| 1. |
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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Machiela, Mitchell J., et al.
(författare)
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Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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| 4. |
- Ntalla, Ioanna, et al.
(författare)
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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
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| 5. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 6. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 7. |
- Jacobs, Kevin B, et al.
(författare)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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| 8. |
- Machiela, Mitchell J, et al.
(författare)
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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
- 2016
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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| 9. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 10. |
- Lindblad-Toh, Kerstin, et al.
(författare)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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| 11. |
- Rao, Mukund P., et al.
(författare)
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A double bootstrap approach to Superposed Epoch Analysis to evaluate response uncertainty
- 2019
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Ingår i: Dendrochronologia. - : Elsevier BV. - 1125-7865 .- 1612-0051. ; 55, s. 119-124
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Tidskriftsartikel (refereegranskat)abstract
- The association between climate variability and episodic events, such as the antecedent moisture conditions prior to wildfire or the cooling following volcanic eruptions, is commonly assessed using Superposed Epoch Analysis (SEA). In SEA the epochal response is typically calculated as the average climate conditions prior to and following all event years or their deviation from climatology. However, the magnitude and significance of the inferred climate association may be sensitive to the selection or omission of individual key years, potentially resulting in a biased assessment of the relationship between these events and climate. Here we describe and test a modified double-bootstrap SEA that generates multiple unique draws of the key years and evaluates the sign, magnitude, and significance of event-climate relationships within a probabilistic framework. This multiple re-sampling helps quantify multiple uncertainties inherent in conventional applications of SEA within dendrochronology and paleoclimatology. We demonstrate our modified SEA by evaluating the volcanic cooling signal in a Northern Hemisphere tree-ring temperature reconstruction and the link between drought and wildfire events in the western United States. Finally, we make our Matlab and R code available to be adapted for future SEA applications.
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| 12. |
- Tenzin, Karma, et al.
(författare)
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Climate and humans interact to shape the fire regime of a chir pine (Pinus roxburghii) forest in eastern Bhutan
- 2024
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Ingår i: Fire Ecology. - 1933-9747. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- Background Chir pine (Pinus roxburghii Sarg.) forests are distributed in the dry valleys of Bhutan Himalaya. In the past, these forests have been heavily influenced by human activities such as grazing, burning, resin tapping, and collection of non-timber forest products. Bhutan’s Forest Act of 1969, which shifted forest management from local community control to centralized governmental control, greatly restricted these activities. To understand the implications of the Forest Act on the chir pine forests, we used tree-rings and fire scars to reconstruct the fire history of a chir pine forest in eastern Bhutan. This provided an opportunity to characterize the fire regime before and after the Forest Act of 1969 was implemented and assess the scale and magnitude of changes that have occurred.Results We developed a 120-year chir pine fire chronology from nine sites within a single forested landscape. Between 1900 and ~ 1970, fires were small and patchy. When fires occurred, they were limited to one to two sites within the larger study area. After 1970, there was a distinct shift in fire activity, with fires in 1985, 1989, 1996, 2000, and 2013 burning > 90% of sample plots. Fire activity was positively associated with La Niña conditions (wetter, cooler) in the preceding year. This is likely the result of increased accumulation and connectivity of fuels on the forest floor in wetter years.Conclusions Prior to 1970, the fire regime in the studied chir pine landscape in eastern Bhutan was dominated by patchy, low-intensity fires indicating that the fire regime was fuel limited. After 1970, fires became larger and more frequent. This shift was associated with the enactment of the Bhutan Forest Act in 1969, which regulated grazing and implemented a policy of strict fire exclusion in government-reserved forests. This likely led to a large buildup of fuels, particularly after La Niña years. Historical patterns of grazing and low-intensity fires prior to the Forest Act kept fuel loads low and disconnected. The cessation of most human activities in these forests after 1969 resulted in an increase in fuel loads and connectivity within the landscape. This has greatly reshaped fire regimes in the chir pine forests of eastern Bhutan over the past half century.
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| 13. |
- Visvanathan, Kala, et al.
