| 1. |
- Vogel, Jacob W., et al.
(författare)
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Four distinct trajectories of tau deposition identified in Alzheimer’s disease
- 2021
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 2. |
- Tinetti, Giovanna, et al.
(författare)
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The EChO science case
- 2015
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 40:2-3, s. 329-391
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of almost two thousand exoplanets has revealed an unexpectedly diverse planet population. We see gas giants in few-day orbits, whole multi-planet systems within the orbit of Mercury, and new populations of planets with masses between that of the Earth and Neptune-all unknown in the Solar System. Observations to date have shown that our Solar System is certainly not representative of the general population of planets in our Milky Way. The key science questions that urgently need addressing are therefore: What are exoplanets made of? Why are planets as they are? How do planetary systems work and what causes the exceptional diversity observed as compared to the Solar System? The EChO (Exoplanet Characterisation Observatory) space mission was conceived to take up the challenge to explain this diversity in terms of formation, evolution, internal structure and planet and atmospheric composition. This requires in-depth spectroscopic knowledge of the atmospheres of a large and well-defined planet sample for which precise physical, chemical and dynamical information can be obtained. In order to fulfil this ambitious scientific program, EChO was designed as a dedicated survey mission for transit and eclipse spectroscopy capable of observing a large, diverse and well-defined planet sample within its 4-year mission lifetime. The transit and eclipse spectroscopy method, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allows us to measure atmospheric signals from the planet at levels of at least 10(-4) relative to the star. This can only be achieved in conjunction with a carefully designed stable payload and satellite platform. It is also necessary to provide broad instantaneous wavelength coverage to detect as many molecular species as possible, to probe the thermal structure of the planetary atmospheres and to correct for the contaminating effects of the stellar photosphere. This requires wavelength coverage of at least 0.55 to 11 mu m with a goal of covering from 0.4 to 16 mu m. Only modest spectral resolving power is needed, with R similar to 300 for wavelengths less than 5 mu m and R similar to 30 for wavelengths greater than this. The transit spectroscopy technique means that no spatial resolution is required. A telescope collecting area of about 1 m(2) is sufficiently large to achieve the necessary spectro-photometric precision: for the Phase A study a 1.13 m(2) telescope, diffraction limited at 3 mu m has been adopted. Placing the satellite at L2 provides a cold and stable thermal environment as well as a large field of regard to allow efficient time-critical observation of targets randomly distributed over the sky. EChO has been conceived to achieve a single goal: exoplanet spectroscopy. The spectral coverage and signal-to-noise to be achieved by EChO, thanks to its high stability and dedicated design, would be a game changer by allowing atmospheric composition to be measured with unparalleled exactness: at least a factor 10 more precise and a factor 10 to 1000 more accurate than current observations. This would enable the detection of molecular abundances three orders of magnitude lower than currently possible and a fourfold increase from the handful of molecules detected to date. Combining these data with estimates of planetary bulk compositions from accurate measurements of their radii and masses would allow degeneracies associated with planetary interior modelling to be broken, giving unique insight into the interior structure and elemental abundances of these alien worlds. EChO would allow scientists to study exoplanets both as a population and as individuals. The mission can target super-Earths, Neptune-like, and Jupiter-like planets, in the very hot to temperate zones (planet temperatures of 300-3000 K) of F to M-type host stars. The EChO core science would be delivered by a three-tier survey. The EChO Chemical Census: This is a broad survey of a few-hundred exoplanets, which allows us to explore the spectroscopic and chemical diversity of the exoplanet population as a whole. The EChO Origin: This is a deep survey of a subsample of tens of exoplanets for which significantly higher signal to noise and spectral resolution spectra can be obtained to explain the origin of the exoplanet diversity (such as formation mechanisms, chemical processes, atmospheric escape). The EChO Rosetta Stones: This is an ultra-high accuracy survey targeting a subsample of select exoplanets. These will be the bright "benchmark" cases for which a large number of measurements would be taken to explore temporal variations, and to obtain two and three dimensional spatial information on the atmospheric conditions through eclipse-mapping techniques. If EChO were launched today, the exoplanets currently observed are sufficient to provide a large and diverse sample. The Chemical Census survey would consist of > 160 exoplanets with a range of planetary sizes, temperatures, orbital parameters and stellar host properties. Additionally, over the next 10 years, several new ground- and space-based transit photometric surveys and missions will come on-line (e.g. NGTS, CHEOPS, TESS, PLATO), which will specifically focus on finding bright, nearby systems. The current rapid rate of discovery would allow the target list to be further optimised in the years prior to EChO's launch and enable the atmospheric characterisation of hundreds of planets.
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| 3. |
- Abdellaoui, G., et al.
(författare)
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Meteor studies in the framework of the JEM-EUSO program
- 2017
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Ingår i: Planetary and Space Science. - : Elsevier. - 0032-0633 .- 1873-5088. ; 143, s. 245-255
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Tidskriftsartikel (refereegranskat)abstract
- We summarize the state of the art of a program of UV observations from space of meteor phenomena, a secondary objective of the JEM-EUSO international collaboration. Our preliminary analysis indicates that JEM-EUSO, taking advantage of its large FOV and good sensitivity, should be able to detect meteors down to absolute magnitude close to 7. This means that JEM-EUSO should be able to record a statistically significant flux of meteors, including both sporadic ones, and events produced by different meteor streams. Being unaffected by adverse weather conditions, JEM-EUSO can also be a very important facility for the detection of bright meteors and fireballs, as these events can be detected even in conditions of very high sky background. In the case of bright events, moreover, exhibiting some persistence of the meteor train, preliminary simulations show that it should be possible to exploit the motion of the ISS itself and derive at least a rough 3D reconstruction of the meteor trajectory. Moreover, the observing strategy developed to detect meteors may also be applied to the detection of nuclearites, exotic particles whose existence has been suggested by some theoretical investigations. Nuclearites are expected to move at higher velocities than meteoroids, and to exhibit a wider range of possible trajectories, including particles moving upward after crossing the Earth. Some pilot studies, including the approved Mini-EUSO mission, a precursor of JEM-EUSO, are currently operational or in preparation. We are doing simulations to assess the performance of Mini-EUSO for meteor studies, while a few meteor events have been already detected using the ground-based facility EUSO-TA.
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| 4. |
- Abdellaoui, G., et al.
(författare)
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First observations of speed of light tracks by a fluorescence detector looking down on the atmosphere
- 2018
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Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- EUSO-Balloon is a pathfinder mission for the Extreme Universe Space Observatory onboard the Japanese Experiment Module (JEM-EUSO). It was launched on the moonless night of the 25(th) of August 2014 from Timmins, Canada. The flight ended successfully after maintaining the target altitude of 38 km for five hours. One part of the mission was a 2.5 hour underflight using a helicopter equipped with three UV light sources (LED, xenon flasher and laser) to perform an inflight calibration and examine the detectors capability to measure tracks moving at the speed of light. We describe the helicopter laser system and details of the underflight as well as how the laser tracks were recorded and found in the data. These are the first recorded laser tracks measured from a fluorescence detector looking down on the atmosphere. Finally, we present a first reconstruction of the direction of the laser tracks relative to the detector.
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| 5. |
- Ederle, Joerg, et al.
(författare)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Tidskriftsartikel (refereegranskat)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 6. |
- Zhou, XP, et al.
(författare)
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Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.
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| 7. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 8. |
- Langlois, M., et al.
(författare)
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The SPHERE infrared survey for exoplanets (SHINE) : II. Observations, data reduction and analysis, detection performances, and initial results
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 651
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Tidskriftsartikel (refereegranskat)abstract
- Context. In recent decades, direct imaging has confirmed the existence of substellar companions (exoplanets or brown dwarfs) on wide orbits (>10 au) around their host stars. In striving to understand their formation and evolution mechanisms, in 2015 we initiated the SPHERE infrared survey for exoplanets (SHINE), a systematic direct imaging survey of young, nearby stars that is targeted at exploring their demographics.Aims. We aim to detect and characterize the population of giant planets and brown dwarfs beyond the snow line around young, nearby stars. Combined with the survey completeness, our observations offer the opportunity to constrain the statistical properties (occurrence, mass and orbital distributions, dependency on the stellar mass) of these young giant planets.Methods. In this study, we present the observing and data analysis strategy, the ranking process of the detected candidates, and the survey performances for a subsample of 150 stars that are representative of the full SHINE sample. Observations were conducted in a homogeneous way between February 2015 and February 2017 with the dedicated ground-based VLT/SPHERE instrument equipped with the IFS integral field spectrograph and the IRDIS dual-band imager, covering a spectral range between 0.9 and 2.3 μm. We used coronographic, angular, and spectral differential imaging techniques to achieve the best detection performances for this study, down to the planetary mass regime.Results. We processed, in a uniform manner, more than 300 SHINE observations and datasets to assess the survey typical sensitivity as a function of the host star and of the observing conditions. The median detection performance reached 5σ-contrasts of 13 mag at 200 mas and 14.2 mag at 800 mas with the IFS (YJ and YJH bands), and of 11.8 mag at 200 mas, 13.1 mag at 800 mas, and 15.8 mag at 3 as with IRDIS in H band, delivering one of the deepest sensitivity surveys thus far for young, nearby stars. A total of sixteen substellar companions were imaged in this first part of SHINE: seven brown dwarf companions and ten planetary-mass companions.These include two new discoveries, HIP 65426 b and HIP 64892 B, but not the planets around PDS70 that had not been originally selected for the SHINE core sample. A total of 1483 candidates were detected, mainly in the large field of view that characterizes IRDIS. The color-magnitude diagrams, low-resolution spectrum (when available with IFS), and follow-up observations enabled us to identify the nature (background contaminant or comoving companion) of about 86% of our subsample. The remaining cases are often connected to crowded-field follow-up observations that were missing. Finally, even though SHINE was not initially designed for disk searches, we imaged twelve circumstellar disks, including three new detections around the HIP 73145, HIP 86598, and HD 106906 systems.Conclusions. Nowadays, direct imaging provides a unique opportunity to probe the outer part of exoplanetary systems beyond 10 au to explore planetary architectures, as highlighted by the discoveries of: one new exoplanet, one new brown dwarf companion, and three new debris disks during this early phase of SHINE. It also offers the opportunity to explore and revisit the physical and orbital properties of these young, giant planets and brown dwarf companions (relative position, photometry, and low-resolution spectrum in near-infrared, predicted masses, and contrast in order to search for additional companions). Finally, these results highlight the importance of finalizing the SHINE systematic observation of about 500 young, nearby stars for a full exploration of their outer part to explore the demographics of young giant planets beyond 10 au and to identify the most interesting systems for the next generation of high-contrast imagers on very large and extremely large telescopes.
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| 9. |
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| 10. |
- Tinetti, G., et al.
(författare)
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A chemical survey of exoplanets with ARIEL
- 2018
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Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 46:1, s. 135-209
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Tidskriftsartikel (refereegranskat)abstract
- Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.
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| 11. |
- Dalton, A. S., et al.
