lisa, et al. (författare) Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci 2021 Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:6, s. 2111-2125 Tidskriftsartikel (refereegranskat)abstract Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
11.	de Vries, Paul S., et al. (författare) Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions 2019 Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054 Tidskriftsartikel (refereegranskat)abstract A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
12.	Feitosa, Mary F., et al. (författare) Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries 2018 Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6 Tidskriftsartikel (refereegranskat)abstract Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
13.	Fullman, Nancy, et al. (författare) Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016 2018 Ingår i: The Lancet. - : Lancet Publishing Group. - 1474-547X .- 0140-6736. ; 391:10136, s. 2236-2271 Tidskriftsartikel (refereegranskat)
14.	Gorski, Mathias, et al. (författare) Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies 2022 Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639 Tidskriftsartikel (refereegranskat)abstract Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
15.	Sarneel, Judith M., et al. (författare) Reading tea leaves worldwide: Decoupled drivers of initial litter decomposition mass-loss rate and stabilization 2024 Ingår i: ECOLOGY LETTERS. - : John Wiley & Sons. - 1461-023X .- 1461-0248. ; 27:5 Tidskriftsartikel (refereegranskat)abstract The breakdown of plant material fuels soil functioning and biodiversity. Currently, process understanding of global decomposition patterns and the drivers of such patterns are hampered by the lack of coherent large-scale datasets. We buried 36,000 individual litterbags (tea bags) worldwide and found an overall negative correlation between initial mass-loss rates and stabilization factors of plant-derived carbon, using the Tea Bag Index (TBI). The stabilization factor quantifies the degree to which easy-to-degrade components accumulate during early-stage decomposition (e.g. by environmental limitations). However, agriculture and an interaction between moisture and temperature led to a decoupling between initial mass-loss rates and stabilization, notably in colder locations. Using TBI improved mass-loss estimates of natural litter compared to models that ignored stabilization. Ignoring the transformation of dead plant material to more recalcitrant substances during early-stage decomposition, and the environmental control of this transformation, could overestimate carbon losses during early decomposition in carbon cycle models.
16.	Begum, Shahina, et al. (författare) Towards a Compositional Service Architecture for Real-Time Cloud Robotics 2016 Ingår i: ACM SIGBED Review. - : Association for Computing Machinery (ACM). - 1551-3688. ; , s. 63-64 Tidskriftsartikel (refereegranskat)abstract In this paper we present our ongoing work towards a compositional service architecture that integrates cloud technology for computational capacity targeting real-time robotics applications. In particular we take a look at the challenges inherent within the data center where the services are executing. We outline characteristics of the services used in the real-time cloud robotics application, along with the service management and corresponding task model used to execute services. We identify several key central challenges that must be addressed towards integrating cloud technology in real-time robotics.
17.	Danielsson, Jakob, et al. (författare) Performance Evaluation of Network Convergence Time Measurement Techniques 2017 Ingår i: International Conference on Emerging Technologies And Factory Automation ETFA'17. - 9781509065059 ; , s. 1-7 Konferensbidrag (refereegranskat)abstract In this paper we evaluate solutions that provide measurements for the network convergence time in switched Ethernet networks when links failures happen. We evaluate three solutions to measure the network convergence time in a faulty situation. Compared to the commercially available solutions, our proposals are cost-effective, portable, and open source. Thus, they are easy to deploy on many testbeds. We show the performance of the solutions by measuring different metrics including jitter, network convergence time and packet loss during the network recovery time. Our measurements indicate that it is possible to accurately measure the network convergence time using a packet sender which does not suffer interference from the overlying operating system. Furthermore, we noticed that the packet sniffer TShark did not suffer from kernel interrupts from overlying operating systems.
18.	Do, Ron, et al. (författare) Common variants associated with plasma triglycerides and risk for coronary artery disease 2013 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345- Tidskriftsartikel (refereegranskat)abstract Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
19.	Gorski, Mathias, et al. (författare) Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline 2021 Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 99:4, s. 926-939 Tidskriftsartikel (refereegranskat)abstract Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
20.	Joshi, Peter K, et al. (författare) Directional dominance on stature and cognition in diverse human populations 2015 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462 Tidskriftsartikel (refereegranskat)abstract Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
21.	Kim, Dae-Kyum, et al. (författare) EVpedia: A Community Web Portal for Extracellular Vesicles Research 2015 Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 31:6, s. 933-939 Tidskriftsartikel (refereegranskat)abstract Motivation: Extracellular vesicles (EVs) are spherical bilayered proteolipids, harboring various bioactive molecules. Due to the complexity of the vesicular nomenclatures and components, online searches for EV-related publications and vesicular components are currently challenging. Results: We present an improved version of EVpedia, a public database for EVs research. This community web portal contains a database of publications and vesicular components, identification of orthologous vesicular components, bioinformatic tools and a personalized function. EVpedia includes 6879 publications, 172 080 vesicular components from 263 high-throughput datasets, and has been accessed more than 65 000 times from more than 750 cities. In addition, about 350 members from 73 international research groups have participated in developing EVpedia. This free web-based database might serve as a useful resource to stimulate the emerging field of EV research.
