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| 2. |
- Librado, P., et al.
(author)
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The origins and spread of domestic horses from the Western Eurasian steppes
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 598, s. 634-640
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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).
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| 3. |
- Fages, A., et al.
(author)
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Tracking Five Millennia of Horse Management with Extensive Ancient Genome Time Series
- 2019
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In: Cell. - : Elsevier BV. - 0092-8674. ; 177:6
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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.
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| 4. |
- Lewis, E. F., et al.
(author)
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Characterization of health-related quality of life in heart failure patients with preserved versus low ejection fraction in CHARM
- 2007
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In: European journal of heart failure. - : Wiley. - 1388-9842. ; 9:1, s. 83-91
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Journal article (peer-reviewed)abstract
- BACKGROUND: Limited comparative studies assessing the health-related quality of life (HRQL) in heart failure (HF) patients with preserved vs. low ejection fraction (LVEF) have been disparate. AIMS: The aims of this study were a) to characterize HRQL in a large population of HF patients with preserved and low LVEF and b) to determine the factors associated with worse HRQL. METHODS: Patients with symptomatic HF (NYHA Class II-IV) enrolled in the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) HRQL study completed the Minnesota Living with Heart Failure questionnaire at randomization. Patients were stratified into 2 HF cohorts: preserved LVEF (>40%) and low LVEF (
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| 5. |
- Fernandez-Rozadilla, C., et al.
(author)
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A genome-wide association study on copy-number variation identifies a 11q11 loss as a candidate susceptibility variant for colorectal cancer
- 2014
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In: Human Genetics. - : Springer Science and Business Media LLC. - 1432-1203 .- 0340-6717. ; 133:5, s. 525-534
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Journal article (peer-reviewed)abstract
- Colorectal cancer (CRC) is a complex disease, and therefore its development is determined by the combination of both environmental factors and genetic variants. Although genome-wide association studies (GWAS) of SNP variation have conveniently identified 20 genetic variants so far, a significant proportion of the observed heritability is yet to be explained. Common copy-number variants (CNVs) are one of the most important genomic sources of variability, and hence a potential source to explain part of this missing genetic fraction. Therefore, we have performed a GWAS on CNVs to explore the relationship between common structural variation and CRC development. Phase 1 of the GWAS consisted of 881 cases and 667 controls from a Spanish cohort. Copy-number status was validated by quantitative PCR for each of those common CNVs potentially associated with CRC in phase I. Subsequently, SNPs were chosen as proxies for the validated CNVs for phase II replication (1,342 Spanish cases and 1,874 Spanish controls). Four common CNVs were found to be associated with CRC and were further replicated in Phase II. Finally, we found that SNP rs1944682, tagging a 11q11 CNV, was nominally associated with CRC susceptibility (p value = 0.039; OR = 1.122). This locus has been previously related to extreme obesity phenotypes, which could suggest a relationship between body weight and CRC susceptibility.
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| 6. |
- Crona, Joakim, et al.
(author)
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ENSAT registry-based randomized clinical trials for adrenocortical carcinoma
- 2021
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In: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 184:2, s. R51-R59
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Research review (peer-reviewed)abstract
- Adrenocortical carcinoma (ACC) is an orphan disease lacking effective systemic treatment options. The low incidence of the disease and high cost of clinical trials are major obstacles in the search for improved treatment strategies. As a novel approach, registry-based clinical trials have been introduced in clinical research, so allowing for significant cost reduction, but without compromising scientific benefit. Herein, we describe how the European Network for the Study of Adrenal Tumours (ENSAT) could transform its current registry into one fit for a clinical trial infrastructure. The rationale to perform randomized registry-based trials in ACC is outlined including an analysis of relevant limitations and challenges. We summarize a survey on this concept among ENSAT members who expressed a strong interest in the concept and rated its scientific potential as high. Legal aspects, including ethical approval of registry-based randomization were identified as potential obstacles. Finally, we describe three potential randomized registry-based clinical trials in an adjuvant setting and for advanced disease with a high potential to be executed within the framework of an advanced ENSAT registry. Thus we, therefore, provide the basis for future registry-based trials for ACC patients. This could ultimately provide proof-of-principle of how to perform more effective randomized trials for an orphan disease.
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| 7. |
- Harrison, J. P., et al.
