| 1. |
- Lind, Lars, et al.
(författare)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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| 2. |
- Bixby, H., et al.
(författare)
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Rising rural body-mass index is the main driver of the global obesity epidemic in adults
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
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Tidskriftsartikel (refereegranskat)abstract
- Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
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| 3. |
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| 4. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 5. |
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| 6. |
- Abdalla, H., et al.
(författare)
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Sensitivity of the Cherenkov Telescope Array for probing cosmology and fundamental physics with gamma-ray propagation
- 2021
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : Institute of Physics Publishing (IOPP). - 1475-7516. ; :2
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Tidskriftsartikel (refereegranskat)abstract
- The Cherenkov Telescope Array (CTA), the new-generation ground-based observatory for gamma-ray astronomy, provides unique capabilities to address significant open questions in astrophysics, cosmology, and fundamental physics. We study some of the salient areas of gamma-ray cosmology that can be explored as part of the Key Science Projects of CTA, through simulated observations of active galactic nuclei (AGN) and of their relativistic jets. Observations of AGN with CTA will enable a measurement of gamma-ray absorption on the extragalactic background light with a statistical uncertainty below 15% up to a redshift z = 2 and to constrain or detect gamma-ray halos up to intergalactic-magnetic-field strengths of at least 0.3 pG. Extragalactic observations with CTA also show promising potential to probe physics beyond the Standard Model. The best limits on Lorentz invariance violation from gamma-ray astronomy will be improved by a factor of at least two to three. CTA will also probe the parameter space in which axion-like particles could constitute a significant fraction, if not all, of dark matter. We conclude on the synergies between CTA and other upcoming facilities that will foster the growth of gamma-ray cosmology.
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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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| 11. |
- Acero, F., et al.
(författare)
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Prospects for Cherenkov Telescope Array Observations of the Young Supernova Remnant RX J1713.7-3946
- 2017
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 840:2
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Tidskriftsartikel (refereegranskat)abstract
- We perform simulations for future Cherenkov Telescope Array (CTA) observations of RX J1713.7-3946, a young supernova remnant (SNR) and one of the brightest sources ever discovered in very high energy (VHE) gamma rays. Special attention is paid to exploring possible spatial (anti) correlations of gamma rays with emission at other wavelengths, in particular X-rays and CO/H I emission. We present a series of simulated images of RX J1713.7-3946 for CTA based on a set of observationally motivated models for the gamma-ray emission. In these models, VHE gamma rays produced by high-energy electrons are assumed to trace the nonthermal X-ray emission observed by XMM-Newton, whereas those originating from relativistic protons delineate the local gas distributions. The local atomic and molecular gas distributions are deduced by the NANTEN team from CO and H I observations. Our primary goal is to show how one can distinguish the emission mechanism(s) of the gamma rays (i.e., hadronic versus leptonic, or a mixture of the two) through information provided by their spatial distribution, spectra, and time variation. This work is the first attempt to quantitatively evaluate the capabilities of CTA to achieve various proposed scientific goals by observing this important cosmic particle accelerator.
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| 12. |
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| 13. |
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| 14. |
- Amati, L., et al.
(författare)
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The THESEUS space mission concept : science case, design and expected performances
- 2018
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Ingår i: Advances in Space Research. - : ELSEVIER SCI LTD. - 0273-1177 .- 1879-1948. ; 62:1, s. 191-244
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Tidskriftsartikel (refereegranskat)abstract
- THESEUS is a space mission concept aimed at exploiting Gamma-Ray Bursts for investigating the early Universe and at providing a substantial advancement of multi-messenger and time-domain astrophysics. These goals will be achieved through a unique combination of instruments allowing GRB and X-ray transient detection over a broad field of view (more than 1 sr) with 0.5-1 arcmin localization, an energy band extending from several MeV down to 0.3 keV and high sensitivity to transient sources in the soft X-ray domain, as well as on-board prompt (few minutes) follow-up with a 0.7 m class IR telescope with both imaging and spectroscopic capabilities. THESEUS will be perfectly suited for addressing the main open issues in cosmology such as, e.g., star formation rate and metallicity evolution of the inter-stellar and intra-galactic medium up to redshift similar to 10, signatures of Pop III stars, sources and physics of re-ionization, and the faint end of the galaxy luminosity function. In addition, it will provide unprecedented capability to monitor the X-ray variable sky, thus detecting, localizing, and identifying the electromagnetic counterparts to sources of gravitational radiation, which may be routinely detected in the late '20s/early '30s by next generation facilities like aLIGO/ aVirgo, eLISA, KAGRA, and Einstein Telescope. THESEUS will also provide powerful synergies with the next generation of multi-wavelength observatories (e.g., LSST, ELT, SKA, CTA, ATHENA).
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| 15. |
- Axelsson, Magnus, et al.