22.	Kyu, Hmwe H, et al. (författare) Global and National Burden of Diseases and Injuries Among Children and Adolescents Between 1990 and 2013 : Findings From the Global Burden of Disease 2013 Study. 2016 Ingår i: JAMA pediatrics. - : American Medical Association (AMA). - 2168-6203 .- 2168-6211. ; 170:3, s. 267-287 Tidskriftsartikel (refereegranskat)abstract IMPORTANCE: The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce.OBJECTIVE: To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged <5 years), older children (aged 5-9 years), and adolescents (aged 10-19 years) between 1990 and 2013 in 188 countries from the Global Burden of Disease (GBD) 2013 study.EVIDENCE REVIEW: Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14 244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35 620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates.FINDINGS: Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905 059 deaths; 95% UI, 810 304-998 125), diarrheal diseases among older children (38 325 deaths; 95% UI, 30 365-47 678), and road injuries among adolescents (115 186 deaths; 95% UI, 105 185-124 870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world's deaths from neonatal encephalopathy. Half of the world's diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia.CONCLUSIONS AND RELEVANCE: Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed.
23.	Ried, Janina S., et al. (författare) A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape 2016 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7 Tidskriftsartikel (refereegranskat)abstract Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
24.	van Setten, Jessica, et al. (författare) PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity 2018 Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9 Tidskriftsartikel (refereegranskat)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.
25.	Vitucci, C., et al. (författare) A Deductive Fault Analysis Method Based on Hypergraphs 2024 Ingår i: IFAC-PapersOnLine. - : Elsevier B.V.. ; , s. 378-383 Konferensbidrag (refereegranskat)abstract Fault tree analysis is a system malfunction hazard evaluation quantitative and qualitative procedure. The method is well-known and widely used, especially in the safety systems domain, where it is a mandatory integral part of the so-called "Hazard Evaluation"documentation. This paper proposes an alternative or complementary deductive fault analysis method: it uses system topology to build a hypergraph representation of the system to identify component criticality and support loss of functionality probability evaluation. Once automated, the proposed method seems promising when the system engineers explore the different architectures. They may have indication about architecture's reliability without continuous feedback from the system safety team. The system safety team must check the solution once the engineers select the final architecture. They can also use the proposed method to validate the correctness of the fault tree analysis.
26.	Willer, Cristen J., et al. (författare) Discovery and refinement of loci associated with lipid levels 2013 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283 Tidskriftsartikel (refereegranskat)abstract Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
27.	Wuttke, Matthias, et al. (författare) A catalog of genetic loci associated with kidney function from analyses of a million individuals 2019 Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972 Tidskriftsartikel (refereegranskat)abstract Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
28.	Abdullah, Syed Md Jakaria, et al. (författare) Towards Implementation of Virtual-Clustered Multiprocessor Scheduling in Linux 2013 Ingår i: Proceedings of the 8th IEEE International Symposium on Industrial Embedded Systems, SIES 2013. - 9781479906581 ; , s. 97-100 Konferensbidrag (refereegranskat)abstract Cluster based multiprocessor scheduling can be seen as a hybrid approach combining benefits of both partitioned and global scheduling. Virtual clustering further enhances it by providing dynamic cluster resource allocation and applying hierarchical scheduling techniques. Over the years, the study of virtual cluster scheduling has been limited to theoretical analysis. In this paper, we present our initial ideas about implementing virtual cluster scheduling in Linux. The purpose of this implementation is twofold: (i) we would like to demonstrate the feasibility of its implementation in an operating system, without modifying the kernel source code, (ii) we present practical insights on the overhead of implementing this framework.
29.	Afshar, Sara, et al. (författare) Flexible spin-lock model for resource sharing in multiprocessor real-time systems 2014 Ingår i: Proc. IEEE Int. Symp. Ind. Embedded Syst., SIES. - 9781479940233 ; , s. 41-51 Konferensbidrag (refereegranskat)abstract Various approaches can be utilized upon resource locking for mutually exclusive resource access in multiprocessor platforms. So far two conventional approaches exist for dealing with tasks that are blocked on a global resource in a multi-processor platform. Either the blocked task performs a busy wait, i.e. spins, at the highest priority level until the resource is released, or it is suspended. Although both approaches provide mutually exclusive access to resources, they can introduce long blocking delays to tasks, which may be unacceptable for many industrial applications. In this paper, we propose a general spin-based model for resource sharing in multiprocessor platforms in which the priority of the blocked tasks during spinning can be selected arbitrarily. Moreover, we provide the analysis for two selected spin-lock priorities and we show by means of a general comparison as well as specific examples that these solutions may provide a better performance for higher priority tasks.
30.	Afshar, Sara, et al. (författare) Integrating independently developed real-time applications on a shared multi-core architecture 2013 Ingår i: ACM SIGBED Review, v. 10, n. 3. - : Association for Computing Machinery (ACM). ; , s. 49-56 Konferensbidrag (refereegranskat)abstract The shift towards multi-core platforms has become inevitable from an industry perspective, therefore proper techniques are needed to deal with challenges related to this migration from single core architectures to a multi-core architecture. One of the main concerns for the system developers in this context is the migration of legacy real-time systems to multi-core architectures. To address this concern and to simplify migration, independently developed subsystems are abstracted with an interface, such that when working with multiple independently-developed subsystems to be integrated on a shared platform, one does not need to be aware of information or policies used in other subsystems in order to determine subsystem-level schedulability. Instead schedulability can be checked through their interfaces at the time of integration on a shared multi-core architecture. In this paper we propose a solution for the case where some of the independently-developed subsystems are distributed over more than one processor and we propose an approach to generate interfaces of subsystems that may share mutually exclusive resources.
31.	Afshar, Sara, et al. (författare) Intra-component Resource Sharing on a Virtual Multiprocessor Platform 2016 Ingår i: ACM SIGBED Review. - : Association for Computing Machinery (ACM). - 1551-3688. ; , s. 31-32 Konferensbidrag (refereegranskat)abstract Component-based software development facilitates the development process of large and complex software systems. By the advent of multiprocessors, the independently developed components can be integrated on a multi-core platform to achieve an efficient use of system hardware and a decrease in system power consumption and costs. In this paper, we consider a virtual multiprocessor platform where each component can be dynamically allocated to any set of processors of the platform with a maximum concurrency level. Global-EDF is used for intra-component scheduling. The existing analysis for such systems have assumed that tasks are independent. In this paper, we enable intra-component resource sharing for this platform. We investigate using a spin-based resource sharing protocol with the accompanying analysis that extends the existing analysis for independent tasks. We briefly illustrate and evaluate our initial results with an example.
32.	Afshar, Sara (författare) Lock-Based Resource Sharing for Real-Time Multiprocessors 2017 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Embedded systems are widely used in the industry and are typically resource constrained, i.e., resources such as processors, I/O devices, shared buffers or shared memory might be limited in the system. Hence, techniques that can enable an efficient usage of processor bandwidths in such systems are of great importance. Locked-based resource sharing protocols are proposed as a solution to overcome resource limitation by allowing the available resources in the system to be safely shared. In recent years, due to a dramatic enhancement in the functionality of systems, a shift from single-core processors to multi-core processors has become inevitable from an industrial perspective to tackle the raised challenges due to increased system complexity. However, the resource sharing protocols are not fully mature for multi-core processors. The two classical multi-core processor resource sharing protocols, spin-based and suspension-based protocols, although providing mutually exclusive access to resources, can introduce long blocking delays to tasks, which may be unacceptable for many industrial applications. In this thesis we enhance the performance of resource sharing protocols for partitioned scheduling, which is the de-facto scheduling standard for industrial real-time multi-core processor systems such as in AUTOSAR, in terms of timing and memory requirements. A new scheduling approach uses a resource efficient hybrid approach combining both partitioned and global scheduling where the partitioned scheduling is used to schedule the major number of tasks in the system. In such a scheduling approach applications with critical task sets use partitioned scheduling to achieve higher level of predictability. Then the unused bandwidth on each core that is remained from partitioning is used to schedule less critical task sets using global scheduling to achieve higher system utilization. These scheduling schema however lacks a proper resource sharing protocol since the existing protocols designed for partitioned and global scheduling cannot be directly applied due to the complex hybrid structure of these scheduling frameworks. In this thesis we propose a resource sharing solution for such a complex structure. Further, we provide the blocking bounds incurred to tasks under the proposed protocols and enhance the schedulability analysis, which is an essential requirement for real-time systems, with the provided blocking bounds.
33.	Afshar, Sara (författare) Lock-Based Resource Sharing in Real-Time Multiprocessor Platforms 2014 Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract Embedded systems are typically resource constrained, i.e., resources such as processors, I/O devices, shared buffers or shared memory can be limited for tasks in the system. Therefore, techniques that enable an efficient usage of such resources are of great importance.In the industry, typically large and complex software systems are divided into smaller parts (applications) where each part is developed independently. Migration towards multiprocessor platforms has become inevitable from an industrial perspective. Due to such migration and to efficient use of system resources, these applications eventually may be integrated on a shared multiprocessor platform. In order to facilitate the integration phase of the applications on a shared platform, the timing and resource requirements of each application can be provided in an interface when the application is developed. The system integrator can benefit from such provided information in the interface of each application to ease the integration process. In this thesis, we have provided the resource and timing requirements of each application in their interfaces for applications that may need several processors to be allocated on when they are developed.Although many scheduling techniques have been studied for multiprocessor systems, these techniques are usually based on the assumption that tasks are independent, i.e. do not share resources other than the processors. This assumption is typically not true. In this thesis, we provide an extension to such systems to handle sharing of resources other than processor among tasks. Two traditional approaches exist for multiprocessor systems to schedule tasks on processors. A recent scheduling approach for multiprocessors has combined the two traditional approaches and achieved a hybrid more efficient approach compared to the two previous one. Due to the complex nature of this scheduling approach the conventional approaches for resource sharing could not be used straight forwardly. In this thesis, we have modified resource sharing approaches such that they can be used in such hybrid scheduling systems. A second concern is that enabling resource sharing in the systems can cause unpredictable delays and variations in response time of tasks which can degrade system performance. Therefore, it is of great significance to improve the resource handling techniques to reduce the effect of imposed delays caused by resource sharing in a multiprocessor platform. In this thesis we have proposed alternative techniques for resource handling that can improve system performance for special setups.
34.	Afshar, Sara, et al. (författare) Per Processor Spin-Lock Priority for Partitioned Multiprocessor Real-Time Systems 2014 Rapport (övrigt vetenskapligt/konstnärligt)abstract Two traditional approaches exist for a task that is blocked on a global resource; a task either performs a non-preemptive busy wait, i.e., spins, or suspends and releases the processor. Previously, we have shown that both approaches can be viewed as spinning either at the highest priority HP or at the lowest priority on the processor LP, respectively. Based on this view, previously we have generalized a task's blocking behavioral model, as spinning at any arbitrary priority level. In this paper, we focus on a particular class of spin-lock protocols from the introduced flexible spin-lock model where spinning is performed at a priority equal to or higher than the highest local ceiling of the global resources accessed on a processor referred to as CP spin-lock approach. In this paper, we assume that all tasks of a specific processor are spinning on the same priority level. Given this class and assumption, we show that there exists a spin-lock protocol in this range that dominates the classic spin-lock protocol which tasks spin on highest priority level (HP). However we show that this new approach is incomparable with the CP spin-lock approach. Moreover, we show that there may exist an intermediate spin-lock approach between the priority used by CP spin-lock approach and the new introduced spin-lock approach that can make a task set schedulable when those two cannot. We provide an extensive evaluation results comparing the HP, CP and the new proposed approach.
35.	Afshar, Sara, et al. (författare) Per Processor Spin-Lock Priority for Partitioned Multiprocessor Real-Time Systems 2017 Ingår i: Leibniz Transactions on Embedded Systems. - 2199-2002. ; :2 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Two traditional approaches exist for a task that is blocked on a global resource; a task either performs a non-preemptive busy wait, i.e., spins, or suspends and releases the processor. Previously, we have shown that both approaches can be viewed as spinning either at the highest priority HP or at the lowest priority on the processor LP, respectively. Based on this view, previously we have generalized a task's blocking behavioral model, as spinning at any arbitrary priority level. In this paper, we focus on a particular class of spin-lock protocols from the introduced flexible spin-lock model where spinning is performed at a priority equal to or higher than the highest local ceiling of the global resources accessed on a processor referred to as CP spin-lock approach. In this paper, we assume that all tasks of a specific processor are spinning on the same priority level. Given this class and assumption, we show that there exists a spin-lock protocol in this range that dominates the classic spin-lock protocol which tasks spin on highest priority level (HP). However we show that this new approach is incomparable with the CP spin-lock approach. Moreover, we show that there may exist an intermediate spin-lock approach between the priority used by CP spin-lock approach and the new introduced spin-lock approach that can make a task set schedulable when those two cannot. We provide an extensive evaluation results comparing the HP, CP and the new proposed approach.
36.	Afshar, Sara, et al. (författare) Resource Sharing among Prioritized Real-Time Applications on Multiprocessors 2015 Ingår i: ACM SIGBED Review - Special Issue on the 6th International Workshop on Compositional Theory and Technology for Real-Time Embedded Systems. - : Association for Computing Machinery (ACM). ; , s. 46-55 Konferensbidrag (refereegranskat)abstract In this paper, we propose a new protocol for handling resource sharing among prioritized real-time applications composed on a multiprocessor platform. We propose an optimal priority assignment algorithm which assigns unique priorities to the applications based on information in their interfaces. We have performed experimental evaluations to compare the proposed protocol (called MSOS-Priority) to the current state of the art locking protocols under multiprocessor partitioned scheduling, i.e., MPCP, MSRP, FMLP, MSOS, and OMLP. The valuations show that MSOS-Priority mostly performs significantly better than alternative approaches.
37.	Afshar, Sara, et al. (författare) Resource sharing in a hybrid partitioned/global scheduling framework for multiprocessors 2015 Ingår i: IEEE International Conference on Emerging Technologies and Factory Automation, ETFA. - 9781467379298 Konferensbidrag (refereegranskat)abstract For resource-constrained embedded real-time systems, resource-efficient approaches are very important. Such an approach is presented in this paper, targeting systems where a critical application is partitioned on a multi-core platform and the remaining capacity on each core is provided to a noncritical application using resource reservation techniques. To exploit the potential parallelism of the non-critical application, global scheduling is used for its constituent tasks. Previously, we enabled intra-application resource sharing for such a framework, i.e. each application has its own dedicated set of resources. In this paper, we enable inter-application resource sharing, in particular between the critical application and the non-critical application. This effectively enables resource sharing in a hybrid partitioned/global scheduling framework on multiprocessors. For resource sharing, we use a spin-based synchronization protocol. We derive blocking bounds and extend existing schedulability analysis for such a system.
38.	Afshar, Sara, et al. (författare) Resource Sharing Under Global Scheduling with Partial Processor Bandwidth 2015 Ingår i: 2015 10th IEEE International Symposium on Industrial Embedded Systems, SIES 2015 - Proceedings. - 9781467377119 ; , s. 195-206 Konferensbidrag (refereegranskat)abstract Resource efficient approaches are of great importance for resource constrained embedded systems. In this paper, we present an approach targeting systems where tasks of a critical application are partitioned on a multi-core platform and by using resource reservation techniques, the remaining bandwidth capacity on each core is utilized for one or a set of non-critical application(s). To provide a resource efficient solution and to exploit the potential parallelism of the extra applications on the multi-core processor, global scheduling is used to schedule the tasks of the non-critical applications. Recently a specific instantiation of such a system has been studied where tasks do not share resources other than the processor. In this paper, we enable semaphore-based resource sharing among tasks within critical and non-critical applications using a suspension-based synchronization protocol. Tasks of non-critical applications have partial access to the processor bandwidth. The paper provides the systems schedulability analysis where blocking due to resource sharing is bounded. Further, we perform experimental evaluations under balanced and unbalanced allocation of tasks of a critical application to cores.
39.	Afshar, Sara, et al. (författare) Resource Sharing under Multiprocessor Semi-Partitioned Scheduling 2012 Ingår i: 18th IEEE International Conference on Embedded and Real-Time Computing Systems and Applications (RTCSA'12). - : IEEE. - 9781467330176 - 9780769548241 ; , s. 290-299 Konferensbidrag (refereegranskat)abstract Semi-partitioned scheduling has become the subject of recent interest for multiprocessors due to better utilization results, compared to conventional global and partitioned scheduling algorithms. Under semi-partitioned scheduling, a major group of tasks are assigned to fixed processors while a low number of tasks are allocated to more than one processor. Various task assigning techniques have recently been proposed in a semi-partitioned environment. However, a synchronization mechanism for resource sharing among tasks in semi-partitioned scheduling has not yet been investigated. In this paper we propose and evaluate two methods for handling resource sharing under semi-partitioned scheduling in multiprocessor platforms. The main challenge addressed in this paper is to serve the resource requests of tasks that are assigned to different processors.
