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1.	Blach, S., et al. (author) Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study 2022 In: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 7:5, s. 396-415 Journal article (peer-reviewed)abstract Background Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. Methods This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age =0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories. Findings Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0.7% (95% UI 0.7-0.9), corresponding to 56.8 million (95% UI 55.2-67.8) infections, on Jan 1, 2020. This number represents a decrease of 6.8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63.6 million (61.8-75.8) infections (0.9% [0.8-1.0] prevalence). By the end of 2020, an estimated 12.9 million (12.5-15.4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641 000 (623 000-765 000) patients initiated treatment. Interpretation At the beginning of 2020, there were an estimated 56.8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
2.	Locke, Adam E, et al. (author) Genetic studies of body mass index yield new insights for obesity biology. 2015 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401 Journal article (peer-reviewed)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.
3.	Asselbergs, Folkert W., et al. (author) Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci 2012 In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 91:5, s. 823-838 Journal article (peer-reviewed)abstract Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering similar to 2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.
4.	Kanoni, Stavroula, et al. (author) Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis. 2022 In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1 Journal article (peer-reviewed)abstract Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
5.	Librado, P., et al. (author) The origins and spread of domestic horses from the Western Eurasian steppes 2021 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 598, s. 634-640 Journal article (peer-reviewed)abstract Analysis of 273 ancient horse genomes reveals that modern domestic horses originated in the Western Eurasian steppes, especially the lower Volga-Don region. Domestication of horses fundamentally transformed long-range mobility and warfare(1). However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling(2-4) at Botai, Central Asia around 3500 bc(3). Other longstanding candidate regions for horse domestication, such as Iberia(5) and Anatolia(6), have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 bc, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association(7) between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 bc(8,9) driving the spread of Indo-European languages(10). This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium bc Sintashta culture(11,12).
6.	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.
7.	Olalde, I., et al. (author) The Beaker phenomenon and the genomic transformation of northwest Europe 2018 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 555:7695, s. 190-196 Journal article (peer-reviewed)abstract From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.
8.	Razavi, H., et al. (author) Hepatitis C virus prevalence and level of intervention required to achieve the WHO targets for elimination in the European Union by 2030: a modelling study 2017 In: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 2:5, s. 325-336 Journal article (peer-reviewed)abstract Background Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide. In the European Union (EU), treatment and cure of HCV with direct-acting antiviral therapies began in 2014. WHO targets are to achieve a 65% reduction in liver-related deaths, a 90% reduction of new viral hepatitis infections, and 90% of patients with viral hepatitis infections being diagnosed by 2030. This study assessed the prevalence of HCV in the EU and the level of intervention required to achieve WHO targets for HCV elimination. Methods We populated country Markov models for the 28 EU countries through a literature search of PubMed and Embase between Jan 1, 2000, and March 31, 2016, and a Delphi process to gain expert consensus and validate inputs. We aggregated country models to create a regional EU model. We used the EU model to forecast HCV disease progression (considering the effect of immigration) and developed a strategy to acehive WHO targets. We used weighted average sustained viral response rates and fibrosis restrictions to model the effect of current therapeutic guidelines. We used the EU model to forecast HCV disease progression (considering the effect of immigration) under current screening and therapeutic guidelines. Additionally, we back-calculated the total number of patients needing to be screened and treated to achieve WHO targets. Findings We estimated the number of viraemic HCV infections in 2015 to be 3 238 000 (95% uncertainty interval [UI] 2 106 000-3 795 000) of a total population of 509 868 000 in the EU, equating to a prevalence of viraemic HCV of 0.64% (95% UI 0.41-0.74). We estimated that 1 180 000 (95% UI 1 003 000-1 357 000) people were diagnosed with viraemia (36.4%), 150 000 (12 000-180 000) were treated (4.6% of the total infected population or 12.7% of the diagnosed population), 133 000 (106 000-160 000) were cured (4.1%), and 57 900 (43 900-67 300) were newly infected (1.8%) in 2015. Additionally, 30 400 (26 600-42 500) HCV-positive immigrants entered the EU. To achieve WHO targets, unrestricted treatment needs to increase from 150 000 patients in 2015 to 187 000 patients in 2025 and diagnosis needs to increase from 88 800 new cases annually in 2015 to 180 000 in 2025. Interpretation Given its advanced health-care infrastructure, the EU is uniquely poised to eliminate HCV; however, expansion of screening programmes is essential to increase treatment to achieve the WHO targets. A united effort, grounded in sound epidemiological evidence, will also be necessary.
