| 1. |
- Thompson, B.A., et al.
(författare)
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Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:2, s. 107-115
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Tidskriftsartikel (refereegranskat)abstract
- The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary expert committee review of the clinical and functional data available for variants, applied to 2,360 sequence alterations, and disseminated online. Assessment using validated criteria altered classifications for 66% of 12,006 database entries. Clinical recommendations based on transparent evaluation are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation and classification of variants in public locus-specific databases. © 2014 Nature America, Inc.
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| 4. |
- Allan, Eric, et al.
(författare)
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Interannual variation in land-use intensity enhances grassland multidiversity
- 2014
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 111:1, s. 308-313
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Tidskriftsartikel (refereegranskat)abstract
- Although temporal heterogeneity is a well-accepted driver of biodiversity, effects of interannual variation in land-use intensity (LUI) have not been addressed yet. Additionally, responses to land use can differ greatly among different organisms; therefore, overall effects of land-use on total local biodiversity are hardly known. To test for effects of LUI (quantified as the combined intensity of fertilization, grazing, and mowing) and interannual variation in LUI (SD in LUI across time), we introduce a unique measure of whole-ecosystem biodiversity, multidiversity. This synthesizes individual diversity measures across up to 49 taxonomic groups of plants, animals, fungi, and bacteria from 150 grasslands. Multidiversity declined with increasing LUI among grasslands, particularly for rarer species and aboveground organisms, whereas common species and belowground groups were less sensitive. However, a high level of interannual variation in LUI increased overall multidiversity at low LUI and was even more beneficial for rarer species because it slowed the rate at which the multidiversity of rare species declined with increasing LUI. In more intensively managed grasslands, the diversity of rarer species was, on average, 18% of the maximum diversity across all grasslands when LUI was static over time but increased to 31% of the maximum when LUI changed maximally over time. In addition to decreasing overall LUI, we suggest varying LUI across years as a complementary strategy to promote biodiversity conservation.
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| 5. |
- Cozen, W., et al.
(författare)
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A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 3856-
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR) = 0.81, 95% confidence interval (95% CI) = 0.76-0.86, P-combined 3.5 x 10(-10)), located in intron 2 of TCF3 (also known as E2A), a regulator of B-and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.
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| 6. |
- Flachenecker, P, et al.
(författare)
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Multiple sclerosis registries in Europe - results of a systematic survey
- 2014
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 20:11, s. 1523-1532
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Tidskriftsartikel (refereegranskat)abstract
- Identification of MS registries and databases that are currently in use in Europe as well as a detailed knowledge of their content and structure is important in order to facilitate comprehensive analysis and comparison of data. Methods: National MS registries or databases were identified by literature search, from the results of the MS Barometer 2011 and by asking 33 national MS societies. A standardized questionnaire was developed and sent to the registries’ leaders, followed by telephone interviews with them. Results: Twenty registries were identified, with 13 completing the questionnaire and seven being interviewed by telephone. These registries differed widely for objectives, structure, collected data, and for patients and centres included. Despite this heterogeneity, common objectives of the registries were epidemiology ( n=10), long-term therapy outcome ( n=8), healthcare research ( n=9) and support/basis for clinical trials ( n=8). While physician-based outcome measures (EDSS) are used in all registries, data from patients’ perspectives were only collected in six registries. Conclusions: The detailed information on a large number of national MS registries in Europe is a prerequisite to facilitating harmonized integration of existing data from MS registries and databases, as well as comprehensive analyses and comparison across European populations.
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| 9. |
- Griggs, David, et al.
(författare)
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An integrated framework for sustainable development goals
- 2014
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Ingår i: Ecology and Society. - 1708-3087. ; 19:4, s. 49-
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Tidskriftsartikel (refereegranskat)abstract
- The United Nations (UN) Rio+20 summit committed nations to develop a set of universal sustainable development goals (SDGs) to build on the millennium development goals (MDGs) set to expire in 2015. Research now indicates that humanity's impact on Earth's life support system is so great that further global environmental change risks undermining long-term prosperity and poverty eradication goals. Socioeconomic development and global sustainability are often posed as being in conflict because of tradeoffs between a growing world population, as well as higher standards of living, and managing the effects of production and consumption on the global environment. We have established a framework for an evidence-based architecture for new goals and targets. Building on six SDGs, which integrate development and environmental considerations, we developed a comprehensive framework of goals and associated targets, which demonstrate that it is possible, and necessary, to develop integrated targets relating to food, energy, water, and ecosystem services goals; thus providing a neutral evidence-based approach to support SDG target discussions. Global analyses, using an integrated global target equation, are close to providing indicators for these targets. Alongside development-only targets and environment-only targets, these integrated targets would ensure that synergies are maximized and trade-offs are managed in the implementation of SDGs.
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| 11. |
- Luterbacher, Jürg, et al.
