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The principles of replacement, reduction and refinement were applied in the design: group sizes were kept to the minimum consistent with the study objectives, animals were assessed at least once daily against a written clinical score sheet, and predefined humane endpoints were used so that no animal was permitted to reach a moribund state. Reporting of the animal work follows the ARRIVE 2.0 guidelines [\n                      \n                      ]. Animals were handled so as to minimise pain and distress, and predefined humane endpoints were applied throughout the experiment.","order":1,"name":"Ethics","label":"Ethics Approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Competing Interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"232"}}