| 1. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 2. |
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| 3. |
- Patterson, Nick, et al.
(författare)
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Large-scale migration into Britain during the Middle to Late Bronze Age
- 2022
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
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Tidskriftsartikel (refereegranskat)abstract
- Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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| 4. |
- Stephens, Lucas, et al.
(författare)
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Archaeological assessment reveals Earth’s early transformation through land use
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 365:6456, s. 897-902
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Tidskriftsartikel (refereegranskat)abstract
- Humans began to leave lasting impacts on Earth’s surface starting 10,000 to 8000 years ago. Through a synthetic collaboration with archaeologists around the globe, Stephens et al. compiled a comprehensive picture of the trajectory of human land use worldwide during the Holocene (see the Perspective by Roberts). Hunter-gatherers, farmers, and pastoralists transformed the face of Earth earlier and to a greater extent than has been widely appreciated, a transformation that was essentially global by 3000 years before the present.Science, this issue p. 897; see also p. 865Environmentally transformative human use of land accelerated with the emergence of agriculture, but the extent, trajectory, and implications of these early changes are not well understood. An empirical global assessment of land use from 10,000 years before the present (yr B.P.) to 1850 CE reveals a planet largely transformed by hunter-gatherers, farmers, and pastoralists by 3000 years ago, considerably earlier than the dates in the land-use reconstructions commonly used by Earth scientists. Synthesis of knowledge contributed by more than 250 archaeologists highlighted gaps in archaeological expertise and data quality, which peaked for 2000 yr B.P. and in traditionally studied and wealthier regions. Archaeological reconstruction of global land-use history illuminates the deep roots of Earth’s transformation and challenges the emerging Anthropocene paradigm that large-scale anthropogenic global environmental change is mostly a recent phenomenon.
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| 5. |
- Abubakar, Awwal Sanusi, et al.
(författare)
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The role of People and Digitalization as an Enabler of Resource Efficiency in Manufacturing
- 2022
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Ingår i: CEUR Workshop Proceedings. - 1613-0073. ; 3239, s. 111-120
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Konferensbidrag (refereegranskat)abstract
- Global sustainability challenges have been escalating in recent times, resulting in climate change, pollution, and resource scarcity. Reducing the amount of resources being used can help to mitigate these challenges by lowering our carbon footprint, reducing waste and improving our economic resilience. To achieve these benefits, researchers and industries have begun looking into Industry 4.0 technologies as a tool to drive resource efficiency gains. In this paper, the research question explores the challenges that hinder companies from adopting digital technologies. Other topics discussed include how digital technologies can support resource efficiency, and how people can support resource efficiency. Data for this study was collected from a face-to-face workshop event which included expert participants from industry, academia, and the UK Government. This workshop aimed to gain insights into the adoption barriers and opportunities for digital technology to target environmental performance. The main adoption barrier identified was lack of knowledge. Other barriers include lack of trust, lack of finance and lack of expertise. Environmental performance is usually not targeted because it is not a priority for many organizations. Nevertheless, external stakeholders are putting pressure on companies to incentivize sustainable change. This paper identifies the challenges that hinder companies from adopting digital technologies and gives insights into how digital technologies can support people for resource efficiency.
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| 6. |
- Axfors, Cathrine, et al.
(författare)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Forskningsöversikt (refereegranskat)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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| 7. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 8. |
- Beer, Tomasz M., et al.
(författare)
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Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer : Extended Analysis of the Phase 3 PREVAIL Study
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 71:2, s. 151-154
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Tidskriftsartikel (refereegranskat)abstract
- Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated the longer-term efficacy and safety of enzalutamide up to the prespecified number of deaths in the final analysis, which included an additional 20 mo of follow-up for investigator-assessed rPFS, 9 mo of follow-up for OS, and 4 mo of follow-up for safety. Enzalutamide reduced the risk of radiographic progression or death by 68% (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.28–0.37; p < 0.0001) and the risk of death by 23% (HR 0.77, 95% CI 0.67–0.88; p = 0.0002). Median investigator-assessed rPFS was 20.0 mo (95% CI 18.9–22.1) in the enzalutamide arm and 5.4 mo (95% CI 4.1–5.6) in the placebo arm. Median OS was 35.3 mo (95% CI 32.2–not yet reached) in the enzalutamide arm and 31.3 mo (95% CI 28.8–34.2) in the placebo arm. At the time of the OS analysis, 167 patients in the placebo arm had crossed over to receive enzalutamide. The most common adverse events in the enzalutamide arm were fatigue, back pain, constipation, and arthralgia. This final analysis of PREVAIL provides more complete assessment of the clinical benefit of enzalutamide. PREVAIL is registered on ClinicalTrials.gov as NCT01212991. Patient summary According to data from longer follow-up, enzalutamide continued to provide benefit over placebo in patients with metastatic castration-resistant prostate cancer.
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| 9. |
- Bocken, Nancy, et al.
