| 1. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 3. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 4. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 5. |
- Nene, Vishvanath, et al.
(författare)
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Genome sequence of Aedes aegypti, a major arbovirus vector.
- 2007
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5832, s. 1718-23
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Tidskriftsartikel (refereegranskat)abstract
- We present a draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at approximately 1376 million base pairs is about 5 times the size of the genome of the malaria vector Anopheles gambiae. Nearly 50% of the Ae. aegypti genome consists of transposable elements. These contribute to a factor of approximately 4 to 6 increase in average gene length and in sizes of intergenic regions relative to An. gambiae and Drosophila melanogaster. Nonetheless, chromosomal synteny is generally maintained among all three insects, although conservation of orthologous gene order is higher (by a factor of approximately 2) between the mosquito species than between either of them and the fruit fly. An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An. gambiae suggests that members of these protein families underpin some of the biological differences between the two mosquito species.
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| 6. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 7. |
- Alimena, Juliette, et al.
(författare)
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Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider
- 2020
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:9
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Tidskriftsartikel (refereegranskat)abstract
- Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton-proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments-as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER-to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
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| 8. |
- Boen, Rune, et al.
(författare)
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Beyond the global brain differences : intraindividual variability differences in 1q21.1 distal and 15q11.2 bp1-bp2 deletion carriers
- 2024
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Ingår i: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 95:2, s. 147-160
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Tidskriftsartikel (refereegranskat)abstract
- Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure.Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference.Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness.Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.
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| 9. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 10. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 11. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 12. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 13. |
- Botvinik-Nezer, Rotem, et al.
(författare)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 14. |
- Heid, Iris M, et al.
(författare)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
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Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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| 15. |
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| 16. |
- Margulies, Elliott H, et al.
(författare)
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Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome
- 2007
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 760-774
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Tidskriftsartikel (refereegranskat)abstract
- A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation, alignment, and evolutionary constraint analyses of 23 mammalian species for all ENCODE targets. Alignments were generated using four different methods; comparisons of these methods reveal large-scale consistency but substantial differences in terms of small genomic rearrangements, sensitivity (sequence coverage), and specificity (alignment accuracy). We describe the quantitative and qualitative trade-offs concomitant with alignment method choice and the levels of technical error that need to be accounted for in applications that require multisequence alignments. Using the generated alignments, we identified constrained regions using three different methods. While the different constraint-detecting methods are in general agreement, there are important discrepancies relating to both the underlying alignments and the specific algorithms. However, by integrating the results across the alignments and constraint-detecting methods, we produced constraint annotations that were found to be robust based on multiple independent measures. Analyses of these annotations illustrate that most classes of experimentally annotated functional elements are enriched for constrained sequences; however, large portions of each class (with the exception of protein-coding sequences) do not overlap constrained regions. The latter elements might not be under primary sequence constraint, might not be constrained across all mammals, or might have expendable molecular functions. Conversely, 40% of the constrained sequences do not overlap any of the functional elements that have been experimentally identified. Together, these findings demonstrate and quantify how many genomic functional elements await basic molecular characterization.
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| 17. |
- Schmidt, Amand F., et al.
(författare)
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PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study
- 2017
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Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 5:2, s. 97-105
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Tidskriftsartikel (refereegranskat)abstract
- Background Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects of PCSK9 inhibitors on diabetes risk. Methods In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA 1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. Findings Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0.09 mmol/L, 95% CI 0.02 to 0.15), bodyweight (1.03 kg, 0.24 to 1.82), waist-to-hip ratio (0.006, 0.003 to 0.010), and an odds ratio for type diabetes of 1.29 (1.11 to 1.50). Based on the collected data, we did not identify associations with HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -0.09 to 0.30). Interpretation PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefi ts of PCSK9 inhibitor treatment, as was previously done for statins.
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| 18. |
- Schmidt, Amand F., et al.
(författare)
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Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
- 2019
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Ingår i: BMC Cardiovascular Disorders. - : BMC. - 1471-2261 .- 1471-2261. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
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| 19. |
- Sønderby, Ida E., et al.
(författare)
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1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
- 2021
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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| 32. |
- Adare, A., et al.