(författare)
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An updated radiocarbon-based ice margin chronology for the last deglaciation of the North American Ice Sheet Complex
- 2020
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 234
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Tidskriftsartikel (refereegranskat)abstract
- The North American Ice Sheet Complex (NAISC; consisting of the Laurentide, Cordilleran and Innuitian ice sheets) was the largest ice mass to repeatedly grow and decay in the Northern Hemisphere during the Quaternary. Understanding its pattern of retreat following the Last Glacial Maximum is critical for studying many facets of the Late Quaternary, including ice sheet behaviour, the evolution of Holocene landscapes, sea level, atmospheric circulation, and the peopling of the Americas. Currently, the most up-to-date and authoritative margin chronology for the entire ice sheet complex is featured in two publications (Geological Survey of Canada Open File 1574 [Dyke et al., 2003]; 'Quaternary Glaciations - Extent and Chronology, Part II' [Dyke, 2004]). These often-cited datasets track ice margin recession in 36 time slices spanning 18 ka to 1 ka (all ages in uncalibrated radiocarbon years) using a combination of geomorphology, stratigraphy and radiocarbon dating. However, by virtue of being over 15 years old, the ice margin chronology requires updating to reflect new work and important revisions. This paper updates the aforementioned 36 ice margin maps to reflect new data from regional studies. We also update the original radiocarbon dataset from the 2003/2004 papers with 1541 new ages to reflect work up to and including 2018. A major revision is made to the 18 ka ice margin, where Banks and Eglinton islands (once considered to be glacial refugia) are now shown to be fully glaciated. Our updated 18 ka ice sheet increased in areal extent from 17.81 to 18.37 million km(2), which is an increase of 3.1% in spatial coverage of the NAISC at that time. Elsewhere, we also summarize, region-by-region, significant changes to the deglaciation sequence. This paper integrates new information provided by regional experts and radiocarbon data into the deglaciation sequence while maintaining consistency with the original ice margin positions of Dyke et al. (2003) and Dyke (2004) where new information is lacking; this is a pragmatic solution to satisfy the needs of a Quaternary research community that requires up-to-date knowledge of the pattern of ice margin recession of what was once the world's largest ice mass. The 36 updated isochrones are available in PDF and shapefile format, together with a spreadsheet of the expanded radiocarbon dataset (n = 5195 ages) and estimates of uncertainty for each interval. (C) 2020 Elsevier Ltd. All rights reserved.
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| 12. |
- Kupers, LK, et al.
(författare)
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Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1893-
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Tidskriftsartikel (refereegranskat)abstract
- Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10−7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10−74) and BMI in pregnancy (3/914, p = 1.13x10−3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
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| 13. |
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| 14. |
- Warrington, N M, et al.
(författare)
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Maternal and fetal genetic contribution to gestational weight gain.
- 2018
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Ingår i: International journal of obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 42:4, s. 775-84
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Tidskriftsartikel (refereegranskat)abstract
- Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG.A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10543 mothers and 16317 offspring of European origin, with replication in 10660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight).Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10-8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG.We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.International Journal of Obesity advance online publication, 21 November 2017; doi:10.1038/ijo.2017.248.
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| 15. |
- Bonnefoy, M., et al.
(författare)
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First light of the VLT planet finder SPHERE IV. Physical and chemical properties of the planets around HR8799
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 587
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Tidskriftsartikel (refereegranskat)abstract
- Context. The system of four planets discovered around the intermediate-mass star HR8799 offers a unique opportunity to test planet formation theories at large orbital radii and to probe the physics and chemistry at play in the atmospheres of self-luminous young (similar to 30 Myr) planets. We recently obtained new photometry of the four planets and low-resolution (R similar to 30) spectra of HR8799 d and e with the SPHERE instrument (Paper III).Aims. In this paper (Paper IV), we aim to use these spectra and available photometry to determine how they compare to known objects, what the planet physical properties are, and how their atmospheres work.Methods. We compare the available spectra, photometry, and spectral energy distribution (SED) of the planets to field dwarfs and young companions. In addition, we use the extinction from corundum, silicate (enstatite and forsterite), or iron grains likely to form in the atmosphere of the planets to try to better understand empirically the peculiarity of their spectrophotometric properties. To conclude, we use three sets of atmospheric models (BT-SETTL14, Cloud-AE60, Exo-REM) to determine which ingredients are critically needed in the models to represent the SED of the objects, and to constrain their atmospheric parameters (T-eff, log g, M/H).Results. We find that HR8799d and e properties are well reproduced by those of L6-L8 dusty dwarfs discovered in the field, among which some are candidate members of young nearby associations. No known object reproduces well the properties of planets b and c. Nevertheless, we find that the spectra and WISE photometry of peculiar and/or young early-T dwarfs reddened by submicron grains made of corundum, iron, enstatite, or forsterite successfully reproduce the SED of these planets. Our analysis confirms that only the Exo-REM models with thick clouds fit (within 2 sigma) the whole set of spectrophotometric datapoints available for HR8799 d and e for T-eff = 1200 K, log g in the range 3.0-4.5, and M/H = +0.5. The models still fail to reproduce the SED of HR8799c and b. The determination of the metallicity, log g, and cloud thickness are degenerate.Conclusions. Our empirical analysis and atmospheric modelling show that an enhanced content in dust and decreased CIA of H-2 is certainly responsible for the deviation of the properties of the planet with respect to field dwarfs. The analysis suggests in addition that HR8799c and b have later spectral types than the two other planets, and therefore could both have lower masses.
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| 16. |
- Bonnefoy, M., et al.
(författare)
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The GJ 504 system revisited Combining interferometric, radial velocity, and high contrast imaging data
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 618
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Tidskriftsartikel (refereegranskat)abstract
- Context. The G-type star GJ504A is known to host a 3-35 M-Jup companion whose temperature, mass, and projected separation all contribute to making it a test case for planet formation theories and atmospheric models of giant planets and light brown dwarfs. Aims. We aim at revisiting the system age, architecture, and companion physical and chemical properties using new complementary interferometric, radial-velocity, and high-contrast imaging data. Methods. We used the CHARA interferometer to measure GJ504A's angular diameter and obtained an estimation of its radius in combination with the HIPPARCOS parallax. The radius was compared to evolutionary tracks to infer a new independent age range for the system. We collected dual imaging data with IRDIS on VLT/SPHERE to sample the near-infrared (1.02-2.25 mu m) spectral energy distribution (SED) of the companion. The SED was compared to five independent grids of atmospheric models (petitCODE, Exo-REM, BT-SETTL, Morley et al., and ATMO) to infer the atmospheric parameters of GJ 504b and evaluate model-to-model systematic errors. In addition, we used a specific model grid exploring the effect of different C/O ratios. Contrast limits from 2011 to 2017 were combined with radial velocity data of the host star through the MESS2 tool to define upper limits on the mass of additional companions in the system from 0.01 to 100 au. We used an MCMC fitting tool to constrain the companion's orbital parameters based on the measured astrometry, and dedicated formation models to investigate its origin. Results. We report a radius of 1.35 +/- 0.04 R-circle dot for GJ504A. The radius yields isochronal ages of 21 +/- 2 Myr or 4.0 +/- 1.8 Gyr for the system and line-of-sight stellar rotation axis inclination of 162.4(-4.3)(+3.8) degrees or 18.6(-3.8)(+4.3) degrees. We re-detect the companion in the Y2, Y3, J3, H2, and K1 dual-band images. The complete 1-4 mu m SED shape of GJ504b is best reproduced by T8-T9.5 objects with intermediate ages (<= 1.5Gyr), and/or unusual dusty atmospheres and/or super-solar metallicities. All atmospheric models yield T-eff = 550 +/- 50 K for GJ504b and point toward a low surface gravity (3.5-4.0 dex). The accuracy on the metallicity value is limited by model-to-model systematics; it is not degenerate with the C/O ratio. We derive log L/L-circle dot = 6.15 +/- 0.15 dex for the companion from the empirical analysis and spectral synthesis. The luminosity and T-eff yield masses of M = 1.3(-0.3)(+0.6) M-Jup and M = 23(-9)(+10) M-Jup for the young and old age ranges, respectively. The semi-major axis (sma) is above 27.8 au and the eccentricity is lower than 0.55. The posterior on GJ 504b's orbital inclination suggests a misalignment with the rotation axis of GJ 504A. We exclude additional objects (90% prob.) more massive than 2.5 and 30 M-Jup with semi-major axes in the range 0.01-80 au for the young and old isochronal ages, respectively. Conclusions. The mass and semi-major axis of GJ 504b are marginally compatible with a formation by disk-instability if the system is 4 Gyr old. The companion is in the envelope of the population of planets synthesized with our core-accretion model. Additional deep imaging and spectroscopic data with SPHERE and JWST should help to confirm the possible spin-orbit misalignment and refine the estimates on the companion temperature, luminosity, and atmospheric composition.
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| 17. |
- Stenman, U H, et al.
(författare)
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Summary report of the TD-3 workshop: characterization of 83 antibodies against prostate-specific antigen
- 1999
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Ingår i: Tumor Biology. - : Springer Science and Business Media LLC. - 1423-0380 .- 1010-4283. ; 20:Suppl. 1, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Twelve research groups participated in the ISOBM TD-3 Workshop in which the reactivity and specificity of 83 antibodies against prostate-specific antigen (PSA) were investigated. Using a variety of techniques including cross-inhibition assays, Western blotting, BIAcore, immunoradiometric assays and immunohistochemistry, the antibodies were categorized into six major groups which formed the basis for mapping onto two- and three-dimensional (2-D and 3-D) models of PSA. The overall findings of the TD-3 Workshop are summarized in this report. In agreement with all participating groups, three main antigenic domains were identified: free PSA-specific epitopes located in or close to amino acids 86-91; discontinuous epitopes specific for PSA without human kallikrein (hK2) cross-reactivity located at or close to amino acids 158-163; and continuous or linear epitopes shared between PSA and hK2 located close to amino acids 3-11. In addition, several minor and partly overlapping domains were also identified. Clearly, the characterization of antibodies from this workshop and the location of their epitopes on the 3-D model of PSA illustrate the importance of selecting appropriate antibody pairs for use in immunoassays. It is hoped that these findings and the epitope nomenclature described in this TD-3 Workshop are used as a standard for future evaluation of anti-PSA antibodies.
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| 18. |
- Castellanos-Jankiewicz, A., et al.
(författare)
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Short Article Hypothalamic bile acid-TGR5 signaling protects from obesity
- 2021
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 33:7
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Tidskriftsartikel (refereegranskat)abstract
- Bile acids (BAs) improve metabolism and exert anti-obesity effects through the activation of the Takeda G protein-coupled receptor 5 (TGR5) in peripheral tissues. TGR5 is also found in the brain hypothalamus, but whether hypothalamic BA signaling is implicated in body weight control and obesity pathophysiology remains unknown. Here we show that hypothalamic BA content is reduced in diet-induced obese mice. Central administration of BAs or a specific TGR5 agonist in these animals decreases body weight and fat mass by activating the sympathetic nervous system, thereby promoting negative energy balance. Conversely, genetic downregulation of hypothalamic TGR5 expression in the mediobasal hypothalamus favors the development of obesity and worsens established obesity by blunting sympathetic activity. Lastly, hypothalamic TGR5 signaling is required for the anti-obesity action of dietary BA supplementation. Together, these findings identify hypothalamic TGR5 signaling as a key mediator of a top-down neural mechanism that counteracts diet induced obesity.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Sandström, Camilla, Professor, 1967-, et al.
(författare)
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Mainstreaming biodiversity and nature's contributions to people in Europe and Central Asia: insights from IPBES to inform the CBD post-2020 agenda
- 2023
-
Ingår i: Ecosystems and People. - : Informa UK Limited. - 2639-5908 .- 2639-5916. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Recent global and regional assessments of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) show that Nature's Contributions to People (NCP) are under an alarming threat due to the continuing loss of biodiversity. These assessments call for increasing conservation efforts and a more sustainable use of biodiversity to enhance the chances of halting biodiversity loss and reversing current trends. One of the strategies to achieve change is to mainstream biodiversity into sectoral policies. Mainstreaming, a concept that can be traced back to the Brundtland report, promotes the integration of the environment into political, societal, and economic planning and decision-making. Based on the review of key studies undertaken during the regional assessment for Europe and Central Asia, we develop a stepwise approach to analyze the current status of mainstreaming of biodiversity and NCP. The approach can be used both for policy design purposes and diagnostic evaluations. It demonstrates that mainstreaming has the potential to improve the conservation and sustainable use of biodiversity as well as the sustained provision of NCP. However, based on the status of implementation across Europe and Central Asia, we conclude that mainstreaming needs to be pursued and implemented in a stronger and more systematic way. The results of our assessment provide important input to national strategies and policies but also to the ongoing process of the Conference of the Parties to the Convention on Biological Diversity while developing the post-2020 global biodiversity framework.