(författare)
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A value mapping tool for sustainable business modelling
- 2013
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Ingår i: Corporate Governance: the international journal of business in society. - 1472-0701. ; 13:5, s. 482-497
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Although business models that deliver sustainability are increasingly popular in the literature, few tools that assist in sustainable business modelling have been identified. This paper investigates how businesses might create balanced social, environmental and economic value through integrating sustainability more fully into the core of their business. A value mapping tool is developed to help firms create value propositions better suited for sustainability. Design/methodology/approach: In addition to a literature review, six sustainable companies were interviewed to understand their approaches to business modelling, using a case study approach. Building on the literature and practice, a tool was developed which was pilot tested through use in a workshop. The resulting improved tool and process was subsequently refined through use in 13 workshops. Findings: A novel value mapping tool was developed to support sustainable business modelling, which introduces three forms of value (value captured, missed/destroyed or wasted, and opportunity) and four major stakeholder groups (environment, society, customer, and network actors). Practical implications: This tool intends to support business modelling for sustainability by assisting firms in better understanding their overall value proposition, both positive and negative, for all relevant stakeholders in the value network. Originality/value: The tool adopts a multiple stakeholder view of value, a network rather than firm centric perspective, and introduces a novel way of conceptualising value that specifically introduces value destroyed or wasted/ missed, in addition to the current value proposition and new opportunities for value creation.
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| 10. |
- Bocken, Nancy, et al.
(författare)
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Business Model Experimentation for Circularity: Driving sustainability in a large international clothing retailer
- 2017
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Ingår i: Economics and Policy of Energy and the Environment (EPEE). - 2280-7659. ; 2017:1, s. 85-122
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Tidskriftsartikel (refereegranskat)abstract
- Business model experimentation for sustainability is an intentional and systematic approach to identify, test and learn about value creation strategies that could be adopted by a business in response to current unsustainable trajectories. For businesses such as large clothing retailers the need to alter course is acute as pressure builds from economic, environmental and social angles. The circular economy concept provides a potential powerful lever for change. To date, however, scant research has been conducted on how circular business model experimentation is conducted.We present an in-depth action research case study of a large international clothing retailer embarking on a journey of business model experimentation for circularity: the processes, methods, roles and the organisation in light of the need to address broad sustainability challenges in the business. It was found that experimentation activities oscillated between slow and loaded, and faster and un- weighted modes. While an intentional and stepwise process was sought, in reality it was largely emergent and highly iterative. Through this iterative process, new circular business models were generated that co-exist with current non-circular ones. Confidence in experimentation as a business capability also increased through this collaborative project.This study provides insights into how to conduct lean startup type business model experimentation for circularity in a large organisation. For practitioners, the benefits of academic-industry collaboration, and the oscillating dynamics of business model experimentation are illuminated.
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| 11. |
- Bocken, Nancy, et al.
(författare)
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Slowing resource loops in the circular economy : An experimentation approach in fashion retail
- 2019
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Ingår i: Sustainable Design and Manufacturing - Proceedings of the 5th International Conference on Sustainable Design and Manufacturing KES-SDM-18. - Cham : Springer International Publishing. - 2190-3026 .- 2190-3018. - 9783030042899 ; 130, s. 164-173
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Konferensbidrag (refereegranskat)abstract
- The Circular Economy is viewed as an important driver for resolving resource issues and tackling sustainability issues more broadly. The fashion industry operates in a largely linear way and suffers from various environmental, societal and economic challenges. In a Circular Economy, first and foremost, products need to be retained at the highest level, thus slowing resource loops. Slowing resource loops goes against current fast fashion trends and therefore appears the most difficult approach to pursue. This paper investigates how a large established retailer aims to slow resource loops as part of a broader project targeted to significantly reduce textile waste to landfill. The retailer collaborated with a university partner to pursue circular business model experiments. This paper reports on the approach for a slowing resource loops experiment around building sewing capabilities. Suggestions for future research and practice on circular business model experimentation are included.
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| 12. |
- Bocken, Nancy, et al.
(författare)
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Understanding environmental performance variation in manufacturing companies
- 2013
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Ingår i: International Journal of Productivity and Performance Management. - 1741-0401. ; 62:8, s. 856-870
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Sustainability is an area of increasing interest for industry and its stakeholders, and some companies now aspire to address sustainability issues (e.g. carbon emissions) at strategic and operational levels. As companies are exploring the issues, they attempt to embed sustainability in their planning and management systems. It is at this point that the domains of environmental concern and performance management meet. The research questions explored in this paper are: what is the size of environmental performance variation? What are the challenges for sustainability performance management in practice? Design/methodology/approach: First, interviews in manufacturing companies were conducted to understand the size of environmental performance variation. Subsequently, a survey, interviews and a workshop were conducted with ten organisations to gain insight in environmental performance management in companies. Findings: It was observed that, across three sectors, environmental performance between manufacturing plants differed up to 500 per cent between worst and best performing factories which make similar products using similar technology, all in well-run companies which have environmental management programmes in place. This means that learning within the company between different sites is important but can be difficult. Some initial success stories observed include a quid-pro-quo approach between factory sites (teach-learn-do-teach) and dedicated individuals (champions) in factories who strive to make year-on-year efficiency improvements. Originality/value: The paper gives insights in the size of environmental performance variation, self-reported by internal company specialists in sustainable manufacturing, and sustainability performance management in practice.
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| 13. |
- de Vries, Paul S., et al.
(författare)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Tidskriftsartikel (refereegranskat)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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| 14. |
- Despeisse, Mélanie, 1985, et al.
(författare)
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A Collection of Tools for Factory Eco-efficiency
- 2016
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Ingår i: Procedia CIRP. - : Elsevier BV. - 2212-8271. ; 40, s. 542-546
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Konferensbidrag (refereegranskat)abstract
- Eco-efficiency is generally defined as doing more with less, aiming to decouple environmental impact from economic and social value creation. This paper presents three tools to guide the implementation of eco-efficiency in factories: (1) definition and patterns of good practices for sustainable manufacturing, (2) a self-assessment tool and maturity grid, and (3) a factory modelling framework.
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| 15. |
- Despeisse, Mélanie, 1985, et al.
(författare)
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Improving Factory Resource and Energy Efficiency: The FREE Toolkit
- 2015
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Ingår i: IFIP Advances in Information and Communication Technology. - Cham : Springer International Publishing. - 1868-4238 .- 1868-422X. ; 459, s. 640-646
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Konferensbidrag (refereegranskat)abstract
- Eco-efficiency is defined as the concept of doing more with less; in other words, creating goods and services while preserving natural resources and reducing waste and pollution during manufacturing. This paper presents a toolkit for eco-efficiency at factory level: the Factory Resource and Energy Efficiency (FREE) toolkit. It contains five key elements; (1) see waste, (2) find solutions, (3) set targets, (4) assess yourself, and (5) create good habits. The FREE toolkit contains a range of games, tools and methods mapped against these five elements to integrate sustainability into factory activities. This paper presents the toolkit structure and an example of the journey for eco-efficiency.
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| 16. |
- Despeisse, Mélanie, 1985, et al.
(författare)
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Industrial ecology at factory level – a conceptual model
- 2012
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Ingår i: Journal of Cleaner Production. - : Elsevier BV. - 0959-6526. ; 31, s. 30-39
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Tidskriftsartikel (refereegranskat)abstract
- Growing environmental concerns caused by natural resource depletion and pollution need to be addressed. One approach to these problems is Sustainable Development, a key concept for our society to meet present as well as future needs worldwide. Manufacturing clearly has a major role to play in the move towards a more sustainable society. However it appears that basic principles of environmental sustainability are not systematically applied, with practice tending to focus on local improvements. The aim of the work presented in this paper is to adopt a more holistic view of the factory unit to enable opportunities for wider improvement. This research analyses environmental principles and industrial practice to develop a conceptual manufacturing ecosystem model as a foundation to improve environmental performance. The model developed focuses on material, energy and waste flows to better understand the interactions between manufacturing operations, supporting facilities and surrounding buildings. The research was conducted in three steps: (1) existing concepts and models for industrial sustainability were reviewed and environmental practices in manufacturing were collected and analysed; (2) gaps in knowledge and practice were identified; (3) the outcome is a manufacturing ecosystem model based on industrial ecology (IE). This conceptual model has novelty in detailing IE application at factory level and integrating all resource flows. The work is a base on which to build quantitative modelling tools to seek integrated solutions for lower resource input, higher resource productivity, fewer wastes and emissions, and lower operating cost within the boundary of a factory unit.
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| 17. |
- Despeisse, Mélanie, 1985, et al.
(författare)
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Industrial ecology at factory level: a prototype methodology
- 2012
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Ingår i: Proceedings of the Institution of Mechanical Engineers, Part B: Journal of Engineering Manufacture. - : SAGE Publications. - 0954-4054 .- 2041-2975. ; 226:10, s. 1648-1664
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Tidskriftsartikel (refereegranskat)abstract
- The concept of sustainable manufacturing is a form of pollution prevention that integrates environmental considerations in the production of goods while focusing on efficient resource use. Taking the industrial ecology perspective, this efficiency comes from improved resource flow management. The assessment of material, energy and waste resource flows, therefore, offers a route to viewing and analysing a manufacturing system as an ecosystem using industrial ecology biological analogy and can, in turn, support the identification of improvement opportunities in the material, energy and waste flows. This application of industrial ecology at factory level is absent from the literature. This article provides a prototype methodology to apply the concepts of industrial ecology using material, energy and waste process flows to address this gap in the literature. Various modelling techniques were reviewed and candidates selected to test the prototype methodology in an industrial case. The application of the prototype methodology showed the possibility of using the material, energy and waste resource flows through the factory to link manufacturing operations and supporting facilities, and to identify potential improvements in resource use. The outcomes of the work provide a basis to build the specifications for a modelling tool that can support those analysing their manufacturing system to improve their environmental performance and move towards sustainable manufacturing.
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| 18. |
- Despeisse, Mélanie, 1985, et al.
(författare)
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Sustainable Value Roadmapping Framework for Additive Manufacturing
- 2017
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Ingår i: Procedia CIRP. - : Elsevier BV. - 2212-8271. ; 61, s. 594-599
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Konferensbidrag (refereegranskat)abstract
- Recent developments around the use of additive manufacturing (AM) for making components and end-products is radically changing the way manufacturing activities are organized. Many researchers are now turning their attention to AM technology and its potential benefits for boosting economic, social, and environmental sustainability. However, there is still much uncertainty on the full impact from a life cycle perspective. Previous work has reviewed the implications of AM from a sustainability and life cycle point of view, but it is unclear whether the technology can fully realize the potential benefits identified, and whether it will lead to unintended consequences such as increased material consumption, thereby further straining the planet's carrying capacity and pushing society towards unsustainable, more materialistic values. This research builds on previous work to customize a tool, the Sustainable Value Roadmapping Tool (SVRT), which combines the strategic roadmapping technique with the sustainable value analysis tool. Roadmapping is a well-established approach for businesses to strategically plan activities for the short-, medium- and long-term; combined with the value analysis tools, it can identify opportunities for sustainable value creation for all stakeholders, including society and the planet. While SVRT has been developed and tested in a more generic context (i.e. not technology-specific), it also has good promises to help companies to explore the potential benefits and challenges of AM adoption across products’ life cycle and the associated business model implications. This paper will present the prototype version of SVRT for AM. The findings consolidate and expand the opportunities and challenges already identified in the literature. Further work will conduct case studies to use the SVRT with companies adopting AM technology and better understand the sustainability impacts from a business perspective.
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| 19. |
- Ding, Yuan C, et al.
(författare)
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A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
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| 20. |
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| 21. |
- Evans, Margery L, et al.
(författare)
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The bacterial curli system possesses a potent and selective inhibitor of amyloid formation
- 2015
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Ingår i: Molecular Cell. - : Elsevier BV. - 1097-4164 .- 1097-2765. ; 57:3, s. 445-455
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Tidskriftsartikel (refereegranskat)abstract
- Curli are extracellular functional amyloids that are assembled by enteric bacteria during biofilm formation and host colonization. An efficient secretion system and chaperone network ensures that the major curli fiber subunit, CsgA, does not form intracellular amyloid aggregates. We discovered that the periplasmic protein CsgC was a highly effective inhibitor of CsgA amyloid formation. In the absence of CsgC, CsgA formed toxic intracellular aggregates. In vitro, CsgC inhibited CsgA amyloid formation at substoichiometric concentrations and maintained CsgA in a non-β-sheet-rich conformation. Interestingly, CsgC inhibited amyloid assembly of human α-synuclein, but not Aβ42, in vitro. We identified a common D-Q-Φ-X0,1-G-K-N-ζ-E motif in CsgC client proteins that is not found in Aβ42. CsgC is therefore both an efficient and selective amyloid inhibitor. Dedicated functional amyloid inhibitors may be a key feature that distinguishes functional amyloids from disease-associated amyloids.
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| 22. |
- Falster, Daniel, et al.
(författare)
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AusTraits, a curated plant trait database for the Australian flora
- 2021
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Ingår i: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge.
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| 23. |
- Freitag, Daniel F., et al.
(författare)
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Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis
- 2015
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Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595. ; 3:4, s. 243-253
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Tidskriftsartikel (refereegranskat)abstract
- Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND.
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| 24. |
- Jones, Benedict C, et al.
(författare)
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To which world regions does the valence-dominance model of social perception apply?
- 2021
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Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
-
Tidskriftsartikel (refereegranskat)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
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| 25. |
- Kardeby, Caroline, et al.
(författare)
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Heparin and heparin proteoglycan-mimetics activate platelets via PEAR1 and PI3K beta
- 2023
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier. - 1538-7933 .- 1538-7836. ; 21:1, s. 101-116
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Tidskriftsartikel (refereegranskat)abstract
- Background: Platelet endothelial aggregation receptor 1 (PEAR1) is a singletransmembrane orphan receptor primarily expressed on platelets and endothelial cells. Genetic variants of PEAR1 have repeatedly and independently been identified to be associated with cardiovascular diseases, including coronary artery disease.Objectives: We have identified sulfated fucoidans and their mimetics as ligands for PEAR1 and proposed that its endogenous ligand is a sulfated proteoglycan. The aim of this study was to test this hypothesis.Methods: A heparin proteoglycan-mimetic (HPGM) was created by linking unfractionated heparin (UFH) to albumin. The ability of the HPGM, UFH and selectively desulfated heparins to stimulate platelet aggregation and protein phosphorylation was investigated. Nanobodies against the 12th to 13th epidermal growth factor-like repeat of PEAR1 and phosphoinositide 3-kinase (PI3K) isoform-selective inhibitors were tested for the inhibition of platelet activation.Results: We show that HPGM, heparin conjugated to an albumin protein core, stimulates aggregation and phosphorylation of PEAR1 in washed platelets. Platelet aggregation was abolished by an anti-PEAR1 nanobody, Nb138. UFH stimulated platelet aggregation in washed platelets, but desulfated UFH did not. Furthermore, HPGM, but not UFH, stimulated maximal aggregation in platelet-rich plasma. However, both HPGM and UFH increased integrin alpha IIb(33 activation in whole blood. By using PI3K isoform-selective inhibitors, we show that PEAR1 activates PI3K(3, leading to Akt phosphorylation.Conclusion: Our findings reveal that PEAR1 is a receptor for heparin and HPGM and that PI3K(3 is a key signaling molecule downstream of PEAR1 in platelets. These findings may have important implications for our understanding of the role of PEAR1 in cardiovascular disease.
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| 26. |
- 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
-
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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| 27. |
- McCarthy, Randy J., et al.