(författare)
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Circulating vitamin D and breast cancer risk : an international pooling project of 17 cohorts
- 2023
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Ingår i: European Journal of Epidemiology. - : Springer Science+Business Media B.V.. - 0393-2990 .- 1573-7284. ; 38, s. 11-29
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Tidskriftsartikel (refereegranskat)abstract
- Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42–68) years at blood collection and 63 (49–75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, calibrated to this assay to permit using a common metric. Study-specific relative risks (RRs) for season-standardized 25(OH)D concentrations were estimated by conditional logistic regression and combined by random-effects models. Circulating 25(OH)D increased from a median of 22.6 nmol/L in consortium-wide decile 1 to 93.2 nmol/L in decile 10. Breast cancer risk in each decile was not statistically significantly different from risk in decile 5 in models adjusted for breast cancer risk factors, and no trend was apparent (P-trend = 0.64). Compared to women with sufficient 25(OH)D based on Institute of Medicine guidelines (50– < 62.5 nmol/L), RRs were not statistically significantly different at either low concentrations (< 20 nmol/L, 3% of controls) or high concentrations (100– < 125 nmol/L, 3% of controls; ≥ 125 nmol/L, 0.7% of controls). RR per 25 nmol/L increase in 25(OH)D was 0.99 [95% confidence intervaI (CI) 0.95–1.03]. Associations remained null across subgroups, including those defined by body mass index, physical activity, latitude, and season of blood collection. Although none of the associations by tumor characteristics reached statistical significance, suggestive inverse associations were seen for distant and triple negative tumors. Circulating 25(OH)D, comparably measured in 17 international cohorts and season-standardized, was not related to subsequent incidence of invasive breast cancer over a broad range in vitamin D status.
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| 14. |
- Barack, Leor, et al.
(författare)
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Black holes, gravitational waves and fundamental physics : a roadmap
- 2019
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Ingår i: Classical and quantum gravity. - : IOP Publishing. - 0264-9381 .- 1361-6382. ; 36:14
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Forskningsöversikt (refereegranskat)abstract
- The grand challenges of contemporary fundamental physics dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'.
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| 15. |
- Benjamin, Daniel J., et al.
(författare)
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Redefine statistical significance
- 2018
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Ingår i: Nature Human Behaviour. - : Nature Research (part of Springer Nature). - 2397-3374. ; 2:1, s. 6-10
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 16. |
- Büntgen, Ulf, et al.
(författare)
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Global wood anatomical perspective on the onset of the Late Antique Little Ice Age (LALIA) in the mid-6th century CE
- 2022
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Ingår i: Science Bulletin. - : Elsevier BV. - 2095-9273. ; 67:22, s. 2336-2344
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Tidskriftsartikel (refereegranskat)abstract
- Linked to major volcanic eruptions around 536 and 540 CE, the onset of the Late Antique Little Ice Age has been described as the coldest period of the past two millennia. The exact timing and spatial extent of this exceptional cold phase are, however, still under debate because of the limited resolution and geographical distribution of the available proxy archives. Here, we use 106 wood anatomical thin sections from 23 forest sites and 20 tree species in both hemispheres to search for cell-level fingerprints of ephemeral summer cooling between 530 and 550 CE. After cross-dating and double-staining, we identified 89 Blue Rings (lack of cell wall lignification), nine Frost Rings (cell deformation and collapse), and 93 Light Rings (reduced cell wall thickening) in the Northern Hemisphere. Our network reveals evidence for the strongest temperature depression between mid-July and early-August 536 CE across North America and Eurasia, whereas more localised cold spells occurred in the summers of 532, 540–43, and 548 CE. The lack of anatomical signatures in the austral trees suggests limited incursion of stratospheric volcanic aerosol into the Southern Hemisphere extra-tropics, that any forcing was mitigated by atmosphere-ocean dynamical responses and/or concentrated outside the growing season, or a combination of factors. Our findings demonstrate the advantage of wood anatomical investigations over traditional dendrochronological measurements, provide a benchmark for Earth system models, support cross-disciplinary studies into the entanglements of climate and history, and question the relevance of global climate averages.
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| 17. |
- Cook, Edward R., et al.