(författare)
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GRB110721A : AN EXTREME PEAK ENERGY AND SIGNATURES OF THE PHOTOSPHERE
- 2012
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Ingår i: Astrophysical Journal Letters. - 2041-8205. ; 757:2
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Tidskriftsartikel (refereegranskat)abstract
- GRB110721A was observed by the Fermi Gamma-ray Space Telescope using its two instruments, the Large Area Telescope (LAT) and the Gamma-ray Burst Monitor (GBM). The burst consisted of one major emission episode which lasted for similar to 24.5 s (in the GBM) and had a peak flux of (5.7 +/- 0.2) x 10(-5) erg s(-1) cm(-2). The time-resolved emission spectrum is best modeled with a combination of a Band function and a blackbody spectrum. The peak energy of the Band component was initially 15 +/- 2 MeV, which is the highest value ever detected in a GRB. This measurement was made possible by combining GBM/BGO data with LAT Low Energy events to achieve continuous 10-100 MeV coverage. The peak energy later decreased as a power law in time with an index of -1.89 +/- 0.10. The temperature of the blackbody component also decreased, starting from similar to 80 keV, and the decay showed a significant break after similar to 2 s. The spectrum provides strong constraints on the standard synchrotron model, indicating that alternative mechanisms may give rise to the emission at these energies.
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| 16. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 17. |
- Tuskan, G A, et al.
(författare)
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The genome of black cottonwood, Populus trichocarpa (Torr. & Gray).
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 313:5793, s. 1596-604
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Tidskriftsartikel (refereegranskat)abstract
- We report the draft genome of the black cottonwood tree, Populus trichocarpa. Integration of shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction of the genome. More than 45,000 putative protein-coding genes were identified. Analysis of the assembled genome revealed a whole-genome duplication event; about 8000 pairs of duplicated genes from that event survived in the Populus genome. A second, older duplication event is indistinguishably coincident with the divergence of the Populus and Arabidopsis lineages. Nucleotide substitution, tandem gene duplication, and gross chromosomal rearrangement appear to proceed substantially more slowly in Populus than in Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene. However, the relative frequency of protein domains in the two genomes is similar. Overrepresented exceptions in Populus include genes associated with lignocellulosic wall biosynthesis, meristem development, disease resistance, and metabolite transport.
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| 18. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 19. |
- Werren, John H, et al.
(författare)
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Functional and evolutionary insights from the genomes of three parasitoid Nasonia species.
- 2010
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 327:5963, s. 343-8
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Tidskriftsartikel (refereegranskat)abstract
- We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.
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| 20. |
- Freitag, Daniel F., et al.
(författare)
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Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis
- 2015
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Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595. ; 3:4, s. 243-253
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Tidskriftsartikel (refereegranskat)abstract
- Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND.
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| 21. |
- Hillier, Ladeana W, et al.
(författare)
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Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
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Tidskriftsartikel (refereegranskat)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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| 22. |
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| 23. |
- Sungnak, W., et al.
(författare)
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SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes
- 2020
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Ingår i: Nature Medicine. - : Nature Research. - 1078-8956 .- 1546-170X. ; 26:5, s. 681-687
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Tidskriftsartikel (refereegranskat)abstract
- We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells’ potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org.
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| 24. |
- Greiner, J., et al.
(författare)
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GRIPS - Gamma-Ray Imaging, Polarimetry and Spectroscopy
- 2012
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 34:2, s. 551-582
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Tidskriftsartikel (refereegranskat)abstract
- We propose to perform a continuously scanning all-sky survey from 200 keV to 80 MeV achieving a sensitivity which is better by a factor of 40 or more compared to the previous missions in this energy range (COMPTEL, INTEGRAL; see Fig. 1). These gamma-ray observations will be complemented by observations in the soft X-ray and (near-)infrared region with the corresponding telescopes placed on a separate satellite. The Gamma-Ray Imaging, Polarimetry and Spectroscopy ("GRIPS") mission with its three instruments Gamma-Ray Monitor (GRM), X-Ray Monitor (XRM) and InfraRed Telescope (IRT) addresses fundamental questions in ESA's Cosmic Vision plan. Among the major themes of the strategic plan, GRIPS has its focus on the evolving, violent Universe, exploring a unique energy window. We propose to investigate γ-ray bursts and blazars, the mechanisms behind supernova explosions, nucleosynthesis and spallation, the enigmatic origin of positrons in our Galaxy, and the nature of radiation processes and particle acceleration in extreme cosmic sources including pulsars and magnetars. The natural energy scale for these non-thermal processes is of the order of MeV. Although they can be partially and indirectly studied using other methods, only the proposed GRIPS measurements will provide direct access to their primary photons. GRIPS will be a driver for the study of transient sources in the era of neutrino and gravitational wave observatories such as IceCUBE and LISA, establishing a new type of diagnostics in relativistic and nuclear astrophysics. This will support extrapolations to investigate star formation, galaxy evolution, and black hole formation at high redshifts.
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| 25. |
- Pellissier, V., et al.