40.	Afshar, Sara, et al. (författare) Semi-partitioning under a Blocking-Aware Task Allocation 2015 Ingår i: Proceedings - Real-Time Systems Symposium. - 9781467395076 ; , s. 379-379 Konferensbidrag (refereegranskat)abstract Semi-partitioned scheduling is a resource efficient scheduling approach compared to the conventional multiprocessor scheduling approaches in terms of system utilization and migration overhead. Semi-partitioned scheduling can better utilize processor bandwidth compared to the partitioned scheduling while introducing less overhead compared to the global scheduling. Various techniques have been proposed to schedule tasks in a semi-partitioned environment, however, they have used blockingagnostic allocation mechanisms in presence of resource sharing protocols. Since, the allocation mechanism can highly affect the system schedulability, in this paper we provide a blocking-aware allocation mechanism for semi-partitioned scheduling framework under a suspension-based resource sharing protocol. We have applied new heuristics for sorting the tasks in the algorithm that shows improvements upon system schedulability. Finally, we present our preliminary results.
41.	Afshar, Sara, et al. (författare) Towards Resource Sharing under Multiprocessor Semi-Partitioned Scheduling 2012 Ingår i: 7th IEEE International Symposium on Industrial Embedded Systems (SIES'12). - : IEEE. - 9781467326834 - 9781467326858 ; , s. 315-318 Konferensbidrag (refereegranskat)abstract Semi-partitioned scheduling has been the subject of recent interest, compared with conventional global and partitioned scheduling algorithms for multiprocessors, due to better utilization results. In semi-partitioned scheduling most tasks are assigned to fixed processors while a low number of tasks are split up and allocated to different processors. Various techniques have recently been proposed to assign tasks in a semi-partitioned environment. However, an appropriate resource sharing mechanism for handling the resource requests between tasks in semi-partitioned scheduling has not yet been investigated. In this paper we propose two methods for handling resource sharing under semi-partitioned scheduling in multiprocessor platforms. The main challenge is to handle the resource requests of tasks that are split over multiple processors.
42.	Afshar, Sara Zargari, et al. (författare) An optimal spin-lock priority assignment algorithm for real-time multi-core systems 2017 Ingår i: The 23th IEEE International Conference on Embedded and Real-Time Computing Systems and Applications RTCSA'17. Konferensbidrag (refereegranskat)abstract Support for exclusive access to shared (global) resources is instrumental in the context of embedded real-time multi-core systems, and mechanisms for achieving such access must be deterministic and efficient. There exist two traditional approaches for multiprocessors when a task requests a global resource that is locked by a task on a remote core: a spin-based approach, i.e. non-preemptive busy waiting for the resource to become available, and a suspension-based approach, i.e. the task relinquishes the processor. A suspension-based approach can be viewed as a spin-based approach where the lowest priority on a core is used during spinning, similar to a non-preemptive spin-based approach where the highest priority on a core is used. By taking such a view, we previously provided a general model for spinning, where any arbitrary priority can be used for spinning, i.e. from the lowest to the highest priority on a core. Targeting partitioned fixed-priority preemptive scheduled multiprocessors and spin-based approaches that use a fixed priority for spinning per core for all tasks, we aim at increasing the schedulability of multiprocessor systems by using the spin-lock priority per core as parameter. In this paper, we present (i) a generalization of the traditional worst-case response-time analysis for non-preemptive spin-based approaches addressing an arbitrary but fixed spin-lock priority per core, (ii) an optimal spin-lock priority assignment (OSPA) algorithm per core, i.e. an algorithm that will find a fixed spin-lock priority per core that will make the system schedulable, whenever such an assignment exists and, (iii) comparative evaluations of the OSPA algorithm with the spin-based and suspension-based approaches where OSPA showed up to 38% improvement compared to both approaches.
