Showing papers by "University of Iceland published in 2015"
TL;DR: In a longitudinal study of patients with NAFLD, fibrosis stage, but no other histologic features of steatohepatitis, were associated independently with long-term overall mortality, liver transplantation, and liver-related events.
2,061 citations
TL;DR: This article conducted a meta-analysis of coronary artery disease (CAD) cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 millions low-frequency (0.005 < MAF < 0.5) variants.
Abstract: Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
1,839 citations
TL;DR: A genome-wide association study in the Nordic region identifying a novel MM risk locus at ELL2 that encodes a stoichiometrically limiting component of the super-elongation complex that drives secretory-specific immunoglobulin mRNA production and transcriptional regulation in plasma cells is reported.
Abstract: Multiple myeloma (MM) is characterized by an uninhibited, clonal growth of plasma cells. While first-degree relatives of patients with MM show an increased risk of MM, the genetic basis of inherited MM susceptibility is incompletely understood. Here we report a genome-wide association study in the Nordic region identifying a novel MM risk locus at ELL2 (rs56219066T; odds ratio (OR)=1.25; P=9.6 × 10(-10)). This gene encodes a stoichiometrically limiting component of the super-elongation complex that drives secretory-specific immunoglobulin mRNA production and transcriptional regulation in plasma cells. We find that the MM risk allele harbours a Thr298Ala missense variant in an ELL2 domain required for transcription elongation. Consistent with a hypomorphic effect, we find that the MM risk allele also associates with reduced levels of immunoglobulin A (IgA) and G (IgG) in healthy subjects (P=8.6 × 10(-9) and P=6.4 × 10(-3), respectively) and, potentially, with an increased risk of bacterial meningitis (OR=1.30; P=0.0024).
1,342 citations
University of Edinburgh1, University of Greifswald2, University of London3, Queen Mary University of London4, University of Trieste5, Vita-Salute San Raffaele University6, University of Tartu7, National Institutes of Health8, University of Oxford9, Johns Hopkins University10, Erasmus University Rotterdam11, University of Verona12, University of Iceland13, University of Otago14, Uppsala University15, University of Lübeck16, University of Split17, Harvard University18, University Hospital of Lausanne19, Ludwig Maximilian University of Munich20, University of Auckland21, VU University Amsterdam22, University of Regensburg23, Max Planck Society24, Greifswald University Hospital25, University of Helsinki26, Charles III University of Madrid27, Wellcome Trust Sanger Institute28, University College London29, Leiden University30, Catholic University of the Sacred Heart31, University of Bern32, University of Freiburg33
TL;DR: Interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, and regression-type analyses in a non BMI-stratified overall sample suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum.
Abstract: We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.
1,293 citations
SLAC National Accelerator Laboratory1, Stockholm University2, Santa Cruz Institute for Particle Physics3, Istituto Nazionale di Fisica Nucleare4, University of Wisconsin-Madison5, Goddard Space Flight Center6, University of Montpellier7, École Polytechnique8, INAF9, George Mason University10, University of Padua11, Instituto Politécnico Nacional12, Fermilab13, C. N. Yang Institute for Theoretical Physics14, Hiroshima University15, Paris Diderot University16, University of Göttingen17, University of North Florida18, University of Iceland19, Spanish National Research Council20, University of Maryland, College Park21, University of California, Irvine22, University of Denver23, Stony Brook University24, Texas A&M University25, Ohio State University26, United States Naval Research Laboratory27
TL;DR: In this article, the authors report on γ-ray observations of the Milky-Way satellite galaxies (dSphs) based on six years of Fermi Large Area Telescope data processed with the new Pass8 event-level analysis.
Abstract: The dwarf spheroidal satellite galaxies (dSphs) of the Milky Way are some of the most dark matter (DM) dominated objects known. We report on γ-ray observations of Milky Way dSphs based on six years of Fermi Large Area Telescope data processed with the new Pass8 event-level analysis. None of the dSphs are significantly detected in γ rays, and we present upper limits on the DM annihilation cross section from a combined analysis of 15 dSphs. These constraints are among the strongest and most robust to date and lie below the canonical thermal relic cross section for DM of mass ≲100 GeV annihilating via quark and τ-lepton channels.
