SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Pearson James) "

Sökning: WFRF:(Pearson James)

  • Resultat 1-50 av 54
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • 2019
  • Tidskriftsartikel (refereegranskat)
  •  
2.
  •  
3.
  •  
4.
  •  
5.
  • Watson, Hunna J., et al. (författare)
  • Common Genetic Variation and Age of Onset of Anorexia Nervosa
  • 2022
  • Ingår i: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
  •  
6.
  • Abel, I, et al. (författare)
  • Overview of the JET results with the ITER-like wall
  • 2013
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
  • Tidskriftsartikel (refereegranskat)abstract
    • Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
  •  
7.
  • Flannick, Jason, et al. (författare)
  • Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
  • 2017
  • Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
  •  
8.
  • Fuchsberger, Christian, et al. (författare)
  • The genetic architecture of type 2 diabetes
  • 2016
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
  •  
9.
  • Manning, Alisa, et al. (författare)
  • A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
  • 2017
  • Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
  •  
10.
  • Palmer, Nicholette D, et al. (författare)
  • A genome-wide association search for type 2 diabetes genes in African Americans.
  • 2012
  • Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
  • Tidskriftsartikel (refereegranskat)abstract
    • African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
  •  
11.
  • Saxena, Richa, et al. (författare)
  • Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:2, s. 142-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958–30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, β (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 × 10−15). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 × 10−17; ratio of insulin to glucose area under the curve, P = 1.3 × 10−16) and diminished incretin effect (n = 804; P = 4.3 × 10−4). We also identified variants at ADCY5 (rs2877716, P = 4.2 × 10−16), VPS13C (rs17271305, P = 4.1 × 10−8), GCKR (rs1260326, P = 7.1 × 10−11) and TCF7L2 (rs7903146, P = 4.2 × 10−10) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09–1.15, P = 4.8 × 10−18).
  •  
12.
  • Hudson, Thomas J., et al. (författare)
  • International network of cancer genome projects
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
  • Tidskriftsartikel (refereegranskat)abstract
    • The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
  •  
13.
  • Lunt, Daniel J., et al. (författare)
  • The DeepMIP contribution to PMIP4 : experimental design for model simulations of the EECO, PETM, and pre-PETM (version 1.0)
  • 2017
  • Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 10:2, s. 889-901
  • Tidskriftsartikel (refereegranskat)abstract
    • Past warm periods provide an opportunity to evaluate climate models under extreme forcing scenarios, in particular high (>800 ppmv) atmospheric CO2 concentrations. Although a post hoc intercomparison of Eocene (similar to 50 Ma) climate model simulations and geological data has been carried out previously, models of past high-CO2 periods have never been evaluated in a consistent framework. Here, we present an experimental design for climate model simulations of three warm periods within the early Eocene and the latest Paleocene (the EECO, PETM, and pre-PETM). Together with the CMIP6 pre-industrial control and abrupt 4 x CO2 simulations, and additional sensitivity studies, these form the first phase of DeepMIP - the Deep-time Model Intercomparison Project, itself a group within the wider Paleo-climate Modelling Intercomparison Project (PMIP). The experimental design specifies and provides guidance on boundary conditions associated with palaeogeography, greenhouse gases, astronomical configuration, solar constant, land surface processes, and aerosols. Initial conditions, simulation length, and output variables are also specified. Finally, we explain how the geological data sets, which will be used to evaluate the simulations, will be developed.
  •  
14.
  • Romanelli, F, et al. (författare)
  • Overview of the JET results
  • 2011
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower ρ*and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower ρ*and ν*and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2 MW m-2) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling. © 2011 IAEA, Vienna.
  •  
15.
  • Tobias, Deirdre K, et al. (författare)
  • Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
  • 2023
  • Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
  • Forskningsöversikt (refereegranskat)abstract
    • Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
  •  
16.
  • Wang, Haidong, et al. (författare)
  • Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015 : the Global Burden of Disease Study 2015.
  • 2016
  • Ingår i: The lancet. HIV. - : Elsevier. - 2352-3018. ; 3:8, s. e361-e387
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.METHODS: For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification.FINDINGS: Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1-3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5-2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6-40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7-1·9 million) in 2005, to 1·2 million deaths (1·1-1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections.INTERPRETATION: Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030.
  •  
17.
  • Birdsell, Dawn N, et al. (författare)
  • Francisella tularensis subsp. tularensis group A.I, United States
  • 2014
  • Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 20:5, s. 861-865
  • Tidskriftsartikel (refereegranskat)abstract
    • We used whole-genome analysis and subsequent characterization of geographically diverse strains using new genetic signatures to identify distinct subgroups within Francisella tularensis subsp. tularensis group A.I: A.I.3, A.I.8, and A.I.12. These subgroups exhibit complex phylogeographic patterns within North America. The widest distribution was observed for A.I.12, which suggests an adaptive advantage.
  •  
18.
  • Brikell, Isabell, et al. (författare)
  • ADHD medication discontinuation and persistence across the lifespan : a retrospective observational study using population-based databases
  • 2024
  • Ingår i: Lancet psychiatry. - : Elsevier. - 2215-0374 .- 2215-0366. ; 11:1, s. 16-26
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Although often intended for long-term treatment, discontinuation of medication for ADHD is common. However, cross-national estimates of discontinuation are missing due to the absence of standardised measures. The aim of this study was to determine the rate of ADHD treatment discontinuation across the lifespan and to describe similarities and differences across countries to guide clinical practice.METHODS: We did a retrospective, observational study using population-based databases from eight countries and one Special Administrative Region (Australia, Denmark, Hong Kong, Iceland, the Netherlands, Norway, Sweden, the UK, and the USA). We used a common analytical protocol approach and extracted prescription data to identify new users of ADHD medication. Eligible individuals were aged 3 years or older who had initiated ADHD medication between 2010 and 2020. We estimated treatment discontinuation and persistence in the 5 years after treatment initiation, stratified by age at initiation (children [age 4-11 years], adolescents [age 12-17 years], young adults [age 18-24 years], and adults [age ≥25 years]) and sex. Ethnicity data were not available.FINDINGS: 1 229 972 individuals (735 503 [60%] males, 494 469 females [40%]; median age 8-21 years) were included in the study. Across countries, treatment discontinuation 1-5 years after initiation was lowest in children, and highest in young adults and adolescents. Within 1 year of initiation, 65% (95% CI 60-70) of children, 47% (43-51) of adolescents, 39% (36-42) of young adults, and 48% (44-52) of adults remained on treatment. The proportion of patients discontinuing was highest between age 18 and 19 years. Treatment persistence for up to 5 years was higher across countries when accounting for reinitiation of medication; at 5 years of follow-up, 50-60% of children and 30-40% of adolescents and adults were covered by treatment in most countries. Patterns were similar across sex.INTERPRETATION: Early medication discontinuation is prevalent in ADHD treatment, particularly among young adults. Although reinitiation of medication is common, treatment persistence in adolescents and young adults is lower than expected based on previous estimates of ADHD symptom persistence in these age groups. This study highlights the scope of medication treatment discontinuation and persistence in ADHD across the lifespan and provides new knowledge about long-term ADHD medication use.FUNDING: European Union Horizon 2020 Research and Innovation Programme.
