PONE-D-21-30439Active versus sham transcranial direct current stimulation (tDCS) as an adjunct to varenicline treatment for smoking cessation: study protocol for a double-blind single dummy randomized controlled trialPLOS ONE

Dear Dr. Zawertailo,

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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: Partly

Reviewer #3: Yes

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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: Partly

Reviewer #3: Yes

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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

Reviewer #3: Yes

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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

Reviewer #3: Yes

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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

Reviewer #3: Yes

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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: Zawertailo and colleagues aim to investigate in the present study, entitled ‘Active versus sham transcranial direct current stimulation (tDCS) as an adjunct to varenicline treatment for smoking cessation: study protocol for a double-blind single dummy randomized controlled trial’, the current status of knowledge of the effectiveness of tDCS in combination with varenicline for smoking cessation. For this purpose, a double-blind, sham-controlled randomized clinical trial with fifty healthy will be conducted; participants will receive either active tDCS (20 minutes at 2 mA) or sham tDCS (30 seconds at 2 mA, 19.5 minutes at 0 mA) for 10 daily sessions plus 5 follow up sessions. All participants will be given standard varenicline treatment concurrently with stimulations. The primary outcome is a self-reported continuous abstinence from smoking, in addition to an improvement in smoking cessation due to tDCS-varenicline combined treatment.

The main strength of this paper is that it addresses an interesting and timely question, investigating the efficacy of tDCS as an adjunct to varenicline treatment for smoking cessation. In general, I think the idea of this article is really interesting and the authors’ fascinating observations on this timely topic may be of interest to the readers of Plos One. However, some comments, as well as some crucial evidence that should be included to support the authors’ argumentation, need to be addressed to improve the quality of the article, its adequacy, and its readability prior to the publication in the present form. My overall judgment is to publish this article after the authors have carefully considered my suggestions below, in particular reshaping the parts of the Introduction and Discussion sections.

Please consider the following comments:

• Regarding the Abstract: according to the Journal’s guidelines, authors should have provided an abstract of about 300 words maximum. Indeed, the current one includes 356 words. Please correct it.

• In general, I recommend authors to use more evidence to back their claims, especially in the Introduction of the article, which I believe is currently lacking. Thus, I recommend the authors to attempt to deepen the subject of their manuscript, as the bibliography is too concise: nonetheless, in my opinion, less than 70 articles for a research paper are really insufficient. Indeed, currently authors cite only 54 papers, and they are too low. Therefore, I suggest the authors to focus their efforts on researching more relevant literature: I believe that adding more studies and reviews will help them to provide better and more accurate background to this study. In this review, I will try to help the authors by suggesting some relevant literature of my knowledge that suit their manuscript.

• Introduction: The authors take a narrow view of the tDCS direct effect on cortical circuits underlying craving, describing its impact on symptoms among cigarette smokers in detail. Nevertheless, I think that a deeper examination of tDCS potential to modulate cortical excitability and, specifically, to induce motor cortical plasticity in humans would provide a better characterization and useful background in this instance. It is well known that non-invasive brain stimulation can modulate the increased neural activity of cortical areas involved in the control of behavior: in this regard, I would suggest adding evidence from a recent study that could provide interesting insights on the use of non-invasive brain stimulation (in this case, single-pulse TMS) to investigate the time course of the motor system readiness in response to processing of relevant arousing stimuli (i.e., happy and fearful faces), addressing how differences in the experience of aversive feelings modulate corticospinal excitability, hence, the preparation of adaptive motor responses required for the execution of appropriate behaviors (https://doi.org/10.3390/brainsci11091203). Results from this study, which involved healthy participants, helped gaining a better understating of the abnormal cortical excitability that characterizes craving. I also suggest an interesting article on altered excitability in chronic smokers (https://doi.org/10.1503/jpn.130086) that will offer a more coherent and defined background.

