| 1. |
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| 2. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 3. |
- Gregson, J., et al.
(författare)
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Cardiovascular Risk Factors Associated With Venous Thromboembolism
- 2019
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Ingår i: JAMA Cardiology. - : American Medical Association (AMA). - 0965-2590 .- 2380-6583 .- 2380-6591. ; 4:2, s. 163-173
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). OBJECTIVE To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. DESIGN, SETTING, AND PARTICIPANTS This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CND], 25131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). RESULTS Of the 731728 participants from the ERFC. 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. CONCLUSIONS AND RELEVANCE Older age, smoking, and adiposity were consistently associated with higher VTE risk.
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| 4. |
- Gerstung, M, et al.
(författare)
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The evolutionary history of 2,658 cancers
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 122-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.
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| 5. |
- Callaghan, TV, et al.
(författare)
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Key findings and extended summaries
- 2004
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Ingår i: Ambio: a Journal of Human Environment. - 0044-7447. ; 33:7, s. 386-392
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Graham, N. S. N., et al.
(författare)
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Axonal marker neurofilament light predicts long-term outcomes and progressive neurodegeneration after traumatic brain injury
- 2021
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 13:613
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Tidskriftsartikel (refereegranskat)abstract
- Axonal injury is a key determinant of long-term outcomes after traumatic brain injury (TBI) but has been difficult to measure clinically. Fluid biomarker assays can now sensitively quantify neuronal proteins in blood. Axonal components such as neurofilament light (NfL) potentially provide a diagnostic measure of injury. In the multicenter BIO-AX-TBI study of moderate-severe TBI, we investigated relationships between fluid biomarkers, advanced neuroimaging, and clinical outcomes. Cerebral microdialysis was used to assess biomarker concentrations in brain extracellular fluid aligned with plasma measurement. An experimental injury model was used to validate biomarkers against histopathology. Plasma NfL increased after TBI, peaking at 10 days to 6 weeks but remaining abnormal at 1 year. Concentrations were around 10 times higher early after TBI than in controls (patients with extracranial injuries). NfL concentrations correlated with diffusion MRI measures of axonal injury and predicted white matter neurodegeneration. Plasma TAU predicted early gray matter atrophy. NfL was the strongest predictor of functional outcomes at 1 year. Cerebral microdialysis showed that NfL concentrations in plasma and brain extracellular fluid were highly correlated. An experimental injury model confirmed a dose-response relationship of histopathologically defined axonal injury to plasma NfL. In conclusion, plasma NfL provides a sensitive and clinically meaningful measure of axonal injury produced by TBI. This reflects the extent of underlying damage, validated using advanced MRI, cerebral microdialysis, and an experimental model. The results support the incorporation of NfL sampling subacutely after injury into clinical practice to assist with the diagnosis of axonal injury and to improve prognostication.
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| 7. |
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| 9. |
- Gao, Hong, et al.
(författare)
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The landscape of tolerated genetic variation in humans and primates
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6648
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Tidskriftsartikel (refereegranskat)abstract
- Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases.
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| 13. |
- Wood, David A., et al.
(författare)
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Timing of Staged Nonculprit Artery Revascularization in Patients With ST-Segment Elevation Myocardial Infarction COMPLETE Trial
- 2019
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 74:22, s. 2713-2723
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The COMPLETE (Complete vs Culprit-only Revascularization to Treat Multi-vessel Disease After Early PCI for STEMI) trial demonstrated that staged nonculprit lesion percutaneous coronary intervention (PCI) reduced major cardiovascular (CV) events in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (CAD). OBJECTIVES The purpose of this study was to determine the effect of nonculprit-lesion PCI timing on major CV outcomes and also the time course of the benefit of complete revascularization. METHODS Following culprit-lesion PCI, 4,041 patients with STEMI and multivessel CAD were randomized to staged nonculprit-lesion PCI or culprit-lesion only PCI. Randomization was stratified according to investigator-planned timing of nonculprit-lesion PCI: during or after the index hospitalization. The first coprimary outcome was the composite of CV death or myocardial infarction (MI). In pre-specified analyses, hazard ratios (HRs) were calculated for each time stratum. Landmark analyses of the entire population were performed within 45 days and after 45 days. RESULTS For nonculprit-lesion PCI planned during the index hospitalization (actual time: median 1 day), CV death or MI was reduced with complete revascularization compared with culprit-lesion only PCI (HR: 0.77; 95% confidence interval [CI]: 0.59 to 1.00). For nonculprit lesion PCI planned to occur after hospital discharge (actual time: median 23 days), CV death or MI was also reduced with complete revascularization (HR: 0.69; 95% CI: 0.49 to 0.97; interaction p = 0.62). Landmark analyses demonstrated an HR of 0.86 (95% CI: 0.59 to 1.24) during the first 45 days and 0.69 (95% CI: 0.54 to 0.89) from 45 days to the end of follow-up for intended nonculprit lesion PCI versus culprit lesion only PCI. CONCLUSIONS Among STEMI patients with multivessel disease, the benefit of complete revascularization over culprit-lesion only PCI was consistent irrespective of the investigator-determined timing of nonculprit-lesion intervention. The benefit of complete revascularization on hard clinical outcomes emerged mainly over the long term. (C) 2019 by the American College of Cardiology Foundation.