  •  
19.
  • Champion, Mia D, et al. (författare)
  • Comparative genomic characterization of Francisella tularensis strains belonging to low and high virulence subspecies
  • 2009
  • Ingår i: PLoS pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 5:5, s. e1000459-
  • Tidskriftsartikel (refereegranskat)abstract
    • Tularemia is a geographically widespread, severely debilitating, and occasionally lethal disease in humans. It is caused by infection by a gram-negative bacterium, Francisella tularensis. In order to better understand its potency as an etiological agent as well as its potential as a biological weapon, we have completed draft assemblies and report the first complete genomic characterization of five strains belonging to the following different Francisella subspecies (subsp.): the F. tularensis subsp. tularensis FSC033, F. tularensis subsp. holarctica FSC257 and FSC022, and F. tularensis subsp. novicida GA99-3548 and GA99-3549 strains. Here, we report the sequencing of these strains and comparative genomic analysis with recently available public Francisella sequences, including the rare F. tularensis subsp. mediasiatica FSC147 strain isolate from the Central Asian Region. We report evidence for the occurrence of large-scale rearrangement events in strains of the holarctica subspecies, supporting previous proposals that further phylogenetic subdivisions of the Type B clade are likely. We also find a significant enrichment of disrupted or absent ORFs proximal to predicted breakpoints in the FSC022 strain, including a genetic component of the Type I restriction-modification defense system. Many of the pseudogenes identified are also disrupted in the closely related rarely human pathogenic F. tularensis subsp. mediasiatica FSC147 strain, including modulator of drug activity B (mdaB) (FTT0961), which encodes a known NADPH quinone reductase involved in oxidative stress resistance. We have also identified genes exhibiting sequence similarity to effectors of the Type III (T3SS) and components of the Type IV secretion systems (T4SS). One of the genes, msrA2 (FTT1797c), is disrupted in F. tularensis subsp. mediasiatica and has recently been shown to mediate bacterial pathogen survival in host organisms. Our findings suggest that in addition to the duplication of the Francisella Pathogenicity Island, and acquisition of individual loci, adaptation by gene loss in the more recently emerged tularensis, holarctica, and mediasiatica subspecies occurred and was distinct from evolutionary events that differentiated these subspecies, and the novicida subspecies, from a common ancestor. Our findings are applicable to future studies focused on variations in Francisella subspecies pathogenesis, and of broader interest to studies of genomic pathoadaptation in bacteria.
  •  
20.
  • Craddock, Nick, et al. (författare)
  • Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
  • 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.
  •  
21.
  • Day, James M. D., et al. (författare)
  • Early Eocene Arctic volcanism from carbonate-metasomatized mantle
  • 2023
  • Ingår i: Contributions to Mineralogy and Petrology. - : Springer Nature. - 0010-7999 .- 1432-0967. ; 178:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Melilitite, nephelinite, basanite, and alkali basalt, along with phonolite differentiates, form the Freemans Cove Complex (FCC) in the south-eastern extremity of Bathurst Island (Nunavut, Canada). New Ar-40/Ar-39 chronology indicates their emplacement between similar to 56 and similar to 54 million years ago within a localized extensional structure. Melilitites and nephelinites, along with phonolite differentiates, likely relate to the beginning and end phases of extension, whereas alkali basalts were emplaced during a main extensional episode at similar to 55 Ma. The melilitites, nephelinites, and alkali basalts show no strong evidence for significant assimilation of crust, in contrast to some phonolites. Partial melting occurred within both the garnet- and spinel-facies mantle and sampled sources with He, O, Nd, Hf, and Os isotope characteristics indicative of peridotite with two distinct components. The first, expressed in higher degree partial melts, represents a relatively depleted component ("A"; He-3/He-4 similar to 8 R-A, epsilon(i)(Nd) similar to + 3 epsilon(Hf)i similar to + 7, gamma(Os)i similar to 0). The second was an enriched component ("B" He-3/He-4 < 3 R-A, epsilon(Nd)i < - 1 epsilon(Hf)i < + 3, gamma(Os)i > + 70) sampled by the lowest degree partial melts and represents carbonate-metasomatized peridotite. Magmatism in the FCC shows that rifting extended from the Labrador Sea to Bathurst Island and reached a zenith at similar to 55 Ma, during the Eurekan orogeny. The incompatible trace-element abundances and isotopic signatures of FCC rocks indicate melt generation occurred at the base of relatively thin lithosphere at the margin of a thick craton, with no mantle plume influence. FCC melt compositions are distinct from other continental rift magmatic provinces worldwide, and their metasomatized mantle source was plausibly formed synchronously with emplacement of Cretaceous kimberlites. The FCC illustrates that the range of isotopic compositions preserved in continental rift magmas are likely to be dominated by temporal changes in the extent of partial melting, as well as by the timing and degree of metasomatism recorded in the underlying continental lithosphere.
  •  
22.
  • Dhawan, Suhail, et al. (författare)
  • A Uniform Type Ia Supernova Distance Ladder with the Zwicky Transient Facility : Absolute Calibration Based on the Tip of the Red Giant Branch Method
  • 2022
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 934:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The current Cepheid-calibrated distance ladder measurement of H0 is reported to be in tension with the values inferred from the cosmic microwave background (CMB), assuming standard cosmology. However, some tip of the red giant branch (TRGB) estimates report H0 in better agreement with the CMB. Hence, it is critical to reduce systematic uncertainties in local measurements to understand the Hubble tension. In this paper, we propose a uniform distance ladder between the second and third rungs, combining Type Ia supernovae (SNe Ia) observed by the Zwicky Transient Facility (ZTF) with a TRGB calibration of their absolute luminosity. A large, volume-limited sample of both calibrator and Hubble flow SNe Ia from the same survey minimizes two of the largest sources of systematics: host-galaxy bias and nonuniform photometric calibration. We present results from a pilot study using the existing TRGB distance to the host galaxy of ZTF SN Ia SN 2021rhu (aka ZTF21abiuvdk) in NGC7814. Combining the ZTF calibrator with a volume-limited sample from the first data release of ZTF Hubble flow SNe Ia, we infer H0 = 76.94 ± 6.4 km s−1 Mpc−1, an 8.3% measurement. The error budget is dominated by the single object calibrating the SN Ia luminosity in this pilot study. However, the ZTF sample includes already five other SNe Ia within ∼20 Mpc for which TRGB distances can be obtained with the Hubble Space Telescope. Finally, we present the prospects of building this distance ladder out to 80 Mpc with James Webb Space Telescope observations of more than 100 ZTF SNe Ia.
  •  
23.
  • Dwomoh, Arianna M., et al. (författare)
  • Evaluating the Consistency of Cosmological Distances Using Supernova Siblings in the Near-infrared
  • 2024
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 965:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The study of supernova (SN) siblings, supernovae with the same host galaxy, is an important avenue for understanding and measuring the properties of Type Ia SN Ia light curves (LCs). Thus far, sibling analyses have mainly focused on optical LC data. Considering that LCs in the near-infrared (NIR) are expected to be better standard candles than those in the optical, we carry out the first analysis compiling SN siblings with only NIR data. We perform an extensive literature search of all SN siblings and find six sets of siblings with published NIR photometry. We calibrate each set of siblings ensuring they are on homogeneous photometric systems, fit the LCs with the SALT3-NIR and SNooPy models, and find median absolute differences in μ values between siblings of 0.248 and 0.186 mag, respectively. To evaluate the significance of these differences beyond measurement noise, we run simulations that mimic these LCs and provide an estimate for uncertainty on these median absolute differences of ∼0.052 mag, and we find that, statistically, our analysis rules out the nonexistence of intrinsic scatter in the NIR at the 99% level. When comparing the same sets of SN siblings, we observe a median absolute difference in μ values between siblings of 0.177 mag when using optical data alone as compared to 0.186 mag when using NIR data alone. It is unclear if these results may be due to limited statistics or poor quality NIR data, all of which will be improved with the Nancy Grace Roman Space Telescope.
  •  
24.
  • Ebrahimi-Fakhari, Darius, et al. (författare)
  • Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia
  • 2020
  • Ingår i: Brain. - OXFORD ENGLAND : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:10, s. 2929-2944
  • Tidskriftsartikel (refereegranskat)abstract
    • Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.0-49.3 years). While the mean age at symptom onset was 0.8 +/- 0.6 years [standard deviation (SD), range 0.2-5.0], the mean age at diagnosis was 10.2 +/- 8.5 years (SD, range 0.1-46.3). We define a set of core features: early-onset developmental delay with delayed motor milestones and significant speech delay (50% non-verbal); intellectual disability in the moderate to severe range; mild hypotonia in infancy followed by spastic diplegia (mean age: 8.4 +/- 5.1 years, SD) and later tetraplegia (mean age: 16.1 +/- 9.8 years, SD); postnatal microcephaly (83%); foot deformities (69%); and epilepsy (66%) that is intractable in a subset. At last follow-up, 36% ambulated with assistance (mean age: 8.9 +/- 6.4 years, SD) and 54% were wheelchair-dependent (mean age: 13.4 +/- 9.8 years, SD). Episodes of stereotypic laughing, possibly consistent with a pseudobulbar affect, were found in 56% of patients. Key features on neuroimaging include a thin corpus callosum (90%), ventriculomegaly (65%) often with colpocephaly, and periventricular white-matter signal abnormalities (68%). Iron deposition and polymicrogyria were found in a subset of patients. AP4B1-associated SPG47 and AP4M1-associated SPG50 accounted for the majority of cases. About two-thirds of patients were born to consanguineous parents, and 82% carried homozygous variants. Over 70 unique variants were present, the majority of which are frameshift or nonsense mutations. To track disease progression across the age spectrum, we defined the relationship between disease severity as measured by several rating scales and disease duration. We found that the presence of epilepsy, which manifested before the age of 3 years in the majority of patients, was associated with worse motor outcomes. Exploring genotype-phenotype correlations, we found that disease severity and major phenotypes were equally distributed among the four subtypes, establishing that SPG47, SPG50, SPG51 and SPG52 share a common phenotype, an 'AP-4 deficiency syndrome'. By delineating the core clinical, imaging, and molecular features of AP-4-associated hereditary spastic paraplegia across the age spectrum our results will facilitate early diagnosis, enable counselling and anticipatory guidance of affected families and help define endpoints for future interventional trials.
  •  
25.
  • Fazey, Ioan, et al. (författare)
  • Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
  • 2020
  • Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
  • Tidskriftsartikel (refereegranskat)abstract
    • Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
  •  
26.
  •  
27.
  • Frantz, Laurent A. F., et al. (författare)
  • Ancient pigs reveal a near-complete genomic turnover following their introduction to Europe
  • 2019
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:35, s. 17231-17238
  • Tidskriftsartikel (refereegranskat)abstract
    • Archaeological evidence indicates that pig domestication had begun by similar to 10,500 y before the present ( BP) in the Near East, and mitochondrial DNA ( mtDNA) suggests that pigs arrived in Europe alongside farmers similar to 8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process.
  •  
28.
