| 1. |
- Postmus, Iris, et al.
(författare)
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Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
- 2014
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
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| 2. |
- Kraja, Aldi T., et al.
(författare)
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New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475000 Individuals
- 2017
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1942-325X .- 1942-3268. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.Methods and Results - Here, we augment the sample with 140886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, approximate to 475000), and the other in the subset of individuals of European descent (approximate to 423000). Twenty-one SNVs were genome-wide significant (P<5x10(-8) ) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.
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| 3. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 4. |
- Lagou, Vasiliki, et al.
(författare)
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Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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| 5. |
- Bai, Xuemei, et al.
(författare)
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Defining and advancing a systems approach for sustainable cities
- 2016
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Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 23, s. 69-78
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Forskningsöversikt (refereegranskat)abstract
- The sustainable development of cities is increasingly recognized as crucial to meeting collectively agreed sustainability goals at local, regional and global scales, and more broadly to securing human well-being worldwide. The UN Sustainable Development Goals (SDGs) include a goal on cities (Goal 11), with most other goals and targets have urban applications and multi scalar implications for their implementation. Further, the interdependencies - including synergies and trade-offs among the various SDGs are greater in cities, presenting both challenges and opportunities. A systems approach is urgently needed in urban research and policy analysis, but such an approach rarely features in current analysis or urban decision-making for various reasons. This paper explores four questions: why a systems approach is necessary, what defines such an approach, why has this rarely been adopted in practice, and what can be done to promote its use. We argue that a systems approach can reveal unrecognized opportunities to maximize co-benefits and synergies, guide management of inevitable trade-offs, and therefore inform prioritisation and successful solutions. We present four key issues for the effective implementation of the SDGs and the New Urban Agenda, which emerged from UN Habitat III Conference, namely: (a) a radical redesign of the multilateral institutional setup on urban issues; (b) promoting regenerative culture, behaviour, and design; (c) exploring ways to finance a systems approach; and (d) a new and enhanced role for science in sustainable development. The latter issue could be addressed through Future Earth's Urban Knowledge-Action Network, which aims at co-designing and co-producing cutting-edge and actionable knowledge for sustainable cities bringing together researchers and urban decision-makers and practitioners.
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| 6. |
- Chapin, F. Stuart, III, et al.
(författare)
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Ecosystem stewardship : sustainability strategies for a rapidly changing planet
- 2010
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Ingår i: Trends in Ecology & Evolution. - : Elsevier BV. - 0169-5347 .- 1872-8383. ; 25:4, s. 241-249
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Forskningsöversikt (refereegranskat)abstract
- Ecosystem stewardship is an action-oriented framework intended to foster the social ecological sustainability of a rapidly changing planet. Recent developments identify three strategies that make optimal use of current understanding in an environment of inevitable uncertainty and abrupt change: reducing the magnitude of, and exposure and sensitivity to, known stresses; focusing on proactive policies that shape change; and avoiding or escaping unsustainable social ecological traps. As we discuss here, all social ecological systems are vulnerable to recent and projected changes but have sources of adaptive capacity and resilience that can sustain ecosystem services and human well-being through active ecosystem stewardship.
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| 7. |
- Griggs, David, et al.
(författare)
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An integrated framework for sustainable development goals
- 2014
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Ingår i: Ecology and Society. - 1708-3087. ; 19:4, s. 49-
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Tidskriftsartikel (refereegranskat)abstract
- The United Nations (UN) Rio+20 summit committed nations to develop a set of universal sustainable development goals (SDGs) to build on the millennium development goals (MDGs) set to expire in 2015. Research now indicates that humanity's impact on Earth's life support system is so great that further global environmental change risks undermining long-term prosperity and poverty eradication goals. Socioeconomic development and global sustainability are often posed as being in conflict because of tradeoffs between a growing world population, as well as higher standards of living, and managing the effects of production and consumption on the global environment. We have established a framework for an evidence-based architecture for new goals and targets. Building on six SDGs, which integrate development and environmental considerations, we developed a comprehensive framework of goals and associated targets, which demonstrate that it is possible, and necessary, to develop integrated targets relating to food, energy, water, and ecosystem services goals; thus providing a neutral evidence-based approach to support SDG target discussions. Global analyses, using an integrated global target equation, are close to providing indicators for these targets. Alongside development-only targets and environment-only targets, these integrated targets would ensure that synergies are maximized and trade-offs are managed in the implementation of SDGs.
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| 8. |
- Leadley, Paul, et al.