(författare)
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Tree-ring reconstructed summer temperature anomalies for temperate East Asia since 800 CE
- 2013
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Ingår i: Climate Dynamics. - : Springer Science and Business Media LLC. - 0930-7575 .- 1432-0894. ; 41:11-12, s. 2957-2972
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Tidskriftsartikel (refereegranskat)abstract
- We develop a summer temperature reconstruction for temperate East Asia based on a network of annual tree-ring chronologies covering the period 800-1989 C.E. The East Asia reconstruction is the regional average of 585 individual grid point summer temperature reconstructions produced using an ensemble version of point-by-point regression. Statistical calibration and validation tests indicate that the regional average possesses sufficient overall skill to allow it to be used to study the causes of temperature variability and change over the region. The reconstruction suggests a moderately warm early medieval epoch (ca. 850-1050 C.E.), followed by generally cooler 'Little Ice Age' conditions (ca. 1350-1880 C.E.) and 20th century warming up to the present time. Since 1990, average temperature has exceeded past warm epochs of comparable duration, but it is not statistically unprecedented. Superposed epoch analysis reveals a volcanic forcing signal in the East Asia summer temperature reconstruction, resulting in pulses of cooler summer conditions that may persist for several years. Substantial uncertainties remain, however, particularly at lower frequencies, thus requiring caution and scientific prudence in the interpretation of this record.
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| 18. |
- Dukpa, Dorji, et al.
(författare)
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Applied dendroecology informs the sustainable management of Blue Pine forests in Bhutan
- 2018
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Ingår i: Dendrochronologia. - : Elsevier BV. - 1125-7865 .- 1612-0051. ; 49, s. 89-93
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Forskningsöversikt (refereegranskat)abstract
- Tree ring science is a new discipline in Bhutan but has contributed substantially to our understanding of climate history and informed sustainable forest management practices in the country. This paper describes dendroecological contributions to the second aspect for Blue Pine using three case studies. i) The effects of livestock grazing impact on Blue Pine radial growth were quantified. Radial growth increment was tendentially higher after three years of livestock exclosure, as compared to continued grazing. However, differences remained statistically not significant, likely due to the brevity of the treatment period. ii) Radial growth rates of Blue Pine were characterized across a 400m elevation gradient. Cumulative radial growth over 40 years differed by a factor of more than three between the low and the high end of the gradient. However, below 2300 m, radial growth showed a continuous decline from 1990, likely as a results of drought due to climate change. iii) Effects of three levels of prescribed thinning of pole stage (DBH 30-50 cm) Blue Pine in central Bhutan showed distinct response to thinning. Heavy thinning lead to a thinning shock in the year after harvest and did not lead to significantly higher radial growth as compared to moderate thinning, which is thus recommended for the species. A positive thinning effect remained for seven years post operation. The case studies were incorporated into national guidelines on sustainable forest management in Bhutan and prove the demand for tree ring based research to inform policy and practice.
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| 19. |
- Esper, Jan, et al.
(författare)
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The IPCC’s reductive Common Era temperature history
- 2024
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Ingår i: Communications Earth & Environment. - 2662-4435. ; 5
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Forskningsöversikt (refereegranskat)abstract
- Common Era temperature variability has been a prominent component in Intergovernmental Panel on Climate Change reports over the last several decades and was twice featured in their Summary for Policymakers. A single reconstruction of mean Northern Hemisphere temperature variability was first highlighted in the 2001 Summary for Policymakers, despite other estimates that existed at the time. Subsequent reports assessed many large-scale temperature reconstructions, but the entirety of Common Era temperature history in the most recent Sixth Assessment Report of the Intergovernmental Panel on Climate Change was restricted to a single estimate of mean annual global temperatures. We argue that this focus on a single reconstruction is an insufficient summary of our understanding of temperature variability over the Common Era. We provide a complementary perspective by offering an alternative assessment of the state of our understanding in high-resolution paleoclimatology for the Common Era and call for future reports to present a more accurate and comprehensive assessment of our knowledge about this important period of human and climate history.
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| 20. |
- Holbein, Christina E., et al.