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| 23. |
- Sordo, Rosanna, et al.
(författare)
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Stellar libraries for Gaia
- 2011
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Ingår i: Journal of Physics, Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 328:Conference 1, s. 012006-
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Tidskriftsartikel (refereegranskat)abstract
- Gaia will observe up to a billion stellar sources. Automated algorithms are under development to derive the atmospheric parameters of all observed spectra, from low resolution optical spectra alone or in synergy with high resolution spectra in the near-IR Ca II triplet region. To do so, a large database of state-of-the-art stellar libraries has been produced for the Gaia community, computed using different codes optimized for specific purposes. The choice to use different spectral codes in different regions of the H-R diagram raises the problem of the coherence of the different spectra, specifically in the transition zones. We present a comparison between the libraries from the point of view of spectra simulations for training the Gaia algorithms. We also present the implementation of these libraries into a Simple Stellar Population code.
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| 24. |
- Tyrrell, Jessica, et al.
(författare)
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Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight.
- 2016
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 315:11, s. 1129-40
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Tidskriftsartikel (refereegranskat)abstract
- Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain.To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight.Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30,487 women in 18 studies were analyzed. Participants were of European ancestry from population- or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term, singleton offspring born between 1929 and 2013 were included.Genetic scores for BMI, fasting glucose level, type 2 diabetes, systolic blood pressure (SBP), triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, vitamin D status, and adiponectin level.Offspring birth weight from 18 studies.Among the 30,487 newborns the mean birth weight in the various cohorts ranged from 3325 g to 3679 g. The maternal genetic score for BMI was associated with a 2-g (95% CI, 0 to 3 g) higher offspring birth weight per maternal BMI-raising allele (P=.008). The maternal genetic scores for fasting glucose and SBP were also associated with birth weight with effect sizes of 8 g (95% CI, 6 to 10 g) per glucose-raising allele (P=7×10(-14)) and -4 g (95% CI, -6 to -2 g) per SBP-raising allele (P=1×10(-5)), respectively. A 1-SD (≈4 points) genetically higher maternal BMI was associated with a 55-g higher offspring birth weight (95% CI, 17 to 93 g). A 1-SD (≈7.2 mg/dL) genetically higher maternal fasting glucose concentration was associated with 114-g higher offspring birth weight (95% CI, 80 to 147 g). However, a 1-SD (≈10 mm Hg) genetically higher maternal SBP was associated with a 208-g lower offspring birth weight (95% CI, -394 to -21 g). For BMI and fasting glucose, genetic associations were consistent with the observational associations, but for systolic blood pressure, the genetic and observational associations were in opposite directions.In this mendelian randomization study, genetically elevated maternal BMI and blood glucose levels were potentially causally associated with higher offspring birth weight, whereas genetically elevated maternal SBP was potentially causally related to lower birth weight. If replicated, these findings may have implications for counseling and managing pregnancies to avoid adverse weight-related birth outcomes.
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| 25. |
- Veronese, N., et al.
(författare)
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Inverse relationship between body mass index and mortality in older nursing home residents : a meta-analysis of 19,538 elderly subjects
- 2015
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Ingår i: Obesity Reviews. - : Wiley. - 1467-7881 .- 1467-789X. ; 16:11, s. 1001-1015
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Forskningsöversikt (refereegranskat)abstract
- Body mass index (BMI) and mortality in old adults from the general population have been related in a U-shaped or J-shaped curve. However, limited information is available for elderly nursing home populations, particularly about specific cause of death. A systematic PubMed/EMBASE/CINAHL/SCOPUS search until 31 May 2014 without language restrictions was conducted. As no published study reported mortality in standard BMI groups (<18.5, 18.5-24.9, 25-29.9, 30kg/m(2)), the most adjusted hazard ratios (HRs) according to a pre-defined list of covariates were obtained from authors and pooled by random-effect model across each BMI category. Out of 342 hits, 20 studies including 19,538 older nursing home residents with 5,223 deaths during a median of 2 years of follow-up were meta-analysed. Compared with normal weight, all-cause mortality HRs were 1.41 (95% CI=1.26-1.58) for underweight, 0.85 (95% CI=0.73-0.99) for overweight and 0.74 (95% CI=0.57-0.96) for obesity. Underweight was a risk factor for higher mortality caused by infections (HR=1.65 [95% CI=1.13-2.40]). RR results corroborated primary HR results, with additionally lower infection-related mortality in overweight and obese than in normal-weight individuals. Like in the general population, underweight is a risk factor for mortality in old nursing home residents. However, uniquely, not only overweight but also obesity is protective, which has relevant nutritional goal implications in this population/setting.
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| 26. |
- Beaumont, Robin N, et al.
(författare)
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Genome-wide association study of offspring birth weight in 86,577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.
- 2018
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 1460-2083 .- 0964-6906. ; 27:4, s. 742-756
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P<5x10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
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| 27. |
- Formiga-Cruz, M, et al.
(författare)
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Evaluation of potential indicators of viral contamination in shellfish and their applicability to diverse geographical areas.