(författare)
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Effects of Natura 2000 on nontarget bird and butterfly species based on citizen science data
- 2020
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Ingår i: Conservation Biology. - : Wiley. - 0888-8892 .- 1523-1739. ; 34:3, s. 666-676
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Tidskriftsartikel (refereegranskat)abstract
- The European Union's Natura 2000 (N2000) is among the largest international networks of protected areas. One of its aims is to secure the status of a predetermined set of (targeted) bird and butterfly species. However, nontarget species may also benefit from N2000. We evaluated how the terrestrial component of this network affects the abundance of nontargeted, more common bird and butterfly species based on data from long-term volunteer-based monitoring programs in 9602 sites for birds and 2001 sites for butterflies. In almost half of the 155 bird species assessed, and particularly among woodland specialists, abundance increased (slope estimates ranged from 0.101 [SD 0.042] to 3.51 [SD 1.30]) as the proportion of landscape covered by N2000 sites increased. This positive relationship existed for 27 of the 104 butterfly species (estimates ranged from 0.382 [SD 0.163] to 4.28 [SD 0.768]), although most butterflies were generalists. For most species, when land-cover covariates were accounted for these positive relationships were not evident, meaning land cover may be a determinant of positive effects of the N2000 network. The increase in abundance as N2000 coverage increased correlated with the specialization index for birds, but not for butterflies. Although the N2000 network supports high abundance of a large spectrum of species, the low number of specialist butterflies with a positive association with the N2000 network shows the need to improve the habitat quality of N2000 sites that could harbor open-land butterfly specialists. For a better understanding of the processes involved, we advocate for standardized collection of data at N2000 sites.
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| 26. |
- Botvinik-Nezer, Rotem, et al.
(författare)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 27. |
- Sikkema, Lisa, et al.
(författare)
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An integrated cell atlas of the lung in health and disease
- 2023
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Ingår i: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 29:6, s. 1563-1577
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Tidskriftsartikel (refereegranskat)abstract
- Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1 + profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.
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| 28. |
- Bowers, Robert M., et al.
(författare)
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Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea
- 2017
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Ingår i: Nature Biotechnology. - : NATURE PUBLISHING GROUP. - 1087-0156 .- 1546-1696. ; 35:8, s. 725-731
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Tidskriftsartikel (refereegranskat)abstract
- We present two standards developed by the Genomic Standards Consortium (GSC) for reporting bacterial and archaeal genome sequences. Both are extensions of the Minimum Information about Any (x) Sequence (MIxS). The standards are the Minimum Information about a Single Amplified Genome (MISAG) and the Minimum Information about a Metagenome-Assembled Genome (MIMAG), including, but not limited to, assembly quality, and estimates of genome completeness and contamination. These standards can be used in combination with other GSC checklists, including the Minimum Information about a Genome Sequence (MIGS), Minimum Information about a Metagenomic Sequence (MIMS), and Minimum Information about a Marker Gene Sequence (MIMARKS). Community-wide adoption of MISAG and MIMAG will facilitate more robust comparative genomic analyses of bacterial and archaeal diversity.
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| 29. |
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| 30. |
- Palafox, B., et al.
(författare)
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Does greater individual social capital improve the management of hypertension? Cross-national analysis of 61 229 individuals in 21 countries
- 2017
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Ingår i: Bmj Global Health. - : BMJ. - 2059-7908. ; 2:4
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Social capital, characterised by trust, reciprocity and cooperation, is positively associated with a number of health outcomes. We test the hypothesis that among hypertensive individuals, those with greater social capital are more likely to have their hypertension detected, treated and controlled. Methods Cross-sectional data from 21 countries in the Prospective Urban and Rural Epidemiology study were collected covering 61 229 hypertensive individuals aged 35-70 years, their households and the 656 communities in which they live. Outcomes include whether hypertensive participants have their condition detected, treated and/or controlled. Multivariate statistical models adjusting for community fixed effects were used to assess the associations of three social capital measures: (1) membership of any social organisation, (2) trust in other people and (3) trust in organisations, stratified into high-income and low-income country samples. Results In low-income countries, membership of any social organisation was associated with a 3% greater likelihood of having one's hypertension detected and controlled, while greater trust in organisations significantly increased the likelihood of detection by 4%. These associations were not observed among participants in high-income countries. Conclusion Although the observed associations are modest, some aspects of social capital are associated with better management of hypertension in low-income countries where health systems are often weak. Given that hypertension affects millions in these countries, even modest gains at all points along the treatment pathway could improve management for many, and translate into the prevention of thousands of cardiovascular events each year.
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| 31. |
- Pe'er, D, et al.
(författare)
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Tumor heterogeneity
- 2021
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Ingår i: Cancer cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 39:8, s. 1015-1017
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Tidskriftsartikel (refereegranskat)
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| 32. |
- Sartor, O., et al.