9.	Razavi-Shearer, DM, et al. (author) Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study 2023 In: The lancet. Gastroenterology & hepatology. - : Elsevier. - 2468-1253. ; 8:10, s. 879-907 Journal article (peer-reviewed)
10.	Razavi-Shearer, D, et al. (author) Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study 2018 In: The lancet. Gastroenterology & hepatology. - : Elsevier. - 2468-1253. ; 3:6, s. 383-403 Journal article (peer-reviewed)
11.	Speliotes, Elizabeth K., et al. (author) Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index 2010 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948 Journal article (peer-reviewed)abstract Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
12.	Shungin, Dmitry, et al. (author) New genetic loci link adipose and insulin biology to body fat distribution. 2015 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378 Journal article (peer-reviewed)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.
13.	Blach, S, et al. (author) Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study 2022 In: The lancet. Gastroenterology & hepatology. - : Elsevier. - 2468-1253. ; 7:5, s. 396-415 Journal article (peer-reviewed)
14.	Heid, Iris M, et al. (author) Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution 2010 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960 Journal article (peer-reviewed)abstract Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
15.	Palmer, Nicholette D, et al. (author) A genome-wide association search for type 2 diabetes genes in African Americans. 2012 In: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202- Journal article (peer-reviewed)abstract African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
16.	Razavi, H, et al. (author) Hepatitis C virus prevalence and level of intervention required to achieve the WHO targets for elimination in the European Union by 2030: a modelling study 2017 In: The lancet. Gastroenterology & hepatology. - : Elsevier. - 2468-1253. ; 2:5, s. 325-336 Journal article (peer-reviewed)
17.	Filipe, A., et al. (author) White Book on Physical and Rehabilitation Medicine in Europe Introductions, Executive Summary, and Methodology 2018 In: European Journal of Physical and Rehabilitation Medicine. - : Edizioni Minerva Medica. - 1973-9087 .- 1973-9095. ; 54:2, s. 125-155 Journal article (peer-reviewed)abstract The White Book (WB) of Physical and Rehabilitation Medicine (PRM) in Europe is produced by the 4 European PRM Bodies (European Academy of Rehabilitation Medicine - EARM, European Society of PRM - ESPRM, European Union of Medical Specialists - PRM Section, European College of PRM-ECPRM served by the European Union of Medical Specialists-PRM Board) and constitutes the reference book for PRM physicians in Europe. It has now reached its third edition; the first was published in 1989 and the second in 2006/2007. The WB has multiple purposes, including providing a unifying framework for European countries, to inform decision-makers on European and national level, to offer educational material for PRM trainees and physicians and information about PRM to the medical community, other rehabilitation professionals and the public. The WB states the importance of PRM, a primary medical specialty that is present all over Europe, with a specific corpus disciplinae, a common background and history throughout Europe. PRM is internationally recognized and a partner of major international bodies, including the World Health Organization (WHO). PRM activities are strongly based on the documents of the United Nations (UN) and WHO, such as the Convention of the Rights of Persons with Disabilities (2006), the World Report on Disability (2011), the WHO Global Disability Action Plan 2014-2021 (2014) and the WHO initiative "Rehabilitation 2030: a call for action" (2017). The WB is organized in 4 sections, 11 chapters and some appendices. The WB starts with basic definitions and concepts of PRM and continues with why rehabilitation is needed by individuals and society. Rehabilitation focuses not only on health conditions but also on functioning. Accordingly. PRM is the medical specialty that strives to improve functioning of people with a health condition or experiencing disability. The fundamentals of PRM, the history of the PRM specialty, and the structure and activities of PRM organizations in Europe are presented, followed by a thorough presentation of the practice of PRM, i.e. knowledge and skills of PRM physicians, the clinical field of competence of PRM, the place of the PRM specialty in the healthcare system and society, education and continuous professional development of PRM physicians, specificities and challenges of science and research in PRM. The WB concludes with the way forward for the specialty: challenges and perspectives for the future of PRM.