43.	Al-Dulaimy, Auday, et al. (författare) Fault Tolerance in Cloud Manufacturing : An Overview 2023 Ingår i: Lecture Notes of the Institute for Computer Sciences, Social-Informatics and Telecommunications Engineering, LNICST. - : Springer Science and Business Media Deutschland GmbH. - 9783031318900 ; , s. 89-101 Konferensbidrag (refereegranskat)abstract Utilizing edge and cloud computing to empower the profitability of manufacturing is drastically increasing in modern industries. As a result of that, several challenges have raised over the years that essentially require urgent attention. Among these, coping with different faults in edge and cloud computing and recovering from permanent and temporary faults became prominent issues to be solved. In this paper, we focus on the challenges of applying fault tolerance techniques on edge and cloud computing in the context of manufacturing and we investigate the current state of the proposed approaches by categorizing them into several groups. Moreover, we identify critical gaps in the research domain as open research directions. © 2023, ICST Institute for Computer Sciences, Social Informatics and Telecommunications Engineering.
44.	Al-Dulaimy, Auday, et al. (författare) LOOPS : A Holistic Control Approach for Resource Management in Cloud Computing 2021 Ingår i: ICPE 2021 - Proceedings of the ACM/SPEC International Conference on Performance Engineering. - New York, NY, USA : Association for Computing Machinery (ACM). - 9781450381949 ; , s. 117-124 Konferensbidrag (refereegranskat)abstract In cloud computing model, resource sharing introduces major benefits for improving resource utilization and total cost of ownership, but it can create technical challenges on the running performance. In practice, orchestrators are required to allocate sufficient physical resources to each Virtual Machine (VM) to meet a set of predefined performance goals. To ensure a specific service level objective, the orchestrator needs to be equipped with a dynamic tool for assigning computing resources to each VM, based on the run-Time state of the target environment. To this end, we present LOOPS, a multi-loop control approach, to allocate resources to VMs based on the service level agreement (SLA) requirements and the run-Time conditions. LOOPS is mainly composed of one essential unit to monitor VMs, and three control levels to allocate resources to VMs based on requests from the essential node. A tailor-made controller is proposed with each level to regulate contention among collocated VMs, to reallocate resources if required, and to migrate VMs from one host to another. The three levels work together to meet the required SLA. The experimental results have shown that the proposed approach can meet applications' performance goals by assigning the resources required by cloud-based applications.
45.	Al-Furoukh, Natalie, et al. (författare) ClpX stimulates the mitochondrial unfolded protein response (UPRmt) in mammalian cells 2015 Ingår i: Biochimica et Biophysica Acta. Molecular Cell Research. - : Elsevier BV. - 0167-4889 .- 1879-2596. ; 1853:10, s. 2580-2591 Tidskriftsartikel (refereegranskat)abstract Proteostasis is crucial for life and maintained by cellular chaperones and proteases. One major mitochondrial protease is the ClpXP complex, which is comprised of a catalytic ClpX subunit and a proteolytic ClpP subunit. Based on two separate observations, we hypothesized that ClpX may play a leading role in the cellular function of ClpXP. Therefore, we analyzed the effect of ClpX overexpression on a myoblast proteome by quantitative proteomics. ClpX overexpression results in the upregulation of markers of the mitochondria( proteostasis pathway, known as the "mitochondrial unfolded protein response" (UPRmt). Although this pathway is described in detail in Caenorhabditis elegans, it is not clear whether it is conserved in mammals. Therefore, we compared features of the classical nematode UPRmt with our mammalian ClpX-triggered UPRmt dataset. We show that they share the same retrograde mitochondria-to-nucleus signaling pathway that involves the key UPRmt transcription factor CHOP (also known as Ddit3, CEBPZ or GADD153). In conclusion, our data confirm the existence of a mammalian UPRmt that has great similarity to the C elegans pathway. Furthermore, our results illustrate that ClpX overexpression is a good and simple model to study the underlying mechanisms of the UPRmt in mammalian cells.
