| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 3. |
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- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Tidskriftsartikel (refereegranskat)
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| 4. |
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 9. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 14. |
- Richards, Stephen, et al.
(författare)
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Genome Sequence of the Pea Aphid Acyrthosiphon pisum
- 2010
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 8:2, s. e1000313-
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Tidskriftsartikel (refereegranskat)abstract
- Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.
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| 15. |
- Patterson, Nick, et al.
(författare)
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Large-scale migration into Britain during the Middle to Late Bronze Age
- 2022
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
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Tidskriftsartikel (refereegranskat)abstract
- Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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| 16. |
- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 17. |
- Muhlemann, B., et al.
(författare)
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Ancient hepatitis B viruses from the Bronze Age to the Medieval period
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 557:7705, s. 418-423
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis B virus (HBV) is a major cause of human hepatitis. There is considerable uncertainty about the timescale of its evolution and its association with humans. Here we present 12 full or partial ancient HBV genomes that are between approximately 0.8 and 4.5 thousand years old. The ancient sequences group either within or in a sister relationship with extant human or other ape HBV clades. Generally, the genome properties follow those of modern HBV. The root of the HBV tree is projected to between 8.6 and 20.9 thousand years ago, and we estimate a substitution rate of 8.04 x 10(-6-)1.51 x 10(-5) nucleotide substitutions per site per year. In several cases, the geographical locations of the ancient genotypes do not match present-day distributions. Genotypes that today are typical of Africa and Asia, and a subgenotype from India, are shown to have an early Eurasian presence. The geographical and temporal patterns that we observe in ancient and modern HBV genotypes are compatible with well-documented human migrations during the Bronze and Iron Ages(1,2). We provide evidence for the creation of HBV genotype A via recombination, and for a long-term association of modern HBV genotypes with humans, including the discovery of a human genotype that is now extinct. These data expose a complexity of HBV evolution that is not evident when considering modern sequences alone.
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| 18. |
- Price, T. Douglas, et al.
(författare)
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Human remains, context, and place of origin for the Salme, Estonia, boat burials
- 2020
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Ingår i: Journal of Anthropological Archaeology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0278-4165 .- 1090-2686. ; 58
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Tidskriftsartikel (refereegranskat)abstract
- Isotopic proveniencing of all individuals from the ship and boat burials at Salme, Estonia, is the subject of this study of the interred human remains from around AD 750, at the beginning of the Viking period. The isotopic results indicate that the majority of these individuals came from a region with higher strontium isotopic ratios than those found in Estonia. There were five individuals, buried in Salme II-the ship burial with 34 individuals-who exhibited lower strontium isotope ratios that might have come from the Swedish island of Gotland or several other possible places. The combination of isotopic signals and archaeological information suggests that the majority of buried individuals (those with higher strontium isotope ratios) came from the Malaren Valley in east-central Sweden.
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| 19. |
- Thorell, Kaisa, 1983, et al.
(författare)
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The Helicobacter pylori Genome Project: insights into H. pylori population structure from analysis of a worldwide collection of complete genomes
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics.
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| 20. |
- Ahlström, Torbjörn, et al.
(författare)
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Mobile or stationary? An analysis of strontium and carbon isotopes from Västerbjers, Gotland, Sweden
- 2021
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Ingår i: Journal of Archaeological Science: Reports. - : Elsevier BV. - 2352-409X. ; 36
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Tidskriftsartikel (refereegranskat)abstract
- The nature of the Neolithic Pitted Ware Culture (PWC) has been debated in Scandinavian archaeology since the beginning of the 20th century. This material culture post-dates the inception of an agro-pastoral Neolithic economy in the region (TRB) but demonstrate a semi-foraging lifeway. The PWC is considered elusive in the sense that the economy has been interpreted as either based on maritime foraging (isotope analysis), or a mixed-Neolithic economy based on boar (Sus scrofa) (archaeozoology). The mobility of the PWC group on Gotland has not been studied previously. We provide an analysis of strontium data from the site Västerbjers, Gotland, and engage in the question whether this population was mobile (foragers) or stationary (mixed-Neolithic). We also discuss the strontium baseline of the island in the light of new data. The results presented demonstrate a group that was confined to the island and with no strontium data suggesting a supra-regional mobility. We cannot discriminate between a regional mobility pattern on Gotland (mobility between sites) and a local, stationary group (fully sedentary), but we present data that suggest the former. Thus, our conclusion is that the PWC group on Gotland was stationary, the sedentism disclosed being supported by a mixed-Neolithic economy based on boar (Sus scrofa). In fact, the PWC group is depicting less variance with respect to 87Sr/86Sr ratios than the TRB and Late Neolithic groups on the island, being more stationary than the agricultural groups.