(författare)
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Energy loss and flow of heavy quarks in Au+Au collisions at root s(NN) = 200 GeV
- 2007
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Ingår i: Physical Review Letters. - 1079-7114. ; 98:17
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Tidskriftsartikel (refereegranskat)abstract
- The PHENIX experiment at the BNL Relativistic Heavy Ion Collider (RHIC) has measured electrons with 0.3 < p(T) < 9 GeV/c at midrapidity (y < 0.35) from heavy-flavor (charm and bottom) decays in Au + Au collisions at root s(NN) = 200 GeV. The nuclear modification factor R-AA relative to p + p collisions shows a strong suppression in central Au + Au collisions, indicating substantial energy loss of heavy quarks in the medium produced at RHIC energies. A large azimuthal anisotropy v(2) with respect to the reaction plane is observed for 0.5 < p(T) < 5 GeV/c indicating substantial heavy-flavor elliptic flow. Both R-AA and v(2) show a p(T) dependence different from those of neutral pions. A comparison to transport models which simultaneously describe R-AA(p(T)) and v(2)(p(T)) suggests that the viscosity to entropy density ratio is close to the conjectured quantum lower bound, i.e., near a perfect fluid.
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| 33. |
- Adare, A., et al.
(författare)
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Scaling properties of azimuthal anisotropy in Au plus Au and Cu plus Cu collisions at root s(NN)=200 GeV
- 2007
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Ingår i: Physical Review Letters. - 1079-7114. ; 98:16
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Tidskriftsartikel (refereegranskat)abstract
- Differential measurements of elliptic flow (v(2)) for Au+Au and Cu+Cu collisions at root s(NN)=200 GeV are used to test and validate predictions from perfect fluid hydrodynamics for scaling of v(2) with eccentricity, system size, and transverse kinetic energy (KET). For KET equivalent to m(T)-m up to similar to 1 GeV the scaling is compatible with hydrodynamic expansion of a thermalized fluid. For large values of KET mesons and baryons scale separately. Quark number scaling reveals a universal scaling of v(2) for both mesons and baryons over the full KET range for Au+Au. For Au+Au and Cu+Cu the scaling is more pronounced in terms of KET, rather than transverse momentum.
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| 34. |
- Adare, A., et al.
(författare)
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System size and energy dependence of jet-induced hadron pair correlation shapes in Cu+Cu and Au+Au collisions at root S-NN 200 and 62.4 GeV
- 2007
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Ingår i: Physical Review Letters. - 1079-7114. ; 98:23
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Tidskriftsartikel (refereegranskat)abstract
- We present azimuthal angle correlations of intermediate transverse momentum (1-4 GeV/c) hadrons from dijets in Cu+Cu and Au+Au collisions at root s(NN)=62.4 and 200 GeV. The away-side dijet induced azimuthal correlation is broadened, non-Gaussian, and peaked away from Delta phi=pi in central and semicentral collisions in all the systems. The broadening and peak location are found to depend upon the number of participants in the collision, but not on the collision energy or beam nuclei. These results are consistent with sound or shock wave models, but pose challenges to Cherenkov gluon radiation models.
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| 35. |
- Adcox, K, et al.
(författare)
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Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX Collaboration
- 2005
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Ingår i: Nuclear Physics, Section A. - : Elsevier BV. - 0375-9474. ; 757:1-2, s. 184-283
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Forskningsöversikt (refereegranskat)abstract
- Extensive experimental data from high-energy nucleus-nucleus collisions were recorded using the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The comprehensive set of measurements from the first three years of RHIC operation includes charged particle multiplicities, transverse energy, yield ratios and spectra of identified hadrons in a wide range of transverse momenta (PT), elliptic flow, two-particle correlations, nonstatistical fluctuations, and suppression of particle production at high PT. The results are examined with an emphasis on implications for the formation of a new state of dense matter. We find that the state of matter created at RHIC cannot be described in terms of ordinary color neutral hadrons.
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| 36. |
- Afanasiev, S., et al.
(författare)
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Elliptic flow for phi mesons and (Anti)deuterons in Au+Au collisions at root s(NN)=200 GeV
- 2007
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Ingår i: Physical Review Letters. - 1079-7114. ; 99:5
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Tidskriftsartikel (refereegranskat)abstract
- Differential elliptic flow (v(2)) for phi mesons and (anti)deuterons ((d) over bar )d is measured for Au + Au collisions at root s(NN) = 200 GeV. The v(2) for phi mesons follows the trend of lighter pi(+/-) and K-+/- mesons, suggesting that ordinary hadrons interacting with standard hadronic cross sections are not the primary driver for elliptic flow development. The v(2) values for ((d) over bar )d suggest that elliptic flow is additive for composite particles. This further validation of the universal scaling of v(2) per constituent quark for baryons and mesons suggests that partonic collectivity dominates the transverse expansion dynamics.