18.	Justice, Anne E., et al. (author) Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution 2019 In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469 Journal article (peer-reviewed)abstract Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
19.	Berndt, Sonja I., et al. (author) Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture 2013 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69 Journal article (peer-reviewed)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.
20.	Fages, A., et al. (author) Tracking Five Millennia of Horse Management with Extensive Ancient Genome Time Series 2019 In: Cell. - : Elsevier BV. - 0092-8674. ; 177:6 Journal article (peer-reviewed)abstract Horse domestication revolutionized warfare and accelerated travel, trade, and the geographic expansion of languages. Here, we present the largest DNA time series for a non-human organism to date, including genome-scale data from 149 ancient animals and 129 ancient genomes (>= 1-fold coverage), 87 of which are new. This extensive dataset allows us to assess the modem legacy of past equestrian civilisations. We find that two extinct horse lineages existed during early domestication, one at the far western (Iberia) and the other at the far eastern range (Siberia) of Eurasia. None of these contributed significantly to modern diversity. We show that the influence of Persian-related horse lineages increased following the Islamic conquests in Europe and Asia. Multiple alleles associated with elite-racing, including at the MSTN "speed gene," only rose in popularity within the last millennium. Finally, the development of modem breeding impacted genetic diversity more dramatically than the previous millennia of human management.
21.	Voight, Benjamin F., et al. (author) Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis 2010 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:7, s. 579-589 Journal article (peer-reviewed)abstract By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
22.	Aad, G, et al. (author) Measurements of the Higgs boson inclusive and differential fiducial cross sections in the 4 ℓ decay channel at √s = 13 TeV 2020 In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 80:10 Journal article (peer-reviewed)abstract Inclusive and differential fiducial cross sections of the Higgs boson are measured in the H→ ZZ∗→ 4 ℓ (ℓ= e, μ) decay channel. The results are based on proton−proton collision data produced at the Large Hadron Collider at a centre-of-mass energy of 13 TeV and recorded by the ATLAS detector from 2015 to 2018, equivalent to an integrated luminosity of 139 fb - 1. The inclusive fiducial cross section for the H→ ZZ∗→ 4 ℓ process is measured to be σfid= 3.28 ± 0.32 fb, in agreement with the Standard Model prediction of σfid , SM= 3.41 ± 0.18 fb. Differential fiducial cross sections are measured for a variety of observables which are sensitive to the production and decay of the Higgs boson. All measurements are in agreement with the Standard Model predictions. The results are used to constrain anomalous Higgs boson interactions with Standard Model particles. © 2020, The Author(s).
23.	Allentoft, M. E., et al. (author) Population genomics of Bronze Age Eurasia 2015 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 522:7555 Journal article (peer-reviewed)abstract The Bronze Age of Eurasia (around 3000-1000 BC) was a period of major cultural changes. However, there is debate about whether these changes resulted from the circulation of ideas or from human migrations, potentially also facilitating the spread of languages and certain phenotypic traits. We investigated this by using new, improved methods to sequence low-coverage genomes from 101 ancient humans from across Eurasia. We show that the Bronze Age was a highly dynamic period involving large-scale population migrations and replacements, responsible for shaping major parts of present-day demographic structure in both Europe and Asia. Our findings are consistent with the hypothesized spread of Indo-European languages during the Early Bronze Age. We also demonstrate that light skin pigmentation in Europeans was already present at high frequency in the Bronze Age, but not lactose tolerance, indicating a more recent onset of positive selection on lactose tolerance than previously thought.