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| 21. |
- Allentoft, Morten E., et al.
(författare)
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100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
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| 22. |
- Allentoft, Morten E., et al.
(författare)
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Population genomics of post-glacial western Eurasia
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 23. |
- Bergerbrant, Sophie, 1968, et al.
(författare)
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Identifying commoners in the Bronze Age: burials outside barrows
- 2017
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Ingår i: New Perspectives on the Bronze Age: Proceedings from the 13th Nordic Bronze Age Symposium, held in Gothenburg 9th June to 13th June 2015. - Oxford : Archaeopress. - 9781784915988 ; , s. 37-64
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This article discusses the possibility of social division and the presence of commoners in south Scandinavia during the Early Bronze Age. The discussion is based on new scientific and archaeological data generated in the project Travels, transmissions and transformations in temperate northern Europe during the 3rd and 2nd millennium BC: The rise of Bronze Age societies. Based on a comprehensive radiocarbon dating program, we were able to re-assign many skeletons, previously assumed to be Late Neolithic, to the Bronze Age. This accounted for a significant proportion of non-elite burials (including those of children) that had previously been ‘mysteriously’ missing in the archaeological Bronze Age record. Moreover, strontium isotope analyses reveal that individuals seem to be mobile regardless of their wealth status and burial rituals. It suggests a society where workers and perhaps even nonfree labourers were mobile, not only the elite segment.
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| 24. |
- Bäckström, Ylva, et al.
(författare)
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Social Identity and Mobility at a Pre-industrial Mining Complex, Sweden
- 2016
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Ingår i: Journal of Archaeological Science. - : Elsevier BV. - 1095-9238 .- 0305-4403. ; 66, s. 154-168
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Tidskriftsartikel (refereegranskat)abstract
- The early modern period has so far received little attention from archaeologists and anthropologists in Sweden. This study explores demographic patterns, social differences, family structure and mobility in a 16th-century skeletal population (n=102) from a preindustrial mining community (Salberget) in Bergslagen, Sweden, using a bioarchaeological perspective. Methodologically, the results of strontium and oxygen isotope analysis in tooth enamel (n=38) were added to archaeological, anthropological and documentary evidence to detect demographic and/or social differences in mobility. Historical documents provided some indications of the kinds of people working at the mine. Archaeological evidence indicated two distinct grave types and the anthropological analysis documented differences in the age and sex of these individuals. The analysis of strontium, oxygen and carbon isotopes in teeth was used to infer possible place of origin information about these individuals. Various lines of evidence suggest that the cemetery held a mix of family groups, foreign workers and prisoners of war, all associated with the Sala silver mine. Together, the archaeology, osteology and isotope chemistry confirmed the documentary evidence of internal and external migration in the region. Furthermore, this study displays signs of matrilocality and a socially stratified society.
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| 25. |
- Egfjord, Anne Friis Holm, et al.
(författare)
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Genomic Steppe ancestry in skeletons from the Neolithic Single Grave Culture in Denmark
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- The Gjerrild burial provides the largest and best-preserved assemblage of human skeletal material presently known from the Single Grave Culture (SGC) in Denmark. For generations it has been debated among archaeologists if the appearance of this archaeological complex represents a continuation of the previous Neolithic communities, or was facilitated by incoming migrants. We sampled and analysed five skeletons from the Gjerrild cist, buried over a period of c. 300 years, 2600/2500–2200 cal BCE. Despite poor DNA preservation, we managed to sequence the genome (>1X) of one individual and the partial genomes (0.007X and 0.02X) of another two individuals. Our genetic data document a female (Gjerrild 1) and two males (Gjerrild 5 + 8), harbouring typical Neolithic K2a and HV0 mtDNA haplogroups, but also a rare basal variant of the R1b1 Y-chromosomal haplogroup. Genome-wide analyses demonstrate that these people had a significant Yamnaya-derived (i.e. steppe) ancestry component and a close genetic resemblance to the Corded Ware (and related) groups that were present in large parts of Northern and Central Europe at the time. Assuming that the Gjerrild skeletons are genetically representative of the population of the SGC in broader terms, the transition from the local Neolithic Funnel Beaker Culture (TRB) to SGC is not characterized by demographic continuity. Rather, the emergence of SGC in Denmark was part of the Late Neolithic and Early Bronze Age population expansion that swept across the European continent in the 3rd millennium BCE, resulting in various degrees of genetic replacement and admixture processes with previous Neolithic populations.
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