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| 2. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 3. |
- Bertolotto, Corine, et al.
(författare)
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A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 480:7375, s. 94-98
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Tidskriftsartikel (refereegranskat)abstract
- So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes(1); risk factors associated with RCC include smoking, obesity and hypertension(2). A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers(3). The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene(4); it also stimulates the transcription of hypoxia inducible factor(5) (HIF1A), the pathway of which is targeted by kidney cancer susceptibility genes(6). We therefore proposed that MITF might have a role in conferring a genetic predisposition to co-occurring melanoma and RCC. Here we identify a germline missense substitution in MITF (Mi-E318K) that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls. Overall, Mi-E318K carriers had a higher than fivefold increased risk of developing melanoma, RCC or both cancers. Codon 318 is located in a small-ubiquitin-like modifier (SUMO) consensus site (Psi KXE) and Mi-E318K severely impaired SUMOylation of MITF. Mi-E318K enhanced MITF protein binding to the HIF1A promoter and increased its transcriptional activity compared to wild-type MITF. Further, we observed a global increase in Mi-E318K occupied loci. In an RCC cell line, gene expression profiling identified a Mi-E318K signature related to cell growth, proliferation and inflammation. Lastly, the mutant protein enhanced melanocytic and renal cell clonogenicity, migration and invasion, consistent with a gain-of-function role in tumorigenesis. Our data provide insights into the link between SUMOylation, transcription and cancer.
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| 4. |
- Bousquet, Jean, et al.
(författare)
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ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
- 2021
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
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Forskningsöversikt (refereegranskat)abstract
- Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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| 5. |
- Bousquet, J. Jean, et al.
(författare)
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Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
- 2019
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Ingår i: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
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Forskningsöversikt (refereegranskat)abstract
- Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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| 6. |
- Gernay, Thomas, et al.
(författare)
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Experimental investigation of structural failure during the cooling phase of a fire : Timber columns
- 2023
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Ingår i: Fire and Materials. - : John Wiley and Sons Ltd. - 0308-0501 .- 1099-1018. ; 47:4, s. 445-
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes fire tests on loaded glued laminated timber columns in which the structural response was measured during the heating and cooling phases. Identical columns with 280 × 280 mm2 cross-section and 3.7 m length were tested under various heating durations in a standard furnace to investigate integrity to full burnout. Two of the columns were subjected to ISO 834 heating until failure and their measured fire resistance was 55 and 58 min, respectively. Two columns were subjected to 15 min of ISO 834 heating followed by controlled cooling; these columns failed during the cooling phase, respectively after 98 and 153 min. Flame self-extinction occurred after approximately 40 min while smoldering continued locally. Two columns tested under 10 min of ISO 834 heating both survived the defined heating–cooling exposure. Thermocouples inside the columns show sustained temperature increases for hours after the end of the heating phase. These full-scale furnace experiments show that timber columns may fail during the cooling phase after exposure to standard heating for about 25% of the standard fire resistance duration. These results, in line with previous numerical predictions, highlight the need for further investigation into fire safety until full burnout for timber structures.
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| 7. |
- Gernay, Thomas, et al.
(författare)
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Experimental investigation of structural failure during the cooling phase of a fire : Concrete columns
- 2022
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Ingår i: Fire safety journal. - : Elsevier Ltd. - 0379-7112 .- 1873-7226. ; 134
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Tidskriftsartikel (refereegranskat)abstract
- Structures may collapse during the cooling phase of a fire, yet standard furnace tests only measure the response under heating. There lacks experimental test protocols and design methods to assess resistance until burnout. This paper describes a new experimental approach for burnout resistance evaluation, reports experimental data on loaded reinforced concrete columns in furnace tests with cooling down phases, and presents numerical models of the tests. The test results show that columns designed for a standard fire resistance of 60 min exhibited a fire resistance of 83 min in the furnace but failed during the cooling phase when the burners were shut off after 72 min while the load was maintained. Two other specimens survived exposure to heating of 45 and 55 min, respectively, and their residual capacity was measured. Finite element analyses show agreement with the tests, showing applicability of numerical methods for evaluating burnout resistance of concrete columns. These findings demonstrate experimentally that delayed thermal-mechanical effects can jeopardize structural stability in real fires, and provide a framework to measure these effects. Moving beyond fire resistance to quantify the response until burnout will support designs for safety of occupants and firefighters throughout the fire and promote repairability and resilience.
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| 8. |
- Mohaine, Siyimane, et al.
(författare)
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Cross-comparison of screening tests for fire spalling of concrete
- 2021
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Ingår i: Fire and Materials. - : John Wiley and Sons Ltd. - 0308-0501 .- 1099-1018. ; 45:7, s. 929-
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Tidskriftsartikel (refereegranskat)abstract
- Concrete spalling is an important phenomenon to consider when evaluating the fire behavior of concrete, as this can sometimes have an impact on the structural capacity of the studied element. Spalling can be assessed experimentally using screening tests although it is influenced by the size, geometry, and boundary conditions of the tested element, among other factors. No standardized and systematic methods are yet available to assess concrete spalling sensitivity by testing. Plus, comparative results between screenings tests (small and medium scale) and full-scale tests to evaluate their representativity remain scarce in the literature. In this study, five different spalling tests—with different geometries and boundary conditions—that are used as screening tests were investigated. A concrete mix known to be sensitive to spalling was used to evaluate the representativity of two types of screening tests (material screening tests and intermediate-scale screening tests). The representativity of these test setups was evaluated by comparing the measured spalling depths to the spalling measured on a full-scale slab test using the same concrete mix. This comparative study confirmed that the presence of load and/or restraint was essential for a good representativity for a screening test but should always be implemented in large enough specimens.
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| 9. |
- Mohaine, Siyimane, et al.
(författare)
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PERFORMANCE OF PASSIVE PROTECTION OF CROSS LAMINATED TIMBER DURING STANDARD FURNACE TESTS AND NATURAL FIRES
- 2023
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Ingår i: 13th World Conference on Timber Engineering, WCTE 2023. - 9781713873297 ; 3, s. 1839-1847
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Konferensbidrag (refereegranskat)abstract
- This paper presents the results of an experimental campaign designed to compare and understand the performance of passive protection under exposure to standard furnace tests and natural fires. As part of this campaign, five natural fire experiments were performed with partially protected cross-laminated timber (CLT) compartments under a range of ventilation conditions. In all the tests, only one side wall was left completely unprotected, and all other timber surfaces were protected with either two layers of 18 mm standard gypsum boards (GB) or two layers of 25 mm standard GBs. The structural CLT ceilings were subjected to a superimposed dead load of 1.35 kN/m² during the natural fire tests, and the fire load was (on average) 950 MJ/m²; chosen to represent the Eurocode 1991-1-2 characteristic value for dwellings. The performance of the passive protection was mainly evaluated with regards to the time to reach a protected timber surface temperature of 250°C. The testing confirms that the resulting fire protection performance of a given gypsum board layout depends on the ventilation conditions of the fire compartment, with more severe (and closest to ISO testing) outcomes when testing under ventilation-controlled scenarios. This paper provides data that sheds light on the co-dependency of the passive protection design and compartment fire dynamics and underlines the importance of considering the safety objectives of a building when defining the performance criteria of its structural elements.
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| 10. |
- Pimienta, Pierre, et al.
(författare)
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Recommendation of RILEM TC 256-SPF on fire spalling assessment during standardised fire resistance tests : complementary guidance and requirements
- 2024
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Ingår i: Materials and Structures/Materiaux et Constructions. - : Springer Science and Business Media B.V.. - 1359-5997 .- 1871-6873. ; 57:1
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Tidskriftsartikel (refereegranskat)abstract
- The recommendation is based on the co-authors’ work organized by the RILEM TC 256-SPF “Spalling of concrete due to fire: testing and modelling”. It aims to provide useful information, guidance and best practices in fire spalling assessment to laboratories that perform large-scale tests based on fire resistance test standards. It provides guidance on the spalling observation techniques during testing, as well as post-test spalling quantification/assessment methods. This document is intended to be used in conjunction with the fire resistance test standards, e.g. EN 1363-1 and ISO 834-1.
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