| 1. |
- Wang, Z., et al.
(författare)
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Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
- 2022
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:9, s. 1332-1344
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Tidskriftsartikel (refereegranskat)abstract
- Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention. Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.
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| 2. |
- Kostopoulou, ON, et al.
(författare)
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Targeted Therapy of HPV Positive and Negative Tonsillar Squamous Cell Carcinoma Cell Lines Reveals Synergy between CDK4/6, PI3K and Sometimes FGFR Inhibitors, but Rarely between PARP and WEE1 Inhibitors
- 2022
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus positive (HPV+) tonsillar and base of tongue squamous cell carcinoma (TSCC/BOTSCC) have a favorable outcome, but upon relapse, survival is poor and new therapeutical options are needed. Recently, we found synergistic effects by combining the food and drug administration approved (FDA) phosphoinositide 3-kinase (PI3K) and fibroblast-growth-factor-receptor (FGFR) inhibitors BYL719 and JNJ-42756493 on TSCC cell lines. Here this approach was extended and Cyclin-Dependent-Kinase-4/6 (CDK4/6) and Poly-ADP-ribose-polymerase (PARP) and WEE1 inhibitors PD-0332991, and MK-1775 respectively were also examined. HPV+ CU-OP-2, -3, -20, and HPV− CU-OP-17 TSCC cell lines were treated with either BYL719 and JNJ-42756493, PD-0332991 BMN-673 and MK-1775 alone or in different combinations. Viability, proliferation, and cytotoxicity were followed by WST-1 assays and the IncuCyte S3 Live® Cell Analysis System. All inhibitors presented dose-dependent inhibitory effects on tested TSCC lines. Synergy was frequently obtained when combining CDK4/6 with PI3K inhibitors, but only sometimes or rarely when combining CDK4/6 with FGFR inhibitors or PARP with WEE1 inhibitors. To conclude, using CDK4/6 with PI3K or FGFR inhibitors, especially PD-0332991 with BYL719 presented synergy and enhanced the decrease of viability considerably, while although dose dependent responses were obtained with PARP and WEE1 inhibitors (BMN-673 and MK-1775 resp.), synergy was rarely disclosed.
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| 3. |
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| 4. |
- Krege, Susanne, et al.
(författare)
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European consensus conference on diagnosis and treatment of germ cell cancer: A report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): Part I
- 2008
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 53:3, s. 478-496
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Forskningsöversikt (refereegranskat)abstract
- Objectives: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, Amsterdam, The Netherlands. Methods: Medical oncologists, urological surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference, and incorporated the new data into updated and revised guidelines. As for the first meeting, the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. Results: The first part of the consensus paper describes the clinical presentation of the primary tumor, its treatment, the importance and treatment of testicular intraepithelial neoplasia (TIN), histological classification, staging and prognostic factors, and treatment of stage I seminoma and non-seminoma. Conclusions: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early- and advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged. (C) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 5. |
- Krege, Susanne, et al.
(författare)
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European consensus conference on diagnosis and treatment of germ cell cancer: A report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): Part II
- 2008
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 53:3, s. 497-513
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Forskningsöversikt (refereegranskat)abstract
- Objectives: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, The Netherlands. Methods: Medical oncologists, urologic surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference and incorporated the new data into updated and revised guidelines. As for the first meeting the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. Results: The second part of the consensus paper includes the treatment of metastasised disease, residual tumour resection, salvage therapy, follow-up, and late toxicities. Conclusions: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early-stage as well as of advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. in addition, the particular needs of testicular cancer survivors have been acknowledged. (C) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 6. |
- Bacchin, Taneha K., et al.
(författare)
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A multi-scale approach in the planning and design of water sensitive environments
- 2013
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Ingår i: Proceedings 8th International Conference NOVATECH Lyon.
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Konferensbidrag (refereegranskat)abstract
- A spatial analytical framework to support landscape planning and urban design practices was introduced in this study aiming to integrate different scales of analysis and their effect when retrofitting Water Sensitive Urban Design (WSUD) in the existing urban environment. The multi-scale analyses are performed using a geographic information system (GIS) platform to capture landscape patterns (spatial structure and composition) and processes (e.g. water cycle). The macro-scale analysis at the urban catchment level allows the development of planning strategies and performance objectives for the urbanized landscape, whilst the meso-scale, comprising the ecological (green) corridors, connects core areas conveying surface flows across the sub-catchments. At the neighbourhood scale, urban form parameters measured the territorial depth (permeability) between public and private land and the suitability of each site to retrofit Water Sensitive Urban Design. The feasibility to improve or extend the existing green-blue landscape matrix is assessed, and its implications discussed, by using a sequence of landscape metrics, land suitability and network analysis techniques. The study focused on modelling opportunities for the introduction of landscape features designed to improve surface stormwater management and, at the same time, provide multiple ecosystem services.
