Signals of tree volume and temperature in a high-resolution record of pollen accumulation rates in northern Finland

International audiencePollen accumulation rates (PARs) provide a potential proxy for quantitative tree volume (m3 ha 1) reconstruction with reliable absolute pollen productivity estimates (APPEs). We obtained APPEs for pine, spruce and birch at their range limits in northern Finland under two temperature periods ('warm' and 'cold') based on long-term pollen trap and tree volume records within a 14-km radius of each trap. APPEs (mean SE; 108 grains m 3 a 1) tend to be higher for the 'warm' periods (pine 123.8 24.4, birch 528.0 398.4, spruce 434.3 113.7) compared with the 'cold' periods (pine 95.5 37.3, birch 317.3 282.6, spruce 119.6 37.6), although the difference is only significant for spruce. Using an independent temperature record and the APPEs obtained, we reconstruct a low-frequency record of pine volume changes over the last 1000 years at Palomaa mire, where a high-resolution record of Pinus PARs is available. Five phases are distinguished in the reconstruction: moderate pine volume, AD 1080-1170; high volume, AD 1170-1340; low volume, AD 1340-1630; very low volume, AD 1630-1810; and rising pine volume, AD 1810- 1950. These phases do not coincide with periods of high or low June-July-August temperatures, and thus appear to reflect regional variations in tree volume, while high-frequency changes within each time-period block show variations in PARs in response to temperatur

Pollen-Based Maps of Past Regional Vegetation Cover in Europe Over 12 Millennia-Evaluation and Potential

Realistic and accurate reconstructions of past vegetation cover are necessary to study past environmental changes. This is important since the effects of human land-use changes (e.g. agriculture, deforestation and afforestation/reforestation) on biodiversity and climate are still under debate. Over the last decade, development, validation, and application of pollen-vegetation relationship models have made it possible to estimate plant abundance from fossil pollen data at both local and regional scales. In particular, the REVEALS model has been applied to produce datasets of past regional plant cover at 1 degrees spatial resolution at large subcontinental scales (North America, Europe, and China). However, such reconstructions are spatially discontinuous due to the discrete and irregular geographical distribution of sites (lakes and peat bogs) from which fossil pollen records have been produced. Therefore, spatial statistical models have been developed to create continuous maps of past plant cover using the REVEALS-based land cover estimates. In this paper, we present the first continuous time series of spatially complete maps of past plant cover across Europe during the Holocene (25 time windows covering the period from 11.7 k BP to present). We use a spatial-statistical model for compositional data to interpolate REVEALS-based estimates of three major land-cover types (LCTs), i.e., evergreen trees, summer-green trees and open land (grasses, herbs and low shrubs); producing spatially complete maps of the past coverage of these three LCTs. The spatial model uses four auxiliary data sets-latitude, longitude, elevation, and independent scenarios of past anthropogenic land-cover change based on per-capita land-use estimates ("standard" KK10 scenarios)-to improve model performance for areas with complex topography or few observations. We evaluate the resulting reconstructions for selected time windows using present day maps from the European Forest Institute, cross validate, and compare the results with earlier pollen-based spatially-continuous estimates for five selected time windows, i.e., 100 BP-present, 350-100 BP, 700-350 BP, 3.2-2.7 k BP, and 6.2-5.7 k BP. The evaluations suggest that the statistical model provides robust spatial reconstructions. From the maps we observe the broad change in the land-cover of Europe from dominance of naturally open land and persisting remnants of continental ice in the Early Holocene to a high fraction of forest cover in the Mid Holocene, and anthropogenic deforestation in the Late Holocene. The temporal and spatial continuity is relevant for land-use, land-cover, and climate research

Pollen-Based Maps of Past Regional Vegetation Cover in Europe Over 12 Millennia-Evaluation and Potential

Realistic and accurate reconstructions of past vegetation cover are necessary to study past environmental changes. This is important since the effects of human land-use changes (e.g. agriculture, deforestation and afforestation/reforestation) on biodiversity and climate are still under debate. Over the last decade, development, validation, and application of pollen-vegetation relationship models have made it possible to estimate plant abundance from fossil pollen data at both local and regional scales. In particular, the REVEALS model has been applied to produce datasets of past regional plant cover at 1 degrees spatial resolution at large subcontinental scales (North America, Europe, and China). However, such reconstructions are spatially discontinuous due to the discrete and irregular geographical distribution of sites (lakes and peat bogs) from which fossil pollen records have been produced. Therefore, spatial statistical models have been developed to create continuous maps of past plant cover using the REVEALS-based land cover estimates. In this paper, we present the first continuous time series of spatially complete maps of past plant cover across Europe during the Holocene (25 time windows covering the period from 11.7 k BP to present). We use a spatial-statistical model for compositional data to interpolate REVEALS-based estimates of three major land-cover types (LCTs), i.e., evergreen trees, summer-green trees and open land (grasses, herbs and low shrubs); producing spatially complete maps of the past coverage of these three LCTs. The spatial model uses four auxiliary data sets-latitude, longitude, elevation, and independent scenarios of past anthropogenic land-cover change based on per-capita land-use estimates ("standard" KK10 scenarios)-to improve model performance for areas with complex topography or few observations. We evaluate the resulting reconstructions for selected time windows using present day maps from the European Forest Institute, cross validate, and compare the results with earlier pollen-based spatially-continuous estimates for five selected time windows, i.e., 100 BP-present, 350-100 BP, 700-350 BP, 3.2-2.7 k BP, and 6.2-5.7 k BP. The evaluations suggest that the statistical model provides robust spatial reconstructions. From the maps we observe the broad change in the land-cover of Europe from dominance of naturally open land and persisting remnants of continental ice in the Early Holocene to a high fraction of forest cover in the Mid Holocene, and anthropogenic deforestation in the Late Holocene. The temporal and spatial continuity is relevant for land-use, land-cover, and climate research

Multicentre comparison of a diagnostic assay: Aquaporin-4 antibodies in neuromyelitis optica

Objective Antibodies to cell surface central nervous system proteins help to diagnose conditions which often respond to immunotherapies. The assessment of antibody assays needs to reflect their clinical utility. We report the results of a multicentre study of aquaporin (AQP) 4 antibody (AQP4-Ab) assays in neuromyelitis optica spectrum disorders (NMOSD). Methods Coded samples from patients with neuromyelitis optica (NMO) or NMOSD (101) and controls (92) were tested at 15 European diagnostic centres using 21 assays including live (n=3) or fixed cell-based assays (n=10), flow cytometry (n=4), immunohistochemistry (n=3) and ELISA (n=1). Results Results of tests on 92 controls identified 12assays as highly specific (0-1 false-positive results). 32 samples from 50 (64%) NMO sera and 34 from 51 (67%) NMOSD sera were positive on at least two of the 12 highly specific assays, leaving 35 patients with seronegative NMO/spectrum disorder (SD). On the basis of a combination of clinical phenotype and the highly specific assays, 66 AQP4-Ab seropositive samples were used to establish the sensitivities (51.5-100%) of all 21 assays. The specificities (85.8-100%) were based on 92 control samples and 35 seronegative NMO/SD patient samples. Conclusions The cell-based assays were most sensitive and specific overall, but immunohistochemistry or flow cytometry could be equally accurate in specialist centres. Since patients with AQP4-Ab negative NMO/SD require different management, the use of both appropriate control samples and defined seronegative NMOSD samples is essential to evaluate these assays in a clinically meaningful way. The process described here can be applied to the evaluation of other antibody assays in the newly evolving field of autoimmune neurology

Maternal outcomes and risk factors for COVID-19 severity among pregnant women.

Pregnant women may be at higher risk of severe complications associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to obstetrical complications. We performed a case control study comparing pregnant women with severe coronavirus disease 19 (cases) to pregnant women with a milder form (controls) enrolled in the COVI-Preg international registry cohort between March 24 and July 26, 2020. Risk factors for severity, obstetrical and immediate neonatal outcomes were assessed. A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented with severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. Pregnant women with severe maternal outcomes were at higher risk of caesarean section [70.7% (n = 53/75)], preterm delivery [62.7% (n = 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n = 31/75)]. In this study, several risk factors for developing severe complications of SARS-CoV-2 infection among pregnant women were identified including pulmonary comorbidities, hypertensive disorders and diabetes. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease

Particulate matter exposure during pregnancy is associated with birth weight, but not gestational age, 1962-1992: a cohort study

<p>Abstract</p> <p>Background</p> <p>Exposure to air pollutants is suggested to adversely affect fetal growth, but the evidence remains inconsistent in relation to specific outcomes and exposure windows.</p> <p>Methods</p> <p>Using birth records from the two major maternity hospitals in Newcastle upon Tyne in northern England between 1961 and 1992, we constructed a database of all births to mothers resident within the city. Weekly black smoke exposure levels from routine data recorded at 20 air pollution monitoring stations were obtained and individual exposures were estimated via a two-stage modeling strategy, incorporating temporally and spatially varying covariates. Regression analyses, including 88,679 births, assessed potential associations between exposure to black smoke and birth weight, gestational age and birth weight standardized for gestational age and sex.</p> <p>Results</p> <p>Significant associations were seen between black smoke and both standardized and unstandardized birth weight, but not for gestational age when adjusted for potential confounders. Not all associations were linear. For an increase in whole pregnancy black smoke exposure, from the 1^st(7.4 μg/m³) to the 25^th(17.2 μg/m³), 50^th(33.8 μg/m³), 75^th(108.3 μg/m³), and 90^th(180.8 μg/m³) percentiles, the adjusted estimated decreases in birth weight were 33 g (SE 1.05), 62 g (1.63), 98 g (2.26) and 109 g (2.44) respectively. A significant interaction was observed between socio-economic deprivation and black smoke on both standardized and unstandardized birth weight with increasing effects of black smoke in reducing birth weight seen with increasing socio-economic disadvantage.</p> <p>Conclusions</p> <p>The findings of this study progress the hypothesis that the association between black smoke and birth weight may be mediated through intrauterine growth restriction. The associations between black smoke and birth weight were of the same order of magnitude as those reported for passive smoking. These findings add to the growing evidence of the harmful effects of air pollution on birth outcomes.</p

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.NovartisEli Lilly and CompanyAstraZenecaAbbViePfizer UKCelgeneEisaiGenentechMerck Sharp and DohmeRocheCancer Research UKGovernment of CanadaArray BioPharmaGenome CanadaNational Institutes of HealthEuropean CommissionMinistère de l'Économie, de l’Innovation et des Exportations du QuébecSeventh Framework ProgrammeCanadian Institutes of Health Researc

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores