| 1. |
- Schael, S, et al.
(author)
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Precision electroweak measurements on the Z resonance
- 2006
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In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Research review (peer-reviewed)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 2. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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| 21. |
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- 2019
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Journal article (peer-reviewed)
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| 22. |
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| 23. |
- Wuttke, Matthias, et al.
(author)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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In: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Journal article (peer-reviewed)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 24. |
- Sawcer, Stephen, et al.
(author)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Journal article (peer-reviewed)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 25. |
- Nijkamp, P., et al.
(author)
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Towards a regional science academy : A manifesto
- 2016
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In: Region. - : European Regional Science Association. - 2409-5370. ; 3:1, s. R1-R16
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Journal article (peer-reviewed)abstract
- This Manifesto provides a joint proposal to create a Regional Science Academy as a think-tank support platform for a strategic development of the spatial sciences. The Regional Science Academy is a strategic spatial knowledge catalyst: it acts as a global intellectual powerhouse for new knowledge network initiatives and scholarly views on regions and cities as vital centrepieces of interconnected spatial systems. This contribution highlights its role and presents various activity plans.
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| 26. |
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| 27. |
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| 28. |
- Mourikis, TP, et al.
(author)
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Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3101-
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Journal article (peer-reviewed)abstract
- The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy.
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| 29. |
- Pattaro, Cristian, et al.
(author)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)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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| 30. |
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| 31. |
- MacLellan, D. A., et al.
(author)
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Annular Fast Electron Transport in Silicon Arising from Low-Temperature Resistivity
- 2013
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In: Physical Review Letters. - 1079-7114. ; 111:9
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Journal article (peer-reviewed)abstract
- Fast electron transport in Si, driven by ultraintense laser pulses, is investigated experimentally and via 3D hybrid particle-in-cell simulations. A transition from a Gaussian-like to an annular fast electron beam profile is demonstrated and explained by resistively generated magnetic fields. The results highlight the potential to completely transform the beam transport pattern by tailoring the resistivity-temperature profile at temperatures as low as a few eV.
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| 32. |
- MacLellan, D A, et al.
(author)
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Tunable mega-ampere electron current propagation in solids by dynamic control of lattice melt.
- 2014
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In: Physical Review Letters. - 1079-7114. ; 113:18
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Journal article (peer-reviewed)abstract
- The influence of lattice-melt-induced resistivity gradients on the transport of mega-ampere currents of fast electrons in solids is investigated numerically and experimentally using laser-accelerated protons to induce isochoric heating. Tailoring the heating profile enables the resistive magnetic fields which strongly influence the current propagation to be manipulated. This tunable laser-driven process enables important fast electron beam properties, including the beam divergence, profile, and symmetry to be actively tailored, and without recourse to complex target manufacture.
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| 33. |
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| 34. |
- Turkington, RC, et al.
(author)
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Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma
- 2019
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In: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:11, s. 1918-1927
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Journal article (peer-reviewed)abstract
- Current strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability of a DNA damage immune response (DDIR) assay to predict response following neoadjuvant chemotherapy in OAC.DesignTranscriptional profiling of 273 formalin-fixed paraffin-embedded prechemotherapy endoscopic OAC biopsies was performed. All patients were treated with platinum-based neoadjuvant chemotherapy and resection between 2003 and 2014 at four centres in the Oesophageal Cancer Clinical and Molecular Stratification consortium. CD8 and programmed death ligand 1 (PD-L1) immunohistochemical staining was assessed in matched resection specimens from 126 cases. Kaplan-Meier and Cox proportional hazards regression analysis were applied according to DDIR status for recurrence-free survival (RFS) and overall survival (OS).ResultsA total of 66 OAC samples (24%) were DDIR positive with the remaining 207 samples (76%) being DDIR negative. DDIR assay positivity was associated with improved RFS (HR: 0.61; 95% CI 0.38 to 0.98; p=0.042) and OS (HR: 0.52; 95% CI 0.31 to 0.88; p=0.015) following multivariate analysis. DDIR-positive patients had a higher pathological response rate (p=0.033), lower nodal burden (p=0.026) and reduced circumferential margin involvement (p=0.007). No difference in OS was observed according to DDIR status in an independent surgery-alone dataset.DDIR-positive OAC tumours were also associated with the presence of CD8+ lymphocytes (intratumoural: p<0.001; stromal: p=0.026) as well as PD-L1 expression (intratumoural: p=0.047; stromal: p=0.025).ConclusionThe DDIR assay is strongly predictive of benefit from DNA-damaging neoadjuvant chemotherapy followed by surgical resection and is associated with a proinflammatory microenvironment in OAC.
