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1.
  • Botvinik-Nezer, Rotem, et al. (author)
  • Variability in the analysis of a single neuroimaging dataset by many teams
  • 2020
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
  • Journal article (peer-reviewed)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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2.
  • Holmbo, S., et al. (author)
  • Discovery and progenitor constraints on the Type Ia supernova 2013gy
  • 2019
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 627
  • Journal article (peer-reviewed)abstract
    • We present an early-phase g-band light curve and visual-wavelength spectra of the normal Type Ia supernova (SN) 2013gy. The light curve is constructed by determining the appropriate S-corrections to transform KAIT natural-system B- and V-band photometry and Carnegie Supernova Project natural-system g-band photometry to the Pan-STARRS1 g-band natural photometric system. A Markov chain Monte Carlo calculation provides a best-fit single power-law function to the first ten epochs of photometry described by an exponent of 2.16(-0.06)(+0.06) and a time of first light of MJD 56629.4(-0.1)(+0.1), which is 1.93(-0.13)(+0.12) days (i.e., <48 h) before the discovery date (2013 December 4.84 UT) and -19.10(-0.13)(+0.12) days before the time of B- band maximum (MJD 56648.5 +/- 0.1). The estimate of the time of first light is consistent with the explosion time inferred from the evolution of the Si II lambda 6355 Doppler velocity. Furthermore, discovery photometry and previous nondetection limits enable us to constrain the companion radius down to R-c <= 4 R-circle dot. In addition to our early-time constraints, we used a deep +235 day nebular-phase spectrum from Magellan/IMACS to place a stripped H-mass limit of <0.018 M-circle dot. Combined, these limits effectively rule out H-rich nondegenerate companions.
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3.
  • Olijnik, Aude-Anais, et al. (author)
  • Genetic and functional insights into CDA-I prevalence and pathogenesis
  • 2021
  • In: Journal of Medical Genetics. - : BMJ Publishing Group Ltd. - 0022-2593 .- 1468-6244. ; 58:3, s. 185-195
  • Journal article (peer-reviewed)abstract
    • Background Congenital dyserythropoietic anaemia type I (CDA-I) is a hereditary anaemia caused by biallelic mutations in the widely expressed genes CDAN1 and C15orf41. Little is understood about either protein and it is unclear in which cellular pathways they participate. Methods Genetic analysis of a cohort of patients with CDA-I identifies novel pathogenic variants in both known causative genes. We analyse the mutation distribution and the predicted structural positioning of amino acids affected in Codanin-1, the protein encoded by CDAN1. Using western blotting, immunoprecipitation and immunofluorescence, we determine the effect of particular mutations on both proteins and interrogate protein interaction, stability and subcellular localisation. Results We identify six novel CDAN1 mutations and one novel mutation in C15orf41 and uncover evidence of further genetic heterogeneity in CDA-I. Additionally, population genetics suggests that CDA-I is more common than currently predicted. Mutations are enriched in six clusters in Codanin-1 and tend to affect buried residues. Many missense and in-frame mutations do not destabilise the entire protein. Rather C15orf41 relies on Codanin-1 for stability and both proteins, which are enriched in the nucleolus, interact to form an obligate complex in cells. Conclusion Stability and interaction data suggest that C15orf41 may be the key determinant of CDA-I and offer insight into the mechanism underlying this disease. Both proteins share a common pathway likely to be present in a wide variety of cell types; however, nucleolar enrichment may provide a clue as to the erythroid specific nature of CDA-I. The surprisingly high predicted incidence of CDA-I suggests that better ascertainment would lead to improved patient care.
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4.