(författare)
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Circulation dynamics and its influence on European and Mediterranean January–April climate over the past half millennium : results and insights from instrumental data,documentary evidence and coupled climate models
- 2010
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Ingår i: Climatic Change. - Netherlands : Springer. - 0165-0009 .- 1573-1480. ; 101:1-2, s. 201-234
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Tidskriftsartikel (refereegranskat)abstract
- We use long instrumental temperature series together with available field reconstructions of sea-level pressure (SLP) and three-dimensional climate modelsimulations to analyze relations between temperature anomalies and atmospheric circulation patterns over much of Europe and the Mediterranean for the late winter/early spring (January–April, JFMA) season. A Canonical Correlation Analysis(CCA) investigates interannual to interdecadal covariability between a new gridded SLP field reconstruction and seven long instrumental temperature series covering the past 250 years. We then present and discuss prominent atmospheric circulation patterns related to anomalous warm and cold JFMA conditions within different European areas spanning the period 1760–2007. Next, using a data assimilation technique, we link gridded SLP data with a climate model (EC-Bilt-Clio) for a better dynamical understanding of the relationship between large scale circulationand European climate. We thus present an alternative approach to reconstruct climate for the pre-instrumental period based on the assimilated model simulations.Furthermore, we present an independent method to extend the dynamic circulation analysis for anomalously cold European JFMA conditions back to the sixteenth century. To this end, we use documentary records that are spatially representative for the long instrumental records and derive, through modern analogs, large-scale SLP, surface temperature and precipitation fields. The skill of the analog method is tested in the virtual world of two three-dimensional climate simulations (ECHOGand HadCM3). This endeavor offers new possibilities to both constrain climate model into a reconstruction mode (through the assimilation approach) and to better assess documentary data in a quantitative way.
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| 12. |
- Trachsel, Mathias, et al.
(författare)
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Multi-archive summer temperature reconstruction for the European Alps, AD 1053-1996
- 2012
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Ingår i: Quaternary Science Reviews. - : Elsevier. - 0277-3791 .- 1873-457X. ; 46, s. 66-79
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Tidskriftsartikel (refereegranskat)abstract
- We present a multi-archive, multi-proxy summer temperature reconstruction for the European Alpscovering the period AD 1053-1996 using tree-ring and lake sediment data. The new reconstruction isbased on nine different calibration approaches and errors were estimated conservatively. Summertemperatures of the last millennium are characterised by two warm (AD 1053-1171 and 1823-1996) andtwo cold phases (AD 1172-1379 and 1573-1822). Highest pre-industrial summer temperatures of the12th century were 0.3 degC warmer than the 20th century mean but 0.35 degC colder than proxy derivedtemperatures at the end of the 20th century. The lowest temperatures at the end of the 16th centurywere ~1 degC lower than the 20th century mean.
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| 13. |
- Wunderer, C. B., et al.
(författare)
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The PERCIVAL soft X-ray imager
- 2014
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- With the increased brilliance of state-of-the-art Synchrotron radiation sources and the advent of Free Electron Lasers enabling revolutionary science with EUV to X-ray photons comes an urgent need for suitable photon imaging detectors. Requirements include high frame rates, very large dynamic range, single-photon counting capability with low probability of false positives, and (multi)-megapixels. PERCIVAL (''Pixelated Energy Resolving CMOS Imager, Versatile and Large'') is currently being developed by a collaboration of DESY, RAL, Elettra and DLS to address this need for the soft X-ray regime. PERCIVAL is a monolithic active pixel sensor (MAPS), i.e. based on CMOS technology. It will be back-thinned to access its primary energy range of 250 eV to 1 keV with target efficiencies above 90%. According to its preliminary specifications, the roughly 10 × 10 cm2, 3520 × 3710 pixel monolithic sensor will operate at frame rates up to 120 Hz (commensurate with most FELs) and use multiple gains within its 27 μm pixels to measure (e.g. at 500 eV) 1 to ∼ 105 simultaneously-arriving photons. Currently, small-scale front-illuminated prototype systems (160 × 210 pixels) are undergoing detailed testing with visible-light as well as X-ray photons. © 2014 IOP Publishing Ltd and Sissa Medialab srl.
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| 14. |
- Zhu, C. H., et al.
(författare)
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Topological Ferroelectric Bistability in a Polarization-Modulated Orthogonal Smectic Liquid Crystal
- 2012
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 134:23, s. 9681-9687
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Tidskriftsartikel (refereegranskat)abstract
- We report a bent-core liquid crystal (LC) compound exhibiting two fluid smectic phases in which two-dimensional, polar, orthorhombic layers order into three-dimensional ferroelectric states. The lower-temperature phase has a uniform polarization field which responds in an analog fashion to applied electric field. The higher-temperature phase is a new smectic state with periodic undulation of the polarization, structurally modulated layers, and a bistable response to applied electric field which originates in the periodically splay-modulated bulk of the LC rather than by surface stabilization at the cell boundaries.
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