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closeReferee comments: Referee 2
Posted by PLOS_ONE_Group on 03 Mar 2008 at 12:50 GMT
Referee 2's review:
General comment:
This is an impressive and detailed study of the histo-pathological changes associated with bubonic plague in a mouse model. Strengths of the manuscript include the complex histo-pathological scoring system used, the blinded scoring, the sophisticated method of statistical analysis, and the use of Yersinia pseudotuberculosis as a control.
The only significant methodologic weakness is the lack of repeated assessment of the histological scores for individual animals, either by the same observer (using multiple slides from the same animal or repeated readings of re-coded slides), or by two independent scorers. [The manuscript doesn't actually state the number of observers, so I assumed one observer generated one score for each criterion for each lymph node.] Repeated scoring would allow the inter- and intra-observer reproducibilities to be assessed for each of the histopathological criteria. This would provide a second measure of the value of each criterion for this type of study, and increase the confidence that these criteria could be successfully applied by other researchers. The repeated scoring could be done only on a subset of lymph nodes, or on the entire set.
Minor comments:
Figure 1 data was censured after 48 hours due to high mortality in the Y. pestis group. This is an appropriate approach to the problem of survivor bias in statistical analysis. The data for the later time points for the Yersinia pseudotuberculosis group should be shown since survival was higher. Also, the authors might state a specific criterion for data censure to avoid survivor bias in the statistical analysis, such as the loss of 20% or 50% of the experimental group.
The authors state that the series of infective loads were "statistically identical" for the Y. pestis and Y. pseudotuberculosis groups. The actual data should be shown. Imbalanced dosing can alter the experimental results without being statistically significant. The similar bacterial loads a time point 0 in Figure 1 suggest that this was not a major problem.
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N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication the manuscript has been revised in light of these comments and to address other editorial requirements.