  • Ganio, Matthew S., et al. (författare)
  • Aerobic Fitness Is Disproportionately Low in Adult Burn Survivors Years After Injury
  • 2015
  • Ingår i: Journal of Burn Care & Research. - 1559-047X .- 1559-0488. ; 36:4, s. 513-519
  • Tidskriftsartikel (refereegranskat)abstract
    • A maximal aerobic capacity below the 20th percentile is associated with an increased risk of all-cause mortality (Blair 1995). Adult Adult burn survivors have a lower aerobic capacity compared with nonburned adults when evaluated 38 +/- 23 days postinjury (deLateur 2007). However, it is unknown whether burn survivors with well-healed skin grafts (ie, multiple years postinjury) also have low aerobic capacity. This project tested the hypothesis that aerobic fitness, as measured by maximal aerobic capacity (VO2max), is reduced in well-healed adult burn survivors when compared with normative values from nonburned individuals. Twenty-five burn survivors (36 +/- 12 years old; 13 females) with well-healed split-thickness grafts (median, 16 years postinjury; range, 1-51 years) covering at least 17% of their BSA (mean, 40 +/- 16%; range, 17-75%) performed a graded cycle ergometry exercise to test volitional fatigue. Expired gases and minute ventilation were measured via a metabolic cart for the determination of VO2max. Each subject's VO2max was compared with sex- and age-matched normative values from population data published by the American College of Sports Medicine, the American Heart Association, and recent epidemiological data (Aspenes 2011). Subjects had a VO2max of 29.4 +/- 10.1ml O-2/kg body mass/min (median, 27.5; range, 15.9-53.3). The use of American College of Sports Medicine normative values showed that mean VO2max of the subjects was in the lower 24th percentile (median, 10th percentile). A total of 88% of the subjects had a VO2max below American Heart Association age-adjusted normative values. Similarly, 20 of the 25 subjects had a VO2max in the lower 25% percentile of recent epidemiological data. Relative to nongrafted subjects, 80 to 88% of the evaluated skin-graft subjects had a very low aerobic capacity. On the basis of these findings, adult burn survivors are disproportionally unfit relative to the general U.S. population, and this puts them at an increased risk of all-cause mortality (Blair 1995).
  •  
29.
  • Ganio, Matthew S., et al. (författare)
  • Nongrafted Skin Area Best Predicts Exercise Core Temperature Responses in Burned Humans
  • 2015
  • Ingår i: Medicine & Science in Sports & Exercise. - 0195-9131 .- 1530-0315. ; 47:10, s. 2224-2232
  • Tidskriftsartikel (refereegranskat)abstract
    • Grafted skin impairs heat dissipation, but it is unknown to what extent this affects body temperature during exercise in the heat.Purpose: We examined core body temperature responses during exercise in the heat in a group of individuals with a large range of grafts covering their body surface area (BSA; 0%-75%).Methods: Forty-three individuals (19 females) were stratified into groups based on BSA grafted: control (0% grafted, n = 9), 17%-40% (n = 19), and >40% (n = 15). Subjects exercised at a fixed rate of metabolic heat production (339 +/- 70 W; 4.3 +/- 0.8 Wkg(-1)) in an environmental chamber set at 40 degrees C, 30% relative humidity for 90 min or until exhaustion (n = 8). Whole-body sweat rate and core temperatures were measured.Results: Whole-body sweat rates were similar between the groups (control: 14.7 +/- 3.4 mLmin(-1), 17%-40%: 12.6 +/- 4.0 mLmin(-1); and >40%: 11.7 +/- 4.4 mLmin(-1); P > 0.05), but the increase in core temperature at the end of exercise in the >40% BSA grafted group (1.6 degrees C +/- 0.5 degrees C) was greater than the 17%-40% (1.2 degrees C +/- 0.3 degrees C) and control (0.9 degrees C +/- 0.2 degrees C) groups (P < 0.05). Absolute BSA of nongrafted skin (expressed in square meters) was the strongest independent predictor of the core temperature increase (r(2) = 0.41). When regrouping all subjects, individuals with the lowest BSA of nongrafted skin (<1.0 m(2)) had greater increases in core temperature (1.6 degrees C +/- 0.5 degrees C) than those with more than 1.5 m(2) nongrafted skin (1.0 degrees C +/- 0.3 degrees C; P < 0.05).Conclusions: These data imply that individuals with grafted skin have greater increases in core temperature when exercising in the heat and that the magnitude of this increase is best explained by the amount of nongrafted skin available for heat dissipation.
  •  
30.
  • Goobar, Ariel, 1962-, et al. (författare)
  • Uncovering a population of gravitational lens galaxies with magnified standard candle SN Zwicky
  • 2023
  • Ingår i: Nature Astronomy. - 2397-3366. ; 7:9, s. 1098-1107
  • Tidskriftsartikel (refereegranskat)abstract
    • Detecting gravitationally lensed supernovae is among the biggest challenges in astronomy. It involves a combination of two very rare phenomena: catching the transient signal of a stellar explosion in a distant galaxy and observing it through a nearly perfectly aligned foreground galaxy that deflects light towards the observer. Here we describe how high-cadence optical observations with the Zwicky Transient Facility, with its unparalleled large field of view, led to the detection of a multiply imaged type Ia supernova, SN Zwicky, also known as SN 2022qmx. Magnified nearly 25-fold, the system was found thanks to the standard candle nature of type Ia supernovae. High-spatial-resolution imaging with the Keck telescope resolved four images of the supernova with very small angular separation, corresponding to an Einstein radius of only θE = 0.167″ and almost identical arrival times. The small θE and faintness of the lensing galaxy are very unusual, highlighting the importance of supernovae to fully characterize the properties of galaxy-scale gravitational lenses, including the impact of galaxy substructures.
  •  
31.
  • Hakkaart, C, et al. (författare)
  • Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers
  • 2022
  • Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1061-
  • Tidskriftsartikel (refereegranskat)abstract
    • The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09–1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.
  •  
32.
  • Horikoshi, Momoko, et al. (författare)
  • New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
  •  
33.
