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- Sliz, E., et al.
(författare)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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- Kiviniemi, T., et al.
(författare)
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A randomized prospective multicenter trial for stroke prevention by prophylactic surgical closure of the left atrial appendage in patients undergoing bioprosthetic aortic valve surgery––LAA-CLOSURE trial protocol
- 2021
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 237, s. 127-134
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Tidskriftsartikel (refereegranskat)abstract
- Patients undergoing surgical aortic valve replacement (SAVR) are at high risk for atrial fibrillation (AF) and stroke after surgery. There is an unmet clinical need to improve stroke prevention in this patient population. The LAA-CLOSURE trial aims to assess the efficacy and safety of prophylactic surgical closure of the left atrial appendage for stroke and cardiovascular death prevention in patients undergoing bioprosthetic SAVR. This randomized, open-label, prospective multicenter trial will enroll 1,040 patients at 13 European sites. The primary endpoint is a composite of cardiovascular mortality, stroke and systemic embolism at 5 years. Secondary endpoints include cardiovascular mortality, stroke, systemic embolism, bleed fulfilling academic research consortium (BARC) criteria, hospitalization for decompensated heart failure and health economic evaluation. Sample size is based on 30% risk reduction in time to event analysis of primary endpoint. Prespecified reports include 30-day safety analysis focusing on AF occurrence and short-term outcomes and interim analyses at 1 and 3 years for primary and secondary outcomes. Additionally, substudies will be performed on the completeness of the closure using transesophageal echocardiography/cardiac computed tomography and long-term ECG recording at one year after the operation. © 2021 The Author(s)
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- Mainini, A. G., et al.
(författare)
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Demonstration in Relevant Environments
- 2022
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Ingår i: SpringerBriefs in Applied Sciences and Technology. - Cham : Springer Science and Business Media Deutschland GmbH. ; , s. 95-119
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Bokkapitel (refereegranskat)abstract
- Three building case studies were chosen with the purpose of demonstrating the BIM4EEB BIM-based toolkit. The selected buildings are both social houses and residential apartments respecting the needs of vulnerable inhabitants. To increase the representativeness of the test case the buildings are located in three different locations with different climatic conditions, specifically Italy, Poland, Finland. For all the case studies analysed, BIM models were created with different levels of detail (LOD), which, thanks to the interaction with the BIMMS, make it possible to create a common environment for the representation and use of the data collected and subsequently shared between the different tools. Among the three demonstration sites, the Italian site is undergoing building envelope renovation interventions such as the realization of the thermal insulation with ETICS technologies and the replacement of external windows. In order to test the different tools, a demonstration procedure has been defined for them, constituted mainly by workshop activities and quantitative and qualitative evaluations. To assess the level of accomplishment with respect to stated objectives and project success a validation methodology based on Key Performance Indicators (KPIs) was delineated. Precisely, two categories of KPIs have been identified: “mandatory” and “secondary” addressing project objectives and in connection with the literature review and project use cases and tools. To calculate the KPIs standard baselines were estimated, such as are currently in an ongoing process to assess the traditional process that can be compared with the actual value associated with the BIM-based process. The chapter will present the methods and the first intermediate results of a demonstration process that is currently not yet completed and will later see a further application of the tools in dedicated demo sites. Environmental monitoring sensors were installed in selected apartments in Polish and Italian demo site, while were installed in common spaces for the Finnish building. Specific sensors set up have been analysed and chosen to fulfil the different needs related to the specific project outcomes. Inhabitants’ availability, technical condition and flat exposition were criteria followed for the choice of apartments. Sensors allowed to improve the occupancy monitoring and to have a historical record of environmental values such as temperature, humidity and light strictly connected to users’ preferences. The mobile application about renovation activities performed and residents’ indoor home conditions—BIM4Occupants—has been installed by the users and specific workshops with inhabitants were carried out for registration purposes. The BIM Management System is currently collecting sensors’ data stream and data stream between tools such as BIM4Occupants and BIMPlanner. Project monitoring and better communication among users were tested in a different workshop by applying the BIMPlanner tool in the plans and progress site operations. The functionalities of the refurbishment scenario simulation tool—BIMeaser—were tested in qualitative and quantitative design workshops respectively with the construction professionals using the two pilot sites in Italy and in Finland and with the aim of assessing the achieved time savings of using this tool compared to the manual data input process of the scenario simulation. © 2022, The Author(s).
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- Ham, C. J., et al.
(författare)
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Towards understanding reactor relevant tokamak pedestals
- 2021
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 61:9
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Tidskriftsartikel (refereegranskat)abstract
- The physics of the tokamak pedestal is still not fully understood, for example there is no fully predictive model for the pedestal height and width. However, the pedestal is key in determining the fusion power for a given scenario. If we can improve our understanding of reactor relevant pedestals we will improve our confidence in designing potential fusion power plants. Work has been carried out as part of a collaboration on reactor relevant pedestal physics. We report some of the results in detail here and review some of the wider work which will be reported in full elsewhere. First, we attempt to use a gyrokinetic-based calculation to eliminate the pedestal top density as a model input for Europed/EPED pedestal predictions. We assume power balance at the top of the pedestal, that is, the heat flux crossing the separatrix must be equal to the heat source at the top of the pedestal and investigate the consequences of this assumption. Unfortunately, the transport assumptions of the EPED model mean that this method does not discriminate between different pairs of density and temperature profiles for a given pressure profile. Second, we investigate the effects of non flux surface density on the bootstrap current. Third, type I ELMs will not be tolerable for a reactor relevant regime due to the damage that they are expected to cause to plasma facing components. In recent years various methods of running tokamak plasmas without large ELMs have been developed. These include small and no ELM regimes, the use of resonant magnetic perturbations and the use of vertical kicks. We discuss the quiescent H-mode here. Finally we give a summary and directions for future work.
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