| 1. |
- Bettegowda, Chetan, et al.
(författare)
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Detection of circulating tumor DNA in early- and late-stage human malignancies
- 2014
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 6:224, s. 224ra24-
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Tidskriftsartikel (refereegranskat)abstract
- The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.
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| 2. |
- 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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| 3. |
- Ameen, Carly, et al.
(författare)
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Specialized sledge dogs accompanied Inuit dispersal across the North American Arctic
- 2019
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 286:1916
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Tidskriftsartikel (refereegranskat)abstract
- Domestic dogs have been central to life in the North American Arctic for millennia. The ancestors of the Inuit were the first to introduce the widespread usage of dog sledge transportation technology to the Americas, but whether the Inuit adopted local Palaeo-Inuit dogs or introduced a new dog population to the region remains unknown. To test these hypotheses, we generated mitochondrial DNA and geometric morphometric data of skull and dental elements from a total of 922 North American Arctic dogs and wolves spanning over 4500 years. Our analyses revealed that dogs from Inuit sites dating from 2000 BP possess morphological and genetic signatures that distinguish them from earlier Palaeo-Inuit dogs, and identified a novel mitochondrial clade in eastern Siberia and Alaska. The genetic legacy of these Inuit dogs survives today in modern Arctic sledge dogs despite phenotypic differences between archaeological and modern Arctic dogs. Together, our data reveal that Inuit dogs derive from a secondary pre-contact migration of dogs distinct from Palaeo-Inuit dogs, and probably aided the Inuit expansion across the North American Arctic beginning around 1000 BP.
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| 4. |
- Bechshoft, Thea, et al.
(författare)
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Developing a new research tool for use in free-ranging cetaceans : recovering cortisol from harbour porpoise skin
- 2015
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Ingår i: Conservation Physiology. - : Oxford University Press. - 2051-1434. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- We developed a chemical analytical procedure for sampling, extracting and determining epidermal skin cortisol concentrations (SCCs) in the harbour porpoise (Phocoena phocoena) using gas chromatography–tandem mass spectrometry. In brief, this involved a pressurized liquid extraction with a two-step solid-phase clean-up. A derivatization step was conducted prior to detection. To evaluate the new assay, cortisol was analysed in three different sample types obtained from four harbour porpoises: skin plates, dorsal fin skin plugs (with and without lidocaine) and epidermal scrapes. Skin cortisol concentrations could be measured using the new assay in the majority of the tested skin samples down to a minimal sample size of 49 mg dry weight (dw). Water content ranged from 10 to 46% in the plug samples, which had SCCs from 2.1 to 77.7 ng/g dw. Epidermal scrape samples had the highest water content (83–87%) and lower SCCs (0.6–15 ng/g dw), while the skin plates had intermediate water contents (60–66%) and SCCs of 2.6–13.0 ng/g dw. SCC was slightly higher in plugs with lidocaine than without (average values of 41 and 33 ng/g dw, respectively). Substantial within-individual variations in cortisol concentrations are also common in other matrices such as blood and hair. Some important factors behind this variation could be e.g. the animal's sex, age, body condition, reproductive stage, and the body region sampled, as well as season, moulting cycles and water temperature. Clearly, more research into SCCs is required. The findings described here represent the first critical steps towards using epidermal skin cell samples to assess chronic stress levels in cetaceans and the development of a widely applicable health-assessment tool in these species.
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| 5. |
- Erichsen, Martina M, et al.
(författare)
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Clinical, Immunological, and Genetic Features of Autoimmune Primary Adrenal Insufficiency: Observations from a Norwegian Registry.
- 2009
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94, s. 4882-4890
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Primary adrenal insufficiency [Addison's disease (AD)] is rare, and systematic studies are few, mostly conducted on small patient samples. We aimed to determine the clinical, immunological, and genetic features of a national registry-based cohort. Design: Patients with AD identified through a nationwide search of diagnosis registries were invited to participate in a survey of clinical features, health-related quality of life (HRQoL), autoantibody assays, and human leukocyte antigen (HLA) class II typing. Results: Of 664 registered patients, 64% participated in the study. The prevalence of autoimmune or idiopathic AD in Norway was 144 per million, and the incidence was 0.44 per 100,000 per year (1993-2007). Familial disease was reported by 10% and autoimmune comorbidity by 66%. Thyroid disease was most common (47%), followed by type 1 diabetes (12%), vitiligo (11%), vitamin B12 deficiency (10%), and premature ovarian insufficiency (6.6% of women). The mean daily treatment for AD was 40.5 mg cortisone acetate and 0.1 mg fludrocortisone. The mean Short Form 36 vitality scores were significantly diminished from the norm (51 vs. 60), especially among those with diabetes. Concomitant thyroid autoimmunity did not lower scores. Anti-21-hydroxylase antibodies were found in 86%. Particularly strong susceptibility for AD was found for the DR3-DQ2/ DRB1*0404-DQ8 genotype (odds ratio, 32; P = 4 x 10(-17)), which predicted early onset. Conclusions: AD is almost exclusively autoimmune, with high autoimmune comorbidity. Both anti-21-hydroxylase antibodies and HLA class II can be clinically relevant predictors of AD. HRQoL is reduced, especially among diabetes patients, whereas thyroid disease did not have an impact on HRQoL. Treatment modalities that improve HRQoL are needed.
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| 6. |
- Harris, Alison J. T., 1982-, et al.
(författare)
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Archives of human-dog relationships : Genetic and stable isotope analysis of Arctic fur clothing
- 2020
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Ingår i: Journal of Anthropological Archaeology. - : Elsevier BV. - 0278-4165 .- 1090-2686. ; 59
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Tidskriftsartikel (refereegranskat)abstract
- Among Indigenous populations of the Arctic, domestic dogs (Canislupus familiaris) were social actors aiding in traction and subsistence activities. Less commonly, dogs fulfilled a fur-bearing role in both the North American and Siberian Arctic. Examples of garments featuring dog skins were collected during the 19th-20th centuries and are now curated by the National Museum of Denmark. We sequenced the mitochondrial genomes of macroscopically identified dog skin garments. We conducted stable carbon and nitrogen isotope ratio analysis of the dog furs and of fur samples from contemporaneous pelts of Arctic (C. lupus arctos) and grey (C. lupus) wolves. Despite the presence of biocides used to protect the fur clothing during storage, we extracted well-preserved DNA using a minimally-invasive sampling protocol. Unexpectedly, the mtDNA genomes of one-third of the samples were consistent with wild taxa, rather than domestic dogs. The strong marine component in the diets of North American dogs distinguished them from Greenland and Canadian wolves, but Siberian dogs consumed diets that were isotopically similar to wild species. We found that dog provisioning practices were variable across the Siberian and North American Arctic, but in all cases, involved considerable human labor.
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| 7. |
- Nordström, Birgitta, et al.
(författare)
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The Geneva-Copenhagen Survey of the Solar Neighbourhood
- 2004
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Ingår i: Publications Astronomical Society of Australia. - 1448-6083. ; 21:2, s. 129-133
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Tidskriftsartikel (refereegranskat)abstract
- We report on a new survey of metallicities, ages, and Galactic orbitsfor a complete, magnitude-limited, and kinematically unbiased all-skysample of 16682 nearby F- and G-dwarfs. Our~63000 new, accurate radialvelocities for nearly 13500 of the stars, combined with Hipparcosparallaxes and Tycho-2 proper motions, complete the kinematic data for14139 stars and allow us to identify most of the binary stars in thesample. Isochrone ages have been determined whenever reliable resultsare possible, with particular attention to realistic error estimates.Among the basic properties of the Galactic disk that can bereinvestigated from our data are the metallicity distribution ofG-dwarfs and the age-metallicity and age-velocity relations of the solarneighbourhood. We confirm the lack of metal-poor G-dwarfs relative toclassical model predictions (the `G-dwarf problem'), the near-constancyof the mean metallicity since the formation of the thin disk, and theappearance of the kinematic signature of the thick disk ~ 10Gyr ago.
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| 8. |
- Nordström, Birgitta, et al.
(författare)
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The Geneva-Copenhagen survey of the Solar neighbourhood. Ages, metallicities, and kinematic properties of ∼14 000 F and G dwarfs
- 2004
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 418:3, s. 989-1019
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Forskningsöversikt (refereegranskat)abstract
- We present and discuss new determinations of metallicity, rotation, age,kinematics, and Galactic orbits for a complete, magnitude-limited, andkinematically unbiased sample of 16 682 nearby F and G dwarf stars. Our∼63 000 new, accurate radial-velocity observations for nearly 13 500stars allow identification of most of the binary stars in the sampleand, together with published uvbyβ photometry, Hipparcosparallaxes, Tycho-2 proper motions, and a few earlier radial velocities,complete the kinematic information for 14 139 stars. These high-qualityvelocity data are supplemented by effective temperatures andmetallicities newly derived from recent and/or revised calibrations. Theremaining stars either lack Hipparcos data or have fast rotation. Amajor effort has been devoted to the determination of new isochrone agesfor all stars for which this is possible. Particular attention has beengiven to a realistic treatment of statistical biases and errorestimates, as standard techniques tend to underestimate these effectsand introduce spurious features in the age distributions. Our ages agreewell with those by Edvardsson et al. (cite{edv93}), despite severalastrophysical and computational improvements since then. We demonstrate,however, how strong observational and theoretical biases cause thedistribution of the observed ages to be very different from that of thetrue age distribution of the sample. Among the many basic relations ofthe Galactic disk that can be reinvestigated from the data presentedhere, we revisit the metallicity distribution of the G dwarfs and theage-metallicity, age-velocity, and metallicity-velocity relations of theSolar neighbourhood. Our first results confirm the lack of metal-poor Gdwarfs relative to closed-box model predictions (the ``G dwarfproblem''), the existence of radial metallicity gradients in the disk,the small change in mean metallicity of the thin disk since itsformation and the substantial scatter in metallicity at all ages, andthe continuing kinematic heating of the thin disk with an efficiencyconsistent with that expected for a combination of spiral arms and giantmolecular clouds. Distinct features in the distribution of the Vcomponent of the space motion are extended in age and metallicity,corresponding to the effects of stochastic spiral waves rather thanclassical moving groups, and may complicate the identification ofthick-disk stars from kinematic criteria. More advanced analyses of thisrich material will require careful simulations of the selection criteriafor the sample and the distribution of observational errors.Based on observations made with the Danish 1.5-m telescope at ESO, LaSilla, Chile, and with the Swiss 1-m telescope at Observatoire deHaute-Provence, France.Complete Tables 1 and 2 are only available in electronic form at the CDSvia anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or viahttp://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/418/989
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| 9. |
- 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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| 10. |
- Almehed, Sverker, et al.
(författare)
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A Silicon-Tungsten Electromagnetic Calorimeter for LEP
- 1991
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 305:2, s. 320-330
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Tidskriftsartikel (refereegranskat)abstract
- This report describes a silicon-tungsten electromagnetic calorimeter used to determine some beam properties and luminosity in the DELPHI experiment at LEP. The polar angular range covered by this detector is 5–8 mrad, which allows the detection of a Bhabha rate about 10 times the rate of produced Z particles at the peak cross section.
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