24.	Crosby, Jacy, et al. (author) Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease 2014 In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 371:1, s. 22-31 Journal article (peer-reviewed)abstract Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G -> A and IVS3+1G -> T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1x10(-20)), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8x10(-10)). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4x10(-6)). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.)
25.	Do, Ron, et al. (author) Common variants associated with plasma triglycerides and risk for coronary artery disease 2013 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345- Journal article (peer-reviewed)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.
26.	Gaulton, Kyle J, et al. (author) Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci. 2015 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415 Journal article (peer-reviewed)abstract We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
27.	Gorski, Mathias, et al. (author) Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies 2022 In: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639 Journal article (peer-reviewed)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.
28.	Lange, Leslie A, et al. (author) Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol. 2014 In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:2, s. 233-245 Journal article (peer-reviewed)abstract Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or <2(nd) percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.
29.	Leebens-Mack, James H., et al. (author) One thousand plant transcriptomes and the phylogenomics of green plants 2019 In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679- Journal article (peer-reviewed)abstract Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
30.	Ried, Janina S., et al. (author) A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape 2016 In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7 Journal article (peer-reviewed)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.
31.	Surendran, Praveen, et al. (author) Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension 2016 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1151-1161 Journal article (peer-reviewed)abstract High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
32.	Webb, Thomas R., et al. (author) Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease 2017 In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 69:7, s. 823-836 Journal article (peer-reviewed)abstract BACKGROUND Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.OBJECTIVES This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.METHODS In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs.RESULTS We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 x 10(-4) with a range of other diseases/traits.CONCLUSIONS We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.
33.	Willer, Cristen J., et al. (author) Discovery and refinement of loci associated with lipid levels 2013 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283 Journal article (peer-reviewed)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.
34.	Aaboud, M, et al. (author) Measurement of fiducial and differential W+W- production cross-sections at √s=13 TeV with the ATLAS detector 2019 In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 79:10 Journal article (peer-reviewed)abstract A measurement of fiducial and differential cross-sections for W+W- production in proton–proton collisions at s=13 TeV with the ATLAS experiment at the Large Hadron Collider using data corresponding to an integrated luminosity of 36.1 fb - 1 is presented. Events with one electron and one muon are selected, corresponding to the decay of the diboson system as WW→ e±νμ∓ν. To suppress top-quark background, events containing jets with a transverse momentum exceeding 35 GeV are not included in the measurement phase space. The fiducial cross-section, six differential distributions and the cross-section as a function of the jet-veto transverse momentum threshold are measured and compared with several theoretical predictions. Constraints on anomalous electroweak gauge boson self-interactions are also presented in the framework of a dimension-six effective field theory. © 2019, CERN for the benefit of the ATLAS collaboration.
35.	Aad, G, et al. (author) Performance of electron and photon triggers in ATLAS during LHC Run 2 2020 In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 80:1 Journal article (peer-reviewed)abstract Results are presented from the measurement by ATLAS of long-range (\| Δ η\| > 2) dihadron angular correlations in s=8 and 13 TeV pp collisions containing a Z boson. The analysis is performed using 19.4 fb - 1 of s=8 TeV data recorded during Run 1 of the LHC and 36.1 fb - 1 of s=13 TeV data recorded during Run 2. Two-particle correlation functions are measured as a function of relative azimuthal angle over the relative pseudorapidity range 2 < \| Δ η\| < 5 for different intervals of charged-particle multiplicity and transverse momentum. The measurements are corrected for the presence of background charged particles generated by collisions that occur during one passage of two colliding proton bunches in the LHC. Contributions to the two-particle correlation functions from hard processes are removed using a template-fitting procedure. Sinusoidal modulation in the correlation functions is observed and quantified by the second Fourier coefficient of the correlation function, v2 , 2, which in turn is used to obtain the single-particle anisotropy coefficient v2. The v2 values in the Z-tagged events, integrated over 0.5 < pT< 5 GeV, are found to be independent of multiplicity and s, and consistent within uncertainties with previous measurements in inclusive pp collisions. As a function of charged-particle pT, the Z-tagged and inclusive v2 values are consistent within uncertainties for pT< 3 GeV. © 2020, CERN for the benefit of the ATLAS collaboration.