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| 14. |
- Bakker, R, et al.
(författare)
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Analyzing the Cross-National Comparability of Party Positions on the Socio-Cultural and EU Dimensions in Europe.
- 2022
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Ingår i: Political Science Research and Methods. - : Cambridge University Press (CUP). - 2049-8470 .- 2049-8489. ; 10:2, s. 408-418
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Tidskriftsartikel (refereegranskat)abstract
- Using survey vignettes and scaling techniques, we estimate common socio-cultural and European integration dimensions for political parties across the member states of the European Union. Previous research shows that party placements on the economic left-right dimension are cross-nationally comparable across the EU; however, the socio-cultural dimension is more complex, with different issues forming the core of the dimension in different countries. The 2014 wave of the Chapel Hill Expert Survey included anchoring vignettes which we use as “bridge votes” to place parties from different countries on a common liberal/authoritarian dimension and a separate common scale for European integration. We estimate the dimensions using the Bayesian Aldrich–McKelvey technique. The resulting scales offer cross-nationally comparable, interval-level measures of a party's socio-cultural and EU ideological positions.
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| 15. |
- Bakker, R., et al.
(författare)
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The European Common Space: Extending the Use of Anchoring Vignettes
- 2014
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Ingår i: Journal of Politics. - : University of Chicago Press. - 0022-3816 .- 1468-2508. ; 76:4, s. 1089-1101
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Tidskriftsartikel (refereegranskat)abstract
- In this article, we combine advances in both survey research and scaling techniques to estimate a common dimension for political parties across the member states of the European Union. Most previous scholarship has either ignored or assumed cross-national comparability of party placements across a variety of dimensions. The 2010 wave of the Chapel Hill Expert Survey includes anchoring vignettes which we use as "bridge votes'' to place parties from different countries on a common space. We estimate our dimensions using the "blackbox'' technique. Our results demonstrate both the usefulness of anchoring vignettes and the broad applicability of the blackbox scaling routine. Further, the resulting scale offers a cross-nationally comparable interval-level measure of a party's left/right ideological position with a high degree of face validity. In short, we argue that the left/right economic dimension travels well across European countries.
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| 16. |
- Beck, Judith S, et al.
(författare)
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Beck ungdomsskalor manual inkl. frågehäfte. Svensk version
- 2004
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Beck Ungdomsskalor består av fem korta självskattningsskalor för bedömning av emotionell och social problematik hos barn och ungdomar. Skalorna är standardiserade och normerade på cirka 2400 svenska skolbarn. Manualen innehåller även anvsiningar för administrering till yngre åldersgrupper samt data från kliniska grupper. [från omslag]
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| 17. |
- Callaghan, Terry V., et al.
(författare)
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Arctic tundra and Polar Desert Ecosystems
- 2005
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Ingår i: Arctic Climate Impact Assessment. - 9780521865098 - 0521865093
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 18. |
- Callaghan, T. V., et al.
(författare)
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Effects on the function of arctic ecosystems in the short- and long-term perspectives
- 2004
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Ingår i: Ambio: a Journal of Human Environment. - : Royal Swedish Academy of Sciences. - 0044-7447. ; 33, s. 448-458
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Tidskriftsartikel (refereegranskat)abstract
- Abstract in UndeterminedHistorically, the function of Arctic ecosystems in terms of cycles of nutrients and carbon has led to low levels of primary production and exchanges of energy, water and greenhouse gases have led to low local and regional cooling. Sequestration of carbon from atmospheric CO2, in extensive, cold organic soils and the high albedo from low, snow-covered vegetation have had impacts on regional climate. However, many aspects of the functioning of Arctic ecosystems are sensitive to changes in climate and its impacts on biodiversity. The current Arctic climate results in slow rates of organic matter decomposition. Arctic ecosystems therefore tend to accumulate organic matter and elements despite low inputs. As a result, soil-available elements like nitrogen and phosphorus are key limitations to increases in carbon fixation and further biomass and organic matter accumulation. Climate warming is expected to increase carbon and element turnover, particularly in soils, which may lead to initial losses of elements but eventual, slow recovery. Individual species and species diversity have clear impacts on element inputs and retention in Arctic ecosystems. Effects of increased CO2 and UV-B on whole ecosystems, on the other hand, are likely to be small although effects on plant tissue chemisty, decomposition and nitrogen fixation may become important in the long-term. Cycling of carbon in trace gas form is mainly as CO2 and CH4. Most carbon loss is in the form of CO2, produced by both plants and soil biota. Carbon emissions as methane from wet and moist tundra ecosystems are about 5% of emissions as CO2 and are responsive to warming in the absence of any other changes. Winter processes and vegetation type also affect CH4 emissions as well as exchanges of energy between biosphere and atmosphere. Arctic ecosystems exhibit the largest seasonal changes in energy exchange of any terrestrial ecosystem because of the large changes in albedo from late winter, when snow reflects most incoming radiation, to summer when the ecosystem absorbs most incoming radiation. Vegetation profoundly influences the water and energy exchange of Arctic ecosystems. Albedo during the period of snow cover declines from tundra to forest tundra to deciduous forest to evergreen forest. Shrubs and trees increase snow depth which in turn increases winter soil temperatures. Future changes in vegetation driven by climate change are therefore, very likely to profoundly alter regional climate.
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| 19. |
- Callaghan, Terry V., et al.
(författare)
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Responses to projected changes in climate and UV-B at the species level
- 2004
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Ingår i: Ambio: a Journal of Human Environment. - : Royal Swedish Academy of Sciences. - 0044-7447. ; 33:7, s. 418-435
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Forskningsöversikt (refereegranskat)abstract
- Environmental manipulation experiments showed that species respond individualistically to each environmental-change variable. The greatest responses of plants were generally to nutrient, particularly nitrogen, addition. Summer warming experiments showed that woody plant responses were dominant and that mosses and lichens became less abundant. Responses to warming were controlled by moisture availability and snow cover. Many invertebrates increased population growth in response to summer warming, as long as desiccation was not induced. CO2 and UV-B enrichment experiments showed that plant and animal responses were small. However, some microorganisms and species of fungi were sensitive to increased UV-B and some intensive mutagenic actions could, perhaps, lead to unexpected epidemic outbreaks. Tundra soil heating, CO 2 enrichment and amendment with mineral nutrients generally accelerated microbial activity. Algae are likely to dominate cyanobacteria in milder climates. Expected increases in winter freeze-thaw cycles leading to ice-crust formation are likely to severely reduce winter survival rate and disrupt the population dynamics of many terrestrial animals. A deeper snow cover is likely to restrict access to winter pastures by reindeer/caribou and their ability to flee from predators while any earlier onset of the snow-free period is likely to stimulate increased plant growth. Initial species responses to climate change might occur at the sub-species level: an Arctic plant or animal species with high genetic/racial diversity has proved an ability to adapt to different environmental conditions in the past and is likely to do so also in the future. Indigenous knowledge, air photographs, satellite images and monitoring show that changes in the distributions of some species are already occurring: Arctic vegetation is becoming more shrubby and more productive, there have been recent changes in the ranges of caribou, and "new" species of insects and birds previously associated with areas south of the treeline have been recorded. In contrast, almost all Arctic breeding bird species are declining and models predict further quite dramatic reductions of the populations of tundra birds due to warming. Species-climate response surface models predict potential future ranges of current Arctic species that are often markedly reduced and displaced northwards in response to warming. In contrast, invertebrates and microorganisms are very likely to quickly expand their ranges northwards into the Arctic.
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| 20. |
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| 23. |
- Engebretsen, Ingunn Marie S, et al.
(författare)
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Early infant feeding practices in three African countries : the PROMISE-EBF trial promoting exclusive breastfeeding by peer counsellors.
