Showing papers by "University of Iceland published in 2009"
Atlantic Oceanographic and Meteorological Laboratory1, Earth System Research Laboratory2, Pacific Marine Environmental Laboratory3, Oregon State University4, Monterey Bay Aquarium Research Institute5, University of East Anglia6, Pierre-and-Marie-Curie University7, Hokkaido University8, National Institute for Environmental Studies9, Leibniz Institute of Marine Sciences10, University of Iceland11, Hobart Corporation12, Bjerknes Centre for Climate Research13, Fisheries and Oceans Canada14, University of Liège15
TL;DR: In this article, a global mean distribution for surface water pCO2 over the global oceans in non-El Nino conditions has been constructed with spatial resolution of 4° (latitude) × 5° (longitude) for a reference year 2000 based upon about 3 million measurements of surface water PCO2 obtained from 1970 to 2007.
Abstract: A climatological mean distribution for the surface water pCO2 over the global oceans in non-El Nino conditions has been constructed with spatial resolution of 4° (latitude) ×5° (longitude) for a reference year 2000 based upon about 3 million measurements of surface water pCO2 obtained from 1970 to 2007. The database used for this study is about 3 times larger than the 0.94 million used for our earlier paper [Takahashi et al., 2002. Global sea–air CO2 flux based on climatological surface ocean pCO2, and seasonal biological and temperature effects. Deep-Sea Res. II, 49, 1601–1622]. A time-trend analysis using deseasonalized surface water pCO2 data in portions of the North Atlantic, North and South Pacific and Southern Oceans (which cover about 27% of the global ocean areas) indicates that the surface water pCO2 over these oceanic areas has increased on average at a mean rate of 1.5 μatm y−1 with basin-specific rates varying between 1.2±0.5 and 2.1±0.4 μatm y−1. A global ocean database for a single reference year 2000 is assembled using this mean rate for correcting observations made in different years to the reference year. The observations made during El Nino periods in the equatorial Pacific and those made in coastal zones are excluded from the database.
Seasonal changes in the surface water pCO2 and the sea-air pCO2 difference over four climatic zones in the Atlantic, Pacific, Indian and Southern Oceans are presented. Over the Southern Ocean seasonal ice zone, the seasonality is complex. Although it cannot be thoroughly documented due to the limited extent of observations, seasonal changes in pCO2 are approximated by using the data for under-ice waters during austral winter and those for the marginal ice and ice-free zones.
The net air–sea CO2 flux is estimated using the sea–air pCO2 difference and the air–sea gas transfer rate that is parameterized as a function of (wind speed)2 with a scaling factor of 0.26. This is estimated by inverting the bomb 14C data using Ocean General Circulation models and the 1979–2005 NCEP-DOE AMIP-II Reanalysis (R-2) wind speed data. The equatorial Pacific (14°N–14°S) is the major source for atmospheric CO2, emitting about +0.48 Pg-C y−1, and the temperate oceans between 14° and 50° in the both hemispheres are the major sink zones with an uptake flux of −0.70 Pg-C y−1 for the northern and −1.05 Pg-C y−1 for the southern zone. The high-latitude North Atlantic, including the Nordic Seas and portion of the Arctic Sea, is the most intense CO2 sink area on the basis of per unit area, with a mean of −2.5 tons-C month−1 km−2. This is due to the combination of the low pCO2 in seawater and high gas exchange rates. In the ice-free zone of the Southern Ocean (50°–62°S), the mean annual flux is small (−0.06 Pg-C y−1) because of a cancellation of the summer uptake CO2 flux with the winter release of CO2 caused by deepwater upwelling. The annual mean for the contemporary net CO2 uptake flux over the global oceans is estimated to be −1.6±0.9 Pg-C y−1, which includes an undersampling correction to the direct estimate of −1.4±0.7 Pg-C y−1. Taking the pre-industrial steady-state ocean source of 0.4±0.2 Pg-C y−1 into account, the total ocean uptake flux including the anthropogenic CO2 is estimated to be −2.0±1.0 Pg-C y−1 in 2000.
1,653 citations
Maastricht University Medical Centre1, deCODE genetics2, Utrecht University3, University of California, Los Angeles4, University of Oslo5, University of Bonn6, Ludwig Maximilian University of Munich7, Copenhagen University Hospital8, Wellcome Trust Sanger Institute9, Aarhus University Hospital10, Aarhus University11, University of Iceland12, University of Helsinki13, Bispebjerg Hospital14, Glostrup Hospital15, Heidelberg University16, Semmelweis University17, University of Verona18, Radboud University Nijmegen Medical Centre19, Russian Academy20, University of Valencia21, King's College London22, Royal Cornhill Hospital23, Duke University24, University of Santiago de Compostela25, Hospital General Universitario Gregorio Marañón26, Karolinska Institutet27, Hammersmith Hospital28, GlaxoSmithKline29, Sichuan University30
TL;DR: Findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.
