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| 2. |
- Craddock, Nick, et al.
(author)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Journal article (peer-reviewed)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 3. |
- Hill, Annette, et al.
(author)
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Nordic Noir
- 2017
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In: Oxford Research Encyclopedia of Criminology and Criminal Justice. - : Oxford University Press. ; , s. 1-21
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Book chapter (peer-reviewed)abstract
- Nordic noir is an emerging crime genre that draws on crime fiction, feature film, and television drama. The term Nordic noir is associated with a region (Scandinavia), with a mood (gloomy and bleak), with a look (dark and grim), and with strong characters and a compelling narrative. Such is the popularity of Nordic noir as a brand for crime that it can also, and somewhat confusingly, be associated with disparate, bleak dramas set in particular locations outside the Scandinavian region (Sweden, Denmark, Norway, Iceland, and Finland), such as Wales, Italy, France, Mexico, and the United States. As such, Nordic noir is a global brand that attracts transnational audiences, and at the same time, it is a genre that offers a specific style of storytelling that has the look and feel of a regional, moody, and compelling crime narrative.The approach to Nordic noir taken in this article analyzes the genre as multidimensional, involving production and institutional contexts, creative practices, and the practices of audiences and fans. The research uses empirical and theoretical analysis drawing on genre analysis, as well as production and audience studies, including qualitative interviews and participant observations with executive and creative producers, viewers, and fans. Nordic noir is not a fixed genre; rather, it is in a constant process of iteration as it mutates, hybridizes and migrates from one location to another, where it may be received and understood in different ways. The concept of “genre work” is useful in helping to capture and critically analyze Nordic noir from multiple perspectives, taking into account the complex ways in which this genre is a cocreation between industries and audiences. This is particularly evident in the case of the Danish-Swedish coproduction Broen/Bron/The Bridge (2011), which provides an illuminating case study of these processes at work. It is this constantly ongoing notion of genre work that illuminates the fluidity of Nordic noir, where its meaning and symbolic power is cocreated by institutions, producers, and audiences.
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| 4. |
- Hill, Annette, et al.
(author)
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Saga’s Story : Emotional Engagement in the Production and Reception of The Bridge
- 2018
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In: European Television Crime Drama and Beyond. - 9783319968865 - 9783319968872 ; , s. 269-284
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Book chapter (peer-reviewed)abstract
- This research examines emotional engagement with Nordic crime drama The Bridge, using a cultural approach to genre, affect and emotion, and exploring how executive and creative producers, artistic performers, and audiences all perform specific practices that culminate in the co-production of intense engagement with this crime drama. The fieldwork took place during 2013-2016, with 40 production interviews and 170 audience interviews and participant observations in Sweden, Denmark, and Great Britain. A key research question concerns how genre, affect and emotion are interwoven in the fine details of the production of this crime drama and audience engagement with it.
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| 6. |
- Jones, Robert P., et al.
(author)
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Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma : A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
- 2019
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In: JAMA Surgery. - : AMER MEDICAL ASSOC. - 2168-6254 .- 2168-6262. ; 154:11, s. 1038-1048
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Journal article (peer-reviewed)abstract
- Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P=.03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P=.04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P=.27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P=.85 and P=.35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P=.03).Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.Trial Registration: ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434. This secondary analysis of a randomized clinical trial investigates patterns of recurrence after adjuvant chemotherapy in pancreatic cancer and the association with survival.
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| 7. |
- Stenzinger, Albrecht, et al.
(author)
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Implementation of precision medicine in healthcare—A European perspective
- 2023
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In: Journal of Internal Medicine. - 0954-6820 .- 1365-2796. ; 294:4, s. 437-454
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Research review (peer-reviewed)abstract
- The technical development of high-throughput sequencing technologies and the parallel development of targeted therapies in the last decade have enabled a transition from traditional medicine to personalized treatment and care. In this way, by using comprehensive genomic testing, more effective treatments with fewer side effects are provided to each patient—that is, precision or personalized medicine (PM). In several European countries—such as in England, France, Denmark, and Spain—the governments have adopted national strategies and taken “top-down” decisions to invest in national infrastructure for PM. In other countries—such as Sweden, Germany, and Italy with regionally organized healthcare systems—the profession has instead taken “bottom-up” initiatives to build competence networks and infrastructure to enable equal access to PM. In this review, we summarize key learnings at the European level on the implementation process to establish sustainable governance and organization for PM at the regional, national, and EU/international levels. We also discuss critical ethical and legal aspects of implementing PM, and the importance of access to real-world data and performing clinical trials for evidence generation, as well as the need for improved reimbursement models, increased cross-disciplinary education and patient involvement. In summary, PM represents a paradigm shift, and modernization of healthcare and all relevant stakeholders—that is, healthcare, academia, policymakers, industry, and patients—must be involved in this system transformation to create a sustainable, non-siloed ecosystem for precision healthcare that benefits our patients and society at large.
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| 8. |
- Tesi, Bianca, et al.
(author)
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Precision medicine in rare diseases : What is next?
- 2023
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 294:4, s. 397-412
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Research review (peer-reviewed)abstract
- Molecular diagnostics is a cornerstone of modern precision medicine, broadly understood as tailoring an individual's treatment, follow-up, and care based on molecular data. In rare diseases (RDs), molecular diagnoses reveal valuable information about the cause of symptoms, disease progression, familial risk, and in certain cases, unlock access to targeted therapies. Due to decreasing DNA sequencing costs, genome sequencing (GS) is emerging as the primary method for precision diagnostics in RDs. Several ongoing European initiatives for precision medicine have chosen GS as their method of choice. Recent research supports the role for GS as first-line genetic investigation in individuals with suspected RD, due to its improved diagnostic yield compared to other methods. Moreover, GS can detect a broad range of genetic aberrations including those in noncoding regions, producing comprehensive data that can be periodically reanalyzed for years to come when further evidence emerges. Indeed, targeted drug development and repurposing of medicines can be accelerated as more individuals with RDs receive a molecular diagnosis. Multidisciplinary teams in which clinical specialists collaborate with geneticists, genomics education of professionals and the public, and dialogue with patient advocacy groups are essential elements for the integration of precision medicine into clinical practice worldwide. It is also paramount that large research projects share genetic data and leverage novel technologies to fully diagnose individuals with RDs. In conclusion, GS increases diagnostic yields and is a crucial step toward precision medicine for RDs. Its clinical implementation will enable better patient management, unlock targeted therapies, and guide the development of innovative treatments.
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| 9. |
- Testor, Pierre, et al.
(author)
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OceanGliders: A component of the integrated GOOS
- 2019
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In: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6
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Research review (peer-reviewed)abstract
- The OceanGliders program started in 2016 to support active coordination and enhancement of global glider activity. OceanGliders contributes to the international efforts of the Global Ocean Observation System (GOOS) for Climate, Ocean Health and Operational Services. It brings together marine scientists and engineers operating gliders around the world: (1) to observe the long-term physical, biogeochemical, and biological ocean processes and phenomena that are relevant for societal applications; and, (2) to contribute to the GOOS through real-time and delayed mode data dissemination. The OceanGliders program is distributed across national and regional observing systems and significantly contributes to integrated, multi-scale and multi-platform sampling strategies. OceanGliders shares best practices, requirements, and scientific knowledge needed for glider operations, data collection and analysis. It also monitors global glider activity and supports the dissemination of glider data through regional and global databases, in real-time and delayed modes, facilitating data access to the wider community. OceanGliders currently supports national, regional and global initiatives to maintian and expand the capabilities and application of gliders to meet key global challenges such as improved measurement of ocean boundary currents, water transformation and storm forecast.
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