46.	Alhashimi, Anas, et al. (författare) Change-Point and Model Estimation with Heteroskedastic Noise and Unknown Model Structure 2023 Ingår i: Int. Conf. Control, Decis. Inf. Technol., CoDIT. - : Institute of Electrical and Electronics Engineers Inc.. - 9798350311402 ; , s. 2126-2132 Konferensbidrag (refereegranskat)abstract In this paper, we investigate the problem of modeling time-series as a process generated through (i) switching between several independent sub-models; (ii) where each sub-model has heteroskedastic noise, and (iii) a polynomial bias, describing nonlinear dependency on system input. First, we propose a generic nonlinear and heteroskedastic statistical model for the process. Then, we design Maximum Likelihood (ML) parameters estimation method capable of handling heteroscedasticity and exploiting constraints on model structure. We investigate solving the intractable ML optimization using population-based stochastic numerical methods. We then find possible model change-points that maximize the likelihood without over-fitting measurement noise. Finally, we verify the usefulness of the proposed technique in a practically relevant case study, the execution-time of odometry estimation for a robot operating radar sensor, and evaluate the different proposed procedures using both simulations and field data.
47.	Alhashimi, Anas, et al. (författare) Enhancing Sensor Attack Detection and Mitigating Sensor Compromise Impact in a Switching-Based Moving Target Defense 2024 Ingår i: 2024 European Control Conference, ECC 2024. - : Institute of Electrical and Electronics Engineers Inc.. - 9783907144107 ; , s. 2560-2567 Konferensbidrag (refereegranskat)abstract This study is based on a Moving Target Defence (MTD) algorithm designed to introduce uncertainty into the controller and another layer of uncertainty to intrusion detection. This randomness complicates the adversary's attempts to craft stealthy attacks while concurrently minimizing the impact of false-data injection attacks. Leveraging concepts from state observer design, the method establishes an optimization framework to determine the parameters of the random signals. These signals are strategically tuned to increase the detectability of stealthy attacks while reducing the deviation resulting from false data injection attempts. We propose here to use two different state observers and two associated MTD algorithms. The first one optimizes the parameters of the random signals to reduce the deviation resulting from false data injection attempts and maintain the stability of the closed-loop system with the desired level of performance. In contrast, the second one optimizes the parameters of the random signals to increase the detectability of stealthy attacks. Dividing the optimization problem into two separate optimization processes simplifies the search process and makes it possible to have higher values of the detection cost function. To illustrate the effectiveness of our approach, we present a case study involving a generic linear time-invariant system and compare the results with a recently published algorithm.
48.	Ashjaei, Mohammad, et al. (författare) A Compact Approach to Clustered Master-Slave Ethernet Networks 2012 Ingår i: IEEE International Workshop on Factory Communication Systems - Proceedings, WFCS. - 9781467315739 ; , s. 157-160 Konferensbidrag (refereegranskat)abstract Ethernet switches are increasingly used in real-time distributed systems as a technical solution to guarantee the timeliness in communications. However, there are still limitations related to real-time behavior caused by the limited number of priority levels and the possibility of memory overruns with consequent message losses. These limitations can be eliminated using a master/slave technique such as proposed by the FTT paradigm. This led to the FTT-SE protocol that schedules transmissions centrally in a master node. While this protocol has already been well studied and investigated for small networks with a single switch, its extension to larger networks is still an open issue. In this paper we propose a compact clustered solution to scale the FTT-SE protocol to networks of multiple switches by organizing the network in sub-networks composed of one master and one switch each and which can be connected directly, without bridges. This paper also shows how the timeliness of the traffic can still be enforced. The validation is currently on-going.
49.	Ashjaei, Mohammad, 1980-, et al. (författare) Designing end-to-end resource reservations in predictable distributed embedded systems 2017 Ingår i: Real-time systems. - : Springer Science and Business Media LLC. - 0922-6443 .- 1573-1383. ; 53:6, s. 916-956 Tidskriftsartikel (refereegranskat)
50.	Ashjaei, Mohammad, et al. (författare) Dynamic reconfiguration in HaRTES switched ethernet networks 2016 Ingår i: IEEE International Workshop on Factory Communication Systems - Proceedings, WFCS. - 9781509023394 Konferensbidrag (refereegranskat)abstract The ability of reconfiguring a system during runtime is essential for dynamic real-time applications in which resource usage is traded online for quality of service. The HaRTES switch, which is a modified Ethernet switch, holds this ability for the network resource, and at the same time it provides hard real-time support for both periodic and sporadic traffic. Although the HaRTES switch technologically caters this ability, a protocol to actually perform the dynamic reconfiguration is missing in multi-hop HaRTES networks. In this paper we introduce such a protocol that is compatible with the traffic scheduling method used in the architecture. We prove the correctness of the protocol using a model checking technique. Moreover, we conduct a set of simulation experiments to show the performance of the protocol and we also show that the reconfiguration process is terminated within a bounded time.

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