| 1. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 2. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 3. |
- Ade, Peter, et al.
(författare)
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The Simons Observatory : science goals and forecasts
- 2019
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
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Tidskriftsartikel (refereegranskat)abstract
- The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
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| 4. |
- Eddy, Tyler D., et al.
(författare)
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Energy Flow Through Marine Ecosystems : Confronting Transfer Efficiency
- 2021
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Ingår i: Trends in Ecology & Evolution. - : Elsevier BV. - 0169-5347 .- 1872-8383. ; 36:1, s. 76-86
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Forskningsöversikt (refereegranskat)abstract
- Transfer efficiency is the proportion of energy passed between nodes in food webs. It is an emergent, unitless property that is difficult to measure, and responds dynamically to environmental and ecosystem changes. Because the consequences of changes in transfer efficiency compound through ecosystems, slight variations can have large effects on food availability for top predators. Here, we review the processes controlling transfer efficiency, approaches to estimate it, and known variations across ocean biomes. Both process-level analysis and observed macro-scale variations suggest that ecosystem-scale transfer efficiency is highly variable, impacted by fishing, and will decline with climate change. It is important that we more fully resolve the processes controlling transfer efficiency in models to effectively anticipate changes in marine ecosystems and fisheries resources.
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| 5. |
- Nielsen, Rasmus J., et al.
(författare)
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Integrated ecological–economic fisheries models—Evaluation, review and challenges for implementation
- 2018
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Ingår i: Fish and Fisheries. - : Wiley. - 1467-2960 .- 1467-2979. ; 19:1, s. 1-29
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Forskningsöversikt (refereegranskat)abstract
- Marine ecosystems evolve under many interconnected and area-specific pressures. To fulfil society's intensifying and diversifying needs while ensuring ecologically sustainable development, more effective marine spatial planning and broader-scope management of marine resources is necessary. Integrated ecological–economic fisheries models (IEEFMs) of marine systems are needed to evaluate impacts and sustainability of potential management actions and understand, and anticipate ecological, economic and social dynamics at a range of scales from local to national and regional. To make these models most effective, it is important to determine how model characteristics and methods of communicating results influence the model implementation, the nature of the advice that can be provided and the impact on decisions taken by managers. This article presents a global review and comparative evaluation of 35 IEEFMs applied to marine fisheries and marine ecosystem resources to identify the characteristics that determine their usefulness, effectiveness and implementation. The focus is on fully integrated models that allow for feedbacks between ecological and human processes although not all the models reviewed achieve that. Modellers must invest more time to make models user friendly and to participate in management fora where models and model results can be explained and discussed. Such involvement is beneficial to all parties, leading to improvement of models and more effective implementation of advice, but demands substantial resources which must be built into the governance process. It takes time to develop effective processes for using IEEFMs requiring a long-term commitment to integrating multidisciplinary modelling advice into management decision-making.
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| 6. |
- Cousins, Melanie, et al.
(författare)
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Is scientific evidence enough? Using expert opinion to fill gaps in data in antimicrobial resistance research
- 2023
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Ingår i: PLOS ONE. - 1932-6203. ; 18:8
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAntimicrobial Resistance (AMR) is a global problem with large health and economic consequences. Current gaps in quantitative data are a major limitation for creating models intended to simulate the drivers of AMR. As an intermediate step, expert knowledge and opinion could be utilized to fill gaps in knowledge for areas of the system where quantitative data does not yet exist or are hard to quantify. Therefore, the objective of this study was to identify quantifiable data about the current state of the factors that drive AMR and the strengths and directions of relationships between the factors from statements made by a group of experts from the One Health system that drives AMR development and transmission in a European context.MethodsThis study builds upon previous work that developed a causal loop diagram of AMR using input from two workshops conducted in 2019 in Sweden with experts within the European food system context. A secondary analysis of the workshop transcripts was conducted to identify semi-quantitative data to parameterize drivers in a model of AMR.Main findingsParticipants spoke about AMR by combining their personal experiences with professional expertise within their fields. The analysis of participants’ statements provided semi-quantitative data that can help inform a future of AMR emergence and transmission based on a causal loop diagram of AMR in a Swedish One Health system context.ConclusionUsing transcripts of a workshop including participants with diverse expertise across the system that drives AMR, we gained invaluable insight into the past, current, and potential future states of the major drivers of AMR, particularly where quantitative data are lacking.
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| 7. |
- Graells, Tiscar, et al.
(författare)
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Exploring the factors that contribute to the successful implementation of antimicrobial resistance interventions : a comparison of high-income and low-middle-income countries
- 2023
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Ingår i: Frontiers in Public Health. - 2296-2565. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionAntimicrobial resistance (AMR) is a challenge to modern medicine. Interventions have been applied worldwide to tackle AMR, but these actions are often not reported to peers or published, leading to important knowledge gaps about what actions are being taken. Understanding factors that influence the implementation of AMR interventions and what factors are relevant in low-middle-income countries (LMICs) and high-income countries (HICs) were the key objectives of this exploratory study, with the aim to identifying which priorities these contexts need.MethodsA questionnaire was used to explore context, characteristics, and success factors or obstacles to intervention success based on participant input. The context was analyzed using the AMR-Intervene framework, and success factors and obstacles to intervention success were identified using thematic analysis.ResultsOf the 77 interventions, 57 were implemented in HICs and 17 in LMICs. Interventions took place in the animal sector, followed by the human sector. Public organizations were mainly responsible for implementation and funding. Nine themes and 32 sub-themes emerged as important for intervention success. The themes most frequently reported were 'behavior', 'capacity and resources', 'planning', and 'information'. Five sub-themes were key in all contexts ('collaboration and coordination', 'implementation', 'assessment', 'governance', and 'awareness'), two were key in LMICs ('funding and finances' and 'surveillance, antimicrobial susceptibility testing and preventive screening'), and five were key in HICs ('mandatory', 'multiple profiles', 'personnel', 'management', and 'design').ConclusionLMIC sub-themes showed that funding and surveillance were still key issues for interventions, while important HIC sub-themes were more specific and detailed, including mandatory enforcement, multiple profiles, and personnel needed for good management and good design. While behavior is often underrated when implementing AMR interventions, capacity and resources are usually considered, and LMICs can benefit from sub-themes captured in HICs if tailored to their contexts. The factors identified can improve the design, planning, implementation, and evaluation of interventions.
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| 8. |
- Graells, Tiscar, et al.
(författare)
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Studying Factors Affecting Success of Antimicrobial Resistance Interventions through the Lens of Experience : A Thematic Analysis
- 2022
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Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance (AMR) affects the environment, and animal and human health. Institutions worldwide have applied various measures, some of which have reduced antimicrobial use and AMR. However, little is known about factors influencing the success of AMR interventions. To address this gap, we engaged health professionals, designers, and implementers of AMR interventions in an exploratory study to learn about their experience and factors that challenged or facilitated interventions and the context in which interventions were implemented. Based on participant input, our thematic analysis identified behaviour; institutional governance and management; and sharing and enhancing information as key factors influencing success. Important sub-themes included: correct behaviour reinforcement, financial resources, training, assessment, and awareness of AMR. Overall, interventions were located in high-income countries, the human sector, and were publicly funded and implemented. In these contexts, behaviour patterns strongly influenced success, yet are often underrated or overlooked when designing AMR interventions. Improving our understanding of what contributes to successful interventions would allow for better designs of policies that are tailored to specific contexts. Exploratory approaches can provide encouraging results in complex challenges, as made evident in our study. Remaining challenges include more engagement in this type of study by professionals and characterisation of themes that influence intervention outcomes by context.
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| 9. |
- Delrez, Laetitia, et al.
(författare)
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Transit detection of the long-period volatile-rich super-Earth nu(2) Lupi d with CHEOPS
- 2021
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Ingår i: Nature Astronomy. - : Springer Science and Business Media LLC. - 2397-3366. ; :5, s. 775-787
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Tidskriftsartikel (refereegranskat)abstract
- Exoplanets transiting bright nearby stars are key objects for advancing our knowledge of planetary formation and evolution. The wealth of photons from the host star gives detailed access to the atmospheric, interior and orbital properties of the planetary companions. nu(2) Lupi (HD 136352) is a naked-eye (V = 5.78) Sun-like star that was discovered to host three low-mass planets with orbital periods of 11.6, 27.6 and 107.6 d via radial-velocity monitoring(1). The two inner planets (b and c) were recently found to transit(2), prompting a photometric follow-up by the brand new Characterising Exoplanets Satellite (CHEOPS). Here, we report that the outer planet d is also transiting, and measure its radius and mass to be 2.56 +/- 0.09 R-circle plus and 8.82 +/- 0.94 M-circle plus, respectively. With its bright Sun-like star, long period and mild irradiation (similar to 5.7 times the irradiation of Earth), nu(2) Lupi d unlocks a completely new region in the parameter space of exoplanets amenable to detailed characterization. We refine the properties of all three planets: planet b probably has a rocky mostly dry composition, while planets c and d seem to have retained small hydrogen-helium envelopes and a possibly large water fraction. This diversity of planetary compositions makes the nu(2) Lupi system an excellent laboratory for testing formation and evolution models of low-mass planets.
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| 10. |
- Hirscher, Michael, et al.
(författare)
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Materials for hydrogen-based energy storage - past, recent progress and future outlook
- 2020
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Ingår i: Journal of Alloys and Compounds. - : Elsevier BV. - 0925-8388 .- 1873-4669. ; 827
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Tidskriftsartikel (refereegranskat)abstract
- Globally, the accelerating use of renewable energy sources, enabled by increased efficiencies and reduced costs, and driven by the need to mitigate the effects of climate change, has significantly increased research in the areas of renewable energy production, storage, distribution and end-use. Central to this discussion is the use of hydrogen, as a clean, efficient energy vector for energy storage. This review, by experts of Task 32, Hydrogen-based Energy Storage of the International Energy Agency, Hydrogen TCP, reports on the development over the last 6 years of hydrogen storage materials, methods and techniques, including electrochemical and thermal storage systems. An overview is given on the background to the various methods, the current state of development and the future prospects. The following areas are covered; porous materials, liquid hydrogen carriers, complex hydrides, intermetallic hydrides, electrochemical storage of energy, thermal energy storage, hydrogen energy systems and an outlook is presented for future prospects and research on hydrogen-based energy storage.
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