- 2003
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Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 69:3, s. 1556-63
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Tidskriftsartikel (refereegranskat)abstract
- The distribution of the concentration of potential indicators of fecal viral pollution in shellfish was analyzed under diverse conditions over 18 months in diverse geographical areas. These microorganisms have been evaluated in relation to contamination by human viral pathogens detected in parallel in the analyzed shellfish samples. Thus, significant shellfish-growing areas from diverse countries in the north and south of Europe (Greece, Spain, Sweden, and the United Kingdom) were defined and studied by analyzing different physicochemical parameters in the water and the levels of Escherichia coli, F-specific RNA bacteriophages, and phages infecting Bacteroides fragilis strain RYC2056 in the shellfish produced, before and after depuration treatments. A total of 475 shellfish samples were studied, and the results were statistically analyzed. According to statistical analysis, the presence of human viruses seems to be related to the presence of all potential indicators in the heavily contaminated areas, where E. coli would probably be suitable as a fecal indicator. The F-RNA phages, which are present in higher numbers in Northern Europe, seem to be significantly related to the presence of viral contamination in shellfish, with a very weak predictive value for hepatitis A virus, human adenovirus, and enterovirus and a stronger one for Norwalk-like virus. However, it is important to note that shellfish produced in A or clean B areas can sporadically contain human viruses even in the absence of E. coli or F-RNA phages. The data presented here will be useful in defining microbiological parameters for improving the sanitary control of shellfish consumed raw or barely cooked.
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| 28. |
- Merid, Simon Kebede, et al.
(författare)
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Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
- 2020
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Ingår i: Genome Medicine. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 1756-994X.
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
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| 29. |
- Müller, Christoph, et al.
(författare)
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Global gridded crop model evaluation : Benchmarking, skills, deficiencies and implications
- 2017
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 10:4, s. 1403-1422
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Tidskriftsartikel (refereegranskat)abstract
- Crop models are increasingly used to simulate crop yields at the global scale, but so far there is no general framework on how to assess model performance. Here we evaluate the simulation results of 14 global gridded crop modeling groups that have contributed historic crop yield simulations for maize, wheat, rice and soybean to the Global Gridded Crop Model Intercomparison (GGCMI) of the Agricultural Model Intercomparison and Improvement Project (AgMIP). Simulation results are compared to reference data at global, national and grid cell scales and we evaluate model performance with respect to time series correlation, spatial correlation and mean bias. We find that global gridded crop models (GGCMs) show mixed skill in reproducing time series correlations or spatial patterns at the different spatial scales. Generally, maize, wheat and soybean simulations of many GGCMs are capable of reproducing larger parts of observed temporal variability (time series correlation coefficients (r) of up to 0.888 for maize, 0.673 for wheat and 0.643 for soybean at the global scale) but rice yield variability cannot be well reproduced by most models. Yield variability can be well reproduced for most major producing countries by many GGCMs and for all countries by at least some. A comparison with gridded yield data and a statistical analysis of the effects of weather variability on yield variability shows that the ensemble of GGCMs can explain more of the yield variability than an ensemble of regression models for maize and soybean, but not for wheat and rice. We identify future research needs in global gridded crop modeling and for all individual crop modeling groups. In the absence of a purely observation-based benchmark for model evaluation, we propose that the best performing crop model per crop and region establishes the benchmark for all others, and modelers are encouraged to investigate how crop model performance can be increased. We make our evaluation system accessible to all crop modelers so that other modeling groups can also test their model performance against the reference data and the GGCMI benchmark.
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| 30. |
- Müller, Christoph, et al.
(författare)
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The Global Gridded Crop Model Intercomparison phase 1 simulation dataset
- 2019
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- The Global Gridded Crop Model Intercomparison (GGCMI) phase 1 dataset of the Agricultural Model Intercomparison and Improvement Project (AgMIP) provides an unprecedentedly large dataset of crop model simulations covering the global ice-free land surface. The dataset consists of annual data fields at a spatial resolution of 0.5 arc-degree longitude and latitude. Fourteen crop modeling groups provided output for up to 11 historical input datasets spanning 1901 to 2012, and for up to three different management harmonization levels. Each group submitted data for up to 15 different crops and for up to 14 output variables. All simulations were conducted for purely rainfed and near-perfectly irrigated conditions on all land areas irrespective of whether the crop or irrigation system is currently used there. With the publication of the GGCMI phase 1 dataset we aim to promote further analyses and understanding of crop model performance, potential relationships between productivity and environmental impacts, and insights on how to further improve global gridded crop model frameworks. We describe dataset characteristics and individual model setup narratives.
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| 31. |
- Pervjakova, Natalia, et al.
(författare)
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Multi-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes
- 2022
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 31:19, s. 3377-3391
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Tidskriftsartikel (refereegranskat)abstract
- Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy (GenDIP) Consortium assembled genome-wide association studies (GWAS) of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (p < 5x10-8) with GDM, mapping to/near MTNR1B (p = 4.3x10-54), TCF7L2 (p = 4.0x10-16), CDKAL1 (p = 1.6 × 10-14), CDKN2A-CDKN2B (p = 4.1x10-9) and HKDC1 (p = 2.9x10-8). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D; and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomisation analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.
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| 32. |
- Ruane, Alex C., et al.
(författare)
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Strong regional influence of climatic forcing datasets on global crop model ensembles
- 2021
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Ingår i: Agricultural and Forest Meteorology. - : Elsevier BV. - 0168-1923. ; 300
-
Tidskriftsartikel (refereegranskat)abstract
- We present results from the Agricultural Model Intercomparison and Improvement Project (AgMIP) Global Gridded Crop Model Intercomparison (GGCMI) Phase I, which aligned 14 global gridded crop models (GGCMs) and 11 climatic forcing datasets (CFDs) in order to understand how the selection of climate data affects simulated historical crop productivity of maize, wheat, rice and soybean. Results show that CFDs demonstrate mean biases and differences in the probability of extreme events, with larger uncertainty around extreme precipitation and in regions where observational data for climate and crop systems are scarce. Countries where simulations correlate highly with reported FAO national production anomalies tend to have high correlations across most CFDs, whose influence we isolate using multi-GGCM ensembles for each CFD. Correlations compare favorably with the climate signal detected in other studies, although production in many countries is not primarily climate-limited (particularly for rice). Bias-adjusted CFDs most often were among the highest model-observation correlations, although all CFDs produced the highest correlation in at least one top-producing country. Analysis of larger multi-CFD-multi-GGCM ensembles (up to 91 members) shows benefits over the use of smaller subset of models in some regions and farming systems, although bigger is not always better. Our analysis suggests that global assessments should prioritize ensembles based on multiple crop models over multiple CFDs as long as a top-performing CFD is utilized for the focus region.