  • Stritzinger, M. D., et al. (author)
  • The Carnegie Supernova Project I : Photometry data release of low-redshift stripped-envelope supernovae
  • 2018
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 609
  • Journal article (peer-reviewed)abstract
    • The first phase of the Carnegie Supernova Project (CSP-I) was a dedicated supernova follow-up program based at the Las Campanas Observatory that collected science data of young, low-redshift supernovae between 2004 and 2009. Presented in this paper is the CSP-I photometric data release of low-redshift stripped-envelope core-collapse supernovae. The data consist of optical (uBgVri) photometry of 34 objects, with a subset of 26 having near-infrared (YJH) photometry. Twenty objects have optical pre-maximum coverage with a subset of 12 beginning at least five days prior to the epoch of B-band maximum brightness. In the near-infrared, 17 objects have pre-maximum observations with a subset of 14 beginning at least five days prior to the epoch of J-band maximum brightness. Analysis of this photometric data release is presented in companion papers focusing on techniques to estimate host-galaxy extinction and the light-curve and progenitor star properties of the sample. The analysis of an accompanying visual-wavelength spectroscopy sample of similar to 150 spectra will be the subject of a future paper.
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6.
  • Brout, Dillon, et al. (author)
  • The Pantheon+ analysis : cosmological constraints
  • 2022
  • In: Astrophysical Journal. - : Institute of Physics (IOP). - 0004-637X .- 1538-4357. ; 938:2
  • Journal article (peer-reviewed)abstract
    • We present constraints on cosmological parameters from the Pantheon+ analysis of 1701 light curves of 1550 distinct Type Ia supernovae (SNe Ia) ranging in redshift from z = 0.001 to 2.26. This work features an increased sample size from the addition of multiple cross-calibrated photometric systems of SNe covering an increased redshift span, and improved treatments of systematic uncertainties in comparison to the original Pantheon analysis, which together result in a factor of 2 improvement in cosmological constraining power. For a flat ΛCDM model, we find ΩM = 0.334 ± 0.018 from SNe Ia alone. For a flat w0CDM model, we measure w0 = −0.90 ± 0.14 from SNe Ia alone, H0 = 73.5 ± 1.1 km s−1 Mpc−1 when including the Cepheid host distances and covariance (SH0ES), and w0 = -0.978-+0.0310.024 when combining the SN likelihood with Planck constraints from the cosmic microwave background (CMB) and baryon acoustic oscillations (BAO); both w0 values are consistent with a cosmological constant. We also present the most precise measurements to date on the evolution of dark energy in a flat w0waCDM universe, and measure wa = -0.1-+2.00.9 from Pantheon+ SNe Ia alone, H0 = 73.3 ± 1.1 km s−1 Mpc−1 when including SH0ES Cepheid distances, and wa = -0.65-+0.320.28 when combining Pantheon+ SNe Ia with CMB and BAO data. Finally, we find that systematic uncertainties in the use of SNe Ia along the distance ladder comprise less than one-third of the total uncertainty in the measurement of H0 and cannot explain the present “Hubble tension” between local measurements and early universe predictions from the cosmological model.
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7.
  • Klein, François, et al. (author)
  • Assessing the robustness of Antarctic temperature reconstructions over the past 2 millennia using pseudoproxy and data assimilation experiments
  • 2019
  • In: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 15:2, s. 661-684
  • Journal article (peer-reviewed)abstract
    • The Antarctic temperature changes over the past millennia remain more uncertain than in many other continental regions. This has several origins: (1) the number of high-resolution ice cores is small, in particular on the East Antarctic plateau and in some coastal areas in East Antarctica; (2) the short and spatially sparse instrumental records limit the calibration period for reconstructions and the assessment of the methodologies; (3) the link between isotope records from ice cores and local climate is usually complex and dependent on the spatial scales and timescales investigated. Here, we use climate model results, pseudoproxy experiments and data assimilation experiments to assess the potential for reconstructing the Antarctic temperature over the last 2 millennia based on a new database of stable oxygen isotopes in ice cores compiled in the framework of Antarctica2k (Stenni et al.,). The well-known covariance between δ 18 O and temperature is reproduced in the two isotope-enabled models used (ECHAM5/MPI-OM and ECHAM5-wiso), but is generally weak over the different Antarctic regions, limiting the skill of the reconstructions. Furthermore, the strength of the link displays large variations over the past millennium, further affecting the potential skill of temperature reconstructions based on statistical methods which rely on the assumption that the last decades are a good estimate for longer temperature reconstructions. Using a data assimilation technique allows, in theory, for changes in the δ 18 O-temperature link through time and space to be taken into account. Pseudoproxy experiments confirm the benefits of using data assimilation methods instead of statistical methods that provide reconstructions with unrealistic variances in some Antarctic subregions. They also confirm that the relatively weak link between both variables leads to a limited potential for reconstructing temperature based on δ 18 O. However, the reconstruction skill is higher and more uniform among reconstruction methods when the reconstruction target is the Antarctic as a whole rather than smaller Antarctic subregions. This consistency between the methods at the large scale is also observed when reconstructing temperature based on the real δ 18 O regional composites of Stenni et al. (2017). In this case, temperature reconstructions based on data assimilation confirm the long-term cooling over Antarctica during the last millennium, and the later onset of anthropogenic warming compared with the simulations without data assimilation, which is especially visible in West Antarctica. Data assimilation also allows for models and direct observations to be reconciled by reproducing the east-west contrast in the recent temperature trends. This recent warming pattern is likely mostly driven by internal variability given the large spread of individual Paleoclimate Modelling Intercomparison Project (PMIP)/Coupled Model Intercomparison Project (CMIP) model realizations in simulating it. As in the pseudoproxy framework, the reconstruction methods perform differently at the subregional scale, especially in terms of the variance of the time series produced. While the potential benefits of using a data assimilation method instead of a statistical method have been highlighted in a pseudoproxy framework, the instrumental series are too short to confirm this in a realistic setup.
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8.
  • Kreibich, Heidi, et al. (author)
  • Panta Rhei benchmark dataset : Socio-hydrological data of paired events of floods and droughts
  • 2023
  • In: Earth System Science Data. - : Copernicus Publications. - 1866-3508 .- 1866-3516. ; 15:5, s. 2009-2023
  • Journal article (peer-reviewed)abstract
    • As the adverse impacts of hydrological extremes increase in many regions of the world, a better understanding of the drivers of changes in risk and impacts is essential for effective flood and drought risk management and climate adaptation. However, there is currently a lack of comprehensive, empirical data about the processes, interactions, and feedbacks in complex human-water systems leading to flood and drought impacts. Here we present a benchmark dataset containing socio-hydrological data of paired events, i.e. two floods or two droughts that occurred in the same area. The 45 paired events occurred in 42 different study areas and cover a wide range of socio-economic and hydro-climatic conditions. The dataset is unique in covering both floods and droughts, in the number of cases assessed and in the quantity of socio-hydrological data. The benchmark dataset comprises (1) detailed review-style reports about the events and key processes between the two events of a pair; (2) the key data table containing variables that assess the indicators which characterize management shortcomings, hazard, exposure, vulnerability, and impacts of all events; and (3) a table of the indicators of change that indicate the differences between the first and second event of a pair. The advantages of the dataset are that it enables comparative analyses across all the paired events based on the indicators of change and allows for detailed context- and location-specific assessments based on the extensive data and reports of the individual study areas. The dataset can be used by the scientific community for exploratory data analyses, e.g. focused on causal links between risk management; changes in hazard, exposure and vulnerability; and flood or drought impacts. The data can also be used for the development, calibration, and validation of socio-hydrological models. The dataset is available to the public through the GFZ Data Services (Kreibich et al., 2023, 10.5880/GFZ.4.4.2023.001).
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9.
  • Kreibich, Heidi, et al. (author)
  • The challenge of unprecedented floods and droughts in risk management
  • 2022
  • In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 608:7921, s. 80-86
  • Journal article (peer-reviewed)abstract
    • Risk management has reduced vulnerability to floods and droughts globally, yet their impacts are still increasing. An improved understanding of the causes of changing impacts is therefore needed, but has been hampered by a lack of empirical data4,5. On the basis of a global dataset of 45 pairs of events that occurred within the same area, we show that risk management generally reduces the impacts of floods and droughts but faces difficulties in reducing the impacts of unprecedented events of a magnitude not previously experienced. If the second event was much more hazardous than the first, its impact was almost always higher. This is because management was not designed to deal with such extreme events: for example, they exceeded the design levels of levees and reservoirs. In two success stories, the impact of the second, more hazardous, event was lower, as a result of improved risk management governance and high investment in integrated management. The observed difficulty of managing unprecedented events is alarming, given that more extreme hydrological events are projected owing to climate change.
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10.
  • Phillips, M. M., et al. (author)
  • Carnegie Supernova Project-II : Extending the Near-infrared Hubble Diagram for Type Ia Supernovae to z ∼ 0.1
  • 2019
  • In: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:995
  • Journal article (peer-reviewed)abstract
    • The Carnegie Supernova Project-II (CSP-II) was an NSF-funded, four-year program to obtain optical and near-infrared observations of a Cosmology sample of similar to 100 Type. Ia supernovae located in the smooth Hubble flow (0.03 less than or similar to z less than or similar to 0.10). Light curves were also obtained of a Physics sample composed of 90 nearby Type. Ia supernovae at z <= 0.04 selected for near-infrared spectroscopic timeseries observations. The primary emphasis of the CSP-II is to use the combination of optical and near-infrared photometry to achieve a distance precision of better than 5%. In this paper, details of the supernova sample, the observational strategy, and the characteristics of the photometric data are provided. In a companion paper, the near-infrared spectroscopy component of the project is presented.
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11.
  • Stritzinger, M. D., et al. (author)
  • The Carnegie Supernova Project II : Observations of the luminous red nova AT 2014ej
  • 2020
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 639
  • Journal article (peer-reviewed)abstract
    • We present optical and near-infrared broadband photometry and optical spectra of AT 2014ej from the Carnegie Supernova Project-II. These observations are complemented with data from the CHilean Automatic Supernova sEarch, the Public ESO Spectroscopic Survey of Transient Objects, and from the Backyard Observatory Supernova Search. Observational signatures of AT 2014ej reveal that it is similar to other members of the gap-transient subclass known as luminous red novae (LRNe), including the ubiquitous double-hump light curve and spectral properties similar to that of LRN SN 2017jfs. A medium-dispersion visual-wavelength spectrum of AT 2014ej taken with the Magellan Clay telescope exhibits a P Cygni H alpha feature characterized by a blue velocity at zero intensity of approximate to 110 km s(-1) and a P Cygni minimum velocity of approximate to 70 km s(-1). We attribute this to emission from a circumstellar wind. Inspection of pre-outbust Hubble Space Telescope images yields no conclusive progenitor detection. In comparison with a sample of LRNe from the literature, AT 2014ej lies at the brighter end of the luminosity distribution. Comparison of the ultra-violet, optical, infrared light curves of well-observed LRNe to common-envelope evolution models from the literature indicates that the models underpredict the luminosity of the comparison sample at all phases and also produce inconsistent timescales of the secondary peak. Future efforts to model LRNe should expand upon the current parameter space we explore here and therefore may consider more massive systems and a wider range of dynamical timescales.
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12.
  • Yazdi, Hossein S., et al. (author)
  • Mapping breast cancer blood flow index, composition, and metabolism in a human subject using combined diffuse optical spectroscopic imaging and diffuse correlation spectroscopy
  • 2017
  • In: Journal of Biomedical Optics. - : SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS. - 1083-3668 .- 1560-2281. ; 22:4
  • Journal article (peer-reviewed)abstract
    • Diffuse optical spectroscopic imaging (DOSI) and diffuse correlation spectroscopy (DCS) are modelbased near-infrared (NIR) methods that measure tissue optical properties (broadband absorption, mu(a), and reduced scattering, mu(s)) and blood flow (blood flow index, BFI), respectively. DOSI-derived mu(a) values are used to determine composition by calculating the tissue concentration of oxy- and deoxyhemoglobin(HbO2,HbR), water, and lipid. We developed and evaluated a combined, coregistered DOSI/ DCS handheld probe for mapping and imaging these parameters. We show that uncertainties of 0.3 mm(-1) (37%) in mu(s) and 0.003 mm(-1) (33%) in mu(a) lead to similar to 53% and 9% errors in BFI, respectively. DOSI/ DCS imaging of a solid tissue-simulating flow phantom and a breast cancer patient reveals well-defined spatial distributions of BFI and composition that clearly delineates both the flow channel and the tumor. BFI reconstructed with DOSI-corrected mu(a) and mu(s) values had a tumor/ normal contrast of 2.7, 50% higher than the contrast using commonly assumed fixed optical properties. In conclusion, spatially coregistered imaging of DOSI and DCS enhances intrinsic tumor contrast and information content. This is particularly important for imaging diseased tissues where there are significant spatial variations in mu(a) and mu(s) as well as potential uncoupling between flow and metabolism. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication,
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13.
  • Breidenstein, Annika, et al. (author)
  • PrgE: an OB-fold protein from plasmid pCF10 with striking differences to prototypical bacterial SSBs
  • 2024
  • In: Life Science Alliance. - : Life Science Alliance. - 2575-1077. ; 7:8
  • Journal article (peer-reviewed)abstract
    • A major pathway for horizontal gene transfer is the transmission of DNA from donor to recipient cells via plasmid-encoded type IV secretion systems (T4SSs). Many conjugative plasmids encode for a single-stranded DNA-binding protein (SSB) together with their T4SS. Some of these SSBs have been suggested to aid in establishing the plasmid in the recipient cell, but for many, their function remains unclear. Here, we characterize PrgE, a proposed SSB from the Enterococcus faecalis plasmid pCF10. We show that PrgE is not essential for conjugation. Structurally, it has the characteristic OB-fold of SSBs, but it has very unusual DNA-binding properties. Our DNA-bound structure shows that PrgE binds ssDNA like beads on a string supported by its N-terminal tail. In vitro studies highlight the plasticity of PrgE oligomerization and confirm the importance of the N-terminus. Unlike other SSBs, PrgE binds both double- and single-stranded DNA equally well. This shows that PrgE has a quaternary assembly and DNA-binding properties that are very different from the prototypical bacterial SSB, but also different from eukaryotic SSBs.
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14.
  • Brey, Philip, et al. (author)
  • SIENNA D6.3 : Methods for translating ethical analysis into instruments for the ethical development and deployment of emerging technologies
  • 2021
  • Reports (other academic/artistic)abstract
    • In this SIENNA deliverable we present five general methods for translating ethical analysis into frameworks and methods for the ethical guidance of new emerging technologies. These are:a multistakeholder, coevolutionary strategy for ethically responsible development, deployment and use of new technology,a step-by-step method for the development of ethics guidelines and ways in which guidelines can be operationalized,a general approach for Ethics by Design, that works for all technology fields,suggestions for ethics and human rights projects on new and emerging technologies forengaging with policy-maker, and finallya method on how research ethics committees can support ethics in new emerging technology research.
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15.
  • Cousins, Melanie, et al. (author)
  • Is scientific evidence enough? Using expert opinion to fill gaps in data in antimicrobial resistance research
  • 2023
  • In: PLOS ONE. - 1932-6203. ; 18:8
  • Journal article (peer-reviewed)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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16.
  • Graells, Tiscar, et al. (author)
  • Exploring the factors that contribute to the successful implementation of antimicrobial resistance interventions : a comparison of high-income and low-middle-income countries
  • 2023
  • In: Frontiers In Public Health. - 2296-2565. ; 11
  • Journal article (peer-reviewed)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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17.
  • Graells, Tiscar, et al. (author)
  • Studying Factors Affecting Success of Antimicrobial Resistance Interventions through the Lens of Experience : A Thematic Analysis
  • 2022
  • In: Antibiotics. - : MDPI AG. - 2079-6382. ; 11:5
  • Journal article (peer-reviewed)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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18.
  • Hornung, Klaus, et al. (author)
  • On structural properties of Comet 67/P dust particles collected in situ by ROSETTA/COSIMA from observations of electrical fragmentation
  • 2023
  • In: Planetary and Space Science. ; 236
  • Journal article (peer-reviewed)abstract
    • During ESA’s Rosetta science mission, the COSIMA instrument collected dust particles in the coma of Comet 67P/Churyumov-Gerasimenko during two years near the comet’s nucleus. The largest particles are about 1 m m in size. The collection process involved a low velocity impact on porous gold-black surfaces, often resulting in breakup, from which information on structural properties has previously been derived (Langevin et al., 2016). However, some of the particles were collected with little damage, but fragmented due to charging during subsequent secondary ion mass spectrometry. This report shows that the details of this electrical fragmentation support the concept of the existence of stable units with sizes of tens of ÎŒ m within the incoming cometary dust particles prior to collection, possibly representing remnants of the early accretion processes.
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19.
  • Jardin, Fabrice, et al. (author)
  • Recurrent mutations of the exportin 1 gene (XPO1) and their impact on selective inhibitor of nuclear export compounds sensitivity in primary mediastinal B-cell lymphoma.
  • 2016
  • In: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 91:9, s. 923-30
  • Journal article (peer-reviewed)abstract
    • Primary mediastinal B-cell lymphoma (PMBL) is an entity of B-cell lymphoma distinct from the other molecular subtypes of diffuse large B-cell lymphoma (DLBCL). We investigated the prevalence, specificity, and clinical relevance of mutations of XPO1, which encodes a member of the karyopherin-β nuclear transporters, in a large cohort of PMBL. PMBL cases defined histologically or by gene expression profiling (GEP) were sequenced and the XPO1 mutational status was correlated to genetic and clinical characteristics. The XPO1 mutational status was also assessed in DLBCL, Hodgkin lymphoma (HL) and mediastinal gray-zone lymphoma (MGZL).The biological impact of the mutation on Selective Inhibitor of Nuclear Export (SINE) compounds (KPT-185/330) sensitivity was investigated in vitro. XPO1 mutations were present in 28/117 (24%) PMBL cases and in 5/19 (26%) HL cases but absent/rare in MGZL (0/20) or DLBCL (3/197). A higher prevalence (50%) of the recurrent codon 571 variant (p.E571K) was observed in GEP-defined PMBL and was associated with shorter PFS. Age, International Prognostic Index and bulky mass were similar in XPO1 mutant and wild-type cases. KPT-185 induced a dose-dependent decrease in cell proliferation and increased cell-death in PMBL cell lines harboring wild type or XPO1 E571K mutant alleles. Experiments in transfected U2OS cells further confirmed that the XPO1 E571K mutation does not have a drastic impact on KPT-330 binding. To conclude the XPO1 E571K mutation represents a genetic hallmark of the PMBL subtype and serves as a new relevant PMBL biomarker. SINE compounds appear active for both mutated and wild-type protein. Am. J. Hematol. 91:923-930, 2016. © 2016 Wiley Periodicals, Inc.
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20.
  • Léger, Anaïs, et al. (author)
  • AMR-Intervene : a social-ecological framework to capture the diversity of actions to tackle antimicrobial resistance from a One Health perspective
  • 2021
  • In: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 76:1, s. 1-21
  • Research review (peer-reviewed)abstract
    • The global threat of antimicrobial resistance (AMR) requires coordinated actions by and across different sectors. Increasing attention at the global and national Levels has Led to different strategies to tackle the challenge. The diversity of possible actions to address AMR is currently not well understood from a One Health perspective. AMR-Intervene, an interdisciplinary social-ecological framework, describes interventions to tackle AMR in terms of six components: (i) core information about the publication; (ii) social system; (iii) bio-ecological system; (iv) triggers and goals; (v) implementation and governance; and (vi) assessment. AMR-Intervene provides a broadly applicable framework, which can inform the design, implementation, assessment and reporting of interventions to tackle AMR and, in turn, enable faster uptake of successful interventions to build societal resilience to AMR.
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21.
  • Léger, Anaïs, et al. (author)
  • Characterizing social-ecological context and success factors of antimicrobial resistance interventions across the One Health spectrum : analysis of 42 interventions targeting E. coli
  • 2021
  • In: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 21:1
  • Journal article (peer-reviewed)abstract
    • Background: Antimicrobial resistance (AMR) is among the most pressing One Health issues. While interventions and policies with various targets and goals have been implemented, evidence about factors underpinning success and failure of interventions in different sectors is lacking. The objective of this study is to identify characteristics of AMR interventions that increase their capacity to impact AMR. This study focuses on AMR interventions targeting E. coli.Methods: We used the AMR-Intervene framework to extract descriptions of the social and ecological systems of interventions to determine factors contributing to their success.Results: We identified 52 scientific publications referring to 42 unique E. coli AMR interventions. We mainly identified interventions implemented in high-income countries (36/42), at the national level (16/42), targeting primarily one sector of society (37/42) that was mainly the human sector (25/42). Interventions were primarily funded by governments (38/42). Most intervention targeted a low leverage point in the AMR system, (36/42), and aimed to change the epidemiology of AMR (14/42). Among all included publications, 55% (29/52) described at least one success factor or obstacle (29/52) and 19% (10/52) identified at least one success factor and one obstacle. Most reported success factors related to communication between the actors and stakeholders and the role of media, and stressed the importance of collaboration between disciplines and external partners. Described obstacles covered data quality, access to data and statistical analyses, and the validity of the results.Conclusions: Overall, we identified a lack of diversity regarding interventions. In addition, most published E. coli interventions were poorly described with limited evidence of the factors that contributed to the intervention success or failure. Design and reporting guidelines would help to improve reporting quality and provide a valuable tool for improving the science of AMR interventions.
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22.
  • Matheson, Granville J, et al. (author)
  • Dopamine D1 receptor availability is not associated with delusional ideation measures of psychosis proneness
  • 2020
  • In: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 222, s. 175-184
  • Journal article (peer-reviewed)abstract
    • The dopamine D1 receptor (D1R) is thought to play a role in psychosis and schizophrenia, however positron emission tomography studies comparing patients and controls have been inconsistent. To circumvent some of the limitations of clinical studies, such as antipsychotic exposure, an alternative approach is to examine subclinical psychotic symptoms within the general population, i.e. psychosis proneness traits. In this study, we investigated whether D1R availability is associated with delusional ideation in healthy controls, in four experiments, using [11C]SCH23390 PET (n = 76) and psychometric questionnaires (n = 217). We performed exploratory analyses, direct self-replication, and confirmatory analyses using Bayesian statistical modelling. Collectively, we found strong evidence that there is little to no linear association between delusional ideation and D1R. If hypothesised changes in D1R in drug-naive psychosis patients can be confirmed, our results suggest that they may either occur at disease onset, or that they are associated with specific aspects of psychosis other than delusional ideation.
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23.
  • Rodriguez-Ezpeleta, Naiara, et al. (author)
  • Trade-offs between reducing complex terminology and producing accurate interpretations from environmental DNA : Comment on “Environmental DNA: What's behind the term?” by Pawlowski et al., (2020)
  • 2021
  • In: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 30:19, s. 4601-4605
  • Journal article (peer-reviewed)abstract
    • In a recent paper, “Environmental DNA: What's behind the term? Clarifying the terminology and recommendations for its future use in biomonitoring,” Pawlowski et al. argue that the term eDNA should be used to refer to the pool of DNA isolated from environmental samples, as opposed to only extra-organismal DNA from macro-organisms. We agree with this view. However, we are concerned that their proposed two-level terminology specifying sampling environment and targeted taxa is overly simplistic and might hinder rather than improve clear communication about environmental DNA and its use in biomonitoring. This terminology is based on categories that are often difficult to assign and uninformative, and it overlooks a fundamental distinction within eDNA: the type of DNA (organismal or extra-organismal) from which ecological interpretations are derived.
  •  
24.
  • Schulz, Rita, et al. (author)
  • Comet 67P/Churyumov-Gerasimenko sheds dust coat accumulated over the past four years
  • 2015
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 216-218
  • Journal article (peer-reviewed)abstract
    • Comets are composed of dust and frozen gases. The ices are mixed with the refractory material either as an icy conglomerate, or as an aggregate of pre-solar grains (grains that existed prior to the formation of the Solar System), mantled by an ice layer. The presence of water-ice grains in periodic comets is now well established. Modelling of infrared spectra obtained about ten kilometres from the nucleus of comet Hartley 2 suggests that larger dust particles are being physically decoupled from fine-grained water-ice particles that may be aggregates, which supports the icy-conglomerate model. It is known that comets build up crusts of dust that are subsequently shed as they approach perihelion. Micrometre-sized interplanetary dust particles collected in the Earth's stratosphere and certain micrometeorites are assumed to be of cometary origin. Here we report that grains collected from the Jupiter-family comet 67P/Churyumov-Gerasimenko come from a dusty crust that quenches the material outflow activity at the comet surface. The larger grains (exceeding 50 micrometres across) are fluffy (with porosity over 50 per cent), and many shattered when collected on the target plate, suggesting that they are agglomerates of entities in the size range of interplanetary dust particles. Their surfaces are generally rich in sodium, which explains the high sodium abundance in cometary meteoroids. The particles collected to date therefore probably represent parent material of interplanetary dust particles. This argues against comet dust being composed of a silicate core mantled by organic refractory material and then by a mixture of water-dominated ices. At its previous recurrence (orbital period 6.5 years), the comet's dust production doubled when it was between 2.7 and 2.5 astronomical units from the Sun, indicating that this was when the nucleus shed its mantle. Once the mantle is shed, unprocessed material starts to supply the developing coma, radically changing its dust component, which then also contains icy grains, as detected during encounters with other comets closer to the Sun.
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25.
  • Wernli, Didier, et al. (author)
  • Scope and applicability of social-ecological resilience to antimicrobial resistance
  • 2023
  • In: The Lancet Planetary Health. - 2542-5196. ; 7:7, s. e630-E637
  • Journal article (peer-reviewed)abstract
    • Social-ecological systems conceptualise how social human systems and ecological natural systems are intertwined. In this Personal View, we define the scope and applicability of social-ecological resilience to antimicrobial resistance. Resilience to antimicrobial resistance corresponds to the capacity to maintain the societal benefits of antimicrobial use and One Health systems' performance in the face of the evolutionary behaviour of microorganisms in response to antimicrobial use. Social-ecological resilience provides an appropriate framework to make sense of the disruptive impacts resulting from the emergence and spread of antimicrobial resistance; capture the diversity of strategies needed to tackle antimicrobial resistance and to live with it; understand the conditions that underpin the success or failure of interventions; and appreciate the need for adaptive and coevolutionary governance. Overall, resilience thinking is essential to improve understanding of how human societies dynamically can cope with, adapt, and transform to the growing global challenge of antimicrobial resistance.
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