- 2014
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Ingår i: International Breastfeeding Journal. - : Springer Science and Business Media LLC. - 1746-4358. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Immediate and exclusive initiation of breastfeeding after delivery has been associated with better neonatal survival and child health and are recommended by the WHO. We report its impact on early infant feeding practices from the PROMISE-EBF trial.METHODS: PROMISE-EBF was a cluster randomised behaviour change intervention trial of exclusive breastfeeding (EBF) promotion by peer counsellors in Burkina Faso, Uganda and South Africa implemented during 2006-2008 among 2579 mother-infant pairs. Counselling started in the last pregnancy trimester and mothers were offered at least five postnatal visits. Early infant feeding practices: use of prelacteal feeds (any foods or drinks other than breast milk given within the first 3 days), expressing and discarding colostrum, and timing of initiation of breastfeeding are presented by trial arm in each country. Prevalence ratios (PR) with 95% confidence intervals (95%CI) are given.RESULTS: The proportion of women who gave prelacteal feeds in the intervention and control arms were, respectively: 11% and 36%, PR 0.3 (95% CI 0.2, 0.6) in Burkina Faso, 13% and 44%, PR 0.3 (95% CI 0.2, 0.5) in Uganda and 30% and 33%, PR 0.9 (95% CI 0.6, 1.3) in South Africa. While the majority gave colostrum, the proportion of those who expressed and discarded it in the intervention and control arms were: 8% and 12%, PR 0.7 (95% CI 0.3, 1.6) in Burkina Faso, 3% and 10%, PR 0.3 (95% CI 0.1, 0.6) in Uganda and 17% and 16%, PR 1.1 (95% CI 0.6, 2.1) in South Africa. Only a minority in Burkina Faso (<4%) and roughly half in South Africa initiated breastfeeding within the first hour with no large or statistically significant differences between the trial arms, whilst in Uganda the proportion of early initiation of breastfeeding in the intervention and control arms were: 55% and 41%, PR 0.8 (95% CI 0.7, 0.9).CONCLUSIONS: The PROMISE-EBF trial showed that the intervention led to less prelacteal feeding in Burkina Faso and Uganda. More children received colostrum and started breastfeeding early in the intervention arm in Uganda. Late breastfeeding initiation continues to be a challenge. No clear behaviour change was seen in South Africa.TRIAL REGISTRATION: NCT00397150.
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| 24. |
- Fortes-Lima, Cesar A., PhD, 1985-, et al.
(författare)
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Population structure and admixture during the expansion of Bantu-speaking peoples across sub-Saharan Africa
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The migration of Bantu-speaking groups out of West Africa, thought to have started around 4 000 years ago, is known as the Bantu expansion. This movement of people changed the genetic landscape of sub-equatorial Africa. To investigate the demographic history and population structure in Bantu-speaking populations (BSP), we genotyped 1,740 individuals, including 1,487 Bantu speakers from 143 populations across 13 sub-Saharan African countries. We find patterns of fine-scale population structure that correlate with linguistics and geography. Bantu speakers received significant amounts of admixture through interaction with local groups from the regions that they expanded into. Spatial modeling indicated possible migration corridors during the Bantu-expansion. Inferences based on modern-day genomes, however, need to be supported by ancient DNA studies. We demonstrated the utility of our dataset as an exhaustive modern-day African comparative dataset for ancient DNA studies by comparing our data to published aDNA studies. By gathering the largest set of genome-wide data to date, enriched with new data from previously unsampled regions and people, we shed new light on the intricacies of the Bantu expansion.
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| 25. |
- Fortes-Lima, Cesar A., PhD, 1985-, et al.
(författare)
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The genetic legacy of the expansion of Bantu-speaking peoples in Africa
- 2024
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 625:7995, s. 540-547
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Tidskriftsartikel (refereegranskat)abstract
- The expansion of people speaking Bantu languages is the most dramatic demographic event in Late Holocene Africa and fundamentally reshaped the linguistic, cultural and biological landscape of the continent1-7. With a comprehensive genomic dataset, including newly generated data of modern-day and ancient DNA from previously unsampled regions in Africa, we contribute insights into this expansion that started 6,000-4,000 years ago in western Africa. We genotyped 1,763 participants, including 1,526 Bantu speakers from 147 populations across 14 African countries, and generated whole-genome sequences from 12 Late Iron Age individuals8. We show that genetic diversity amongst Bantu-speaking populations declines with distance from western Africa, with current-day Zambia and the Democratic Republic of Congo as possible crossroads of interaction. Using spatially explicit methods9 and correlating genetic, linguistic and geographical data, we provide cross-disciplinary support for a serial-founder migration model. We further show that Bantu speakers received significant gene flow from local groups in regions they expanded into. Our genetic dataset provides an exhaustive modern-day African comparative dataset for ancient DNA studies10 and will be important to a wide range of disciplines from science and humanities, as well as to the medical sector studying human genetic variation and health in African and African-descendant populations.
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