(författare)
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Registered Replication Report on Srull and Wyer (1979)
- 2018
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Ingår i: Advances in Methods and Practices in Psychological Science. - : SAGE Publications Inc. - 2515-2459 .- 2515-2467. ; 1:3, s. 321-336
-
Tidskriftsartikel (refereegranskat)abstract
- Srull and Wyer (1979) demonstrated that exposing participants to more hostility-related stimuli caused them subsequently to interpret ambiguous behaviors as more hostile. In their Experiment 1, participants descrambled sets of words to form sentences. In one condition, 80% of the descrambled sentences described hostile behaviors, and in another condition, 20% described hostile behaviors. Following the descrambling task, all participants read a vignette about a man named Donald who behaved in an ambiguously hostile manner and then rated him on a set of personality traits. Next, participants rated the hostility of various ambiguously hostile behaviors (all ratings on scales from 0 to 10). Participants who descrambled mostly hostile sentences rated Donald and the ambiguous behaviors as approximately 3 scale points more hostile than did those who descrambled mostly neutral sentences. This Registered Replication Report describes the results of 26 independent replications (N = 7,373 in the total sample; k = 22 labs and N = 5,610 in the primary analyses) of Srull and Wyer?s Experiment 1, each of which followed a preregistered and vetted protocol. A random-effects meta-analysis showed that the protagonist was seen as 0.08 scale points more hostile when participants were primed with 80% hostile sentences than when they were primed with 20% hostile sentences (95% confidence interval, CI = [0.004, 0.16]). The ambiguously hostile behaviors were seen as 0.08 points less hostile when participants were primed with 80% hostile sentences than when they were primed with 20% hostile sentences (95% CI = [?0.18, 0.01]). Although the confidence interval for one outcome excluded zero and the observed effect was in the predicted direction, these results suggest that the currently used methods do not produce an assimilative priming effect that is practically and routinely detectable.
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| 28. |
- Mohr, Steve, et al.
(författare)
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Projection of Australian coal production : Comparisons of four models
- 2011
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Ingår i: Proceedings of the International Pittsburgh Coal Conference 2011.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Coal exports are an important source of revenue for Australia and for this reason Australian coal production and resources have been examined in detail. Two recoverable resource estimates, a Standard case and a High case, were determined. The Standard case calculated the likely recoverable coal resources in Australia to be 317 Gt, whereas the High scenario determined the maximal amount of recoverable coal resources at 367 Gt. The study performed forecasting by use of curve-fitting with Logistic and Gompertz curves as well as Static and Dynamic versions of a supply and demand model based on real world mineral exploitation. The different modelling approaches were used to project fossil fuel production and the outlooks were compared. Good agreement was found between the Logistic, Static and Dynamic supply and demand models with production peaking in 2119±6 at between 1.9 and 3.3 Gt/y. Contrasting these projections the Gompertz curves peak in 2084±5 at 1–1.1 Gt/y. It was argued that the Logistic, Static and Dynamic models are more likely to produce accurate projections than the Gompertz curve. The production forecast is based on existing technology and constraints and a qualitative discussion is presented on possible influences on future production, namely: export capacity, climate change, overburden management, environmental and social impacts and export market issues.
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| 29. |
- Mohr, Steve, et al.
(författare)
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Projection of long-term paths for Australian coal production : comparisons of four models
- 2011
-
Ingår i: International Journal of Coal Geology. - : Elsevier BV. - 0166-5162 .- 1872-7840. ; 86:4, s. 329-341
-
Tidskriftsartikel (refereegranskat)abstract
- Coal exports are an important source of revenue for Australia and for this reason Australian coal production and resources have been examined in detail and two recoverable resource estimates determined namely Standard and High. The Standard case calculated the likely recoverable coal resources in Australia to be 317 Gt, whereas the High scenario determined the maximal amount of recoverable coal resources at 367 Gt. Different modelling approaches (Logistic, Gompertz, Static and Dynamic supply and demand models) were used to project fossil fuel production and the projections of the relative approaches were compared. Good agreement was found between the Logistic, Static and Dynamic supply and demand models with production peaking in 2119 +/- 6 at between 1.9 and 3.3 Gt/y. Contrasting these projections the Gompertz curves peak in 2084 +/- 5 at 1-1.1 Gt/y. It was argued that the Logistic, Static and Dynamic models are more likely to produce accurate projections than the Gompertz curve. The production forecast is based on existing technology and constraints and a qualitative discussion is presented on possible influences on future production, namely: export capacity, climate change, overburden management, environmental and social impacts and export market issues.
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| 30. |
- Moshontz, Hannah, et al.
(författare)
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The Psychological Science Accelerator: Advancing Psychology Through a Distributed Collaborative Network
- 2018
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Ingår i: Advances in Methods and Practices in Psychological Science. - : SAGE Publications. - 2515-2459 .- 2515-2467. ; 1:4, s. 501-515
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Tidskriftsartikel (refereegranskat)abstract
- Concerns about the veracity of psychological research have been growing. Many findings in psychological science are based on studies with insufficient statistical power and nonrepresentative samples, or may otherwise be limited to specific, ungeneralizable settings or populations. Crowdsourced research, a type of large-scale collaboration in which one or more research projects are conducted across multiple lab sites, offers a pragmatic solution to these and other current methodological challenges. The Psychological Science Accelerator (PSA) is a distributed network of laboratories designed to enable and support crowdsourced research projects. These projects can focus on novel research questions or replicate prior research in large, diverse samples. The PSA’s mission is to accelerate the accumulation of reliable and generalizable evidence in psychological science. Here, we describe the background, structure, principles, procedures, benefits, and challenges of the PSA. In contrast to other crowdsourced research networks, the PSA is ongoing (as opposed to time limited), efficient (in that structures and principles are reused for different projects), decentralized, diverse (in both subjects and researchers), and inclusive (of proposals, contributions, and other relevant input from anyone inside or outside the network). The PSA and other approaches to crowdsourced psychological science will advance understanding of mental processes and behaviors by enabling rigorous research and systematic examination of its generalizability.
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| 31. |
- Muhle, Franz, et al.
(författare)
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Blind test comparison on the wake behind a yawed wind turbine
- 2018
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Ingår i: Wind Energy Science. - : COPERNICUS GESELLSCHAFT MBH. - 2366-7443 .- 2366-7451. ; 3:2, s. 883-903
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Tidskriftsartikel (refereegranskat)abstract
- This article summarizes the results of the "Blind test 5" workshop, which was held in Visby, Sweden, in May 2017. This study compares the numerical predictions of the wake flow behind a model wind turbine operated in yaw to experimental wind tunnel results. Prior to the workshop, research groups were invited to predict the turbine performance and wake flow properties using computational fluid dynamics (CFD) methods. For this purpose, the power, thrust, and yaw moments for a 30 degrees yawed model turbine, as well as the wake's mean and turbulent streamwise and vertical flow components, were measured in the wind tunnel at the Norwegian University of Science and Technology (NTNU). In order to increase the complexity, a non-yawed downstream turbine was added in a second test case, while a third test case challenged the modelers with a new rotor and turbine geometry. Four participants submitted predictions using different flow solvers, three of which were based on large eddy simulations (LES) while another one used an improved delayed detached eddy simulation (IDDES) model. The performance of a single yawed turbine was fairly well predicted by all simulations, both in the first and third test cases. The scatter in the downstream turbine performance predictions in the second test case, however, was found to be significantly larger. The complex asymmetric shape of the mean streamwise and vertical velocities was generally well predicted by all the simulations for all test cases. The largest improvement with respect to previous blind tests is the good prediction of the levels of TKE in the wake, even for the complex case of yaw misalignment. These very promising results confirm the mature development stage of LES/DES simulations for wind turbine wake modeling, while competitive advantages might be obtained by faster computational methods.
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| 32. |
- Oliveira, Ana, et al.
(författare)
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Holistic management of patients with progressive pulmonary fibrosis
- 2023
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Ingår i: Breathe. - 1810-6838. ; 19:3
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Forskningsöversikt (refereegranskat)abstract
- Progressive pulmonary fibrosis (PF) is a complex interstitial lung disease that impacts substantially on patients’ daily lives, requiring personalised and integrated care. We summarise the main needs of patients with PF and their caregivers, and suggest a supportive care approach. Individualised care, education, emotional and psychological support, specialised treatments, and better access to information and resources are necessary. Management should start at diagnosis, be tailored to the patient’s needs, and consider end-of-life care. Pharmacological and non-pharmacological interventions should be individualised, including oxygen therapy and pulmonary rehabilitation, with digital healthcare utilised as appropriate. Further research is needed to address technical issues related to oxygen delivery and digital healthcare.
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| 33. |
- Osorio, Ana, et al.
(författare)
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DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7×10-3) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8×10-3). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
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| 34. |
- Peng, Chen, et al.
(författare)
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Industrial Internet of Things enabled supply-side energy modelling for refined energy management in aluminium extrusions manufacturing
- 2021
-
Ingår i: Journal of Cleaner Production. - : Elsevier Science Ltd. - 0959-6526 .- 1879-1786. ; 301
-
Tidskriftsartikel (refereegranskat)abstract
- To improve industrial sustainability performance in manufacturing, energy management and optimi-sation are key levers. This is particularly true for aluminium extrusions manufacturing dan energy -intensive production system with considerable environmental impacts. Many energy management and optimisation approaches have been studied to relieve such negative impact. However, the effectiveness of these approaches is compromised without the support of refined supply-side energy consumption information. Industrial internet of things provides opportunities to acquire refined energy consumption information in its data-rich environment but also poses a range of difficulties in implementation. The existing sensors cannot directly obtain the energy consumption at the granularity of a specific job. To acquire that refined energy consumption information, a supply-side energy modelling method based on existing industrial internet of things devices for energy-intensive production systems is proposed in this paper. First, the job-specified production event concept is proposed, and the layout of the data acqui-sition network is designed to obtain the event elements. Second, the mathematical models are developed to calculate the energy consumption of the production event in three process modes. Third, the energy consumption information of multiple manufacturing element dimensions can be derived from the mathematical models, and therefore, the energy consumption information on multiple dimensions is easily scaled. Finally, a case of refined energy cost accounting is studied to demonstrate the feasibility of the proposed models. ? 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 35. |
- Pälike, Heiko, et al.
(författare)
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A Cenozoic record of the equatorial Pacific carbonate compensation depth
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 488:7413, s. 609-614
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Tidskriftsartikel (refereegranskat)abstract
- Atmospheric carbon dioxide concentrations and climate are regulated on geological timescales by the balance between carbon input from volcanic and metamorphic outgassing and its removal by weathering feedbacks; these feedbacks involve the erosion of silicate rocks and organic-carbon-bearing rocks. The integrated effect of these processes is reflected in the calcium carbonate compensation depth, which is the oceanic depth at which calcium carbonate is dissolved. Here we present a carbonate accumulation record that covers the past 53 million years from a depth transect in the equatorial Pacific Ocean. The carbonate compensation depth tracks long-term ocean cooling, deepening from 3.0-3.5 kilometres during the early Cenozoic (approximately 55 million years ago) to 4.6 kilometres at present, consistent with an overall Cenozoic increase in weathering. We find large superimposed fluctuations in carbonate compensation depth during the middle and late Eocene. Using Earth system models, we identify changes in weathering and the mode of organic-carbon delivery as two key processes to explain these large-scale Eocene fluctuations of the carbonate compensation depth.