Abstract: Schizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders. The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the 'genomic disorders', have not yet been characterized. Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.
1,625 citations
TL;DR: A seminal view on recent advances in techniques for hyperspectral image processing, focusing on the design of techniques able to deal with the high-dimensional nature of the data, and to integrate the spa- tial and spectral information.
1,481 citations
TL;DR: In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 × 10−7 and included previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity.
Abstract: Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of obesity, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on obesity-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 x 10(-7). This includes previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity.
1,340 citations
National Institutes of Health1, University of Geneva2, Johns Hopkins University3, University of Washington4, Erasmus University Rotterdam5, University of Texas Health Science Center at Houston6, University of Iceland7, Boston University8, Cedars-Sinai Medical Center9, Harvard University10, Group Health Cooperative11
TL;DR: A genome-wide association study of systolic (SBP) and diastolic (DBP) blood pressure and hypertension in the CHARGE Consortium identifies 13 SNPs for SBP, 20 for DBP and 10 for hypertension at P < 4 × 10−7.
Abstract: Blood pressure is a major cardiovascular disease risk factor. To date, few variants associated with interindividual blood pressure variation have been identified and replicated. Here we report results of a genome-wide association study of systolic (SBP) and diastolic (DBP) blood pressure and hypertension in the CHARGE Consortium (n = 29,136), identifying 13 SNPs for SBP, 20 for DBP and 10 for hypertension at P < 4 × 10(-7). The top ten loci for SBP and DBP were incorporated into a risk score; mean BP and prevalence of hypertension increased in relation to the number of risk alleles carried. When ten CHARGE SNPs for each trait were included in a joint meta-analysis with the Global BPgen Consortium (n = 34,433), four CHARGE loci attained genome-wide significance (P < 5 × 10(-8)) for SBP (ATP2B1, CYP17A1, PLEKHA7, SH2B3), six for DBP (ATP2B1, CACNB2, CSK-ULK3, SH2B3, TBX3-TBX5, ULK4) and one for hypertension (ATP2B1). Identifying genes associated with blood pressure advances our understanding of blood pressure regulation and highlights potential drug targets for the prevention or treatment of hypertension.
1,333 citations
Harvard University1, Broad Institute2, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico3, McMaster University4, McGill University5, University of Leicester6, University of Lübeck7, University of Pennsylvania8, Vanderbilt University9, University of Missouri–Kansas City10, University of Münster11, University of Verona12, Queen's University Belfast13, University of Washington14, Boston University15, University of Helsinki16, National Institute for Health and Welfare17, Lund University18, University of Cambridge19, Vita-Salute San Raffaele University20, University of Ferrara21, University of Turin22, Hebrew University of Jerusalem23, University of Girona24, University of Milan25, University of Leeds26, University of Regensburg27, Ludwig Maximilian University of Munich28, University of Kiel29, Wellcome Trust Sanger Institute30, University of Paris31, MedStar Washington Hospital Center32, deCODE genetics33, University of Iceland34
TL;DR: SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with my Cardiovascular Infarction risk.
Abstract: We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls We carried out replication in an independent sample with an effective sample size of up to 19,492 SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations1, 2, 3, 4 (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9) We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10-3) We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk
1,092 citations
deCODE genetics1, University of Iceland2, University of Western Australia3, Sir Charles Gairdner Hospital4, University Medical Center Groningen5, University of Freiburg6, University of Groningen7, Queen's University8, University of Cologne9, Sogang University10, Soonchunhyang University11, Copenhagen University Hospital12, Uppsala University13, The Chinese University of Hong Kong14, Duke University15, Emory University16, University of Pennsylvania17, University of Otago18, University of Verona19
TL;DR: A genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly with myocardial infarction in six different populations.