(författare)
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Re-treatment with radium-223 : first experience from an international, open-label, phase I/II study in patients with castration-resistant prostate cancer and bone metastases
- 2017
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Ingår i: Annals of Oncology. - : OXFORD UNIV PRESS. - 0923-7534 .- 1569-8041. ; 28:10, s. 2464-2471
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Six radium-223 injections at 4-week intervals is indicated for patients with castration-resistant prostate cancer and symptomatic bone metastases. However, patients usually develop disease progression after initial treatment. This prospective phase I/II study assessed re-treatment safety and efficacy of up to six additional radium-223 injections. Patients and methods: Patients had castration-resistant prostate cancer and bone metastases and six initial radium-223 injections with no on-treatment bone progression; all had subsequent radiologic or clinical progression. Concomitant agents were allowed at investigator discretion, excluding chemotherapy and initiation of new abiraterone or enzalutamide. The primary endpoint was safety; additional exploratory endpoints included time to radiographic bone progression, time to total alkaline phosphatase and prostate-specific antigen progression, radiographic progression-free survival, overall survival, time to first symptomatic skeletal event (SSE), SSE-free survival, and time to pain progression. Results: Among 44 patients, 29 (66%) received all six re-treatment injections. Median time from end of initial radium-223 treatment was 6 months. Forty-one (93%) reported >= 1 treatment-emergent adverse event. No grade 4-5 hematologic treatment-emergent adverse events occurred. Only one (2%) patient had radiographic bone progression; eight (18%) had radiographic soft tissue tumor progression (three lymph node and five visceral metastases). Median times to total alkaline phosphatase and prostate-specific antigen progression were not reached and 2.2 months, respectively. Median radiographic progression-free survival was 9.9 months (12.8-month maximum follow-up). Five (11%) patients died and eight (18%) experienced first SSEs. Median overall survival, time to first SSE, and SSE-free survival were not reached. Five (14%) of 36 evaluable patients (baseline worst pain score <= 7) had pain progression. After 2 years of follow-up, 28 (64%) patients died, and the median overall survival was 24.4 months. Conclusions: Re-treatment with a second course of six radium-223 injections after disease progression is well tolerated, with minimal hematologic toxicity and low radiographic bone progression rates in this small study with limited follow-up. Favorable safety and early effects on disease progression indicate that radium-223 re-treatment is feasible and warrants further evaluation in larger prospective trials.
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| 33. |
- Schmidt, Keith T, et al.
(författare)
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Population pharmacokinetic analysis of nanoparticle-bound and free camptothecin after administration of NLG207 in adults with advanced solid tumors.
- 2020
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Ingår i: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 86:4, s. 475-486
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: NLG207 (formerly CRLX101) is a nanoparticle-drug conjugate (NDC) of the potent topoisomerase I inhibitor, camptothecin (CPT). The present study sought to characterize the complex pharmacokinetics (PK) of NLG207 and better describe CPT release from nanoparticles using a population PK (popPK) model.METHODS: From 27 patients enrolled on two phase II clinical trials (NCT02769962 and NCT03531827), dense sampling was performed up to 48 h post-administration of NLG207 during cycle one and six of treatment; samples were also collected at ~ 360 h post-dose. Conjugated and free CPT concentrations were quantified from each sample, resulting in 477 observations to build a popPK model using non-linear mixed-effects modeling.RESULTS: The PK of NLG207 was characterized by combining two linear two-compartment models with first-order kinetics each to describe nanoparticle-bound (conjugated) and free CPT. Allometric scaling based on body weight provided the best body-size descriptor for all PK parameters. The typical volumes of distribution of the conjugated CPT central and free CPT central compartments were 3.16 L (BSV CV%; 18.1%) and 21.1 L (CV%; 79.8%), respectively. CPT release from the nanoparticle formulation was characterized via an initial rapid clearance of 5.71 L/h (CV%; 62.6%), which decreased via first-order decay (estimated half-life of 0.307 h) to the steady-state value of 0.0988 L/h (CV%; 33.5%) by ~ 4 h after end of infusion. Renal clearance of free CPT was 0.874 L/h (CV%; 42.2%).CONCLUSION: The popPK model confirmed nanoparticle behavior of conjugated CPT and mechanistically characterized CPT release from NLG207. The current analysis provides a strong foundation for future study as a potential predictive tool in ongoing NLG207 clinical trials.
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| 34. |
- Al-Nawas, Bilal, et al.
(författare)
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ITI consensus report on zygomatic implants : indications, evaluation of surgical techniques and long-term treatment outcomes
- 2023
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Ingår i: International Journal of Implant Dentistry. - : Springer Nature. - 2198-4034. ; 9
-
Forskningsöversikt (refereegranskat)abstract
- Objectives: The aim of the ITI Consensus Workshop on zygomatic implants was to provide Consensus Statements and Clinical Recommendations for the use of zygomatic implants.Materials and methods: Three systematic reviews and one narrative review were written to address focused questions on (1) the indications for the use of zygomatic implants; (2) the survival rates and complications associated with surgery in zygomatic implant placement; (3) long-term survival rates of zygomatic implants and (4) the biomechanical principles involved when zygoma implants are placed under functional loads. Based on the reviews, three working groups then developed Consensus Statements and Clinical Recommendations. These were discussed in a plenary and finalized in Delphi rounds.Results: A total of 21 Consensus Statements were developed from the systematic reviews. Additionally, the group developed 17 Clinical Recommendations based on the Consensus Statements and the combined expertise of the participants.Conclusions: Zygomatic implants are mainly indicated in cases with maxillary bone atrophy or deficiency. Long-term mean zygomatic implant survival was 96.2% [95% CI 93.8; 97.7] over a mean follow-up of 75.4 months (6.3 years) with a follow-up range of 36-141.6 months (3-11.8 years). Immediate loading showed a statistically significant increase in survival over delayed loading. Sinusitis presented with a total prevalence of 14.2% [95% CI 8.8; 22.0] over a mean 65.4 months follow-up, representing the most common complication which may lead to zygomatic implant loss. The international experts suggested clinical recommendations regarding planning, surgery, restoration, outcomes, and the patient's perspective.
