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: THE ISOGENIE DATABASE: AN INTERDISCIPLINARY DATA MANAGEMENT SOLUTION FOR ECOSYSTEMS BIOLOGY AND ENVIRONMENTAL RESEARCH
Review round: 1
Reviewer: 1

Output:
Basic reporting: The paper is relatively clearly written. The literature is well referenced and the figures are relevant, high quality and well described.

The paper describes an online data management solution for environmental (!) and ecosystem ecology research together with a web platform for the IsoGenie project consortium with 13 laboratories.

The title is somehow misleading and should include the word “environmental”, because the majority of datasets listed in Table 1 do not refer to biological data. Proposal: “…. for ecosystems biology and environmental research”.

The introduction broadly describes the landscape of data repositories, online data management platforms and bioinformatics processing tools in the field of environmental and life sciences. It is also explaining some of the challenges to process and integrate data across discipline boundaries.

Nevertheless the introduction should be generally improved and better distinguish between basic terms like “data”, “data processing”, “datasets” and their processing and define “data types” (see “myriad data types” line 168, but https://en.wikipedia.org/wiki/Data_type) and “IsoGenie data types” as well as “metadata” in the sense of this paper. This is a pre-requisite to make it more clear what is the innovative power of the approach to create a “data structure to mimic the physical relationships between the data” (line 138, better datasets?) and “mirror the physical relationships and workflow between datasets” (line 155).

The introduction should also refer to some of the existing technical as well as content schemas, standards and norms. These (de facto) standards/ schemas for data exchange do not only exist in microbiology as suggested in line 106 but in other fields in biology, ecology and geosciences (e.g. like ISO norms, INSPIRE, ABCD, EML, ISA Abstract Model, MIxS Scheme). They give a certain level of abstraction and provide frameworks with rules and guidelines to integrate data in common interdisciplinary platforms and make them better exchangeable and reusable (FAIR data) also outside of joint (large) research projects and their “data silos”. The introduction also does not refer on approaches in using ontologies like ENVO http://www.obofoundry.org/ontology/envo.html with structured parameters to lower the boundaries between heterogeneous datasets.

Chapter “Results”

The chapter describes the IsoGenie project with A2A project addition (datasets with microbial communities), the data queries on the IsoGenie graph database as well as the web platform. Especially the “interdisciplinary data queries” should confirm the strength of graph data bases. This paragraph (line 233 until 251) is central and should be extended. Perhaps the author could add a diagram as in Yoon et al. (2017, Fig. 1) indicating the performance of the IsoGenieDB?

The access permission organised according nodes and the security risks shortly mentioned in line 248 and in legend to Figure 3 is not clear to the reviewer.

Chapters “Discussion” and “Conclusions”

Line 307: “discipline-specific jargon”, please see remarks on standards and ontologies above
Line 307: I would not regard databases in NCBI as “specialist databases”.

Line 323 ff. This is a good example for a complex query. Is it realised by the advanced query described under line 242 ff.? If so please refer to figure 5 there.

The chapter “Conclusions” refer again to the (future) advantages of the Graph database solution with the data structure set up for the IsoGenie project. The planned extensions for the advanced queries and for administration of user accounts and rights management should be better described. Some hints for future IsoGenieDB guided publication of FAIR data files using e.g. functions for DOI assignment and broadly accepted schemas for (meta-) data exchange might be envisaged. The current data download page (well organised with versioned download packages and quality control!) and browsing sampling site option is at the moment held separately from the graph database. Are there plans to change this?

The “Acknowledgements” could be shortened by linking websites where the project coordinators and team members as well as lab and analytic teams are listed.
Experimental design: The paper describes the design of a new database application and the web platform where the database is integrated and the set up and use of the database. This is done as an original primary research approach in life sciences and environmental sciences and - as such - meets the scope of the journal.

The original design of the IsoGenieDB (based on graph structure; powered by Neo4j) is visualised with the basic nodes for organizing scales (Fig. 4) and – more special – with the node structure for microbial sequencing data with “collection node” (Fig. 5). This design seems appropriate and is a useful precision of the property graph model to organize heterogeneous datasets from environmental research at a given geographic area not only according their metadata but also following the “has” relationships between them, the area, sites, date as well as physical samples as cores and create thereby nodes for organizing scales and a stable data network with standardized identifiers automatically inherited.

The design of the database and the programming code including the documentation of the “IsoGenieDB import code” and “metadata nomenclature standardized by the data team” mentioned in line 257 should be deposited in an open source code repository like https://gitlab.com/gitlab-org to fulfil the FAIR principles for data and research software.
Validity of the findings: The implementation and description of such a Graph database for heterogeneous datasets from environmental and ecosystems ecology research is challenging and worth to be published.

The IsoGenieDB is a valid approach to organise and process datasets and data in an interdisciplinary project. Its proper use in the IsoGenie + A2A project as pilot is certainly of great advantage. At the moment, however, the query options realised with Cypher are very limited and the results seen on the public web site are scarce and might be not appropriate for further scientific analysis in a world of open data.

There are also online services to register software tools, services for the life sciences and data repositories, e.g., https://bio.tools/ and https://www.re3data.org/. The IsoGenieDB implementations, other IsoGenie tools as well as the data repository with the advanced data download options are worth to be registered there.

For the future the authors should explore how to add certain standard scheme elements and further naming conventions to the automatic labelling with core names, sampling data etc. Adding labels to the graph nodes compliant to core elements of existing community-accepted metadata standards might possibly facilitate further global analyses of the datasets, e.g. with online tools like https://www.gfbio.org/de/visualize in a world of open science.

The “Conclusions” should be extended (see under basic reporting).
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: THE ISOGENIE DATABASE: AN INTERDISCIPLINARY DATA MANAGEMENT SOLUTION FOR ECOSYSTEMS BIOLOGY AND ENVIRONMENTAL RESEARCH
Review round: 1
Reviewer: 2

Output:
Basic reporting: This manuscript was well written and easy to understand; however some more explicit examples (e.g. of specific queries) of how the database could serve as a model for other cross-scale ecosystem studies would improve the manuscript by providing some more solid grounding. Although the database is clearly well designed from the description, the lack of these concrete examples makes it challenging to envision the advantage of this approach over other existing approaches.
Experimental design: Cross-scale ecosystem studies involving heterogenous data from multiple research groups are increasingly becoming the norm. Increasing attention is paid to the importance of data management and the ability to best utilize available data across studies and researchers. As described, this database could serve as a model for other similar projects.
Validity of the findings: While the design of this system is clearly well thought out and effective (especially given the research that has been supported and enabled by it), it would helpful for those considering using it as a model database if more detail was provided on how critical design decisions were made. For example, why was the decision made to use a hierarchical organization based on location and data type, followed by information on spatial and temporal resolution? This piece of information would help readers to easily identify whether this approach could be useful for their project and potentially to identify modifications that would need to be made to suit their research questions and vision.
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: THE ISOGENIE DATABASE: AN INTERDISCIPLINARY DATA MANAGEMENT SOLUTION FOR ECOSYSTEMS BIOLOGY AND ENVIRONMENTAL RESEARCH
Review round: 2
Reviewer: 1

Output:
Basic reporting: After the revision the paper is now very clear, well-structured and unambiguous. The reviewer is especially appreciating the revised introduction with the new terminology chapter and that the software developers are documenting pieces of code and make the code freely available under https://bitbucket.org/MAVERICLab/isogeniedb-tools/ .
Experimental design: The experimental design, results and the discussion, especially on the advantages of graph structures and the ideas on future developments are well done. Only a small comment: Figure 3 is cited before Figure 2.
Validity of the findings: The paper is of great interest for interdisciplinary teams in microbial and ecosystem sciences who are looking for a concept and realisation of a data management and exploration platform. The IsoGenieDB described in detail (especially the figures 3 and 4 are very informative) with its flexible architecture might be an useful model and example for processing and accessing heterogeneous ecosystems biology and environmental research data.
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: STEROID HORMONES AND CHONDRICHTHYAN REPRODUCTION: PHYSIOLOGICAL FUNCTIONS, SCIENTIFIC RESEARCH, AND IMPLICATIONS FOR CONSERVATION
Review round: 1
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: Authors summarized steroid hormone levels in Chondrichthyans using 59 published literatures during 1963-2020. This review will be used for researchers focused on Chondrichthyans.
Comments are as follows:
1.	The title looks too broad. This review is mostly focused on steroid hormone levels. The present reviewer cannot understand the “physiological effects” in the title.
2.	Line 26: literatures?
3.	Lines 44, 272 and throughout the text: need consistency to use oestrogen or estrogen
4.	Lines 269-270: use small capital for “androstane”, hydroxypregnenolone
5.	Line 290: Oestradiol or Estradiol
6.	Lines 323, 394 and throughout the text: delete a space between 88.1 and %
7.	Line 660: physiol should be Physiol
8.	Line 671: scientific name of animals should be italic
9.	Line 686: world should be World
10.	Line 689: biochem should be Biochem
11.	Line 754: delete this space (line)
12.	Line 831: reproduction of vertebrates should be Reproduction of Vertebrates
13.	Line 836: bull should be Bull
14.	Line 838: textbook should be Textbook
15.	Line 839: endocrinology should be Endocrinology
16.	Line 873: brain research should be Brain Research
17.	Lines 882, 894-895: title should be small capital
18.	Lines 900-901: The Reproduction and Development of Shards, Rays and Ratfishes
19.	Add a space between line 917 and 918
20.	Lines 951-952, lines 970-971: use large capital for the book title
21.	Line 974: Plos should be PLoS
22.	Figure 3: better to add full name of each method in the legend.
23.	Legends of Tables 2 and 4, line 6: 17beta-oestradiol?  Dihydrotestosterone should be 5alpha-dihydrotestosterone, 11-ketotestosterone
24.	Table 2, Line 8: androstane-3alpha, 17beta-diol?
25.	Table 2, Line 9: hydroxypregnenolone, 11-dehydrocorticosterone


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: STEROID HORMONES AND CHONDRICHTHYAN REPRODUCTION: PHYSIOLOGICAL FUNCTIONS, SCIENTIFIC RESEARCH, AND IMPLICATIONS FOR CONSERVATION
Review round: 1
Reviewer: 2

Output:
Basic reporting: The authors addressed an important nitch, which was steroid hormones and the reproduction of chondrichthyans.  The manuscript is fascinating and well-organized.
Experimental design: The authors focused on percentages of studies covered certain steroid hormones.  However, it is more important to discuss data quality, such as replicates and assay specificities.
Validity of the findings: The authors should describe their thought based on previous data rather than summarizing thought by previous studies.
Additional comments: There are a couple of points to improve the manuscripts.  Please find them in an attached PDF.


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: STEROID HORMONES AND CHONDRICHTHYAN REPRODUCTION: PHYSIOLOGICAL FUNCTIONS, SCIENTIFIC RESEARCH, AND IMPLICATIONS FOR CONSERVATION
Review round: 1
Reviewer: 3

Output:
Basic reporting: In this review article, the authors studied literatures on cartilaginous fish reproduction with special reference to sex steroid hormones. This study covers a total 59 peer reviewed scientific papers from 1963-2020, and analyzed with regard to species investigated, methodologies and steroids investigated, which is unique and provides important information to this scientific field.
Experimental design: This review article contains four major analyses, namely, analyzed species, methods and biological matrices, steroid hormones and reproductive biology, and scientific research. The first three analyses are clear, but the section “scientific research” seems not to be clear in terms of the purpose of this study. In the “steroid hormones and reproductive biology” section, the data in literatures were well described for each steroid, but it was not easy to understand systematic contribution of multiple steroids to biological actions (phenomena). I strongly suggest that, in addition to the data for each steroid, the authors should analyze data in literature with regard to each biological phenomenon (such as follicle development, ovulation, reproductive behavior, and so on) and describe possible contribution of steroids to each phenomenon (if necessary, with additional table). I am afraid that the readers cannot understand how each biological phenomenon is regulated by steroid hormones. Discussion with other vertebrates, in particular with teleost fish, would also be required.
Validity of the findings: As described above, the analyses are unique and provide important information to the scientific field, but more analysis on biological function of steroid hormones are necessary. Currently, looks like just reviewed methodology, more biological values are necessary.
Additional comments: 1. The authors mention that “there is no general pattern that could describe the specific actions of sex steroids in cartilaginous fish” (lines 115~, and others). For this reason, the authors mentioned such as diversity of species, variety of embryonic nutrition strategies, paucity of species investigated, and so on. I agree these in part, but more serious problem in the cartilaginous fish research would be the lack of comprehensive (detailed, systematic) research using captive model species.
2. line 135; “improved our understanding of the endocrinology”. Please mention more in detail.
3. lines 228-230; “In the case of blood, the original volume per sample ranged between 0.5-20 mL, while the volume for analysis was 50-1000uL”. In Table 2, the volume for analysis should be included in addition to the volume per sample. The authors discuss about the sample volume (for example, lines 235-239 and 532-533) that the methods have generally require a large sample mass for assays. Is this correct? In particular for RIA and EIA, the plasma sample volume required for E2, T, P4 would be less than 0.5 mL in total.
4. lines 246-249 and others; did steroid hormone levels in skeletal muscle show parallel changes with plasma levels?
5. The authors described about corticosterone as a corticosteroid. However, in cartilaginous fish, 1alpha-hydroxycorticosterone (1alpha-OH-B) is a major corticosteroid, and the levels of 1alpha-OH-B in plasma seem to be 100-times higher than the levels of corticosterone in a recent study (Iki et al., Gen. Comp. Endocrinol., 292, 113440, 2020). The authors should at least state in the text that the major corticosteroid of cartilaginous fish is 1alpha-OH-B.
6. The authors frequently mentioned in the text that “most studies measured only three steroids (E2, T and P4), and the limited number of studies reporting other steroids”, and this is one reason why biological actions of steroid hormones in reproduction have not been well clarified in cartilaginous fish. I agree in part, but function of E2, T and P4 have not been clarified yet. Again, the lack of comprehensive (detailed, systematic) research using captive model species would be the most serious problem.
7. line 606; “potential bias from immunoassays”, unclear.
8. The Conclusion section seems to be repetitive. For future perspectives, biological aspects such as “how to clarify biological actions of steroid hormones in cartilaginous fish reproduction” seem to be lacking.
9. This reviewer consider “sex steroid (hormone)” is appropriate than “sexual steroid (hormone)”.


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: STEROID HORMONES AND CHONDRICHTHYAN REPRODUCTION: PHYSIOLOGICAL FUNCTIONS, SCIENTIFIC RESEARCH, AND IMPLICATIONS FOR CONSERVATION
Review round: 2
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: Authors adequately revised the manuscript following comments from reviewers. No further comments on this manuscript.


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: STEROID HORMONES AND CHONDRICHTHYAN REPRODUCTION: PHYSIOLOGICAL FUNCTIONS, SCIENTIFIC RESEARCH, AND IMPLICATIONS FOR CONSERVATION
Review round: 2
Reviewer: 2

Output:
Basic reporting: The authors addressed all my previous comments.  Here are all the minor comments.  Please find them in an attached PDF.
Experimental design: The authors need to describe more about the extraction method.  To compare the extraction efficiencies, it is critical whether extraction methods were the same or different.  Also, describe what "-" indicates in Table 2.
Validity of the findings: no comment
Additional comments: Overall, very informative.  This manuscript will help to find where the gaps are for future studies.


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: STEROID HORMONES AND CHONDRICHTHYAN REPRODUCTION: PHYSIOLOGICAL FUNCTIONS, SCIENTIFIC RESEARCH, AND IMPLICATIONS FOR CONSERVATION
Review round: 2
Reviewer: 3

Output:
Basic reporting: No more comment
Experimental design: No more comment
Validity of the findings: No more comment
Additional comments: The authors have adequately addressed all the comments. The manuscript has been sufficiently improved; in particular, newly added Figures 5 and 6, and descriptions concerning current whole picture on regulation of reproductive phenomena by steroid hormones are highly meaningful.


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: EVALUATION OF SALT TOLERANCE IN ERUCA SATIVA ACCESSIONS BASED ON MORPHO-PHYSIOLOGICAL TRAITS
Review round: 1
Reviewer: 1

Output:
Basic reporting: The manuscript represents an actual and original contribution to the knowledge about Eruca sativa tolerance to abiotic stresses. However, I consider the manuscript suitable for publication only after some revision. Some improvement could be done in the structure of the manuscript and in the way to present and discuss the obtained results. There is need to improve the English language of the manuscript.

Specific comments
Title
- The title gets to the point but is too long. Rephrased.
Introduction
It is detailed, comprehensive, and well presented, based on recent up to date bibliography.
-	Line 87: “. Eruca sativa” and check how it is reported throughout the text after the dot.
Materials and Methods
-	Line 106: What were controlled conditions in growth chamber? Specify.
Results, figures and tables
-	It is difficult to follow the statistics shown in tables, please distinguish the various interactions with upper- and lower-case letters.
-	Report the same abbreviation E. sativa in all figure and table captions.
Discussion
The presentation of these section is indeed very extensive to the point that its understanding is problematic. This work is rather interesting but considering the amount of data I suggest rewriting it in some parts making it more fluid to the reader and including more attention in the discussion of the results for the observed species.
Experimental design: Methods described with sufficient detail & information to replicate.
Validity of the findings: Conclusions are well stated, linked to original research question & limited to supporting results.
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: EVALUATION OF SALT TOLERANCE IN ERUCA SATIVA ACCESSIONS BASED ON MORPHO-PHYSIOLOGICAL TRAITS
Review round: 1
Reviewer: 2

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: The present paper is an investigation on 25 accessions of Eruca sativa aiming at characterizing them for salt tolerance through the analysis of morphological and physiological traits.
The topic could represent a contribution to the knowledge of traits useful for the screening of salt tolerant accessions. Moreover, some salt tolerant accessions of E. sativa were identified by the authors.
The manuscript is well presented and well written, therefore I consider it suitable for publication after minor revision.
Specific comments for the authors:

Introduction
-Line 55 – The difference between “cultivated” and “irrigated” lands is not much clear, since I suppose that the cultivated lands are also irrigated. The sentence should be reformulated.
-Lines 57-58 – this sentence should be better explained. What the authors mean with “global food security”? Moreover, it is not clear the meaning of “to develop salt tolerance species”. The authors refer to genetically modify the plants or just screening natural tolerant species? Please reformulate the whole sentence.
The same doubt is for lines 71 and line 75 (“developing salt-tolerant genotypes”).
-Lines 88-89 – “Although…. However…”, use only one of the two conjunctions and remove the other one.

Materials and methods
-The authors should specify also in this section (Plant material, growth conditions and salt stress treatment) the number of E. sativa accessions which were investigated. Moreover, the number of control and treated replicates for each accession is never reported. It should be specified in the text.
-Lines 156-157 – The sentence sounds strange since the experiment was conducted in controlled conditions. What the authors mean with “the measurements were conducted in a sunny day”?
-Lines 180-182 – The description of statistical analysis is not much clear to me. The Duncan test was used as post hoc test after two way ANOVA analysis? Was the data-normality tested before?

Results
-All the figures seem to have a low resolution, therefore the quality should be improved.
-In the tables I would use “accessions” instead of “cultivars”
-Figures: letters of statistical analysis results are reported only in fig. 3. It would be useful to show statistics also in all the other graphs.
-Tables: letters of statistical analysis should be reported also for comparison between the total mean of control and treated samples.
-Lines 238-239 – The last sentence is not completely correct. Some of the accessions did not show significant difference between control and salt treatment.
-Lines 265-266 – It is not clear why the authors could not measure gas exchange parameters in Es-7 and 16. What they mean with seed unavailability? Since gas exchange measurements are not-disruptive, the same plants used for the other analyses could have been used before to this aim prior to the final sampling.

Discussion
-In this section the authors should follow the same order and structure followed in Materials and methods and Results. Therefore, the discussion should start with the morphological traits and biomass and the paragraph in lines 360-379 should be moved later in the 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: EVALUATION OF SALT TOLERANCE IN ERUCA SATIVA ACCESSIONS BASED ON MORPHO-PHYSIOLOGICAL TRAITS
Review round: 2
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: I consider the manuscript suitable for publication.


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: EVALUATION OF SALT TOLERANCE IN ERUCA SATIVA ACCESSIONS BASED ON MORPHO-PHYSIOLOGICAL TRAITS
Review round: 2
Reviewer: 2

Output:
Basic reporting: -
Experimental design: -
Validity of the findings: -
Additional comments: The authors have answered to all my comments and made all the suggested modifications. Therefore, the paper is now suitable for publication.
I have only the follwing correction to suggest:
Lines 74-75 the word "subsequently" is double-repeated


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: PREVALENCE OF AND RISK FACTORS ASSOCIATED WITH LATENT TUBERCULOSIS INFECTION IN A LATIN AMERICAN REGION
Review round: 1
Reviewer: 1

Output:
Basic reporting: •	The English language should be improved to ensure that an international audience can clearly understand your text. For example, the inconsistent use of abbreviations and certain terms/words.
•	I have annotated and highlighted the PDF for errors, abbreviations and other sections of the manuscript which need to be corrected.
Experimental design: No comment
Validity of the findings: I thank the authors for providing the raw data. Although study results are compelling, there are few issues which need to be addressed/explained in order to improve this manuscript.

•	Authors imply the study’s findings represent epidemiology and risk of LTBI in the general population, but this cannot true. Study participants were recruited from healthcare facilities (3 primary healthcare facilities/clinics and 1 hospital), Health facility-based participants do not represent people with LTBI in the general population.
•	Authors have not made a compelling justification of fitting different models for different cut-offs and skin induration. I would suggest they only present a model for ≥10 mm cut-off in the main text. And other models can be presented as supplementary materials.
•	Authors present findings and discuss findings on joint effects such as education and BMI. It is not clear what they mean by joint effects. They also need to describe in the analysis section how they assess joint effects
Additional comments: I commend the authors the important study on one of public health problem in Colombia. In addition, the manuscript is clearly written in professional. If there is a weakness, it is in the statistical analysis (as I have noted above) which should be improved upon before Acceptance.


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: PREVALENCE OF AND RISK FACTORS ASSOCIATED WITH LATENT TUBERCULOSIS INFECTION IN A LATIN AMERICAN REGION
Review round: 1
Reviewer: 2

Output:
Basic reporting: Double check figures and tables
•	The figures and tables were double-checked.
•	There were no clear titles for the figures and tables
•	Figure 2, the age categories will read better as years instead of year for example 14-19 years not 14-19 year.
•	Table 1 the average age stated in line 187 was not found in the table, BMI was not labeled correctly (Table 1 and 4).
•	 Table 3 the age groups start at 40-49.
•	 Highlighting the significant variables in the tables (bolded/ by using and asterisks * -used in text as a pointer to an annotation or footnote) would simplify interpretation of the tables.

Open the raw data
•	I managed to open raw data and it was well described in English, the dataset had information on the 589 participants.

English language check
•	Language is clear, intelligible and professional but some sentences could be paraphrased.

Basic Reporting
Clear and unambiguous, professional English used throughout
•	The article was written in English, fairly clear, unambiguous and technically correct. The professional standards of courtesy and expression.
•	For the abstract line 24 and identifying the associated risk factors reads better than knowing the associated risk factors.
•	The authors started most sentences with numbers, line 29, 120, 189 and it does not read well please paraphrase and start the sentences with words.
•	Please paraphrase lines 30-33 …Logistic regression showed that being aged between 40 to 69, male, employed and low alcohol consumption were risk factors for TST positivity , while living in the north and suburb zone and having secondary education were protective factors against TST positivity.
•	The use of gender (men and women) throughout the manuscript could be replace with sex. Please stick to using females and males (14 year olds cannot be classified as men and women). Sex is a biological concept based on biological characteristics such as differences in genitalia and on the other hand, gender primarily deals with personal, societal and cultural perceptions of sexuality.
•	Paraphrase lines 37-39 ...Being an employed male, over 40 years of age with lower level of education, low alcohol consumption and being overweight should be a priority group for the prophylactic treatment as a strategy for the TB control in the city.
Experimental design: The primary research is within the Aims and scope of the journal.
Introduction
•	The introduction is well done and the reviewed literature is properly referenced.
•	Maybe introduce the different cut off points for the TST in paragraph 4 (Lines 85-92).
•      The aim is clear and to the point. The research question is well defined and relevant.

The investigation was rigorous and performed to a high technical and ethical standard.

The methods were described in detail.
Materials & Methods
•	There is no clear justification for the selection of the 4 hospitals (line 107).
•	Line 108-109 please introduce the zones fully. It is not clear whether north, suburb and center were the only zones in Cali.
•	Line 151 and 551-552. MinSalud, its not clear whether it is a citation or not, there is no year.
•	Line 169 is or the proper conjunction to use.
Validity of the findings: Results
•	Line 186 there is typo its 14-70 not 19-70 years-old.
•	Paraphrase lines 186-187.
•	Line 200 its males not male.
•	Lines 202-203, males, and females not male and female. Please consider exchanging (line 202) with growing age to increasing age.
•	Line 232 from table 3 does not have age group 3o above it starts at 40-49 years.
•	Line 241 specify that the results presented are for the bivariate analysis.
•	Line 243 male should be males and female females. Plural and not singular.
•	Paraphrase line 253-258…it was found that being aged 30 and above with OR from 4.29-8.30, being male [OR = 1.71, CI not IC 95 1.04-2.84], Please consider exchanging being employed not be active at work …
•	Line 275, please consider exchanging belonging to the male gender to being male.

Discussion
•	Lines 293-300, the sentence is too long, please restructure. Remove the citations within the sentence and place the citations at the end of the sentence.
•	Paraphrase 301-304, please consider exchanging …without chronic diseases underlying to any underlying chronic diseases.
•	Paraphrase lines 306-308. Please remove the citations within the sentence and place the citations at the end of the sentence. It can be …the LTBI prevalence reported in Singapore (Yap et al., 2018).
•	Paraphrase lines 333-337. Please consider exchanging men with males and women with females (lines 333 and 337-338) and place the citations at the end of the sentence.
•	Paraphrase lines 350-353, the sentence is too long.
•	Lines 360-367 there is repetition, Narasimhan et al (210) is not correctly cited and it not in the reference list. There is a typo in line 362 it is in not In.
•	Line 377… Please consider exchanging …Being male and low alcohol consumption increased the LTBI risk not the male gender.
•	Lines 382-384 restructure the sentence and place the citations at the end of the sentence.
•	Paraphrase lines 391-394 Shero et al (Shero et al., 2014) can be removed and the citation can be at the end of the sentence for better comprehension.
•	Paraphrase lines 402-405 cite properly.
•	Lines 408 and 409 the numbers (170) and (187) are misplaced.
•	The zone East and South were mentioned for the first time in line 419.

Conclusion
•	It is well stated and linked to the aim and limited to the stated limitations

The underlying data has been provided and are robust, statistically sound and controlled.
Additional comments: •	The writing style and the English language can be improved to ensure that the paper can be clearly understood by the international audience, the current phrasing makes comprehension difficult.
•	Citations can be presented better to help with the flow of ideas and to avoid repetition.
•	Presentation of results should be improved upon before acceptance.


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: PREVALENCE OF AND RISK FACTORS ASSOCIATED WITH LATENT TUBERCULOSIS INFECTION IN A LATIN AMERICAN REGION
Review round: 1
Reviewer: 3

Output:
Basic reporting: -	Ethics Statement should be under its own section and not combined with participant information
-	Global comment: grammar and writing style not very strong throughout and needs to be reworked. For e.g. abstract, lines 193-194 should be in past tense, etc.
-	Common writing guidelines should be followed. For e.g. M. tuberculosis can be abbreviated to Mtb, after first mention
-	In line 184 the title reads “Socio-demographic and behavioral characteristics”, but the authors don’t discussion any behavioral traits. I would assume that mentioning tendencies of mood, depression, anxiety, etc. would constitute behavioral traits and not just addiction patterns.
-	Line 272/73 are repetitive
-	Multiple times in the results, authors use the term ‘low alcohol consumption’. This is very misleading in the style it is currently written and only in line 350 does the comparison become clear. Needs rewording
-	Line 407: are overweight and obesity really protective factors? Needs rewording
Experimental design: -	Line 274 and 254-257: being an employee or being active at work leads to increased LTBI risk? Poorly worded
-	Lines 260 and 280: very poor sensitivity
Validity of the findings: -	Lines 294-305: authors are comparing LTBI prevalence in this study to other population-based studies, but are the evaluation criteria the same? There’s no mention of what criteria these studies used, especially was it TST alone or TST+IGRA? Doesn’t seem to be a fair comparison
-	Lines 344-347: authors claim that employment (being employed) is a risk factor for LTBI. Although they provide some reasoning as to why this may be, this is still a lofty claim. For this to be substantiated, there needs to be additional analysis done to correlate the ‘type’ of employment, for e.g. the nature of work seen in subjects from low-income strata vs those individuals that work in corporate/office jobs
-	The authors at multiple occasions suggest ‘lack of gold standard’, but globally Quantiferon is still considered highly indicative of LTBI status
Additional comments: Significant drawbacks of this manuscript include lack of IGRA testing among subjects and/or comparative analysis with similar studies from other parts of the world, which have used TST 10/15mm for detecting LTBI prevalence


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: PREVALENCE OF AND RISK FACTORS ASSOCIATED WITH LATENT TUBERCULOSIS INFECTION IN A LATIN AMERICAN REGION
Review round: 2
Reviewer: 1

Output:
Basic reporting: No comment
Experimental design: No comment
Validity of the findings: No comment
Additional comments: The authors  made the suggested corrections to my satisfaction. The manuscript reads well now.


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: PREVALENCE OF AND RISK FACTORS ASSOCIATED WITH LATENT TUBERCULOSIS INFECTION IN A LATIN AMERICAN REGION
Review round: 2
Reviewer: 2

Output:
Basic reporting: Reads well, all previous concerns addressed
Experimental design: Study design is fine
Validity of the findings: Relevant findings reported
Additional comments: Manuscript can be accepted for publication


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: PERILS AND PITFALLS OF MIXED-EFFECTS REGRESSION MODELS IN BIOLOGY
Review round: 1
Reviewer: 1

Output:
Basic reporting: The review will be of broad interest for biologists, ecologists and other scientists using mixed models to deal with difficult data sets. I've seen a number of texts and reviews on mixed models, but this manuscript focuses explicitly on 7 common pitfalls, using easily understandable language and examples. The introduction is excellent. There are some unnecessary adjectives and overly-complex word usage. But this is easy to fix. The writing is excellent.
Experimental design: The study focuses on 7 common pitfalls for scientists using mixed effect models. I would say the selection of pitfalls is broad ranging and doesn't appear biased. Some of the pitfalls did not contain much referencing. For example, pitfall 1 has one reference; pitfall 2 has no references. Perhaps the referencing could be improved, at very least to back up that these are well-known pitfalls in biology. The review is organized logically.
Validity of the findings: I am not a statistician. Please look to other reviews for advice on the robustness of the statistical pitfall and reporting.
Additional comments: I am a regular user of mixed effect models, and do feel that I do not know many of the pitfalls. This paper is an excellent reader for people like me.

I think detail missing form the paper is about "detection" of pitfalls.  I realize the authors cover this briefly in the section "Detecting and resolving problems with mixed model estimation". However, I think the paper would benefit from suggesting explicit tests for each of the pitfalls, integrated into Table 1 (as a column) as well as the supporting R code. Many readers will not be able to fully understand the textual description of pitfalls and the R code supporting these descriptions, and they will just want to know how to detect if they have an issue or not.

Minor comments:
Line 22: Awkward sentence, and perhaps "careless" instead of "incautious."
Line 103: remove "extreme" and be careful with unnecessary adjectives.
Line 115: Word choice: "Anathema." It feels like the authors are using unnecessarily complex words in places. Keep the language simple and readable - just like you're keeping the statistical explanations simple.  People will thank you for it!
Line 218: "provided"


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: PERILS AND PITFALLS OF MIXED-EFFECTS REGRESSION MODELS IN BIOLOGY
Review round: 1
Reviewer: 2

Output:
Basic reporting: This manuscript presents seven perils and pitfalls of mixed-effects models. It is very well written, clear and concise. Therefore, I expect it to be useful to a broader audience. Nothing within the manuscript is entirely new, but the combination, I hope, will create awareness of particular issues and will thus promote better statistical modelling across the fields.
Experimental design: The manuscript is very well presented and I really like how simple and clear simulations are introduced to illustrate the main points. This is very well done.
Validity of the findings: The points raised in the manuscript are all reasonably obvious. My only small concern is that the manuscript has an overall slightly negative tone as if there were many hidden pitfalls. Some of those, however, are rather special cases such as when the number of groups is very low. The manuscript is overall very good in highlighting specific problems, so I think the general massage could be a little more encouraging: There are pitfalls, but they can be rather clearly identified and are manageable.
Additional comments: I’ve made one of my main points above (a slightly more optimistic/encouraging tone). This can be addressed with quite minor changes to the manuscript. I’ve got a few more specific comments that I list below. And I’ve got one pitfall that I think is worth being added:

Random effects do not control for all kinds of non-independence. I’ve frequently seen people fitting random effects for cases where outcomes are not necessarily positively correlated within groups. A common case are choices of alternative outcomes measured in the same trial (e.g. time spent in different parts of an arena in behavioral trials) or area covered by different plant species that compete with each other. In such cases, outcomes are actually negatively correlated and a random effect TRIAL or PLOT does not control for this kind of non-independence. There seems to be a rather widespread believe that random effects care for everything when group levels have the same name. This point is related to Peril #2 and Peril #7.

Specific comments

L24: I don’t think “as long … are conservative” is the ultimate goal. If this was the case, we would use lower alpha levels. Something like “as long as statements are sufficiently cautious and well-informed” sounds better.

L92: Update the reference to R. The most recent versions have a reference to 2019 or 2020. Furthermore, the “authors” of R are called “R Core Team”.

L123 (and throughout the section): Since I don’t see why one would like to do model simplification in the first place, I don’t like that this seems to be the default here. I am aware that this is frequently done, but the manuscript could be a bit more nuanced. Forstmeier et al. (2017) Biological Reviews, 92: 1941-1968. is a useful reference.

L128: Suggest “it is safe” for style.

L128 and L144+: I think this is overstating the issue. The simulation is quite extreme: 12 datapoints in 6 groups, actually a paired t test situation. With 100 datapoints in 12 groups this issue is almost completely gone (L156+). When people use mixed models, they typically have many datapoints, so that the second situation seems much more realistic and the issue overall rather minor.

L162: Suggest “do not cure all pseudoreplication”

L174-177: This is a rather heavy sentence for a manuscript that is supposed to be very low level. Furthermore, I find the issue again a bit overstated, because it applies to the case of few groups and many observations.

L194: This is one of the few places where the manuscript is too unspecific. What does it mean “must have a clear understanding”? Being more specific helps readers to avoid the issues.

L213: “absurd” seems overstated and unnecessary.

L213: “always” seems overstated and unnecessary.

L291: A rather complicated sentences for a low entry-level manuscript

L323: I think the issue is a bit overstated. Often enough, some coarse control for spatial (or temporal) structure is better than none at all. However, absence of random effect variance with coarse structure does not mean absence of a spatial structure. Random effects do not take care of all non-independence (my point above).

Reference list:
- Several references lack volume and/or page numbers.
- The reference to lme4 is Bates et al. 2015 J Stat Software.
- First and last names are mixed up in Dormann et al. 2007.
- Fletcher et al. is lacking information on editors.
- Harting 2020 is incomplete.
- Lüdecke “sjPlot”

Table 1:
Some suggestions to be more specific about the actual perils:
#1 Anticonservative significance tests at low sample size.
#2 Pseudoreplication with group-level predictors
#4 Random-intercepts when random-slopes are need (or Random-intercepts when groups vary in response to treatment)

Table 1
The example for 5a is actually not clear. It is not obvious from the example that there is within and between-group variation and that the causal relationship might differ between levels. Btw: This is something to clarify in the main text as well, that the problem is specific to cases where causal relationships vary across the hierarchy (surely, this does occur, but it might not be all that common).

Table 1:
In example 6 suggest to remove “binary”


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: EVALUATION OF EPIDEMIOLOGICAL LECTURES USING PEER INSTRUCTION: FOCUSING ON THE IMPORTANCE OF CONCEPTESTS
Review round: 1
Reviewer: 1

Output:
Basic reporting: Review of paper by Dr Mitsuhashi, Okayama University Hospital titled “Evaluation of epidemiologicval lectures using peer instructions. Focusing on the importance of concepTests.

The manuscript considers the effect of peer instructions conducted in a single 80 minutes lecture in epidemiology. Approx 120 students participated after providing written informed consent. Data consist of the outcome of 5 multiple choice questions before and after students were allowed to discuss the concept (Peer instructions, PI). In 3 cases outcome improved, in on case there was no difference, in the last of the 5 cases the outcome was worse than anticipated after PI.

Generally the manuscript is well written and easy to follow for the reader.

Abstract
The first-time-reader would benefit from having PI efficiency defined already in the abstract.

Introduction
Limited number of references provided,however all are relevant.
Few newer studies overlooked, e.g. Katyal et al, intl J Biomed and Adv Res 2016, reporting on among others the effect of PI in epidemiology lectures, and https://ucl.ac.uk/teaching-learning/case-studies/2018/sep/peer-instruction-transforms-medical-science-classroom.
There is quite a number of other new studies on PI in medical sciences as well, however not necessarily touching upon epidemiology.
I recommend the author to specify which gap this specific study addresses – which gap is filled. It is indirectly touched upon lines 62-66 & 71-72. Aim is clear, lines 73-74

Reference list: seems complete and without formatting errors
Tables and figures: reads well and seem of good resolution

Data tables and figures
2 excel files provided – one “appendix Table” with ConcepTests and “raw data responses” with conceptest outcomes before and after PI
Forms for informed consent + IRB approval enclosed.
Raw figures not encluded, but do.file is enclosed, which describes the code for generation of the graphs in stata
Experimental design: Methods section: described sufficiently and understandable.
Ethics are described. Approval obtained. It may be a matter of preference, but I recommend ethics section is moved up front in the methods section.
Author refers to “exercises and ConcepTests” line 82, were other activities than ConcepTests with PI used in the lectures?
How were students instructed to prepare for the lecture? As usual? Or were instructions different vs normal?

The data supporting the manuscript are limited! see section above.

The question is whether the manuscript in nature is more a case study, rather than a research study, since only one single lecture with 5 ConcepTests was used as data basis.

Suggestions are provided below to add data to provide the manuscript a more solid body.

Study / first data collection NOT confirmed by independent observations.

Specific suggestions for improving the data and discussion:

I find it difficult to understand which specific method (line 183) and empirical research methods (lines 184 and 185) the author is pointing at. Clarification /revision of sentence recommended.
In lines 186-195 the author discusses whether the topic taught will influence the efficiency of PI, did the author consider whether the way MCQs, i.e. The ConceptTests were phrased influenced the results? Were MCQ of the same type, although topic varied? Some variation is, as described – and as supported by references – expected. So 1 of 5 providing a worse outcome and 1 of 5 with no change seems quite good, but questions might require revision before being used another time. Any thought on this might be a valuable addition.
This links to the next questions, since the %of correct answers should be high enough (35% at least, as also referenced by Crouch and Mazur) to facilitate the PI. How was the nature of the most difficult ConcepTests in this study? What pedagogical considerations were behind the concepTests and design of concepTests used? see also comment below on design of MCQ.

Were any attempts done to prepare the students for the different lecture format before the lecture? Or were ConcepTests introduced “without any warning”?
Was culture considered as negatively influencing the students’ engagement in the PI? Cf Shimizu et al BMC Med Educ 2019
The study would benefit from including students’ evaluation of the use of concepTests, i.e.addition of  qualitative data on students’ perception of the lectures.  It is unclear whether this was considered in the limitations section (line225).
If students’ perception of the new teaching method cannot be added, did the author consider looking at the impact of the addition of PI on the exam grades? Maybe even comparing classes’ performances the year before and the current term (exam following october 2019) for exam questions in epidemiology? Some reports are available comparing students exam performance within the same course between lectures where PI was used and those taught conventionally cf. Carstensen et al Eur J Pharmacol. 2019

What was the teachers perception of using PI in epidemiology? Was it more difficult? Did it require much more time for preparing for the lecture? Was it difficult to use the mentimeter?

It is discussed that the negative outcome of ConcepTest 2 might be due to difficulties of the students to adhere or participate in the PI due to the novelty of the use of PI in the lectures. However, as the appendix Table indicate, the students are asked to choose the LEAST appropriate item. A good rule of thumb when preparing and designing MCQ is to not confuse students and to no ask for choices on negative terms like “choose the least appropriate” or “which of the following does NOT apply”. Cf e.g. Case and Swanson 2002 NBME, or Shank 2019 elearningIndustry. I recommend the author to add this point to the discussion for future investigators to consider design of the concepTests as well.
Validity of the findings: please see section above on suggestions for improvements.

The data body is very limited.
Limitations are discussed, few suggestions are indicated in section 2 for improvements.

underlying data are provided, nothing is wrong with these, however, more data might be available to support the study.

Given some of the references above (sections 1 and 2) I am afraid the author cannot conclude that this is the first report on PI efficency in epidemiological education (line 241), however the addition of the study is highly warranted cf Goldman et al Am J Epidem 2018
Additional comments: Author is commended on submitting data evaluating use of PI in the medical curriculum. Is a valuable contribution, however databody is very limited and author is recommended to consider whether further data can be added in support of the study cf sections 1-2-3 above.
language and structure is clear and manuscript is easy to read and follow


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: EVALUATION OF EPIDEMIOLOGICAL LECTURES USING PEER INSTRUCTION: FOCUSING ON THE IMPORTANCE OF CONCEPTESTS
Review round: 1
Reviewer: 2

Output:
Basic reporting: This article addresses and interesting and timely research topic, building on prior data outside of the field of medicine.

Professional English used, writing clear and concise.

Introduction contains a good overview of the subject material, major references cited.  Good context for this study provided.  Research question clearly stated.

Article structure appropriate, tables understandable and add value to text.

Article is self contiained
Experimental design: Experimental design is conventional, statistics are straightforward.
Methods described in sufficient detail to replicate
Appropriate ethical approval and oversight documented
Validity of the findings: Findings are valid and not overstated.
Findings are consistent with prior research in the subject area.
Underlying data provided, statistical analysis is reasonable

Conclusions based on the data, confined to the research question.
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: EVALUATION OF EPIDEMIOLOGICAL LECTURES USING PEER INSTRUCTION: FOCUSING ON THE IMPORTANCE OF CONCEPTESTS
Review round: 1
Reviewer: 3

Output:
Basic reporting: It is a good article that only describes what is significant about examining the effect of using Peer Instruction in epidemiological lectures. The article is written in clear English and with a structure that is easy to follow. In addition, the article contains relevant use of references and has a good introduction to the pedagogical method Peer Instruction. All appropriate raw data have been made available in in fine tables and associated graphs.
Experimental design: The article stays within the aims and scope of the journal.
The research question well defined and supported by relevant references. It is relevant and meaningful, and it is stated how the research fills the identified knowledge gap. The introduction to the pedagogical method Peer Instruction is clearly described. In the article referred to by Crouch & Mazur (2001), there is also a focus on pre-class activities such as reading and solving quizzes. These activities are important in relation to how well-prepared students worked with the ConceptTests in-class. So, in order to better understand your results, I suggest that you write a few sentences about what kinds of pre-class activities your students were asked to do.

The experimental design is well described and easy to follow and reproducible. The PI method is also well described. However, in step IV, it is unclear whether it is students with opposite answers to CT who should try to convince each other of what is the correct answer. Did your students move around to find other students with opposite answers or what exactly happened? There is a learning difference between whether the starting point of discussion is a cognitive conflict between two students or whether students discuss with someone with more or less the same opinion as themselves. Please add more details about how your students interacted.
Validity of the findings: The internal validity is good, although it is a small experiment. However, the external validity is not usable as the cohort effect is too small. The limitations of the study are well described and highlight very precisely which factors influence the results. In addition, the conclusions are well stated and linked to the original research question. Finally, the article highlights areas that need to be followed up with new studies to better determine the effect of using PI in epidemiological lectures.
Additional comments: You have written an interesting article regarding the use of PI in the field of epidemiological lectures. It could be interesting if you could experiment more with the preparatory online pre-class activities and at the same time investigate the in-class activities (PI lecture) in more detail. See, e.g. Rowley, N., & Green, J. (2015). Just-in-time teaching and peer instruction in the flipped classroom to enhance student learning. Education in Practice, 2 (1), 2015.


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: MULTIVARIATE STATISTICAL EVALUATION OF DISSOLVED HEAVY METALS AND A WATER QUALITY ASSESSMENT IN THE LAKE AHA WATERSHED, SOUTHWEST CHINA
Review round: 1
Reviewer: 1

Output:
Basic reporting: 1.     The manuscript presents assessment of dissolved heavy metals and a water quality assessment in the Lake Aha watershed, Southwest China with a combined approach using statistical analysis and water quality index, which is interesting. The subject addressed is within the scope of the journal.
2.      However, the manuscript, in its present form, contains several weaknesses. Appropriate revisions to the following points should be undertaken in order to justify recommendation for publication.
Experimental design: 3.      For readers to quickly catch your contribution, it would be better to highlight major difficulties and challenges, and your original achievements to overcome them, in a clearer way in abstract and introduction.
4.      It is mentioned in line 71  that Lake Aha watershed is adopted as the case study. What are other feasible alternatives? What are the advantages of adopting this particular case study over others in this case? How will this affect the results? The authors should provide more details on this.
5.      It is mentioned in line 143 that  the standard of Chinese drinking water are adopted as benchmark for comparison. What are the other feasible alternatives? What are the advantages of adopting these particular standards over others in this case? How will this affect the results? More details should be furnished.
6.      It is mentioned in line 106 that multivariate statistical methods are adopted to assist the interpretation of the relationships between the parameters and the results. What are the other feasible alternatives? What are the advantages of adopting these particular methods over others in this case? How will this affect the results? The authors should provide more details on this.
7.      It is mentioned in line135 that Water Quality Index is adopted to evaluate water quality status. What are the other feasible alternatives? What are the advantages of adopting this particular index over others in this case? How will this affect the results? The authors should provide more details on this.
8.      It is mentioned in line 117 that hazard quotient and hazard index are adopted to evaluate health risk status. What are the other feasible alternatives? What are the advantages of adopting these particular indices over others in this case? How will this affect the results? The authors should provide more details on this.
9.     It is mentioned in line96 that several physicochemical parameters are adopted in this study. What are the other feasible alternatives? What are the advantages of adopting these particular parameters over others in this case? How will this affect the results? The authors should provide more details on this.
10.     It is mentioned in line 107 that PCA were used to identify the possible origin of nine heavy metals in the study area.  What are the other feasible alternatives? What are the advantages of adopting this particular technique over others in this case? How will this affect the results? The authors should provide more details on this.
11.    What statistical method is adopted to analyze spatial and temporal changes in water quality. The authors need to present statistical analyses in the text.
12.     It is mentioned in line 156 that "… Overall, the pH, DO and EC values in the Lake Aha watershed show a noticeable variability. .…" More justification should be furnished on this issue.  how and when the spatial and temporal changes in water quality occur?
Validity of the findings: 13.     It is mentioned in line 195 that "…We compare our water samples with the data of other rivers (Li et al. 2007). Mn, Co, Ba and V, heavy metal concentrations of our study were higher than world average concentrations but were significantly lower than the Danjiangkou Reservoir …" More justification should be furnished on this issue. The author may present a table to show comparisons.
14.     Some key parameters are not mentioned. The rationale on the choice of the particular set of parameters should be explained with more details. Have the authors experimented with other sets of values? What are the sensitivities of these parameters on the results?
15.     Some assumptions are stated in various sections. Justifications should be provided on these assumptions. Evaluation on how they will affect the results should be made.
16.     The discussion section in the present form is relatively weak and should be strengthened with more details and justifications.
Additional comments: 17.     Moreover, the manuscript could be substantially improved by relying and citing more on recent literatures about contemporary real-life case studies on sustainability and/or water quality such as the followings:

Ustaoğlu, F., Tepe, Y., & Taş, B. (2019). Assessment of stream quality and health risk in a subtropical Turkey river system: A combined approach using statistical analysis and water quality index. Ecological Indicators, 105815.

Ustaoğlu Fikret, Tepe Yalçın, Aydin Handan (2020) Heavy metals in Sediments of Two Nearby Streams from Southeastern Black Sea Coast: Contamination and Ecological Risk Assessment
Environmental Forensics 21 (02), 145-156

Ustaoglu, F., Tepe, Y., Aydin, H., & Akbas, A. (2020). EVALUATION OF SURFACE WATER QUALITY BY MULTIVARIATE STATISTICAL ANALYSES AND WQI: CASE OF COMLEKCI STREAM,(GIRESUN-TURKEY). FRESENIUS ENVIRONMENTAL BULLETIN, 29(1), 167-177.

Taş, B., Tepe, Y., Ustaoğlu, F., & Alptekin, S. (2019). Benthic algal diversity and water quality evaluation by biological approach of Turnasuyu Creek, NE Turkey. Desalination and water treatment, 155, 402-415.

Ustaoğlu, F., & Tepe, Y. (2019). Water quality and sediment contamination assessment of Pazarsuyu Stream, Turkey using multivariate statistical methods and pollution indicators. International Soil and Water Conservation Research, 7(1), 47-56.

18.     In the conclusion section, the limitations of this study, suggested improvements of this work and future directions should be highlighted.


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: MULTIVARIATE STATISTICAL EVALUATION OF DISSOLVED HEAVY METALS AND A WATER QUALITY ASSESSMENT IN THE LAKE AHA WATERSHED, SOUTHWEST CHINA
Review round: 1
Reviewer: 2

Output:
Basic reporting: This manuscript presents new data on the heavy metals at 18 sampling points with 108 samples in the Lake Aha watershed, Southwest China. The authors interpret their heavy metals results by applying a couple of statistical techniques to better understand their data along with distribution, sources, controlling factors, and water quality for human consumption. Although the analysis and methods used are nothing new, I assume that this kind of study will continue in the future and this first compilation will be essential. As the quality of surface water is one of the most sensitive issues worldwide, this study will be of great importance not only at a local scale but all over the world and the amount of data on a new river system is worthy of publication. However, there are some major and minor issues needed to be considered prior to publication.
Experimental design: In fact, the paper mostly deals with the heavy metals with some minor description of the pH and even minor of the EC and DO from abstract to the conclusion. I recommend a more appropriate description of the physicochemical variables along with the heavy metals.
Validity of the findings: In statistics, the consistency of data is fundamental: if the dataset is not adequate, the output of the statistical analysis is not significant. For example, are there any missing data? Please do clarify. In the same section, before applying Pearson’s correlation, did you test the normality of the dataset? I do not think the dataset is normal in this study. If data are not normal you have to use Spearman’s correlation. Please, make sure and elaborate it.
Additional comments: The authors did not acknowledge the importance of pH and EC for the abundance and distribution of heavy metals in the inflowing tributaries. Specify that these issues are within the scope of this study.
In addition, maybe authors should explain better that on what basis they select the sampling points. Why only three sampling points from the Jinzhong River basin? It is not sufficient to show a map! In addition to how many points are selected, why you select these points is more important. In general, a higher description of the hydrology and climatology of the basins must be added


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: LARVAL LONGEVITY AND COMPETENCY PATTERNS OF CARIBBEAN REEF-BUILDING CORALS
Review round: 1
Reviewer: 1

Output:
Basic reporting: The manuscript is written in clear English and is properly formatted. It could stand a few more literature references (I have suggested expanding the discussion), but the articles that are cited are appropriate.
Experimental design: The methods are appropriate for the question and are well-described. The authors did a particularly good job of describing the differences in their methods between years.
Validity of the findings: The conclusions are well-supported by the data. The results match the questions posed.
Additional comments: This is a very good manuscript. I find research on the early life-history stages of invertebrates to be important for a broad range of questions and especially timely in the case of corals. The authors have identified a critical knowledge gap and conducted well-designed experiments to fill it. Even though the exact methods varied from year to year, the authors are exceptionally clear and up-front about how the methods varied. They have also been clear about limitations to the experiment (relocation from the field, termination of an experiment by hurricane evacuation). I fully support publication of this manuscript following minor revision. My specific comments are below.

Abstract, line 25: Missing an article before “reef”

Abstract, line 26: In the present manuscript, the length of time a larva survives is described as “longevity,” “persistence,” and “survival,” so I suggest the authors decide on a single term, which they clearly define and use throughout the manuscript. Survival seems most fitting to me.

Introduction, line 46: Without an appropriate citation, the claim that coral larvae are especially poorly studied in Caribbean species is unsubstantiated. I suggest citing a review paper at the end of this sentence.

Introduction, lines 58-65: I suggest the authors add the names of the species that were studied in the cited papers to this paragraph, in order to provide more context. Larval duration can vary substantially among species, so referring to studies on coral larvae in general is less valuable.

Methods, line 90: What is meant by larval fitness? In my mind, fitness refers to an individual’s reproductive potential in an evolutionary context, but I doubt that is the authors’ meaning here. Perhaps “larval condition” is a better term?

Methods, line 90: Give mesh size.

Methods, line 101 and elsewhere: “at least 5 um” – does this phrase mean water was filtered to 5 um or less?

Methods, line 101: Reef water being “hauled” is an unconventional phrasing. I suggest replacing this word with “collected.”

Methods, line 157: There seems to be an asterisk here where a parenthesis belongs.

Results, line 197: I suggest saying “run” instead of “trial run” because the latter makes it sound like the runs being referred to were a pilot experiment.

Results, line 213: “Ramping up” sounds like slang, so I suggest replacing it with “increase” or a similarly equivalent wording.

Discussion, line 219: “timing pattern of settlement” – something should be plural here

Discussion, line 232: Wait, high incidence of MUPs is related to culture density? I am very interested in the significance of MUPs. Is this a commonly-observed phenomenon in corals? What might be the evolutionary or ecological significance of midwater metamorphosis? I suggest expanding the discussion on this phenomenon.

Discussion: I would like to see the authors expand their discussion on the implications of their findings for coral reef connectivity studies. How might their results for larval survival and competency affect modelling efforts? What does the variability between years/cohorts tell us about settlement success and connectivity in the field? How can these results be used for conservation efforts in the future?


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: LARVAL LONGEVITY AND COMPETENCY PATTERNS OF CARIBBEAN REEF-BUILDING CORALS
Review round: 1
Reviewer: 2

Output:
Basic reporting: This manuscript presents valuable data on larval longevity and competency in major reef-building corals in the Caribbean. There is a lot unknown about larval longevity, although long-distance dispersal is likely in broadcast spawning corals. Therefore the data presented here is of high value for the community and for informing parameters of biophysical dispersal models. The authors have transparently laid out their data and presented all the data in a relatively clear way.

I have only minor comments and I think this work is an important contribution to the field. One major clarification would be every time the authors refer to the first observed metamorphosis that this is without interaction with the cue, correct? Making sure this distinction is clear throughout will help the reader.
Experimental design: The research question is well defined, relevant and meaningful. The data here fills an important knowledge gap and this type of data is relatively logistically difficult to collect. This data is also important in the context of reef restoration. The methods are described in sufficient detail but a few clarifications are necessary.

Line 56: I might also include some of the population connectivity for Caribbean building corals, work such as recent manuscripts by Michael Studivan and Rippe et al. 2017 to bolster the argument for needing this important life-history data.

I would recommend changing the in text citations from “and others” to “et al.”

Lines 93-98: Could you elaborate on how many adult  individuals were represented in each of the crosses? This is something that could be incorporated into Table 1.

Line 103: Could you clarify the replication here? As I am reading it now it looks like 5 replicate dishes of larvae per treatment (heat and control) for each species? Is that correct?

Lines 148-152: What was the level of replication for each competency assay?

Table 3: I would include information on what years the data was taken for each of these and across how many years of data each value includes.

Table 3: The third row, do you mean the % larvae remaining alive at first metamorphosis in the longevity experiments (w/o cue)?

Figure 2: typo in legend, line 3 “shows” not “sows”. Can you clarify that the dashed line refers to the onset of metamorphosis without exposure to cue? Also, you say to note the difference x-axis scales but they seem the same too me and the scale on the first row panels is missing.

Sup Fig 1: This could use some polishing up as many of the lines are staggered and some lines in the frames are missing.
Validity of the findings: The findings are valid and appropriately discussed.
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: GLOBAL EXPANSION OF COVID-19 PANDEMIC IS DRIVEN BY POPULATION SIZE AND AIRPORT CONNECTIONS
Review round: 1
Reviewer: 1

Output:
Basic reporting: The article fulfils all the criteria.
Experimental design: The article fulfils all the criteria.
Validity of the findings: The article fulfils all the criteria.
Additional comments: Congratulations to the authors for such an elegant and timely paper.

I only have a few minor suggestions, these are listed below.

Line 32 (abstract) I am not sure to what extent the sentence "Geographic distance and climate were significant barriers in the past but were surpassed by the human engine that allowed us to colonize most of our planet land surface." adds meaning here, but I cannot put my finger on the why. Probably it could help not to mix geographic distance and climate together since the second part of the sentence only refers to the former. Maybe the authors could just remove it, and the abstract wouldn't lose any meaning.

Line 58: As one of the authors of Chipperfield et al. (2020), I think my coauthors would appreciate you changing the reference to "Carlson et al. (2020)", which is the final published version of Chipperfield et al. 2020. However, and considering the conflict of interest I have here, please, feel free to proceed as you wish regarding this suggestion.

Just in case, the complete reference would be:

Carlson, C.J., Chipperfield, J.D., Benito, B.M., Telford, R.J., O'Hara, R.B. 2020. Species distribution models are inappropriate for COVID-19. Nature Ecology and Evolution. URL: https://www.nature.com/articles/s41559-020-1212-8, DOI: 10.1038/s41559-020-1212-8

Line 87: maybe the authors want to say "...to investigate the drivers of the growth rate of SARS-CoV-2".

Line 94: I believe "detected cases" better reflects what the authors want to say with "people infected", since the amount of people infected is usually larger than the number of detected cases, and the used dataset is based on the results of PCR tests.

Line 189: Maybe the authors want to start the paragraph with "Network centrality measures are widely used...", unless they are specifically referring to the actual measure used in the analysis. If that is the case, please, name it again, the reader might not remember which one was used.

Line 205: I suggest to replace "countries that invested less in health" with "countries with a lower investment in healthcare". This is not an important suggestion though!

Line 217: there should be a citation at the end of "...of what has been suggested by climate suitability models."

Line 218: I am not a native English speaker, and I am having troubles to understand the meaning of "ephemeral" in this context, so maybe a rewording would help here.

Lines 231 to 236: Asymptomatic transmission of SARS-CoV-2 could go through airport screenings (unless mandatory quarantine is implemented), so maybe the authors could comment on how even board control measures might not be enough to limit the spread of a pandemic like the one we are undergoing at the moment. There are several papers talking about presymptomatic and asymptomatic transmission, for example:

Gandhi, M., Yokoe, D.S., Havlir, D.V., (2020) Asymptomatic transmission, the Achilles' heel of current strategies to control Covid-19. The New England Journal of Medicine. URL: https://www.nejm.org/doi/full/10.1056/NEJMe2009758, DOI: 10.1056/NEJMe2009758

Bai, Y., Yao, L., Wei, T., 2020. Presumed asymptomatic carrier tranmission of Covid-19. JAMA 323(14) 1406-1407. URL:  DOI: https://jamanetwork.com/journals/jama/article-abstract/2762028, 10.1001/jama.2020.2565

Figure 2: I imagine it will save a lot of empty space to put panel A on top of the other panels.

Blas M. Benito.


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: GLOBAL EXPANSION OF COVID-19 PANDEMIC IS DRIVEN BY POPULATION SIZE AND AIRPORT CONNECTIONS
Review round: 1
Reviewer: 2

Output:
Basic reporting: Other remarks

Lines 47-48: The range of R0 reported in the literature is more [2-4], numerous models found values greater than 3.

Lines 100-102: It would be interesting to show some example of the exponential portion in comparison with the 30 days of the data.

Lines 105: For an analysis of an epidemic, it would be better to use the intrinsic growth rate (r) than the regression coefficient of the log growth series

Lines 136-143: About the airport network and the collapse of the airports’ network into a country-level network. This means that USA, China or Brazil is just one node in the network as Fiji, Suriname or Guyana. Then what are the consequences of the different population size between the countries of the network? Wouldn't it be better to standardize the connectivity of each country according to its population or some other economic variable?

Lines 136-143: What has been the role of airport closures and the sharp reduction in air traffic? How is this taken into account?

Lines 136-143: If you are flying from Europe to Australia, you stop in Thailand or in Singapore. How is this processed in the air traffic data? If I remember correctly just the IATA data take into account the different air stops for a given route.

Lines 154-156: What is the sensitivity of the results to the transformations used?

Results: Nothing is said about the link between the exponential growth rate of the epidemic at the beginning of the epidemic and the epidemic size. This would shed some light on the analysis

Line 159: “The models used to estimate COVID-19 growth rate on different countries” The growth rate or the regression coefficient of the log growth series as indicated in the Methods? And this question must be answer at each time of the expression “growth rate” is used in the rest of the manuscript.

Lines 185-188: “… we show that countries’ importance in the global transportation network has a key role on the severity of COVID-19 pandemic in different countries as it is strongly associated with the growth rates of the disease…” It’s not clear what is the meaning of the word “severity” in this sentence. Is it linked to mortality? But in this study, just the initial growth rate of the epidemic has been analyzed.

Lines 196: “secondary transmissions”: Definition?

Line 243-245: “However, we expect that our analyses show that current claims that growth of COVID-19 pandemics may be lower in developing tropical countries should be taken very carefully” Nevertheless there is less connection in developing tropical countries than in countries from the northern hemisphere? This low connectivity may also explain the lower development of the epidemics in some tropical countries.
The same remark can be made about “invested less in health”.

Figure 2: The readability of Fig 2 is low. I suggest to put Fig. 2A on a new Fig. 2 and the rest of Fig 2 and a new Fig. 3.
Experimental design: See below.
Validity of the findings: See below.
Additional comments: In this well written work the authors have used a classical macroecological approach to analyze the Covid-19 epidemics around the world. They have analyzed the growth rate at the beginning of the epidemic in numerous countries in relation with socioeconomic, climatic and transport variables. The key point of this study is the use of data from air traffic and the construction of the global air transportation network.

This study presents linear model analysis showing that the growth rate of the Covid-19 epidemic is mainly related to the airline connectivity between countries. With this kind of correlative analysis is important to propose potential explanations to the observed correlations. However the authors proposed no clear explanations to their main results, the effect of airline connectivity. This is one of the weaknesses of this work. Is this correlation observed, linked to the increase of the importation of severe cases? More discussion is needed on the role of air traffic. For instance, at the early beginning of the pandemic, the group of Colizza (Pullano et al., 2020. Novel coronavirus (2019-nCoV) early-stage importation risk to Europe, January 2020. Eurosurveillance, 25(4), 2000057.) has analyzed the risk of importation of the SARS-COV-19 in the European countries due to air traffic. The results showed that UK, France and Germany were the 3 countries with the higher risk of importation of this virus. Nevertheless, in real life, the epidemic started first and was strongest in Spain and Italy and started later in UK, which shows that the flow of passengers between airports is not always very reliable for making epidemiological predictions (similar results have been observed for the Ebola crisis).

One of my other concerns would be to better clarify the new contributions of this study compared to those already published on this topic (Pullano et al., 2020; Kraemer et al., 2020; Chinazzi et al., 2020; …).

Another of my concerns is about the fact that most of the Discussion is on the results of the influence of the warmer and humid climate on the propagation on tropical countries. It seems that the design of the statistical analysis is done, in the current work, for all the countries with climatic explicative variables (Mean Temperature and Mean Precipitation). With this analysis they cab only conclude that these 2 climatic variables have mild or no effect on the growth rate at the beginning of the Covid-19 epidemic. If the authors wanted to analyze the effect of climatic variables on the Covid-19 epidemic in tropical countries they would have to focus on the sub-set of tropical countries with other similar confounding factors. This concern is also true for the Abstract and the Conclusion.

To conclude, in this special time of crisis with an impressive flow of papers on Covid-19, it would be important that the authors associate their correlative with results some potential explanations that could convince epidemiologists. This is an important aspect that needed to be improved upon before publication in a journal with a large audience.


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: SPATIAL VARIABILITY OF MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS SURVIVAL RATES AND MORTALITY HAZARD IN SAUDI ARABIA, 2012–2019
Review round: 1
Reviewer: 1

Output:
Basic reporting: The manuscript by Al-Ahmadi et al is timely given the current outbreak of coronavirus disease (COVID-19).
The introduction is well written, though too long and the literature cited are adequately. There are few grammatical errors here and there, eg. None-healthcare workers should be non-healthcare workers, line 325 “over died”.
The major strength of this study (as stated by the title and objective) should be the use of spatial analysis accounting for regional risk factors. However, the authors almost failed to capitalize on this.
Experimental design: The major aim of this study was “to estimate the survival rates and hazard ratios of MERS-CoV mortality for 14- and 45-day post-symptom periods and to assess spatial variations by both the region in Saudi Arabia and the patient characteristics between 2012 and 2019.“

There is no single spatial component in the survival analysis described in the methods section. No regional/provincial level risk factors incorporated in the model described.
Validity of the findings: The spatial part of the results provided descriptive summaries of MERS-CoV across the regions. On line 241, the authors claimed the spatial variations were assessed but did not provide any detail information on the technique(s) used in the methods. What I can deduce from their findings on Table 2 & 3 is that either the authors conducted a separate survival analysis for each of the regions, thus, assuming no spatial dependencies or used region as interaction in the model. The authors use appropriate spatial survival analysis and account for regional risk factors as they mentioned is one of the drawbacks of previous studies.

Given that spatial variability is one of the main objectives of this said, the authors almost failed to discuss this aspect of their study in the discussion and conclusion.
Additional comments: Abstract:
Line 18-20: There is no mention of spatial analysis/variability.
Materials and Methods
Line 120-138: The authors mentioned one of the previous studies that used spatial modeling approach did not consider province level risk factors. One would have expect that this study will include such risk factors that are lacking in previous studies.
Check through for few grammatical errors


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: SPATIAL VARIABILITY OF MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS SURVIVAL RATES AND MORTALITY HAZARD IN SAUDI ARABIA, 2012–2019
Review round: 1
Reviewer: 2

Output:
Basic reporting: Sufficient literature references were given.
Experimental design: Methods didn't describe with sufficient details but research question was well defined, relevant and meaningful.
Validity of the findings: The methods are not novel but the paper addressed the gap of not modeling the multivariate risk factors.
Additional comments: The paper addressed the gap in the literature in terms of modeling the multivariate risk factors for MERS-CoV using multivariate analysis to investigate variations between mortality risk factors in different geographic areas of Saudi Arabia. It is an interesting applied paper. However, I did not see in the paper on how they addressed the geographic variation, For example, adding into the model structured and unstructured random effects to take into account the spatial correlation between the regions (or provinces) and noise in the data, respectively. Here are my specific comments.
1. It would be good to mention on how the authors handle the spatial correlation between the regions (or Provinces)
2. It would be great if the authors jointly models the risk at both Province and regional level simultaneously to borrow information from the province to the regional level. As such, it would be interesting if they displayed the risk variations across the province and regional levels.
3. In the introduction section, page 6, line 65-69 is not clear. It may be reworded as The severity of
illness such as for patients receiving vasopressor therapy (Almekhlafi et al. 2016), requiring invasive mechanical ventilation (Almekhlafi et al. 2016), and with higher chest radiographic scores (Das et al. 2015) are also associated with the risk for mortality resulting from MERS-CoV (Adegboye et al.2017; Ahmed 2017a).
4. In the introduction section, page 6, line 72-72, is not clear. It may be reworded as:
Researchers found that being healthcare workers (HCWs) is associated with higher mortality rates (Alsahafi & Cheng 2016), but other studies conversely linked being none-healthcare workers (none-HCWs) with higher mortality rates (Adegboye et al. 2017; Ahmed 2017b; Ahmed 2018; Rivers et al. 2016; Sha et al. 2017).
5. In the introduction section, page 6, line 83, 4-5 should be 4-5 days.
6. In the introduction section, page 7, line 92, it says `However, the virus..' but it doesn't look this sentence contradicts with the previous one. Using the phrase `However ' is not clear for me.
7. On page 8, line 158-159, it says `However, the log-rank test delivers a statistical, but not clinical, appraisal of the factors’ effects (Bradburn et al. 2003). Thus, the Cox proportional-hazards (CPH) model was applied...'. What do you mean by log-rank test delivers a statistical but not clinical appraisal of the factors effect? Does it mean CPH delivers a statistical but not clinical factors effect?
8. On page 9, line 194-195, it says `A lower mortality rate was found among those exposed to camels compared to those not exposed' . This looks unexpected result. Can the authors provide a justification why?
9. On page 12, line 319-323, it says `The univariate analysis showed that the hazard of
 14- and 45-day mortality in MERS-CoV male patients is higher than that for females only at the
national level and in the Central and West regions. In contrast, the multivariate analysis could not..' Why it is higher in the Central and West regions but not in the other regions?
10. On Page 28, For Figure 2, it would be more interesting if you could replace it at 45-day instead of 14 day.


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: SPATIAL VARIABILITY OF MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS SURVIVAL RATES AND MORTALITY HAZARD IN SAUDI ARABIA, 2012–2019
Review round: 2
Reviewer: 1

Output:
Basic reporting: The introduction is unambiguous and sufficient literatures were cited.
Experimental design: Adequately written. ALthough univariate local spatial autocorrelation was used, this does not really provide any useful information regarding the spatial interaction between the outcome and covariates examined in the study. The authors should include bivariate spatial autocorrelation (e.g. Bivariate Moran's Index) to measure the spatial interaction between the outcome and covariates.
Validity of the findings: Addition of bivariate spatial autocorrelation will add credence to the spatial analysis
Additional comments: This is a much imporved version of the manuscript. I will recommend this manuacript for publication after minor revision.


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: MAGNITUDE OF NON-ADHERENCE TO ANTIRETROVIRAL THERAPY AND ASSOCIATED FACTORS AMONG ADULT PEOPLE LIVING WITH HIV/AIDS IN BENISHANGUL-GUMUZ REGIONAL STATE, ETHIOPIA
Review round: 1
Reviewer: 1

Output:
Basic reporting: comments:
a) Title:
  -better to make it more self-explanatory
  -it should reflect the main aim of the study in unambiguous ways..
  -it lacks clarity and seems a bit uneasy and
  - hence it should be corrected as " Treatment adherence and associated factors among adult PLWHA......."
b) Author's address: should be complete (e.g; P.O.box, phone,emails etc.
c) grammatical errors and idea flow:
       - some statements do not give sense (e.g;under introduction line No.69& 70 should be re-written in grammatical order,line No.80 referencing style, in result part line No.229 lacks unit of measurement,line No.251-57 incorrect statement,
        -result presentation in number and % is not uniform (see comments)
Experimental design: comments on Methods and Participants
-Methods employed are not described with sufficient information
-The knowledge gap being investigated has not been adequately identified
-Sampling procedure (allocation) is unclear and not convincing (it should be depicted graphically how the sample is drawn)
-the investigation does not seem rigorous (if not sufficient justification should be given)
-inclusion-exclusion criteria lacks clarity
-conceptual frame work is not provided for variables
- findings of pre-test should be explained if any
-lacks data quality managements methods used
-justification  should be given for selection of adherence assessment methods(since there are many methods) ...why VAS  method??? its validity ??? applicability in clinical practice?
-Issue of confidentiality is not adequately addressed
-specific objectives should be clearly stated
otherwise the study is good.
Validity of the findings: -findings should  reflect the set specific objectives(not stated) of the study
-inconclusive/inconsistence findings have not been adequately discussed
and please,check aforementioned comments.
Additional comments: General comments:
The following things have not been adequately addressed or no justification given...
a)	patients with co-morbid conditions (TB,CHF,HTN,CKD,DM etc...??)
b)	data on history of substance use(alcohol or tobacco use vs adherence??)
c)	drug related factors (data on concurrently used medications, type of regimen used, if any(drug-drug interaction, ADR etc..??)
d)    duration of illness vs adherence ?????
e)    length of ART use  (in years) vs adherence ?????
f)     Hx of hospitalization while on treatment ???
g)  health care system related factors (drug availability, counseling service, care provider ????etc...)
h) research question should be clearly stated
Otherwise,the study is legible, of current government and community concern and has clearly forwarded recommendations.
Finally, I appreciate the  authors for their effort and commitment and I assuredly tell you that my constructive comments will further enhance the quality of your study. And hence please,go through all my concerns and improve accordingly.
Kind regards!


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: MAGNITUDE OF NON-ADHERENCE TO ANTIRETROVIRAL THERAPY AND ASSOCIATED FACTORS AMONG ADULT PEOPLE LIVING WITH HIV/AIDS IN BENISHANGUL-GUMUZ REGIONAL STATE, ETHIOPIA
Review round: 1
Reviewer: 2

Output:
Basic reporting: No comments
Experimental design: no comments
Validity of the findings: No comments
Additional comments: This manuscript titled "Adherence to antiretroviral therapy among people living with HIV in Benishangul-Gumuz Regional State, Ethiopia" is very well drafted and written. However, there is no novelty in this paper, but maybe it will help in planning future antiviral therapy program in Gumuz Regional State, Ethiopia