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| 37. |
- Brindle, Joanne T, et al.
(författare)
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Rapid and Nonivasive Diagnosis of the Presence and Severity of Coronary Heart Disease Using 1H-NMR-Based Metabonomics
- 2002
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 8, s. 1439-45
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Tidskriftsartikel (refereegranskat)abstract
- Although a wide range of risk factors for coronary heart disease have been identified from population studies, these measures, singly or in combination, are insufficiently powerful to provide a reliable, noninvasive diagnosis of the presence of coronary heart disease. Here we show that pattern-recognition techniques applied to proton nuclear magnetic resonance (1H-NMR) spectra of human serum can correctly diagnose not only the presence, but also the severity, of coronary heart disease. Application of supervised partial least squares-discriminant analysis to orthogonal signal-corrected data sets allows >90% of subjects with stenosis of all three major coronary vessels to be distinguished from subjects with angiographically normal coronary arteries, with a specificity of >90%. Our studies show for the first time a technique capable of providing an accurate, noninvasive and rapid diagnosis of coronary heart disease that can be used clinically, either in population screening or to allow effective targeting of treatments such as statins.
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| 38. |
- Dima, Danai, et al.
(författare)
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Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3-90 years.
- 2022
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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| 39. |
- Farnocchia, Davide, et al.
(författare)
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The Second International Asteroid Warning Network Timing Campaign: 2005 LW3
- 2023
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Ingår i: The Planetary Science Journal. - : Institute of Physics (IOP). - 2632-3338. ; 4:11
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Tidskriftsartikel (refereegranskat)abstract
- The Earth close approach of near-Earth asteroid 2005 LW3 on 2022 November 23 represented a good opportunity for a second observing campaign to test the timing accuracy of astrometric observation. With 82 participating stations, the International Asteroid Warning Network collected 1046 observations of 2005 LW3 around the time of the close approach. Compared to the previous timing campaign targeting 2019 XS, some individual observers were able to significantly improve the accuracy of their reported observation times. In particular, U.S. surveys achieved good timing performance. However, no broad, systematic improvement was achieved compared to the previous campaign, with an overall negative bias persisting among the different observers. The calibration of observing times and the mitigation of timing errors should be important future considerations for observers and orbit computers, respectively.
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| 40. |
- Farooq, Vasim, et al.
(författare)
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Anatomical and clinical characteristics to guide decision making between coronary artery bypass surgery and percutaneous coronary intervention for individual patients : development and validation of SYNTAX score II
- 2013
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 381:9867, s. 639-650
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Tidskriftsartikel (refereegranskat)abstract
- Background The anatomical SYNTAX score is advocated in European and US guidelines as an instrument to help clinicians decide the optimum revascularisation method in patients with complex coronary artery disease. The absence of an individualised approach and of clinical variables to guide decision making between coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) are limitations of the SYNTAX score. SYNTAX score II aimed to overcome these limitations. Methods SYNTAX score II was developed by applying a Cox proportional hazards model to results of the randomised all comers SYNTAX trial (n=1800). Baseline features with strong associations to 4-year mortality in either the CABG or the PCI settings (interactions), or in both (predictive accuracy), were added to the anatomical SYNTAX score. Comparisons of 4-year mortality predictions between CABG and PCI were made for each patient. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling. External validation was done in the multinational all comers DELTA registry (n=2891), a heterogeneous population that included patients with three-vessel disease (26%) or complex coronary artery disease (anatomical SYNTAX score >= 33, 30%) who underwent CABG or PCI. The SYNTAX trial is registered with ClinicalTrials.gov, number NCT00114972. Findings SYNTAX score II contained eight predictors: anatomical SYNTAX score, age, creatinine clearance, left ventricular ejection fraction (LVEF), presence of unprotected left main coronary artery (ULMCA) disease, peripheral vascular disease, female sex, and chronic obstructive pulmonary disease (COPD). SYNTAX score II significantly predicted a difference in 4-year mortality between patients undergoing CABG and those undergoing PCI (p(interaction) 0.0037). To achieve similar 4-year mortality after CABG or PCI, younger patients, women, and patients with reduced LVEF required lower anatomical SYNTAX scores, whereas older patients, patients with ULMCA disease, and those with COPD, required higher anatomical SYNTAX scores. Presence of diabetes was not important for decision making between CABG and PCI (p(interaction) 0.67). SYNTAX score II discriminated well in all patients who underwent CABG or PCI, with concordance indices for internal (SYNTAX trial) validation of 0.725 and for external (DELTA registry) validation of 0.716, which were substantially higher than for the anatomical SYNTAX score alone (concordance indices of 0.567 and 0.612, respectively). A nomogram was constructed that allowed for an accurate individualised prediction of 4-year mortality in patients proposing to undergo CABG or PCI. Interpretation Long-term (4-year) mortality in patients with complex coronary artery disease can be well predicted by a combination of anatomical and clinical factors in SYNTAX score II. SYNTAX score II can better guide decision making between CABG and PCI than the original anatomical SYNTAX score.
