Understanding the relationships between 24-hour movement behavior, community mobility and the neighborhood built environment for healthy aging in Brazil: The EpiMove study protocol

Viviane Nogueira de Zorzi; Janio Carlos Pessanha Coelho; Carla Elane Silva dos Santos; Joel de Almeida Siqueira Junior; Daniel Alexander Scheller; Eleonora d ‘Orsi; Cassiano Ricardo Rech

doi:10.1371/journal.pone.0315021

Peer Review History

Original SubmissionSeptember 17, 2024
9 Oct 2024 Decision Letter - Zulkarnain Jaafar, Editor PONE-D-24-37986Understanding the relationships among 24-hour movement behavior, active commuting and the neighborhood built environment for healthy aging in Brazil: The EpiMove Study protocolPLOS ONE Dear Dr. Zorzi, 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: Dear Author, please attend to all the comments provided by the reviewers and make necessary corrections. ============================== Please submit your revised manuscript by Nov 23 2024 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. 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Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions? The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses? The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory. Reviewer #1: Yes Reviewer #2: Yes ****** 3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable? Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors described where all data underlying the findings will be made available when the study is complete? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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 ****** 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: No ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics. You may also provide optional suggestions and comments to authors that they might find helpful in planning their study. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: TO THE AUTHORS Title: I recommend changing the title for grammatical clarity from “the relationships among...” to “the relationships between...”. Background: • It is unclear why commuting is being quantified in a population aged 60+. Many participants may be retired or close to retirement, making commuting less relevant. If you meant mobility within the local community, please rephrase both the relevant sentences in the manuscript and the study title. • Line 34: The statement is unclear. What is the projected 12% meant to indicate? • Line 43: Physical activity advice now emphasizes that "any amount of physical activity is important," rather than just 150 minutes per week. Please refer to the UK Chief Medical Officers' recommendations for older adults, particularly based on the study by Onambele-Pearson et al. (2019) (Front Physiol 2019;10:408). Methods • Line 104: An HDI of 0.847 (Very High Human Development) is significantly greater than 0.760 (High Human Development). Although the difference seems small (0.087), the HDI scale is sensitive, indicating meaningful disparities in quality of life, healthcare access, and overall well-being. This could affect the generalizability of your results, which should be highlighted in your reports. • Line 105: The Gini index of 0.450 suggests notable income inequality in your region of study. Ensure broad recruitment across socio-economic strata to maintain the representativeness of your sample. • Line 125: It would be helpful to include statistics on the percentage of the older population in your region living in long-term care institutions, hospitals, or prisons. • Lines 132-133: Please provide a brief explanation of your sample size justification. • Line 142: Five attempts to contact participants at Phase 1 (plus six in Phase 2, Line 202) seems excessive and may create undue pressure. Could this be considered borderline harassment? To mitigate this: o A) Specify how contact attempts will be spaced out (e.g., days/weeks between attempts). o B) Have participants previously agreed to multiple contact attempts? o C) Consider reducing in-person visits (3 seems intrusive); a mix of phone, email, and one in-person visit may be less burdensome. o D) Ensure that participants fully understand why they are being contacted and what their participation involves. • Lines 145-148: Ethical best practices recommend providing clear study information in advance, giving participants time to review it, and allowing them to ask questions before consenting. Immediate consent, especially in their homes, may create discomfort and pressure. This is not reflected in your current approach, which raises concerns. • Lines 175-189: The rationale for using the IPAQ is unclear when: o a) Accelerometers will provide more reliable physical activity data. o b) The IPAQ adds to participant burden by extending the interview. o c) The IPAQ does not effectively capture sedentary behaviour, which is a key aspect of the physical activity spectrum (Ryan et al., PLoS One 2018;13). I recommend reconsidering the use of the IPAQ. • Line 193: Please specify the time or distance for the walking ability test (e.g., walk for 2 minutes? Walk 30 meters?). • Lines 249-254: Provide details on the origin of the cut-off values, including whether they were calibrated in a similar population. Reviewer #2: The explanation of the research in the introduction is quite weak and does not adequately explain the characteristics and reasons for acquiring them. Need more references for citing in the discussion. The text contains many grammatical errors. Language editing is essential for resubmission. ****** 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: Yes: DR. YAHYA H. Y. ALFARRA, BDS (Hons), MSc, PhD ******** [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.0315021.r001
Revision 1
8 Nov 2024 Author Response Reviewer #1 Title: 1. I recommend changing the title for grammatical clarity from “the relationships among...” to “the relationships between...”. Response: Thank you for the suggestion! Changing the title from "the relationships among..." to "the relationships between..." will enhance grammatical clarity. Background: 1. It is unclear why commuting is being quantified in a population aged 60+. Many participants may be retired or close to retirement, making commuting less relevant. If you meant mobility within the local community, please rephrase both the relevant sentences in the manuscript and the study title. Response: We appreciate your observation regarding the term "active commuting" and agree that "mobility within the local community" more accurately describes the focus of our study. In response, we defined this term in the introduction and made changes to the title and body of the text to reflect this terminology. Although approximately 80% of our sample is retired, the concept of "community mobility" encompasses an individual's movement outside the home, including both active modes of transportation (such as walking) and passive modes (such as driving and using public transportation) to navigate within the community. This concept is essential for promoting health among older adults, regardless of their occupational status. In the Brazilian context, where access to public transportation is limited in some regions, many older adults still rely on active commuting as their primary means of mobility for daily activities, often out of necessity. Investigating how the built environment facilitates or hinders this active mobility is crucial for developing public policies aimed at healthy aging. 2. Line 34: The statement is unclear. What is the projected 12% meant to indicate? Response: Thank you for your feedback. The sentence highlights the increasing proportion of older adults in the population of Latin America compared to the global projection for the same age group. Currently, 13.2% of the population in Latin America is composed of older adults, and this percentage is expected to rise to 16.5% by 2030. This indicates that while Latin America is experiencing a more pronounced aging trend, the global average for older adults is projected to be only 12% in 2030. This comparison underscores the significance of the aging population in Latin America. The text has been modified for better clarity. 3. Line 43: Physical activity advice now emphasizes that "any amount of physical activity is important," rather than just 150 minutes per week. Please refer to the UK Chief Medical Officers' recommendations for older adults, particularly based on the study by Onambele-Pearson et al. (2019) (Front Physiol 2019;10:408). Response: Thank you for your comment and suggestion. We agree that the guidance on physical activity should emphasize that "any amount of physical activity is important." Our guidelines also include similar recommendations. We recognize the importance of reviewing this section and have made the necessary changes in the text to reflect these guidelines. Methods: 1. Line 104: An HDI of 0.847 (Very High Human Development) is significantly greater than 0.760 (High Human Development). Although the difference seems small (0.087), the HDI scale is sensitive, indicating meaningful disparities in quality of life, healthcare access, and overall well-being. This could affect the generalizability of your results, which should be highlighted in your reports. Response: We appreciate your observation regarding the difference in the Human Development Index (HDI) between the city of Florianópolis (0.847) and Brazil as a whole (0.760). We agree that this difference is significant and may limit the direct generalization of our findings to all regions of the country. However, we would like to emphasize that the Gini index for Florianópolis (0.450) reflects a marked income distribution inequality within the city itself, which somewhat mirrors the disparities present throughout Brazil. This inequality can impact the quality of life and access to healthcare services among older adults, which should also be considered when interpreting the results of our study. Therefore, the combination of these indices provides a more comprehensive view of living conditions in Florianópolis. We have incorporated this limitation at the end of the discussion section to highlight it in the manuscript. 2. Line 105: The Gini index of 0.450 suggests notable income inequality in your region of study. Ensure broad recruitment across socio-economic strata to maintain the representativeness of your sample. Response: We appreciate your observation regarding the Gini index of 0.450, which indicates notable income inequality in our study region. To address this issue, we would like to clarify that the recruitment was conducted through a two-stage sampling process. In the first stage, we selected 80 urban census sectors of the municipality based on the decile of income of the household head. In the second stage, we performed a random selection of households within those sectors. This approach, as described by Confortin et al. (2022) [43], aims to ensure the representativeness of our sample. This information has been included in the article for clarity. 3. Line 125: It would be helpful to include statistics on the percentage of the older population in your region living in long-term care institutions, hospitals, or prisons. Response: Thank you for the suggestion. We have included the relevant national data on the percentage of older adults residing in Long-Term Care Institutions for the Elderly and in prisons in the Methods section to contextualize our exclusion criteria. Specifically, a survey in Brazil has shown that less than 1% of the older adult population resides in Long-Term Care Institutions for the Elderly (ILPIs) (Camarano & Kanso, 2010), and another study indicated that 1.93% of the Brazilian prison population is composed of older adults (Brazil, 2023); however, we lack regional data (Pollo & Assis, 2020). Our search in studies and government databases did not yield public information on the percentage of elderly individuals in hospitals, either nationally or regionally. We requested this data from the Public Prosecutor's Office but, to date, have not received a response within the necessary timeframe. Camarano, Ana Amélia, and Solange Kanso. "As instituições de longa permanência para idosos no Brasil." Revista brasileira de estudos de população 27 (2010): 232-235. Pollo, Sandra Helena Lima, and Mônica de Assis. "Instituições de longa permanência para idosos-ILPIS: desafios e alternativas no município do Rio de Janeiro." Revista Brasileira de Geriatria e Gerontologia 11 (2019): 29-44. Brazil. Custodial Procedures for Elderly People in the Prison System. National Secretariat of Penal Policies. Brasília: Ministry of Justice and Public Security, 2023. 24 p. 4. Lines 132-133: Please provide a brief explanation of your sample size justification. Response: Thank you for your comment. The justification for the sample size in this study is based on previous waves of the longitudinal research. In the first wave (2009/2010), 1,702 interviews were conducted with older adults. In the third wave, a sample replenishment of 592 older adults was carried out to compensate for participant losses over the follow-up period. The planned sample for this protocol study maintains this structure to ensure the representativeness of the target population and the statistical robustness needed for longitudinal analyses. We will adjust the text to improve clarity and understanding. 5. Line 142: Five attempts to contact participants at Phase 1 (plus six in Phase 2, Line 202) seems excessive and may create undue pressure. Could this be considered borderline harassment? To mitigate this: Response: We appreciate the detailed comments. We believe that respectful interaction and clear communication are essential, especially when working with an older population that may face access and comprehension challenges related to technology. Participants are repeatedly reminded that participation in the project is voluntary and that they may withdraw at any stage without any consequences. The contact attempts follow a carefully planned approach to minimize any discomfort, based on the specific needs of this population and on ethical research practices. A) Specify how contact attempts will be spaced out (e.g., days/weeks between attempts). Response: Contact attempts are spaced a minimum of one week apart, alternating days and times to respect participants’ routines and avoid intrusions. For example, after an attempt on Monday morning, the next attempt would take place on Tuesday afternoon of the following week. This spacing, which has been clarified in the manuscript, aims to increase the likelihood of effective contact without pressuring the participant, keeping attempts to the minimum necessary to achieve a representative sample. B) Have participants previously agreed to multiple contact attempts? Response: In the first phase, participants are informed about the possibility of multiple contacts throughout the study. Only three interactions are considered essential and effective: the initial interview and the visits for device setup and retrieval in the second phase. The nature and frequency of the contacts are explained from the start, and participants have the freedom to accept or decline each step, ensuring complete autonomy. C) Consider reducing in-person visits (3 seems intrusive); a mix of phone, email, and one in-person visit may be less burdensome. Response: Due to the participants’ age and education profile (with approximately 32% having 4 years of education or less), the three in-person visits are necessary to ensure instruction clarity and correct device usage. The visits for device setup and retrieval are brief, lasting between five and 10 minutes, and aim to instruct and answer questions regarding device usage. Practical experience indicates that in-person communication reduces uncertainty and increases data reliability, ensuring that devices are used correctly. D) Ensure that participants fully understand why they are being contacted and what their participation involves. Response: Transparency is prioritized in each interaction. Participants receive a detailed invitation letter before the study, and during the first interview, they receive a full explanation of the study phases and the purpose of each visit. We reinforce this information in each subsequent contact to ensure they understand the value of their participation and what each study stage entails. These measures aim to ensure fully informed consent and that participants feel comfortable to participate or decline without any pressure. We hope these clarifications address your concerns, and we are available to discuss any additional adjustments necessary to ensure maximum respect and comfort for participants during data collection. 6. Lines 145-148: Ethical best practices recommend providing clear study information in advance, giving participants time to review it, and allowing them to ask questions before consenting. Immediate consent, especially in their homes, may create discomfort and pressure. This is not reflected in your current approach, which raises concerns. Response: We appreciate the opportunity to clarify our consent and recruitment process. Our approach follows rigorous ethical practices, considering both the longitudinal nature of the study and the specific vulnerabilities and needs of the older population. Here are some important points: A) This study includes participants involved since 2009 or 2015, who are familiar with the study’s goals and procedures. All participants receive a detailed invitation letter before any contact, explaining the study's objectives, methods, and expectations. This provides ample time to consider participation. Those who are not interested may decline participation upon receiving the letter (which includes our contact information for follow-up) or during the phone contact, without any need for a home visit. If they decline or wish to withdraw at any stage, we respect their decision without further contact attempts. Any refusal or withdrawal is respected without additional contact attempts. B) Only participants who agree