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ACKNOWLEDGMENTS We thank the Geological Survey of Australia for permission to sample the Empress 1A and Lancer 1 cores, the Natural Sciences and Engineering Research Council of Canada for financial support (grant #7961–15) of U. Brand, and the National Natural Science Foundation of China for support of F. Meng and P. Ni (grants 41473039 and 4151101015). We thank M. Lozon (Brock University) for drafting and constructing the figures. We thank the editor, Brendan Murphy, as well as three reviewers (Steve Kesler, Erik Sperling, and an anonymous reviewer), for improving the manuscript into its final form ©The Authors Gold Open Access: This paper is published under the terms of the CC-BY license.

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Copyright © 2016 the authors 0270-6474/16/360714-16$15.00/0. This research was supported by National Science Foundation INSPIRE Grant 1248076, which was awarded to Y.L. and A.M.N.

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Open Access funded by Medical Research Council Acknowledgments We thank Richard Kolodner, Grant Brown, and Daniel Durocher for strains and plasmids. We thank Anne Donaldson, Alexander Lorenz, and Shin-ichiro Hiraga from University of Aberdeen for careful reading of the manuscript. Research in T.K.’s lab is supported by Medical Research Council Career Development Fellowship L019698/1. V.K.G. was supported by Biotechnology and Biological Sciences Research Council grant K006304/1. T.S.T. was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (nos. 23131507 and 25131712).

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Acknowledgements We thank Ruth B Murray for reviewing and editing this manuscript. We thank Joan B Soriano for his critical review and constructive comments. We thank Helga Mikkelsen and Alessandra Cifra for their assistance with manuscript editing and revision. Finally, we thank the Journal blind peer reviewers, whose suggestions and critical appraisal significantly improved our original submission. FUNDING This study was funded by Meda, Solna, Sweden. Data acquisition and analyses were funded by Meda. The study was conducted by Research in Real Life as an independent research organisation; Meda had no role in the conduct or reporting of the study.

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Acknowledgements We thank B. Lahner, E. Yakubova and S. Rikiishi for ICP-MS analysis, N. Komiyama, Iowa State University Plant Transformation Facility and Prashant Hosmani for generation of transgenic rice, K. Wang for providing pTF101.1 vector and N. Verbruggen for providing pYES2 and pYEC2/CT-GFP vectors. We also thank Rice T-DNA Insertion Sequence Database center for providing the T-DNA insertion line and X. Wang, T. Zheng and Z. Li for accessing 3 K rice genome sequence, and Graeme Paton for helpful discussions on Cu bioavailability in water-logged soils. This research was supported by a Grant-in-Aid for Specially promoted Research (JSPS KAKENHI Grant Number 16H06296 to J.F.M), and the US National Science Foundation, Plant Genome Research Program (Grant #IOS 0701119 to D.E.S., M.L.G. and S.R.M.P.).

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This project was funded by National Institute for Health Research (NIHR) Health Technology Assessment Programme and will be published in full in Health Technology Assessment; Vol. 20, No. 50. See the NIHR Journals Library website for further project information.

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Blood biochemistry analysis and serum analysis were performed by the Easter Bush Pathology Department, University of Edinburgh. Animal husbandry was performed by Centre for Integrative Physiology bio-research restructure technical staff, University of Edinburgh. Assistance with intravenous injections was provided by Ian Coldicott (University of Sheffield) and Hannah Shorrock (University of Edinburgh). Human blood cDNA was a gift to GH from Kathy Evans, University of Edinburgh. Imaging was performed at the IMPACT imaging facility, University of Edinburgh, with technical assistance from Anisha Kubasik-Thayil. The authors would also like to thank Lyndsay Murray for technical discussions relating to qRT-PCR analysis. This work was supported by funding from the SMA Trust and the Anatomical Society (via grants to THG); the Euan MacDonald Centre for Motor Neurone Disease Research (via grants to THG and SHP); the Wellcome Trust (via grants to EJNG and THG); Muscular Dystrophy UK (via grants to THG and CGB); a Elphinstone Scholarship from the University of Aberdeen (to SHP); and The French Muscular Dystrophy Association (via grants to CM and JC).

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Funding The EuroFIT study is funded by the European Union’s Seventh Framework Program for research technological development and demonstration under Grant Agreement no: 602170. The Health Services Research Unit, University of Aberdeen, is core funded by the Chief Scientist Office of the Scottish Government Health Directorates.

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Open Access funded by Medical Research Council Acknowledgment The work reported here was funded by a grant from the Medical Research Council, UK, grant number: MR/J013838/1.

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Acknowledgements The authors would like to thank, Estelle Payerne (article screening, data extraction and bias assessment); Trish Boyton (article retrieval and screening) and Laura Cawley (search terms and title screening) for their invaluable help in conducting this systematic review. Funding The research was funded by the UK National Institute for Health Research Health Technology Assessment Programme.

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We cordially thank Alma Rute for excellent technical assistance and the DFG (GRK 1431-1 and 1431-2) for financial support (PB). We thank the Microscope and Histology Facility of the University of Aberdeen for providing their equipment. We also thank Jacob Hargreaves for proofreading the manuscript.

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Funding: The research presented in this manuscript was wholly funded by National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), https://www.nc3rs.org.uk/. ‘The Snail Assay as an Alternative to the Rodent Hershberger Assay for Detecting Androgens and Anti-androgens’ funding reference: G0900802/1 to SJ, EJR, CSJ, and LRN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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The authors thank Professor Iber^e Luiz Caldas for the suggestions and encouragement. The authors F.F.G.d.S., R.M.R., J.C.S., and H.A.A. acknowledge the Brazilian agency CNPq and state agencies FAPEMIG, FAPESP, and FAPESC, and M.S.B. also acknowledges the EPSRC Grant Ref. No. EP/I032606/1.

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Peer reviewed