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| 35. |
- Altenhoff, Adrian M., et al.
(författare)
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Standardized benchmarking in the quest for orthologs
- 2016
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Ingår i: Nature Methods. - 1548-7091 .- 1548-7105. ; 13:5, s. 425-
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Tidskriftsartikel (refereegranskat)abstract
- Achieving high accuracy in orthology inference is essential for many comparative, evolutionary and functional genomic analyses, yet the true evolutionary history of genes is generally unknown and orthologs are used for very different applications across phyla, requiring different precision-recall trade-offs. As a result, it is difficult to assess the performance of orthology inference methods. Here, we present a community effort to establish standards and an automated web-based service to facilitate orthology benchmarking. Using this service, we characterize 15 well-established inference methods and resources on a battery of 20 different benchmarks. Standardized benchmarking provides a way for users to identify the most effective methods for the problem at hand, sets a minimum requirement for new tools and resources, and guides the development of more accurate orthology inference methods.
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| 36. |
- Begue, D., et al.
(författare)
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Bethe-Heitler Signature in Proton Synchrotron Models for Gamma-Ray Bursts
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 937:2, s. 101-
-
Tidskriftsartikel (refereegranskat)abstract
- We study the effect of Bethe-Heitler (BeHe) pair production on a proton synchrotron model for the prompt emission in gamma-ray bursts (GRBs). The possible parameter space of the model is constrained by consideration of the synchrotron radiation from the secondary BeHe pairs. We find two regimes of interest. (1) At high bulk Lorentz factor, large radius, and low luminosity, proton synchrotron emission dominates and produces a spectrum in agreement with observations. For part of this parameter space, a subdominant (in the MeV band) power law is created by the synchrotron emission of the BeHe pairs. This power law extends up to few tens or hundreds of MeV. Such a signature is a natural expectation in a proton synchrotron model, and it is seen in some GRBs, including GRB 190114C recently observed by the MAGIC observatory. (2) At low bulk Lorentz factor, small radius, and high luminosity, BeHe cooling dominates. The spectrum achieves the shape of a single power law with spectral index alpha = -3/2 extending across the entire Gamma-ray Burst Monitor/Swift energy window, incompatible with observations. Our theoretical results can be used to further constrain the spectral analysis of GRBs in the guise of proton synchrotron models.
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| 37. |
- Bégué, D., et al.
(författare)
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The problematic connection between gamma-ray bursts and ultra-high energy cosmic rays
- 2019
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Ingår i: High Energy Phenomena in Relativistic Outflows VII. - Trieste, Italy : Sissa Medialab Srl.
-
Konferensbidrag (refereegranskat)abstract
- The acceleration site for UHECR is still an open question despite extended research and GRBs are considered one of the most promising source candidates. Under the likely assumption that electrons are also accelerated at the UHECR acceleration site, synchrotron emission from these co-accelerated electrons is inevitable. We characterize this synchrotron emission and compare it to observed GRB spectra and find that for standard parameters, the synchrotron flux from these electrons would be much too luminous. This result challenges both high- and low-luminosity GRBs as accelerators of UHECR. A detailed discussion on GRB 060218 as UHECR source is also presented.
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| 38. |
- Burgess, J. Michael, et al.
(författare)
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AN OBSERVED CORRELATION BETWEEN THERMAL AND NON-THERMAL EMISSION IN GAMMA-RAY BURSTS
- 2014
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 784:2
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Tidskriftsartikel (refereegranskat)abstract
- Recent observations by the Fermi Gamma-ray Space Telescope have confirmed the existence of thermal and non-thermal components in the prompt photon spectra of some gamma-ray bursts (GRBs). Through an analysis of six bright Fermi GRBs, we have discovered a correlation between the observed photospheric and non-thermal gamma-ray emission components of several GRBs using a physical model that has previously been shown to be a good fit to the Fermi data. From the spectral parameters of these fits we find that the characteristic energies, E-p and kT, of these two components are correlated via the relation E-p proportional to T-alpha which varies from GRB to GRB. We present an interpretation in which the value of the index alpha indicates whether the jet is dominated by kinetic or magnetic energy. To date, this jet composition parameter has been assumed in the modeling of GRB outflows rather than derived from the data.
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| 39. |
- Dieckmann, Mark E, 1969-, et al.
(författare)
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Change of a Weibel-type to an Alfvénic shock in pair plasma by upstream waves
- 2020
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Ingår i: Physics of Plasmas. - : American Institute of Physics (AIP). - 1070-664X .- 1089-7674. ; 27:6
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Tidskriftsartikel (refereegranskat)abstract
- We examine with particle-in-cell simulations how a parallel shock in pair plasma reacts to upstream waves, which are driven by escaping downstream particles. Initially, the shock is sustained in the two-dimensional simulation by a magnetic filamentation (beam-Weibel) instability. Escaping particles drive an electrostatic beam instability upstream. Modifications of the upstream plasma by these waves hardly affect the shock. In time, a decreasing density and an increasing temperature of the escaping particles quench the beam instability. A larger thermal energy along than perpendicular to the magnetic field destabilizes the pair-Alfvén mode. In the rest frame of the upstream plasma, the group velocity of the growing pair-Alfvén waves is below that of the shock and the latter catches up with the waves. Accumulating pair-Alfvén waves gradually change the shock in the two-dimensional simulation from a Weibel-type shock into an Alfvénic shock with a Mach number that is about 6 for our initial conditions.
