Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: GEO-REFERENCING BIRD-WINDOW COLLISIONS FOR TARGETED MITIGATION
Review round: 1
Reviewer: 3

Output:
Basic reporting: The writing is clear and understandable with only minor edits needed, see below. The literature cited is satisfactory but does include several incomplete references.
Experimental design: The authors point out that there is insufficient experimental setup to warrant statistical analyses. The reporting is mostly qualitative in nature but is sufficient given the nature of the approach.
Validity of the findings: The authors have done a good job of summarizing the data.
Additional comments: Manuscript 21227
PeerJ
Overall Assessment
The authors report on a new method to better track the location of birds killed by window strikes. Most studies simply record the wall of the building, or perhaps the direction of the wall, at a very coarse scale. Without more specific information, attempts at mitigation may be more difficult if there are particular areas of the wall that are more likely to be prone to bird strike. The authors argue that GPS locations are better than simply compass directions. The authors apply these findings to two other locations where data was input using iNaturalist, a citizen science program for reporting natural history observations. The authors recommend using iNaturalist in an effort to thwart large-scale bird-window collisions.
The authors point out that a recent approach used by Loss et al (2015) involves a google form datasheet that lacks a space for GPS coordinates. In addition, the data platforms recommended by Loss et al do not contain any public datasets so the present authors warn that these databases are not being used by scientists or members of the public interested in bird-window kill data. As a result, the authors recommend yet another platform, iNaturalist, because it allows for GPS coordinates, crowd-sourced identification, and citizen science data collection.
Because the dataset is small and without proper control design, the authors do not use statistics but, instead, report the results as qualitative statements.
I think figure 1 illustrates quite well what the issues are relative to using simple cardinal direction vs GPS coordinates. The kernel function in figure 1C and the point density function in 1D show clearly where the problem areas on the buildings are.
Overall I think this approach is important and will make a nice contribution to the burgeoning field of bird-window mortalities.
Line Edits
20 If you are going to tease the reader with “second-greatest”, you should probably let them know what the highest source is.
25 “bird-deterrent films”, compound modifier should be hyphenated
29 Inconsistent single vs double quotes for quotations. See, for example, line 227 where the authors write “zoom in as you see fit”
39 franchise is singular so it should be “has been publicly”
40 The authors imply that it was up to the Minnesota Vikings to invest in a bird-friendly facility. But, the stadium is not owned by them. “U.S. Bank Stadium is owned by the state of Minnesota, represented by the Minnesota Sports Facilities Authority. The Minnesota Sports Facilities Authority (MSFA) was established by the legislature in 2012 and charged with the design, construction and operation of U.S. Bank Stadium. The MSFA consists of five members and is chaired by Michele Kelm-Helgen. The other members are John D. Griffith, Tony Sertich, Bill McCarthy and Barbara Butts Williams. Ted Mondale serves at the CEO/Executive Director.” Source: https://www.usbankstadium.com/stadium-info/faq. As such, it seems the criticism should be redirected to the state of Minnesota, not to the Vikings.
42 The authors should reference the statement “according to the popular narrative…”
57 Data are plural so it should read “so data are not always”
65 coordinates are plural so it should be “suggested by Loss et al. (2015) are GPS coordinates”
94 Better to use “autumn” instead of “fall”. The latter is generally only used by North Americans.
96 Statement about methods being adopted by dozens of campuses should be referenced.
110 Suggest inserting “that” so it reads “Two urban areas in the United States that have been” to match the syntax “are downtown….”.
129 The abbreviation “Penn” has not been formally introduced.
136 Better to write “collisions reported”
233 (and 45) Better to use the full name National Audubon Society. “Audubon” is short form.
Reference
Inconsistent capitalization for titles. Bayne et al uses Sentence style. But, Borden and Lockhart capitalize each word.
Audubon reference is incomplete.
Forbes reference is incomplete.
Klem 1990 does not list the journal name.
Nelson reference is incomplete.
Ocampo-Peñuela et al. 2016 does not list journal name.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: ON THE EXPONENT IN THE VON BERTALANFFY GROWTH MODEL
Review round: 1
Reviewer: 1

Output:
Basic reporting: the English is clear and references and background context are sufficient.  No issues with the structure of the papers , figures or the tables.
article met these criteria.
Experimental design: the experimental design area meets the criteria. The research question is defined and relevant. The investigation was reported and carried out to technical standards. The authors appear transparent in addressing issues with the data sets and analyses. Methods reported in sufficient detail.
Validity of the findings: the authors are clear on the validity of their findings. The authors used data from numerous sources for their analyzes and were transparent and the conclusions are well stated.
There is no over speculation.
Additional comments: Line 23 – size but also mass of the animal
Line 55 – how many of these data sets included repeated observations (measurements ) on individual animals?  Really better analyses  If mixed model approaches used like that of Strathe et al. ? Strathe, A. B., A. Danfær, H. Sørensen, and E. Kebreab. 2010. A multilevel nonlinear mixed-effects approach to model growth in pigs1. J. Anim. Sci. 88:638-649. doi:10.2527/jas.2009-1822

Note line 81 – BW to the 0.75 is used widely in animal sciences as metabolic size.

Line 194 -195 – did you also check enough points before and after the expected inflection point ?
Data with 1 or 2 points above or below the IP – results in greater SE for the model parameters ..
it is not clear why the transformation was done in figure 6 and how often this was done in the data sets
note the variation in Bw increases as animals grow and ordinary least squares do not account for this and using the means at each age as mentioned in line 203 --- does not really take the equal variances into account as the SE of the BW means increase as BW increases – it should be discussed what was assumed and the better methods of doing the statistics when actual data is available included mixed models and accounting for heterogeneous variances


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: ON THE EXPONENT IN THE VON BERTALANFFY GROWTH MODEL
Review round: 1
Reviewer: 2

Output:
Basic reporting: The manuscript is generally well-written. Yet, I recommend authors to address the following:

1) Authors present parts of their methods and results in other sections of the manuscript. Please move lines 57-58 (including Fig 1) and lines 387-401 to the result section. Secondly, please move line 33 “this paper assumes b=1”, Lines 100-101 “Figure 2 displays ....”, lines 115-118 and lines 356-359 to the method section.

2) Multiple times the line of reasoning is unclear to me. Please clarify:
o	Lines 26-30 and how this relates to the text before. Improved otolith analysis is not an application. Why do authors also write a full sentence about starfish populations? This is not related to their own work. Please broaden the first paragraph of the introduction. Potentially with text from lines 119-122.
o	Explain 41-43 in more detail. Explain why authors describe the inflection point? Is this detail needed in the introduction?
o	Again for lines 72-77, is this amount of detail needed in the introduction? If so, please rephrase.
o	Lines 117-118. Is this comment related to the literature or to the work described in this study (if the latter, please move to method section).
o	Lines 122-126 change to: In addition, a search in google scholar identified approximately 24800 papers related to the von Bertalanffy growth model in fish (using the search terms “...”). The use of VBGF in the literature was also specifically surveyed for elasmobranch species, showing that the VBGF model was studied twice as often as any other model (Smart et al. 2016).
o	Lines 146-148: what is the “weight” at the inflection point. Secondly, how can it vary 0% of mmax. Please clarify.
o	Lines 368-369 Why is this sentence included? For which type of animals do authors expect sex change? Has this been reported in the data they use?

3) Authors use Excel annotation to describe how they analyzed their data (e.g. line 225, 230, 232-235, 249). This makes the text unclear. Please rephrase (to standard text annotation) and include all Excel code in supplement.

4) Change lines 155-193 from text into a table with numbers, names, references and additional information on the growth data (number of time steps (days, months, years), whether the data is based on an individual growth trajectory or the mean of a group and whether the original data is in length or weight).
Experimental design: The authors did a very good job to get an extensive dataset on growth to analyze their research question. The question is well-defined and highly relevant. No further comments.
Validity of the findings: The work essentially shows that there is large variability in parameter a when other parameters (mmax, q and m0) are also optimized. This highlights that different combinations of these 4 parameters fit the data best, but that the data quality is not good enough / the growth model too flexible (with many free parameters) to quantify parameter a (and q, mmax and m0) in a consistent way.  What is interesting is that in many species parameter a can vary over a very large range (between 0-0.99) without affecting the fit to the data. This is to me the main finding of the paper and it is also described by the authors in lines 410-414.

Given that combinations of the other parameters affect parameter a so much, I have some suggestions/comments about the other parameters:
o	The mass at age 0 (m0) is largely similar for fishes (see Andersen et al 2008 Theoretical Population Biology), while m0 might be known for the other species in the dataset. It is perhaps better to derive m0 from the literature (instead of optimizing this parameter). This will reduce the flexibility of the optimization, since there are less “free” parameters, and hopefully lower the parameter space that can fit the data in an adequate way.
o	Authors have constrained Mmax and assumed that this parameter needs to be higher than the maximum observed mass. Authors state mmax can exceed the maximum observed mass up to 100 times (lines 275-276). I’m not convinced with this as any mmax that is ~2-100 times larger than the observed maximum basically shows that the data is not strong enough to do the analysis (no data point close to mmax). This is very important as uncertainty in mmax is directly affecting parameter a (as these parameters are dependent on each other in the model). Hence, I would suggest removing all the species that have a mmax that is much higher (e.g. 2 x as high) than the maximum mass observed in the data.
o	Finally, it is not clear to me why authors did not optimize parameter b. Is there evidence in the literature that b should be 1? How will variation in b affect the optimization of parameter a?

