| 1. |
- Kehoe, Laura, et al.
(author)
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Make EU trade with Brazil sustainable
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Journal article (other academic/artistic)
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| 2. |
- Fernandez-Anez, Nieves, et al.
(author)
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Current Wildland Fire Patterns and Challenges in Europe : A Synthesis of National Perspectives
- 2021
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In: Air, Soil and Water Research. - : SAGE Publications. - 1178-6221. ; 14, s. 1-19
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Research review (peer-reviewed)abstract
- Changes in climate, land use, and land management impact the occurrence and severity of wildland fires in many parts of the world. This is particularly evident in Europe, where ongoing changes in land use have strongly modified fire patterns over the last decades. Although satellite data by the European Forest Fire Information System provide large-scale wildland fire statistics across European countries, there is still a crucial need to collect and summarize in-depth local analysis and understanding of the wildland fire condition and associated challenges across Europe. This article aims to provide a general overview of the current wildland fire patterns and challenges as perceived by national representatives, supplemented by national fire statistics (2009–2018) across Europe. For each of the 31 countries included, we present a perspective authored by scientists or practitioners from each respective country, representing a wide range of disciplines and cultural backgrounds. The authors were selected from members of the COST Action “Fire and the Earth System: Science & Society” funded by the European Commission with the aim to share knowledge and improve communication about wildland fire. Where relevant, a brief overview of key studies, particular wildland fire challenges a country is facing, and an overview of notable recent fire events are also presented. Key perceived challenges included (1) the lack of consistent and detailed records for wildland fire events, within and across countries, (2) an increase in wildland fires that pose a risk to properties and human life due to high population densities and sprawl into forested regions, and (3) the view that, irrespective of changes in management, climate change is likely to increase the frequency and impact of wildland fires in the coming decades. Addressing challenge (1) will not only be valuable in advancing national and pan-European wildland fire management strategies, but also in evaluating perceptions (2) and (3) against more robust quantitative evidence.
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| 3. |
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| 4. |
- Gräsner, Jan-Thorsten, et al.
(author)
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EuReCa ONE-27 Nations, ONE Europe, ONE Registry : A prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe.
- 2016
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In: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 105, s. 188-195
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Journal article (peer-reviewed)abstract
- INTRODUCTION: The aim of the EuReCa ONE study was to determine the incidence, process, and outcome for out of hospital cardiac arrest (OHCA) throughout Europe.METHODS: This was an international, prospective, multi-centre one-month study. Patients who suffered an OHCA during October 2014 who were attended and/or treated by an Emergency Medical Service (EMS) were eligible for inclusion in the study. Data were extracted from national, regional or local registries.RESULTS: Data on 10,682 confirmed OHCAs from 248 regions in 27 countries, covering an estimated population of 174 million. In 7146 (66%) cases, CPR was started by a bystander or by the EMS. The incidence of CPR attempts ranged from 19.0 to 104.0 per 100,000 population per year. 1735 had ROSC on arrival at hospital (25.2%), Overall, 662/6414 (10.3%) in all cases with CPR attempted survived for at least 30 days or to hospital discharge.CONCLUSION: The results of EuReCa ONE highlight that OHCA is still a major public health problem accounting for a substantial number of deaths in Europe. EuReCa ONE very clearly demonstrates marked differences in the processes for data collection and reported outcomes following OHCA all over Europe. Using these data and analyses, different countries, regions, systems, and concepts can benchmark themselves and may learn from each other to further improve survival following one of our major health care events.
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| 5. |
- Gräsner, Jan-Thorsten, et al.
(author)
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Survival after out-of-hospital cardiac arrest in Europe - Results of the EuReCa TWO study.
- 2020
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In: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 148, s. 218-226
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Journal article (peer-reviewed)abstract
- BACKGROUND: The epidemiology and outcome after out-of-hospital cardiac arrest (OHCA) varies across Europe. Following on from EuReCa ONE, the aim of this study was to further explore the incidence of and outcomes from OHCA in Europe and to improve understanding of the role of the bystander.METHODS: This prospective, multicentre study involved the collection of registry-based data over a three-month period (1st October 2017 to 31st December 2017). The core study dataset complied with the Utstein-style. Primary outcomes were return of spontaneous circulation (ROSC) and survival to hospital admission. Secondary outcome was survival to hospital discharge.RESULTS: All 28 countries provided data, covering a total population of 178,879,118. A total of 37,054 OHCA were confirmed, with CPR being started in 25,171 cases. The bystander cardiopulmonary resuscitation (CPR) rate ranged from 13% to 82% between countries (average: 58%). In one third of cases (33%) ROSC was achieved and 8% of patients were discharged from hospital alive. Survival to hospital discharge was higher in patients when a bystander performed CPR with ventilations, compared to compression-only CPR (14% vs. 8% respectively).CONCLUSION: In addition to increasing our understanding of the role of bystander CPR within Europe, EuReCa TWO has confirmed large variation in OHCA incidence, characteristics and outcome, and highlighted the extent to which OHCA is a public health burden across Europe. Unexplained variation remains and the EuReCa network has a continuing role to play in improving the quality management of resuscitation.
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| 6. |
- Lamers, Fieke, et al.