• Introduction: Following the first point raised, for a more thorough and comprehensive overview on this topic, I believe that it may be useful to have more information from additional evidence that focused on autonomic nervous system responses evoked by arousing stimuli (i.e., emotional stimuli or addiction-related stimuli). Importantly, recent findings suggest that responses to approaching emotional stimuli (i.e., emotional faces) modulate autonomic arousal as a function of the distance between the observer and the stimuli, resulting in an appropriate organization of defensive responses (https://doi.org/10.1007/s00221-020-05829-4). Similarly, results from another recent study showed that interpretation of potentially threatening situations, such as others’ proximity, triggers a number of physiological responses that help regulating the distance between ourselves and others during social interaction (https://doi.org/10.1038/s41598-021-82223-2). Moreover, authors might also see studies that have focused on this topic (https://doi.org/10.1152/ajpregu.00226.2018; https://doi.org/10.1111/psyp.13636).

• Cognitive behavioural reading material (weeks 1 through 12): I suggest the authors to reorganize/reshape this section, providing detailed information about cognitive tests, as well as relevant scientific references, utilized in this session.

• Participant follow-up and retention: Could the authors discuss how they intend to manage probable drop-outs? Please explain it.

• Page 8, Discussion: In this section, authors thoroughly addressed their expected outcomes and their argumentation; however, I would have liked to see some views on a way forward. Hence, I ask them to include some thoughtful as well as in-depth considerations, making an effort, trying to explain the theoretical as well as the translational application of their research. In this respect, I believe that it could be useful to have more information from additional research that have focused on the pathophysiology underlying addiction, specifically on frontal cortex abnormalities and executive dysfunctions associated with impairments in memory and learning. Evidence from a recent study conducted on patients with lesion in the ventromedial portion of prefrontal cortex revealed that this brain structure is involved in the acquisition of emotional conditioning (i.e., learning) and assessed how naturally occurring bilateral lesion centered on the vmPFC compromises the generation of conditioned psychophysiological response during the acquisition of conditioning (https://doi.org/10.1523/JNEUROSCI.0304-20.2020). Accordingly, in a recent theoretical review that focused on neurobiology of fear conditioning, the distinct contributions of anterior/posterior subregions of the vmPFC in the processing of safety-threat information was discussed: here authors provided evidence for the fundamental role of this how region in the evaluation and representation of stimulus-outcome’s value needed to produce sustained physiological responses (https://doi.org/10.1038/s41380-021-01326-4). These findings highlight prefrontal cortex’s key role in the acquisition of new learning, and how its disrupted function may contribute to irregular behavioral responses and therefore to the development of neuropsychiatric disorders characterized by altered value attribution, reward anticipation or fear extinction (e.g., depression, anxiety, PTSD, substance-related and addictive disorders).

• Even though it is not mandatory, I believe that the ‘Conclusions’ section would be useful to adequately indicate convey what the authors believe will be the take-home message of their study, and therefore provide possible keys to advancing research and understanding of the prevalence of depression in post-stroke patients.

• In according to the previous comment, I would ask the authors to better define a ‘Limitations and future directions’ section before the end of the manuscript, in which authors can describe in detail and report all the technical issues that may be brought to the surface.

• Figures: I suggest to add a figure that displays stimulation sites’ position on the scalp. Also, I would appreciate some current flow modeling that could provide a better understanding of estimated current flow, for example using any of the free software like ROAST, COMETS, SimNIBS.

• References: According to the Journal’s guidelines, do not use a numbered list to include citations in the 'References' section.

Overall, the manuscript contains 3 figures and 54 references. In my opinion, the number of references it is too low for an original research article, and this issue may prevent the possibility of publishing it in this form. However, I believe that the manuscript may carry important value providing preliminary evidence of the efficacy of tDCS as an adjunct to 12 weeks of varenicline treatment for smoking cessation.

I hope that, after these careful revisions, the manuscript can meet the Journal’s high standards for publication. I am available for a new round of revision of this review.

I declare no conflict of interest regarding this manuscript.