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| 33. |
- Vallenari, A., et al.
(författare)
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Synthetic stellar libraries and SSP simulations in the Gaia Era
- 2009
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Ingår i: Proceedings of the International Astronomical Union. ; , s. 444-445
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Konferensbidrag (refereegranskat)abstract
- The Gaia mission will obtain accurate positions, parallaxes and proper motions for 109 object all over the sky. In addition, it will collect low resolution spectroscopy in the optical range for ∼ 109 objects, stars, galaxies, and QSOs. Parameters of those objects are expected to be part of the final Catalog. Complete and up-to-date libraries of synthetic stellar spectra are needed to train the algorithms to classify this huge amount of data. Here we focus on the use of the synthetic libraries of spectra calculated by the Gaia community to derive grids of Single Stellar Populations as building blocks of population synthesis models. © International Astronomical Union 2010.
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| 34. |
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Allard, Per, et al.
(författare)
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Loss of dopamine uptake sites labeled with [3H]GBR-12935 in Alzheimer's disease.
- 1990
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Ingår i: European Neurology. - 0014-3022 .- 1421-9913. ; 30:4, s. 181-5
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Tidskriftsartikel (refereegranskat)abstract
- The binding of the dopamine uptake inhibitor [3H]GBR-12935 to postmortem putamen from a control group and patients with Alzheimer's disease/senile dementia of Alzheimer type (AD/SDAT) or vascular dementia (VD) was studied. The binding density (Bmax) in AD/SDAT was significantly reduced to 50% of control. A reduction of Bmax in VD was also noted, but it did not reach statistical significance. No differences in apparent binding affinity (Kd) between controls and dementia groups were obtained. The concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid were also determined. The concentrations of DA and DOPAC were reduced by 30-40% in AD/SDAT and VD, but the reductions did not reach statistical significance. The concentration of 3-MT was reduced by 40% in AD/SDAT and by 30% in VD. The [3H]GBR-12935-binding densities correlated significantly with corresponding concentrations of DA in control brains. It is suggested that the loss of [3H]GBR-12935-binding sites in human putamen in AD/SDAT reflects a degeneration of dopamine neurites.
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| 39. |
- Bergh, Johanna, et al.
(författare)
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No link between viral findings in the prostate and subsequent cancer development
- 2007
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Ingår i: British Journal of Cancer. - London : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 96:1, s. 137-139
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Tidskriftsartikel (refereegranskat)abstract
- In an investigation of 201 prostate tissue samples from patients with benign prostate hyperplasia that later progressed to prostate cancer and 201 matched controls that did not, there were no differences in the prevalence of adenovirus, herpesvirus, papilloma virus, polyoma virus and Candida albicans DNA.
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| 40. |
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| 41. |
- Formiga-Cruz, M., et al.
(författare)
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Distribution of human virus contamination in shellfish from different growing areas in Greece, Spain, Sweden, and the United Kingdom
- 2002
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Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 68:12, s. 5990-5998
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Tidskriftsartikel (refereegranskat)abstract
- Viral pollution in shellfish has been analyzed simultaneously across a wide range of geographical regions, with emphasis on the concomitant variations in physicochemical characteristics and social features. The methods for sample treatment and for the detection of human enteric viruses were optimized by the participating laboratories. The second part of this study involves the selection of a protocol for virus detection, which was validated by analyzing the distribution and concentration of human viral pathogens under diverse conditions during an 18-month period in four European countries. Shellfish-growing areas from diverse countries in the north and south of Europe were defined and studied, and the microbiological quality of the shellfish was analyzed. Human adenovirus, Norwalk-like virus, and enterovirus were identified as contaminants of shellfish in all the participating countries. Hepatitis A virus was also isolated in all areas except Sweden. The seasonal distribution of viral contamination was also described. Norwalk-like virus appeared to be the only group of viruses that demonstrated seasonal variation, with lower concentrations occurring during warm months. The depuration treatments currently applied were shown to be adequate for reducing Escherichia coli levels but ineffective for the elimination of viral particles. The human adenoviruses detected by PCR correlate with the presence of other human viruses and could be useful as a molecular index of viral contamination in shellfish.
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| 42. |
- Formiga-Cruz, M, et al.
(författare)
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Evaluation of potential indicators of viral contamination in shellfish and their applicability to diverse geographical areas
- 2003
-
Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 69:3, s. 1556-1563
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Tidskriftsartikel (refereegranskat)abstract
- The distribution of the concentration of potential indicators of fecal viral pollution in shellfish was analyzed under diverse conditions over 18 months in diverse geographical areas. These microorganisms have been evaluated in relation to contamination by human viral pathogens detected in parallel in the analyzed shellfish samples. Thus, significant shellfish-growing areas from diverse countries in the north and south of Europe (Greece, Spain, Sweden, and the United Kingdom) were defined and studied by analyzing different physicochemical parameters in the water and the levels of Escherichia coli, F-specific RNA bacteriophages, and phages infecting Bacteroides fragilis strain RYC2056 in the shellfish produced, before and after depuration treatments. A total of 475 shellfish samples were studied, and the results were statistically analyzed. According to statistical analysis, the presence of human viruses seems to be related to the presence of all potential indicators in the heavily contaminated areas, where E. coli would probably be suitable as a fecal indicator. The F-RNA phages, which are present in higher numbers in Northern Europe, seem to be significantly related to the presence of viral contamination in shellfish, with a very weak predictive value for hepatitis A virus, human adenovirus, and enterovirus and a stronger one for Norwalk-like virus. However, it is important to note that shellfish produced in A or clean B areas can sporadically contain human viruses even in the absence of E. coli or F-RNA phages. The data presented here will be useful in defining microbiological parameters for improving the sanitary control of shellfish consumed raw or barely cooked.