36.	Aidas, Kestutis, et al. (author) The Dalton quantum chemistry program system 2014 In: WIREs Computational Molecular Science. - : Wiley. - 1759-0876 .- 1759-0884. ; 4:3, s. 269-284 Journal article (peer-reviewed)abstract Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree-Fock, Kohn-Sham, multiconfigurational self-consistent-field, MOller-Plesset, configuration-interaction, and coupled-cluster levels of theory. Apart from the total energy, a wide variety of molecular properties may be calculated using these electronic-structure models. Molecular gradients and Hessians are available for geometry optimizations, molecular dynamics, and vibrational studies, whereas magnetic resonance and optical activity can be studied in a gauge-origin-invariant manner. Frequency-dependent molecular properties can be calculated using linear, quadratic, and cubic response theory. A large number of singlet and triplet perturbation operators are available for the study of one-, two-, and three-photon processes. Environmental effects may be included using various dielectric-medium and quantum-mechanics/molecular-mechanics models. Large molecules may be studied using linear-scaling and massively parallel algorithms. Dalton is distributed at no cost from for a number of UNIX platforms.
37.	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.
38.	Garcia-Loro, F., et al. (author) PILAR : A Federation of VISIR Remote Laboratory Systems for Educational Open Activities 2018 In: Proceedings of 2018 IEEE International Conference on Teaching, Assessment, and Learning for Engineering, TALE 2018. - : Institute of Electrical and Electronics Engineers Inc.. - 9781538665220 ; , s. 134-141 Conference paper (peer-reviewed)abstract Social demands have promoted an educational approach based on an 'anywhere and anytime' premise. Remote laboratories have emerged as the answer to the demands of technical educational areas for adapting themselves to this scenario. The result has not only benefit distance learning students but has provided new learning scenarios both for teachers and students as well as allowing a flexible approach to experimental topics. However, as any other solution for providing practical scenarios (hands-on labs, virtual labs or simulators), remote labs face several constraints inherited from the subsystems of its deployment - hardware (real instruments, equipment and scenario) and software (analog/digital conversions, communications, workbenches, etc.}. This paper describes the Erasmus+ project Platform Integration of Laboratories based on the Architecture of visiR (PILAR) which deals with several units of the federation installed in different educational institutions and devoted to analog electronics and electrical circuits. Based on the limitations of remote labs, the need for the federation will be justified and its benefits will be described by taking advantage of its strengths. The challenges that have come up during the different stages and the different approaches to design are also going to be described and analyzed. © 2018 IEEE.