  • Howitt, Richard, et al. (författare)
  • Intercultural capacity deficits : contested geographies of coexistence in natural resource management
  • 2013
  • Ingår i: Asia Pacific Viewpoint. - : Wiley. - 1360-7456 .- 1467-8373. ; 54:2, s. 126-140
  • Forskningsöversikt (refereegranskat)abstract
    • Focusing on the coexistence of competing and contested interests in intercultural natural resource management (NRM) systems in Australia and Malaysia, this paper explores the ways in which ontological pluralism and the interplay of socio-cultural, political-economic and biophysical influences shape NRM systems. We aim to foster a discursive space in which to reframe the challenges of capacity building in the rapidly changing spaces of intercultural NRM systems. The paper synthesizes the conceptual arguments of field research to conclude that capacity deficits of dominant institutions, processes and knowledge systems drive many systemic failures in land and sea management affecting Indigenous peoples. We advocate urgent action to build intercultural competence and new capacities and competencies in those institutions. The paper reframes intercultural NRM in terms of coexistence and invites wider debate about these ` new geographies of coexistence' in intercultural NRM systems.
  •  
34.
  • Hummel, Kevin, et al. (författare)
  • Development of an international standard set of clinical and patient-reported outcomes for children and adults with congenital heart disease : a report from the International Consortium for Health Outcomes Measurement Congenital Heart Disease Working Group.
  • 2021
  • Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - : Oxford University Press (OUP). - 2058-5225 .- 2058-1742. ; 7:4, s. 354-365
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: Congenital heart disease (CHD) is the most common congenital malformation. Despite the worldwide burden to patient wellbeing and health system resource utilization, tracking of long-term outcomes is lacking, limiting the delivery and measurement of high-value care. To begin transitioning to value-based healthcare in CHD, the International Consortium for Health Outcomes Measurement aligned an international collaborative of CHD experts, patient representatives, and other stakeholders to construct a standard set of outcomes and risk-adjustment variables that are meaningful to patients.METHODS AND RESULTS: The primary aim was to identify a minimum standard set of outcomes to be used by health systems worldwide. The methodological process included four key steps: (i) develop a working group representative of all CHD stakeholders; (ii) conduct extensive literature reviews to identify scope, outcomes of interest, tools used to measure outcomes, and case-mix adjustment variables; (iii) create the outcome set using a series of multi-round Delphi processes; and (iv) disseminate set worldwide. The Working Group established a 15-item outcome set, incorporating physical, mental, social, and overall health outcomes accompanied by tools for measurement and case-mix adjustment variables. Patients with any CHD diagnoses of all ages are included. Following an open review process, over 80% of patients and providers surveyed agreed with the set in its final form.CONCLUSION: This is the first international development of a stakeholder-informed standard set of outcomes for CHD. It can serve as a first step for a lifespan outcomes measurement approach to guide benchmarking and improvement among health systems.
  •  
35.
  • Ikram, M. Arfan, et al. (författare)
  • Common variants at 6q22 and 17q21 are associated with intracranial volume
  • 2012
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 539-544
  • Tidskriftsartikel (refereegranskat)abstract
    • During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
  •  
36.
  • Kümpornsin, Krittikorn, et al. (författare)
  • Generation of a mutator parasite to drive resistome discovery in Plasmodium falciparum
  • 2023
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • In vitro evolution of drug resistance is a powerful approach for identifying antimalarial targets, however, key obstacles to eliciting resistance are the parasite inoculum size and mutation rate. Here we sought to increase parasite genetic diversity to potentiate resistance selections by editing catalytic residues of Plasmodium falciparum DNA polymerase δ. Mutation accumulation assays reveal a ~5–8 fold elevation in the mutation rate, with an increase of 13–28 fold in drug-pressured lines. Upon challenge with the spiroindolone PfATP4-inhibitor KAE609, high-level resistance is obtained more rapidly and at lower inocula than wild-type parasites. Selections also yield mutants with resistance to an “irresistible” compound, MMV665794 that failed to yield resistance with other strains. We validate mutations in a previously uncharacterised gene, PF3D7_1359900, which we term quinoxaline resistance protein (QRP1), as causal for resistance to MMV665794 and a panel of quinoxaline analogues. The increased genetic repertoire available to this “mutator” parasite can be leveraged to drive P. falciparum resistome discovery.
  •  
37.
  • Li, Josephine H., et al. (författare)
  • Identification of Genetic Variation Influencing Metformin Response in a Multiancestry Genome-Wide Association Study in the Diabetes Prevention Program (DPP)
  • 2023
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 72:8, s. 1161-1172
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not been repli-cated in the Diabetes Prevention Program (DPP). To as-sess pharmacogenetic interactions in prediabetes, we conducted a genome-wide association study (GWAS) in the DPP. Cox proportional hazards models tested associations with diabetes incidence in the metformin (MET; n = 876) and placebo (PBO; n = 887) arms. Multiple linear regression assessed association with 1-year change in metformin-related quantitative traits, adjusted for baseline trait, age, sex, and 10 ancestry principal compo-nents. We tested for gene-by-treatment interaction. No significant associations emerged for diabetes inci-dence. We identified four genome-wide significant variants after correcting for correlated traits (P < 9 × 1029). In the MET arm, rs144322333 near ENOSF1 (minor al-lele frequency [MAF]AFR = 0.07; MAFEUR = 0.002) was associated with an increase in percentage of glycated hemoglobin (per minor allele, b = 0.39 [95% CI 0.28, 0.50]; P = 2.8 × 10212). rs145591055 near OMSR (MAF = 0.10 in American Indians) was associated with weight loss (kilograms) (per G allele, b = 27.55 [95% CI 29.88, 25.22]; P = 3.2 × 10210) in the MET arm. Neither variant was significant in PBO; gene-by-treatment interaction was significant for both variants [P(G×T) < 1.0 × 1024 ]. Replication in individuals with diabetes did not yield significant findings. A GWAS for metformin response in prediabetes revealed novel ethnic-specific associations that require further investigation but may have implications for tailored therapy.
  •  
38.
  • Lucas, Rebekah A. I., et al. (författare)
  • Age-related changes to cardiac systolic and diastolic function during whole-body passive hyperthermia
  • 2015
  • Ingår i: Experimental Physiology. - : Wiley. - 0958-0670 .- 1469-445X. ; 100:4, s. 422-434
  • Tidskriftsartikel (refereegranskat)abstract
    • New Findings What is the central question of this study? The effect of ageing on hyperthermia-induced changes in cardiac function is unknown. What is the main finding and its importance? Using echocardiography, we show that during hyperthermia the systolic and diastolic function can be appropriately augmented to meet cardiac demand in healthy older adults, although overall age-related impairments remain. One exception was late diastolic ventricular filling [i.e. E/A ratio and A/(A+E) ratio], which in the older adults was not further augmented during hyperthermia, unlike their young counterparts. To meet cardiac demand, therefore, healthy older adults appear to depend on an increased left ventricular systolic strain and proportion of their cardiac reserve. The effect of ageing on hyperthermia-induced changes in cardiac function is unknown. This study tested the hypothesis that hyperthermia-induced changes in left ventricular systolic and diastolic function are attenuated in older adults when compared with young adults. Eight older (71 +/- 5years old) and eight young adults (29 +/- 5years old), matched for sex, physical activity and body mass index, underwent whole-body passive hyperthermia. Mean arterial pressure (Finometer Pro), heart rate, forearm vascular conductance (venous occlusion plethysmography) and echocardiographic indices of diastolic and systolic function were measured during a normothermic supine period and again after an increase in internal temperature of approximate to 1.0 degrees C. Hyperthermia decreased mean arterial pressure and left ventricular end-diastolic volumes and increased heart rate to a similar extent in both groups (P>0.05). Ageing did not alter the magnitude of hyperthermia-induced changes in indices of systolic (lateral mitral annular S velocity) or diastolic function (lateral mitral annular E velocity, peak early diastolic filling and isovolumic relaxation time; P>0.05). However, with hyperthermia the global longitudinal systolic strain increased in the older group, but was unchanged in the young group (P=0.03). Also, older adults were unable to augment late diastolic ventricular filling [i.e. E/A ratio and A/(A+E) ratio] during hyperthermia, unlike the young (P<0.05). These findings indicate that older adults depend on a greater systolic contribution (global longitudinal systolic strain) to meet hyperthermic demand and that the atrial contribution to diastolic filling was not further augmented in older adults when compared with young adults.
  •  
39.
  • Lucas, Rebekah A. I., et al. (författare)
  • Hypercapnia-induced increases in cerebral blood flow do not improve lower body negative pressure tolerance during hyperthermia
  • 2013
  • Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 305:6, s. R604-R609
  • Tidskriftsartikel (refereegranskat)abstract
    • Heat-related decreases in cerebral perfusion are partly the result of ventilatory-related reductions in arterial CO2 tension. Cerebral perfusion likely contributes to an individual's tolerance to a challenge like lower body negative pressure (LBNP). Thus increasing cerebral perfusion may prolong LBNP tolerance. This study tested the hypothesis that a hypercapnia-induced increase in cerebral perfusion improves LBNP tolerance in hyperthermic individuals. Eleven individuals (31 +/- 7 yr; 75 +/- 12 kg) underwent passive heat stress (increased intestinal temperature similar to 1.3 degrees C) followed by a progressive LBNP challenge to tolerance on two separate days (randomized). From 30 mmHg LBNP, subjects inhaled either (blinded) a hypercapnic gas mixture (5% CO2, 21% oxygen, balanced nitrogen) or room air (SHAM). LBNP tolerance was quantified via the cumulative stress index (CSI). Mean middle cerebral artery blood velocity (MCAv(mean),) and end-tidal CO2 (PETCO2) were also measured. CO2 inhalation of 5% increased PETCO2 at similar to 40 mmHg LBNP (by 16 +/- 4 mmHg) and at LBNP tolerance (by 18 +/- 5 mmHg) compared with SHAM (P < 0.01). Subsequently, MCAvmean was higher in the 5% CO2 trial during similar to 40 mmHg LBNP (by 21 +/- 12 cm/s, similar to 31%) and at LBNP tolerance (by 18 +/- 10 cm/s, similar to 25%) relative to the SHAM (P < 0.01). However, hypercapnia-induced increases in MCAvmean did not alter LBNP tolerance (5% CO2 CSI: 339 +/- 155 mmHg X min; SHAM CSI: 273 +/- 158 mmHg X min; P = 0.26). These data indicate that inhaling a hypercapnic gas mixture increases cerebral perfusion during LBNP but does not improve LBNP tolerance when hyperthermic.
  •  
40.
  • Lynch, David K., et al. (författare)
  • NOVA V2362 CYGNI (NOVA CYGNI 2006): SPITZER, SWIFT, AND GROUND-BASED SPECTRAL EVOLUTION
  • 2008
  • Ingår i: Astronomical Journal. - 1538-3881 .- 0004-6256. ; 136:number 5, 2008 November, s. 1815-1827
  • Tidskriftsartikel (refereegranskat)abstract
    • Nova V2362 Cygni has undergone a number of very unusual changes. Ground-based spectroscopy initially revealed a normal sequence of events: the object faded and its near-infrared emission lines gradually shifted to higher excitation conditions until about day 100 when the optical fading reversed and the object slowly brightened. This was accompanied by a rise in the Swift X-ray telescope flux and a sudden shift in excitation of the visible and IR spectrum back to low levels. The new lower excitation spectrum revealed broad line widths and many P-Cygni profiles, all indicative of the ejection of a second shell. Eventually, dust formed, the X-ray brightness—apparently unaffected by dust formation—peaked and then declined, and the object faded at all wavelengths. The Spitzer dust spectra revealed a number of solid-state emission features that, at this time, are not identified.
  •  
41.
  • Meagher, N. S., et al. (författare)
  • Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes
  • 2022
  • Ingår i: Clinical Cancer Research. - 1078-0432. ; 28:24, s. 5383-5395
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primaryMOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and geneexpression data were analyzed to identify prognostic and diagnostic features. Experimental Design: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors ( MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). Results: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio ( HR), 2.77; 95% confidence interval (CI), 1.04-7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04-1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01-1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). Conclusions: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.
  •  
42.
  • Menkveld, Albert J., et al. (författare)
  • Nonstandard Errors
  • 2024
  • Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
  • Tidskriftsartikel (refereegranskat)abstract
    • In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
  •  
43.
