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In: R Foundation for Statistical Computing V, Austria."},{"key":"ref46","unstructured":"Douglas B, Martin M, Ben B (2011) lme4: Linear mixed-effects models using S4 classes. In: 0.999375-42 Rpv."},{"key":"ref47","doi-asserted-by":"crossref","unstructured":"Wickham H (2009) ggplot2: elegant graphics for data analysis. 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