1,166 citations
TL;DR: This review outlines some of the advantages and challenges that may accompany a transition from macroscopic to microfluidic cell culture and focuses on decisive factors that distinguish Macroscopic from microfluidity cell culture to encourage a reconsideration of how macroscopy cell culture principles might apply to micro fluidiccell culture.
760 citations
TL;DR: In this paper, the authors conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts.
Abstract: The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.
721 citations
TL;DR: The first IGRB measurement with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope (Fermi) used 10 months of sky-survey data and considered an energy range between 200 MeV and 100 GeV.
Abstract: The gamma-ray sky can be decomposed into individually detected sources, diffuse emission attributed to the interactions of Galactic cosmic rays with gas and radiation fields, and a residual all-sky emission component commonly called the isotropic diffuse gamma-ray background (IGRB). The IGRB comprises all extragalactic emissions too faint or too diffuse to be resolved in a given survey, as well as any residual Galactic foregrounds that are approximately isotropic. The first IGRB measurement with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope (Fermi) used 10 months of sky-survey data and considered an energy range between 200 MeV and 100 GeV. Improvements in event selection and characterization of cosmic-ray backgrounds, better understanding of the diffuse Galactic emission, and a longer data accumulation of 50 months, allow for a refinement and extension of the IGRB measurement with the LAT, now covering the energy range from 100 MeV to 820 GeV. The IGRB spectrum shows a significant high-energy cutoff feature, and can be well described over nearly four decades in energy by a power law with exponential cutoff having a spectral index of 2.32 plus or minus 0.02 and a break energy of (279 plus or minus 52) GeV using our baseline diffuse Galactic emission model. The total intensity attributed to the IGRB is (7.2 plus or minus 0.6) x 10(exp -6) cm(exp -2) s(exp -1) sr(exp -1) above 100 MeV, with an additional +15%/-30% systematic uncertainty due to the Galactic diffuse foregrounds.
680 citations
TL;DR: The insights gained from sequencing the whole genomes of Icelanders to a median depth of 20× provide a study design that can be used to determine how variation in the sequence of the human genome gives rise to human diversity.
Abstract: Here we describe the insights gained from sequencing the whole genomes of 2,636 Icelanders to a median depth of 20×. We found 20 million SNPs and 1.5 million insertions-deletions (indels). We describe the density and frequency spectra of sequence variants in relation to their functional annotation, gene position, pathway and conservation score. We demonstrate an excess of homozygosity and rare protein-coding variants in Iceland. We imputed these variants into 104,220 individuals down to a minor allele frequency of 0.1% and found a recessive frameshift mutation in MYL4 that causes early-onset atrial fibrillation, several mutations in ABCB4 that increase risk of liver diseases and an intronic variant in GNAS associating with increased thyroid-stimulating hormone levels when maternally inherited. These data provide a study design that can be used to determine how variation in the sequence of the human genome gives rise to human diversity.
671 citations
TL;DR: The third catalog of active galactic nuclei (AGNs) detected by the Fermi-LAT (3LAC) is presented in this paper, which is based on the 3FGL of sources detected between 100 MeV and 300 GeV.
Abstract: The third catalog of active galactic nuclei (AGNs) detected by the Fermi-LAT (3LAC) is presented. It is based on the third Fermi-LAT catalog (3FGL) of sources detected between 100 MeV and 300 GeV w ...
668 citations
Thomas W. Winkler1, Anne E. Justice2, Mariaelisa Graff2, Llilda Barata3 +435 more•Institutions (106)
TL;DR: In this paper, the authors performed meta-analyses of 114 studies with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium.
Abstract: Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.
TL;DR: Survival rates of most types of all-ceramic SCs were similar to those reported for metal-ceramic SCs, both in anterior and posterior regions, and feldspathic/silica-based ceramics should be limited to applications in the anterior region.