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| 43. |
- Hernroth, Bodil, 1951, et al.
(författare)
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Environmental factors influencing human viral pathogens and their potential indicator organisms in the blue mussel, Mytilus edulis: the first Scandinavian report
- 2002
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Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 68:9, s. 4523-4533
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Tidskriftsartikel (refereegranskat)abstract
- This study was carried out in order to investigate human enteric virus contaminants in mussels from three sites on the west coast of Sweden, representing a gradient of anthropogenic influence. Mussels were sampled monthly during the period from February 2000 to July 2001 and analyzed for adeno-, entero-, Norwalk-like, and hepatitis A viruses as well as the potential viral indicator organisms somatic coliphages, F-specific RNA bacteriophages, bacteriophages infecting Bacteroides fragilis, and Escherichia coli. The influence of environmental factors such as water temperature, salinity, and land runoff on the occurrence of these microbes was also included in this study. Enteric viruses were found in 50 to 60% of the mussel samples, and there were no pronounced differences between the samples from the three sites. E. coli counts exceeded the limit for category A for shellfish sanitary safety in 40% of the samples from the sites situated in fjords. However, at the site in the outer archipelago, this limit was exceeded only once, in March 2001, when extremely high levels of atypical indole-negative strains of E. coli were registered at all three sites. The environmental factors influenced the occurrence of viruses and phages differently, and therefore, it was hard to find a coexistence between them. This study shows that, for risk assessment, separate modeling should be done for every specific area, with special emphasis on environmental factors such as temperature and land runoff. The present standard for human fecal contamination, E. coli, seems to be an acceptable indicator of only local sanitary contamination; it is not a reliable indicator of viral contaminants in mussels. To protect consumers and get verification of "clean" mussels, it seems necessary to analyze for viruses as well. The use of a molecular index of the human contamination of Swedish shellfish underscores the need for reference laboratories with high-technology facilities.
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| 44. |
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| 45. |
- Krantz-Rülcker, C., et al.
(författare)
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Adsorption of IIB-metals by three common soil fungi-comparison and assessment of importance for metal distribution in natural soil systems
- 1996
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Ingår i: Soil Biology and Biochemistry. - : Elsevier. - 0038-0717 .- 1879-3428. ; 28:7, s. 967-975
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Tidskriftsartikel (refereegranskat)abstract
- Interactions of IIb-elements, Zn, Cd and Hg, with three common soil fungi, Trichoderma harzianum, Penicillium spinulosum and Mortierella isabellina, have been studied. The accumulation of the metals by the fungi was studied as a function of pH at constant ionic strength and at concentration levels of the metals representative of natural systems. Two stages of fungal activity were considered in the experiments. The fungi generally exhibited high affinity for metal ions indicated by distribution coefficients (log K-d, in 1 kg(-1)) of about 3.5 +/- 1, 2.5 +/- 1 and 4 +/- 1 for Zn, Cd and Hg, respectively. The pH-dependence of the accumulation as well as the isotherms at constant pH were similar between the fungi, and the maximum capacities were at least 50 mmoles kg(-1) mycelium (dw). Metal accumulation by starved mycelia was almost independent of pH, while non-starved mycelia in two cases accumulated more metals at low pH. Calculations of the distribution of metals in a model soil system of inorganic and organic constituents as well as fungal biomass indicated that the amounts of metal associated to the fungi are negligible at neutral pH. However, due to the ability of these fungi to accumulate metals independently of pH, the fraction of metals associated to fungal biomass at low pH may be significant, and, in some cases, predominant. This illustrates that the effects of fungi on metal distribution in soil should not be neglected, e.g. during a progressing acidification.
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| 46. |
- Krantz-Rülcker, C., et al.
(författare)
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Interactions between a soil fungus, Trichoderma harzianum, and IIb metals—adsorption to mycelium and production of complexing metabolites
- 1993
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Ingår i: Biometals. - : Springer. - 0966-0844 .- 1572-8773. ; 6:4, s. 223-230
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Tidskriftsartikel (refereegranskat)abstract
- Fungi are capable of accumulating metals and, in soil, such accumulation may influence metal speciation and transport. The interactions between a common soil fungus, Trichoderma harzianum, and IIb elements were studied in the present investigation. The accumulation of the metals zinc, cadmium and mercury by starved and non-starved mycelium at different pH was determined by a batch technique using radioactive tracers; uptake of the metals was found to be large, with respective distribution coefficients of about 10(3.5), 10(2.5) and 10(4.0) for zinc, cadmium and mercury, respectively. Metal accumulation by a starved system was largely independent of pH in the range 3-9, where in a non-starved system an increased accumulation of zinc (at 10(-8) m) was observed at low pH (3-5). Potentiometric titrations performed on the two systems revealed significant differences in acid capacities, i.e. values close to zero for the starved system and 500-800 meq kg-1 for the non-starved system. The maximum metal uptake was at least 50 mmol kg-1 at pH 6.5 (calculated from adsorption isotherms). The present findings suggests that in the non-starved system a metabolite is produced and then released when the pH is within a certain range.
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| 47. |
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| 48. |
- Lopez-Garcia, SC, et al.
(författare)
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Treatment and long-term outcome in primary distal renal tubular acidosis
- 2019
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 34:6, s. 981-991
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Tidskriftsartikel (refereegranskat)
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| 49. |
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| 50. |
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