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| 36. |
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| 37. |
- Rebbeck, Timothy R., et al.
(författare)
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Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women
- 2016
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood. Methods: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. Results: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p < 0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC. Conclusions: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2.
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| 38. |
- Schurig, Alexander, et al.
(författare)
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Factors for Effective Learning in Production Networks to Improve Environmental Performance
- 2015
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Ingår i: IFIP Advances in Information and Communication Technology. - Cham : Springer International Publishing. - 1868-4238 .- 1868-422X. ; 459, s. 697-704
-
Konferensbidrag (refereegranskat)abstract
- There is evidence that the environmental performances of factories operating under similar circumstances vary greatly, even within one company. This indicates that production sites are operated in different ways which suggests a potential for improvement. Previous research shows that collaboration within production networks can improve factory performance. Learning collaboratively across factories is a promising approach to reduce the environmental impact of production sites. Several companies recognised this opportunity. Processes and systems to support knowledge and know-how exchange within their production network are already in place. In this research a literature review and interviews were carried out to explore factors that influence learning between factories. Such factors are critical to develop an effective tool enabling learning across factories and thus environmental performance improvements.
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| 39. |
- Singleton, Caitlin M., et al.
(författare)
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Methanotrophy across a natural permafrost thaw environment
- 2018
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Ingår i: The ISME Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 12:10, s. 2544-2558
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Tidskriftsartikel (refereegranskat)abstract
- The fate of carbon sequestered in permafrost is a key concern for future global warming as this large carbon stock is rapidly becoming a net methane source due to widespread thaw. Methane release from permafrost is moderated by methanotrophs, which oxidise 20-60% of this methane before emission to the atmosphere. Despite the importance of methanotrophs to carbon cycling, these microorganisms are under-characterised and have not been studied across a natural permafrost thaw gradient. Here, we examine methanotroph communities from the active layer of a permafrost thaw gradient in Stordalen Mire (Abisko, Sweden) spanning three years, analysing 188 metagenomes and 24 metatranscriptomes paired with in situ biogeochemical data. Methanotroph community composition and activity varied significantly as thaw progressed from intact permafrost palsa, to partially thawed bog and fully thawed fen. Thirteen methanotroph population genomes were recovered, including two novel genomes belonging to the uncultivated upland soil cluster alpha (USCa) group and a novel potentially methanotrophic Hyphomicrobiaceae. Combined analysis of porewater delta C-13-CH 4 isotopes and methanotroph abundances showed methane oxidation was greatest below the oxic-anoxic interface in the bog. These results detail the direct effect of thaw on autochthonous methanotroph communities, and their consequent changes in population structure, activity and methane moderation potential.
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| 40. |
- Sumaila, U. Rashid, et al.
(författare)
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WTO must ban harmful fisheries subsidies
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 41. |
- Verschuere, Bruno, et al.
(författare)
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Registered Replication Report on Mazar, Amir, and Ariely (2008)
- 2018
-
Ingår i: Advances in Methods and Practices in Psychological Science. - : SAGE Publications. - 2515-2459 .- 2515-2467. ; 1:3, s. 299-317
-
Tidskriftsartikel (refereegranskat)abstract
- The self-concept maintenance theory holds that many people will cheat in order to maximize self-profit, but only to the extent that they can do so while maintaining a positive self-concept. Mazar, Amir, and Ariely (2008, Experiment 1) gave participants an opportunity and incentive to cheat on a problem-solving task. Prior to that task, participants either recalled the Ten Commandments (a moral reminder) or recalled 10 books they had read in high school (a neutral task). Results were consistent with the self-concept maintenance theory. When given the opportunity to cheat, participants given the moral-reminder priming task reported solving 1.45 fewer matrices than did those given a neutral prime (Cohen’s d = 0.48); moral reminders reduced cheating. Mazar et al.’s article is among the most cited in deception research, but their Experiment 1 has not been replicated directly. This Registered Replication Report describes the aggregated result of 25 direct replications (total N = 5,786), all of which followed the same preregistered protocol. In the primary meta-analysis (19 replications, total n = 4,674), participants who were given an opportunity to cheat reported solving 0.11 more matrices if they were given a moral reminder than if they were given a neutral reminder (95% confidence interval = [−0.09, 0.31]). This small effect was numerically in the opposite direction of the effect observed in the original study (Cohen’s d = −0.04).
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| 42. |
- Vigorito, Elena, et al.