Abstract: Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
754 citations
Wellcome Trust Centre for Human Genetics1, Medical Research Council2, Broad Institute3, Harvard University4, King's College London5, Wellcome Trust Sanger Institute6, deCODE genetics7, Boston University8, University of Michigan9, Erasmus University Rotterdam10, National Institutes of Health11, VU University Amsterdam12, University of Oulu13, Lund University14, University of Virginia15, University of Lausanne16, University Hospital of Lausanne17, University of Southern California18, Imperial College London19, Ninewells Hospital20, University of California, Los Angeles21, University of Düsseldorf22, Novartis23, Swiss Institute of Bioinformatics24, European Bioinformatics Institute25, University of Eastern Finland26, GlaxoSmithKline27, University of North Carolina at Chapel Hill28, Oulu University Hospital29, University Medical Center Groningen30, University of Helsinki31, Ludwig Maximilian University of Munich32, University of Cambridge33, Leiden University Medical Center34, VU University Medical Center35, Brigham and Women's Hospital36, Massachusetts Institute of Technology37, University of Iceland38, University of Oxford39
TL;DR: Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten genome-wide association scans, and previous associations of fasting glucose with variants at the G6PC2 and GCK loci are confirmed.
Abstract: To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.
716 citations
TL;DR: A new spectral-spatial classification scheme for hyperspectral images is proposed that improves the classification accuracies and provides classification maps with more homogeneous regions, when compared to pixel wise classification.
Abstract: A new spectral-spatial classification scheme for hyperspectral images is proposed. The method combines the results of a pixel wise support vector machine classification and the segmentation map obtained by partitional clustering using majority voting. The ISODATA algorithm and Gaussian mixture resolving techniques are used for image clustering. Experimental results are presented for two hyperspectral airborne images. The developed classification scheme improves the classification accuracies and provides classification maps with more homogeneous regions, when compared to pixel wise classification. The proposed method performs particularly well for classification of images with large spatial structures and when different classes have dissimilar spectral responses and a comparable number of pixels.
704 citations
University of Leicester1, Pennsylvania State University2, University of Warwick3, Harvard University4, University of Copenhagen5, Max Planck Society6, Goddard Space Flight Center7, University of California, Berkeley8, University of Amsterdam9, University of Iceland10, University of Exeter11, University of Bristol12, Spanish National Research Council13, European Southern Observatory14, Australian National University15, Special Astrophysical Observatory16, Space Telescope Science Institute17, Universities Space Research Association18, California Institute of Technology19, Liverpool John Moores University20, Pomona College21, University of Oxford22, McGill University23, University College London24, Stockholm University25, George Washington University26
TL;DR: In this paper, the authors reported that GRB 090423 lies at a redshift of z approximate to 8.2, implying that massive stars were being produced and dying as GRBs similar to 630 Myr after the Big Bang.
Abstract: Long-duration gamma-ray bursts (GRBs) are thought to result from the explosions of certain massive stars(1), and some are bright enough that they should be observable out to redshifts of z > 20 using current technology(2-4). Hitherto, the highest redshift measured for any object was z = 6.96, for a Lyman-alpha emitting galaxy(5). Here we report that GRB 090423 lies at a redshift of z approximate to 8.2, implying that massive stars were being produced and dying as GRBs similar to 630 Myr after the Big Bang. The burst also pinpoints the location of its host galaxy.
689 citations
Cecilia M. Lindgren1, Iris M. Heid2, Joshua C. Randall1, Claudia Lamina3 +152 more•Institutions (36)
TL;DR: By focusing on anthropometric measures of central obesity and fat distribution, a meta-analysis of 16 genome-wide association studies informative for adult waist circumference and waist–hip ratio identified three loci implicated in the regulation of human adiposity.
Abstract: To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.
deCODE genetics1, Radboud University Nijmegen Medical Centre2, University of Iceland3, University of Turin4, Karolinska Institutet5, German Cancer Research Center6, St James's University Hospital7, University of Brescia8, Katholieke Universiteit Leuven9, Maastricht University10, University of Birmingham11, University of Zaragoza12, Northwestern University13, Radboud University Nijmegen14, University of Gothenburg15, Imperial College London16
TL;DR: It is found that rs401681[C] on chromosome 5p15 satisfied the threshold for genome-wide significance and seems to confer protection against cutaneous melanoma, and investigation of the region led to rs2736098[A], which showed stronger association with some cancer types, but neither variant could fully account for the association of the other.
Abstract: The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.25, P = 3.7 x 10(-12)). We tested rs401681 for association with 16 additional cancer types in over 30,000 cancer cases and 45,000 controls and found association with lung cancer (OR = 1.15, P = 7.2 x 10(-8)) and urinary bladder, prostate and cervix cancer (ORs = 1.07-1.31, all P < 4 x 10(-4)). However, rs401681[C] seems to confer protection against cutaneous melanoma (OR = 0.88, P = 8.0 x 10(-4)). Notably, most of these cancer types have a strong environmental component to their risk. Investigation of the region led us to rs2736098[A], which showed stronger association with some cancer types. However, neither variant could fully account for the association of the other. rs2736098 corresponds to A305A in the telomerase reverse transcriptase (TERT) protein and rs401681 is in an intron of the CLPTM1L gene.