Furthermore, I suggest to focus less on the fact that a=0.67 is weakly universal for fish, also because the percentage of non-rejection (fig 8) varies weakly when parameter a is larger than 0.65 (probably the effect of 1 or 2 fishes). If authors would have chosen a threshold of 80% or 85% (see line 106), all values higher than 0.65 of parameter a would be defined as weakly universal. It now seems as if VBGF is supported by the data, while the 0.75 exponent not. However, the differences are very small and as such I find the choice of threshold (90%) a bit misleading.

Lastly, the difference between fish and non-fish is also a difference between highly controlled experiments (where food is not limiting) (non-fish) versus natural conditions (most fish). As such, I would not do a comparison as in Table 3 and only show that both fish and non-fish species have a large range of values for parameter a that fit the data adequately. The difference between fish and non-fish seems to be an artefact and authors provide no biological explanation why fish potentially differ from other taxonomic groups. As such, I also recommend removing lines 18-19 in the abstract.
Additional comments: Line 47 Can authors provide more explanation what (mt/mmax)^1-a exactly is. And what are the units (mass per time)?

Line 83 please explain “noisy data may hide” or remove.

Lines 201-202 please clarify this sentence.

Lines 212-215 please explain how this is standardized across the 60 datasets?

Lines 217 Why has parameter b a value of 2 in Figure 5? Previously it was stated that the value of parameter b is assumed to be 1, please explain?

Line 295 remove “that”

Lines 294-298 maybe add “ FNR shows the parameter space that fits the data adequately. The lower the FNR the less uncertain the value of parameter a”.

Lines 299-300 please clarify where this is justified (discussion section?).

Lines 402-409 I’m very much agreeing with the conclusion, yet the conclusion is not supported by the last lines of the abstract. Please rephrase the ending of the abstract.

Lines 413-414 do authors think this is only a data quality aspect or perhaps also the result of a growth model with too many “free/ unknown” parameters?

Figure 1 which m0, mmax and q are used for the two lines? Do the lines differ in these parameters?

Figure 5 what is the selection criterion from Knight 1968? Is this explained in the method?


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: ON THE EXPONENT IN THE VON BERTALANFFY GROWTH MODEL
Review round: 2
Reviewer: 1

Output:
Basic reporting: English is clear -- and revisions improved the paper
Experimental design: the question is well defined -- and revisions add clarity  --- no issues
Validity of the findings: findings are valid -- no issues -- conclusions stated well --
Additional comments: the revisions have added clarity to the paper -- less potential reader misunderstandings with the revisions.  --ready to be published -


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: ON THE EXPONENT IN THE VON BERTALANFFY GROWTH MODEL
Review round: 2
Reviewer: 2

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: The authors did a good job in revising the manuscript. Below some minor comments to improve clarity.

Line 35 maybe rephrase  to “and applications in ecology, e.g. understanding outbreak dynamics (Pratchett 2005).

Lines 62-69 This is a bit confusing as the first sentence is about mass growth, while the rest relates to length growth. As authors state later, typically length growth with exponent a=0 is equal to mass growth with exponent a=2/3. Hence, “a=0” at the start of line 63 is not equal to the second “a=0” in the same line. Maybe call the length exponent aL.

Line 64 Note that Koch et al 2015 is about shellfish. Please change reference or sentence.

198-208 not fully clear when these tests are used in the analysis, e.g. what are location parameters and where are they compared?

Lines 218-243 could be moved to discussion

Lines 253-254 maybe include, “resulting in 100 models for each dataset” as authors refer in line 304 to “the 100 models”.

Line 442 change “here” to “there”

Line 450 I suggest to rephrase “model (1)” to be understandable for someone who only reads the conclusion paragraphs

Line 452 perhaps add: as the biological meaning of the model exponent, and the variation in the exponent, is not clear.

Line 453 Authors could discuss the consequences of their findings a bit further (perhaps in relation to fisheries management). What do the findings imply in relation to the widely used estimated growth parameters in FishBase and the approximately 25,000 other papers that modeled fish growth?

More a matter of style, but I would rephrase full sentences in round brackets, e.g. line 212-213,310-311, 425-426

Figure 2: maybe include mmax and minfl in fig2a

Figure 9, the example does not show that the combination of male and female data leads to “higher residuals making refutations more difficult and increasing FNR” (line 417-418), right? Yet, it shows there are large differences between males and females. So maybe move reference of figure 9 to line 416-417 “In case that these groups had a different growth pattern (different optimal exponents) (Figure 9)”

Figure 9 include y-axis label


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: SMALL-SCALE SCREENING OF ANTICANCER DRUGS ACTING SPECIFICALLY ON NEURAL STEM/PROGENITOR CELLS DERIVED FROM HUMAN-INDUCED PLURIPOTENT STEM CELLS USING A TIME-COURSE CYTOTOXICITY TEST
Review round: 1
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: Well-designed
Validity of the findings: The finding that the slow-acting drug, methotrexate has cytotoxic effects on human iPS cell-derived NSPCs specifically but not on human tissue-derived NSPCs is new and interesting.
Additional comments: This article provides very valuable information for the development of drug discovery toxicology, and could be published if the authors modify the text as directed.

1, Time-course assay was performed by image-based and noninvasive procedure. I think that it is better for the authors to emphasize this a little more. Because the acceptance of image-based morphological assays of cells and living matters has been increased with advances in information technology currently.

2, Authors should describe a relational expression to calculate the percentage of neurosphere size indicated in y-axis of Fig. 3.

3, Authors should indicate the number of samples used in the experiment.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: SMALL-SCALE SCREENING OF ANTICANCER DRUGS ACTING SPECIFICALLY ON NEURAL STEM/PROGENITOR CELLS DERIVED FROM HUMAN-INDUCED PLURIPOTENT STEM CELLS USING A TIME-COURSE CYTOTOXICITY TEST
Review round: 1
Reviewer: 2

Output:
Basic reporting: The paper is well organized.
Experimental design: 1. In the time-course assay, the drug responses of cells may be varied by the neurosphere sizes. Why did the authors use the cell density of 200 cells/micowell?

2. Did the authors exchange the culture medium including drug in the time-course assay?
Validity of the findings: This study describes the efficiency of time-course cytotoxicity assay using 3D (neurosphere) culture. The idea that this assay applies as a backup safety measure for stem-cell therapies is unique and original. Furthermore, this assay has potential of wide use for drug screening method, because the protocol is very simple.

The findings are novel and consistent. However, the following point is unclear.

It is difficult to understand the degree of cytotoxic effect in the time-course assay, compared to the endpoint assay. Please add the discussion about the criteria for judgment of cytotoxicity on the time-course assay.
Additional comments: No additional comments


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: SMALL-SCALE SCREENING OF ANTICANCER DRUGS ACTING SPECIFICALLY ON NEURAL STEM/PROGENITOR CELLS DERIVED FROM HUMAN-INDUCED PLURIPOTENT STEM CELLS USING A TIME-COURSE CYTOTOXICITY TEST
Review round: 1
Reviewer: 3

Output:
Basic reporting: No comments
Experimental design: The authors wisely combined two methods, one using the ATP measurement for cell proliferation/viable cells and cytotoxic effects of drugs after 2 days and the second  (MSA assay) to follow the real time effects of the drugs by measuring the neurosphere size during 7 days. This expermimental design was relevant and meaningful.
Validity of the findings: The combination of these two methods allowed to refine the effects of drugs concentration and with time. These results allowed to classify cisplatin and etoposide as fast-acting drugs with early cytotoxicity, and mercaptopurine and methotrexate as slow-acting drugs with late cytotoxicity. These results highlighted the need to reassess cytostatic drugs from the viewpoint of their time-dependent action. These effects were obtained in vitro and should be confirmed in vivo.
Additional comments: This manuscript approaches scientifically how to overcome the risks of teratoma formation and the overgrowth of transplanted cells. This manuscript describes concicely but very convingly and  elegantly the specificity of drugs able to reduce the potential tumorigenicity of transplanted cells.
The paper is well written with figures highly informative.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: SMALL-SCALE SCREENING OF ANTICANCER DRUGS ACTING SPECIFICALLY ON NEURAL STEM/PROGENITOR CELLS DERIVED FROM HUMAN-INDUCED PLURIPOTENT STEM CELLS USING A TIME-COURSE CYTOTOXICITY TEST
Review round: 1
Reviewer: 4

Output:
Basic reporting: The article is well written, clear description of findings.
The topic is very important,
Experimental design: The experimental design is good, although the work would benefit from inclusion more compounds into studies
Validity of the findings: The findings are valid, but somewhat limited
Additional comments: The recommendation would be to extend study to include more compounds. Also, the paper would benefit from more discussion of challenges of cell therapies and guidance for the characterization of stem cell tissues for transplantation. For example, recent works of S. Yamanaka were related to characterization of proliferation potential of stem cell derived tissues and also genotyping of cell lines used for transplantation. More discussion may be beneficial for the paper.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: MURINE PLURIPOTENT STEM CELLS THAT ESCAPE DIFFERENTIATION INSIDE TERATOMAS MAINTAIN PLURIPOTENCY
Review round: 1
Reviewer: 1

Output:
Basic reporting: The English language needs to be improved throughout all parts of the manuscript to ensure that the text becomes clearly understandable. The language should be reviewed by a native English speaking colleague or a professional service for language editing. I will try to exemplify this for parts of the abstract only: The first half-sentence of the background is understandable; afterwards the reader has to guess what the authors want to say. Methods: abbreviations such as MES, EGFP, iPSCs are not defined and at least MES is an ambiguous abbreviation. Moreover, iPSC are generated by reprogramming, which might involve the transduction of cells by a virus to introduce the reprogramming factors. However, it is wrong to write that iPSCs were generated by virus infection as the authors did. I am also not a native speaker but it is clear that the sentence “And the differentiate ability were study by the assays of in vivo teratoma formation” is understanable or interpretable but it is not a correct English sentence. Results: MES-FT and iPS-FT as MES-ST and iPS-ST are not explained. These abbreviation are even not explained when they are first used in the manuscript, i. e. Fig 2, making the understanding of the manuscript very difficult.

Due the problems regarding the language, it is currently difficult to comment on the scientific background. However, the introductory statement that in vivo differentiation systems are superior to in vitro differentiation systems and even “more adapt to clinical application” is not based on sufficient evidence.

The structure of the article appears to be conform with PeerJ standards. However, the quality of several figures needs to be improved. On all pictures showing cells or tissues scale bars are missing. All figures have very poor legends. Data from which MES and iPS cells are shown in Fig. 2 (is it OCT4-MES and TG iPS1-7)?. In Fig. 2 (TR-PCR) several bands for the housekeeping gene Hprt are not clearly visible making the results for the other genes analyzed questionable. In Figs. 3a, 5c, 5d no specific tissues within the tumors can be identified since the magnification is not sufficient. In Fig 3b, I can identify an endodermal and a mesodermal differentiation but no ectodermal differentiation. Therefore, these pictures do not convincingly demonstrate pluripotency of the cells that were injected to generate these tumors. In Fig. 3c and 5e, the OCT staining is also not very convincing, the brown color looks more like a background staining (and this is different from Figs 3d and 5f). Fig. 7 is, in view of the raw data provided for the qPCR experiment, highly suspicious for showing means plus SD of technical replicates only. Technical replicates would not justify the statistical analysis. Moreover, the use of a Student’s t-test is likely not justified since it requires normal distribution data and equal variations between the data sets. Moreover, which “mES” are shown here? In addition,, some genes are indicated correctly (first letter in capitals) but most others are not. Raw data are supplied for the qPCR data only.

The study by Pei and colleagues is in principle interesting. While many studies have shown the presence of cells expressing pluripotency markers in teratomas (some of which could have been cited), this study suggests that pluripotent cells can be recovered from teratomas and can be sequentially transplanted to generate new teratomas. This has to my knowledge not been shown before (assumed that the tumors are teratomas). However, the tumors shown cannot be clearly identified as teratomas in this manuscript. Diagnosis of a tumor as a teratoma require the presence of tissues derived from all three germ layers and this is not clearly shown. Moreover, the PCR and qPCR data are currently also not convincing (see my comments above).
Experimental design: The design of the study is in principle reasonable and the research question is relevant. The methods used are generally very poorly described (see e.g. “mouse strains” which contains hardly any meaningful information so that strains including the genetic background cannot been identified). Moreover, no antibodies used are identified unambiguously and no information on primers are given. The teratoma experiments are hardly described; it is, e.g., not mentioned to which tissue the cells have been injected or how long the tumors were grown. More similar examples could be given easily.
Validity of the findings: The technical standard of the experiments (or the results presented) is in my view currently not sufficient to justify publication. The authors need to provide data, which unambiguous demonstrate that the tumors are teratomas and they need to provide sound gene expression data.

Currently, the conclusions are rather broad and not very specific with respect to the data shown. However, with respect to the language it is difficult to assess these issues.
Additional comments: The basic critique regarding the experiments (unambiguous demonstration that the tumors are teratomas; providing sound gene expression data) needs to be addressed and the methods needs to be described according to common standards. If this is possible, the authors should work on issues such as language and presentation in the context of the literature.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: MURINE PLURIPOTENT STEM CELLS THAT ESCAPE DIFFERENTIATION INSIDE TERATOMAS MAINTAIN PLURIPOTENCY
Review round: 1
Reviewer: 2

Output:
Basic reporting: The English language should be improved. There are many typographical errors, including: s everal, detials, fonud, tarotoma… that could be corrected using Word. Several sentences start with ‘And’; Thus, your manuscript need to be reviewed/edited by a native English speaking colleague.

Another important point is that all acronyms should be clearly defined as they first appear in the text. Some are not defined. For example, what are MES-FT? (I guess that it means Mouse Embryonic Stem- from First Teratoma?).

I suggest that you change the title for: “Pluripotent mouse stem cells persist and can be isolated from in vivo teratoma”.

Background section: To my knowledge, there is no clear demonstration that PSCs derivatives obtained in vivo are superior to derivatives obtained in vitro. So I would remove or at least temper this statement and I would rather write that “Teratoma is a widely used assay in the field of stem cells and regenerative medicine but the cell composition of teratoma is still elusive”.
Experimental design: 1.	You have used a GFP construct that reports Oct4 expression. First, it seems important to confirm that the GFP signal does report for Oct4 endogenous expression. To tackle this issue, I suggest that you perform immunostaining on your PSC cultures using an anti-OCT4 antibody and a secondary antibody coupled to Cy3 to determine whether or not GFP and Cy3 signals merge. Please note that the correct gene name is Pou5f1, not Oct4, even if Oct4 is widely used and accepted.

2.	In your teratoma assays (Figs. 3, 5 and 6), immunostainings were performed using an OCT4 antibody, which could detect endogenous OCT4 that is expressed in adult tissues (see Bhartiya, Stem cells int., 2013). To rule out that you detected Oct4 expressed from the host and to show that your Oct4 signal came from the PSCs that you injected, I suggest that you perform additional stainings on teratoma using an anti-GFP antibody or that you show GFP fluorescence.

3.	I suggest that you perform immunostainings on teratoma using antibodies against markers of the three germ layers, as this is the accepted standard in the field.

4.	To confirm the pluripotency of your PSC cultures, in particular those issued from teratoma dissection (FT and ST), I suggest that you perform alkaline phosphatase staining.

5.	It is not clear whether or not the green signal shown for Oct4 in Figs. 1, 5 and 6 is the fluorescence emitted by GFP driven by Oct4 promoter or whether it comes from an immunostaining? Please explain and mention it in the text.

6.	The composition of the different culture media should be detailed in the material and methods part.

7.	Scale bars should be included in photographs.

8.	Please use an additional housekeeping gene in your PCR experiments (figure 2), as there is a great variability in your Hprt expression (use for example Gapdh, as in your qPCR). Please also provide a legend.

9.	I thank you for providing raw qPCR data (Table S1). Your qPCR were performed in triplicates and were correctly analysed. But these triplicates are three measures performed on the same cDNA and therefore it only takes into account the technical variability. To take into account biological variability, RT-qPCR should be performed on at least two more biological samples for each line (so to have n=3 biological samples for each line).You might use Genorm to select three or 4 housekeeping genes to accurately compare expression in your different samples by qPCR (see Vandesompele et al., Genome Biology, 2002, 'Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes').

10.	It’s not clear if MEFs were removed so that RNA were extracted from pure PSCs samples? Please explain.
Validity of the findings: Overall, the findings are valid and the conclusion are well stated and linked to the original research question.
However, I have found that your conclusion on PGC markers is overstated.Indeed, your PGC markers are weakly expressed in your qPCR assay (levels that of course depend on the efficiency of your primers); Therefore I suggest that you mention that there is an increase in the levels of PGC markers but that they remain weakly expressed. Moreover, it is important to reproduce these findings on more biological samples.
Additional comments: The study by Pei et al. reports the isolation and characterization of pluripotent stem cells (PSCs) from in vivo teratoma. As previously reported for cancer stem cells, the authors found that PSCs can be injected in immunocompromised mice, harvested from teratomas, expanded in vitro, and reinjected several times while keeping some molecular and functional characteristics of PSCs. This is an interesting study that requires a major revision, in particular the English language should be improved and additional experiments must be performed to reach higher standard.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: MURINE PLURIPOTENT STEM CELLS THAT ESCAPE DIFFERENTIATION INSIDE TERATOMAS MAINTAIN PLURIPOTENCY
Review round: 2
Reviewer: 1

Output:
Basic reporting: The authors have made a substantial progress in the presentation of their study. The English is now understandable and the content is mostly clear. The authors should consider further clarification of the sentences in lines 14, 49-50, and 109-110. The figures have been significantly improved. Some abbreviations are not defined at their first appearance (MEF, line 83; DMEM, line 85; FBS, line 85; LIF line 86). The primer sequences should be better provided in a separate table than within the text.
Experimental design: The description of the methods has been improved but some aspects need further attention:
- the secondary antibodies, which have been used, are not identified (lines 98 and 119)
- the description of the qPCR and statistics is mixed up
- the injection site of the stem cells in the NOD/SCID mice is not mentioned
Validity of the findings: The quality of the data has been improved but some aspects need further attention:
- In Fig. 2 a negative control such as MEFs is missing.
- The quality of the histology of the teratomas is much better now. However, the differentiations shown for endoderm in Fig. 3a and ectoderm in Fig. 5c are not completely undisputable in my view. Therefore, I would encourage the authors to do immunohistochemistry for germ layer-specific markers to further support their findings, although this might not be an absolute requirement since the reader can now decide whether she/he wants to follow the interpretation of the authors or not.
- It is essential to reconsider the statistics for Fig. 7: The Wilcoxon test is suitable to compare two paired samples. One might discuss whether samples are paired in these experiments. However, it is clear that always three samples need to be compared. Therefore a Kruskal-Wallis test might be appropriate.
Additional comments: No additional comments


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: MURINE PLURIPOTENT STEM CELLS THAT ESCAPE DIFFERENTIATION INSIDE TERATOMAS MAINTAIN PLURIPOTENCY
Review round: 2
Reviewer: 2

Output:
Basic reporting: The English language is now correct. But there are still some mistakes that need to be corrected, including:

Takahashiand Yamanaka (a space is missing after the name of the first author)
Teratoma and not Tarotoma as in the panel A of figure 4 and of figure 6.
Nanog and not Naong as written (last page of results)
Mean and not MS in methods
MES-FT and iPS-FT are not defined when they first appear in the text.
SAS program (SAS stands for what?, please define this term)
Experimental design: The anti-GFP antibody that was used is not indicated in the mat and methods

I should have noticed this before but when I read again your manuscript I realize that a negative control line is missing for you PCR and qPCR data.
So please add a negative control, such as fibroblasts, which do not express pluripotency/germ cell markers for PCR in figure 2 and qPCR in figure 7.
.
Validity of the findings: Overall it is good.

However, I would temper and remove ‘highly’ from the sentence “OCT4-positive cells … highly express germ cell markers”. To affirm this, you should have compared the expression levels of these markers in your cells to those in primordial germ cells (positive control) and to a negative control line (such as fibroblasts). So, in your situation, you can conclude that they express germ cell markers,  but not that they highly express them.
Additional comments: Your manuscript is now much better. I will add a negative control for your PCR and qPCRs and pay attention to details in your text.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: DOMESTIC CARNIVORE INTERACTIONS WITH WILDLIFE IN THE CAPE HORN BIOSPHERE RESERVE, CHILE: HUSBANDRY AND PERCEPTIONS OF IMPACT FROM A COMMUNITY PERSPECTIVE
Review round: 1
Reviewer: 1

Output:
Basic reporting: The paper shows a clear language throughout. However, I’m not a native English speaker and can’t not assess if it can be improved.
Context and background in intro are well raised and most references are adequate. Structure fits the journal standards. Figures and tables are adequate.
Experimental design: Research and experiment are well designed and performed to ethical standards. Methods are described in detail and data allow replications. Statistical procedures are adequate and especially GLMs well applied, as well as model selection based on AICc ranking.
Validity of the findings: My main concern about the paper is the application and weakness of the results. Sample size is relatively small and geographic ambit restricted. Although data seems robust and statistically significant results seem of limited application. I suggest dealing with this discussing what happens in the rest of the area (Biosphere Reserve). Is the problem with dogs similar in rest of the reserve? Do property and households follow the same pattern than in the island?
The conclusion of the paper is “free-roaming dogs are perceived to interact in an anthropogenic context” and the recommendation is to develop environmental education actions. In most of the places where free-roaming dogs cause problems the solution comes from control actions or culling and always in the origin of the problem is the man hand. What kind of education actions does propose the authors? More details are needed here. Environmental education can be a proposal for the future but does not solve actual problems. Therefore, this kind of guidelines should be complementary of other actions. Which other solutions can be applied there?
Additional comments: No additional comments


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: DOMESTIC CARNIVORE INTERACTIONS WITH WILDLIFE IN THE CAPE HORN BIOSPHERE RESERVE, CHILE: HUSBANDRY AND PERCEPTIONS OF IMPACT FROM A COMMUNITY PERSPECTIVE
Review round: 1
Reviewer: 2

Output:
Basic reporting: Introcution lack of relevant information that help to define the necesity of this research
Experimental design: - Research questions are difficult to understand
- Methods are not well described
Validity of the findings: - Although data obtained from questionaires are used to obtain information regarding impact of domestic animals upon wildlife, this data must be used with caution and be very autocritic with the data obtained if no other confirmation method is used. If valid, data provided in this MS would fit better in a local journal.
- It is not clear enough how model building was carried out biological and stasticaly.
Additional comments: General comments
Ms aimed to understand perceptions of impacts of free-roaming dogs and cats to wildlife. Although the objectives of this MS are of interest in the area, there are several aspects that difficult fulfilling the objectives proposed in this study. Overall, it’s not clear for this reviewer what authors wanted to test with the questionnaire and if data they could get with this could be used for what they wanted to predict, which difficult interpretation.
In introduction it’s is not clear what was the aim of the study. 1) it’s about how free-ranging dogs and cats can get access to a conservation area? Can that be assessed through questionnaires??, The questionnaire can give perceptions more that access to a conservation area. Also, questions are applied to determine predictor of dog’s access to wildlife, which is not clear how questions asked can help to explain this. Methods are not clear and result section is not well written. The MS is about domestic carnivores and in some paragraph cats are included, models run, but in others only dogs are mentioned.

Specific comments
Introduction
L68-69: Dogs and cats hybridization...this has proved with some species only. Clarify or remove sentence.
L82-88: access to wildlife? Or allowing dogs roaming freely?

Methods
L92-99: Ethics should go at the end of methods
L116-126: This paragraph would fit better at the introduction where could add more emphasis on the need for conducting this study.
L135: CI of 95%?
L145-146: how degree of confinement was defined?
L166: what’s the aim of include rural and urban dogs as factors? Not clear the response variables on this analysis.
Definitions: How free-ranging dogs were defined?? How feral dogs are defined and how authors are sure they are not owned dogs? Just by interviews?
Statistic: aims is about dog and cats but the statistic is just regarding dogs, please clarify. Data on the questionnaire: it is not clear enough what authors wanted to test with the questionnaire. In methods it is not clear the method for model building and is confused with results section. M1: How a dog can be part of a free-roaming population? What is the response variable here? Dog restriction? M2, is regarding if a dog bring wild prey at home?? Model 3 not explained at all.
Discussion
There is data first given in the discussion and not informed in result section, such as distance of sighting dogs in wild area, among others.
Conclusion
How authors can be sure dogs and cats interact with wildlife?, only by interview?, there is any confirmatory method such as faecal analysis?

Tables and Figures
Figure 2. How sighting of dogs was defined??


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: DOMESTIC CARNIVORE INTERACTIONS WITH WILDLIFE IN THE CAPE HORN BIOSPHERE RESERVE, CHILE: HUSBANDRY AND PERCEPTIONS OF IMPACT FROM A COMMUNITY PERSPECTIVE
Review round: 2
Reviewer: 1

Output:
Basic reporting: commented on the previous version
Experimental design: commented on the previous version
Validity of the findings: commented on the previous version
Additional comments: No additional comments


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: DOMESTIC CARNIVORE INTERACTIONS WITH WILDLIFE IN THE CAPE HORN BIOSPHERE RESERVE, CHILE: HUSBANDRY AND PERCEPTIONS OF IMPACT FROM A COMMUNITY PERSPECTIVE
Review round: 2
Reviewer: 2

Output:
Basic reporting: The background and rationale for this research are described clearly, and the importance of exploring possible interactions between dogs, cats, people and wildlife in the Cape Horn Biosphere Reserve (CHBR) is made exlicit. In general, the standard of English expression is good (I have noted a small number of places for improvement below), and figures and tabular materials are clear. I have just a couple of suggestions to make on the basic reporting (in giving line numbers below I refer to the track-changed Word version, not the pdf), including a couple of references that may be relevant:

Line 54: The Cape Horn Biosphere Reserve is certainly a long way south, but it isn't strictly the southernmost protected area of the globe. That area would be Antarctica, a great deal of which is protected under international treaties.

Lines 74 onward: A recent reference that quantifies the global impacts of domestic dogs on wildlife is: Doherty et al. (2017 The global impacts of domestic dogs on threatened vertebrates. Biol Conservation 210, 56-59).

Conclusions: This section reads well and makes several well justified arguments about how the impacts of domestic dogs and cats might be reduced in the CHBR, based on the questionnaire survey results. A recent study by Hall et al. (2016, PLOS ONE 11(4) e151962) made similar recommendations, and more, based on questionnaire surveys carried out in six different countries, and should have some further recommendations of relevance here.
Experimental design: The questionnaire surveys and analyses of results appear to have been done well, and the results are presented clearly and fully. Importantly, the sampling and analytical designs allow the study's four main questions to be addressed and, with provision of the questionnaire, could be replicated by later researchers. The third aim could be clarified slightly. This says: "... examine experiences and perceptions of the impact of free-roaming dogs and cats on wildlife and corroborate those with an analysis of prey remains of dog feces". Why could clarification not be attempted with cat feces too? I presume these were too hard to find, but a short explanation would be helpful.
Validity of the findings: In general, I think the findings and conclusions are well made, with appropriate tempering of the initial results and conclusions that are drawn from them. Limitations are clearly identified and ways forward presented. This work will hopefully lead to actual quantification of the impacts of domestic dogs and cats on wildlife and other values in the CHBR, and to better mitigation of these impacts in future.
Additional comments: I was not a reviewer of the original manuscript, but my reading of the current version (with the track-changes) and of the authors' rebuttal letter suggests that it has been very extensively reworked and revised. It reads well, and most of the concerns that appear to have been present in the original version have been effectively addressed here. I noted just a small number of corrections that could be made to improve clarity or to improve the English expression:

Lines 101-102: "... a population of free-roaming dogs and cats ..." should be "... populations of free-roaming dogs and cats ...".