(författare)
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Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
- 2016
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
-
Tidskriftsartikel (refereegranskat)abstract
- Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95% CI: 0.68 to 0.79, p-value 2x 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95% CI: 0.59 to 0.80, p-value 1.0 x 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
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| 43. |
- Wasserbaur, Raphael, 1989-
(författare)
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Simulation Modelling of a Shift to Service-Based Offerings : Resource efficiency and operational implications in the context of the circular economy
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The unsustainable levels of resource use and emissions of our economies and their threat to future generations are core issues of our time. The circular economy (CE) conceptualises a different type of economy that is restorative and regenerative by design and aims to keep products, components and materials at their highest utility and value at all times, distinguishing between technical and biological cycles.The novelty of the CE requires the development of new analytical tools and methods as well as ways of thinking to understand its consequences. This research summarises four years of research on the topic of systems analysis and simulation modelling in the domain of the CE. Three topics were of major interest: First, what are the resource efficiency implications of a shift toward a CE? Second, what are the operational implications of a shift to a CE? And finally, how can systemic changes towards a CE be understood and planned? Four studies were conducted addressing the three research questions. The first study applies material flow analysis to a washing machine manufacturer case and looks at how different business models affect the resource flows of critical resources. It finds that service-based offerings lead to higher overall resource efficiency. The second study focuses on the implications of CE initiatives on the maintenance activities of a heat-as-a-service provider. It shows that the shift to service-based offerings requires service providers to face worse-before-better situations where long-term benefits offset short-term disadvantages. The third study is a simulation-based case study of laundry practices in Sweden. It compares a sharing economy scenario where a population shares washing machines with a scenario where the majority of people own the washing machines they are using. The results indicate that in Sweden and Europe in general, sharing has significant resource savings potential in the domestic laundry sector. The fourth study is a conceptualisation of design fixation to higher levels of analysis. It identifies examples of fixations on the organisational and institutional level. In addition, it argues that in order to design sustainable sociotechnical systems, aspects like governmental policies and business models need to be considered design parameters.A shift to a CE needs to happen on many levels of society. This research presents simulation models that can support corporate and political decision makers in the shift to a CE. It shows that in order to understand the CE, the analysis has to be, on the one hand, able to simulate system dynamics, and on the other hand connect the multiple levels of society.
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| 44. |
- Williams, Frances M. K., et al.
(författare)
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Ischemic stroke is associated with the ABO locus : the EuroCLOT study
- 2013
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Ingår i: Annals of Neurology. - : Wiley-Blackwell. - 0364-5134 .- 1531-8249. ; 73:1, s. 16-31
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Tidskriftsartikel (refereegranskat)abstract
- Objective: End-stage coagulation and the structure/function of fibrin are implicated in the pathogenesis of ischemic stroke. We explored whether genetic variants associated with end-stage coagulation in healthy volunteers account for the genetic predisposition to ischemic stroke and examined their influence on stroke subtype. Methods: Common genetic variants identified through genome-wide association studies of coagulation factors and fibrin structure/function in healthy twins (n = 2,100, Stage 1) were examined in ischemic stroke (n = 4,200 cases) using 2 independent samples of European ancestry (Stage 2). A third clinical collection having stroke subtyping (total 8,900 cases, 55,000 controls) was used for replication (Stage 3). Results: Stage 1 identified 524 single nucleotide polymorphisms (SNPs) from 23 linkage disequilibrium blocks having significant association (p < 5 x 10(-8)) with 1 or more coagulation/fibrin phenotypes. The most striking associations included SNP rs5985 with factor XIII activity (p = 2.6 x 10(-186)), rs10665 with FVII (p = 2.4 x 10(-47)), and rs505922 in the ABO gene with both von Willebrand factor (p = 4.7 x 10(-57)) and factor VIII (p = 1.2 x 10(-36)). In Stage 2, the 23 independent SNPs were examined in stroke cases/noncases using MOnica Risk, Genetics, Archiving and Monograph (MORGAM) and Wellcome Trust Case Control Consortium 2 collections. SNP rs505922 was nominally associated with ischemic stroke (odds ratio = 0.94, 95% confidence interval = 0.88-0.99, p = 0.023). Independent replication in Meta-Stroke confirmed the rs505922 association with stroke, beta (standard error, SE) = 0.066 (0.02), p = 0.001, a finding specific to large-vessel and cardioembolic stroke (p = 0.001 and p = < 0.001, respectively) but not seen with small-vessel stroke (p = 0.811). Interpretation: ABO gene variants are associated with large-vessel and cardioembolic stroke but not small-vessel disease. This work sheds light on the different pathogenic mechanisms underpinning stroke subtype.
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| 45. |
- Woodcroft, Ben J., et al.
(författare)
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Genome-centric view of carbon processing in thawing permafrost
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 560:7716, s. 49-
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Tidskriftsartikel (refereegranskat)abstract
- As global temperatures rise, large amounts of carbon sequestered in permafrost are becoming available for microbial degradation. Accurate prediction of carbon gas emissions from thawing permafrost is limited by our understanding of these microbial communities. Here we use metagenomic sequencing of 214 samples from a permafrost thaw gradient to recover 1,529 metagenome-assembled genomes, including many from phyla with poor genomic representation. These genomes reflect the diversity of this complex ecosystem, with genus-level representatives for more than sixty per cent of the community. Meta-omic analysis revealed key populations involved in the degradation of organic matter, including bacteria whose genomes encode a previously undescribed fungal pathway for xylose degradation. Microbial and geochemical data highlight lineages that correlate with the production of greenhouse gases and indicate novel syntrophic relationships. Our findings link changing biogeochemistry to specific microbial lineages involved in carbon processing, and provide key information for predicting the effects of climate change on permafrost systems.
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