| 1. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 2. |
- Ovadia, C., et al.
(author)
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Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis
- 2021
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In: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 6:7
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Journal article (peer-reviewed)abstract
- Background Ursodeoxycholic acid is commonly used to treat intrahepatic cholestasis of pregnancy, yet its largest trial detected minimal benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission). We aimed to examine whether ursodeoxycholic acid affects specific adverse perinatal outcomes. Methods In this systematic review and individual participant data meta-analysis, we searched PubMed, Web of Science, Embase, MEDLINE, CINAHL, Global Health, MIDIRS, and Cochrane without language restrictions for relevant articles published between database inception, and Jan 1, 2020, using search terms referencing intrahepatic cholestasis of pregnancy, ursodeoxycholic acid, and perinatal outcomes. Eligible studies had 30 or more study participants and reported on at least one individual with intrahepatic cholestasis of pregnancy and bile acid concentrations of 40 mu mol/L or more. We also included two unpublished cohort studies. Individual participant data were collected from the authors of selected studies. The primary outcome was the prevalence of stillbirth, for which we anticipated there would be insufficient data to achieve statistical power. Therefore, we included a composite of stillbirth and preterm birth as a main secondary outcome. A mixed-effects meta-analysis was done using multi-level modelling and adjusting for bile acid concentration, parity, and multifetal pregnancy. Individual participant data analyses were done for all studies and in different subgroups, which were produced by limiting analyses to randomised controlled trials only, singleton pregnancies only, or two-arm studies only. This study is registered with PROSPERO, CRD42019131495. Findings The authors of the 85 studies fulfilling our inclusion criteria were contacted. Individual participant data from 6974 women in 34 studies were included in the meta-analysis, of whom 4726 (67.8%) took ursodeoxycholic acid. Stillbirth occurred in 35 (0.7%) of 5097 fetuses among women with intrahepatic cholestasis of pregnancy treated with ursodeoxycholic acid and in 12 (0.6%) of 2038 fetuses among women with intrahepatic cholestasis of pregnancy not treated with ursodeoxycholic acid (adjusted odds ratio [aOR] 1.04, 95% CI 0.35-3.07; p=0.95). Ursodeoxycholic acid treatment also had no effect on the prevalence of stillbirth when considering only randomised controlled trials (aOR 0.29, 95% CI 0.04-2.42; p=0.25). Ursodeoxycholic acid treatment had no effect on the prevalence of the composite outcome in all studies (aOR 1.28, 95% CI 0.86-1.91; p=0.22), but was associated with a reduced composite outcome when considering only randomised controlled trials (0.60, 0.39-0.91; p=0.016). Interpretation Ursodeoxycholic acid treatment had no significant effect on the prevalence of stillbirth in women with intrahepatic cholestasis of pregnancy, but our analysis was probably limited by the low overall event rate. However, when considering only randomised controlled trials, ursodeoxycholic acid was associated with a reduction in stillbirth in combination with preterm birth, providing evidence for the clinical benefit of antenatal ursodeoxycholic acid treatment. Copyright (C) 2021 The Authors(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 3. |
- Lappalainen, H. K., et al.
(author)
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Overview: Recent advances in the understanding of the northern Eurasian environments and of the urban air quality in China - a Pan-Eurasian Experiment (PEEX) programme perspective
- 2022
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In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 22:7, s. 4413-4469
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Journal article (peer-reviewed)abstract
- The Pan-Eurasian Experiment (PEEX) Science Plan, released in 2015, addressed a need for a holistic system understanding and outlined the most urgent research needs for the rapidly changing Arctic-boreal region. Air quality in China, together with the long-range transport of atmospheric pollutants, was also indicated as one of the most crucial topics of the research agenda. These two geographical regions, the northern Eurasian Arctic-boreal region and China, especially the megacities in China, were identified as a "PEEX region". It is also important to recognize that the PEEX geographical region is an area where science-based policy actions would have significant impacts on the global climate. This paper summarizes results obtained during the last 5 years in the northern Eurasian region, together with recent observations of the air quality in the urban environments in China, in the context of the PEEX programme. The main regions of interest are the Russian Arctic, northern Eurasian boreal forests (Siberia) and peatlands, and the megacities in China. We frame our analysis against research themes introduced in the PEEX Science Plan in 2015. We summarize recent progress towards an enhanced holistic understanding of the land-atmosphere-ocean systems feedbacks. We conclude that although the scientific knowledge in these regions has increased, the new results are in many cases insufficient, and there are still gaps in our understanding of large-scale climate-Earth surface interactions and feedbacks. This arises from limitations in research infrastructures, especially the lack of coordinated, continuous and comprehensive in situ observations of the study region as well as integrative data analyses, hindering a comprehensive system analysis. The fast-changing environment and ecosystem changes driven by climate change, socio-economic activities like the China Silk Road Initiative, and the global trends like urbanization further complicate such analyses. We recognize new topics with an increasing importance in the near future, especially "the enhancing biological sequestration capacity of greenhouse gases into forests and soils to mitigate climate change" and the "socio-economic development to tackle air quality issues".
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| 4. |
- Schiller, D, et al.
(author)
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The Human Affectome
- 2024
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In: Neuroscience and biobehavioral reviews. - 1873-7528. ; 158, s. 105450-
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Journal article (peer-reviewed)
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| 5. |
- van Cappellen, W., et al.
(author)
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Apertif: Phased array feeds for the Westerbork Synthesis Radio Telescope: System overview and performance characteristics
- 2022
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 658
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Journal article (peer-reviewed)abstract
- We describe the APERture Tile In Focus (Apertif) system, a phased array feed (PAF) upgrade of the Westerbork Synthesis Radio Telescope that transforms this telescope into a high-sensitivity, wide-field-of-view L-band imaging and transient survey instrument. Using novel PAF technology, up to 40 partially overlapping beams are formed on the sky simultaneously, significantly increasing the survey speed of the telescope. With this upgraded instrument, an imaging survey covering an area of 2300 deg2 is being performed that will deliver both continuum and spectral line datasets, of which the first data have been publicly released. In addition, a time domain transient and pulsar survey covering 15 000 deg2 is in progress. An overview of the Apertif science drivers, hardware, and software of the upgraded telescope is presented, along with its key performance characteristics.
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| 6. |
- Barbateskovic, Marija, et al.
(author)
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A new tool to assess Clinical Diversity In Meta-analyses (CDIM) of interventions
- 2021
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In: Journal of Clinical Epidemiology. - : Elsevier BV. - 0895-4356 .- 1878-5921. ; 135, s. 29-41
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Journal article (peer-reviewed)abstract
- Objective: To develop and validate Clinical Diversity In Meta-analyses (CDIM), a new tool for assessing clinical diversity between trials in meta-analyses of interventions. Study design and setting: The development of CDIM was based on consensus work informed by empirical literature and expertise. We drafted the CDIM tool, refined it, and validated CDIM for interrater scale reliability and agreement in three groups. Results: CDIM measures clinical diversity on a scale that includes four domains with 11 items overall: setting (time of conduct/country development status/units type); population (age, sex, patient inclusion criteria/baseline disease severity, comorbidities); interventions (intervention intensity/strength/duration of intervention, timing, control intervention, cointerventions); and outcome (definition of outcome, timing of outcome assessment). The CDIM is completed in two steps: first two authors independently assess clinical diversity in the four domains. Second, after agreeing upon scores of individual items a consensus score is achieved. Interrater scale reliability and agreement ranged from moderate to almost perfect depending on the type of raters. Conclusion: CDIM is the first tool developed for assessing clinical diversity in meta-analyses of interventions. We found CDIM to be a reliable tool for assessing clinical diversity among trials in meta-analysis.
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| 7. |
- Pilla, Rachel M., et al.
(author)
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Global data set of long-term summertime vertical temperature profiles in 153 lakes
- 2021
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In: Scientific Data. - : Springer Nature. - 2052-4463. ; 8:1
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Journal article (peer-reviewed)abstract
- Climate change and other anthropogenic stressors have led to long-term changes in the thermal structure, including surface temperatures, deepwater temperatures, and vertical thermal gradients, in many lakes around the world. Though many studies highlight warming of surface water temperatures in lakes worldwide, less is known about long-term trends in full vertical thermal structure and deepwater temperatures, which have been changing less consistently in both direction and magnitude. Here, we present a globally-expansive data set of summertime in-situ vertical temperature profiles from 153 lakes, with one time series beginning as early as 1894. We also compiled lake geographic, morphometric, and water quality variables that can influence vertical thermal structure through a variety of potential mechanisms in these lakes. These long-term time series of vertical temperature profiles and corresponding lake characteristics serve as valuable data to help understand changes and drivers of lake thermal structure in a time of rapid global and ecological change.
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| 8. |
- Ackloo, S, et al.
(author)
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Target 2035 - an update on private sector contributions
- 2023
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In: RSC medicinal chemistry. - : Royal Society of Chemistry (RSC). - 2632-8682. ; 14:6, s. 1002-1011
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Journal article (other academic/artistic)abstract
- Target 2035, an international federation of biomedical scientists from the public and private sectors, is leveraging ‘open’ principles to develop a pharmacological tool for every human protein.
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| 9. |
- Au, M., et al.
(author)
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In-source and in-trap formation of molecular ions in the actinide mass range at CERN-ISOLDE
- 2023
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In: Nuclear Instruments & Methods in Physics Research Section B-Beam Interactions with Materials and Atoms. - 0168-583X. ; 541, s. 375-379
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Journal article (peer-reviewed)abstract
- The use of radioactive molecules for fundamental physics research is a developing interdisciplinary field limited dominantly by their scarce availability. In this work, radioactive molecular ion beams containing actinide nuclei extracted from uranium carbide targets are produced via the Isotope Separation On-Line technique at the CERN-ISOLDE facility. Two methods of molecular beam production are studied: extraction of molecular ion beams from the ion source, and formation of molecular ions from the mass-separated ion beam in a gas-filled radio-frequency quadrupole ion trap. Ion currents of U+, UO1-3+, UC1-3+, UF1-4+, UF1,2O1,2+ are reported. Metastable tantalum and uranium fluoride molecular ions are identified. Formation of UO1-3+, U(OH)1-3+, UC1-3+, UF1,2O1,2+ from mass-separated beams of U+, UF1,2+ with residual gas is observed in the ion trap. The effect of trapping time on molecular formation is presented.
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| 10. |
- Balibrea-Correa, J., et al.
(author)
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First measurement of the 94Nb(n,γ) cross section at the CERN n_TOF facility
- 2023
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In: EPJ Web of Conferences. - : EDP Sciences. - 2100-014X. ; 279
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Journal article (peer-reviewed)abstract
- One of the crucial ingredients for the improvement of stellar models is the accurate knowledge of neutron capture cross-sections for the different isotopes involved in the s-,r- and i- processes. These measurements can shed light on existing discrepancies between observed and predicted isotopic abundances and help to constrain the physical conditions where these reactions take place along different stages of stellar evolution.In the particular case of the radioactive 94Nb, the 94Nb(n,γ) cross-section could play a role in the determination of the s-process production of 94Mo in AGB stars, which presently cannot be reproduced by state-of-the-art stellar models. There are no previous 94Nb(n,γ) experimental data for the resolved and unresolved resonance regions mainly due to the difficulties in producing highquality samples and also due to limitations in conventional detection systems commonly used in time-of-flight experiments.Motivated by this situation, a first measurement of the 94Nb(n,γ) reaction was carried out at CERN n_TOF, thereby exploiting the high luminosity of the EAR2 area in combination with a new detection system of small-volume C6D6-detectors and a high quality 94Nb-sample. The latter was based on hyper-pure 93Nb material activated at the high-flux reactor of ILL-Grenoble. An innovative ring-configuration detection system in close geometry around the capture sample allowed us to significantly enhance the signal-to-background ratio. This set-up was supplemented with two conventional C6D6-detectors and a highresolution LaCl3(Ce)-detector, which will be employed for addressing reliably systematic effects and uncertainties.At the current status of the data analysis, 18 resonance in 94Nb+n have been observed for the first time in the neutron energy range from thermal up to 10 keV.
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