Lines 210-211: "(ii) report experienced problems associated with dogs ...". This is not clear; perhaps something like "(ii) report problems reported by respondents that were associated with dogs ..." better describes what is meant. Or, even more simply, just: "(ii) report problems associated with dogs ...".

Line 271: Were the 'street dogs' that were being fed on a regular basis owned or feral dogs?

Line 309: "Predominant experienced dog problems in town were conflicts ..." would read better as: "Predominant dog problems experienced in town were conflicts ...".

Line 470: Is 'provenience' meant to be 'provenance' or something similar?

Table 1: Please define what was meant by NAs.

Fig. 1: Yendegaia National Park is mentioned in the figure caption, but is not shown on the map. Can its location be added to the map?


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: CHARACTERIZATION AND TOXICITY OF CITRAL INCORPORATED WITH NANOSTRUCTURED LIPID CARRIER
Review round: 1
Reviewer: 1

Output:
Basic reporting: The article is well written, clear, structured and it is within the field of the journal. The article describes the production of lipid nanoparticles of citral with a good particle size, PI, ZP, EE and biocompatibility. The article is well illustrated. This article can be accepted for publication after a major revision.
Experimental design: The design of the production and caracterization of the NLC prepared is well done.
The methods are well described. The article is well illustrated.
Validity of the findings: The article is well written and it is within the field of the journal. The results and conclusions are acceptable.
Additional comments: The article is well written and it is within the field of the journal. The article describes the production of lipid nanoparticles of citral with a particle size, PI, ZP and good EE. The article is well illustrated. This article can be accepted for publication after a major revision.

Minor Changes:
•	Add a list of abbreviations in the end of the article, after the conclusions subchapter (in the abstract have the abbreviation NO?! I know what is but some authors no…. a list of abbreviations solve this problem);

•	In the introduction, the authors should highlight the advantages of lipid nanoparticles compared to other colloidal carriers. Explain why you chose the NLC and not SLN! Describe the advantages of this kind of second generation of lipid nanoparticles. Authors can see these in the article: (cite the article)
Almeida H, Amaral MH, Lobão P, Silva AC, Sousa Lobo JM. Applications of lipid and polymeric nanoparticles in ophthalmic pharmaceutical formulations: present and futures considerations. J. Pharm Pharm Sci. 2014; 17(3)278-293.

•	Why you chose these solid and liquid lipids to prepare the NLC? Are you sure that are the best choice? Justify!

•	In the preparation of NLC detail the rpm of the stirring and time.

•	In the determination of EE% describe the wave-length (nm) used in the UV-Vis spectrophotometer. The same in the in vitro dug release study.

•	In the in vitro splenocyte viability (MTT) why you use these rage of concentrations of the formulation? Support with bibliography.

•	ZP values prove that the optimized formulation is not stable over time. Why you did n´t optimized the formulation or add something to improve this parameter? How you justified this? Improve this because your explanation is not enough…

Major Changes

•	In order to improve the quality of the article, the subchapter results and discussion must be united in only one subchapter. It is better for the readers to understand your research.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: CHARACTERIZATION AND TOXICITY OF CITRAL INCORPORATED WITH NANOSTRUCTURED LIPID CARRIER
Review round: 1
Reviewer: 2

Output:
Basic reporting: Manuscript title: Characterization and Toxicity of Citral Incorporated With Nanostructured Lipid Carrier
Authors: Nordin et al
The manuscript describes the physicochemical characterization of the Citral loaded NLC. Works appear to be systematically carried out and trustworthy. The manuscript is worthy to be published. However, some corrections are to be made before a final decision could be made.
The level of English in its present form is not acceptable. Besides there are some typos and merged words. Authors should have made a general correlation between the different experimental data set. Some specific comments are appended below:
1.	In the introduction section the authors should make some statement as how the present manuscript is going to add further information in the field of NLC research. What is the novelty of the present work?
2.	Abstract: Polydispersity index does not have any unit.
3.	Authors should justify such a higher extent of entrapment efficiency (99%). Is it trustworthy?
4.	The interpretation on the TEM images (Figure 1) is completely wrong. NLCs are elsewhere, which the authors have failed to mark.
5.	Authors have not shown the control experiment. This is absolutely essential to prove that the citral release from the NLC is sustained. Also authors should propose as which model is best fitted to the release kinetics.
6.	I failed to follow the meaning of 105% cell viability (Figure 3), especially for the blank NLC. What does it signify?
7.	Line 399: statement is wrong. Authors should rather justify as how the systems with lower magnitude of zeta potential is stable. Author should specifically mention that the used Tween provided steric stabilization to the NLC formulations.
8.	Figure 3: Authors should comment on the optimum concentration of the formulation.
9.	The conclusion section should be rewritten. Some future perspectives are worth mentioning.
Experimental design: Looks fine
Validity of the findings: Alright
Additional comments: No additional comments


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: CHARACTERIZATION AND TOXICITY OF CITRAL INCORPORATED WITH NANOSTRUCTURED LIPID CARRIER
Review round: 2
Reviewer: 1

Output:
Basic reporting: I accept the changes done by the authors! The manuscript must be published! Thanks
Experimental design: I accept the changes done by the authors! The manuscript must be published! Thanks
Validity of the findings: I accept the changes done by the authors! The manuscript must be published! Thanks
Additional comments: I accept the changes done by the authors! The manuscript must be published! Thanks


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: TRANSLATING GENOMICS INTO PRACTICE FOR REAL-TIME SURVEILLANCE AND RESPONSE TO CARBAPENEMASE-PRODUCING ENTEROBACTERIACEAE: EVIDENCE FROM A COMPLEX MULTI-INSTITUTIONAL KPC OUTBREAK
Review round: 1
Reviewer: 1

Output:
Basic reporting: No comment
Experimental design: No comment.
Validity of the findings: No comment.
Additional comments: This article describes the enhanced effect of combining WGS information with traditional field epidemiology to inform management of an established KPC producing Enterobacteriaceae outbreak.The text is well written, clear and unambiguous with sufficient relevant references and background provided.

General comments

The value of the WGS in the context of patient benefit and healthcare economics is difficult to quantify and the manuscript would benefit from estimates of these in this study, i.e. the authors state that further transmission has slowed because of increased intervention but is there an estimate of the healthcare saving and patient benefit because of this? This is a subjective area but if screening had been introduced at an earlier stage would there be an estimated saving in terms of hospital bed days for example?

The authors discuss the revision of guidelines for outbreak management since the study was performed, a discussion of further improvements/recommendations and how they would be implemented would be of value.

Throughout the manuscript the term real-time is used to describe how WGS informed transmission dynamics and subsequent infection control management. Near real-time is more accurate as it still takes at least a week to take appropriate samples, culture, sequence and analyse the information.

The ability to determine whom infected whom in these investigations is an interesting point for discussion and also has potentially difficult ethical/legal considerations that could also be discussed.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: TRANSLATING GENOMICS INTO PRACTICE FOR REAL-TIME SURVEILLANCE AND RESPONSE TO CARBAPENEMASE-PRODUCING ENTEROBACTERIACEAE: EVIDENCE FROM A COMPLEX MULTI-INSTITUTIONAL KPC OUTBREAK
Review round: 1
Reviewer: 2

Output:
Basic reporting: The article is clearly written and easy to follow, with an extensive bibliography and appropriate context provided via the Introduction.

DNA Data Checks:
The raw data and assemblies, along with a useful assortment of sample-level metadata, have been deposited at NCBI and I was able to successfully access them. The accession number is included in the manuscript. Scripts used in the analyses have also been made available via two GitHub repos.

Human Participant Checks:
The investigation was undertaken by a public health agency as part of an outbreak response. No identifying information is included in the article or in the publicly available data.
Experimental design: The article is well-suited to publication in PeerJ, offering an extremely comprehensive investigation of a pathogen of international concern. The objective of the study is clearly described, and the work presents an exemplary model for uniting genomic and epidemiological investigations of hospital-associated infections. Each of the many analyses was done to high technical standards, and described in enough detail for others to be able to replicate the work.
Validity of the findings: The conclusions around the origins and the transmission of the outbreak isolates are well-supported by the data, and clearly linked to downstream infection control activities. Limitations of the study are clearly identified.
Additional comments: This is wonderfully detailed and fascinating investigation of CPEs circulating in Victoria, Australia over 2012-2015, which links genomic and epidemiological data in a way that very few papers in this domain have. It was a very enjoyable read, and my suggestions for improvement are all very minor and addressing them is left to the author's discretion.