to participate or whom we have been unable to contact by phone—due to outdated contact information, lack of a phone, or other limitations (including death, which is more common in this age group, especially following the pandemic)—are visited at home. In Brazil, especially in this age group, access to technology can be challenging, and in some cases, a home visit becomes the only way to confirm availability to participate. During the visit, participants receive explanations and have the opportunity to ask questions (noting that they have participated at least once before). If they decline, we respect their right to immediately refuse without further contact attempts. Any refusal, at any stage, is respected without additional contact attempts. C) Recognizing the challenges many participants face with technology, we are initiating an innovative project called Conecta EpiFloripa to train older adults in basic smartphone functions, such as sending emails, messages, and making and receiving calls. This parallel initiative aims to facilitate contact and make the study more accessible, enhancing participants' digital inclusion. We hope this information addresses your concerns, ensuring that our approach fully respects participants' autonomy and comfort while facilitating participation in an ethical and transparent manner. 7. Lines 175-189: The rationale for using the IPAQ is unclear when: a) Accelerometers will provide more reliable physical activity data. b) The IPAQ adds to participant burden by extending the interview. c) The IPAQ does not effectively capture sedentary behaviour, which is a key aspect of the physical activity spectrum (Ryan et al., PLoS One 2018;13). I recommend reconsidering the use of the IPAQ. Response: Thank you for the feedback on the use of the IPAQ. While accelerometers provide reliable objective data on physical activity, sedentary behavior, and sleep, the IPAQ adds essential context by capturing the domain of physical activity—whether driven by necessity or choice. Studies such as Salvo et al. (2023) emphasize that understanding this distinction is fundamental for promoting more equitable aging. This distinction is particularly critical, as older adults in low- and middle-income contexts often engage in physical activities not as a health choice, but due to environmental or economic needs (e.g., commuting to access services). Capturing this information is particularly relevant in the context of the older population in Brazil, where disparities in activity domains often reflect and amplify existing health inequalities. Additionally, we recognize the additional time burden that the IPAQ may impose. To mitigate this impact, our interviewers are extensively trained and use optimized tablet-based tools, which minimize participants' time and improve the efficiency of the data collection process. Salvo, D., Jáuregui, A., Adlakha, D., Sarmiento, O. L., & Reis, R. S. (2023). When moving is the only option: the role of necessity versus choice for understanding and promoting physical activity in low-and middle-income countries. Annual Review of Public Health, 44(1), 151-169. 8. Line 193: Please specify the time or distance for the walking ability test (e.g., walk for 2 minutes? Walk 30 meters?) Response: Thank you for the insightful comment. In Phase 2, the inclusion criterion of “independent walking ability” refers to participants' capacity to move independently without human assistance, regardless of distance, while allowing the use of assistive devices such as canes or walkers. This criterion aligns with recommendations in the literature, such as in Studenski et al. (2011), which emphasize the importance of functional autonomy for older adults, even when assistive devices are required. Studenski, S., Perera, S., Patel, K., Rosano, C., Faulkner, K., Inzitari, M., ... & Guralnik, J. (2011). Gait Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0315021.r002
20 Nov 2024 Decision Letter - Zulkarnain Jaafar, Editor Understanding the relationships between 24-hour movement behavior, community mobility and the neighborhood built environment for healthy aging in Brazil: The EpiMove Study protocol PONE-D-24-37986R1 Dear Dr. de Zorzi, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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, Zulkarnain Jaafar Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions? The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses? The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory. Reviewer #1: Yes Reviewer #2: Yes ****** 3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable? Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors described where all data underlying the findings will be made available when the study is complete? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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: 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: Yes Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics. You may also provide optional suggestions and comments to authors that they might find helpful in planning their study. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: All comments have been addressed by the authors to the satisfaction of this reviewer. No further comment remain Reviewer #2: The authors amended the original manuscript to incorporate the recommendations of the reviewers. Therefore, I have no further suggestions for this article. ****** 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: Yes: DR. YAHYA H. Y. ALFARRA, BDS (Hons), MSc, PhD ******** https://doi.org/10.1371/journal.pone.0315021.r003
Formally Accepted
25 Nov 2024 Acceptance Letter - Zulkarnain Jaafar, Editor PONE-D-24-37986R1 PLOS ONE Dear Dr. Zorzi, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, 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 customercare@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. Zulkarnain Jaafar Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0315021.r004

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