| 1. |
- Nelson, Laura, et al.
(author)
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FKBPL: a marker of good prognosis in breast cancer.
- 2015
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:14, s. 12209-12223
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Journal article (peer-reviewed)abstract
- FK506-binding protein-like (FKBPL) has established roles as an anti-tumor protein, with a therapeutic peptide based on this protein, ALM201, shortly entering phase I/II clinical trials. Here, we evaluated FKBPL's prognostic ability in primary breast cancer tissue, represented on tissue microarrays (TMA) from 3277 women recruited into five independent retrospective studies, using immunohistochemistry (IHC). In a meta-analysis, FKBPL levels were a significant predictor of BCSS; low FKBPL levels indicated poorer breast cancer specific survival (BCSS) (hazard ratio (HR) = 1.30, 95% confidence interval (CI) 1.14-1.49, p < 0.001). The prognostic impact of FKBPL remained significant after adjusting for other known prognostic factors (HR = 1.25, 95% CI 1.07-1.45, p = 0.004). For the sub-groups of 2365 estrogen receptor (ER) positive patients and 1649 tamoxifen treated patients, FKBPL was significantly associated with BCSS (HR = 1.34, 95% CI 1.13-1.58, p < 0.001, and HR = 1.25, 95% CI 1.04-1.49, p = 0.02, respectively). A univariate analysis revealed that FKBPL was also a significant predictor of relapse free interval (RFI) within the ER positive patient group, but it was only borderline significant within the smaller tamoxifen treated patient group (HR = 1.32 95% CI 1.05-1.65, p = 0.02 and HR = 1.23 95% CI 0.99-1.54, p = 0.06, respectively). The data suggests a role for FKBPL as a prognostic factor for BCSS, with the potential to be routinely evaluated within the clinic.
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| 2. |
- Byun, Jinyoung, et al.
(author)
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Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer
- 2022
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In: Nature Genetics. - : Nature Research. - 1061-4036 .- 1546-1718. ; 54:8, s. 1167-1177
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Journal article (peer-reviewed)abstract
- To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage.
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| 3. |
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| 4. |
- Ely, Adrian, et al.
(author)
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Structured Collaboration Across a Transformative Knowledge Network-Learning Across Disciplines, Cultures and Contexts?
- 2020
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In: Sustainability. - : MDPI AG. - 2071-1050. ; 12:6
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Journal article (peer-reviewed)abstract
- Realising the Sustainable Development Goals (SDGs) will require transformative changes at micro, meso and macro levels and across diverse geographies. Collaborative, transdisciplinary research has a role to play in documenting, understanding and contributing to such transformations. Previous work has investigated the role of this research in Europe and North America, however the dynamics of transdisciplinary research on 'transformations to sustainability' in other parts of the world are less well-understood. This paper reports on an international project that involved transdisciplinary research in six different hubs across the globe and was strategically designed to enable mutual learning and exchange. It draws on surveys, reports and research outputs to analyse the processes of transdisciplinary collaboration for sustainability that took place between 2015-2019. The paper illustrates how the project was structured in order to enable learning across disciplines, cultures and contexts and describes how it also provided for the negotiation of epistemological frameworks and different normative commitments between members across the network. To this end, it discusses lessons regarding the use of theoretical and methodological anchors, multi-loop learning and evaluating emergent change (including the difficulties encountered). It offers insights for the design and implementation of future international transdisciplinary collaborations that address locally-specific sustainability challenges within the universal framework of the 2030 Agenda for Sustainable Development.
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| 5. |
- Fazey, Ioan, et al.
(author)
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Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
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In: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Journal article (peer-reviewed)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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| 6. |
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| 7. |
- Karpouzoglou, Timon, et al.
(author)
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Towards a peri-urban political ecology of water quality decline
- 2018
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In: Land use policy. - : Elsevier. - 0264-8377 .- 1873-5754. ; 70:November 2017, s. 485-493
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Journal article (peer-reviewed)abstract
- Recent years have witnessed an expanding body of peri-urban and urban scholarship. However, recent scho- larship has yet to adequately address the central role of politics and power shaping water quality decline. The article focuses on the trans-Hindon region which is part of Ghaziabad city, close to India’s capital, Delhi. We draw upon urban political ecology and peri-urban scholarship to explain the role of politics and power shaping water quality decline. We argue in favour of creating stronger synergy between peri-urban and UPE debates as part of conceptualizing water quality decline. The article shows that as a complex socio-political challenge, water quality decline is centrally shaped by the intensifying linkages between urban and peri-urban forms of development and as a result deserves central attention as part of both these debates.
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| 8. |
- Larson, Greger, et al.
