PONE-D-21-20741Anxiety and depression in Guatemala: sociodemographic characteristics and service accessPLOS ONE

Dear Dr. Naber,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

ACADEMIC EDITOR: This is an interesting paper and is potentially a very useful addition to the literature. But need to address some critical points as reviewers pointed out.==============================

Please submit your revised manuscript by Nov 15 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Seo Ah Hong, PhD

Academic Editor

PLOS ONE

Journal requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf.

2. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match.

When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section.

3. Thank you for stating the following in the Acknowledgments Section of your manuscript:

“CONADI, CBM, and UNICEF for financing this study.”

We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

“The Guatemala survey was funded by CBM Latin America and CONADI (the National Council on Disability), in a grant to Dr. Sarah Polack. No specific funding was received for these analyses of the data.”

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

4. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability.

Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized.

Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access.

We will update your Data Availability statement to reflect the information you provide in your cover letter.

5.We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For more information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

6. We note that you have included the phrase “data not shown” in your manuscript. Unfortunately, this does not meet our data sharing requirements. PLOS does not permit references to inaccessible data. We require that authors provide all relevant data within the paper, Supporting Information files, or in an acceptable, public repository. Please add a citation to support this phrase or upload the data that corresponds with these findings to a stable repository (such as Figshare or Dryad) and provide and URLs, DOIs, or accession numbers that may be used to access these data. Or, if the data are not a core part of the research being presented in your study, we ask that you remove the phrase that refers to these data.

7. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section.

Additional Editor Comments (if provided):

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: No

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: No

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: General comments:

This article contribute to the lack of epidemiological data on mental health disorders in Guatemala. Studies like this are crucial to improve people’s life through the needed policy changes at the regional and national level.

It is important to notice that the data collection took place in 2016, reducing is validity and direct implications. However, there is a high need of mental health data from Guatemala and other neighboring countries that make the study significant.

Another major concern is the assessment selected. Even though it is promising, The Washington Group extended set on functioning (WG-ES) is s recent tool. I recommend a more extended description of the tool and justification of its use. Also to include any available data on psychometric characteristics of the survey along with validity and comparison with other more commonly used assessments of mental health disorders.

The discussion does not go deep on the inconsistent findings. More reflection and potential hypothesis should be presented to better discuss the interesting results.

Specific Comments:

Introduction:

Page 4: While this study generated important data for Guatemala, it only included adults between the ages of 18 and 65, effectively excluding a large part of the population.4

Population from 18-65 does not exclude a large part of the general population. Please be more accurate with the statements. Maybe you can say excluding older adults which represent and children X % of the population.

Methods:

Page 6: Self-reported functional difficulties

This is a very vague term. Is this the formal term used by the questionnaire? If so, please explain. Starting the case definition with this term reduces the article credibility.

Page 7: Variables description.

More information about the variables is needed. From the main outcomes to the covariates. What combined depression and anxiety means? Explain outcome variables and scoring in detail to increase test validity (and author’s credibility). It would be useful to have more information about the survey questions. For example, number of items, examples of questions related to access to health services or livelihood, ect. More information about the variables is needed.

Page 8: The WG instrument was translated into the four leading non-Spanish languages of Guatemala - K’iche’, Kaqchikel, Mam, and Q’eqchi’.

Was this translation process similar to the English to Spanish or was it translated directly from the Spanish translation? Did you calculate internal validity of the tool in the different languages? Any information about its psychometric characteristics would be useful.

Page 8: Two weeks of mop-up were conducted at the end of the survey in clusters with low response rates or incomplete data, primarily in the Central and Northwest regions.

In what this consisted. I guess that if you mention it is because it is enough important to be better explained. Please provide further details.

Results:

The age distribution is very limited. The sample is not evenly distributed at all after all the sampling described in the methods. From the 13073 total sample, only 2035 are above 50 years old. Is it representative of the Guatemaltecan population (15% of people are >50).

Page 14: However, of 385 cases with impaired affect, only 25 (6%) had received medication for depression or anxiety in the past 12 months.

My recommendation is to avoid any judgement in the results section and leave them for the discussion.

Discussion:

Page 19: There is an increased need for mental health services targeting the 50+ segment of the population.

What percentage of the total population it represents? What kind of disorders they may be facing. What are the implications or future studies related ot that?

In general, results could be compared with other similar studies/surveys from neighboring countries or at least other Latino countries.

Page 20: it also found that literacy was not significantly associated with impaired affect. However, ENSM found that people who ‘’Know how to read and write’’ had a higher likelihood of affective and anxiety disorders.4 This disagreement calls for further research on the relationship between low literacy and impaired affect, considering a review by Maughan et al. which found some co-occurrence of reading failure with anxiety and depression.24

It would be interesting to know, if available, how many people had a low literacy level from the survey and how the informed consent was done on those cases. If you have this data, it would be useful in order to increase the information about the results.

Page 20: We found no significant association between ethnic group and impaired affect in this study. This was unexpected given that ENSM found greatly-increased odds of having depression or post-traumatic stress disorder (PTSD) in indigenous people who had been exposed to violence when compared to non-indigeous people who had also been exposed to violence.27 Another study, however, found that “socioeconomic and health-related variables” greatly confounded the relationship between ethnic group and impaired affect.25,28 We found no association between SES and impaired affect in this study. This was surprising given the expanding evidence on the inverse relationship between SES and depression.29 Further research on ethnicity and socioeconomic status is needed to clarify these unexpected results.

These are indeed very odd results. Please expand on potential explanations and what the literature from other countries says on this respect as it questions the validity of the study (test validity). For example, is there any literature about resilient factors among indigenous population that may explain that 9 years later this subgroup is doing better? At least, you should mention the limitation of the lack of use of this survey and culturally adapted tools for these subgroups as this might be the reason for not finding any differences.

Page 21: Community health workers staffing these posts should be trained and equipped to provide mental health services in addition to physical health services to address their co-occurrence.

If the authors decide to recommend interventions, more justifications and detail should be provided. This sentence should at least be referenced. See “Alegría M, et al. Effectiveness of a Disability Preventive Intervention for Minority and Immigrant Elders: The Positive Minds-Strong Bodies Randomized Clinical Trial. Am J Geriatr Psychiatry. 2019 Dec;27(12):1299-1313. doi: 10.1016/j.jagp.2019.08.008. Epub 2019 Aug 13. PMID: 31494015; PMCID: PMC6842701.” For a useful reference.

Page 21: or from ‘.... cultural differences in interpretation of the tools….’

I don’t understand what this sentence means in the middle of the discussion. Is this a qualitative quote from an investigator? This sentence lacks scientific rigor. Please review and correct for accuracy and add references to discuss this important aspect of the study. This is the most important limitation.

Page 22: Conclusions

Some indication to the policy level needed changes should be included here. How these results can serve the policy makers to improve the quality of life and services among people with impaired affect?

Reviewer #2: General comments

The study deals with a relevant topic and is based on national epidemiological data. However, there are several issues that are unclear and make it difficult to understand the theoretical framework, methods, results and conclusions.

The term “impaired affect” is inadequate to designate people with anxiety and depressive symptoms. This issue is central to the study, as the authors assume this concept, including the terms anxiety and depression in the title, when in fact there is no formal assessment of these symptoms/disorders.

Specific comments

Introduction:

The correct name of the instrument used (CIDI) is not Compact International Diagnostic Interview, but Composite International Diagnostic Interview.

The entire theoretical framework of the study is based on the lack of studies/epidemiological data on mental health in Guatemala. The authors review these studies and describe the prevalence of mental disorders, showing that anxiety/somatoform and mood disorders are the most prevalent. However, there is no description of studies that have evaluated impaired affect and we cannot infer that these can be automatically translated into anxiety and mood disorders.

Thus, there is an important gap in the theoretical framework, which does not allow us to support the assertion that “The substantial gap in mental health spending and treatment in Guatemala suggests that people with impaired affect may face heightened burdens compared to people with other disabilities or with no disabilities.”

Methods

Case definition

The instrument/questionnaire used to define the case should be described in greater detail. How was this questionnaire constructed? It would be important to include references to the instrument.

The authors describe that both anxiety and depression were assessed using two questions, which included frequency (daily and a lot) for their classification. It would be important for the authors to provide references for the criteria adopted for the definition of impaired affect considering these questions. Which studies have used these criteria?

Returning to the question raised above, the definition of impaired affect, based on direct questions about feelings of anxiety, nervousness, worry and depression, and the frequency of such feelings, seems inadequate to me.

The study does not describe how exposure variables were measured.

Another methodological problem lies in the fact that there is no time definition for the onset of symptoms that led to the case definition. So how do we know about the exposure window for cases and controls? It would be correct to make a pairing of cases and controls, so that the onset date of the symptoms that classify the cases was taken to the time of exposure to the exposure variables also for the controls. In the current, nested case-control format, we have no way of knowing the temporality between a series of evaluated exposures and the outcome under study, such as marital status (for example, which came first, separation/divorce or mental disorder?), or even other variables. Such a format can lead to important biases.

Other important points:

The description of the study design (nested case-control) is insufficient. Include more details on eligibility criteria, etc. Were all non-cases included in the study?

The inclusion of children – how was data collection conducted? There is no indication whether there has been an adaptation of the instrument, or whether it is suitable for children aged 5 years and over. Has any kind of assessment been made of the validity of questions about anxiety and depression symptoms for such young children? There is a straightforward question about depression. How does a child interpret this?

My suggestion is that the study only includes people aged 18 and over.

Results

The format for presenting the results is confusing. “Impaired affect” is the outcome under study; therefore, the tables should present the prevalence of the outcome according to the categories of the exposure variables. What the tables show is the frequency of exposures according to the outcomes, which is not adequate to meet the proposed objectives.

The results should include the crude and adjusted odds ratios.

Discussion

The study has limitations that have been insufficiently discussed, namely:

Diagnostic criteria for defining anxiety/depression:

The fact that WG-ES is based on self-report is an important limitation, but not the main one. In the case of the present study, not determining the onset of symptoms leads to problems that can lead to biases in the estimates found:

Temporality – there is no guarantee that some exposures occurred before the outcome.

Exposure windows for cases and controls may be different. If there was information about the date of onset of symptoms, there would be a possibility of pairing cases and controls, considering the exposure time in the paired control to be the same as in the case.

The comparison with the results found in other studies does not consider differences in these criteria, which can lead to differences in the prevalence of the outcomes under study.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-21-20741R1Anxiety and depression in Guatemala: sociodemographic characteristics and service accessPLOS ONE

Dear Dr. Naber,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Thanks for the revision.

A reviewer requests to revise a few minor issues so please address them. And a few minor things should be corrected as follows.

1. Revise from “Cases (indicating ‘A lot’ or ‘Cannot do’ in 1+ functional domain) and age-/sex-matched controls were administered a structured questionnaire” to “Cases (indicating ‘A lot of difficulty’ or ‘Cannot do’ in one or more functional domain) and age-/sex-matched controls were administered a structured questionnaire. “ in the Abstract. (Page 2, Line 16)

2. Delete “(WG-ES)” and “(CFM)” in the sentences “The WG ES was developed, tested and adopted by the Washington Group on Disability Statistics (WG-ES)” and “The CFM was developed and tested by the WG together with UNICEF (CFM).” (Page 6, Line 101-2)

3. “We found no significant association between ethnic group and impaired affect in this study.” And additional 5-6 places having the term in the text.

=>correct “impaired affect” into “anxiety and/or depression”

4. Correct from “with/out” to “without” (Page 10, Line 176)

Please submit your revised manuscript by Jul 29 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Seo Ah Hong, PhD

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #3: (No Response)

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have responded to all my specific comments. The article has improved after the revision and the topic is significant enough to be published at PLOS ONE

Reviewer #3: Excellently written article. Case control design and analysis are well designed and systematically carried out.

Tables are very clear.

Discussion refers to the references and findings.

Minor point: What is the reason to include 5-17 group? (Table3) The sample description in the table 2 showed 0-14 groups.

If authors are serious to add these age group, I think the logic to include them should be discussed.

Otherwise comparing children and old age may not make sense.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #3: Yes: Myo Nyein Aung

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Anxiety and depression in Guatemala: sociodemographic characteristics and service access

PONE-D-21-20741R2

Dear Dr. Naber,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Seo Ah Hong, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #3: I found that the authors have addressed the reviewers' comment and revised the article as much as they can improve.

It is acceptable in current situation to be published.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #3: Yes: Myo Nyein Aung

**********