TL;DR: The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and collaborating non-member studies or consortia provide an excellent framework for the identification of the genetic determinants of risk factors, subclinical-disease measures, and clinical events.
Abstract: Background— The primary aim of genome-wide association studies is to identify novel genetic loci associated with interindividual variation in the levels of risk factors, the degree of subclinical disease, or the risk of clinical disease. The requirement for large sample sizes and the importance of replication have served as powerful incentives for scientific collaboration.
Methods— The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium was formed to facilitate genome-wide association studies meta-analyses and replication opportunities among multiple large population-based cohort studies, which collect data in a standardized fashion and represent the preferred method for estimating disease incidence. The design of the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium includes 5 prospective cohort studies from the United States and Europe: the Age, Gene/Environment Susceptibility—Reykjavik Study, the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study. With genome-wide data on a total of about 38 000 individuals, these cohort studies have a large number of health-related phenotypes measured in similar ways. For each harmonized trait, within-cohort genome-wide association study analyses are combined by meta-analysis. A prospective meta-analysis of data from all 5 cohorts, with a properly selected level of genome-wide statistical significance, is a powerful approach to finding genuine phenotypic associations with novel genetic loci.
Conclusions— The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and collaborating non-member studies or consortia provide an excellent framework for the identification of the genetic determinants of risk factors, subclinical-disease measures, and clinical events.
Received October 17, 2008; accepted December 17, 2008.
TL;DR: It is shown that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined and a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes is observed.
Abstract: Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site.
Johns Hopkins University1, University of Washington2, Erasmus University Rotterdam3, National Institutes of Health4, Boston University5, University of Iceland6, University of Texas Health Science Center at Houston7, Geneva College8, Cedars-Sinai Medical Center9, Tufts University10, Harvard University11, University of California, San Francisco12
TL;DR: These findings provide new insights into CKD pathogenesis and underscore the importance of common genetic variants influencing renal function and disease.
Abstract: Caroline Fox and colleagues report results of a genome-wide association study to identify common variants associated with indices of renal function. They show that variants at UMOD, a gene previously implicated in rare monogenic forms of kidney disease, are associated with risk of chronic kidney disease in the general population.
TL;DR: In this article, the potential antioxidant activities of water and 70% acetone extracts from ten species of Icelandic seaweeds were evaluated using three antioxidant assays. But no correlation was found with their TPC, suggesting that other components such as polysaccharides, proteins or peptides in the extracts were more effective chelators of ferrous ions than phenolic compounds.
deCODE genetics1, Emory University2, University of Iceland3, University Hospital of North Norway4, University of Tromsø5, Norwegian University of Science and Technology6, Norwegian Institute of Public Health7, Vanderbilt University Medical Center8, The Chinese University of Hong Kong9, Ludwig Maximilian University of Munich10, University of Kiel11, University of Münster12, St George's, University of London13, Karolinska University Hospital14
TL;DR: A variant in the ZFHX3 gene on chromosome 16q22, rs7193343-T, associated significantly with AF is identified, and this variant also associated with ischemic stroke and cardioembolic stroke in a combined analysis of five stroke samples.
Abstract: Daniel Gudbjartsson and colleagues report a genome-wide association study for atrial fibrillation, a condition associated with increased risk of stroke. They report a variant in ZFHX3 associated with atrial fibrillation as well as ischemic stroke. We expanded our genome-wide association study on atrial fibrillation (AF) in Iceland, which previously identified risk variants on 4q25, and tested the most significant associations in samples from Iceland, Norway and the United States. A variant in the ZFHX3 gene on chromosome 16q22, rs7193343-T, associated significantly with AF (odds ratio OR = 1.21, P = 1.4 × 10−10). This variant also associated with ischemic stroke (OR = 1.11, P = 0.00054) and cardioembolic stroke (OR = 1.22, P = 0.00021) in a combined analysis of five stroke samples.
University of Copenhagen1, University of Iceland2, University of California, Santa Cruz3, European Southern Observatory4, International School for Advanced Studies5, University of Leicester6, Stockholm University7, University of Chicago8, INAF9, University of California, Berkeley10, Spanish National Research Council11, Space Telescope Science Institute12, University of Oslo13, Marshall Space Flight Center14, University of Warwick15, Trieste Astronomical Observatory16
TL;DR: In this article, the authors presented a sample of 77 optical afterglows (OAs) of Swift detected gamma-ray bursts (GRBs) for which spectroscopic follow-up observations have been secured.