(författare)
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A multinational observational investigation of illness perceptions and quality of life among patients with a Fontan circulation
- 2018
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Ingår i: Congenital Heart Disease. - : Computers, Materials and Continua (Tech Science Press). - 1747-079X .- 1747-0803. ; 13:3, s. 392-400
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Tidskriftsartikel (refereegranskat)abstract
- Objective First, to compare QOL and illness perceptions between patients with a Fontan circulation and patients with anatomically simple defects (ie, atrial septal defects [ASD] or ventricular septal defects [VSD]). Second, to explore illness perceptions as a mediator of the association between congenital heart disease (CHD) diagnosis and QOL. Design Cross-sectional observational study. Setting Twenty-four cardiology centers from 15 countries across five continents. Patients Four hundred thirty-five adult patients with congenital heart disease (177 Fontan and 258 ASD/VSD) ages 18-83 years. Outcome Measures QOL and illness perceptions were assessed by the Satisfaction With Life Scale and the Brief Illness Perceptions Questionnaire, respectively. Results Patients with a Fontan circulation reported lower QOL (Wald Z = −3.59, p = <.001) and more negative perceptions of their CHD (Wald Z = −7.66, p < .001) compared with patients with ASD/VSD. After controlling for demographics, anxiety, depressive symptoms, and New York Heart Association functional class, path analyses revealed a significant mediation model, αβ = 0.15, p = .002, 95% CI = 0.06-0.25, such that CHD diagnosis was indirectly related to QOL through illness perceptions. Conclusions The Fontan sample’s more negative perceptions of CHD were likely a reflection of life with a more complex defect. Illness perceptions appear to account for unique differences in QOL between groups of varying CHD complexity. Psychosocial screening and interventions may be important treatment components for patients with CHD, particularly those with Fontan circulations.
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| 21. |
- Holbein, Christina E, et al.
(författare)
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Perceived Health Mediates Effects of Physical Activity on Quality of Life in Patients With a Fontan Circulation
- 2019
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 124:1, s. 144-150
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Tidskriftsartikel (refereegranskat)abstract
- Patients with a Fontan circulation are at risk of a sedentary lifestyle. Given the direct relationship between physical activity and health, promotion of physical activity has the potential to improve outcomes, including quality of life (QOL). This study aimed to describe self-reported physical activity levels in adult Fontan patients and examine associations between physical activity, perceived health status and QOL. The sample consisted of 177 Fontan patients (Mage = 27.5 ± 7.6 years, 52% male) who reported their physical activity, perceived health status, and QOL as part of the cross-sectional Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease - International Study. Descriptive statistics and univariate analyses of variance with planned contrasts were computed to describe physical activity characteristics. Mediation analyses tested whether perceived health status variables mediated the association between physical activity and QOL. Forty-six percent of patients were sedentary while only 40% met international physical activity guidelines. Higher physical activity was associated with younger age, lower NYHA class, higher perceived general health, and greater QOL. Patients who commuted by walking and engaged in sports reported better perceived health and QOL. Mediation analyses revealed that perceived general health but not NYHA functional class mediated the association between physical activity and QOL (αβ = 0.22, 95% confidence interval = 0.04 to 0.49). In conclusion, Fontan patients likely benefit from regular physical activity, having both higher perceived general health and functional capacity; greater perceived health status may contribute to enhanced QOL. In conclusion, these data support the pivotal role of regular physical activity for Fontan patients.
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| 22. |
- Leland, Caroline, et al.
(författare)
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Missing Rings, Synchronous Growth, and Ecological Disturbance in a 36-Year Pitch Pine (Pinus rigida) Provenance Study
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Provenance studies are an increasingly important analog for understanding how trees adapted to particular climatic conditions might respond to climate change. Dendrochronological analysis can illuminate differences among trees from different seed sources in terms of absolute annual growth and sensitivity to external growth factors. We analyzed annual radial growth of 567 36-year-old pitch pine (Pinus rigida Mill.) trees from 27 seed sources to evaluate their performance in a New Jersey Pine Barrens provenance experiment. Unexpectedly, missing rings were prevalent in most trees, and some years-1992, 1999, and 2006-had a particularly high frequency of missing rings across the plantation. Trees from local seed sources (<55 km away from the plantation) had a significantly smaller percentage of missing rings from 1980-2009 (mean: 5.0%), relative to northernmost and southernmost sources (mean: 9.3% and 7.9%, respectively). Some years with a high frequency of missing rings coincide with outbreaks of defoliating insects or dry growing season conditions. The propensity for missing rings synchronized annual variations in growth across all trees and might have complicated the detection of potential differences in interannual variability among seed sources. Average ring width was significantly larger in seed sources from both the southernmost and warmest origins compared to the northernmost and coldest seed sources in most years. Local seed sources had the highest average radial growth. Adaptation to local environmental conditions and disturbances might have influenced the higher growth rate found in local seed sources. These findings underscore the need to understand the integrative impact of multiple environmental drivers, such as disturbance agents and climate change, on tree growth, forest dynamics, and the carbon cycle.
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| 23. |
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| 24. |
- Palmer, Jonathan G., et al.
(författare)
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Changes in El Niño – Southern Oscillation (ENSO) conditions during the Greenland Stadial 1 (GS-1) chronozone revealed by New Zealand tree-rings
- 2016
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 153, s. 139-155
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Tidskriftsartikel (refereegranskat)abstract
- The warming trend at the end of the last glacial was disrupted by rapid cooling clearly identified in Greenland (Greenland Stadial 1 or GS-1) and Europe (Younger Dryas Stadial or YD). This reversal to glacial-like conditions is one of the best known examples of abrupt change but the exact timing and global spatial extent remain uncertain. Whilst the wider Atlantic region has a network of high-resolution proxy records spanning GS-1, the Pacific Ocean suffers from a scarcity of sub-decadally resolved sequences. Here we report the results from an investigation into a tree-ring chronology from northern New Zealand aimed at addressing the paucity of data. The conifer tree species kauri (Agathis australis) is known from contemporary studies to be sensitive to regional climate changes. An analysis of a ‘historic’ 452-year kauri chronology confirms a tropical-Pacific teleconnection via the El Niño – Southern Oscillation (ENSO). We then focus our study on a 1010-year sub-fossil kauri chronology that has been precisely dated by comprehensive radiocarbon dating and contains a striking ring-width downturn between ∼12,500 and 12,380 cal BP within GS-1. Wavelet analysis shows a marked increase in ENSO-like periodicities occurring after the downturn event. Comparison to low- and mid-latitude Pacific records suggests a coherency with ENSO and Southern Hemisphere atmospheric circulation change during this period. The driver(s) for this climate event remain unclear but may be related to solar changes that subsequently led to establishment and/or increased expression of ENSO across the mid-latitudes of the Pacific, seemingly independent of the Atlantic and polar regions.
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| 25. |
- Petimar, Joshua, et al.
(författare)
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A Pooled Analysis of 15 Prospective Cohort Studies on the Association between Fruit, Vegetable, and Mature Bean Consumption and Risk of Prostate Cancer.
- 2017
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 26:8, s. 1276-1287
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Tidskriftsartikel (refereegranskat)abstract
- Background: Relationships between fruit, vegetable, and mature bean consumption and prostate cancer risk are unclear.Methods: We examined associations between fruit and vegetable groups, specific fruits and vegetables, and mature bean consumption and prostate cancer risk overall, by stage and grade, and for prostate cancer mortality in a pooled analysis of 15 prospective cohorts, including 52,680 total cases and 3,205 prostate cancer-related deaths among 842,149 men. Diet was measured by a food frequency questionnaire or similar instrument at baseline. We calculated study-specific relative risks using Cox proportional hazards regression, and then pooled these estimates using a random effects model.Results: We did not observe any statistically significant associations for advanced prostate cancer or prostate cancer mortality with any food group (including total fruits and vegetables, total fruits, total vegetables, fruit and vegetable juice, cruciferous vegetables, and tomato products), nor specific fruit and vegetables. In addition, we observed few statistically significant results for other prostate cancer outcomes. Pooled multivariable relative risks comparing the highest versus lowest quantiles across all fruit and vegetable exposures and prostate cancer outcomes ranged from 0.89 to 1.09. There was no evidence of effect modification for any association by age or body mass index.Conclusions: Results from this large, international, pooled analysis do not support a strong role of collective groupings of fruits, vegetables, or mature beans in prostate cancer.Impact: Further investigation of other dietary exposures, especially indicators of bioavailable nutrient intake or specific phytochemicals, should be considered for prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 26(8); 1276-87. ©2017 AACR.
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| 26. |
- Rassart, Jessica, et al.
(författare)
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Illness perceptions in adult congenital heart disease : A multi-center international study.