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| 35. |
- Carrière, Yves, et al.
(author)
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Crop rotation mitigates impacts of corn rootworm resistance to transgenic Bt corn
- 2020
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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. ; 117:31, s. 18385-18392
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Journal article (peer-reviewed)abstract
- Transgenic crops that produce insecticidal proteins from Bacillus thuringiensis (Bt) can suppress pests and reduce insecticide sprays, but their efficacy is reduced when pests evolve resistance. Although farmers plant refuges of non-Bt host plants to delay pest resistance, this tactic has not been sufficient against the western corn rootworm, Diabrotica virgifera virgifera. In the United States, some populations of this devastating pest have rapidly evolved practical resistance to Cry3 toxins and Cry34/35Ab, the only Bt toxins in commercially available corn that kill rootworms. Here, we analyzed data from 2011 to 2016 on Bt corn fields producing Cry3Bb alone that were severely damaged by this pest in 25 cropreporting districts of Illinois, Iowa, and Minnesota. The annual mean frequency of these problem fields was 29 fields (range 7 to 70) per million acres of Cry3Bb corn in 2011 to 2013, with a cost of $163 to $227 per damaged acre. The frequency of problem fields declined by 92% in 2014 to 2016 relative to 2011 to 2013 and was negatively associated with rotation of corn with soybean. The effectiveness of corn rotation for mitigating Bt resistance problems did not differ significantly between crop-reporting districts with versus without prevalent rotation-resistant rootworm populations. In some analyses, the frequency of problem fields was positively associated with planting of Cry3 corn and negatively associated with planting of Bt corn producing both a Cry3 toxin and Cry34/35Ab. The results highlight the central role of crop rotation for mitigating impacts of D. v. virgifera resistance to Bt corn.
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| 36. |
- Carriere, Yves, et al.
(author)
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Governing evolution : A socioecological comparison of resistance management for insecticidal transgenic Bt crops among four countries
- 2020
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In: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 49:1, s. 1-16
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Research review (peer-reviewed)abstract
- Cooperative management of pest susceptibility to transgenic Bacillus thuringiensis (Bt) crops is pursued worldwide in a variety of forms and to varying degrees of success depending on context. We examine this context using a comparative socioecological analysis of resistance management in Australia, Brazil, India, and the United States. We find that a shared understanding of resistance risks among government regulators, growers, and other actors is critical for effective governance. Furthermore, monitoring of grower compliance with resistance management requirements, surveillance of resistance, and mechanisms to support rapid implementation of remedial actions are essential to achieve desirable outcomes. Mandated resistance management measures, strong coordination between actors, and direct linkages between the group that appraises resistance risks and growers also appear to enhance prospects for effective governance. Our analysis highlights factors that could improve current governance systems and inform other initiatives to conserve susceptibility as a contribution to the cause of public good.
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| 37. |
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| 38. |
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| 39. |
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| 40. |
- Ishigaki, Kazuyoshi, et al.
(author)
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Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis
- 2022
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:11, s. 1640-1651
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Journal article (peer-reviewed)abstract
- Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P < 5 × 10−8), of which 34 are novel. Candidate genes at the novel loci suggest essential roles of the immune system (for example, TNIP2 and TNFRSF11A) and joint tissues (for example, WISP1) in RA etiology. Multi-ancestry fine-mapping identified putatively causal variants with biological insights (for example, LEF1). Moreover, PRS based on multi-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance between populations of European and East Asian ancestries. Our study provides several insights into the etiology of RA and improves the genetic predictability of RA.
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| 41. |
- Strålin, Kristoffer, et al.
(author)
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Performance of PCR/electrospray ionization-mass spectrometry on whole blood for detection of bloodstream microorganisms in patients with suspected sepsis
- 2020
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In: Journal of Clinical Microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 58:9, s. e01860-19
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Journal article (peer-reviewed)abstract
- Blood culture (BC) often fails to detect bloodstream microorganisms in sepsis. However, molecular diagnostics hold great potential. The molecular method PCR/electrospray ionization-mass spectrometry (PCR/ESI-MS) can detect DNA from hundreds of different microorganisms in whole blood. The aim of the present study was to evaluate the performance of this method in a multicenter study including 16 teaching hospitals in the USA (n=13) and Europe (n=3). First, on 2,754 contrived whole blood samples, with or without spiked microorganisms, PCR/ESI-MS produced 99.1% true positive and 97.2% true negative results. Secondly, among 1,460 patients with suspected sepsis (sepsis-2 definition), BC and PCR/ESI-MS on whole blood were positive in 14.6% and 25.6% of cases, respectively, with the following result combinations: BC+/PCR/ESI-MS-, 4.3%; BC+/PCR/ESI-MS+, 10.3%; BC-/PCR/ESI-MS+, 15.3%; and BC-/PCR/ESI-MS-, 70.1%. Compared with BC, PCR/ESI-MS showed the following sensitivities (coagulase-negative staphylococci not included): Gram-positive bacteria, 58%; Gram-negative bacteria, 78%; and Candida species, 83%. The specificities were > 94% for all individual species. Patients treated with prior antimicrobial medications (n=603) had significantly increased PCR/ESI-MS positivity rates compared with patients without prior antimicrobial treatment, 31% vs 22% (p<0.0001), with pronounced differences for Gram-negative bacteria and Candida species. In conclusion, PCR/ESI-MS showed excellent performance on contrived samples. On clinical samples, it showed high specificities, moderately high sensitivities for Gram-negative bacteria and Candida species, and elevated positivity rates during antimicrobial treatment. These promising results encourage further development of molecular diagnostics on whole blood for detection of bloodstream microorganisms in sepsis.
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| 42. |
- Søgaard Jørgensen, Peter, et al.
(author)
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Antibiotic and pesticide susceptibility and the Anthropocene operating space
- 2018
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In: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 1:11, s. 632-641
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Research review (peer-reviewed)abstract
- Rising levels of antimicrobial and pesticide resistance increasingly undermine human health and systems for biomass production, and emphasize the sustainability challenge of preserving organisms susceptible to these biocides. In this Review, we introduce key concepts and examine dynamics of biocide susceptibility that must be governed to address this challenge. We focus on the impact of biocides on the capacity of susceptible organisms to prevent spread of resistance, and we then review how biocide use affects a broader suite of ecosystem services. Finally, we introduce and assess the state of what we term the Anthropocene operating space of biocide susceptibility, a framework for assessing the potential of antibiotic and pesticide resistance to undermine key functions of human society. Based on current trends in antibiotic, insecticide and herbicide resistance, we conclude that the states of all six assessed variables are beyond safe zones, with three variables surpassed regionally or globally.
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| 43. |
- Søgaard Jørgensen, Peter, et al.
(author)
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Coevolutionary Governance of Antibiotic and Pesticide Resistance
- 2020
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In: Trends in Ecology & Evolution. - : Elsevier BV. - 0169-5347 .- 1872-8383. ; 35:6, s. 484-494
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Research review (peer-reviewed)abstract
- Development of new biocides has dominated human responses to evolution of antibiotic and pesticide resistance. Increasing and uniform biocide use, the spread of resistance genes, and the lack of new classes of compounds indicate the importance of navigating toward more sustainable coevolutionary dynamics between human culture and species that evolve resistance. To inform this challenge, we introduce the concept of coevolutionary governance and propose three priorities for its implementation: (i) new norms and mental models for lowering use, (ii) diversifying practices to reduce directional selection, and (iii) investment in collective action institutions to govern connectivity. We highlight the availability of solutions that facilitate broader sustainable development, which for antibiotic resistance include improved sanitation and hygiene, strong health systems, and decreased meat consumption.
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| 44. |
- Baldwin, Scott A., et al.