39.	Larsson, D. G. Joakim, 1969, et al. (author) Critical knowledge gaps and research needs related to the environmental dimensions of antibiotic resistance 2018 In: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 117, s. 132-138 Research review (peer-reviewed)abstract There is growing understanding that the environment plays an important role both in the transmission of antibiotic resistant pathogens and in their evolution. Accordingly, researchers and stakeholders world-wide seek to further explore the mechanisms and drivers involved, quantify risks and identify suitable interventions. There is a clear value in establishing research needs and coordinating efforts within and across nations in order to best tackle this global challenge. At an international workshop in late September 2017, scientists from 14 countries with expertise on the environmental dimensions of antibiotic resistance gathered to define critical knowledge gaps. Four key areas were identified where research is urgently needed: 1) the relative contributions of different sources of antibiotics and antibiotic resistant bacteria into the environment; 2) the role of the environment, and particularly anthropogenic inputs, in the evolution of resistance; 3) the overall human and animal health impacts caused by exposure to environmental resistant bacteria; and 4) the efficacy and feasibility of different technological, social, economic and behavioral interventions to mitigate environmental antibiotic resistance.(1)
40.	Milstead, David A., et al. (author) Properties of g→b¯b at small opening angles in pp collisions with the ATLAS detector at √s=13 TeV 2019 In: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 99:5 Journal article (peer-reviewed)abstract The fragmentation of high-energy gluons at small opening angles is largely unconstrained by present measurements. Gluon splitting to b-quark pairs is a unique probe into the properties of gluon fragmentation because identified b-tagged jets provide a proxy for the quark daughters of the initial gluon. In this study, key differential distributions related to the g→bb process are measured using 33 fb-1 of s=13 TeV pp collision data recorded by the ATLAS experiment at the LHC in 2016. Jets constructed from charged-particle tracks, clustered with the anti-kt jet algorithm with radius parameter R=0.2, are used to probe angular scales below the R=0.4 jet radius. The observables are unfolded to particle level in order to facilitate direct comparisons with predictions from present and future simulations. Multiple significant differences are observed between the data and parton shower Monte Carlo predictions, providing input to improve these predictions of the main source of background events in analyses involving boosted Higgs bosons decaying into b-quarks. © 2019 CERN.
41.	Milstead, David A., et al. (author) Search for heavy long-lived multicharged particles in proton-proton collisions at s =13 TeV using the ATLAS detector 2019 In: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 99:5 Journal article (peer-reviewed)abstract A search for heavy long-lived multicharged particles is performed using the ATLAS detector at the LHC. Data with an integrated luminosity of 36.1 fb-1 collected in 2015 and 2016 from proton-proton collisions at s=13 TeV are examined. Particles producing anomalously high ionization, consistent with long-lived massive particles with electric charges from \|q\|=2e to \|q\|=7e, are searched for. No events are observed, and 95% confidence level cross-section upper limits are interpreted as lower mass limits for a Drell-Yan production model. Multicharged particles with masses between 50 and 980-1220 GeV (depending on their electric charge) are excluded. © 2019 CERN.
42.	Milstead, David A., et al. (author) Search for long-lived particles produced in pp collisions at s =13 TeV that decay into displaced hadronic jets in the ATLAS muon spectrometer 2019 In: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 99:5 Journal article (peer-reviewed)abstract A search for the decay of neutral, weakly interacting, long-lived particles using data collected by the ATLAS detector at the LHC is presented. The analysis in this paper uses 36.1 fb-1 of proton-proton collision data at s=13 TeV recorded in 2015-2016. The search employs techniques for reconstructing vertices of long-lived particles decaying into jets in the muon spectrometer exploiting a two-vertex strategy and a novel technique that requires only one vertex in association with additional activity in the detector that improves the sensitivity for longer lifetimes. The observed numbers of events are consistent with the expected background and limits for several benchmark signals are determined. © 2019 CERN.
43.	Pearce, Neil E, et al. (author) IARC Monographs : 40 Years of Evaluating Carcinogenic Hazards to Humans 2015 In: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 507-514 Journal article (peer-reviewed)abstract BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' failures to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.OBJECTIVES: The authors of this paper are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We have examined here criticisms of the IARC classification process to determine the validity of these concerns. We review the history of IARC evaluations and describe how the IARC evaluations are performed.DISCUSSION: We conclude that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various discipline and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.
44.	Sikora, M., et al. (author) The population history of northeastern Siberia since the Pleistocene 2019 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 570:7760 Journal article (peer-reviewed)abstract Northeastern Siberia has been inhabited by humans for more than 40,000 years but its deep population history remains poorly understood. Here we investigate the late Pleistocene population history of northeastern Siberia through analyses of 34 newly recovered ancient genomes that date to between 31,000 and 600 years ago. We document complex population dynamics during this period, including at least three major migration events: an initial peopling by a previously unknown Palaeolithic population of 'Ancient North Siberians' who are distantly related to early West Eurasian hunter-gatherers; the arrival of East Asian-related peoples, which gave rise to 'Ancient Palaeo-Siberians' who are closely related to contemporary communities from far-northeastern Siberia (such as the Koryaks), as well as Native Americans; and a Holocene migration of other East Asian-related peoples, who we name 'Neo-Siberians', and from whom many contemporary Siberians are descended. Each of these population expansions largely replaced the earlier inhabitants, and ultimately generated the mosaic genetic make-up of contemporary peoples who inhabit a vast area across northern Eurasia and the Americas.
45.	Stitziel, Nathan O., et al. (author) Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease 2016 In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 374:12, s. 1134-1144 Journal article (peer-reviewed)abstract BACKGROUND The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes. RESULTS We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9. We also found significant associations between coronary artery disease and low-frequency missense variants in the genes SVEP1 (p.D2702G; minor-allele frequency, 3.60%; odds ratio for disease, 1.14; P = 4.2x10(-10)) and ANGPTL4 (p.E40K; minor-allele frequency, 2.01%; odds ratio, 0.86; P = 4.0x10(-8)), which encodes angiopoietin-like 4. Through sequencing of ANGPTL4, we identified 9 carriers of loss-of-function mutations among 6924 patients with myocardial infarction, as compared with 19 carriers among 6834 controls (odds ratio, 0.47; P = 0.04); carriers of ANGPTL4 loss-of-function alleles had triglyceride levels that were 35% lower than the levels among persons who did not carry a loss-of-function allele (P = 0.003). ANGPTL4 inhibits lipoprotein lipase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was associated with an increased risk of coronary artery disease (p.D36N; minor-allele frequency, 1.9%; odds ratio, 1.13; P = 2.0x10(-4)) and a gain-of-function variant that was associated with protection from coronary artery disease (p.S447*; minor-allele frequency, 9.9%; odds ratio, 0.94; P = 2.5x10(-7)). CONCLUSIONS We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease.
46.	Aad, G, et al. (author) Measurement of the top-quark mass in tt¯ + 1-jet events collected with the ATLAS detector in pp collisions at √s = 8 TeV 2019 In: Journal of High Energy Physics. - : SPRINGER. - 1029-8479 .- 1126-6708. ; 2019:11 Journal article (peer-reviewed)abstract A determination of the top-quark mass is presented using 20.2 fb−1 of 8 TeV proton-proton collision data produced by the Large Hadron Collider and collected by the ATLAS experiment. The normalised differential cross section of top-quark pair production in association with an energetic jet is measured in the lepton+jets final state and unfolded to parton and particle levels. The unfolded distribution at parton level can be described using next-to-leading-order QCD predictions in terms of either the top-quark pole mass or the running mass as defined in the (modified) minimal subtraction scheme. A comparison between the experimental distribution and the theoretical prediction allows the top-quark mass to be extracted in the two schemes. The value obtained for the pole-mass scheme is: mtpole=171.1±0.4(stat)±0.9(syst)−0.3+0.7(theo)GeV The extracted value in the running-mass scheme is: mt(mt)=162.9±0.5(stat)±1.0(syst)−1.2+2.1(theo)GeV. The results for the top-quark mass using the two schemes are consistent, when translated from one scheme to the other. [Figure not available: see fulltext.] © 2019, The Author(s).