University of Texas Southwestern Medical Center1, University of Glasgow2, Harvard University3, Novartis4, Université de Montréal5, Medical University of South Carolina6, University of Iceland7, University of Western Ontario8, Charles University in Prague9, Saarland University10, Stellenbosch University11, University of Santiago de Compostela12, National Yang-Ming University13, Comenius University in Bratislava14, University of Latvia15, University of Gothenburg16, Universidad Autónoma de Santo Domingo17, University of Paris18, Nanjing Medical University19, Khon Kaen University20, Catholic University of Daegu21, Dokuz Eylül University22, National University of Cordoba23, Semmelweis University24, Central University of Venezuela25, Wrocław Medical University26, University of Eastern Finland27, University of São Paulo28, Aarhus University29, University of Porto30, University of Leicester31, Cleveland Clinic32, University of California, San Francisco33, Katholieke Universiteit Leuven34, Carol Davila University of Medicine and Pharmacy35
TL;DR: Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotens in-converting enzyme inhibition.
Abstract: Background—Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs ...
Yonsei University1, University of Indonesia2, Aga Khan University3, University of Tartu4, Alfaisal University5, Ziauddin University6, Dubai Health Authority7, Shaikh Zayed Hospital8, Baqiyatallah University of Medical Sciences9, King Saud University10, King Saud bin Abdulaziz University for Health Sciences11, American University of Beirut12, Sungkyunkwan University13, University of Balamand14, Khyber Medical University15, University of Peshawar16, Reykjavík University17, RMIT University18, University of Ljubljana19, La Trobe University20, University of New South Wales21, University of Pécs22, University Medical Center Rizk Hospital23, University of Iceland24, Soonchunhyang University25, Cleveland Clinic26, Vilnius University27, Vilnius Gediminas Technical University28, University of Ulsan29, Tehran University of Medical Sciences30, Aims Community College31, Eijkman Institute for Molecular Biology32, University of Sydney33, Memorial Hospital of South Bend34, Pakistan Institute of Development Economics35, Military Hospital36, Saint Joseph's University37, Allama Iqbal Medical College38, Hiroshima University39, Lahore General Hospital40, Holy Family Hospital41, Rawalpindi Medical College42, Dow Medical College43
TL;DR: The current treatment rate and efficacy are not sufficient to manage the disease burden of hepatitis C virus and alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver‐related deaths from increasing.
Abstract: The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.
TL;DR: Lateral dyke growth with segment barrier breaking by pressure build-up in the dyke distal end explains how focused upwelling of magma under central volcanoes is effectively redistributed over long distances to create new upper crust at divergent plate boundaries.
Abstract: Crust at many divergent plate boundaries forms primarily by the injection of vertical sheet-like dykes, some tens of kilometres long1. Previous models of rifting events indicate either lateral dyke growth away from a feeding source, with propagation rates decreasing as the dyke lengthens2, 3, 4, or magma flowing vertically into dykes from an underlying source5, 6, with the role of topography on the evolution of lateral dykes not clear. Here we show how a recent segmented dyke intrusion in the Barðarbunga volcanic system grew laterally for more than 45 kilometres at a variable rate, with topography influencing the direction of propagation. Barriers at the ends of each segment were overcome by the build-up of pressure in the dyke end; then a new segment formed and dyke lengthening temporarily peaked. The dyke evolution, which occurred primarily over 14 days, was revealed by propagating seismicity, ground deformation mapped by Global Positioning System (GPS), interferometric analysis of satellite radar images (InSAR), and graben formation. The strike of the dyke segments varies from an initially radial direction away from the Barðarbunga caldera, towards alignment with that expected from regional stress at the distal end. A model minimizing the combined strain and gravitational potential energy explains the propagation path. Dyke opening and seismicity focused at the most distal segment at any given time, and were simultaneous with magma source deflation and slow collapse at the Barðarbunga caldera, accompanied by a series of magnitude M > 5 earthquakes. Dyke growth was slowed down by an effusive fissure eruption near the end of the dyke. Lateral dyke growth with segment barrier breaking by pressure build-up in the dyke distal end explains how focused upwelling of magma under central volcanoes is effectively redistributed over long distances to create new upper crust at divergent plate boundaries.
TL;DR: Evidence is provided that low‐frequency non‐coding variants have large effects on BMD and fracture, thereby providing rationale for whole‐genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
Abstract: The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
12 Nov 2015
TL;DR: An electrically pumped polariton laser based on a microcavity containing multiple quantum wells is presented, which can be extended to room-temperature operation using wide-bandgap materials and proves polariton Laser emission unambiguously.
Abstract: Exciton-polaritons are bosonic quasi-particles originating in the strong coupling regime. They can undergo a condensation process leading to coherent emission. We show a realisation of electrically driven polariton condensates using a p-i-n doped microcavity.
TL;DR: A new feature selection approach that is based on the integration of a genetic algorithm and particle swarm optimization is proposed and is able to automatically select the most informative features in terms of classification accuracy within an acceptable CPU processing time.
Abstract: A new feature selection approach that is based on the integration of a genetic algorithm and particle swarm optimization is proposed. The overall accuracy of a support vector machine classifier on validation samples is used as a fitness value. The new approach is carried out on the well-known Indian Pines hyperspectral data set. Results confirm that the new approach is able to automatically select the most informative features in terms of classification accuracy within an acceptable CPU processing time without requiring the number of desired features to be set a priori by users. Furthermore, the usefulness of the proposed method is also tested for road detection. Results confirm that the proposed method is capable of discriminating between road and background pixels and performs better than the other approaches used for comparison in terms of performance metrics.
TL;DR: Cardiovascular risk should be addressed with all patients affected by psoriasis, PsA or RA and an interaction between disease status and disease-modifying antirheumatic drug (DMARD) use is hypothesised.
Abstract: Objectives We aimed to quantify the risk of major adverse cardiovascular events (MACE) among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA) and psoriasis without known PsA compared with the general population after adjusting for traditional cardiovascular risk factors. Methods A population-based longitudinal cohort study from 1994 to 2010 was performed in The Health Improvement Network (THIN), a primary care medical record database in the UK. Patients aged 18–89 years of age with PsA, RA or psoriasis were included. Up to 10 unexposed controls matched on practice and index date were selected for each patient with PsA. Outcomes included cardiovascular death, myocardial infarction, cerebrovascular accidents and the composite outcome (MACE). Cox proportional hazards models were used to calculate the HRs for each outcome adjusted for traditional risk factors. A priori, we hypothesised an interaction between disease status and disease-modifying antirheumatic drug (DMARD) use. Results Patients with PsA (N=8706), RA (N=41 752), psoriasis (N=138 424) and unexposed controls (N=81 573) were identified. After adjustment for traditional risk factors, the risk of MACE was higher in patients with PsA not prescribed a DMARD (HR 1.24, 95% CI 1.03 to 1.49), patients with RA (No DMARD: HR 1.39, 95% CI 1.28 to 1.50, DMARD: HR 1.58, 95% CI 1.46 to 1.70), patients with psoriasis not prescribed a DMARD (HR 1.08, 95% CI 1.02 to 1.15) and patients with severe psoriasis (DMARD users: HR 1.42, 95% CI 1.17 to 1.73). Conclusions Cardiovascular risk should be addressed with all patients affected by psoriasis, PsA or RA.
TL;DR: This paper performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry, and identified 49 distinct association signals at these loci including five mapping in or near KCNQ1.
Abstract: We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
TL;DR: In this paper, the relationship between specific mutations in BRCA1 and cancer risk has been investigated and limited information about the relationship has been available about specific mutations for specific mutations.
Abstract: Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists.
TL;DR: Experimental results on three widely used real HSIs indicate that the proposed SC-MK approach outperforms several well-known classification methods.
Abstract: For the classification of hyperspectral images (HSIs), this paper presents a novel framework to effectively utilize the spectral–spatial information of superpixels via multiple kernels, which is termed as superpixel-based classification via multiple kernels (SC-MK). In the HSI, each superpixel can be regarded as a shape-adaptive region, which consists of a number of spatial neighboring pixels with very similar spectral characteristics. First, the proposed SC-MK method adopts an oversegmentation algorithm to cluster the HSI into many superpixels. Then, three kernels are separately employed for the utilization of the spectral information, as well as spatial information, within and among superpixels. Finally, the three kernels are combined together and incorporated into a support vector machine classifier. Experimental results on three widely used real HSIs indicate that the proposed SC-MK approach outperforms several well-known classification methods.
TL;DR: The main objective of this survey paper is to recall the concept of the APs along with all its modifications and generalizations with special emphasis on remote sensing image classification and summarize the important aspects of its efficient utilization while also listing potential future works.
Abstract: Just over a decade has passed since the concept of morphological profile was defined for the analysis of remote sensing images. Since then, the morphological profile has largely proved to be a powerful tool able to model spatial information (e.g., contextual relations) of the image. However, due to the shortcomings of using the morphological profiles, many variants, extensions, and refinements of its definition have appeared stating that the morphological profile is still under continuous development. In this case, recently introduced theoretically sound attribute profiles (APs) can be considered as a generalization of the morphological profile, which is a powerful tool to model spatial information existing in the scene. Although the concept of the AP has been introduced in remote sensing only recently, an extensive literature on its use in different applications and on different types of data has appeared. To that end, the great amount of contributions in the literature that address the application of the AP to many tasks (e.g., classification, object detection, segmentation, change detection, etc.) and to different types of images (e.g., panchromatic, multispectral, and hyperspectral) proves how the AP is an effective and modern tool. The main objective of this survey paper is to recall the concept of the APs along with all its modifications and generalizations with special emphasis on remote sensing image classification and summarize the important aspects of its efficient utilization while also listing potential future works.
TL;DR: In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer’s disease: TOMM40, APOE, ABCG1 and MEF2C.
Abstract: General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53,949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10(-9), MIR2113; rs17522122, P=2.55 × 10(-8), AKAP6; rs10119, P=5.67 × 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.
TL;DR: Survival rates of all types of all-ceramic FDPs were lower than those reported for metal-ceramics, and the incidence of framework fractures and loss of retention was significantly higher for densely sintered zirconia F DPs compared to all other types of FDPS.
TL;DR: Creativity and psychosis share genetic roots, and higher polygenic risk scores for schizophrenia and bipolar disorder would predict creativity could not be accounted for by increased relatedness between creative individuals and those with psychoses.
Abstract: We tested whether polygenic risk scores for schizophrenia and bipolar disorder would predict creativity. Higher scores were associated with artistic society membership or creative profession in both Icelandic (P = 5.2 × 10(-6) and 3.8 × 10(-6) for schizophrenia and bipolar disorder scores, respectively) and replication cohorts (P = 0.0021 and 0.00086). This could not be accounted for by increased relatedness between creative individuals and those with psychoses, indicating that creativity and psychosis share genetic roots.
Boston Children's Hospital1, University of Southampton2, University Hospital Southampton NHS Foundation Trust3, Charité4, German Agency for Quality in Medicine5, Vilnius University6, National and Kapodistrian University of Athens7, University of Iceland8, Manchester Academic Health Science Centre9, University of Würzburg10
TL;DR: Cow's milk allergy (CMA) is one of the most commonly reported childhood food problems and community‐based incidence and prevalence estimates vary widely, due to possible misinterpretations of presumed reactions to milk and differences in study design, particularly diagnostic criteria.
Abstract: BACKGROUND: Cow's milk allergy (CMA) is one of the most commonly reported childhood food problems. Community-based incidence and prevalence estimates vary widely, due to possible misinterpretations of presumed reactions to milk and differences in study design, particularly diagnostic criteria. METHODS: Children from the EuroPrevall birth cohort in 9 European countries with symptoms possibly related to CMA were invited for clinical evaluation including cows' milk-specific IgE antibodies (IgE), skin prick test (SPT) reactivity and double-blind, placebo-controlled food challenge. RESULTS: Across Europe, 12�049 children were enrolled, and 9336 (77.5%) were followed up to 2�years of age. CMA was suspected in 358 children and confirmed in 55 resulting in an overall incidence of challenge-proven CMA of 0.54% (95% CI 0.41-0.70). National incidences ranged from 1% (in the Netherlands and UK) to <0.3% (in Lithuania, Germany and Greece). Of all children with CMA, 23.6% had no cow's milk-specific IgE in serum, especially those from UK, the Netherlands, Poland and Italy. Of children with CMA who were re-evaluated one year after diagnosis, 69% (22/32) tolerated cow's milk, including all children with non-IgE-associated CMA and 57% of those children with IgE-associated CMA. CONCLUSIONS: This unique pan-European birth cohort study using the gold standard diagnostic procedure for food allergies confirmed challenge-proven CMA in <1% of children up to age 2. Affected infants without detectable specific antibodies to�cow's milk were very likely to tolerate cow's milk one year after diagnosis, whereas only half of those with specific antibodies in serum 'outgrew' their disease so soon.
Felix R. Day1, Katherine S. Ruth2, Deborah J. Thompson1, Kathryn L. Lunetta1 +238 more•Institutions (50)
TL;DR: A dual strategy to identify common and low-frequency protein-coding variation associated with age at natural menopause and enrichment of signals in or near genes involved in delayed puberty are reported, highlighting the first molecular links between the onset and end of reproductive lifespan.
Abstract: Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.
TL;DR: An important characteristic of the presented approach is that it does not require any regularization parameters to control the weights of considered features so that different types of features can be efficiently exploited and integrated in a collaborative and flexible way.
Abstract: Hyperspectral image classification has been an active topic of research in recent years. In the past, many different types of features have been extracted (using both linear and nonlinear strategies) for classification problems. On the one hand, some approaches have exploited the original spectral information or other features linearly derived from such information in order to have classes which are linearly separable. On the other hand, other techniques have exploited features obtained through nonlinear transformations intended to reduce data dimensionality, to better model the inherent nonlinearity of the original data (e.g., kernels) or to adequately exploit the spatial information contained in the scene (e.g., using morphological analysis). Special attention has been given to techniques able to exploit a single kind of features, such as composite kernel learning or multiple kernel learning, developed in order to deal with multiple kernels. However, few approaches have been designed to integrate multiple types of features extracted from both linear and nonlinear transformations. In this paper, we develop a new framework for the classification of hyperspectral scenes that pursues the combination of multiple features. The ultimate goal of the proposed framework is to be able to cope with linear and nonlinear class boundaries present in the data, thus following the two main mixing models considered for hyperspectral data interpretation. An important characteristic of the presented approach is that it does not require any regularization parameters to control the weights of considered features so that different types of features can be efficiently exploited and integrated in a collaborative and flexible way. Our experimental results, conducted using a variety of input features and hyperspectral scenes, indicate that the proposed framework for multiple feature learning provides state-of-the-art classification results without significantly increasing computational complexity.
deCODE genetics1, University of Eastern Finland2, Emory University3, Karolinska Institutet4, University of Oslo5, Stavanger University Hospital6, Akershus University Hospital7, Oslo University Hospital8, Norwegian University of Science and Technology9, Norwegian Institute of Public Health10, Martin Luther University of Halle-Wittenberg11, Pierre-and-Marie-Curie University12, University of Iceland13
TL;DR: It is found that loss-of-function variants in ABCA7 confer risk of Alzheimer's disease in Icelanders and the association replicated in study groups from Europe and the United States.
Abstract: Stacy Steinberg, Hreinn Stefansson, Thorlakur Jonsson and colleagues found that rare variants predicted to alter the function of ABCA7 are associated with risk of Alzheimer's disease. The association was found in Iceland and replicated in northern Europe and the United States. We conducted a search for rare, functional variants altering susceptibility to Alzheimer's disease that exploited knowledge of common variants associated with the same disease. We found that loss-of-function variants in ABCA7 confer risk of Alzheimer's disease in Icelanders (odds ratio (OR) = 2.12, P = 2.2 × 10−13) and discovered that the association replicated in study groups from Europe and the United States (combined OR = 2.03, P = 6.8 × 10−15).