PONE-D-20-09300

Vibration thresholds in non-diabetic subjects

PLOS ONE

Dear Mrs. Nolte,

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.

As this manuscript was a resubmission of a previous one, we have invited to the reviewers of the old manuscript to provide a revision of the new manuscript. Their reports are very positive, both considering that the manuscript has highly improved. Additionally, two new reviewers, unaware of the previous submission, were also invited to review the manuscript. Their comments are also rather positive, but some remarks are still to be addressed. In general, most of the comments imply minor changes in order to make it clearer for the readers and better situate your study in the general field of tactile thresholds in this population.

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We look forward to receiving your revised manuscript.

Kind regards,

Inmaculada Riquelme

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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

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

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: No

Reviewer #4: Yes

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

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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5. Review Comments to the Author

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

Reviewer #1: This is a hugely interesting study. Patient population is clear and so are methods and results.

Minor comments:

1. Please shorten the Introduction.

This is a hugely interesting study. Patient population is clear and so are methods and results.

Minor comments:

1. Please shorten the Introduction.

This is a hugely interesting study. Patient population is clear and so are methods and results.

Minor comments:

1. Please shorten the Introduction.

Reviewer #2: Thank you for the invitation to review this paper with the title “Vibration thresholds in non-diabetic subjects.”

The paper presents how vibration perception thresholds are effected by age and height on. The

The Experiments, statistics, and other analyses are done in a proper way and are described in detail.

In general the conclusions are supported by the data presented.

I have only some minor questions, comments, and suggestions:

1. Data on tables 3-6 could be presented in one table. There are a lot of small tables also in the supplement part that could be presented together.

2. Are the regression equations presented for logarithmic values? The authors state that “the obtained thresholds were log transformed”

3. Regarding last line in conclusion: (“The established equations can be used to determine loss of vibration perception in clinical practice.”) Is it possible to calculate standard deviations from these equations? That would be needed if one would use them to determine a specific threshold that is above normal. (Figures 6-7) could be used for that purpose.

4. Line 57 “By using the biothesiometer and thus detecting the first sensation of vibration, adaption to the sensation of vibration is less likely to develop” According to reference 5, this is true for upper limbs but I can not see that this was the case for measurements in the lower limb.

Reviewer #3: Please make note of the published study by Rinkel et al. on normative data, with decline in sensibility, of static, moving and one-point discrimination.

Please make a statement on comparability or superiority of VPT measurements measured with the Biothesiometer compared to Rydel Seiffer tuning fork.

See further comments in the attached document.

Reviewer #4: These are my comments. i hope you find them useful

1. Sample size is too small. How did you come up with this sample size?

2. Value sof VPT are equipment specific and machines are not standardized. It sa common observation that the values form 2 different machines are not the same. Can the resuls be generalized to other equipments

3. Mean value of VP is less than 2, whereas for diabetic neuropathy thresholds such as 15 and 25 are used. Given the low mean value, minor differences after adustment for age and hieght are practically non-significant and unikely to be benificial in any clinical condition. In addition VPT values are partly subjective with significant variation and minor differences are unlikely to be of any importance. Which cliincal condition do you think your research is going to be beneficial?

4. Median age of the study population of 59 years is somewhat strange to generate normative values and adjustments for age/height. You shoud have chosen a healthy populaion below 50 yars of age

5. VPT is not as sensitive a test for diabetic neuroathy compared to nerve conduction studies. Can you enumeate which clinical condions is VPT preferred as diagnostic test for early detection

6. There are too many figures and tables which need to be cut-down to 1-2 each

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Willem D. Rinkel MD

Reviewer #4: Yes: Shivaprasad Channabasappa

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

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 us at figures@plos.org. Please note that Supporting Information files do not need this step.

Attachments

Attachment

Submitted filename: PONE-D-20-09300_reviewer.pdf

PONE-D-20-09300R1

Vibration thresholds in non-diabetic subjects

PLOS ONE

Dear Dr. Nolte,

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 minor points raised during the review process.

Please submit your revised manuscript by Aug 29 2020 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Inmaculada Riquelme

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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

Reviewer #1: All comments have been addressed

Reviewer #3: All comments have been addressed

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

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

Reviewer #1: Yes

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #3: Yes

**********

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

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

Reviewer #1: Yes

Reviewer #3: 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

**********

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 further comments no further comments no further comments no further comments no further comments no further comments

Reviewer #3: It is wise to state that the Rydel Seiffer tuning fork with weights attached tests at 64 hz. Without weights, one tests at 128 Hz.

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

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

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

Reviewer #1: No

Reviewer #3: 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.

Vibration thresholds in non-diabetic subjects

PONE-D-20-09300R2

Dear Dr. Nolte,

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,

Inmaculada Riquelme

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: