| 1. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 2. |
- Hubberten, HW, et al.
(författare)
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The periglacial climate and environment in northern Eurasia during the Last Glaciation
- 2004
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 23:11-13, s. 1333-1357
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Forskningsöversikt (refereegranskat)abstract
- This paper summarizes the results of studies of the Late Weichselian periglacial environments carried out in key areas of northern Eurasia by several QUEEN teams (European Science Foundation (ESF) programme: "Quaternary Environment of the Eurasian North"). The palaeoglaciological boundary conditions are defined by geological data on timing and extent of the last glaciation obtained in the course of the EU funded project "Eurasian Ice Sheets". These data prove beyond any doubt, that with the exception of the northwestern fringe of the Taymyr Peninsula, the rest of the Eurasian mainland and Severnaya Zemlya were not affected by the Barents-Kara Sea fee Sheet during the Last Glacial Maximum (LGM). Inversed modelling based on these results shows that a progressive cooling which started around 30 ka BP, caused ice growth in Scandinavia and the northwestern areas of the Barents-Kara Sea shelf, due to a maritime climate with relatively high precipitation along the western flank of the developing ice sheets. In the rest of the Eurasian Arctic extremely low precipitation rates (less than 50 mm yr(-1)), did not allow ice sheet growth in spite of the very cold temperatures. Palaeoclimatic and palaeoenvironmental conditions for the time prior to, during, and after the LGM have been reconstructed for the non-glaciated areas around the LGM ice sheet with the use of faunal and vegetation records, permafrost, eolian sediments, alluvial deposits and other evidences. The changing environment, from interstadial conditions around 30 ka BP to a much colder and drier environment at the culmination of the LGM at 20-15 ka BP, and the beginning of warming around 15 ka BP have been elaborated from the field data, which fits well with the modelling results. (C) 2003 Elsevier Ltd. All rights reserved.
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| 3. |
- Schroeder, Kari B., et al.
(författare)
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Haplotypic background of a private allele at high frequency in the Americas
- 2009
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 26:5, s. 995-1016
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Forskningsöversikt (refereegranskat)abstract
- Recently, the observation of a high-frequency private allele,the 9-repeat allele at microsatellite D9S1120, in all sampledNative American and Western Beringian populations has been interpretedas evidence that all modern Native Americans descend primarilyfrom a single founding population. However, this inference assumedthat all copies of the 9-repeat allele were identical by descentand that the geographic distribution of this allele had notbeen influenced by natural selection. To investigate whetherthese assumptions are satisfied, we genotyped 34 single nucleotidepolymorphisms across 500 kilobases (kb) around D9S1120 in 21Native American and Western Beringian populations and 54 otherworldwide populations. All chromosomes with the 9-repeat alleleshare the same haplotypic background in the vicinity of D9S1120,suggesting that all sampled copies of the 9-repeat allele areidentical by descent. Ninety-one percent of these chromosomesshare the same 76.26 kb haplotype, which we call the "AmericanModal Haplotype" (AMH). Three observations lead us to concludethat the high frequency and widespread distribution of the 9-repeatallele are unlikely to be the result of positive selection:1) aside from its association with the 9-repeat allele, theAMH does not have a high frequency in the Americas, 2) the AMHis not unusually long for its frequency compared with otherhaplotypes in the Americas, and 3) in Latin American mestizopopulations, the proportion of Native American ancestry at D9S1120is not unusual compared with that observed at other genomewidemicrosatellites. Using a new method for estimating the timeto the most recent common ancestor (MRCA) of all sampled copiesof an allele on the basis of an estimate of the length of thegenealogy descended from the MRCA, we calculate the mean timeto the MRCA of the 9-repeat allele to be between 7,325 and 39,900years, depending on the demographic model used. The resultssupport the hypothesis that all modern Native Americans andWestern Beringians trace a large portion of their ancestry toa single founding population that may have been isolated fromother Asian populations prior to expanding into the Americas.
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| 4. |
- Svendsen, JI, et al.
(författare)
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Late quaternary ice sheet history of northern Eurasia
- 2004
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 23:11-13, s. 1229-1271
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Forskningsöversikt (refereegranskat)abstract
- The maximum limits of the Eurasian ice sheets during four glaciations have been reconstructed: (1) the Late Saalian (> 140 ka), (2) the Early Weichselian (100-80 ka), (3) the Middle Weichselian (60-50 ka) and (4) the Late Weichselian (25-15 ka). The reconstructed ice limits are based on satellite data and aerial photographs combined with geological field investigations in Russia and Siberia, and with marine seismic- and sediment core data. The Barents-Kara Ice Sheet got progressively smaller during each glaciation, whereas the dimensions of the Scandinavian Ice Sheet increased. During the last Ice Age the Barents-Kara Ice Sheet attained its maximum size as early as 90-80,000 years ago when the ice front reached far onto the continent. A regrowth of the ice sheets occurred during the early Middle Weichselian, culminating about 60-50,000 years ago. During the Late Weichselian the Barents-Kara Ice Sheet did not reach the mainland east of the Kanin Peninsula, with the exception of the NW fringe of Taimyr. A numerical ice-sheet model, forced by global sea level and solar changes, was run through the full Weichselian glacial cycle. The modeling results are roughly compatible with the geological record of ice growth, but the model underpredicts the glaciations in the Eurasian Arctic during the Early and Middle Weichselian. One reason for this is that the climate in the Eurasian Arctic was not as dry then as during the Late Weichselian glacial maximum.
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