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- 2019
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Journal article (peer-reviewed)
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| 2. |
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| 3. |
- Loza, M. J., et al.
(author)
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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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| 4. |
- Reifarth, R., et al.
(author)
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Nuclear astrophysics with radioactive ions at FAIR
- 2016
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In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 665:1
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Conference paper (peer-reviewed)abstract
- The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process flow and r-process beta-decay chains. These nuclei are attributed to the p and rp process. For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections. The Facility for Antiproton and Ion Research (FAIR) will offer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes.
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| 5. |
- Abele, H., et al.
(author)
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Particle physics at the European Spallation Source
- 2023
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In: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 1023, s. 1-84
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Research review (peer-reviewed)abstract
- Presently under construction in Lund, Sweden, the European Spallation Source (ESS) will be the world’s brightest neutron source. As such, it has the potential for a particle physics program with a unique reach and which is complementary to that available at other facilities. This paper describes proposed particle physics activities for the ESS. These encompass the exploitation of both the neutrons and neutrinos produced at the ESS for high precision (sensitivity) measurements (searches).
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| 6. |
- 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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| 7. |
- Palmer, Nicholette D, et al.
(author)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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In: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Journal article (peer-reviewed)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.
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| 8. |
- 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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| 9. |
- 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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| 10. |
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| 11. |
- 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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| 12. |
- 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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| 13. |
- 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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| 14. |
- 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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| 15. |
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| 16. |
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| 17. |
- Aggarwal, MM, et al.
(author)
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Centrality dependence of charged-neutral particle fluctuations in 158A (GeVPb)-Pb-208+Pb-208 collisions
- 2003
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In: Physical Review C (Nuclear Physics). - 0556-2813. ; 67:4
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Journal article (peer-reviewed)abstract
- Results on the study of localized fluctuations in the multiplicity of charged particles and photons produced in 158A GeV/c Pb+Pb collisions are presented for varying centralities. The charged versus neutral particle multiplicity correlations in common phase space regions of varying azimuthal sizes are analyzed by two different methods. Various types of mixed events are constructed to probe fluctuations arising from different sources. The measured results are compared to those from simulations and from mixed events. The comparison indicates the presence of nonstatistical fluctuations in both the charged particle and photon multiplicities in limited azimuthal regions. However, no correlated charged-neutral fluctuations, a possible signature of formation of disoriented chiral condensates, are observed. An upper limit on the production of disoriented chiral condensates is set.
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| 18. |
- Aggarwal, MM, et al.
(author)
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Event-by-event fluctuations in particle multiplicities and transverse energy produced in 158A GeVPb plus Pb collisions
- 2002
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In: Physical Review C (Nuclear Physics). - 0556-2813. ; 65:5
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Journal article (peer-reviewed)abstract
- Event-by-event fluctuations in the multiplicities of charged particles and photons, and the total transverse energy in 158A GeV Pb+Pb collisions are studied for a wide range of centralities. For narrow centrality bins the multiplicity and transverse energy distributions are found to be near perfect Gaussians. The effect of detector acceptance on the multiplicity fluctuations has been studied and demonstrated to follow statistical considerations. The centrality dependence of the charged particle multiplicity fluctuations in the measured data has been found to agree reasonably well with those obtained from a participant model. However, for photons the multiplicity fluctuations have been found to be lower compared to those obtained from a participant model. The multiplicity and transverse energy fluctuations have also been compared to those obtained from the VENUS event generator.
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| 19. |
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| 20. |
- Aggarwal, M M, et al.
(author)
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Azimuthal anisotropy of photon and charged particle emission in Pb-208+Pb-208 collisions at 158 center dot A GeV/c
- 2005
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 41:3, s. 287-296
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Journal article (peer-reviewed)abstract
- The azimuthal distributions of photons and charged particles with respect to the event plane are investigated as a function of centrality in Pb-208 + Pb-208 collisions at 158 (.) A GeV/c in the WA98 experiment at the CERN SPS. The anisotropy of the azimuthal distributions is characterized using a Fourier analysis. For both the photon and charged particle distributions the first two Fourier coefficients are observed to decrease with increasing centrality. The observed anisotropies of the photon distributions compare well with the expectations from the charged particle measurements for all centralities.
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| 21. |
- Aggarwal, MM, et al.
(author)
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Transverse mass distributions of neutral pions from Pb-208-induced reactions at 158 center dot A GeV
- 2002
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 23:2, s. 225-236
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Journal article (peer-reviewed)abstract
- Results on transverse mass spectra of neutral pious measured at central rapidity are presented for impact parameter selected 158-A GeV Pb + Pb-1 and Pb + Nb collisions. The distributions cover the range 0.5 GeV/c(2) less than or equal to MT - Mo less than or equal to 4 GeV/c(2). The change of the spectral shape and the multiplicity with centrality is studied in detail. In going from p+p to semi-peripheral Pb+Pb collisions there is a nuclear enhancement increasing with transverse mass similar to the well known Cronin effect, while for very central collisions this enhancement appears to be weaker than expected.
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| 22. |
- Fuchsberger, Christian, et al.
(author)
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The genetic architecture of type 2 diabetes
- 2016
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Journal article (peer-reviewed)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.
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| 23. |
- Aggarwal, MM, et al.
(author)
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Centrality and transverse momentum dependence of collective flow in 158 A GeV Pb+Pb collisions measured via inclusive photons
- 2005
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In: Nuclear Physics, Section A. - : Elsevier BV. - 0375-9474. ; 762:1-2, s. 129-146
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Journal article (peer-reviewed)abstract
- Directed and elliptic flow of inclusive photons near mid-rapidity in 158 A GeV Pb + Pb collisions has been studied. The data have been obtained with the photon spectrometer LEDA of the WA98 experiment at the CERN SPS. The flow strength has been measured for various centralities as a function of p(T) and rapidity over 0. 18 < p(T) < 1.5 GeV/c and 2.3 < y < 2.9. The angular anisotropy has been studied relative to an event plane obtained in the target fragmentation region that shows the elliptic flow to be in-plane. The elliptic flow has also been studied using two-particle correlations and shown to give similar results. A small directed flow component is observed. Both the directed and elliptic flow strengths increase with p(T). The photon flow results are used to estimate the corresponding neutral pion flow.
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| 24. |
- Flannick, Jason, et al.
(author)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Journal article (peer-reviewed)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.
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| 25. |
- Pattaro, Cristian, et al.
(author)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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