Introduction
1. The abstract mentions that the genomic epidemiology investigation proved more fruitful than genomics or traditional epidemiology alone. Perhaps towards the end of the Introduction, the authors could describe what the state of the epidemiological understanding was at the time the genomic investigation was launched - were there obvious gaps that the genomic analysis was aimed at closing?

Methods
1. The authors are to be commended for the incredible breadth and depth of their analyses! That being said, there is definitely a lot for the reader to keep track of here, so perhaps a figure outlining the study workflow could be provided to orient the reader.

2. Along those lines, the Bioinformatics subsection contains many analyses - these could be further subdivided into smaller sections to facilitate reading.

Results
1. Line 310: Would be helpful to briefly differentiate KPC-2 and KPC-3 earlier in the manuscript for the reader unfamiliar with these designations - perhaps a brief comment in the Introduction, including their incidence in other settings like the US.

2. Line 311: "from one patient" instead of "from the one patient"

3. Figure 1: The annual peaks in Sept/Oct/Nov are interesting and might merit some comment in the Conclusions section.

4. Line 313: delete the "of"

5. Line 315: For the readers who skip the Intro and Methods and head straight to result, it would be helpful to explain what the "Initial Analysis" was - from my reading of the methods, it was a retrospective 2014 look at the isolates from the 29 patients identified to date, with further work happening prospectively.

6. Figure 2: Depending on the actual geography, it might be interesting to colour the facility nodes according to their distance from each other, maybe with the most central Melbourne facility as a saturated colour with the other facilities less saturated as one moves out. This would, of course, only be really interesting if there was some spatial structure to the phylogeny, but it is suggested in the Combined Analysis section. It would be interesting to note Facility F, though, which is mentioned later on in the text.

7. Figure 4: No suggestions here, just wanted to compliment you on this super figure!

8. Line 392: A lot of the TransPhylo transmission events arise from unsampled individuals (white nodes), whereas I imagine the screening in place knowing that KPC was circulating meant that most of the population should have been fully sampled. I think (as a TransPhylo author ;) that this is a bit of a shortcoming of this current implementation – I think it sometimes overestimates the proportion of unsampled cases. This might be worth commenting on, as would noting whether any of the chains it did identify amongst the sequenced isolates (I spot an interesting one involving five B1-harbouring individuals) were reflected in the epidemiology.

9. Line 430: I wonder if a figure summarizing the plasmid content of each isolate might be helpful here, to give a quick visual of which isolates across which species harboured identical or near-identical plasmids.

10. Line 475: What sort of accessory genome changes?

11. Figure 9: I see environmental sampling isolates in this tree that appear to be closely linked to one of the patients for whom multiple isolates were sequenced (bright pink patient) and another singly-sequenced patient. This is interesting, but I don’t see a mention of it in the main text.

Supplement:
1. Figure S6: The black (overall) regression line seems to be missing, though the R^2 value is there.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: DEVELOPMENTAL EFFECTS OF ENVIRONMENTAL LIGHT ON MALE NUPTIAL COLORATION IN LAKE VICTORIA CICHLID FISH
Review round: 1
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: The cichlid species pair Pundamilia pundamilia and P. nyererei represents a well-studied model system to identify mechanisms of ecological speciation. In the present manuscript, Wright et al. investigate environmental light-induced plasticity in nuptial colouration in this cichlid sister species pair from Lake Victoria. To this end, both species (and their hybrids) were reared under light conditions, which mimic their natural habitats, and male nuptial colouration was quantified based on photographs of fish. The study finds very limited plastic responses in male colouration, and importantly not in the species-specific nuptial colours (blue and red), which have been shown to be subject to divergent selection by female choice.
The paper is nicely written, the methods and statistical analyses are sound and the results are generally interpreted adequately. However, a weak point of the study involves the relatively low sample sizes (9 to 10 individuals per species/hybrid and treatment in Experiment 1, and 3 to 4 individuals per species/hybrid and treatment in Experiment 2). This should be addressed in the discussion when interpreting the results.
Please find more specific comments below:

- Presentation of results, lines 288-307. Are the results presented here based on individuals from both shallow and deep ambient light conditions? This is not made clear, and given the aim of the study (lines 130-139), it would make more sense to present the results for each treatment separately (also in Fig. 1 & 2).

- Methods, lines 148-151. Please explain why you used both F1 and F2 crosses.

- Lines 158-160. Differences in body size and species identity between neighbours (and also the number of neighbours) might influence the social rank/dominance among males and thus the expression of nuptial colouration. This was (partly) accounted for in the linear mixed models (line 252), however, whether any of these random effects were significant or not is not mentioned in the results.

- Lines 202-203. Quantifying nuptial colouration in cichlids is notoriously difficult due to the fact that fish change colouration quickly when stressed - which might be the case when transferring the fish into a glass cuvette. How did you standardize photographs, i.e. make sure that you didn’t take pictures of stressed fish with faded colours?

- Please provide legends for supplementary figures and tables.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: FORMONONETIN INHIBITS LIPOPOLYSACCHARIDE-INDUCED RELEASE OF HIGH MOBILITY GROUP BOX 1 BY UPREGULATING SIRT1 IN A PPARΔ-DEPENDENT MANNER
Review round: 1
Reviewer: 1

Output:
Basic reporting: The article is clear and english is correct.
Results of figure 2 should be inserted in figure 1 as panels C and D. Similarly, data of figure 4 should be inserted in figure 3 as panels C to F. Data presented in the supplemental figures should be inserted in the main figures.
Some references should be added in particular on the effect of resveratrol on HMGB1 release (e.g. Xu et al. Shock 2014; Dong et al. Free Radic Biol. Med 2015).
Experimental design: The objective of the study is to assess if formononetin modulates HMGB1 secretion in response to LPS. Overall, the methods are well described, the experiments are well designed with appropriate controls and technical replicates.
The authors should provide the quantification of the western-blots in figure 2A-B. In figure 2B, it seems that the total amount of HMGB1 is increased with LPS or formononetin treatment. The authors should analyze HMGB1 mRNA level upon formononetin treatment.
RAW264.7 cell line is not the most suitable model to study HMGB1 release and the effect of formononetin on HMGB1 secretion should be confirmed in human primary macrophages.
Validity of the findings: The novelty of the study is rather limited as a large number of studies already demonstrated that many herbal compounds inhibit HMGB1 release by preventing its acetylation. It might be interesting to focus on the advantage of using formononetin compared to other similar compounds. Hence, it might be useful to compare the effect of formononetin on HMGB1 release with other similar compounds.
In figure 5A, treatment with formononetin alone significantly increased the level of SIRT1 and in figure 1B it seems that formononetin alone decreases the level of HMGB1 in the cytoplasm. It might be interesting to perform a pre-treatment with formononetin and then wash the cells and activate them with LPS in order to evaluate if the effect of formononetin treatment persists in time.
From authors conclusions, formononetin and resveratrol appear to modulate HMGB1 release via SIRT1 expression. Hence, why did they observe a synergic effect in figure 5D? If these two compounds modulate HMGB1 release via the same mechanism, no synergic effect should be observed. The authors should also analyze the level of SIRT1 in this experiment.
Additional comments: No additional comments


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: FORMONONETIN INHIBITS LIPOPOLYSACCHARIDE-INDUCED RELEASE OF HIGH MOBILITY GROUP BOX 1 BY UPREGULATING SIRT1 IN A PPARΔ-DEPENDENT MANNER
Review round: 1
Reviewer: 2

Output:
Basic reporting: The paper deals with the role of formononetin as anti-inflammatory molecule. Basically, formononetin acts by inhibiting HMGB1 release via Sirt1 up-regulation. English form is correct and appropriate. References are accurate. Line 165: Please fix “. At which time”
Experimental design: The study is well designed. The results are well presented and understandable. Methods are well described with the exception of statistical analysis, which should be explained in a wider way.
Validity of the findings: Authors provide a functional explanation for HMGB1 release inhibition by formononetin. All experiments are well showed, results are consistent and statistically sounding. Conclusions are well written and results support the conclusions.
Additional comments: No additional comments


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: FORMONONETIN INHIBITS LIPOPOLYSACCHARIDE-INDUCED RELEASE OF HIGH MOBILITY GROUP BOX 1 BY UPREGULATING SIRT1 IN A PPARΔ-DEPENDENT MANNER
Review round: 2
Reviewer: 1

Output:
Basic reporting: The results of the two reference figures should be inserted in the manuscript (as figure 1C for reference figure 1 and as figure 2D for reference figure 2). In addition, it would be useful to highlight in the text that the maximal inhibitory effect of formononetin is observed with a pre-treatment of 24 hours which corresponds to the time of maximal induction of SIRT1 expression upon formononetin treatment (Fig.2B and C).
Experimental design: no comment
Validity of the findings: no comment
Additional comments: The authors replied to all my comments.
The results of the two reference figures are convincing and should be inserted in the manuscript (as figure 1C for reference figure 1 and as figure 2D for reference figure 2). In addition, it would be useful to highlight in the text that the maximal inhibitory effect of formononetin is observed with a pre-treatment of 24 hours which corresponds to the time of maximal induction of SIRT1 expression upon formononetin treatment (Fig.2B and C).