(författare)
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Interacting Regional-Scale Regime Shifts for Biodiversity and Ecosystem Services
- 2014
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Ingår i: BioScience. - : Oxford University Press (OUP). - 0006-3568 .- 1525-3244. ; 64:8, s. 665-679
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Tidskriftsartikel (refereegranskat)abstract
- Current trajectories of global change may lead to regime shifts at regional scales, driving coupled human-environment systems to highly degraded states in terms of biodiversity, ecosystem services, and human well-being. For business-as-usual socioeconomic development pathways, regime shifts are projected to occur within the next several decades, to be difficult to reverse, and to have regional- to global-scale impacts on human society. We provide an overview of ecosystem, socioeconomic, and biophysical mechanisms mediating regime shifts and illustrate how these interact at regional scales by aggregation, synergy, and spreading processes. We give detailed examples of interactions for terrestrial ecosystems of central South America and for marine and coastal ecosystems of Southeast Asia. This analysis suggests that degradation of biodiversity and, ecosystem services over the twenty-first century could be far greater than was previously predicted. We identify key policy and management opportunities at regional to global scales to avoid these shifts.
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| 9. |
- Nilsson, Måns, et al.
(författare)
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Mapping interactions between the sustainable development goals : lessons learned and ways forward
- 2018
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Ingår i: Sustainability Science. - : SPRINGER JAPAN KK. - 1862-4065 .- 1862-4057. ; 13:6, s. 1489-1503
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Tidskriftsartikel (refereegranskat)abstract
- Pursuing integrated research and decision-making to advance action on the sustainable development goals (SDGs) fundamentally depends on understanding interactions between the SDGs, both negative ones (trade-offs) and positive ones (co-benefits). This quest, triggered by the 2030 Agenda, has however pointed to a gap in current research and policy analysis regarding how to think systematically about interactions across the SDGs. This paper synthesizes experiences and insights from the application of a new conceptual framework for mapping and assessing SDG interactions using a defined typology and characterization approach. Drawing on results from a major international research study applied to the SDGs on health, energy and the ocean, it analyses how interactions depend on key factors such as geographical context, resource endowments, time horizon and governance. The paper discusses the future potential, barriers and opportunities for applying the approach in scientific research, in policy making and in bridging the two through a global SDG Interactions Knowledge Platform as a key mechanism for assembling, systematizing and aggregating knowledge on interactions.
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| 10. |
- Norström, Albert, et al.
(författare)
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Principles for knowledge co-production in sustainability research
- 2020
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Ingår i: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 3:3, s. 182-190
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Tidskriftsartikel (refereegranskat)abstract
- Research practice, funding agencies and global science organizations suggest that research aimed at addressing sustainability challenges is most effective when 'co-produced' by academics and non-academics. Co-production promises to address the complex nature of contemporary sustainability challenges better than more traditional scientific approaches. But definitions of knowledge co-production are diverse and often contradictory. We propose a set of four general principles that underlie high-quality knowledge co-production for sustainability research. Using these principles, we offer practical guidance on how to engage in meaningful co-productive practices, and how to evaluate their quality and success. Research addressing sustainability issues is more effective if 'co-produced' by academics and non-academics, but definitions of co-production vary. This Perspective presents four knowledge co-production principles for sustainability research and guides on how to engage in co-productive practices.
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| 11. |
- Reyers, Belinda, et al.
(författare)
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Essential Variables help to focus Sustainable Development Goals monitoring
- 2017
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Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 26-27, s. 97-105
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Forskningsöversikt (refereegranskat)abstract
- The imperative to measure progress towards Sustainable Development Goals (SDGs) has resulted in a proliferation of targets and indicators fed by an ever-expanding set of observations. This proliferation undermines one principal purpose of the SDGs: to provide a framework for coordinated action across policy domains. Systems approaches to defining Essential Variables have focused monitoring of climate, biodiversity and oceans and offer opportunities to coordinate SDG monitoring. We propose four criteria and a process to identify Essential SDG Variables (ESDGVs), which will highlight interactions and gaps in current monitoring. The ESDGV criteria suggest a research agenda to: develop and test interdisciplinary system models; test transformations theory for sustainable development; analyse policy interactions; and formulate models to support further refinements of ESDGVs and SDG monitoring.
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| 12. |
- Seitzinger, Sybil P., et al.
(författare)
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Planetary Stewardship in an Urbanizing World : Beyond City Limits
- 2012
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 41:8, s. 787-794
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Tidskriftsartikel (refereegranskat)abstract
- Cities are rapidly increasing in importance as a major factor shaping the Earth system, and therefore, must take corresponding responsibility. With currently over half the world's population, cities are supported by resources originating from primarily rural regions often located around the world far distant from the urban loci of use. The sustainability of a city can no longer be considered in isolation from the sustainability of human and natural resources it uses from proximal or distant regions, or the combined resource use and impacts of cities globally. The world's multiple and complex environmental and social challenges require interconnected solutions and coordinated governance approaches to planetary stewardship. We suggest that a key component of planetary stewardship is a global system of cities that develop sustainable processes and policies in concert with its non-urban areas. The potential for cities to cooperate as a system and with rural connectivity could increase their capacity to effect change and foster stewardship at the planetary scale and also increase their resource security.
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| 13. |
- Stafford-Smith, Mark, et al.
(författare)
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Integration : the key to implementing the Sustainable Development Goals
- 2017
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Ingår i: Sustainability Science. - : Springer Science and Business Media LLC. - 1862-4065 .- 1862-4057. ; 12:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- On 25 September, 2015, world leaders met at the United Nations in New York, where they adopted the Sustainable Development Goals. These 17 goals and 169 targets set out an agenda for sustainable development for all nations that embraces economic growth, social inclusion, and environmental protection. Now, the agenda moves from agreeing the goals to implementing and ultimately achieving them. Across the goals, 42 targets focus on means of implementation, and the final goal, Goal 17, is entirely devoted to means of implementation. However, these implementation targets are largely silent about interlinkages and interdependencies among goals. This leaves open the possibility of perverse outcomes and unrealised synergies. We demonstrate that there must be greater attention on interlinkages in three areas: across sectors (e.g., finance, agriculture, energy, and transport), across societal actors (local authorities, government agencies, private sector, and civil society), and between and among low, medium and high income countries. Drawing on a global sustainability science and practice perspective, we provide seven recommendations to improve these interlinkages at both global and national levels, in relation to the UN's categories of means of implementation: finance, technology, capacity building, trade, policy coherence, partnerships, and, finally, data, monitoring and accountability.
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| 14. |
- Steffen, Will, et al.
(författare)
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Planetary boundaries, equity and global sustainability : why wealthy countries could benefit from more equity
- 2013
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Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 5:3-4, s. 403-408
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Forskningsöversikt (refereegranskat)abstract
- The planetary boundaries concept, which aims to define a safe operating space for humanity within the dynamics of the Earth System, has often been criticised on the basis of a presumed conflict between global equity and environmental sustainability goals. However, a re-analysis of the equity-environmental sustainability relationship suggests that significant synergies can be developed to build a more unified approach for working towards global sustainability. The synergies are especially strong for those planetary boundaries based on processes that are aggregated from very heterogeneous distributions at sub-global levels. It is possible to address the biophysical aspects of these boundaries from an Earth System perspective in ways that often may be, and sometimes must be, compatible with enhancing many aspects of social equity. Furthermore, it may well be in the self-interest of wealthy nations to achieve a more spatially equitable world in terms of access to resources and ecosystem services. Combining social equity considerations with the biophysical planetary boundaries approach may therefore constitute a necessary, and perhaps even sufficient, condition for achieving global sustainability.
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| 15. |
- van Vuuren, Detlef P., et al.
(författare)
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Horses for courses : analytical tools to explore planetary boundaries
- 2016
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Ingår i: Earth System Dynamics. - : Copernicus GmbH. - 2190-4979 .- 2190-4987. ; 7:1, s. 267-279
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Tidskriftsartikel (refereegranskat)abstract
- There is a need for more integrated research on sustainable development and global environmental change. In this paper, we focus on the planetary boundaries framework to provide a systematic categorization of key research questions in relation to avoiding severe global environmental degradation. The four categories of key questions are those that relate to (1) the underlying processes and selection of key indicators for planetary boundaries, (2) understanding the impacts of environmental pressure and connections between different types of impacts, (3) better understanding of different response strategies to avoid further degradation, and (4) the available instruments to implement such strategies. Clearly, different categories of scientific disciplines and associated model types exist that can accommodate answering these questions. We identify the strength and weaknesses of different research areas in relation to the question categories, focusing specifically on different types of models. We discuss that more interdisciplinary research is need to increase our understanding by better linking human drivers and social and biophysical impacts. This requires better collaboration between relevant disciplines (associated with the model types), either by exchanging information or by fully linking or integrating them. As fully integrated models can become too complex, the appropriate type of model (the racehorse) should be applied for answering the target research question (the race course).
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| 16. |
- Webb, Robert, et al.
(författare)
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Sustainable urban systems : Co-design and framing for transformation
- 2018
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 47:1, s. 57-77
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Tidskriftsartikel (refereegranskat)abstract
- Rapid urbanisation generates risks and opportunities for sustainable development. Urban policy and decision makers are challenged by the complexity of cities as social-ecological-technical systems. Consequently there is an increasing need for collaborative knowledge development that supports a whole-of-system view, and transformational change at multiple scales. Such holistic urban approaches are rare in practice. A co-design process involving researchers, practitioners and other stakeholders, has progressed such an approach in the Australian context, aiming to also contribute to international knowledge development and sharing. This process has generated three outputs: (1) a shared framework to support more systematic knowledge development and use, (2) identification of barriers that create a gap between stated urban goals and actual practice, and (3) identification of strategic focal areas to address this gap. Developing integrated strategies at broader urban scales is seen as the most pressing need. The knowledge framework adopts a systems perspective that incorporates the many urban trade-offs and synergies revealed by a systems view. Broader implications are drawn for policy and decision makers, for researchers and for a shared forward agenda.
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