- 2017
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 244, s. 130-138
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Illness perceptions are cognitive frameworks that patients construct to make sense of their illness. Although the importance of these perceptions has been demonstrated in other chronic illness populations, few studies have focused on the illness perceptions of adults with congenital heart disease (CHD). This study examined (1) inter-country variation in illness perceptions, (2) associations between patient characteristics and illness perceptions, and (3) associations between illness perceptions and patient-reported outcomes.METHODS: Our sample, taken from APPROACH-IS, consisted of 3258 adults with CHD from 15 different countries. Patients completed questionnaires on illness perceptions and patient-reported outcomes (i.e., quality of life, perceived health status, and symptoms of depression and anxiety). Patient characteristics included sex, age, marital status, educational level, employment status, CHD complexity, functional class, and ethnicity. Linear mixed models were applied.RESULTS: The inter-country variation in illness perceptions was generally small, yet patients from different countries differed in the extent to which they perceived their illness as chronic and worried about their illness. Patient characteristics that were linked to illness perceptions were sex, age, employment status, CHD complexity, functional class, and ethnicity. Higher scores on consequences, identity, and emotional representation, as well as lower scores on illness coherence and personal and treatment control, were associated with poorer patient-reported outcomes.CONCLUSIONS: This study emphasizes that, in order to gain a deeper understanding of patients' functioning, health-care providers should focus not only on objective indicators of illness severity such as the complexity of the heart defect, but also on subjective illness experiences.
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| 27. |
- Rydval, Milos, et al.
(författare)
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Spatial reconstruction of Scottish summer temperatures from tree rings
- 2017
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Ingår i: International Journal of Climatology. - : Wiley. - 0899-8418 .- 1097-0088. ; 37:3, s. 1540-1556
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Tidskriftsartikel (refereegranskat)abstract
- A detailed understanding of past temporal patterns and spatial expression of temperature variations is important to place recent anthropogenic climate change into a longer term context. In order to fill the current gap in our understanding of northwest European temperature variability, point-by-point principal component regression was used to reconstruct a spatial field of 0.5 degrees temperature grids across Scotland. A sequence of reconstructions utilizing several combinations of detrending and disturbance correction procedures, and a selection of tree-ring parameters [including ring width (RW), maximum latewood density (MXD) and blue intensity (BI)] was used in an evaluation of reconstruction skill. The high resolution of the reconstructed field serves also as a diagnostic tool to spatially assess the temperature reconstruction potential of local chronologies. Best reconstruction results, reaching calibration r(2)=65.8% and verification r(2)=63.7% in central Scotland over the 1901-1976 period, were achieved using disturbance-corrected and signal-free detrended RW chronologies merged with BI data after low-pass (high-pass) filtering the RW (BI) chronologies. Calibration and verification r(2)>50% was attained for central, north and east Scotland, >40% in west and northwest, and >30% in southern Scotland with verification of nearly all grids showing some reconstruction skill. However, the full calibration potential of reconstructions outside central Scotland was reduced either due to residual disturbance trends undetected by the disturbance correction procedure or due to other climatic or non-climatic factors which may have adversely affected the strength of the climate signal.
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| 28. |
- Watts, Eleanor L., et al.
(författare)
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The associations of anthropometric, behavioural and sociodemographic factors with circulating concentrations of IGF‐I, IGF‐II, IGFBP‐1, IGFBP‐2 and IGFBP‐3 in a pooled analysis of 16,024 men from 22 studies
- 2019
-
Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 145:12, s. 3244-3256
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Tidskriftsartikel (refereegranskat)abstract
- Insulin‐like growth factors (IGFs) and insulin‐like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross‐sectional associations of these exposures with circulating concentrations of IGFs (IGF‐I and IGF‐II) and IGFBPs (IGFBP‐1, IGFBP‐2 and IGFBP‐3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22–89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP‐1 and IGFBP‐2 and lower concentrations of IGF‐I, IGF‐II and IGFBP‐3. Higher body mass index was associated with lower concentrations of IGFBP‐1 and IGFBP‐2. Taller height was associated with higher concentrations of IGF‐I and IGFBP‐3 and lower concentrations of IGFBP‐1. Smokers had higher concentrations of IGFBP‐1 and IGFBP‐2 and lower concentrations of IGFBP‐3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF‐II and lower concentrations of IGF‐I and IGFBP‐2. African Americans had lower concentrations of IGF‐II, IGFBP‐1, IGFBP‐2 and IGFBP‐3 and Hispanics had lower IGF‐I, IGF‐II and IGFBP‐3 than non‐Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.
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| 29. |
- Wilson, Rob, et al.