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| 41. |
- Frangou, Sophia, et al.
(författare)
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Cortical thickness across the lifespan : Data from 17,075 healthy individuals aged 3-90 years
- 2022
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Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 431-451
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Tidskriftsartikel (refereegranskat)abstract
- Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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| 42. |
- Holmes, Natalie P., et al.
(författare)
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Engineering Two-Phase and Three-Phase Microstructures from Water-Based Dispersions of Nanoparticles for Eco-Friendly Polymer Solar Cell Applications
- 2018
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Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 30:18, s. 6521-6531
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Tidskriftsartikel (refereegranskat)abstract
- Nanoparticle organic photovoltaics, a subfield of organic photovoltaics (OPV), has attracted increasing interest in recent years due to the eco-friendly fabrication of solar modules afforded by colloidal ink technology. Importantly, using this approach it is now possible to engineer the microstructure of the light absorbing/charge generating layer of organic photovoltaics; decoupling film morphology from film deposition. In this study, single-component nanoparticles of poly(3-hexylthiophene) (P3HT) and phenyl-C61 butyric acid methyl ester (PC61BM) were synthesized and used to generate a two-phase microstructure with control over domain size prior to film deposition. Scanning transmission X-ray microscopy (STXM) and electron microscopy were used to characterize the thin film morphology. Uniquely, the measured microstructure was a direct input for a nanoscopic kinetic Monte Carlo (KMC) model allowing us to assess exciton transport properties that are experimentally inaccessible in these single-component particles. Photoluminescence, UV-vis spectroscopy measurements, and KMC results of the nanoparticle thin films enabled the calculation of an experimental exciton dissociation efficiency (ηED) of 37% for the two-phase microstructure. The glass transition temperature (Tg) of the materials was characterized with dynamic mechanical thermal analysis (DMTA) and thermal annealing led to an increase in ηED to 64% due to an increase in donor-acceptor interfaces in the thin film from both sintering of neighboring opposite-type particles in addition to the generation of a third mixed phase from diffusion of PC61BM into amorphous P3HT domains. As such, this study demonstrates the higher level of control over donor-acceptor film morphology enabled by customizing nanoparticulate colloidal inks, where the optimal three-phase film morphology for an OPV photoactive layer can be designed and engineered.
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| 43. |
- Kageyama, Shigetaka, et al.
(författare)
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Geographic disparity in 10-year mortality after coronary artery revascularization in the SYNTAXES trial
- 2022
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Ingår i: International Journal of Cardiology. - : Elsevier. - 0167-5273 .- 1874-1754. ; 368, s. 28-38
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate geographic disparity in long-term mortality following revascularization in patients with complex coronary artery disease (CAD).Methods and results: The SYNTAXES trial randomized 1800 patients with three-vessel and/or left main CAD to percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) and assessed their survival at 10 years. Patients were stratified according to the region of recruitment: North America (N-A, n = 245), Eastern Europe (E-E, n = 189), Northern Europe (N-E, n = 425), Southern Europe (S-E, n = 263), and Western Europe (W-E, n = 678), which also served as the reference group. Compared to W-E, patients were younger in E-E (62 vs 65 years, p < 0.001), and less frequently male in N-A (65.3% vs 79.6%, p < 0.001). Diabetes (16.0% vs 25.4%, p < 0.001) and peripheral vascular disease (6.8% vs 10.9%, p = 0.025) were less frequent in N-E than W-E. Ejection fraction was highest in W-E (62% vs 56%, p < 0.001). Compared to W-E, the mean anatomic SYNTAX score was higher in S-E (29 vs 31, p = 0.008) and lower in N-A (26, p < 0.001). Crude ten-year mortality was similar in N-A (31.6%), and W-E (30.7%), and significantly lower in E-E (22.5%, p = 0.041), N-E (21.9%, p = 0.003) and S-E (22.0%, p = 0.014). Compared to W-E, adjusted mortality in N-E (HR 0.85, p = 0.019) and S-E (HR 0.72, p = 0.043) remain significantly lower after adjustment for pre-and peri-procedural factors, but no significant interaction (Pinteraction = 0.728) between region and modality of revascularization was seen.Conclusion: In the era of globalization, knowledge, and understanding of geographic disparity are of paramount importance for the correct interpretation of global studies.
