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  • September 19, 2016

    Basic reporting No comments

    Experimental design Materials and Methods

    1. Page 3 – Lines 132-133: Could the authors briefly mention how was sample size calculated, instead of referencing them? Authors cited a reference to a study regarding the sampling technique. However, it is difficult to gauge if this study was part of the previous study (Wang et al., 2014) as cited. In addition, the sample participated in the study and the reported mean age of the respondents should be described in the results part, under descriptive statistics.
    2. Page 4 - Line 146: The phrase “face-to-face interviews” is inappropriate for a quantitative study that uses a questionnaire. Please rephrase to “interviewer administered questionnaire”. And, in what language was the questionnaire administered? Was it in local language? If yes, did the questionnaire undergo forward and backward translations? Were psychometric properties assessed either by Exploratory Factor Analysis and further validated by Confirmatory Factor Analysis for this study population? Otherwise, please mention the Cronbach’s alpha values.
    3. Page 4 – Please add a sub-topic, “baseline clinical data” under data collection and measurement. These measurements should be included under this sub-topic: fasting plasma glucose, and definitions – DM, BMI, other chronic illnesses, family history of DM. They are currently seemed to be a little out of space. The definitions for education level, marital status, occupation could be defined under “socio-demographics.” Please add other demographics variables as well in this section, how were they defined, coded and categorized?
    4. Page 5 – Line 178: Classification of education level states primary school and “blow”. It should be “below.” Please correct the typo.
    5. Page 5 – Lines 187-189: Could the authors cite with reference how was the classification for occupations obtained? The classified workers to groups seemed to be similar of International Labour Organization (ILO) but it’s not quite clear. Reference is required.
    6. Page 5 – Lines 190-191: Since the study was conducted in an Asian country, it would be appropriate to classify the BMI according to Asian cut-offs point.
    7. Page 5 – Lines 195-196: Could the classification of “additional diseases” be substituted with the word “co-morbids?” It would be more appropriate. In addition, how were the following clinical conditions confirmed? Was it from patient records? Please mention.
    8. Page 4-5 – lines 175-177: The authors set criteria regarding the awareness of DM status, those who were diagnosed by a medical doctor in hospital (self-reported) were considered aware, but those diagnosed with DM during the study were considered unaware? Is this an assumption or a validated classification? Numerous studies have exhibited that awareness of DM is shown among the general population, diabetes patients or non-diabetes patients. Such assumption is contradicting authors effort in studying this variable among diabetes population.

    Validity of the findings Statistical Analysis

    1. The authors used Chi-squared tests for univariate analysis. Please report odds ratios (ORs) yielded in the results description. Please remove Chi-square tests values in table 2 and report ORs.
    2. Were multi-collinearity between independent variables checked? Were standard errors less than 5 upon conducting logistic regression analysis?
    3. The description of results in univariate analysis is incorrect. It should report the ORs as “how likely would this factor be associated with the primary outcome?” Please consult your statistician for further interpretation.
    4. Page 9-Lines 252-254: Correlation analysis was not performed, therefore it is inappropriate to say a great correlation between DM status and psychological distress.
    5. In table 3, instead of “dashes -”, please state “Ref” to exhibit reference category.
    6. What would be the most significant factor associated with psychological distress? This could be explored using the highest Beta value showing level of significance. Please consult your statistician for this evaluation.


    1. The discussion is a little unfocused, when authors are merely stating comparisons with previous studies. It should be more focused on principle issue, probably the central focus could be discussing the factor most significantly associated with primary outcome measure.
    2. It would be interesting to know, what are the gaps of previous studies? What this study adds? How could future studies replicate the findings of this study for more robust investigations?
    3. Authors could speculate on how the big health data assessing psychological and behavioural factors through psycho-informatics be used to evaluate these hypotheses in future studies. It would be interesting to know.

    Comments for the author The authors conducted a descriptive cross-sectional study that explored the prevalence and correlates of psychological distress among diabetes adults in Jilin province, China. While this is an interesting study, there are several concerns that need attention. The authors should address these concerns thoroughly. If authors have any native English speaking colleagues in his/her institution, I suggest that authors may request advice on English language corrections. You may cite them under acknowledgements.

    December 2, 2016

    Basic reporting No comments

    Experimental design No comments

    Validity of the findings No comments

    Comments for the author The authors have addressed all suggested comments and concerns. I am satisfied with the revision.

    Good luck on your paper.

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  • Your Review Basic reporting Nothing Experimental design Nothing Validity of the findings Nothing Comments for the Author The Authors addressed all of my concerns correctly

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  • Basic reporting Nothing to fail to meet journal criteria. The only problem is lack of detailed methodological explanation. Experimental design No experiments were performed. Validity of the findings Nothing to fail to meet journal criteria. The only problem is lack of detailed methodological explanation. Comments for the Author Scientifically, the content is OK. However, there is no enough information to reproduce their results, especially following.

    1 In Fig.2, there are less than 243 genes. Authors must specify how they selected genes shown in Fig. 1 from 243 genes.

    1. L412 in the revised manuscript, they denoted 43 genes, The description "combined DEGs, topological and cluster analyze to get 43 genes" is not enough. More specified explanation is needed.

    2. No explanation about how they adjusted P-values. If the application provided adjusted P-values, they must denote it explicitly.

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  • Dear authors, Herein is my response to the manuscript entitled “Neural and endocranial anatomy of Triassic phytosaurian reptiles and convergence with fossil and modern crocodylians”, submitted to the journal PeerJ (MS #10457).

    Lautenschlager and Butler present an impressive and detailed investigation of the comparative neurocranial anatomy between phytosaurs and modern and extinct crocodylomorphs. This is an exciting development in the field of convergent evolution, something that has long been discussed between these two groups. The study uses impressive techniques to compare the digital endocasts of phytosaur taxa, and compares these to existing information. The only caveat I would add to this study is that some of the interpretations are perhaps taking the data a little too far. This is not a fault of the study, as creating endocranial casts for all Crocodyliformes would be a monolithic task, but more a problem that this is a relatively emerging field of study and the data availability for comparisons is limited (i.e., a constrained sample size).

    I note at the beginning of this review that I am neither an expert in phytosaurs or neuroanatomy, and my relevant expertise is in the systematics and anatomy of crocodyliforms. As such, my suggested revisions are extremely minor, and I recommend publication, pending peer review from an expert on phytosaurs or neuroanatomy.

    Basic reporting Figures The figures are well annotated, numerous, and informative. I strongly recommend that these be used in a press release for this paper, seeing as it pushes our boundary about what we know about phytosaurs in an exciting way.

    Data See comments below.

    Experimental design The study presents new research, and is well within the scope of PeerJ. The research question is well-defined, but could do with a bit more information on the scope and importance of the study. The technical standard of work performed is very high. If the scans are deposited in a more public repository, then this study should be broadly replicable (this is somewhat unclear at the present, see comments below).

    Validity of the findings The data collected in this study is of high quality. No statistical tests were performed. The conclusions are broadly supported by the data, but a couple of caveats/limitations could be added for increased context.

    General comments Abstract The abstract is concise, with a good balance of context and novel findings. My only comment is that it could do with a single final sentence on the broader implications or importance of the present study. Line 22-23: It might not be necessary for the abstract, but could authority information be provided here for a little more context for the taxon names? Line 28: Which taxa/group? Assume it means Crocodylia, but could be more explicit. Line 34: Might be worth adding a couple more keywords to enhance discoverability? Archosauria, Pseudosuchia, Crocodyliformes etc?

    Introduction Line 37: What makes them unusual? I mean, compared to all the other unusual groups around at that time! Line 42: For clarity, it should be mentioned what the other major archosaur branch is here. Line 45: Should cite Ezcurra (2016), if this is the study mentioned. Is the reason for this due to different methods, character sampling, and/or taxon sampling and newer discoveries? Is this what prompted the present analysis – to see if endocranial characteristics could help refine their phylogenetic relationships? Line 45: Is it just the skulls that are superficially similar? Or just the snouts? Or the whole skeleton? Line 47: How large? What is the variation? And what about other longirostrine crocodyliforms like dyrosaurids, thalattosuchians, and some pholidosaurids (all non-crocodylians)? Is there a reason why you chose to solely focus on Crocodylia for this comparison? Have any studies looked at comparisons between phytosaurs and these groups (i.e., non-crocodylian crocodyliforms) before? Line 47: How many rows of osteoderms for each group? This is a highly taxonomically informative feature within crocodyliforms. Line 54: It might also be worth noting that there is around 100 million years of temporal difference between the extinction of phytosaurs and the origin of Crocodylia? And also a fairly large phylogenetic distance. Line 59: What is meant here by ‘ecological niche’? Does it mean piscivory, in which case ‘diet’ might just be more appropriate? Line 64. This sentence is a bit complicated and could do with being broken down. It could do with some citations here to support this range of research topics. Line 69. Did this study comment at all on similarity with crocodylians? How is the present study distinct from this (apart from taxonomic choice)? Where there any limiting factors to the Holloway study, or limitations of what one could infer from it?

    Materials and Methods Regarding specimens, why were these two specifically chosen? Because they’re both accessible at the BSPG? I know doing so would be a humungous study beyond the scope of the present one, but why just two specimens from these particular taxa? Do they capture the full variation of a fairly speciose clade in order to facilitate meaningful comparison both within Phytosauria and with Crocodylia? A little more justification could be provided here for clarity. Can the CT data be made available more broadly? I don’t know what the supplementary file size is with PeerJ, but perhaps with Figshare just to make them a little more available? Obviously deposition within the BSPG collection satisfies criteria, but would they be available offsite there? (i.e., to those unable to travel to Munich)

    Results Line 125: What does it mean for an endocast to be ‘straight’, as a 3D object? In which orientation are they ‘elongate’? How long are the olfactory tracts? Line 132: Which taxon has this mid- and hind-brain region morphology? I wonder if this section could do with being structured with separate descriptions for each taxa, noting the similarities and differences? Line 165: How important is it that information about potentially smaller structures is not being captured by the methods applied? Is there a way around this for future studies, or is it a trivial point? It was mentioned that Machaeroprosopus mccauleyi had also had a recent digital endocast constructed. It might be nice to have a bit more comparative anatomical discussion between the results of the present study and of that, in order to differentiate between mystriosuchine and non-mystriosuchine taxa, especially given that available information on phytosaur endocasts is relatively few, at the present. Line 231: Details of the retrodeformation process should be provided more in the methods section, and not in this subsection. How did the ~40% dorsoventral compression factor be reached? Line 264. This needs a citation to support that the features a plesiomorphic for Crocodyliformes. Line 268. It should be noted that Cricosaurus is a metriorhynchoid, which might actually be a non-crocodyliform crocodylomorph, if the analyses of Wilberg (2015) are found to be supported. Also, for Pholidosaurus it should be noted that it is a neosuchian, and not a crocodylian, closely related to goniopholidids (so perhaps considered as a grade of ‘basal’ neosuchian). I feel it is important to note that these comparisons are been made to a very wide phylogenetic range of crocodylomorph taxa, that themselves are phylogenetically disparate. Also, the title might be misleading in this respect, as these are not fossil crocodylians, but crocodyliforms/morphs. Wilberg, E. W. (2015) What's in an outgroup? The impact of outgroup choice on the phylogenetic position of Thalattosuchia (Crocodylomorpha) and the origin of Crocodyliformes. Systematic Biology, (64): 621-637. Line 277: Which taxa does this refer to? How do the paranasal sinuses vary between those taxa? I think more comparison should be given here if possible, as this is a central theme indicated by the title. Also, these two comparative paragraphs should emphasise, or make more explicit, how the morphologies represent convergence, as indicated in the title. Indeed, the second paragraph is about differences between phytosaurs and Cricosaurus.

    Discussion Line 294: This might hold in comparison to birds and dinosaurs, but more generally is untrue of crocodyliforms. We see a vast ecological and physiological range in their history, from 12 metre long pelagic forms with streamlined body forms to terrestrial herbivores which were like armoured tanks. Compared to the ‘stock’ of ‘basal’ Crocodyliformes, I’d say some of these bauplans were quite divergent, including at least two independent fully marine radiations, which undoubtedly were coupled with different ecological and physiological demands. Not as dramatic as the ‘bird-dinosaur’ transition, but still representative of large changes. Line 299: It should be clear that this is based on a relatively small sample of Crocodyliformes, which are a fairly diverse clade historically. Nothing to do with the study, but simply based on the available information at this stage. Line 300. I appreciate that functional morphology of this sort is extremely complicated. Are there any documented cases where the changes you have identified have been correlated with ecological/behavioural factors? Even in distantly related groups? Do the apparent convergences identified share the same function? Can we say anything about their comparative ecology based on this? Line 302: I don’t fully agree with this conclusion. Cricosaurus was a fully aquatic, pelagic, taxon. Pholidosaurus was also probably at least semi-aquatic, spending much of its time out to sea. Other longirostrine crocodyliforms were also semi-aquatic or fully aquatic (teleosauroids, dyrosaurids, gavialoids, other pholidosaurids), and adapted to a range of ‘ecological niches’ beyond those explored here (I would still avoid this term to be more specific). I think this is a bit too much of a stretch due to the limited comparisons made here across such a broad suite of taxa. Again, not a fault of the study, but due to availability of that data. Only three extant crocodylians where comparatively analysed, and two extinct crocodylomorphs. Therefore making inferences for either all longirostrine crocodyliforms, or all crocodyliforms, is perhaps stretching what can be inferred a little too far. I don’t think there is any harm in restricting conclusions to be explicit about those taxa and those groups. It should also be very clear that longirostrine crocodyliforms are not a monophyletic grouping, but that snout elongation has probably evolved multiple times in different lineages. Line 309: Is this morphology found in any crocodyliforms that are not exclusively aquatic? At the present, the sampling of crocodyliform taxa doesn’t account for a huge range of groups and morphologies (e.g., goniopholidids, atoposaurids, paralligatorids, dyrosaurids, bernissartiids, allodaposuchids etc.), and I feel the limitations of possible inference because of this should be made more explicit.

    Conclusions Line 325: As above, I think implying that based on a very small sample, you can extrapolate to all of Crocodyliformes, as this seems to imply. The next sentence conveys this, but I would integrate this into the preceding sentence for clarity, and instead finish the conclusions with what needs to be done in order to facilitate larger-scale comparisons. I congratulate the authors on a well-conducted study, and look forward to seeing it published. Best, Jonathan Tennant

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  • Basic reporting

    see below

    Experimental design

    see below

    Validity of the findings

    see below

    Comments for the author

    In my opinion the following issues should be addressed before the paper is suitable for publication

    1. The following Information needs to be provided (as text files on, e.g. Figshare ) for reproducibility: a. The smiles strings used for Amanitin and Cabergoline. b. Start coordinates used for simulations c. Coordinates for the structures shown in Figures 4 and 5 d. In addition, the authors should describe the protonation state they used for Cabergoline

    2. The authors may want to note in the manuscript (warn the reader) that Babel smiles conversion can produce the wrong stereo isomers for chiral centers in fused rings.

    3. a. The authors may want to note that their scheme identifies the lowest free energy conformer rather than the lowest potential energy conformer (which is what oBabel and related methods do). B. related to this, a discussion of whether the simulation is run sufficiently long to yield meaningful free energy differences would be useful

    4. In the Solvation of Solute subsection the authors mention the generation of CHARMM-format parameters, but later write “The potential energy terms for the solute were described using the General Amber Force Field (GAFF).” This was confusing to me and the authors should clarify.

    5. Cabergoline contains two tertiary amines which represent particular challenges for conformational searches since they, in effect, are chiral centers and inversion is not considered a degree of freedom in the oBabel conformer search when these N atoms are in a ring. The starting “chirality” of these centers in the starting structure is thus more or less arbitrary. Furthermore, if the N is protonated this degree is certainly not sampled in the MD as it would effectively require deprotonation. For deprotonated centers it is also not obvious that the inversion barrier is low enough to allow this degree of freedom to be sampled. The authors should discuss this point.


    The PeerJ Team

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