(författare)
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Last millennium northern hemisphere summer temperatures from tree rings : Part I
- 2016
-
Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 134, s. 1-18
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Forskningsöversikt (refereegranskat)abstract
- Large-scale millennial length Northern Hemisphere (NH) temperature reconstructions have been progressively improved over the last 20 years as new datasets have been developed. This paper, and its companion (Part II, Anchukaitis et al. in prep), details the latest tree-ring (TR) based NH land air temperature reconstruction from a temporal and spatial perspective. This work is the first product of a consortium called N-TREND (Northern Hemisphere Tree-Ring Network Development) which brings together dendroclimatologists to identify a collective strategy for improving large-scale summer temperature reconstructions. The new reconstruction, N-TREND2015, utilises 54 records, a significant expansion compared with previous TR studies, and yields an improved reconstruction with stronger statistical calibration metrics. N-TREND2015 is relatively insensitive to the compositing method and spatial weighting used and validation metrics indicate that the new record portrays reasonable coherence with large scale summer temperatures and is robust at all time-scales from 918 to 2004 where at least 3 TR records exist from each major continental mass. N-TREND2015 indicates a longer and warmer medieval period (similar to 900 1170) than portrayed by previous TR NH reconstructions and by the CMIP5 model ensemble, but with better overall agreement between records for the last 600 years. Future dendroclimatic projects should focus on developing new long records from data-sparse regions such as North America and eastern Eurasia as well as ensuring the measurement of parameters related to latewood density to complement ring-width records which can improve local based calibration substantially.
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| 30. |
- Wilson, Rob, et al.
(författare)
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Last millennium northern hemisphere summer temperatures from tree rings: Part I: The long term context
- 2016
-
Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 134, s. 1-18
-
Tidskriftsartikel (refereegranskat)abstract
- Large-scale millennial length Northern Hemisphere (NH) temperature reconstructions have been progressively improved over the last 20 years as new datasets have been developed. This paper, and its companion (Part II, Anchukaitis et al. in prep), details the latest tree-ring (TR) based NH land air temperature reconstruction from a temporal and spatial perspective. This work is the first product of a consortium called N-TREND (Northern Hemisphere Tree-Ring Network Development) which brings together dendroclimatologists to identify a collective strategy for improving large-scale summer temperature reconstructions. The new reconstruction, N-TREND2015, utilises 54 records, a significant expansion compared with previous TR studies, and yields an improved reconstruction with stronger statistical calibration metrics. N-TREND2015 is relatively insensitive to the compositing method and spatial weighting used and validation metrics indicate that the new record portrays reasonable coherence with large scale summer temperatures and is robust at all time-scales from 918 to 2004 where at least 3 TR records exist from each major continental mass. N-TREND2015 indicates a longer and warmer medieval period (~900-1170) than portrayed by previous TR NH reconstructions and by the CMIP5 model ensemble, but with better overall agreement between records for the last 600 years. Future dendroclimatic projects should focus on developing new long records from data-sparse regions such as North America and eastern Eurasia as well as ensuring the measurement of parameters related to latewood density to complement ring-width records which can improve local based calibration substantially.
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| 31. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 32. |
- Yang, Bao, et al.
(författare)
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Long-term decrease in Asian monsoon rainfall and abrupt climate change events over the past 6,700 years
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - Washington : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:30
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Tidskriftsartikel (refereegranskat)abstract
- Asian summer monsoon (ASM) variability and its long-term ecological and societal impacts extending back to Neolithic times are poorly understood due to a lack of high-resolution climate proxy data. Here, we present a precisely dated and well-calibrated treering stable isotope chronology from the Tibetan Plateau with 1- to 5-y resolution that reflects high- to low-frequency ASM variability from 4680 BCE to 2011 CE. Superimposed on a persistent drying trend since the mid-Holocene, a rapid decrease in moisture availability between similar to 2000 and similar to 1500 BCE caused a dry hydroclimatic regime from similar to 1675 to similar to 1185 BCE, with mean precipitation estimated at 42 +/- 4% and 5 +/- 2% lower than during themid-Holocene and the instrumental period, respectively. This second-millennium-BCE megadrought marks the mid-to late Holocene transition, during which regional forests declined and enhanced aeolian activity affected northern Chinese ecosystems. We argue that this abrupt aridification starting similar to 2000 BCE contributed to the shift of Neolithic cultures in northern China and likely triggered human migration and societal transformation.
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| 33. |
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