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| 44. |
- Lakens, Daniel, et al.
(författare)
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Justify your alpha
- 2018
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Ingår i: Nature Human Behaviour. - : Nature Publishing Group. - 2397-3374. ; 2:3, s. 168-171
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Tidskriftsartikel (refereegranskat)abstract
- In response to recommendations to redefine statistical significance to P ≤ 0.005, we propose that researchers should transparently report and justify all choices they make when designing a study, including the alpha level.
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| 45. |
- McEvoy, Peter M., et al.
(författare)
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Assessing the efficacy of imagery-enhanced cognitive behavioral group therapy for social anxiety disorder : Study protocol for a randomized controlled trial
- 2017
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Ingår i: Contemporary Clinical Trials. - : ELSEVIER SCIENCE INC. - 1551-7144 .- 1559-2030. ; 60, s. 34-41
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive behavior group therapy (CBGT) is effective for social anxiety disorder (SAD), but a substantial proportion of patients do not typically achieve normative functioning. Cognitive behavioral models of SAD emphasize negative self-imagery as an important maintaining factor, and evidence suggests that imagery is a powerful cognitive mode for facilitating affective change. This study will compare two group CBGT interventions, one that predominantly uses verbally-based strategies (VB-CBGT) and another that predominantly uses imagery-enhanced strategies (IE-CBGT), in terms of (a) efficacy, (b) mechanisms of change, and (c) cost-effectiveness. This study is a parallel groups (two-arm) single-blind randomized controlled trial. A minimum of 96 patients with SAD will be recruited within a public outpatient community mental health clinic in Perth, Australia. The primary outcomes will be self-reported symptom severity, caseness (SAD present: yes/no) based on a structured diagnostic interview, and clinician-rated severity and life impact. Secondary outcomes and mechanism measures include blind observer-rated use of safety behaviors, physiological activity (heart rate variability and skin conductance level) during a standardized speech task, negative self-beliefs, imagery suppression, fear of negative and positive evaluation, repetitive negative thinking, anxiety, depression, self-consciousness, use of safety behaviors, and the EQ-5D-5L and TiC-P for the health economic analysis. Homework completion, group cohesion, and working alliance will also be monitored. The outcomes of this trial will inform clinicians as to whether integrating imagery-based strategies in cognitive behavior therapy for SAD is likely to improve outcomes. Common and distinct mechanisms of change might be identified, along with relative cost-effectiveness of each intervention.
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| 46. |
- McEvoy, Peter M., et al.
(författare)
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Imagery-enhanced v. verbally-based group cognitive behavior therapy for social anxiety disorder : a randomized clinical trial
- 2022
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 52:7, s. 1277-1286
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCognitive behavior therapy (CBT) is effective for most patients with a social anxiety disorder (SAD) but a substantial proportion fails to remit. Experimental and clinical research suggests that enhancing CBT using imagery-based techniques could improve outcomes. It was hypothesized that imagery-enhanced CBT (IE-CBT) would be superior to verbally-based CBT (VB-CBT) on pre-registered outcomes.MethodsA randomized controlled trial of IE-CBT v. VB-CBT for social anxiety was completed in a community mental health clinic setting. Participants were randomized to IE (n = 53) or VB (n = 54) CBT, with 1-month (primary end point) and 6-month follow-up assessments. Participants completed 12, 2-hour, weekly sessions of IE-CBT or VB-CBT plus 1-month follow-up.ResultsIntention to treat analyses showed very large within-treatment effect sizes on the social interaction anxiety at all time points (ds = 2.09-2.62), with no between-treatment differences on this outcome or clinician-rated severity [1-month OR = 1.45 (0.45, 4.62), p = 0.53; 6-month OR = 1.31 (0.42, 4.08), p = 0.65], SAD remission (1-month: IE = 61.04%, VB = 55.09%, p = 0.59); 6-month: IE = 58.73%, VB = 61.89%, p = 0.77), or secondary outcomes. Three adverse events were noted (substance abuse, n = 1 in IE-CBT; temporary increase in suicide risk, n = 1 in each condition, with one being withdrawn at 1-month follow-up).ConclusionsGroup IE-CBT and VB-CBT were safe and there were no significant differences in outcomes. Both treatments were associated with very large within-group effect sizes and the majority of patients remitted following treatment.
