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- 2019
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Journal article (peer-reviewed)
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- Loza, M. J., et al.
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Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study
- 2016
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In: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 17:1
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Journal article (peer-reviewed)abstract
- Background: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods: Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results: Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions: Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. Trial registration:NCT01274507(ADEPT), registered October 28, 2010 and NCT01982162(U-BIOPRED), registered October 30, 2013.
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- Thompson, Paul M., et al.
(author)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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In: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Journal article (peer-reviewed)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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- Hudson, Lawrence N, et al.
(author)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Journal article (peer-reviewed)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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- Davies, G., et al.
(author)
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Genetic contributions to variation in general cognitive function : a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)
- 2015
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 20:2, s. 183-192
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Journal article (peer-reviewed)abstract
- General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health-and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N = 53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P = 3.93 x 10(-9), MIR2113; rs17522122, P = 2.55 x 10(-8), AKAP6; rs10119, P = 5.67 x 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P = 1x10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N = 6617) and the Health and Retirement Study (N = 5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e. = 5%) and 28% (s.e. = 7%), respectively. Using polygenic prediction analysis, similar to 1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N = 5487; P = 1.5 x 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.
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- Aggarwal, M. M., et al.
(author)
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Event-by-event charged-neutral fluctuations in Pb plus Pb collisions at 158 A GeV
- 2011
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 701:3, s. 300-305
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Journal article (peer-reviewed)abstract
- Charged particles and photons have been measured in central Pb + Pb collisions at 158 A GeV in a common (eta-phi)-phase space region in the WA98 experiment at the CERN SPS. The measured distributions have been analyzed to quantify the frequency with which phase space regions of varying sizes have either small or large neutral pion fraction. The measured results are compared with VENUS model simulated events and with mixed events. Events with both large and small charged-neutral fluctuations are observed to occur more frequently than expected statistically, as deduced from mixed events, or as predicted by model simulations, with the difference becoming more prominent with decreasing size of the A Delta eta-Delta phi region. (C) 2011 Elsevier B.V. All rights reserved.
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- Aggarwal, M. M., et al.
(author)
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Photon and eta production in p plus Pb and p plus C collisions at root(NN)-N-S=17.4 GeV
- 2013
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In: Nuclear Physics, Section A. - : Elsevier BV. - 0375-9474. ; 898, s. 14-23
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Journal article (peer-reviewed)abstract
- Measurements of direct photon production in p + Pb and p + C collisions at root(NN)-N-s = 17.4 GeV are presented. Upper limits on the direct photon yield as a function of p(T) are derived and compared to the results for Pb + Pb collisions at root(NN)-N-s = 17.3 GeV. The production of the eta meson, which is an important input to the direct photon signal extraction, has been determined in the eta -> 2 gamma channel for p + C collisions at root(NN)-N-s = 17.4 GeV. (c) 2012 Elsevier B.V. All rights reserved.
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| 9. |
- Aggarwal, M. M., et al.
(author)
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Pion freeze-out time in Pb plus Pb collisions at 158 AGeV/c studied via pi(-)/pi(+) and K-/K+ ratios
- 2006
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 48:2, s. 343-352
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Journal article (peer-reviewed)abstract
- The effect of the final state Coulomb interaction on particles produced in Pb + Pb collisions at 158AGeV/c has been investigated in the WA98 experiment through the study of the pi(-)/pi(+) and K-/K+ ratios measured as a function of T-m- (m)0. While the ratio for kaons shows no significant T-m dependence, the pi(-)/pi(+) ratio is enhanced at small T-m - (m)0 values with an enhancement that increases with centrality. A silicon pad detector located near the target is used to estimate the contribution of hyperon decays to the pi(-)/pi(+) ratio. The comparison of results with predictions of the RQMD model in which the Coulomb interaction has been incorporated allows to place constraints on the time of the pion freeze-out.
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| 10. |
- Aggarwal, M. M., et al.
(author)
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Suppression of high-p(T) neutral pion production in central Pb+Pb collisions at root s(NN)=17.3 GeV relative to p+C and p+Pb collisions
- 2008
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In: Physical Review Letters. - 1079-7114. ; 100:24
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Journal article (peer-reviewed)abstract
- Neutral pion transverse momentum spectra were measured in p+C and p+Pb collisions at root s(NN) = 17.4 GeV at midrapidity (2.3 less than or similar to eta(lab)less than or similar to 3.0) over the range 0.7 less than or similar to p(T)less than or similar to 3.5 GeV/c. The spectra are compared to pi(0) spectra measured in Pb+Pb collisions at root s(NN) = 17.3 GeV in the same experiment. For a wide range of Pb+Pb centralities (N-part less than or similar to 300), the yield of pi(0)'s with p(T)greater than or similar to 2 GeV/c is larger than or consistent with the p+C or p+Pb yields scaled with the number of nucleon-nucleon collisions (N-coll), while for central Pb+Pb collisions with N-part greater than or similar to 350, the pi(0) yield is suppressed.
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