Abstract: We present a sample of 77 optical afterglows (OAs) of Swift detected gamma-ray bursts (GRBs) for which spectroscopic follow-up observations have been secured. Our first objective is to measure the redshifts of the bursts. For the majority (90%) of the afterglows, the redshifts have been determined from the spectra. We provide line lists and equivalent widths (EWs) for all detected lines redward of Lyα covered by the spectra. In addition to the GRB absorption systems, these lists include line strengths for a total of 33 intervening absorption systems. We discuss to what extent the current sample of Swift bursts with OA spectroscopy is a biased subsample of all Swift detected GRBs. For that purpose we define an X-ray-selected statistical sample of Swift bursts with optimal conditions for ground-based follow-up from the period 2005 March to 2008 September; 146 bursts fulfill our sample criteria. We derive the redshift distribution for the statistical (X-ray selected) sample and conclude that less than 18% of Swift bursts can be at z > 7. We compare the high-energy properties (e.g., γ-ray (15-350 keV) fluence and duration, X-ray flux, and excess absorption) for three subsamples of bursts in the statistical sample: (1) bursts with redshifts measured from OA spectroscopy; (2) bursts with detected optical and/or near-IR afterglow, but no afterglow-based redshift; and (3) bursts with no detection of the OA. The bursts in group (1) have slightly higher γ-ray fluences and higher X-ray fluxes and significantly less excess X-ray absorption than bursts in the other two groups. In addition, the fractions of dark bursts, defined as bursts with an optical to X-ray slope βOX 39% in group (3). For the full sample, the dark burst fraction is constrained to be in the range 25%-42%. From this we conclude that the sample of GRBs with OA spectroscopy is not representative for all Swift bursts, most likely due to a bias against the most dusty sight lines. This should be taken into account when determining, e.g., the redshift or metallicity distribution of GRBs and when using GRBs as a probe of star formation. Finally, we characterize GRB absorption systems as a class and compare them to QSO absorption systems, in particular the damped Lyα absorbers (DLAs). On average GRB absorbers are characterized by significantly stronger EWs for H I as well as for both low and high ionization metal lines than what is seen in intervening QSO absorbers. However, the distribution of line strengths is very broad and several GRB absorbers have lines with EWs well within the range spanned by QSO-DLAs. Based on the 33 z > 2 bursts in the sample, we place a 95% confidence upper limit of 7.5% on the mean escape fraction of ionizing photons from star-forming galaxies. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere, Chile, under programs 275.D-5022 (PI: Chincarini), 075.D-0270 (PI: Fynbo), 077.D-0661 (PI: Vreeswijk), 077.D-0805 (PI: Tagliaferri), 177.A-0591 (PI: Hjorth), 078.D-0416 (PI: Vreeswijk), 079.D-0429 (PI: Vreeswijk), 080.D-0526 (PI: Vreeswijk), 081.A-0135 (PI: Greiner), 281.D-5002 (PI: Della Valle), and 081.A-0856 (PI: Vreeswijk). Also based on observations made with the Nordic Optical Telescope, operated on the island of La Palma jointly by Denmark, Finland, Iceland, Norway, and Sweden, in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias. Some of the data obtained herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck foundation.
TL;DR: The importance of listening to children's perspectives has been emphasised in a wide range of recent research, using a variety of strategies, such as drawing as a strategy to engage with young children around the topic of starting school.
Abstract: The importance of listening to children’s perspectives has been emphasised in a wide range of recent research, using a variety of strategies. This paper explores the use of drawing as a strategy to engage with young children around the topic of starting school. It describes the approaches we have used, examines the benefits and challenges we have encountered and discusses implications of using drawings as a strategy for engaging with young children (aged 4–6 years) in research.
TL;DR: Two common variants, located on 9q22.33 and 14q13.3, are shown to be associated with thyroid cancer, and both risk alleles are associated with low concentrations of thyroid stimulating hormone (TSH) and high concentration of triiodothyronine (T3).
Abstract: In order to search for sequence variants conferring risk of thyroid cancer we conducted a genome-wide association study in 192 and 37,196 Icelandic cases and controls, respectively, followed by a replication study in individuals of European descent. Here we show that two common variants, located on 9q22.33 and 14q13.3, are associated with the disease. Overall, the strongest association signals were observed for rs965513 on 9q22.33 (OR = 1.75; P = 1.7 x 10(-27)) and rs944289 on 14q13.3 (OR = 1.37; P = 2.0 x 10(-9)). The gene nearest to the 9q22.33 locus is FOXE1 (TTF2) and NKX2-1 (TTF1) is among the genes located at the 14q13.3 locus. Both variants contribute to an increased risk of both papillary and follicular thyroid cancer. Approximately 3.7% of individuals are homozygous for both variants, and their estimated risk of thyroid cancer is 5.7-fold greater than that of noncarriers. In a study on a large sample set from the general population, both risk alleles are associated with low concentrations of thyroid stimulating hormone (TSH), and the 9q22.33 allele is associated with low concentration of thyroxin (T(4)) and high concentration of triiodothyronine (T(3)).
deCODE genetics1, University of Iceland2, University of Tampere3, Vanderbilt University4, University of Zaragoza5, Radboud University Nijmegen Medical Centre6, Radboud University Nijmegen7, Washington University in St. Louis8, Northwestern University9, University of Turin10, Veterans Health Administration11
TL;DR: In a multivariate analysis using 22 prostate cancer risk variants typed in the Icelandic population, it is estimated that carriers in the top 1.3% of the risk distribution are at a 2.5 times greater risk of developing the disease than members of the general population.
Abstract: We report a prostate cancer genome-wide association follow-on study. We discovered four variants associated with susceptibility to prostate cancer in several European populations: rs10934853[A] (OR = 1.12, P = 2.9 x 10(-10)) on 3q21.3; two moderately correlated (r2 = 0.07) variants, rs16902094[G] (OR = 1.21, P = 6.2 x 10(-15)) and rs445114[T] (OR = 1.14, P = 4.7 x 10(-10)), on 8q24.21; and rs8102476[C] (OR = 1.12, P = 1.6 x 10(-11)) on 19q13.2. We also refined a previous association signal on 11q13 with the SNP rs11228565[A] (OR = 1.23, P = 6.7 x 10(-12)). In a multivariate analysis using 22 prostate cancer risk variants typed in the Icelandic population, we estimated that carriers in the top 1.3% of the risk distribution are at a 2.5 times greater risk of developing the disease than members of the general population.
Boston University1, National Institutes of Health2, University of Washington3, Johns Hopkins University4, Technische Universität München5, Erasmus University Rotterdam6, University of Mainz7, University of Texas Health Science Center at Houston8, Ludwig Maximilian University of Munich9, Harvard University10, University of Iceland11, Wake Forest University12, Group Health Cooperative13, University of Minnesota14, Cedars-Sinai Medical Center15, University of North Carolina at Chapel Hill16, United States Department of Veterans Affairs17
TL;DR: Meta-analyses of genome-wide association studies for atrial fibrillation in participants from five community-based cohorts identified a new locus for AF as ZFHX3, rs2106261, which was replicated in an independent cohort from the German AF Network.
Abstract: We conducted meta-analyses of genome-wide association studies for atrial fibrillation (AF) in participants from five community-based cohorts. Meta-analyses of 896 prevalent (15,768 referents) and 2,517 incident (21,337 referents) AF cases identified a new locus for AF (ZFHX3, rs2106261, risk ratio RR = 1.19; P = 2.3 x 10(-7)). We replicated this association in an independent cohort from the German AF Network (odds ratio = 1.44; P = 1.6 x 10(-11); combined RR = 1.25; combined P = 1.8 x 10(-15)).
National Institutes of Health1, Johns Hopkins University2, University of Vermont3, Erasmus University Rotterdam4, Wellcome Trust Sanger Institute5, King's College London6, Boston University7, University of Washington8, University of Iceland9, University of Greifswald10, Geneva College11, University of Cambridge12, University of Texas Health Science Center at Houston13, Cedars-Sinai Medical Center14, Leiden University15, Leiden University Medical Center16, Harvard University17
TL;DR: This study has identified new determinants of erythrocyte traits, offering insight into common variants underlying variation in ery throatcyte measures, and identifies 23 loci significantly associated with these traits.
Abstract: Measurements of erythrocytes within the blood are important clinical traits and can indicate various hematological disorders. We report here genome-wide association studies (GWAS) for six erythrocyte traits, including hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red blood cell count (RBC). We performed an initial GWAS in cohorts of the CHARGE Consortium totaling 24,167 individuals of European ancestry and replication in additional independent cohorts of the HaemGen Consortium totaling 9,456 individuals. We identified 23 loci significantly associated with these traits in a meta-analysis of the discovery and replication cohorts (combined P values ranging from 5 x 10(-8) to 7 x 10(-86)). Our findings include loci previously associated with these traits (HBS1L-MYB, HFE, TMPRSS6, TFR2, SPTA1) as well as new associations (EPO, TFRC, SH2B3 and 15 other loci). This study has identified new determinants of erythrocyte traits, offering insight into common variants underlying variation in erythrocyte measures.
TL;DR: Four new genome-wide significant loci near the SOST gene at 17q21, the MARK3 gene at 14q32, the SP7 gene at 12q13 and the TNFRSF11A (RANK) gene at 18q21 are identified and nonsynonymous SNPs in the C17orf53, LRP4, ADAM19 and IBSP genes were suggestively associated with bone density.
Abstract: In an extended genome-wide association study of bone mineral density among 6,865 Icelanders and a follow-up in 8,510 subjects of European descent, we identified four new genome-wide significant loci. These are near the SOST gene at 17q21, the MARK3 gene at 14q32, the SP7 gene at 12q13 and the TNFRSF11A (RANK) gene at 18q21. Furthermore, nonsynonymous SNPs in the C17orf53, LRP4, ADAM19 and IBSP genes were suggestively associated with bone density.
TL;DR: In this paper, a case study examines methods chosen for the development and implementation of questionnaires used to obtain information on knowledge and perception of volcanic hazards in a tourist region in southern Iceland.
Abstract: . Questionnaires are popular and fundamental tools for acquiring information on public knowledge and perception of natural hazards. Questionnaires can provide valuable information to emergency management agencies for developing risk management procedures. Although many natural hazards researchers describe results generated from questionnaires, few explain the techniques used for their development and implementation. Methodological detail should include, as a minimum, response format (open/closed questions), mode of delivery, sampling technique, response rate and access to the questionnaire to allow reproduction of or comparison with similar studies. This article reviews current knowledge and practice for developing and implementing questionnaires. Key features include questionnaire design, delivery mode, sampling techniques and data analysis. In order to illustrate these aspects, a case study examines methods chosen for the development and implementation of questionnaires used to obtain information on knowledge and perception of volcanic hazards in a tourist region in southern Iceland. Face-to-face interviews highlighted certain issues with respect to question structure and sequence. Recommendations are made to overcome these problems before the questionnaires are applied in future research projects. In conclusion, basic steps that should be disclosed in the literature are provided as a checklist to ensure that reliable, replicable and valid results are produced from questionnaire based hazard knowledge and risk perception research.
deCODE genetics1, University of Iceland2, German Cancer Research Center3, University of Zaragoza4, Karolinska Institutet5, Radboud University Nijmegen6, Radboud University Nijmegen Medical Centre7, Erasmus University Rotterdam8, Medical University of Vienna9, Dartmouth College10, University of Minnesota11
TL;DR: It is reported conclusive evidence that rs401681[C] in the TERT-CLPTM1L locus confers susceptibility to BCC but protects against melanoma.
Abstract: In a follow-up to our previously reported genome-wide association study of cutaneous basal cell carcinoma (BCC), we describe here several new susceptibility variants. SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of BCC (OR = 1.35, P = 2.1 x 10(-9)). A variant at 9p21 near CDKN2A and CDKN2B also confers susceptibility to BCC (rs2151280[C]; OR = 1.19, P = 6.9 x 10(-9)), as does rs157935[T] at 7q32 near the imprinted gene KLF14 (OR = 1.23, P = 5.7 x 10(-10)). The effect of rs157935[T] is dependent on the parental origin of the risk allele. None of these variants were found to be associated with melanoma or fair-pigmentation traits. A melanoma- and pigmentation-associated variant in the SLC45A2 gene, L374F, is associated with risk of both BCC and squamous cell carcinoma. Finally, we report conclusive evidence that rs401681[C] in the TERT-CLPTM1L locus confers susceptibility to BCC but protects against melanoma.
TL;DR: In this article, the authors attributed long-term climate moderation to chemical weathering; the higher the temperature and precipitation, the faster the weathering rate, and the more divalent cations were released to the environment.
TL;DR: It is proposed that the optimal strategy is to evaluate the temporal changes in relevant molecular pathways during sleep and, in particular, the alterations from before to after sleep when assessed in blood and/or urine.
Abstract: The consequences of obstructive sleep apnea (OSA) are largely mediated by chronic intermittent hypoxia and sleep fragmentation. The primary molecular domains affected are sympathetic activity, oxidative stress and inflammation. Other affected domains include adipokines, adhesion molecules and molecules that respond to endoplasmic reticulum stress. Changes in molecular domains affected by OSA, assessed in blood and/or urine, can provide a molecular signature for OSA that could potentially be used diagnostically and to predict who is likely to develop different OSA-related comorbidities. High-throughput discovery strategies such as microarrays, assessing changes in gene expression in circulating blood cells, have the potential to find new candidates and pathways thereby expanding the molecular signatures for OSA. More research is needed to fully understand the pathophysiological significance of these molecular signatures and their relationship with OSA comorbidities. Many OSA subjects are obese, and obesity is an independent risk factor for many comorbidities associated with OSA. Moreover, obesity affects the same molecular pathways as OSA. Thus, a challenge to establishing a molecular signature for OSA is to separate the effects of OSA from obesity. We propose that the optimal strategy is to evaluate the temporal changes in relevant molecular pathways during sleep and, in particular, the alterations from before to after sleep when assessed in blood and/or urine. Such changes will be at least partly a consequence of chronic intermittent hypoxia and sleep fragmentation that occurs during sleep.
TL;DR: The 5-year survival rates estimated from annual failure rates appeared to be similar for ceramic and metal abutments, and a meta-analysis of the laboratory data was impossible due to the non-standardized test methods of the studies included.
Abstract: OBJECTIVES: The objective of this systematic review was to assess the 5-year survival rates and incidences of complications associated with ceramic abutments and to compare them with those of metal abutments. METHODS: An electronic Medline search complemented by manual searching was conducted to identify randomized-controlled clinical trials, and prospective and retrospective studies providing information on ceramic and metal abutments with a mean follow-up time of at least 3 years. Patients had to have been examined clinically at the follow-up visit. Assessment of the identified studies and data abstraction was performed independently by three reviewers. Failure rates were analyzed using standard and random-effects Poisson regression models to obtain summary estimates of 5-year survival proportions. RESULTS: Twenty-nine clinical and 22 laboratory studies were selected from an initial yield of 7136 titles and data were extracted. The estimated 5-year survival rate of ceramic abutments was 99.1% [95% confidence interval (CI): 93.8-99.9%] and 97.4% (95% CI: 96-98.3%) for metal abutments. The estimated cumulative incidence of technical complications after 5 years was 6.9% (95% CI: 3.5-13.4%) for ceramic abutments and 15.9% (95% CI: 11.6-21.5%) for metal abutments. Abutment screw loosening was the most frequent technical problem, occurring at an estimated cumulative incidence after 5 years of 5.1% (95% CI: 3.3-7.7%). All-ceramic crowns supported by ceramic abutments exhibited similar annual fracture rates as metal-ceramic crowns supported by metal abutments. The cumulative incidence of biological complications after 5 years was estimated at 5.2% (95% CI: 0.4-52%) for ceramic and 7.7% (95% CI: 4.7-12.5%) for metal abutments. Esthetic complications tended to be more frequent at metal abutments. A meta-analysis of the laboratory data was impossible due to the non-standardized test methods of the studies included. CONCLUSION: The 5-year survival rates estimated from annual failure rates appeared to be similar for ceramic and metal abutments. The information included in this review did not provide evidence for differences of the technical and biological outcomes of ceramic and metal abutments. However, the information for ceramic abutments was limited in the number of studies and abutments analyzed as well as the accrued follow-up time. Standardized methods for the analysis of abutment strength are needed.
19 Apr 2009
TL;DR: This work proposes the first scheduling algorithm with approximation guarantee independent of the topology of the network, and proves that the analysis of the algorithm is extendable to higher-dimensional Euclidean spaces, and to more realistic bounded-distortion spaces, induced by non-isotropic signal distortions.
Abstract: In this work we study the problem of determining the throughput capacity of a wireless network. We propose a scheduling algorithm to achieve this capacity within an approximation factor. Our analysis is performed in the physical interference model, where nodes are arbitrarily distributed in Euclidean space. We consider the problem separately from the routing problem and the power control problem, i.e., all requests are single-hop, and all nodes transmit at a fixed power level. The existing solutions to this problem have either concentrated on special-case topologies, or presented optimality guarantees which become arbitrarily bad (linear in the number of nodes) depending on the network's topology. We propose the first scheduling algorithm with approximation guarantee independent of the topology of the network. The algorithm has a constant approximation guarantee for the problem of maximizing the number of links scheduled in one time-slot. Furthermore, we obtain a O(log n) approximation for the problem of minimizing the number of time slots needed to schedule a given set of requests. Simulation results indicate that our algorithm does not only have an exponentially better approximation ratio in theory, but also achieves superior performance in various practical network scenarios. Furthermore, we prove that the analysis of the algorithm is extendable to higher-dimensional Euclidean spaces, and to more realistic bounded-distortion spaces, induced by non-isotropic signal distortions. Finally, we show that it is NP-hard to approximate the scheduling problem to within n 1-epsiv factor, for any constant epsiv > 0, in the non-geometric SINR model, in which path-loss is independent of the Euclidean coordinates of the nodes.