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| 47. |
- McEvoy, Peter M., et al.
(författare)
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Impacts of imagery-enhanced versus verbally-based cognitive behavioral group therapy on psychophysiological parameters in social anxiety disorder : Results from a randomized-controlled trial
- 2022
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Ingår i: Behaviour Research and Therapy. - : Elsevier. - 0005-7967 .- 1873-622X. ; 155
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Tidskriftsartikel (refereegranskat)abstract
- Social anxiety disorder (SAD) is associated with marked physiological reactivity in social-evaluative situations. However, objective measurement of biomarkers is rarely evaluated in treatment trials, despite potential utility in clarifying disorder-specific physiological correlates. This randomized controlled trial sought to examine the differential impact of imagery-enhanced vs. verbal-based cognitive behavioral group therapy (IE-CBGT, n = 53; VB-CBGT, n = 54) on biomarkers of emotion regulation and arousal during social stress in people with SAD (pre and post-treatment differences in heart rate variability (HRV) and skin conductance). We acquired psycho physiological data from randomized participants across four social stress test phases (baseline, speech preparation, speech, interaction) at pre-treatment, and 1-and 6-months post-treatment. Analyses revealed that IECBGT selectively attenuated heart rate as indexed by increases in median heart rate interval (median-RR) compared to VB-CBGT at post-treatment, whereas one HRV index showed a larger increase in the VB-CBGT condition before but not after controlling for median-RR. Other psychophysiological indices did not differ between conditions. Lower sympathetic arousal in the IE-CBGT condition may have obviated the need for parasympathetic downregulation, whereas the opposite was true for VB-CBGT. These findings provide preliminary insights into the impact of imagery-enhanced and verbally-based psychotherapy for SAD on emotion regulation biomarkers.
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| 48. |
- Wang, Rutao, et al.
(författare)
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Impact of chronic obstructive pulmonary disease on 10-year mortality after percutaneous coronary intervention and bypass surgery for complex coronary artery disease : insights from the SYNTAX Extended Survival study
- 2021
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Ingår i: Clinical Research in Cardiology. - : Springer Nature. - 1861-0684 .- 1861-0692. ; 110:7, s. 1083-1095
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Tidskriftsartikel (refereegranskat)abstract
- AimsTo evaluate the impact of chronic obstructive pulmonary disease (COPD) on 10-year all-cause death and the treatment effect of CABG versus PCI on 10-year all-cause death in patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) and COPD.MethodsPatients were stratified according to COPD status and compared with regard to clinical outcomes. Ten-year all-cause death was examined according to the presence of COPD and the revascularization strategy.ResultsCOPD status was available for all randomized 1800 patients, of whom, 154 had COPD (8.6%) at the time of randomization. Regardless of the revascularization strategy, patients with COPD had a higher risk of 10-year all-cause death, compared with those without COPD (43.1% vs. 24.9%; hazard ratio [HR]: 2.03; 95% confidence interval [CI]: 1.56–2.64; p < 0.001). Among patients with COPD, CABG appeared to have a slightly lower risk of 10-year all-cause death compared with PCI (42.3% vs. 43.9%; HR: 0.96; 95% CI: 0.59–1.56, p = 0.858), whereas among those without COPD, CABG had a significantly lower risk of 10-year all-cause death (22.7% vs. 27.1%; HR: 0.81; 95% CI: 0.67–0.99, p = 0.041). There was no significant differential treatment effect of CABG versus PCI on 10-year all-cause death between patients with and without COPD (p interaction = 0.544).ConclusionsCOPD was associated with a higher risk of 10-year all-cause death after revascularization for complex coronary artery disease. The presence of COPD did not significantly modify the beneficial effect of CABG versus PCI on 10-year all-cause death.Trial registration: SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050
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| 49. |
- Wierenga, Lara M., et al.
(författare)
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Greater male than female variability in regional brain structure across the lifespan
- 2022
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Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 470-499
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Tidskriftsartikel (refereegranskat)abstract
- For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
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| 50. |
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