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: FORMONONETIN INHIBITS LIPOPOLYSACCHARIDE-INDUCED RELEASE OF HIGH MOBILITY GROUP BOX 1 BY UPREGULATING SIRT1 IN A PPARΔ-DEPENDENT MANNER
Review round: 2
Reviewer: 2

Output:
Basic reporting: The authors have reviewed the paper and fixed where requested. Indeed, English form is now correct and references accurate.
Experimental design: Statistical analysis section has been enriched and it is now well understandable.
Validity of the findings: The paper is clear and results are well written. Experimental section is accurate and well designed. Conclusions are consistent.
Additional comments: No additional comments


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: A HISTORICAL LEGACY OF ANTIBIOTIC UTILIZATION ON BACTERIAL SEED BANKS IN SEDIMENTS
Review round: 1
Reviewer: 1

Output:
Basic reporting: •	The paper is overall well written in a clear language. There are a few minor errors (see general comments below).
•	The introduction relies heavily on a relatively small number of references (particularly Taylor et al 2011), and widening the perspective slightly would not hurt. For example, all the work of Fernando Baquero and José Martinez on environmental antibiotic resistance is entirely left without reference.
•	The figures are relevant, but Table 2 seems inappropriate and contains much information that does not concern this manuscript. In Figure 2B, it is however unclear how the years were imposed on the PCoA.
•	I could not find the raw data for the chemical analysis of iron and manganese associated with the manuscript.
Experimental design: •	The study is original and within the scope of PeerJ.
•	The manuscript aims to investigate if dormant microbial seedbanks in lake sediments can be used to track the abundance of antibiotic resistance genes in the environment over time. This is an important question for retrospective monitoring and such analysis would fill an important knowledge gap regarding baseline for antibiotic resistance prevalence in the environment.
•	Although the scope is small (onty two genes – sul1 and tetW – are investigated) this is an important proof-of-concept study, and it conforms to methodological standards.
•	However, the qPCR for the non-seedbank community would need a better description.
•	Furthermore, it must be described how the chemical analysis for Mn and Fe in the sediments was carried out. Now, this analysis is just mentioned in passing on lines 241-242 in the manuscript.
Validity of the findings: •	The data underlying the results seem to be robust and statistically sound.
•	However, I have a major problem with one of the conclusions by the authors. The idea that tet(W) abundance would be a result of antibiotic pollution (or pollution by human bacteria carrying tet(W) genes) seem quite farfetched to me, given that the lake at the same time (according the authors) underwent eutrophication. Since eutrophication would lead to more anaerobic conditions, and the bacteria co-enriched with tet(W) are obligate anaerobes it seems that the explanation to the tet(W) increase would be increased abundances of these bacteria – not a selection for tet(W) by antibiotic residues. Indeed, some of these bacteria are known to harbour the tet(W) gene. If the authors want to make claims along the lines of “tetracycline exposure caused selection for tet(W) in the sediment communities”, they need to support this hypothesis with chemical measurements of tetracycline in the sediments.
•	The paragraph on lines 278-301 is entirely speculative, but is presented as if it was well supported by the results. This needs to be modified.
Additional comments: •	Line 19-20. It is unclear from the abstract why legacy of antimicrobial agent disposal is important.
•	Line 41: “mitigates” seems to be me to be a weird choice of word in this context.
•	Line 45-46: As far as I know the idea that ARGs are a fundamental component of microbial ecosystems is a hypothesis (albeit plausible), and should be presented as such rather than as a fact.
•	Line 50-51: I don’t understand what the authors mean with “further hone naturally occurring antibiotic resistance systems”. Maybe it is the use of the word “hone” that confuses me.
•	The entire first paragraph of the Introduction mixes the clinical/human society and environmental components of antibiotic resistance development in a quite confusing way, and particularly the lines 51-55 about risks really suffer from this problem. I would recommend the authors to read a recent review in FEMS microbiology (https://doi.org/10.1093/femsre/fux053), which may help in structuring the Introduction better.
•	Line 56-58: I think that studies by Gerry Wrights lab make an even more convincing case for that ARGs were present before the antibiotic era, particularly these two papers: https://doi.org/10.1038/nature10388 & https://doi.org/10.1371/journal.pone.0034953
•	Line 59: “in” -> “over”
•	Line 71: “made” -> “make”
•	Line 71: I think it is overstating the importance of sediments by attributing it “a highly likely source of resistance determinants” just because it is diverse. I would recommend that the language of this sentence is toned down.
•	Line 79: “or” -> “and”
•	Line 153: Which version of the SILVA database? This matters for reproducibility.
•	Line 163: “OTUs relative abundance and ARGs frequency” -> “OTU relative abundances and ARG frequencies”
•	Line 188: Where in the methods section is the total community DNA extraction protocol described?
•	Line 198: “ARG” -> “ARGs”
•	Line 239-240: I disagree with the authors here. To me, it looks like the observed changes in tet(W) could be entirely due to the effect of eutrophication (i.e. the increase of anaerobic bacteria). I would rather say that the results of the total community composition imply that eutrophication would be the cause of the tet(W) changes (although it is of course not the only possible explanation)
•	Line 241-242: Where did the Fe and Mn data come from? How was those levels determined?
•	Line 255: Insert “make it” after “Lake Geneva”.
•	Line 257: “ARG” -> “ARGs”
•	Line 278-280: This sentence is pure speculation, and it should be stressed as such. Actually, I would refrain from making this connection at all, given the vast number of possible confounding factors.
•	Line 285-301: This entire paragraph is just pure speculation. If the authors want to make a claim that tetracycline has selected for tet(W), they should also quantify antibiotic residues in the sediment. The correlation between medical use and ARGs in sediments in a single lake is not a very convincing argument.
•	Line 312-313: I disagree with that HGT would be a major pathway for dissemination of ARGs in aquatic environments. There are many environments that are more likely to be hotbeds for resistance transfer. However, waterways are great for dissemination of resistant bacteria, but that has nothing to do with HGT. I recommend the authors to read the review by Baquero et al (https://doi.org/10.1016/j.copbio.2008.05.006) or the aforementioned FEMS Microbiology review (https://doi.org/10.1093/femsre/fux053) to straighten out these concepts, as they again seem to be intermixed here by the authors.
•	Line 316-319: The relation to penicillin and cotrimoxazole here is an interesting speculation, but how come that sul1 has not been enriched earlier when sulfonamides where widely used in healthcare? This would need an explanation as well.
•	Line 321-323: How is this last sentence related to sulfonamide resistance?
•	Line 329: “can” -> “may”
•	Line 336-337: I would rather spell it out as that the taxonomy of the seed bank community influences the ARG content.
•	Line 338: Contaminated in what sense? Are these genes really contaminations if they allow better resilience to the bacterial community?
•	Table 2 contains much information that does not concern this manuscript and could probably be left out.
•	Figure 2B: How were the years imposed on the PCoA?


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: A HISTORICAL LEGACY OF ANTIBIOTIC UTILIZATION ON BACTERIAL SEED BANKS IN SEDIMENTS
Review round: 1
Reviewer: 2

Output:
Basic reporting: The manuscript is nicely written and clear. It was very enjoyable to read through the study.
Experimental design: The research presented in the manuscript is original and interesting. Also, consistent with the Aims and Scope of PeerJ journal.

The research results are interesting and have a good contribution to study of antibiotic resistance in aquatic environment throughout the history of anthropogenic used of antibiotics.

Although the methods were described thoroughly, there are some information that would be better to be added in the material and methods, as follow:
1. Correlation of the depth of sediment core with the years of study (Line 98-102), also in Figure 1 and Supplementary Figure 1 (This information was only described in supplementary metadata)
2. Efficiency of DNA extraction from each sample (L 122)
3. Limit of quantification from the qPCR measurement of each gene (L 139)
4. The explanation to use the amount of DNA concentration as normalisation instead of using the amount of 16S rRNA gene
Validity of the findings: The finding is well reported and giving new contribution on providing insightful information to prevent the spread of ARGs in the environment. If there is one question, it is in the decision to study tetW gene as the representative of more than 20 types of tetracycline resistance genes that are known. Several studies shown that tetM gene is the most abundant of tetracycline resistance gene found in sediment environments.
Additional comments: No additional comments


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: EFFECT OF DARK SWEET CHERRY POWDER CONSUMPTION ON THE GUT MICROBIOTA, SHORT-CHAIN FATTY ACIDS, AND BIOMARKERS OF GUT HEALTH IN OBESE DB/DB MICE
Review round: 1
Reviewer: 1

Output:
Basic reporting: Nothing to report here
Experimental design: Were the lean mice db/db as well, or another strain? It may be good to fully describe the lines used (db/db is not the complete descriptor)...
L186 colon mucosal cells normally implies host cells, which would not be Bacteria! Maybe you mean mucosal samples?
Validity of the findings: Figure 1: I am not convinced that showing results at the order level is acceptable. It is way more common to present phylum and genus (family) level.
Figure 2 has no place has a main figure, this is not "valuable" data
Figure 3: The ANOSIM should give you a p-value which is needed to conclude on the clustering!
Figure 4: It would be so much easier if you had the taxon name on each plot! H, L, J, O appear to show very similar values, which raises questions about the statistics...
Table 2: I personally have doubts about the validity of Picrust, and seems like the differences you report are all extremely slight. Without a way to test if such differences are not due to stochastic variations in the sampling, I would not report them.
Table 3: These results seem completely flawed. There is no way butyrate and propionate are not produced by gut microbes! And the 100X more values in the obese supplemented mice don't make any sense
Additional comments: No additional comments


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: EFFECT OF DARK SWEET CHERRY POWDER CONSUMPTION ON THE GUT MICROBIOTA, SHORT-CHAIN FATTY ACIDS, AND BIOMARKERS OF GUT HEALTH IN OBESE DB/DB MICE
Review round: 1
Reviewer: 2

Output:
Basic reporting: Discussion could be implemented (see general comments to the author).
Experimental design: Seems quite adapted to the question raised. Studies seem competently performed.
Validity of the findings: The findings are interesting and seem valid and =adequately interpreted.
Additional comments: This is an interesting study, which questions the "power" of the gut microbiota to change metabolism of the host. Basically, from a healthy dieting (cherry powder, fiber-enriched), inducing a healthy microbiota composition (enriched in "beneficial" bacteria), and producing "beneficial" metabolites deriving from fermentation of soluble fibers (short-chain fatty acids), no substantial change in several important  gut health parameters of the host was observed in a mouse model of diabetes (db/db mice). This is an important set of results, suggesting that the power of microbiota to significantly alter the host metabolism is limited by the genetic bakground of the host. This study resonates in me with another study in relation with the role of fiber-derived SCFAs to improve host glucose control by activating intestinal gluconeogenesis, the benefits being absent in intestinal gluconeogenesis-deficient mice despite the presence of SCFAs and the modification of microbiota (De Vadder et al, Cell, 2014). This suggests that host genetics may dominate the microbiota composition as for regards host metabolism. The paper would be greatly improved by inclusion of a paragraph od discussion addressing this point


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: SEX DIFFERENCES IN THE USE OF SOCIAL INFORMATION EMERGE UNDER CONDITIONS OF RISK
Review round: 1
Reviewer: 1

Output:
Basic reporting: Generally the basic reporting is good. A few issues below:
- You use sex and gender interchangeable. Sex is biological, gender is cultural. See for example line 77 compared to line 121 and line 345. If you let people self-identify, I suspect you should use gender throughout rather than sex.
-Along this same line, you note that you had four options for participants to select for gender including other and prefer not to say. Did anyone select these options? If so, were they excluded from the analyses? Please specify.
- Line 116 Typo: of not f
-Line 143: You haven't used the term league table before. Perhaps reword to standings list or something like that.
-Line 204: I believe you mean Figure 3 in this line.
-Line 306 Typo, a period, at the beginning of the line.
Experimental design: The methods themselves were fine. However, I have questions about how they relate to the research question. See comments in the validity section.
Validity of the findings: I am unclear why you decided to make this a competitive task. It seems like risk preferences may well vary when in a competitive situation versus other situations. I would like to see some information about how being a competitive task or not influences risk preference. In other words, do competitive situations change risk tolerance?

My biggest issue is that you are confounding risk preference and score maximization. This is an issue that many studies examining risk preferences have. For example, in the asocial risky condition, since the asocial option is more risky, the social option will lead to higher rewards, since it has a higher expected value. Thus, women may be maximizing their score rather than interacting with risk, per se. In the other conditions, their performance is also consistent with reward maximization. Therefore, an alternate interpretation of your findings is that women are more sensitive to rewards (not punishments as you say in line 349) or that they are more willing to switch strategies when it is optimal to do so. Thus, I find your explanations for this behavior (punishment and lack of confidence) quite unsatisfactory. What I think is perhaps the most interesting is that men continue to avoid social information even when doing so leads to higher scores. So, men are not maximizing their rewards in the asocial risky condition. This suggests to me that men my be more averse to social information than women.

Because of the conflation or risk and score maximization, I think what you actually tested is willingness to use social information. You show in your control condition that in labs people avoid social information (this is also supported by the literature). Then, in your social risky condition you show that people continue to avoid social information even when there is a potential, but not guaranteed, benefit. Finally, you show in the asocial risk condition that women, but less so men, are willing to use social information when it is beneficial.

I am not sure how you can disentangle risk preferences and score maximization with your existing data. Perhaps there is another control condition you could add, but I am having trouble imagining what that would be. Alternatively, you could restructure the paper to focus on preferences for asocial/social information across various payout schedules.
Additional comments: No additional comments


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: SEX DIFFERENCES IN THE USE OF SOCIAL INFORMATION EMERGE UNDER CONDITIONS OF RISK
Review round: 1
Reviewer: 2

Output:
Basic reporting: The article is well-written and nicely presented. I found it very clear and easy to follow. The literature review places the work suitably in context.

The raw data file was easy to access and understand. I found that the column headers did not line up with the data when I opened the file in Excel (the column headers were misaligned by one cell, relative to where they should have been), but this may have been a quirk of using Excel to open a txt file which might otherwise have displayed correctly in some alternative package. However, perhaps the authors can take a quick look at this and check that everything displays correctly in the most commonly used software packages that they would expect readers to be using.

The figures were reasonably helpful. Having looked at the response to reviewers' comments for the previous submission, I think the decision to include the "real" means in one of the figures was prudent, and actually these do potentially cast a slightly different light on the results, as I will elaborate in Section 3.
Experimental design: The experimental design is essentially very simple. The key manipulation was that participants were told that one option available to them was risky (operationalised as potentially reducing score, but also potentially significantly increasing it), and the other safe (operationalised as guaranteed not to reduce to score, but with only marginal increases possible). These possibilities were counterbalanced across the option types ("social" operationalised as the ostensive attempt of another participant, and "asocial" operationalised as an alternative source of solution elements not presented as having originated from another's attempt). In a control condition both sources were presented as being safe. The measure of interest is simply the choice made by the participant (which could be variously: social safe over asocial safe; social risky over asocial safe; social safe over asocial risky).

In spite its simplicity (and I regard simplicity as compliment rather than criticism!), it is clear from the manuscript how the manipulation makes a novel contribution, in looking at how gender differences in risk sensitivity might interact with increased reliance on social sources of information under conditions of risk. The design is appropriate to tackle this question.

From the information provided, the study appears to have been run with due attention to methodological rigour, and the methods are described in sufficient detail.
Validity of the findings: The authors' conclusion (that female participants are particularly likely to rely on social sources of information when asocial sources are known to be more risky) appears to be upheld by the data.

My only concern here is that I suspect that this might present a somewhat incomplete picture of the results. There are a couple of things that I think the authors might want to consider in order to present a more fleshed out interpretation.  I do want to emphasise however that this would entail in one case a speculative interpretation, and in another case, a post-hoc analysis of results. So if the authors take either of these suggestions on board then of course it is important that they make these caveats clear.  In addition, given the need for the caveats, I think it is fine if the authors prefer not to stray into this territory at all. However, for me, it would make for a slightly more thought-provoking paper, and one that might be more likely to generate further literature investigating these possibilities in a more a priori fashion.

The first suggestion concerns my point about the "real" means in the Figure. I'm really glad the authors included these. Perhaps it makes me very old-school but I much prefer to see real data over the outputs of models.  And in this instance I think that it is particularly helpful as these seem to suggest that something quite interesting might be going on which is not captured by the models.  It looks like in the control condition (safe, safe), female participants are actually LESS likely than males to opt for the social source of information. This seems quite interesting, and not what one would expect based on general assumptions and theories about gender and social learning? And then in the social risky condition, women actually appear to INCREASE their tendency to select the social source. This is really interesting too, and certainly it seems consistent with the authors' interpretation that female participants are not simply more risk-avoidant.  The pattern of results suggests that actually female participants may respond to ANY cues to potential risk by increasing reliance on information from social sources (even when it is that very social source that has been identified as risky).  Of course, I may be completely wrong, and this might not be upheld in the data at all.  But it looks intriguing, and therefore potentially worth a bit of post-hoc analysis (explicitly flagged as such, of course) to see whether there might be anything in this interpretation.

And regarding the interpretation, the authors state quite clearly (and correctly, based on their data), that the female participants are not just more risk-averse. And indeed, in line with this, the effect appears not to be explained by risk aversion anyway, based on the lack of relationship with the personality measures. However, the authors do little to propose an alternative interpretation, and I think this would be merited.  What exactly IS driving the effect, if it is not simply risk sensitivity?  Personally I would like to see the authors propose an alternative interpretation which might be testable in future research. My hunch would be that female participants are particularly sensitive to something that might be labelled as social shame, or similar.  If one turns out to have made a choice that sets one apart from the crowd in a "good" way, then there's no shame. But if one underperforms relative to the crowd then perhaps the sense of having foolishly deviated from established behaviour is possibly more aversive to women than to men.  This might even explain why women appear to be slightly more inclined to use the social information even when it has been identified as risky, relative to the control condition where it is identified as safe. It might be the case that the mere possibility of one's score going down at all leads women to rely more heavily on social information (since it is not so much the possibility of having made an adverse decision that is disturbing, as the possibility of being the only one to have done so - and copying another's design guarantees that this will not be the case).

Anyway, as previously indicated, these are merely suggestions. I leave it up to the authors whether they take them on board (here or elsewhere). I have no problem with the very neutral interpretation as currently presented.
Additional comments: No additional comments