Gestational diabetes in women with obesity; an analysis of clinical history and simple clinical/anthropometric measures

Sara L. White; Dharmintra Pasupathy; Shahina Begum; Naveed Sattar; Scott M. Nelson; Paul Seed; Lucilla Poston; on behalf of the UPBEAT consortium

doi:10.1371/journal.pone.0279642

Peer Review History

Original SubmissionJune 27, 2022
26 Aug 2022 Decision Letter - Callam Davidson, Editor PONE-D-22-18267Gestational Diabetes in Women with Obesity; an analysis of Clinical History and Simple Clinical/Anthropometric MeasuresPLOS ONE Dear Dr. White, 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 Oct 09 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. 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Please add the following statement, or similar, to the Methods: \\"This study is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline (S1 Checklist).\\"\\n\\nThe STROBE guideline can be found here: http://www.equator-network.org/reporting-guidelines/strobe/\\n\\nWhen completing the checklist, please use section and paragraph numbers, rather than page numbers."}" style="color: rgb(0, 0, 0); font-size: 10pt; font-family: Arial;"> -->Please ensure that the study is reported according to the STROBE guideline, and include the completed STROBE checklist as Supporting Information. Please add the following statement, or similar, to the Methods: "This study is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline (S1 Checklist)." The STROBE guideline can be found here: http://www.equator-network.org/reporting-guidelines/strobe/ When completing the checklist, please use section and paragraph numbers, rather than page numbers. [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: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 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: Yes ****** 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: Authors analyzed 1117 women with obesity to investigate the association of the development of GDM with clinical risk factors and anthropometric measurements. The results showed that age, previous GDM, systolic blood pressure, second trimester, subscapular skinfold thickness and neck circumference were associated with later development of GDM. 1. Line 79. Women with hypertension were excluded. Please clarify the reason for the exclusion criteria. Will this influence the generalization of results from current study? 2. Line 84. Women were randomized to intervention and control group in the UPBEAT trial. Will different treatments matter in the final results reported in this study? 3. Line 96. Please provide more detail information on the imputation strategy. 4. Line 98. Please provide the definition of outliers here. 5. Line 139. “the factor with the strongest association…. Selected for inclusion.” As the model included more than one variable, please clarify this. 6. Line 160. “measure falling >=4SD from the mean” what if the skewed data? Or any skewed variables in the analysis? Reviewer #2: The authors present the results of a secondary analysis of the UPBEAT interventional trial. This secondary analysis aimed to examine the association of maternal clinical and demographic factors and anthropometric measures, assessed in the early second and third trimester, with the development of GDM. The authors confirmed the association of classic risk factors with the development of GDM and added information on the risk of GDM that is related to certain adiposity indices. The paper is very well presented and importantly, doesn’t over interpret their findings. 1. General : Overall well written but some sentences are long and hard to follow (example introduction line 68-72) 2. Small issue but in the original RCT 1555 were randomized but in this paper (results line 165) it is stated that there were 1554. Typo? 3. As this is a cohort study, I feel that it would be worthwhile mentioning how the RCT cohort was developed and specifically that 6704 (76%) of the eligible women declined participation. Speaks to potential selection bias and generalizability. 4. Table 1: I would suggest adding Upbeat study group assignment as this would be considered a “baseline” characteristic 5. Was there consideration of Bonferroni correction for multiple comparisons? 6. Tables 3 and 4 – the explanation of the meaning of “/” and “`” in the footnote is confusing as a part of one continuous sentence. Please give each symbol its own line. 7. I wonder how the measures of adiposity would be represented in a non obese group. Any data from the literature? This is relevant as SC adiposity and/or visceral adiposity can be increased without leading to a BMI defined obesity. Consider addressing in the discussion as this would provide context for implications in all pregnancies (future research?). 8. The authors appropriately provide information on the correlation of the different adiposity measurements with visceral vs superficial adiposity in the discussion. I wonder whether there should be some explanation of this in the introduction to explain the rationale for the use of the chosen anthropometric measurements in this study. 9. Discussion line 350 – grammar - plural vs singular. ****** 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: Yes: Howard Berger ******** [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/. 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Revision 1
27 Oct 2022 Author Response Dear reviewers and editorial team, Thank you very much for reviewing this manuscript and for the comments provided. Please find our point-by-point response below. Reviewer #1: 1. Line 79. Women with hypertension were excluded. Please clarify the reason for the exclusion criteria. Will this influence the generalization of results from current study? Women with pre-existing hypertension were not randomised to the original study, however no women were excluded if they subsequently developed hypertension during pregnancy, a much more common scenario in this group of women. 2. Line 84. Women were randomized to intervention and control group in the UPBEAT trial. Will different treatments matter in the final results reported in this study? We note that there was no impact of the intervention on the primary outcomes, but cannot completely exclude some effect of the intervention, however we have minimised any impact by adjusting for randomisation arm in any relevant analysis (noted in section 2.4: selection of confounders). 3. Line 96. Please provide more detail information on the imputation strategy. We have added further detail on the imputation strategy into the text as requested (Section 2.1) 4. Line 98. Please provide the definition of outliers here. Thank you – we have now added this detail here. 5. Line 139. “the factor with the strongest association…. Selected for inclusion.” As the model included more than one variable, please clarify this. Thank you for this astute observation. Each variable from the group was tested for its association individually with GDM and the variable with the highest z score selected for inclusion. I have updated the text to reflect this. 6. Line 160. “measure falling >=4SD from the mean” what if the skewed data? Or any skewed variables in the analysis? The only variable noted as significantly skewed was BMI and it was not included in the identification of outliers. Reviewer #2 1. General : Overall well written but some sentences are long and hard to follow (example introduction line 68-72) Thank you. We agree and have simplified the above paragraph. 2. Small issue but in the original RCT 1555 were randomized but in this paper (results line 165) it is stated that there were 1554. Typo? Thank you – I have corrected the text. (This was not actually a typo - the number of women randomised was indeed 1555, however one woman was subsequently excluded from the standard arm as she was recruited concurrently into a different trial as shown in the original trial flow diagram (https://www.thelancet.com/journals/landia/article/PIIS2213-8587(15)00227-2/fulltext#figures – however to avoid confusion, we have corrected to the original total RCT figure). 3. As this is a cohort study, I feel that it would be worthwhile mentioning how the RCT cohort was developed and specifically that 6704 (76%) of the eligible women declined participation. Speaks to potential selection bias and generalizability. Thank you for this suggestion. On balance, although we agree that it does speak to potential selection bias, we feel that this level of numerical detail might be excessive for this manuscript. We have however added a sentence to the limitations section to this effect (L384). 4. Table 1: I would suggest adding Upbeat study group assignment as this would be considered a “baseline” characteristic Thank you – we have added this into Table 1. 5. Was there consideration of Bonferroni correction for multiple comparisons? During the planning stages of this analysis careful consideration was given to the variables that would be tested, and only those felt to be ‘a priori’ associated with GDM, out of a much larger dataset, were chosen for analysis. As a result of this, the team, including the statistician, agreed that Bonferroni correction for multiple comparisons was not necessary. 6. Tables 3 and 4 – the explanation of the meaning of “/” and “`” in the footnote is confusing as a part of one continuous sentence. Please give each symbol its own line. Thank you – this has been rectified. 7. I wonder how the measures of adiposity would be represented in a non obese group. Any data from the literature? This is relevant as SC adiposity and/or visceral adiposity can be increased without leading to a BMI defined obesity. Consider addressing in the discussion as this would provide context for implications in all pregnancies (future research?). Thank you for this observation; there is reference to some measures in normal and weight heterogeneous women in the text (refs 34, 40, 45, 47) however there is room for further exploration and we have added a sentence reflecting this to the discussion. 8. The authors appropriately provide information on the correlation of the different adiposity measurements with visceral vs superficial adiposity in the discussion. I wonder whether there should be some explanation of this in the introduction to explain the rationale for the use of the chosen anthropometric measurements in this study. Thank you – we have added an explanatory phrase in the Section 2.2 maternal clinical factors 9. Discussion line 350 – grammar - plural vs singular. Thank you – rectified. In response to your prompt with regards to data sharing, we recommend the following text: “Due to the limitations of the consent provided by the patients in our study, and restrictions imposed by our funders we cannot make the data generally available. The UPBEAT Scientific Advisory Committee accept applications for use of data from those who make a formal request, providing a description of the intended study on a research application form (UPBEAT RAF) available from Glen Nishku (glen.nishku@gstt.nhs.uk). Providing the proposed studies do not conflict with consent, the data will be freely available.” With regards to Point 4 regarding a data repository, as explained in the data sharing paragraph above the data will only be available on request. Finally, here is our updated competing interests statement: “SLW, DP, SB, SMN, PS and LP none. I have read the journal's policy and NS has consulted for Abbott Diagnostics, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Novo Nordisk, Pfizer, and Sanofi and his University has received funding from grants from Astrazeneca, Boehringer Ingelheim, Roche diagnostics. This does not alter our adherence to PLOS ONE policies on sharing data and materials.” With best wishes and thank you very much for your patience, Dr Sara L White MRCP MSc FRCPath EuSpLM PhD Clinician Scientist and Maternal Diabetes Clinical Research Lead, Department of Women and Children’s Health, King’s College London Honorary Consultant in Metabolic Medicine (Clinical Biochemistry), Guy’s and St Thomas’ NHS Foundation Trust https://doi.org/10.1371/journal.pone.0279642.r002
14 Nov 2022 Decision Letter - Stephen L Atkin, Editor PONE-D-22-18267R1Gestational Diabetes in Women with Obesity; an analysis of Clinical History and Simple Clinical/Anthropometric MeasuresPLOS ONE Dear Dr. White, 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. ==============================The comments of reviewer 1 have been satisfied but reviewer 2 has raised queries that need to be addressed including modification of your overall conclusion and addressing the Strobe requirements ============================== Please submit your revised manuscript by Dec 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, Stephen L Atkin, MD Academic Editor PLOS ONE [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 #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: Yes Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: I Don't Know ****** 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: 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 #1: (No Response) 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: (No Response) Reviewer #2: I would like to thank the authors for their thoughtful revisions in response to the reviewers’ comments. A few residual comments, questions: 1. Abstract : conclusions. I just am not sure how “modifiable” the identified risk factors are. Age is not modifiable and blood pressure is possibly a marker of GDM risk but not a causative factor. Furthermore, I am not aware of any methods of modifying subscapular adiposity and neck thickness and whether these are again just indicators of baseline increased insulin resistance. I suggest modifying the conclusions in the abstract so that they are more in keeping with the correctly worded (in my opinion) conclusions in the discussion. 2. Methods, Page 5, line 108: Not sure what 27+8 weeks means. Is it 28+1? 3. If the GTT was performed at gestational ages beyond the accepted window of 24-28 weeks of gestation (as mentioned in the methods line 106-108) then I suggest adding the GA at GTT as a demographic variable in Table 1. If there is a difference in mean GA at GTT between GDM and non GDM then this variable would need to be added to the logistic regression models. 4. Thank you for your explanation regarding the reasoning behind not presenting the base population from which the cohort was derived which is actually the base population that created the UPBEAT trial study population. I still think that if adhering to the STROBE guidelines (as indicated by the authors) one needs to present the results starting with a figure showing the cohort development, starting with the 8820 women screened for UPBEAT. I will leave it to the editor to decide whether this is correct. ****** 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.] 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. https://doi.org/10.1371/journal.pone.0279642.r003
Revision 2
15 Nov 2022 Author Response Dear Professor Atkin, Thank you very much for reviewing our updated manuscript and for the comments provided. Please find our point-by-point response below. Reviewer #2: 1. Abstract : conclusions. I just am not sure how “modifiable” the identified risk factors are. Age is not modifiable and blood pressure is possibly a marker of GDM risk but not a causative factor. Furthermore, I am not aware of any methods of modifying subscapular adiposity and neck thickness and whether these are again just indicators of baseline increased insulin resistance. I suggest modifying the conclusions in the abstract so that they are more in keeping with the correctly worded (in my opinion) conclusions in the discussion. Thank you for identifying this ambiguity in the abstract – we have now updated the abstract to reflect the discussion conclusion more closely. 2. Methods, Page 5, line 108: Not sure what 27+8 weeks means. Is it 28+1? Apologies, this was an error – it should have read 27+5, now corrected. 3. If the GTT was performed at gestational ages beyond the accepted window of 24-28 weeks of gestation (as mentioned in the methods line 106-108) then I suggest adding the GA at GTT as a demographic variable in Table 1. If there is a difference in mean GA at GTT between GDM and non GDM then this variable would need to be added to the logistic regression models. Gestational age at visit 2 (OGTT) is included in Table 3 as the timepoint of these data measures; it does not differ between GDM and non GDM groups. We have added a note to this variable in Table 3 to improve clarity. 4. Thank you for your explanation regarding the reasoning behind not presenting the base population from which the cohort was derived which is actually the base population that created the UPBEAT trial study population. I still think that if adhering to the STROBE guidelines (as indicated by the authors) one needs to present the results starting with a figure showing the cohort development, starting with the 8820 women screened for UPBEAT. I will leave it to the editor to decide whether this is correct. We appreciate your request and have added a phrase into the Study Design noting the total number of women approached for inclusion. Editor comment: The comments of reviewer 1 have been satisfied but reviewer 2 has raised queries that need to be addressed including modification of your overall conclusion and addressing the Strobe requirements We hope that we have now responded adequately to these queries. With best wishes and thank you once again for considering our manuscript, Dr Sara L White MRCP MSc FRCPath EuSpLM PhD https://doi.org/10.1371/journal.pone.0279642.r004
12 Dec 2022 Decision Letter - Stephen L Atkin, Editor Gestational Diabetes in Women with Obesity; an analysis of Clinical History and Simple Clinical/Anthropometric Measures PONE-D-22-18267R2 Dear Dr. White, 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, Stephen L Atkin, MD 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 #2: 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 #2: (No Response) ****** 3. Has the statistical analysis been performed appropriately and rigorously? 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 #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 #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 #2: (No Response) ****** 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 #2: No ******** https://doi.org/10.1371/journal.pone.0279642.r005
Formally Accepted
21 Dec 2022 Acceptance Letter - Stephen L Atkin, Editor PONE-D-22-18267R2 Gestational diabetes in women with obesity; an analysis of clinical history and simple clinical/anthropometric measures Dear Dr. White: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Stephen L Atkin Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0279642.r006

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