| 1. |
- Surendran, Praveen, et al.
(författare)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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| 2. |
- Cristescu, Carmen, et al.
(författare)
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Design for deconstruction and reuse of timber structures – state of the art review
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report is a state-of-the-art on timber construction in selected european countries and and discusses technical premises for a potential circular use of timber in building construction, focusing on Design for Deconstruction and Reuse (DfDR) in low-rise timber buildings, up to 3 storeys. It describes the historic and contemporary building techniques of timber buildings in all project countries (Sweden, Finland, Ireland, UK, Spain, Germany, Slovenia) and finds, that all of these countries have a long history of building with timber, but in most regions other materials dominated the housing output from the beginning of the 20th century. Only in the second half of the 20th century timber started gaining importance as a building material in Europe again, with light timber frame construction becoming an important construction system. From the beginning of the 21st century, innovations in the sector started transforming the construction industry. Mass timber products like CLT opened the market for high-rise timber buildings and in some countries office blocks, schools and hotels are built using timber, although the majority of timber construction remains residential. An even more important development might be the uptake of offsite construction, that makes timber construction more accurate, material efficient, fast and it reduces waste. These modern methods of construction are gaining importance in the construction sector of all partner countries and are likely to dominate the European housing output in the future. There will be some regional differences in the level of prefabrication, material choices and designs, so that any design guidelines for DfDR need to be adapted to the regional context. However, modern timber construction is not currently aligned with circular economy principles and is seldomly taking buildings endof-life-into account.Therefore, the report continues to summarise novel design concepts for deconstruction and reuse, that could be used in modern timber buildings. It outlines that the feasibility as well as the reuse potential depends on the scale of reclaimed components, where larger components and assemblies are often considered beneficial in terms of time, greenhouse gas emissions and waste production. If volumetric or planar units could be salvaged in the future, they also need to be adaptable for altered regulations or standards or alternative functions. It is further necessary that assemblies can be altered within buildings, since different building components have different life expectancies. Various examples for DfDR in buildings with the accompanying design strategies are presented. The buildings in the examples are often designed to be in one place for a limited timeframe and can be deconstructed and re-erected elsewhere without replacement of components. Key-features often include modularity of components, reversible connections, adaptability of the floor-plan and circular procurement. Even though it is evidently possible, the structural reuse of timber is not a wide-spread approach to date. Barriers to the use of reclaimed structural components are mainly a lack in demand for salvaged materials, but also prohibitive building regulations and the lack of design standards. Demolition practices play a crucial role as well and need to be considered in the design of buildings, to avoid damage to the components.Finally, the report summarises principles and guidelines for DfDR by different authors. As a generic approach an indicator system for deconstructability and reusability could be introduced. Time, Separability, Risk and Safety, Simplicity and Interchangeability are identified5as the main indicators for DfDR, that remain somewhat abstract. As opposed to using a generic indicator system, a more practical approach of assessing DfDR on an individual basis could be taken. This way specific shortcomings of the design can be addressed. But if DfDR found a wider application in the future, this approach may be too time consuming and there is a need for a more directed decision-making tool that can be used during the design phase of buildings to enhance DfDR. As the InFutUReWood project proceeds, it will examine a more granular approach to DfDR, relating it to the actual construction stages used in practice, developing a general template to be appropriated and adjusted to account for regional variations in construction. A strategic matrix is in development which will provide designers with a methodology based on relating principles, strategies and specific tactics to the typical design stages, to aid design decisions that promote DfDR.
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| 3. |
- Abreu, Soraia Carvalho, et al.
(författare)
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Differential effects of the cystic fibrosis lung inflammatory environment on mesenchymal stromal cells
- 2020
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Ingår i: American Journal of Physiology: Lung Cellular and Molecular Physiology. - : American Physiological Society. - 1040-0605 .- 1522-1504.
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Tidskriftsartikel (refereegranskat)abstract
- Growing evidence demonstrates that human mesenchymal stromal cells (MSCs) modify their in vivo anti-inflammatory actions depending on the specific inflammatory environment encountered. Understanding this better is crucial to refine MSC-based cell therapies for lung and other diseases. Using acute exacerbations of cystic fibrosis (CF) lung disease as a model, the effects of ex vivo MSC exposure to clinical bronchoalveolar lavage fluid (BALF) samples, as a surrogate for the in vivo clinical lung environment, on MSC viability, gene expression, secreted cytokines, and mitochondrial function was compared to effects of BALF collected from healthy volunteers. CF BALF samples which cultured positive for Aspergillus sp. (Asp) induced rapid MSC death, usually within several hours of exposure. Further analyses suggested the fungal toxin gliotoxin as a potential mediator contributing to CF BALF-induced MSC death. RNA sequencing analyses of MSCs exposed to either Asp+ or Asp- CF BALF samples identified a number of differentially expressed transcripts, including those involved in interferon-signaling, anti-microbial gene expression, and cell death. Toxicity did not correlate with bacterial lung infections. These results suggest that the potential use of MSC-based cell therapies for CF or other lung diseases may not be warranted in the presence of Aspergillus.
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| 4. |
- Fazey, Ioan, et al.
(författare)
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Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
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Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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| 5. |
- Franklin, Oskar, et al.
(författare)
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Organizing principles for vegetation dynamics
- 2020
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Ingår i: Nature plants. - : Springer Science and Business Media LLC. - 2055-026X .- 2055-0278. ; 6:5, s. 444-453
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Tidskriftsartikel (refereegranskat)abstract
- Plants and vegetation play a critical-but largely unpredictable-role in global environmental changes due to the multitude of contributing processes at widely different spatial and temporal scales. In this Perspective, we explore approaches to master this complexity and improve our ability to predict vegetation dynamics by explicitly taking account of principles that constrain plant and ecosystem behaviour: natural selection, self-organization and entropy maximization. These ideas are increasingly being used in vegetation models, but we argue that their full potential has yet to be realized. We demonstrate the power of natural selection-based optimality principles to predict photosynthetic and carbon allocation responses to multiple environmental drivers, as well as how individual plasticity leads to the predictable self-organization of forest canopies. We show how models of natural selection acting on a few key traits can generate realistic plant communities and how entropy maximization can identify the most probable outcomes of community dynamics in space- and time-varying environments. Finally, we present a roadmap indicating how these principles could be combined in a new generation of models with stronger theoretical foundations and an improved capacity to predict complex vegetation responses to environmental change. Integrating natural selection and other organizing principles into next-generation vegetation models could render them more theoretically sound and useful for earth system applications and modelling climate impacts.
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| 6. |
- Mehta, Raghav, et al.
(författare)
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QU-BraTS : MICCAI BraTS 2020 Challenge on QuantifyingUncertainty in Brain Tumor Segmentation - Analysis of Ranking Scores and Benchmarking Results
- 2022
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Ingår i: Journal of Machine Learning for Biomedical Imaging. - 2766-905X. ; , s. 1-54
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Tidskriftsartikel (refereegranskat)abstract
- Deep learning (DL) models have provided the state-of-the-art performance in a wide variety of medical imaging benchmarking challenges, including the Brain Tumor Segmentation (BraTS) challenges. However, the task of focal pathology multi-compartment segmentation (e.g., tumor and lesion sub-regions) is particularly challenging, and potential errors hinder the translation of DL models into clinical workflows. Quantifying the reliability of DL model predictions in the form of uncertainties, could enable clinical review of the most uncertain regions, thereby building trust and paving the way towards clinical translation. Recently, a number of uncertainty estimation methods have been introduced for DL medical image segmentation tasks. Developing scores to evaluate and compare the performance of uncertainty measures will assist the end-user in making more informed decisions. In this study, we explore and evaluate a score developed during the BraTS 2019-2020 task on uncertainty quantification (QU-BraTS), and designed to assess and rank uncertainty estimates for brain tumor multi-compartment segmentation. This score (1) rewards uncertainty estimates that produce high confidence in correct assertions, and those that assign low confidence levels at incorrect assertions, and (2) penalizes uncertainty measures that lead to a higher percentages of under-confident correct assertions. We further benchmark the segmentation uncertainties generated by 14 independent participating teams of QU-BraTS 2020, all of which also participated in the main BraTS segmentation task. Overall, our findings confirm the importance and complementary value that uncertainty estimates provide to segmentation algorithms, and hence highlight the need for uncertainty quantification in medical image analyses. Our evaluation code is made publicly available at https://github.com/RagMeh11/QU-BraTS
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| 7. |
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| 8. |
- Sandin, Ylva, et al.
(författare)
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Design of Timber Buildings for Deconstruction and Reuse — Three methods and five case studies
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- There is a need for a shift towards circular economy in the construction sector and design philosophies as Design for Deconstruction and Reuse (DfDR) and Design for Adaptability (DfA) are being developed as means to design out waste and enhance resource efficiency. However, applying these philosophies is not yet common practice. The amount of DfDR/A timber buildings described in literature is limited. This study aims at increasing and spreading knowledge on DfDR/A for timber buildings. It has four goals: 1) To suggest methods to apply DfDR/A. 2) To suggest new design solutions. 3) To collect experiences on connections in relation to DfDR. 4) To suggest how guidelines for deconstruction and reuse can be formulated. The study presents three methods that all proved valuable in applying DfDR/A: one discussion-based method to improve an already existing timber building design, one indicator system to assess the DfDR/A potential of building designs, and one matrix to guide design decisions. We used the first method to conduct five case studies in four European countries. The studied designs were judged to be well or relatively well adapted for deconstruction and reuse already today. The fact that the studied buildings are all offsite manufactured and of modular composition benefits the deconstruction process, partly because construction and deconstruction are similar processes so that the knowledge and infrastructure that companies have can be directly transferred to enable deconstruction and reuse. Where large modules can be recovered, the time and energy needed for deconstruction as well as the risk for damage will be reduced. Disadvantages to deconstruction and reuse identified were typically linked to the complexity of building modules and that individual components are not independent. This was reflected as irreversible or hidden connections, inaccessible services, interconnected layers of the structural modules and many different component sizes. One of the case study buildings, designed with mass timber panels, excelled in the simplicity and reduction of number of steps required for maximum material recovery. New designs suggested included making fasteners more accessible to deconstruction, avoiding letting sensitive materials as plastic foils and particle boards pass continuously over joints between elements, and (for cases where standard units are not already used) standardizing elements. One case suggested using solid wood components instead of engineered wood products to achieve durability. The study showed that simple changes in design can lead to an augmented reuse potential. Some of the new design solutions generated will be taken into production by the participating manufacturers. Insights on connections included recognizing the fact that the use of reversible screwed connections is not sufficient to ensure deconstructability and that although nailed or glued connections severely complicate reuse of components, they might be accepted within elements in case reuse on element level is the target. Guidelines for deconstruction and reuse were developed in all case studies. Taken as a group of studies, there are advantageous additions proposed to earlier guidance documents. Despite being based on the same source, the different plans suggested varied substantially. There was a noteworthy difference between manufacturers’ in-house plans to those proposed by architects, engineers, or researchers, which speaks to the uncertainty regarding the appropriate structure and format.
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