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| 7. |
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| 8. |
- Berghauser Pont, Meta, 1972, et al.
(författare)
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Quantitative comparison of cities : Distribution of street and building types based on density and centrality measures
- 2017
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Ingår i: Proceedings - 11th International Space Syntax Symposium, SSS 2017. - : Instituto Superior Tecnico, Departamento de Engenharia Civil, Arquitetura e Georrecursos. - 9789729899447 ; 2, s. 44.1-44.18
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Konferensbidrag (refereegranskat)abstract
- It has been argued that different urban configurations-planned vs. organic, treelike vs. grid like-perform differently when it comes to the intensity and distribution of pedestrian flows, built density and land uses. However, definitions of urban configurations are often rather abstract, ill-defined and at worse end in fixed stereotypes hiding underlying spatial complexity. Recent publications define morphological typologies based on quantitative variables (e.g. Barthelemy, 2015; Serra, 2013a; Gil et al., 2012; Berghauser Pont and Haupt, 2010) and solve some of these shortcomings. These approaches contribute to the discussion of types in two ways: firstly, they allow for the definition of types based on multiple variables in a precise and repeattable manner, enabling the study of large samples and the comparison between both cities and regions; secondly, they frame design choices in terms of types without being fixed and so open up for design explorations where the relation between the variables can be challenged to propose new types. This paper explores the typologies defined by Serra (2013a) and Berghauser Pont and Haupt (2010) further, as these target two of the most important morphological entities of urban form, namely the street network and the building structure. The purpose is to gain a better understanding of how types are composed and distributed within and across different cities. The method is based on GIS and statistical modeling of four cities to allow for a comparative analysis of four cities: Amsterdam, London, Stockholm and Gothenburg. For the street network, we process the Road-Centre-line maps to obtain a clean network model, then run segment angular analysis to calculate the space syntax measures of betweenness at different metric radii, defining the "centrality palimpsest" (Serra, 2013a). For the building structure, we process elevation data to obtain building height, then run accessible density analysis for all building density metrics (FSI, GSI, OSR, L) using the Place Syntax Tool (Berghauser Pont and Marcus, 2014). The street and building types are defined using cluster analysis (unsupervised classification), following a similar approach to Serra (2013a). The result is a typology of street ('paths') and building types ('places'), with different profiles of centrality and density across scales. The spatial distribution and frequency of these types across the four cities gives an objective summary of their spatial structure, identifying common as well as unique traits.
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| 9. |
- Berghauser Pont, Meta, 1972, et al.
(författare)
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The spatial distribution and frequency of street, plot and building types across five European cities
- 2019
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Ingår i: Environment and Planning B-Urban Analytics and City Science. - : SAGE Publications. - 2399-8083 .- 2399-8091. ; 46:7, s. 1226-1242
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Tidskriftsartikel (refereegranskat)abstract
- Typologies have always played an important role in urban planning and design practice and formal studies have been central to the field of urban morphology. These studies have predominantly been of a historical-qualitative nature and do not support quantitative comparisons between urban areas and between different cities, nor offer the precise and comprehensive descriptions needed by those engaged in urban planning and design practice. To describe contemporary urban forms, which are more diffuse and often elude previous historic typologies, systematic quantitative methods can be useful but, until recently, these have played a limited role in typo-morphological studies. This paper contributes to recent developments in this field by integrating multi-variable geometric descriptions with inter-scalar relational descriptions of urban form. It presents typologies for three key elements of urban form (streets, plots and buildings) in five European cities, produced using statistical clustering methods. In a first instance, the resulting typologies contribute to a better understanding of the characteristics of streets, plots and buildings. In particular, the results offer insight into patterns between the types (i.e. which types are found in combination and which not) and provide a new large scale comparative analysis across five European cities. To conclude, a link between quantitative analysis and theory is established, by testing two well-known theoretical propositions in urban morphology: the concept of the burgage cycle and the theory of natural movement.
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