(author)
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Rock engineering design and the evolution of Eurocode 7 : The critical six years to 2020
- 2017
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In: 13th ISRM International Congress of Rock Mechanics. - : International Society for Rock Mechanics. - 9781926872254
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Conference paper (peer-reviewed)abstract
- In 2010, the Eurocode for Geotechnical Design, EN-1997-1:2004 (CEN, 2004), informally known as Eurocode 7 or EC7, became the Reference Design Code (RDC) for geotechnical design - including rock engineering design - within the European Union (EU). EC7 is one standard within the comprehensive Structural Eurocode suite, which as a whole has been also adopted by a number of other countries beyond the EU. EC7 is thus becoming a key design standard for geotechnical engineering worldwide. As part of the Structural Eurocode suite, EC7 requires designs to adhere to the principles of Limit State Design. However, it is not clear that current rock engineering design practice can satisfy this requirement. In addition, evidence is accumulating that EC7 is currently difficult to apply to, and may even be inappropriate for, rock engineering design. These issues may be due to the fact that the development of EC7 to date took place without any formal input from the international rock mechanics and rock engineering community. In early 2011 under the auspices of CEN (Comité Européen de Normalisation / European Committee for Standardisation), EC7 entered a formal period of maintenance which was aimed at improving the applicability and ease-of-use of the Code. This maintenance cycle will conclude in 2020 with the publication of a revised version of EC7. This paper describes a number of critical aspects for rock engineering in the context of EC7, in particular the following: - the history of the Structural Eurocodes and the concepts they embody; - the nature of Limit State Design and the challenges and opportunities it poses for rock engineering design; - the formal means by which the Structural Eurocode maintenance cycle proceeds; - the plans currently being developed for improving EC7 with regard to rock engineering design and construction; - the unique and vital opportunity for the entire international rock mechanics and rock engineering community to comment on the Code and make suggestions for its improvement.
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| 8. |
- Alejano, L. R., et al.
(author)
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Rock engineering design and the evolution of Eurocode 7
- 2013
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In: ISRM International Symposium - EUROCK 2013. - : International Society for Rock Mechanics. - 9781138000803 ; , s. 777-782
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Conference paper (peer-reviewed)abstract
- The Eurocode for Geotechnical Design, EN-1997-1:2004, informally known as Eurocode 7 or EC7, was fully implemented within the European Union in 2010. This Eurocode is intended to apply to all geotechnical engineering design, including rock engineering. In recognition that all codes must continue to evolve in order to remain applicable, and the long time that such evolution takes, work is already underway under the auspices of the European Committee for Standardisation, CEN, to identify how the code should develop for future revisions. This paper presents a summary of the maintenance procedures for Eurocodes in general and the specific maintenance work currently being undertaken on EC7 in respect of rock engineering design. It also highlights potential future development of EC7, and the need for enthusiastic involvement by the European rock engineering community to direct these developments.
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| 9. |
- Lamas, L., et al.
(author)
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Revision of the Eurocodes – aspects of geotechnical and rock engineering design
- 2020
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In: ISRM International Symposium - EUROCK 2020. - : International Society for Rock Mechanics.
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Conference paper (peer-reviewed)abstract
- The Structural Eurocodes (EN 199x) are a suite of European standards for the design of buildings and civil engineering works, published in 2006 by the European Committee for Standardization (CEN) and with implementation starting in 2010. EN 1990 sets the basis of structural design, with the other Eurocodes dealing with different materials and specific aspects of the design; Eurocode 7 (EN 1997) deals with geotechnical aspects. In 2010, CEN began a process of evolving the Eurocodes in order to incorporate improvements that reflect the state-of-the-art in engineering design and the needs of the civil engineering market; to improve the ease-of-use of the standards; and to harmonize practice between countries. The existing EN 1990 is founded on limit state concepts, and reliability of design is provided mainly by a semi-probabilistic method based on partial factors. Applying the same method to geotechnical design has proved to be difficult, and the revised EN 1990 will present improvements concerning geotechnical design. Reflecting these changes, the title of EN 1990 was changed to “Basis of structural and geotechnical design”. Although initially developed for structures involving soils, Eurocode 7 is also applicable to rock engineering design. A major target of the current revision is that the code should treat soil and rock on an equal basis. The evolution of the Eurocode 7 has been accompanied by a group of rock engineering experts working under CEN, who started their activity in 2011. The paper is authored by the current members of this group and presents the situation of the revision of Eurocode 7 in October 2019, namely: the main objectives of the revision; the new structure adopted for the code, with three parts, and the implementation schedule of the revised Eurocodes; the main changes implemented so far in geotechnical design and rock engineering; the main rock engineering aspects still needing to be addressed.
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| 10. |
- Yu, He, et al.
(author)
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Palaeogenomic analysis of black rat (Rattus rattus) reveals multiple European introductions associated with human economic history
- 2022
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- The distribution of the black rat (Rattus rattus) has been heavily influenced by its association with humans. The dispersal history of this non-native commensal rodent across Europe, however, remains poorly understood, and different introductions may have occurred during the Roman and medieval periods. Here, in order to reconstruct the population history of European black rats, we first generate a de novo genome assembly of the black rat. We then sequence 67 ancient and three modern black rat mitogenomes, and 36 ancient and three modern nuclear genomes from archaeological sites spanning the 1st-17th centuries CE in Europe and North Africa. Analyses of our newly reported sequences, together with published mitochondrial DNA sequences, confirm that black rats were introduced into the Mediterranean and Europe from Southwest Asia. Genomic analyses of the ancient rats reveal a population turnover in temperate Europe between the 6th and 10th centuries CE, coincident with an archaeologically attested decline in the black rat population. The near disappearance and re-emergence of black rats in Europe may have been the result of the breakdown of the Roman Empire, the First Plague Pandemic, and/or post-Roman climatic cooling. 'Archaeogenetic analysis of black rat remains reveals that this species was introduced into temperate Europe twice, in the Roman and medieval periods. This population turnover was likely associated with multiple historical and environmental factors.'
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