(author)
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Intraclass correlation associated with therapists : estimates and applications in planning psychotherapy research
- 2011
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In: Cognitive Behaviour Therapy. - : Routledge, Taylor and Francis Group. - 1650-6073 .- 1651-2316. ; 40:1, s. 15-33
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Journal article (peer-reviewed)abstract
- It is essential that outcome research permit clear conclusions to be drawn about the efficacy of interventions. The common practice of nesting therapists within conditions can pose important methodological challenges that affect interpretation, particularly if the study is not powered to account for the nested design. An obstacle to the optimal design of these studies is the lack of data about the intraclass correlation coefficient (ICC), which measures the statistical dependencies introduced by nesting. To begin the development of a public database of ICC estimates, the authors investigated ICCs for a variety outcomes reported in 20 psychotherapy outcome studies. The magnitude of the 495 ICC estimates varied widely across measures and studies. The authors provide recommendations regarding how to select and aggregate ICC estimates for power calculations and show how researchers can use ICC estimates to choose the number of patients and therapists that will optimize power. Attention to these recommendations will strengthen the validity of inferences drawn from psychotherapy studies that nest therapists within conditions.
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| 45. |
- Søgaard Jørgensen, Peter, et al.
(author)
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Changing antibiotic resistance : sustainability transformation to a pro-microbial planet
- 2017
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In: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 25, s. 66-76
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Research review (peer-reviewed)abstract
- Decades of overuse, misuse, and environmental antibiotic pollution has increased the global pool of resistant bacteria. With estimates of hundreds of thousands of annual human deaths and a lack of new drugs to replace old ones, antimicrobial resistance probably constitutes one of the greatest human health and sustainability challenges of the 21st century. To safeguard treatable infections, a deliberate social-ecological transformation is needed toward stewardship of the global microbiome and long-term sustainable use of antibiotics. We review the foundation for such a transformation using recent insights from sustainability science, evolutionary biology and health, and the understanding of human interactions with microbes as two intertwined complex adaptive systems. A coherent strategy should acknowledge humans as the source of the world's strongest evolutionary force, reflect that antibiotics are building blocks of modern health systems, and strive to build social-ecological resilience to minimize levels of resistance and avoid over dependency on innovation of new drugs. Bottom up opportunities for seeding the transformation include participatory monitoring and stewardship of our personal and environmental microbiomes, as well as collective consumer action. Top down priorities include regular international institutions to coordinate multi-level action.
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| 46. |
- Søgaard Jørgensen, Peter, et al.
(author)
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Evolution in the Anthropocene : Informing Governance and Policy
- 2019
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In: Annual Review of Ecology, Evolution and Systematics. - : Annual Reviews. - 1543-592X .- 1545-2069. ; 50, s. 527-546
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Research review (peer-reviewed)abstract
- The Anthropocene biosphere constitutes an unprecedented phase in the evolution of life on Earth with one species, humans, exerting extensive control. The increasing intensity of anthropogenic forces in the twenty-first century has widespread implications for attempts to govern both human-dominated ecosystems and the last remaining wild ecosystems. Here, we review how evolutionary biology can inform governance and policies in the Anthropocene, focusing on five governance challenges that span biodiversity, environmental management, food and other biomass production, and human health. The five challenges are: (a) evolutionary feedbacks, (b) maintaining resilience, (c) alleviating constraints, (d) coevolutionary disruption, and (e) biotechnology. Strategies for governing these dynamics will themselves have to be coevolutionary, as eco-evolutionary and social dynamics change in response to each other.
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| 47. |
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| 48. |
- Yuan, X. H., et al.
(author)
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Effects of target pre-heating and expansion on terahertz radiation production from intense laser-solid interactions
- 2014
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In: High Power Laser Science and Engineering. - : Cambridge University Press (CUP). - 2095-4719 .- 2052-3289. ; 2
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Journal article (peer-reviewed)abstract
- The first experimental measurements of intense laser-driven terahertz (THz) radiation from a solid target which is preheated by an intense pulse of laser-accelerated protons is reported. The total energy of the THz radiation is found to decrease by approximately a factor of 2 compared to a cold target reference. This is attributed to an increase in the scale length of the preformed plasma, driven by proton heating, at the front surface of the target, where the THz radiation is generated. The results show the importance of controlling the preplasma scale length for THz production.
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