(author)
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Identification of BIRC6 as a novel intervention target for neuroblastoma therapy
- 2012
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 12
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Journal article (peer-reviewed)abstract
- Background: Neuroblastoma are pediatric tumors of the sympathetic nervous system with a poor prognosis. Apoptosis is often deregulated in cancer cells, but only a few defects in apoptotic routes have been identified in neuroblastoma. Methods: Here we investigated genomic aberrations affecting genes of the intrinsic apoptotic pathway in neuroblastoma. We analyzed DNA profiling data (CGH and SNP arrays) and mRNA expression data of 31 genes of the intrinsic apoptotic pathway in a dataset of 88 neuroblastoma tumors using the R2 bioinformatic platform (http://r2.amc.nl). BIRC6 was selected for further analysis as a tumor driving gene. Knockdown experiments were performed using BIRC6 lentiviral shRNA and phenotype responses were analyzed by Western blot and MTT-assays. In addition, DIABLO levels and interactions were investigated with immunofluorescence and co-immunoprecipitation. Results: We observed frequent gain of the BIRC6 gene on chromosome 2, which resulted in increased mRNA expression. BIRC6 is an inhibitor of apoptosis protein (IAP), that can bind and degrade the cytoplasmic fraction of the pro-apoptotic protein DIABLO. DIABLO mRNA expression was exceptionally high in neuroblastoma but the protein was only detected in the mitochondria. Upon silencing of BIRC6 by shRNA, DIABLO protein levels increased and cells went into apoptosis. Co-immunoprecipitation confirmed direct interaction between DIABLO and BIRC6 in neuroblastoma cell lines. Conclusion: Our findings indicate that BIRC6 may have a potential oncogenic role in neuroblastoma by inactivating cytoplasmic DIABLO. BIRC6 inhibition may therefore provide a means for therapeutic intervention in neuroblastoma.
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| 7. |
- Lamers, Fieke, et al.
(author)
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Targeted BCL2 inhibition effectively inhibits neuroblastoma tumour growth
- 2012
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In: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 48:16, s. 3093-3103
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Journal article (peer-reviewed)abstract
- Genomic aberrations of key regulators of the apoptotic pathway have hardly been identified in neuroblastoma. We detected high BCL2 mRNA and protein levels in the majority of neuroblastoma tumours by Affymetrix expression profiling and Tissue Micro Array analysis. This BCL2 mRNA expression is strongly elevated compared to normal tissues and other malignancies. Most neuroblastoma cell lines lack this high BCL2 expression. Only two neuroblastoma cell lines (KCNR and SJNB12) show BCL2 expression levels representative for neuroblastoma tumours. To validate BCL2 as a therapeutic target in neuroblastoma we employed lentivirally mediated shRNA. Silencing of BCL2 in KCNR and SJNB12 resulted in massive apoptosis, while cell lines with low BCL2 expression were insensitive. Identical results were obtained by treatment of the neuroblastoma cell lines with the small molecule BCL2 inhibitor ABT263, which is currently being clinically evaluated. Combination assays of ABT263 with most classical cytostatics showed strong synergistic responses. Subcutaneous xenografts of a neuroblastoma cell line with high BCL2 expression in NMRI nu/nu mice showed a strong response to ABT263. These findings establish BCL2 as a promising drug target in neuroblastoma and warrant further evaluation of ABT263 and other BCL2 inhibiting drugs. (C) 2012 Elsevier Ltd. All rights reserved.
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| 8. |
- Molenaar, Jan J., et al.
(author)
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Copy Number Defects of G1-Cell Cycle Genes in Neuroblastoma are Frequent and Correlate with High Expression of E2F Target Genes and a Poor Prognosis
- 2012
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In: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 51:1, s. 10-19
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Journal article (peer-reviewed)abstract
- The tightly controlled network of cell cycle genes consists of a core of cyclin dependent kinases (CDKs) that are activated by periodically expressed cyclins. The activity of the cyclin-CDK complexes is regulated by cyclin dependent kinase inhibitors (CDKIs) and multiple signal transduction routes that converge on the cell cycle. Neuroblastoma are pediatric tumors that belong to the group of small round blue cell tumors, characterized by a fast proliferation. Here, we present high throughput analyses of cell cycle regulating genes in neuroblastoma. We analyzed a series of 82 neuroblastomas by comparative genomic hybridization arrays, single nucleotide polymorphism arrays, and Affymetrix expression arrays and analyzed the datasets in parallel with the R2 bioinformatic tool (http://r2.amc.nl). About 30% of the tumors had genomic amplifications, gains, or losses with shortest regions of overlap that suggested implication of a series of G1 cell cycle regulating genes. CCND1 (cyclin D1) and CDK4 were amplified or gained and the chromosomal regions containing the CDKN2 (INK4) group of CDKIs were frequently deleted. Cluster analysis showed that tumors with genomic aberrations in G1 regulating genes over-expressed E2F target genes, which regulate S and G2/M phase progression. These tumors have a poor prognosis. Our findings suggest that pharmacological inhibition of cell cycle genes might bear therapeutic promises for patients with high risk neuroblastoma. (C) 2011 Wiley Periodicals, Inc.
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| 9. |
- Molenaar, Jan J., et al.
(author)
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Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes
- 2012
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 483:7391, s. 107-589
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Journal article (peer-reviewed)abstract
- Neuroblastomais a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour(1). Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%)(2-5). Here we present a whole-genome sequence analysis of 87 neuroblastoma of all stages. Few recurrent amino-acid-changing mutations were found. In contrast, analysis of structural defects identified a local shredding of chromosomes, known as chromothripsis, in 18% of high-stage neuroblastoma(6). These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization(7-9). In addition, ATRX, TIAM1 and a series of regulators of the Rac/Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumours with defects in these genes were aggressive high-stage neuroblastomas, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromothripsis and neuritogenesis gene alterations, which frequently occur in high-risk tumours.
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| 10. |
- Northcott, Paul A, et al.
(author)
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Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.
- 2014
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 511:7510, s. 428-428
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Journal article (peer-reviewed)abstract
- Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.
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