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| 40. |
- Diener, Hans-Christoph, et al.
(författare)
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Topiramate in migraine prophylaxis--results from a placebo-controlled trial with propranolol as an active control
- 2004
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Ingår i: J Neurol. ; 251:8, s. 943-50
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Tidskriftsartikel (refereegranskat)abstract
- Topiramate (TPM) has shown efficacy in migraine prophylaxis in two large placebo-controlled, dose-ranging trials. We conducted a randomised, double-blind, multicentre trial to evaluate the efficacy and safety of two doses of topiramate vs placebo for migraine prophylaxis, with propranolol (PROP) as an active control. Subjects with episodic migraine with and without aura were randomised to TPM 100 mg/d, TPM 200 mg/d, PROP 160 mg/d (active control), or placebo. The primary efficacy measure was the change in mean monthly migraine frequency from the baseline phase relative to the double-blind treatment phase. Five hundred and seventy-five subjects were enrolled from 61 centres in 13 countries. TPM 100 mg/d was superior to placebo as measured by reduction in monthly migraine frequency, overall 50% responder rate, reduction in monthly migraine days, and reduction in the rate of daily rescue medication use. The TPM 100 mg/d and PROP groups were similar with respect to reductions in migraine frequency, responder rate, migraine days, and daily rescue medication usage. TPM 100 mg/d was better tolerated than TPM 200 mg/d, and was generally comparable to PROP. No unusual or unexpected safety risks emerged. These findings demonstrate that TPM 100 mg/d is effective in migraine prophylaxis. TPM 100 mg/d and PROP 160 mg/d exhibited similar efficacy profiles.
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| 41. |
- Ehrling, Sebastian, et al.
(författare)
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Temperature Driven Transformation of the Flexible Metal–Organic Framework DUT-8(Ni)
- 2022
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 28:55
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Tidskriftsartikel (refereegranskat)abstract
- DUT-8(Ni) metal–organic framework (MOF) belongs to the family of flexible pillared layer materials. The desolvated framework can be obtained in the open pore form (op) or in the closed pore form (cp), depending on the crystal size regime. In the present work, we report on the behaviour of desolvated DUT-8(Ni) at elevated temperatures. For both, op and cp variants, heating causes a structural transition, leading to a new, crystalline compound, containing two interpenetrated networks. The state of the framework before transition (op vs. cp) influences the transition temperature: the small particles of the op phase transform at significantly lower temperature in comparison to the macroparticles of the cp phase, transforming close to the decomposition temperature. The new compound, confined closed pore phase (ccp), was characterized by powder X-ray diffraction and spectroscopic techniques, such as IR, EXAFS, and positron annihilation lifetime spectroscopy (PALS). Thermal effects of structural transitions were studied using differential scanning calorimetry (DSC), showing an overall exothermic effect of the process, involving bond breaking and reformation. Theoretical calculations reveal the energetics, driving the observed temperature induced phase transition.
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| 42. |
- Gossmann, Toni I., et al.
(författare)
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Ice-Age Climate Adaptations Trap the Alpine Marmot in a State of Low Genetic Diversity
- 2019
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 29:10, s. 1712-1720.e7
-
Tidskriftsartikel (refereegranskat)abstract
- © 2019 The Author(s) Some species responded successfully to prehistoric changes in climate [1, 2], while others failed to adapt and became extinct [3]. The factors that determine successful climate adaptation remain poorly understood. We constructed a reference genome and studied physiological adaptations in the Alpine marmot (Marmota marmota), a large ground-dwelling squirrel exquisitely adapted to the “ice-age” climate of the Pleistocene steppe [4, 5]. Since the disappearance of this habitat, the rodent persists in large numbers in the high-altitude Alpine meadow [6, 7]. Genome and metabolome showed evidence of adaptation consistent with cold climate, affecting white adipose tissue. Conversely, however, we found that the Alpine marmot has levels of genetic variation that are among the lowest for mammals, such that deleterious mutations are less effectively purged. Our data rule out typical explanations for low diversity, such as high levels of consanguineous mating, or a very recent bottleneck. Instead, ancient demographic reconstruction revealed that genetic diversity was lost during the climate shifts of the Pleistocene and has not recovered, despite the current high population size. We attribute this slow recovery to the marmot's adaptive life history. The case of the Alpine marmot reveals a complicated relationship between climatic changes, genetic diversity, and conservation status. It shows that species of extremely low genetic diversity can be very successful and persist over thousands of years, but also that climate-adapted life history can trap a species in a persistent state of low genetic diversity. Despite being highly abundant and well adapted, Gossmann et al. report that the Alpine marmot is among the least genetically diverse animal species. The low diversity is found to be the consequence of consecutive, climate-related events, including long-term extreme niche adaptation, that also greatly retarded the recovery of its genetic diversity.