Best regards,

Reviewer

Reviewer #2: The current manuscript is a protocol to conduct a study where the impact of transcranial direct current stimulation (tDCS) is studied as an adjunct therapy to varenicline for smoking cessation. The authors put a nice plan together to conduct this study, almost all is in place except two control groups are missing: (1) varenicline group alone and (2) tDCS group alone. Although the effect of these two groups have been reported previously, it is better to include these groups to enable the authors to make a firm conclusion regarding the combination therapy against the single therapy. The authors may argue that the varenicline plus sham tDCS group is the control for the current study. However, if this population do not respond to varenicline alone or tDCS alone, this information can be obtained by including these two additional groups. Also, the authors can make a firm conclusion whether the effect is additive or synergistic. Please also ensure to state that scans are taken during exposure to neutral cues as well as smoking cue to ensure the scans can be correlated to the level of craving. One issue with this approach is that if neuronal connectivity or activation occurs in a delayed manner and during the time the other cues are shown, how the authors can interpret that and differentiate neuronal activation associated with the cues if the signal shows up after the exposure to the cue. Some parts of the manuscripts are written in the future tense and others in past tense. Please ensure that tense is used appropriate for a given sentence. Also, change the following minor typos.

Minor:

1. Please change "nicotine" to "nicotinic" on line 81.

2. Please use the same abbreviation for both lines 144 and 146. I suggest to use RsFC in both lines.

3. Please change to "differences have been" on line 148.

4. The word :respectively" may not be needed on line 149.

5. Please leave a comma between QSU and etc. on line 304.

6. Please change to "at the end of the 12-week treatment" on line 321.

7. Please delete the description about BOLD since this was defined above (line 362).

8. Please change "at end of the treatment" to " at the end of the treatment" throughout the manuscript.

9. Please leave a comma between years and etc. on line 406.

10. Please change "loss" to "lost" and "not quit" to "no-quitter" on line 415.

Reviewer #3: PONE-D-21-30439

Active versus sham transcranial direct current stimulation (tDCS) as an adjunct to varenicline treatment for smoking cessation: study protocol for a double-blind single dummy randomized controlled trial.

General Comments:

This manuscript describes a study protocol for a double-blind RCT examining the effectiveness of tDCS as an adjunctive treatment with varenicline pharmacotherapy (varenicline is a alpha4beta2 nicotinic ligand and is a form of nicotine replacement therapy).

The authors do a good job of establishing the rationale for this study. The effectiveness of pharmacotherapy alone treatment in smoking cessation treatment is limited and thus, examining potential adjunctive treatments (drug, physiological, or behavioral) that may increase long term smoking cessation success is an important and clinically relevant research endeavor.

The methodology is sound and uses best practices of RCT plus sham control groups. Baseline MRI scans will permit determination of changes due to treatment in from both nicotine-deprivation and -satiation conditions. The 12-wk treatment protocol should allow for determination of overall treatment effectiveness. The researchers propose to assess multiple behavioral measures (mood, craving, withdrawal) at each visit and importantly, will also use biological measures of CO ppm and urinary continine levels to verify smoking status. The authors have chosen appropriate doses and employed a standard dose-escalation procedure. As this is a proof-of-concept study to better establish experimental parameters for future work, these methodological details seem appropriate.

Significance: as there is sparse literature on the potential for tDCS to enhance currently approved pharmacotherapies for smoking cessation is great. This protocol has the potential to reveal new avenues for treatments to improve smoking cessation paradigms.

Comments and/or Points for the authors to consider:

1. Current knowledge suggests individualized treatment for smoking cessation is necessary – and may largely be a function of individual experience, history, dependence severity, etc. The authors describe inclusion criteria of at least 8 cigarettes per day, which strikes this reader as setting the bar relatively low and perhaps creating a more heterogeneous sample (e.g., 8 cigarettes/day for 1 year vs 30 cigarettes/day for 10 years would be two very different users in my experience). Thus, this variable sample may hinder the ability to find significant differences. However, if the authors matched their groups on this factor, or somehow controlled for severity statistically, that may mitigate some of these methodological concerns.

2. Exclusion criteria include other drugs of abuse and the authors specifically mention cannabis products but it is not clear if this definition also includes alcohol. This is important because varenicline has interactions with alcohol, thus patients should be at least cautioned about concurrent alcohol use. Varenicline also increases risk for adverse reactions in individuals with renal disease and it’s unclear if subjects will be screened for that.

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Reviewer #1: No

Reviewer #2: Yes: Kabirullah Lutfy

Reviewer #3: No

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PONE-D-21-30439R1Active versus sham transcranial direct current stimulation (tDCS) as an adjunct to varenicline treatment for smoking cessation: study protocol for a double-blind single dummy randomized controlled trialPLOS ONE

Dear Dr. Zawertailo,

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 24 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,

Kabirullah Lutfy

Guest Editor

PLOS ONE

Journal Requirements:

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

Additional Editor Comments:

Dear Dr. Zawertailo,

I served as a reviewer on the original version of your manuscript and requested you to add the varenicline group alone, but I was later assigned to serve as a guest editor on your revised versions. Please make the necessary changes, as I emailed you yesterday, and send us the further revised manuscript addressing the changes requested.

I look forward to receiving your further revised manuscript at your earliest convenience.

Thank you for submitting your work to PLOS ONE.

Sincerely,

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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 #3: Yes

Reviewer #4: 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 #3: Yes

Reviewer #4: Yes

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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 #3: Yes

Reviewer #4: 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 #3: Yes

Reviewer #4: Yes

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

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

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #4: 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: In this article Zawertailo and colleagues explored the effectiveness of tDCS in combination with varenicline for smoking cessation. I really appreciate the Authors’ response to the points I have raised in the first round of review, as well as their clarifications to some of my concerns.

I only have few last suggestions to do, to further improve the theoretical background of the present paper and its argumentation: in this regard, I would recommend deepening the information about the application of Non-invasive brain stimulation in modulating cortical excitability, and how these techniques can be used to investigate altered brain circuits (i.e., primary sensorimotor cortex, dorsolateral prefrontal cortex and the midbrain nucleus cuneiformis) in chronic smokers (https://doi.org/10.3390/biomedicines9070734; https://doi.org/10.3390/biomedicines10030627; https://doi.org/10.1016/j.tins.2022.04.003; https://doi.org/10.1111/psyp.14122; https://doi.org/10.1183/13993003.00362-2019).

Overall, this is a timely and needed study, and I look forward to seeing further studies on this issue by these authors in the future.

Thank You for your work.

Reviewer #3: The authors have done a very thorough job in detailing and addressing the review comments by the reviewers of the previous version of this manuscript.

The authors have adequately addressed all of my previous comments and concerns.

I have no further commentary or suggestions.

Reviewer #4: This is a proof of concept trial, therefore the statistical content is minimal, but seems to be planned well. The other reviewers have given very detailed comments--I was not a reviewer in the first round. The sample size, randomization, blinding, and statistical analysis plan are sound.

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Reviewer #1: No

Reviewer #3: Yes: Joshua S. Rodefer

Reviewer #4: No

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Active versus sham transcranial direct current stimulation (tDCS) as an adjunct to varenicline treatment for smoking cessation: study protocol for a double-blind single dummy randomized controlled trial

PONE-D-21-30439R2

Dear Dr. Zawertailo,

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.

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Kind regards,

Kabirullah Lutfy

Guest 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

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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

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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

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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

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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

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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: The authors did an excellent job clarifying the questions I have raised in my previous round of review. Currently, this paper entitled ‘Active versus sham transcranial direct current stimulation (tDCS) as an adjunct to varenicline treatment for smoking cessation: study protocol for a double-blind single dummy randomized controlled trial’ is a well-written, timely piece of research and provides a useful summary of the existing status of knowledge of the effectiveness of tDCS in combination with varenicline for smoking cessation.

Overall, this is a timely and needed work. It is well researched and nicely written, with a good balance between descriptive and narrative text.

I believe that this paper does not need a further revision, therefore the manuscript meets the Journal’s high standards for publication.

Thank You for your work.

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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

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