  • Narayanan, Anantha, et al. (författare)
  • Broad Responses and Attitudes to Having Music in Surgery (The BRAHMS Study) : An Australia and Aotearoa New Zealand Perspective
  • 2024
  • Ingår i: Surgery Open Science. - : Elsevier. - 2589-8450. ; 17, s. 30-34
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundSurgery is a stressful exercise, and the experience of occupational stress may have impacts on surgical performance, and surgeon well-being. Music is played in operating theatres (OTs) throughout the world, and while it may improve surgical performance, and reduce clinician stress within the OT, concerns exist over its distracting and noise-creating properties.MethodsIn this prospective observational study, between May to August 2022, Vascular, General and Paediatric surgeons and registrars in Australia and Aotearoa New Zealand (AoNZ) responded to a survey investigating the way they use music, and their perceptions and attitudes towards its effect on the OT environment. Binomial logistic regression and Chi squared tests of association were performed, accepting p < 0.05 as significant.ResultsIn this cohort of 120 surgeons, 45 % were vascular specialists, 30 % were female and 59 % were consultant surgeons. The most commonly preferred music genres were easy listening and pop. Over 75 % of surgeons enjoyed having music in their OTs with the majority reporting it improved their temperament, how mentally fatiguing a procedure felt and how anxious or stressed they felt. Vascular surgeons were more likely to believe music had a positive influence on communication than their general and paediatric surgery colleagues (p < 0.01). Registrars had significantly higher odds of believing music had a positive effect on their temperament, and how stressed and anxious they felt when operating, when compared to consultants (p < 0.05).ConclusionsThis study provides a window into the surgeons' use of and attitudes towards intra-operative background music and its effect on stress and cognitive load in Australia and AoNZ. While overall, music is viewed positively by this cohort, there was some difference seen across specialties and level of experience. Further subjective and objective data in this field may provide useful information to guide hospital policy and inform pathways for clinician wellbeing.
  •  
44.
  • Newell, Felicity, et al. (författare)
  • Whole-genome landscape of mucosal melanoma reveals diverse drivers and therapeutic targets
  • 2019
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Knowledge of key drivers and therapeutic targets in mucosal melanoma is limited due to the paucity of comprehensive mutation data on this rare tumor type. To better understand the genomic landscape of mucosal melanoma, here we describe whole genome sequencing analysis of 67 tumors and validation of driver gene mutations by exome sequencing of 45 tumors. Tumors have a low point mutation burden and high numbers of structural variants, including recurrent structural rearrangements targeting TERT, CDK4 and MDM2. Significantly mutated genes are NRAS, BRAF, NF1, KIT, SF3B1, TP53, SPRED1, ATRX, HLA-A and CHD8. SF3B1 mutations occur more commonly in female genital and anorectal melanomas and CTNNB1 mutations implicate a role for WNT signaling defects in the genesis of some mucosal melanomas. TERT aberrations and ATRX mutations are associated with alterations in telomere length. Mutation profiles of the majority of mucosal melanomas suggest potential susceptibility to CDK4/6 and/or MEK inhibitors.
  •  
45.
  •  
46.
  • Robles-Zurita, Jose, et al. (författare)
  • SCOT : a comparison of cost-effectiveness from a large randomised phase III trial of two durations of adjuvant Oxaliplatin combination chemotherapy for colorectal cancer
  • 2018
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 119:11, s. 1332-1338
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Short Course Oncology Therapy (SCOT) study is an international, multicentre, non-inferiority randomised controlled trial assessing the efficacy, toxicity, and cost-effectiveness of 3 months (3 M) versus the usually given 6 months (6 M) of adjuvant chemotherapy in colorectal cancer.METHODS: In total, 6088 patients with fully resected high-risk stage II or stage III colorectal cancer were randomised and followed up for 3-8 years. The within-trial cost-effectiveness analysis from a UK health-care perspective is presented using the resource use data, quality of life (EQ-5D-3L), time on treatment (ToT), disease-free survival after treatment (DFS) and overall survival (OS) data. Quality-adjusted partitioned survival analysis and Kaplan-Meier Sample Average Estimator estimated QALYs and costs. Probabilistic sensitivity and subgroup analysis was undertaken.RESULTS: The 3M arm is less costly (-4881; pound 95% CI: -6269; pound -3492) pound and entails (non-significant) QALY gains (0.08; 95% CI: -0.086; 0.230) due to a better significant quality of life. The net monetary benefit was significantly higher in 3M under a wide range of monetary values of a QALY. The subgroup analysis found similar results for patients in the CAPOX regimen. However, for the FOLFOX regimen, 3M had lower QALYs than 6M (not statistically significant).CONCLUSIONS: Overall, 3M dominates 6M with no significant detrimental impact on QALYs. The results provide the economic case that a 3M treatment strategy should be considered a new standard of care.
  •  
47.
  • Schlader, Zachary J., et al. (författare)
  • Baroreceptor unloading does not limit forearm sweat rate during severe passive heat stress
  • 2015
  • Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 118:4, s. 449-454
  • Tidskriftsartikel (refereegranskat)abstract
    • This study tested the hypothesis that sweat rate during passive heat stress is limited by baroreceptor unloading associated with heat stress. Two protocols were performed in which healthy subjects underwent passive heat stress that elicited an increase in intestinal temperature of similar to 1.8 degrees C. Upon attaining this level of hyperthermia, in protocol 1 (n = 10, 3 females) a bolus (19 ml/kg) of warm (similar to 38 degrees C) isotonic saline was rapidly (5-10 min) infused intravenously to elevate central venous pressure (CVP), while in protocol 2 (n = 11, 5 females) phenylephrine was infused intravenously (60-120 mu g/min) to return mean arterial pressure (MAP) to normothermic levels. In protocol 1, heat stress reduced CVP from 3.9 +/- 1.9 mmHg (normothermia) to -0.6 +/- 1.4 mmHg (P < 0.001), while saline infusion returned CVP to normothermic levels (5.1 +/- 1.7 mmHg; P > 0.999). Sweat rate was elevated by heat stress (1.21 +/- 0.44 mg.cm(-2).min(-1)) but remained unchanged during rapid saline infusion (1.26 +/- 0.47 mg.cm(-2).min(-1), P = 0.5), whereas cutaneous vascular conductance increased from 77 +/- 10 to 101 +/- 20% of local heating max (P = 0.029). In protocol 2, MAP was reduced with heat stress from 85 +/- 7 mmHg to 76 +/- 8 mmHg (P = 0.048). Although phenylephrine infusion returned MAP to normothermic levels (88 +/- 7 mmHg; P > 0.999), sweat rate remained unchanged during phenylephrine infusion (1.39 +/- 0.22 vs. 1.41 +/- 0.24 mg.cm(-2).min(-1); P > 0.999). These data indicate that both cardiopulmonary and arterial baroreceptor unloading do not limit increases in sweat rate during passive heat stress.
  •  
48.
  • Schlader, Zachary J., et al. (författare)
  • Hyperthermia does not alter the increase in cerebral perfusion during cognitive activation
  • 2013
  • Ingår i: Experimental Physiology. - : Wiley. - 0958-0670 .- 1469-445X. ; 98:11, s. 1597-1607
  • Tidskriftsartikel (refereegranskat)abstract
    • This study tested the hypothesis that hyperthermia attenuates the increase in cerebral perfusion during cognitive activation. Mean middle cerebral artery blood velocity (MCAV(mean)) served as an index of cerebral perfusion, while the nBack test (a test of working memory) was the cognitive task. Hyperthermia was characterized by elevations (P < 0.001) in skin (by 5.0 +/- 0.8 degrees C) and intestinal temperatures (by 1.3 +/- 0.1 degrees C) and reductions (P < 0.020) in mean arterial pressure (by 11 +/- 10 mmHg), end-tidal CO2 tension (by 3 +/- 6 mmHg) and MCAVmean (by 10 +/- 9 cm s(-1)). Hyperthermia had no influence on nBack test performance (mean difference from normothermia to hyperthermia, -1 +/- 11%; P = 0.276) or, counter to the hypothesis, the increase in MCAV(mean) during nBack testing (mean difference from normothermia to hyperthermia: 0 +/- 16 cm s(-1); P = 0.608). These findings indicate that the capacity to increase cerebral perfusion during cognitive activation is unaffected by hyperthermia.
  •  
49.
  • Sharma, Yashvi, et al. (författare)
  • A Systematic Study of Ia-CSM Supernovae from the ZTF Bright Transient Survey
  • 2023
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 948:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Among the supernovae (SNe) that show strong interaction with a circumstellar medium (CSM), there is a rare subclass of Type Ia supernovae, SNe Ia-CSM, which show strong narrow hydrogen emission lines much like SNe IIn but on top of a diluted Type Ia spectrum. The only previous systematic study of this class identified 16 SNe Ia-CSM, eight historic and eight from the Palomar Transient Factory (PTF). Now using the successor survey to PTF, the Zwicky Transient Facility (ZTF), we have classified 12 additional SNe Ia-CSM through the systematic Bright Transient Survey (BTS). Consistent with previous studies, we find these SNe to have slowly evolving optical light curves with peak absolute magnitudes between -19.1 and -21, spectra having weak H ss and large Balmer ldecrements of similar to 7. Out of the 10 SNe from our sample observed by NEOWISE, nine have 3 sigma detections, with some SNe showing a reduction in the red wing of Ha, indicative of newly formed dust. We do not find our SN Ia-CSM sample to have a significantly different distribution of equivalent widths of He I.5876 than SNe IIn as observed in Silverman et al. The hosts tend to be late-type galaxies with recent star formation. We derive a rate estimate of 29+(27)(21) Gpc(-3) yr(-1) for SNe Ia-CSM, which is similar to 0.02%-0.2% of the SN Ia rate. We also identify six ambiguous SNe IIn/Ia-CSM in the BTS sample and including them gives an upper limit rate of 0.07%-0.8%. This work nearly doubles the sample of well-studied Ia-CSM objects in Silverman et al., increasing the total number to 28.
  •  
50.
  • Taal, H. Rob, et al. (författare)
  • Common variants at 12q15 and 12q24 are associated with infant head circumference
  • 2012
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 532-538
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-50 av 54
Typ av publikation
tidskriftsartikel (52)
forskningsöversikt (2)
Typ av innehåll
refereegranskat (53)
övrigt vetenskapligt/konstnärligt (1)
Författare/redaktör
McCarthy, Mark I (9)
Hattersley, Andrew T (9)
Mohlke, Karen L (8)
Zeggini, Eleftheria (8)
Prokopenko, Inga (8)
Hansen, Torben (7)
visa fler...
Frayling, Timothy M (7)
Tuomi, Tiinamaija (6)
Cooper, Cyrus (6)
Wareham, Nicholas J. (6)
Pedersen, Oluf (6)
Boehnke, Michael (6)
Barroso, Ines (6)
Walker, Mark (6)
Froguel, Philippe (6)
Loos, Ruth J F (6)
Elliott, Paul (6)
Meigs, James B. (6)
Liu, Y. (5)
Wilson, A. (5)
Zhu, Y. (5)
Gupta, A. (5)
Garcia, J. (5)
Martin, D (5)
Nilsson, Peter (5)
Groop, Leif (5)
Gunn, J (5)
Johnson, R (5)
Morgan, A (5)
Sun, Y (5)
Wilson, D (5)
Deloukas, Panos (5)
Franks, Paul W. (5)
Kuusisto, Johanna (5)
Isomaa, Bo (5)
Laakso, Markku (5)
Grarup, Niels (5)
Hu, Frank B. (5)
Langenberg, Claudia (5)
Qi, Lu (5)
Tuomilehto, Jaakko (5)
Gloyn, Anna L (5)
Palmer, Colin N. A. (5)
Wilson, James F. (5)
Altshuler, David (5)
Morris, Andrew D (5)
Dupuis, Josée (5)
Illig, Thomas (5)
Pearson, Ewan R (5)
Horikoshi, Momoko (5)
visa färre...
Lärosäte
Umeå universitet (16)
Uppsala universitet (15)
Karolinska Institutet (13)
Lunds universitet (12)
Stockholms universitet (10)
Göteborgs universitet (6)
visa fler...
Chalmers tekniska högskola (6)
Kungliga Tekniska Högskolan (4)
Mittuniversitetet (2)
Högskolan i Halmstad (1)
Högskolan Väst (1)
Örebro universitet (1)
Linköpings universitet (1)
Handelshögskolan i Stockholm (1)
Karlstads universitet (1)
Högskolan Dalarna (1)
visa färre...
Språk
Engelska (54)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (33)
Naturvetenskap (18)
Samhällsvetenskap (3)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy