PONE-D-26-19334 Outcomes of Damage Control Laparotomy After Trauma in Low and Middle-Income Countries: A Systematic Review and Meta-Analysis PLOS One

Dear Dr. MAKHADI,

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.

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Academic Editor

PLOS One

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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: Partly

Reviewer #2: No

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

Reviewer #1: No

Reviewer #2: No

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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: No

Reviewer #2: No

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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

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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: This study presents a systematic review and meta-analysis evaluating outcomes of damage control laparotomy in low- and middle-income countries (LMICs). Given the relatively high burden of severe trauma in LMICs and the limited availability of consolidated data, this work addresses an important gap in the literature. It also offers a potentially useful basis for future benchmarking and quality improvement efforts, as well as for exploring differences in outcomes between LMICs and high-income countries (HICs).

However, there are several methodological and interpretative aspects that may benefit from further clarification and refinement. In particular, the use of proportional meta-analysis in this context may have inherent limitations, given the substantial clinical and methodological heterogeneity across studies and the lack of adjustment for case-mix differences. As a result, the pooled mortality estimate may be difficult to interpret as a clinically representative summary measure and may warrant more cautious framing. Clarifying these points may also help strengthen the sections on clinical implications and conclusions.

[Methods]

� The manuscript states that MeSH terms and free-text keywords were used; however, the full search strategy is not presented. Providing the detailed search strings would improve transparency and reproducibility.

� It would be helpful to specify which version (year) of the World Bank classification was used.

� The definition of “damage control laparotomy or equivalent staged abdominal surgery” appears somewhat broad. Given its importance to the study, additional clarification on how this was defined and applied during study selection would strengthen the methodology.

� Restricting inclusion to English-language studies may limit generalizability, particularly in the context of LMIC research, and could be briefly discussed as a potential limitation.

� As many included studies are single-arm, further clarification on how the “comparability” domain of the risk-of-bias assessment was interpreted in this context would be helpful.

� Trauma mortality is strongly influenced by anatomical and physiological severity. Because proportional meta-analysis does not allow for case-mix adjustment, the pooled estimates may reflect differences in patient severity as much as differences in health-system factors.

� Given the likely heterogeneity in case mix, resources, and clinical settings across studies, reliance on I² alone may not fully capture the extent of variability. The inclusion of a prediction interval, in addition to confidence intervals, could provide a more clinically informative representation of expected variability across LMIC settings.

� The rationale for the chosen subgroup analyses could be elaborated further. For example, consideration of clinically relevant factors such as blunt versus penetrating trauma might provide additional insight.

[Results]

� In light of the heterogeneity across studies, the pooled mortality estimate may be better interpreted as an average rather than a representative value. Reporting a prediction interval could help contextualize this variability.

� The comparison with HIC outcomes appears to rely on a limited number of studies. If available, referencing broader evidence (e.g., systematic reviews from HIC settings) could strengthen this comparison.

� The variability in mortality definitions (e.g., in-hospital vs. 30-day) may affect the comparability of results and could be more explicitly acknowledged.

� Complication estimates appear to be largely derived from a single study, which may limit generalizability.

� The interpretation of subgroup differences, particularly in relation to infrastructure, is interesting but may benefit from more cautious wording, as formal interaction testing was not performed.

[Discussion]

� The suggestion that the mortality gap is primarily driven by health-system factors is clinically plausible; however, it may be helpful to acknowledge that this study design does not allow for direct evaluation of these factors, particularly given the lack of case-mix adjustment.

� The absence of statistical heterogeneity (I² = 0%) in the South African subgroup could be interpreted with caution, especially considering the relatively small number of studies and the observed range in mortality rates.

� Expanding the limitations section to explicitly address the lack of case-mix adjustment would strengthen the interpretation.

� As the dataset is heavily weighted toward South African studies, a more explicit discussion of generalizability to other LMIC settings would be valuable.

[Conclusions]

� The attribution of the mortality gap to specific health-system factors is not supported by the present analysis and appears speculative.

� Complication data are derived almost entirely from a single centre, and therefore statements regarding surgical technique represent an overinterpretation.

Reviewer #2: Reviewer comments

Thank you for giving me the opportunity to review this manuscript.

This study addresses an important topic, because trauma care in low- and middle-income countries is a major global issue. However, I have several concerns about the scientific validity and interpretation of the current manuscript.

Major comments

1. The main concern is that the authors pooled very different countries and hospitals together as “LMICs”. The included studies are from South Africa, Pakistan, India, Oman, and Brazil. However, trauma systems, hospital resources, blood bank systems, ICU capacity, prehospital care, and surgical systems are likely very different among these settings. Also, South African studies account for most of the patients. Therefore, I am not sure that the pooled mortality can represent “LMIC outcomes” in general. The authors should more clearly state that the result is a crude summary of available published studies, not a representative estimate of all LMIC settings.

2. I understand that patient-level adjustment may not be feasible in an aggregate-data systematic review. However, the current analysis is based on crude mortality rates. Important differences in injury severity, shock status, mechanism of injury, timing to hospital, timing to operation, indication for DCL, transfusion, and ICU availability may strongly influence mortality. A random-effects model can handle statistical heterogeneity, but it cannot adjust for these patient-level or hospital-level differences. Therefore, the pooled mortality should be interpreted as descriptive.

3. The conclusion is too strong. The authors state that higher mortality is mainly due to modifiable health-system factors such as prehospital delay, limited blood products, ICU capacity, and delayed access to theatre. This explanation is possible, but these factors were not systematically measured or compared in the included studies. Therefore, this conclusion is not directly supported by the presented data. It should be described only as a possible explanation or hypothesis.

4. There are numerical inconsistencies. The pooled mortality and I² values are not consistent between the text/Table 2 and Figure 2 legend. The authors should re-check all mortality numbers, denominators, figures, and tables carefully.

5. The inclusion of Oman needs clarification, because the manuscript states that Oman is a high-income country. If the study focuses on LMICs, the inclusion of Oman should be justified more clearly, or a sensitivity analysis excluding Oman should be performed.

Minor comments

1. Please provide the exact search strategy for each database, preferably as supplementary material.

2. Please clarify how duplicate patient populations were identified and excluded.

3. Please clarify how different mortality definitions were handled, because some studies may report in-hospital mortality, 30-day mortality, or unspecified mortality.

4. The complication outcomes are based on limited data. Therefore, SSI, entero-atmospheric fistula, and other complications should be described more cautiously.

5. The interpretation of the funnel plot should be more cautious. With only ten studies and large clinical heterogeneity, Egger’s test has limited meaning. The authors should avoid interpreting a non-significant Egger’s test as evidence of no publication bias.

Overall assessment

Overall, this manuscript has an important topic, but the current analysis is mainly a crude summary of heterogeneous retrospective studies. I think the conclusions are too strong for the available data. Major revision and substantial reframing are necessary before this manuscript can be considered for publication.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-26-19334R1 Outcomes of Damage Control Laparotomy After Trauma in Low and Middle-Income Countries: A Systematic Review and Meta-Analysis PLOS One

Dear Dr. MAKHADI,

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.

Please submit your revised manuscript by Jul 03 2026 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 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.

As the corresponding author, your ORCID iD is verified in the submission system and will appear in the published article. PLOS supports the use of ORCID, and we encourage all coauthors to register for an ORCID iD and use it as well. Please encourage your coauthors to verify their ORCID iD within the submission system before final acceptance, as unverified ORCID iDs will not appear in the published article. Only the individual author can complete the verification step; PLOS staff cannot verify ORCID iDs on behalf of authors.

We look forward to receiving your revised manuscript.

Kind regards,

Ryo Yamamoto

Academic Editor

PLOS One

Journal Requirements:

If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

Additional Editor Comments:

Thank you for revising the manuscript following reviewers' comments.

Whle the great improvement is noted, the reviewers' still have several concerns in your manuscript.

Please see the comments carefully and revise the manuscript precisely again following them.

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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: (No Response)

Reviewer #2: (No Response)

**********

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: Partly

Reviewer #2: No

**********

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

Reviewer #1: Yes

Reviewer #2: No

**********

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 #2: No

**********

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 #2: 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 addressed most of the concerns in the revised manuscript; however, responses to several points were not clearly apparent.

This systematic review primarily synthesises mortality rates in LMIC settings rather than providing a direct comparative analysis. In this context, the applicability of the comparability domain of the Newcastle-Ottawa Scale may be limited. While the use of the Newcastle-Ottawa Scale contributes to the overall assessment of study quality, it would be helpful to explicitly acknowledge this limitation in the manuscript.

The heterogeneity in the definition of “damage control laparotomy or equivalent staged abdominal surgery” may represent a limitation, given the lack of a clear and standardised definition.

Restricting inclusion to English-language studies may limit generalisability, particularly in the context of LMIC research, and could be briefly discussed as a potential limitation.

Reviewer #2: Reviewer comments

Thank you for the opportunity to review the revised manuscript.

The authors have substantially improved the manuscript. They have better acknowledged the crude nature of the pooled estimate, the lack of case-mix adjustment, the predominance of South African studies, and the need for cautious interpretation. The addition of the prediction interval is also helpful.

However, I still have several concerns that should be addressed before the manuscript can be considered for acceptance.

Major comments

1. Numerical inconsistency remains.

In the revised Table 1, the total number of deaths appears to be 327. However, the Results section states that the pooled analysis was based on 331 deaths among 914 patients. The authors should reconcile this discrepancy and ensure that the extracted mortality data, text, tables, figures, and figure legends are fully consistent.

2. Injury mechanism should be presented in Table 1.

The previous version included mechanism of injury, such as GSW, penetrating, mixed, or blunt trauma, but this column appears to have been removed in the revised Table 1. In the revised Methods, the authors state that injury mechanism was extracted. Because differences between blunt and penetrating trauma may strongly influence mortality, DCL indication, and between-study heterogeneity, this information is essential for interpreting the pooled crude mortality. At minimum, each study should be classified as blunt-dominant, penetrating-dominant, mixed, or not reported.

3. The comparison with HIC benchmarks should remain very cautious.

The manuscript compares the pooled crude mortality from LMIC studies with selected HIC benchmark series. However, these HIC studies were not identified through the same systematic review process, and no formal LMIC-versus-HIC comparative meta-analysis was performed. Therefore, the manuscript should not be framed as demonstrating that DCL mortality is higher in LMICs than in HICs. It would be more appropriate to state that published LMIC studies show substantial crude mortality, which appears numerically higher than selected HIC benchmarks.

4. The subgroup comparison should be clarified.

The Results section states that the approximately 20-percentage-point difference between South African and non–South African studies was statistically significant. If this statement is retained, the authors should report the statistical test used for subgroup differences and its p value. Otherwise, this wording should be changed to a descriptive statement.

5. Oman classification still needs to be completely clear.

The authors now define LMICs according to the World Bank classification. However, because Oman was a point of concern in the previous review, the manuscript should clearly explain why Oman was eligible according to the classification year used. If there is any uncertainty, a sensitivity analysis excluding Oman would be useful.

Minor comments

1. Please clarify more specifically how duplicate or overlapping patient populations were identified and excluded.

2. Mortality timeframes differed across studies. The authors now mention this limitation, but a table indicating the mortality definition for each study would improve transparency.

3. The complication outcomes are based on limited and inconsistently reported data. The interpretation of SSI, entero-atmospheric fistula, and other complications should remain descriptive.

4. In Figure 3, the “other LMICs” subgroup should be more clearly labelled. Since this subgroup includes only four studies from Pakistan, India, Oman, and Brazil, the authors should list these countries either in the figure label or in the figure legend. This would help readers understand that this subgroup is not a broad representation of all non–South African LMIC settings.

5. Figure 4 would be more informative if the study points were labelled by country or study name, or at least distinguished by subgroup such as South Africa versus non–South African LMICs. Funnel plot asymmetry in this review may reflect geographic and clinical heterogeneity rather than publication bias alone.

6. Please standardize decimal places across the manuscript, tables, and figures. For example, mortality percentages are sometimes reported to two decimal places and sometimes to one decimal place. One decimal place may be sufficient for most percentages.

7. Please carefully check the manuscript for any remaining old wording or inconsistent phrasing, especially in the Discussion and Conclusions.

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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 #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.]

To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures

You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation.

NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

<div>PONE-D-26-19334R2 Outcomes of Damage Control Laparotomy After Trauma in Low and Middle-Income Countries: A Systematic Review and Meta-Analysis PLOS One

Dear Dr. MAKHADI,

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.

Please submit your revised manuscript by Jul 16 2026 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 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.

As the corresponding author, your ORCID iD is verified in the submission system and will appear in the published article. PLOS supports the use of ORCID, and we encourage all coauthors to register for an ORCID iD and use it as well. Please encourage your coauthors to verify their ORCID iD within the submission system before final acceptance, as unverified ORCID iDs will not appear in the published article. Only the individual author can complete the verification step; PLOS staff cannot verify ORCID iDs on behalf of authors.

We look forward to receiving your revised manuscript.

Kind regards,

Ryo Yamamoto

Academic Editor

PLOS One

Journal Requirements:

If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

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.

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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 #2: (No Response)

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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: (No Response)

Reviewer #2: (No Response)

**********

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

Reviewer #1: (No Response)

Reviewer #2: (No Response)

**********

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: (No Response)

Reviewer #2: (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: (No Response)

Reviewer #2: (No Response)

**********

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: (No Response)

Reviewer #2: Thank you for the opportunity to review the revised manuscript.

The manuscript has improved, and most of my previous concerns have been addressed. I have only a few remaining comments before acceptance.

I have only a few remaining comments before acceptance.

1.The estimates reported in the Figure 2 legend should be made consistent with the Abstract and Results section. The Abstract and Results report an overall pooled mortality of 37.77% with a 95% CI of 31.38%–44.62% and a 95% prediction interval of 20.1%–59.1%. However, the Figure 2 legend reports different confidence and prediction intervals. Please correct the Figure 2 legend so that all reported values are consistent throughout the manuscript.

2.The estimates reported in the Figure 3 legend should also be made consistent with the Results section. In the Results section, the South African subgroup is reported as 31.61% with a 95% CI of 28.27%–35.15%, and the non–South African LMIC subgroup is reported as 53.62% with a 95% CI of 44.47%–62.54% and I² = 31.65%. However, the Figure 3 legend reports different values. Please revise the Figure 3 legend accordingly.

3.Figure 4 itself appears to have been improved with study labels and subgroup markers. However, the figure legend should also clearly explain the symbols used for South African studies and other LMIC studies, and should be consistent with the actual markers shown in the figure.

Overall, the manuscript is close to acceptable. I recommend minor revision to correct the remaining figure-legend and numerical consistency issues.

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Reviewer #1: No

Reviewer #2: No

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Outcomes of Damage Control Laparotomy After Trauma in Low and Middle-Income Countries: A Systematic Review and Meta-Analysis

PONE-D-26-19334R3

Dear Dr. MAKHADI,

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.

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PLOS One

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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 #2: All comments have been addressed

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Reviewer #2: Yes

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Reviewer #2: N/A

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Reviewer #2: Yes

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Reviewer #2: Yes

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Reviewer #2: The authors have addressed my previous comments. I have no further concerns.

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Reviewer #2: No

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