(author)
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Current perspectives and the future of domestication studies
- 2014
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 111:17, s. 6139-6146
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Journal article (other academic/artistic)abstract
- It is difficult to overstate the cultural and biological impacts that the domestication of plants and animals has had on our species. Fundamental questions regarding where, when, and how many times domestication took place have been of primary interest within a wide range of academic disciplines. Within the last two decades, the advent of new archaeological and genetic techniques has revolutionized our understanding of the pattern and process of domestication and agricultural origins that led to our modern way of life. In the spring of 2011, 25 scholars with a central interest in domestication representing the fields of genetics, archaeobotany, zooarchaeology, geoarchaeology, and archaeology met at the National Evolutionary Synthesis Center to discuss recent domestication research progress and identify challenges for the future. In this introduction to the resulting Special Feature, we present the state of the art in the field by discussing what is known about the spatial and temporal patterns of domestication, and controversies surrounding the speed, intentionality, and evolutionary aspects of the domestication process. We then highlight three key challenges for future research. We conclude by arguing that although recent progress has been impressive, the next decade will yield even more substantial insights not only into how domestication took place, but also when and where it did, and where and why it did not.
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| 9. |
- Marshall, Carrie Anne, et al.
(author)
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“Nobody cares about you as a group of people” : a mixed methods study of women living in congregate social housing in Ontario, Canada
- 2021
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In: Housing and Society. - : Informa UK Limited. - 0888-2746 .- 2376-0923. ; 48:1, s. 21-42
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Journal article (peer-reviewed)abstract
- Guided by the social model of disability, we carried out this exploratory study to understand the health and psychosocial needs of women living in social housing in Ontario, Canada. Using a sequential, mixed-methods design, we interviewed 19 women using a 126-item quantitative interview including six standardized measures exploring indicators of psychosocial well-being. From these findings, we designed a qualitative interview protocol and returned to participants. We calculated descriptive statistics for quantitative variables and analyzed qualitative data using thematic analysis. Participants reported a median of six unmet basic psychosocial needs (range 1–16; IQR = 6), a high prevalence of health conditions and associated disability with scores falling above the 80th percentile on all subtests of a disability measure. Qualitative findings revealed that participants were living in an environment that made it challenging to meet their basic needs and felt abandoned by community supports. A persistent lack of safety led to self-isolation, which negatively influenced mental well-being. Social housing is aimed at alleviating poverty and its associated harms, yet women face multiple barriers to meeting their basic needs through existing supports and continue to experience poverty. Social housing can be disabling environments for women living in poverty.
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| 10. |
- Pereira, Laura, et al.
(author)
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Transformative spaces in the making : key lessons from nine cases in the Global South
- 2020
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In: Sustainability Science. - : Springer Science and Business Media LLC. - 1862-4065 .- 1862-4057. ; 15:1, s. 161-178
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Journal article (peer-reviewed)abstract
- Creating a just and sustainable planet will require not only small changes, but also systemic transformations in how humans relate to the planet and to each other, i.e., social-ecological transformations. We suggest there is a need for collaborative environments where experimentation with new configurations of social-ecological systems can occur, and we refer to these as transformative spaces. In this paper, we seek a better understanding of how to design and enable the creation of transformative spaces in a development context. We analyse nine case studies from a previous special issue on Designing Transformative Spaces that aimed to collect examples of cutting-edge action-oriented research on transformations from the Global South. The analysis showed five design phases as being essential: Problem Definition Phase; Operationalisation Phase; Tactical Phase; Outcome Phase; and Reflection Phase. From this synthesis, we distilled five key messages that should be considered when designing research, including: (a) there are ethical dilemmas associated with creating a transformative space in a system; (b) it is important to assess the readiness of the system for change before engaging in it; (c) there is a need to balance between 'safe' and 'safe-enough' spaces for transformation; (d) convening a transformative space requires an assemblage of diverse methodological frameworks and tools; and (e) transformative spaces can act as a starting point for institutionalising transformative change. Many researchers are now engaging in transdisciplinary transformations research, and are finding themselves at the knowledge-action interface contributing to transformative space-making. We hope that by analysing experiences from across different geographies we can contribute towards better understanding of how to navigate the processes needed for the urgent global transformations that are being called for to create a more equitable and sustainable planet Earth.
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| 11. |
- Shumilova, Oleksandra, et al.
(author)
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Simulating rewetting events in intermittent rivers and ephemeral streams : A global analysis of leached nutrients and organic matter
- 2019
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In: Global Change Biology. - : WILEY. - 1354-1013 .- 1365-2486. ; 25:5, s. 1591-1611
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Journal article (peer-reviewed)abstract
- Climate change and human pressures are changing the global distribution and the extent of intermittent rivers and ephemeral streams (IRES), which comprise half of the global river network area. IRES are characterized by periods of flow cessation, during which channel substrates accumulate and undergo physico-chemical changes (preconditioning), and periods of flow resumption, when these substrates are rewetted and release pulses of dissolved nutrients and organic matter (OM). However, there are no estimates of the amounts and quality of leached substances, nor is there information on the underlying environmental constraints operating at the global scale. We experimentally simulated, under standard laboratory conditions, rewetting of leaves, riverbed sediments, and epilithic biofilms collected during the dry phase across 205 IRES from five major climate zones. We determined the amounts and qualitative characteristics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds. In addition, we evaluated the variance in leachate characteristics in relation to selected environmental variables and substrate characteristics. We found that sediments, due to their large quantities within riverbeds, contribute most to the overall flux of dissolved substances during rewetting events (56%-98%), and that flux rates distinctly differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contributed most to the areal fluxes. The largest amounts of leached substances were found in the continental climate zone, coinciding with the lowest potential bioavailability of the leached OM. The opposite pattern was found in the arid zone. Environmental variables expected to be modified under climate change (i.e. potential evapotranspiration, aridity, dry period duration, land use) were correlated with the amount of leached substances, with the strongest relationship found for sediments. These results show that the role of IRES should be accounted for in global biogeochemical cycles, especially because prevalence of IRES will increase due to increasing severity of drying events.
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| 12. |
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| 13. |
- Taylor, Adam, et al.
(author)
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Transforming Growth Factor Beta Gene Signatures are Spatially Enriched in Keloid Tissue Biopsies and Ex vivo-Cultured Keloid Fibroblasts
- 2017
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In: Acta Dermato-Venereologica. - : ACTA DERMATO-VENEREOLOGICA. - 0001-5555 .- 1651-2057. ; 97:1, s. 10-16
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Journal article (peer-reviewed)abstract
- The keloid lesion is recognised as a spatially heterogeneous mass both in cellular and acellular composition and biological activity. Here, we have utilised a bioinformatic approach to determine whether this spatial heterogeneity is also evident at the molecular level and to identify key upstream regulators of signalling pathways enriched in the lesion in a spatially-restricted manner. Differentially expressed genes (20% change, p amp;lt; 0.05) obtained from microarray datasets derived from whole keloid biopsies and ex vivo-cultured keloid fibroblasts, both from distinct regions of the keloid lesion (leading edge, centre, and top) have been analysed to show that the TGF beta family plays a significant but spatially dependent role in regulation of keloid gene expression. Furthermore, we have identified additional upstream signalling molecules involved in driving keloid biology and provide information on therapeutic targets whose modulation might be expected to lead to significant therapeutic efficacy.
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| 14. |
- Turhan, Ethemcan
(author)
-
What does transformative research for sustainability look like?
- 2017
-
Other publication (pop. science, debate, etc.)abstract
- Efforts to nurture more sustainable, just futures are happening all around us, albeit in the context of a rapidly changing and highly unequal world that is on the brink of irrevocably dismantling the ecological foundations that sustain human life. The researchers and partner organizations in the Transformations to Sustainability Programme are learning from and accompanying some of those ongoing efforts, in order to shed light on key processes in transformative change, and to better understand how such efforts might be facilitated, adapted, joined up and enhanced across different contexts and scales.
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| 15. |
- Zanchettin, Davide, et al.
(author)
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The Model Intercomparison Project on the climatic response to Volcanic forcing (VolMIP) : experimental design and forcing input data for CMIP6
- 2016
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In: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 9:8, s. 2701-2719
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Journal article (peer-reviewed)abstract
- The enhancement of the stratospheric aerosol layer by volcanic eruptions induces a complex set of responses causing global and regional climate effects on a broad range of timescales. Uncertainties exist regarding the climatic response to strong volcanic forcing identified in coupled climate simulations that contributed to the fifth phase of the Coupled Model Intercomparison Project (CMIP5). In order to better understand the sources of these model diversities, the Model Intercomparison Project on the climatic response to Volcanic forcing (VolMIP) has defined a coordinated set of idealized volcanic perturbation experiments to be carried out in alignment with the CMIP6 protocol. VolMIP provides a common stratospheric aerosol data set for each experiment to minimize differences in the applied volcanic forcing. It defines a set of initial conditions to assess how internal climate variability contributes to determining the response. VolMIP will assess to what extent volcanically forced responses of the coupled ocean-atmosphere system are robustly simulated by state-of-the-art coupled climate models and identify the causes that limit robust simulated behavior, especially differences in the treatment of physical processes. This paper illustrates the design of the idealized volcanic perturbation experiments in the VolMIP protocol and describes the common aerosol forcing input data sets to be used.
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| 16. |
- Zheng, Hou-Feng, et al.
(author)
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Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
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Journal article (peer-reviewed)abstract
- The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
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