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| 43. |
- Haniffa, Muzlifah, et al.
(författare)
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A roadmap for the Human Developmental Cell Atlas
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 597:7875, s. 196-205
-
Tidskriftsartikel (refereegranskat)abstract
- This Perspective outlines the Human Developmental Cell Atlas initiative, which uses state-of-the-art technologies to map and model human development across gestation, and discusses the early milestones that have been achieved. The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development.
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| 44. |
- Harrington, Robert A., et al.
(författare)
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The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA.CER) trial : study design and rationale
- 2009
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 158:3, s. 327-334
-
Tidskriftsartikel (refereegranskat)abstract
- Background The protease-activated receptor 1 (PAR-1), the main platelet receptor for thrombin, represents a novel target for treatment of arterial thrombosis, and SCH 530348 is an orally active, selective, competitive PAR-1 antagonist. We designed TRA.CER to evaluate the efficacy and safety of SCH 530348 compared with placebo in addition to standard of care in patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) and high-risk features. Trial design TRA.CER is a prospective, randomized, double-blind, multicenter, phase III trial with an original estimated sample size of 10,000 subjects. Our primary objective is to demonstrate that SCH 530348 in addition to standard of care will reduce the incidence of the composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization compared with standard of care alone. Our key secondary objective is to determine whether SCH 530348 will reduce the composite of cardiovascular death, MI, or stroke compared with standard of care alone. Secondary objectives related to safety are the composite of moderate and severe GUSTO bleeding and clinically significant TIMI bleeding. The trial will continue until a predetermined minimum number of centrally adjudicated primary and key secondary end point events have occurred and all subjects have participated in the study for at least I year. The TRA.CER trial is part of the large phase III SCH 530348 development program that includes a concomitant evaluation in secondary prevention. Conclusion TRA.CER will define efficacy and safety of the novel platelet PAR-1 inhibitor SCH 530348 in the treatment of high-risk patients with NSTE ACS in the setting of current treatment strategies.
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| 45. |
- Iyyani, Shabnam, et al.
(författare)
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Synchrotron emission in GRBs observed by Fermi : its limitations and the role of the photosphere
- 2016
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 456:2, s. 2157-2171
-
Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that the prompt emission in gamma-ray bursts consists of several components giving rise to the observed spectral shape. Here we examine a sample of the eight brightest, single pulsed Fermi bursts whose spectra are modelled by using synchrotron emission as one of the components. Five of these bursts require an additional photospheric component (blackbody). In particular, we investigate the inferred properties of the jet and the physical requirements set by the observed components for these five bursts, in the context of a baryonic dominated outflow, motivated by the strong photospheric component. We find similar jet properties for all five bursts: the bulk Lorentz factor decreases monotonously over the pulses and lies between 1000 and 100. This evolution is robust and can neither be explained by a varying radiative efficiency nor a varying magnetization of the jet (assuming the photosphere radius is above the coasting radius). Such a behaviour challenges several dissipation mechanisms, e.g. the internal shocks. Furthermore, in all eight cases the data clearly reject a fast-cooled synchrotron spectrum (in which a significant fraction of the emitting electrons have cooled to energies below the minimum injection energy), inferring a typical electron Lorentz factor of 10(4)-10(7). Such values are much higher than what is typically expected in internal shocks. Therefore, while the synchrotron scenario is not rejected by the data, the interpretation does present several limitations that need to be addressed. Finally, we point out and discuss alternative interpretations.
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| 46. |
- Kambach, S., et al.
(författare)
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How do trees respond to species mixing in experimental compared to observational studies?
- 2019
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 9:19, s. 11254-11265
-
Tidskriftsartikel (refereegranskat)abstract
- For decades, ecologists have investigated the effects of tree species diversity on tree productivity at different scales and with different approaches ranging from observational to experimental study designs. Using data from five European national forest inventories (16,773 plots), six tree species diversity experiments (584 plots), and six networks of comparative plots (169 plots), we tested whether tree species growth responses to species mixing are consistent and therefore transferrable between those different research approaches. Our results confirm the general positive effect of tree species mixing on species growth (16% on average) but we found no consistency in species-specific responses to mixing between any of the three approaches, even after restricting comparisons to only those plots that shared similar mixtures compositions and forest types. These findings highlight the necessity to consider results from different research approaches when selecting species mixtures that should maximize positive forest biodiversity and functioning relationships.
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| 47. |
- Khalil, Asma, et al.
(författare)
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The Role of cfDNA Biomarkers and Patient Data in the Early Prediction of Preeclampsia: Artificial Intelligence Model.
- 2024
-
Ingår i: American journal of obstetrics and gynecology. - 1097-6868.
-
Tidskriftsartikel (refereegranskat)abstract
- Accurate individualized assessment of preeclampsia risk enables the identification of patients most likely to benefit from initiation of low-dose aspirin at 12-16 weeks' gestation when there is evidence for its effectiveness, as well as guiding appropriate pregnancy care pathways and surveillance. The primary objective of this study was to evaluate the performance of artificial neural network models for the prediction of preterm preeclampsia (<37 weeks' gestation) using patient characteristics available at the first antenatal visit and data from prenatal cell-free DNA (cfDNA) screening. Secondary outcomes were prediction of early onset preeclampsia (<34 weeks' gestation) and term preeclampsia (≥37 weeks' gestation).This secondary analysis of a prospective, multicenter, observational prenatal cfDNA screening study (SMART) included singleton pregnancies with known pregnancy outcomes. Thirteen patient characteristics that are routinely collected at the first prenatal visit and two characteristics of cfDNA, total cfDNA and fetal fraction (FF), were used to develop predictive models for early-onset (<34 weeks), preterm (<37 weeks), and term (≥37 weeks) preeclampsia. For the models, the 'reference' classifier was a shallow logistic regression (LR) model. We also explored several feedforward (non-linear) neural network (NN) architectures with one or more hidden layers and compared their performance with the LR model. We selected a simple NN model built with one hidden layer and made up of 15 units.Of 17,520 participants included in the final analysis, 72 (0.4%) developed early onset, 251 (1.4%) preterm, and 420 (2.4%) term preeclampsia. Median gestational age at cfDNA measurement was 12.6 weeks and 2,155 (12.3%) had their cfDNA measurement at 16 weeks' gestation or greater. Preeclampsia was associated with higher total cfDNA (median 362.3 versus 339.0 copies/ml cfDNA; p<0.001) and lower FF (median 7.5% versus 9.4%; p<0.001). The expected, cross-validated area under the curve (AUC) scores for early onset, preterm, and term preeclampsia were 0.782, 0.801, and 0.712, respectively for the LR model, and 0.797, 0.800, and 0.713, respectively for the NN model. At a screen-positive rate of 15%, sensitivity for preterm preeclampsia was 58.4% (95% CI 0.569, 0.599) for the LR model and 59.3% (95% CI 0.578, 0.608) for the NN model.The contribution of both total cfDNA and FF to the prediction of term and preterm preeclampsia was negligible. For early-onset preeclampsia, removal of the total cfDNA and FF features from the NN model was associated with a 6.9% decrease in sensitivity at a 15% screen positive rate, from 54.9% (95% CI 52.9-56.9) to 48.0% (95% CI 45.0-51.0).Routinely available patient characteristics and cfDNA markers can be used to predict preeclampsia with performance comparable to other patient characteristic models for the prediction of preterm preeclampsia. Both LR and NN models showed similar performance.
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| 48. |
- Kleinteich, Julia, et al.
(författare)
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Pole-to-Pole Connections : Similarities between Arctic and Antarctic Microbiomes and Their Vulnerability to Environmental Change
- 2017
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Ingår i: Frontiers in Ecology and Evolution. - : FRONTIERS MEDIA SA. - 2296-701X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- The global biogeography of microorganisms remains poorly resolved, which limits the current understanding of microbial resilience toward environmental changes. Using high-throughput 16S rRNA gene amplicon sequencing, we characterized the microbial diversity of terrestrial and lacustrine biofilms from the Arctic, Antarctic and temperate regions. Our analyses suggest that bacterial community compositions at the poles are more similar to each other than they are to geographically closer temperate habitats, with 32% of all operational taxonomic units (OTUs) co-occurring in both polar regions. While specific microbial taxa were confined to distinct regions, representing potentially endemic populations, the percentage of cosmopolitan taxa was higher in Arctic (43%) than in Antarctic samples (36%). The overlap in polar microbial OTUs may be explained by natural or anthropogenically-mediated dispersal in combination with environmental filtering. Current and future changing environmental conditions may enhance microbial invasion, establishment of cosmopolitan genotypes and loss of endemic taxa.
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| 49. |
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| 50. |
- Li, Liang, et al.
(författare)
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A Cosmological Fireball with 16% Gamma-Ray Radiative Efficiency
- 2023
-
Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 944:2
-
Tidskriftsartikel (refereegranskat)abstract
- Gamma-ray bursts (GRBs) are the most powerful explosions in the universe. How efficiently the jet converts its energy to radiation is a long-standing problem, which is poorly constrained. The standard model invokes a relativistic fireball with a bright photosphere emission component. A definitive diagnosis of GRB radiation components and the measurement of GRB radiative efficiency require prompt emission and afterglow data, with high resolution and wide band coverage in time and energy. Here, we present a comprehensive temporal and spectral analysis of the TeV-emitting bright GRB 190114C. Its fluence is one of the highest for all the GRBs that have been detected so far, which allows us to perform a high-resolution study of the prompt emission spectral properties and their temporal evolutions, down to a timescale of about 0.1 s. We observe that each of the initial pulses has a thermal component contributing ∼20% of the total energy and that the corresponding temperature and inferred Lorentz factor of the photosphere evolve following broken power-law shapes. From the observation of the nonthermal spectra and the light curve, the onset of the afterglow corresponding to the deceleration of the fireball is considered to start at ∼6 s. By incorporating the thermal and nonthermal observations, as well as the photosphere and synchrotron radiative mechanisms, we can directly derive the fireball energy budget with little dependence on hypothetical parameters, measuring a ∼16% radiative efficiency for this GRB. With the fireball energy budget derived, the afterglow microphysics parameters can also be constrained directly from the data.
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