| 1. |
- Thompson, B.A., et al.
(författare)
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Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:2, s. 107-115
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Tidskriftsartikel (refereegranskat)abstract
- The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary expert committee review of the clinical and functional data available for variants, applied to 2,360 sequence alterations, and disseminated online. Assessment using validated criteria altered classifications for 66% of 12,006 database entries. Clinical recommendations based on transparent evaluation are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation and classification of variants in public locus-specific databases. © 2014 Nature America, Inc.
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| 2. |
- Abellán, C., et al.
(författare)
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Challenging Local Realism with Human Choices
- 2018
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 557, s. 212-216
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Tidskriftsartikel (refereegranskat)abstract
- A Bell test is a randomized trial that compares experimental observations against the philosophical worldview of local realism , in which the properties of the physical world are independent of our observation of them and no signal travels faster than light. A Bell test requires spatially distributed entanglement, fast and high-efficiency detection and unpredictable measurement settings. Although technology can satisfy the first two of these requirements, the use of physical devices to choose settings in a Bell test involves making assumptions about the physics that one aims to test. Bell himself noted this weakness in using physical setting choices and argued that human 'free will' could be used rigorously to ensure unpredictability in Bell tests. Here we report a set of local-realism tests using human choices, which avoids assumptions about predictability in physics. We recruited about 100,000 human participants to play an online video game that incentivizes fast, sustained input of unpredictable selections and illustrates Bell-test methodology. The participants generated 97,347,490 binary choices, which were directed via a scalable web platform to 12 laboratories on five continents, where 13 experiments tested local realism using photons, single atoms, atomic ensembles and superconducting devices. Over a 12-hour period on 30 November 2016, participants worldwide provided a sustained data flow of over 1,000 bits per second to the experiments, which used different human-generated data to choose each measurement setting. The observed correlations strongly contradict local realism and other realistic positions in bi-partite and tri-partite 12 scenarios. Project outcomes include closing the 'freedom-of-choice loophole' (the possibility that the setting choices are influenced by 'hidden variables' to correlate with the particle properties), the utilization of video-game methods for rapid collection of human-generated randomness, and the use of networking techniques for global participation in experimental science.
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| 3. |
- Redeker, Cornelia
(författare)
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Rhine cities - urban flood integration (UFI) : German and Dutch adaptation and mitigation strategies
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Flood Risk Management along the Rhine today combines river expanding measures and adaptive strategies with the existing defensive system to cope with the risk increase as a consequence of previous interventions and developments and fluctuations in water levels due to climate change. Differences in landscapes and urgencies and differences in planning cultures between the Upper and Lower Rhine and the Delta have also led to different strategic approaches. Within this research the innovative capacity of the adaptive and anticipatory water-based approach in the Netherlands provides lessons to be learned specifically regarding spatial quality as a strategic component of water-related projects.While agglomerations along the Rhine are confronted with the uncertainties of an increasing flood risk due to climate change, different programs are claiming urban river front sites. Simultaneously, urban development, flood management, as well as navigation and environmental protection are negotiating the border between the river and the urban realm. This produces complex spatial constellations between the river system and the urban realm with a diverse set of interdependencies, where programs have to synergize while adapting to dynamic water levels. Based on an expanding area at risk and the reliance on flood levels to remain within an acceptable spectrum for adaptive measures to be effective, Urban Flood Integration (UFI) involves border negotiations between the river and the urban realm where adaptation and mitigation ideally synergize. In summary, differences in landscape, threat and political structures have produced different planning cultures in Germany and the Netherlands in terms of flood management. Both Dutch and German mitigation measures remain path dependent on the defensive system. Yet, whereas the Dutch approach to flood mitigation is holistic in an extended ecological sense and specifically includes spatial quality, in Germany, planning flood-related issues remains part of a sectoral approach where spatial quality is not initially included, bit remains an additional layer towards the end of the project. Confronted with a strong ecological lobby, the focus is to restore the former alluvial forest in niches. Of the six programs defined in the ICPR Atlas, forestry seems the only one capable of taking on river dynamics and transforming accordingly over time. All other programs (settlements, industries, traffic infrastructure, and to some degree agriculture, specifically when ecological flooding is taken into account) remain reliant on defensive measures, and in case of their failure, infrastructural support and adaptation measures. They are, however, not included in a design strategy that explores potentialities. Part I serves as a narrative for the case study analysis and for the final conclusions and recommendations in Part II. It is made up of three chapters, where Urban Flood Integration is framed historically, theoretically and strategically within the specific geographic context of the navigable Rhine.Directly adressing the design practice, this research proposes to move from a spatial to a strategic design approach byinvolving architects, landscape architects, urban designers from the initial stage to enable their engagement also in the strategic design of a project;enabling design to become part of a systemic approach that aims for capacity building and therefore includes ecological, economic and cultural conditions through a transdisciplinary approach;making the invisible layers visible: Visualize systems/expert information to make them accessible and to enable communication between disciplines;hosting design competitions in cooperation with local stakeholders bringing people and ideas together to trigger emergence;applying back-casting strategies to move beyond existing conceptions: design may thus becomes “telescopic” and allow a challenge of existing givens, the visualization of concepts again playing a central role.
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| 7. |
- ten Broeke, SW, et al.
(författare)
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Cancer Risks for PMS2-Associated Lynch Syndrome
- 2018
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 36:29, s. 2961-
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Zinchuk, A. V., et al.
(författare)
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Physiological Traits and Adherence to Sleep Apnea Therapy in Individuals with Coronary Artery Disease
- 2021
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 204:6, s. 703-712
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Untreated obstructive sleep apnea (OSA) is associated with adverse outcomes in patients with coronary artery disease (CAD). Continuous positive airway pressure (CPAP) is the most common treatment, but despite interventions addressing established adherence determinants, CPAP use remains poor. Objectives: To determine whether physiological traits that cause OSA are associated with long-termCPAP adherence in patients with CAD. Methods: Participants in the RICCADSA (Randomized Intervention with CPAP in CAD and OSA) trial with objective CPAP adherence (h/night) over 2 years and analyzable raw polysomnography data were included (N= 249). The physiological traits-loop gain, arousal threshold (ArTH), pharyngeal collapsibility (<(V)over dot> passive), and pharyngeal muscle compensation (<(V)over dot>comp)-were measured by using polysomnography. Linear mixed models were used to assess the relationship between the traits and adherence. We also compared actual CPAP adherence between those with physiologically predicted "poor" adherence (lowest quartile of predicted adherence) and those with physiologically predicted "good" adherence (all others). Measurements and Main Results: The median (interquartile range) CPAP use declined from 3.2 (1.0-5.8) h/night to 3.0 (0.0-5.6) h/night over 24 months (P, 0.001). In analyses adjusted for demographics, anthropometrics, OSA characteristics, and clinical comorbidities, a lower ArTH was associated with worse CPAP adherence (0.7 h/SD of the ArTH; P = 0.021). Both high and low <(V)over dot> comp were associated with lower adherence (P = 0.008). Those with predicted poor adherence exhibited markedly lower CPAP use than those with predicted good adherence for up to 2 years of follow-up (group differences of 2.0-3.2 h/night; P, 0.003 for all). Conclusions: A low ArTH, as well as a very low and high <(V)over dot> comp, are associated with worse long-term CPAP adherence in patients with CAD and OSA. Physiological traits-alongside established determinants-may help predict and improve CPAP adherence.
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