47.	Aad, G, et al. (author) Measurement of the Z(→ ℓ + ℓ −)γ production cross-section in pp collisions at √s = 13 TeV with the ATLAS detector 2020 In: Journal of High Energy Physics. - : SPRINGER. - 1029-8479 .- 1126-6708. ; 2020:3 Journal article (peer-reviewed)abstract The production of a prompt photon in association with a Z boson is studied in proton-proton collisions at a centre-of-mass energy s = 13 TeV. The analysis uses a data sample with an integrated luminosity of 139 fb−1 collected by the ATLAS detector at the LHC from 2015 to 2018. The production cross-section for the process pp → ℓ+ℓ−γ + X (ℓ = e, μ) is measured within a fiducial phase-space region defined by kinematic requirements on the photon and the leptons, and by isolation requirements on the photon. An experimental precision of 2.9% is achieved for the fiducial cross-section. Differential cross-sections are measured as a function of each of six kinematic variables characterising the ℓ+ℓ−γ system. The data are compared with theoretical predictions based on next-to-leading-order and next-to-next-to-leading-order perturbative QCD calculations. The impact of next-to-leading-order electroweak corrections is also considered.
48.	Aad, G, et al. (author) Search for new non-resonant phenomena in high-mass dilepton final states with the ATLAS detector 2020 In: Journal of High Energy Physics. - : Springer. - 1029-8479 .- 1126-6708. ; 2020:11 Journal article (peer-reviewed)abstract A search for a chargino-neutralino pair decaying via the 125 GeV Higgs boson into photons is presented. The study is based on the data collected between 2015 and 2018 with the ATLAS detector at the LHC, corresponding to an integrated luminosity of 139 fb−1 of pp collisions at a centre-of-mass energy of 13 TeV. No significant excess over the expected background is observed. Upper limits at 95% confidence level for a massless χ˜10 are set on several electroweakino production cross-sections and the visible cross-section for beyond the Standard Model processes. In the context of simplified supersymmetric models, 95% confidence-level limits of up to 310 GeV in m(χ˜1±/χ˜20), where m(χ˜10) = 0.5 GeV, are set. Limits at 95% confidence level are also set on the χ˜1±χ˜20 cross-section in the mass plane of m(χ˜1±/χ˜20) and m(χ˜10), and on scenarios with gravitino as the lightest supersymmetric particle. Upper limits at the 95% confidence-level are set on the higgsino production cross-section. Higgsino masses below 380 GeV are excluded for the case of the higgsino fully decaying into a Higgs boson and a gravitino. [Figure not available: see fulltext.] © 2020, The Author(s).
49.	Aad, G, et al. (author) Search for new phenomena with top quark pairs in final states with one lepton, jets, and missing transverse momentum in pp collisions at √s = 13 TeV with the ATLAS detector 2021 In: Journal of High Energy Physics. - : Springer. - 1029-8479 .- 1126-6708. ; 2021:4 Journal article (peer-reviewed)abstract A search for new phenomena with top quark pairs in final states with one isolated electron or muon, multiple jets, and large missing transverse momentum is performed. Signal regions are designed to search for two-, three-, and four-body decays of the directly pair-produced supersymmetric partner of the top quark (stop). Additional signal regions are designed specifically to search for spin-0 mediators that are produced in association with a pair of top quarks and decay into a pair of dark-matter particles. The search is performed using the Large Hadron Collider proton-proton collision dataset at a centre-of-mass energy of s = 13 TeV recorded by the ATLAS detector from 2015 to 2018, corresponding to an integrated luminosity of 139 fb−1. No significant excess above the Standard Model background is observed, and limits at 95% confidence level are set in the stop-neutralino mass plane and as a function of the mediator mass or the dark-matter particle mass. Stops are excluded up to 1200 GeV (710 GeV) in the two-body (three-body) decay scenario. In the four-body scenario stops up to 640 GeV are excluded for a stop-neutralino mass difference of 60 GeV. Scalar and pseudoscalar dark-matter mediators are excluded up to 200 GeV when the coupling strengths of the mediator to Standard Model and dark-matter particles are both equal to one and when the mass of the dark-matter particle is 1 GeV. [Figure not available: see fulltext.] © 2021, The Author(s).
50.	Ademuyiwa, Adesoji O., et al. (author) Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries 2016 In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4 Journal article (peer-reviewed)abstract Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.

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