A registered report of a crossover study on the effects of face masks on walking adaptability in people with Parkinson’s disease and multiple sclerosis

Mareike Eschweiler; Christopher McCrum; Eleftheria Giannouli

doi:10.1371/journal.pone.0286402

. 2023 Jun 29;18(6):e0286402. doi: 10.1371/journal.pone.0286402

A registered report of a crossover study on the effects of face masks on walking adaptability in people with Parkinson’s disease and multiple sclerosis

Mareike Eschweiler ^1,², Christopher McCrum ^3,^4,^#, Eleftheria Giannouli ^5,^6,^*,^#

Editor: Eric R Anson⁷

PMCID: PMC10309975 PMID: 37384662

Abstract

Background

Face masks protrude into the lower visual field causing reduced perception of visual stimuli, potentially making obstacle avoidance during walking more difficult and increasing fall risk. Recommendations on walking and mask wearing for older adults have been debated, with no clear consensus on the various factors interacting and influencing walking safety while wearing a face mask. It is particularly important to address this issue in populations at an increased risk of falls. Therefore, this study aims to investigate the effects of mask-wearing on objectively measured walking adaptability in people with Parkinson’s disease and Multiple Sclerosis.

Methods

50 patients with either Parkinson’s disease or Multiple Sclerosis attending inpatient neurorehabilitation will be recruited to participate in this crossover study. Performance during a standardized gait adaptability (C-Gait) test on a VR-based treadmill (C-Mill+VR), as well as during clinical mobility tests (10-meter walk test, Timed Up & Go test, and stair ambulation) will be measured with and without an FFP2- mask (order randomized). In addition, participants will be asked about their perceived performance and perceived safety during the tests with and without a mask. Performance on the seven C-Gait subtests is based on centre of pressure-derived measures of foot placement in relation to the different tasks. These are averaged and added to a cognitive C-Gait task to give the overall composite score (primary outcome). Secondary outcomes will include the different subscores and clinical mobility tests.

Potential significance

This study will make an important contribution to an ongoing debate regarding recommendations persons with and without a neurological disease should be given regarding wearing a face mask while walking. Furthermore, the study will complement the existing scientific discourse with clinical data from people with a neurological disease for whom falls, mobility deficits and mask wearing may be more frequent, which can help inform evidence-based recommendations.

Trial registration

German clinical trial register: DRKS00030207.

Background

During the COVID-19 pandemic, one of the most prevalent preventative measures is the wearing of face masks. This is recommended by the World Health Organization (WHO) and, for much of the pandemic, has been required in many indoor or crowded environments, especially when social distancing cannot be maintained. Any mask, whether cloth, surgical or special filtering masks (e.g. FFP2) protrudes into the lower visual field and, as a result, perception of visual stimuli in this area is reduced. The lower visual field provides important information for any necessary adjustments during walking (e.g., avoiding or stepping over obstacles) [1]. Therefore, the visual restriction caused by wearing a face mask could compromise safety and ultimately lead to a fall [2, 3].

A scientific debate regarding the recommendations that older adults should be given when wearing a face mask in order to minimize their fall risk took place recently after the Safe Exercise at Home website (endorsed by the Australian Physiotherapy Association) published recommendations for safe exercising in older adults in the COVID era. Using the motto “Mask Up, Look Down” [4] they advised older adults to look down more often while walking when wearing a mask, as doing so provides the visual information that is otherwise obtained through lower peripheral vision when looking ahead without wearing a mask. Kal et al. [5, 6] argued that such advice is flawed and can even be harmful as frequent and large amplitude movements of the head and the eyes could lead to a mismatch between visual and vestibular feedback and therefore cause instability and ultimately increase fall risk. Instead, Kal et al. recommended that older adults should try to walk more slowly [5, 6], as evidence suggests that this will give them more time to detect potential trip hazards and plan accordingly [7, 8]. Callisaya et al. [9] responded that tilting the head and directing the gaze towards the feet is a common strategy even for young adults [10] and raised concerns that that reducing walking speed may increase the risk of falls, citing studies that suggest stability of head and pelvis accelerations is optimised at one’s comfortable walking speed [11] and that slower speeds may result in reduced gait quality [12]. In response, McCrum [13] highlighted the importance of the definition of stability. Citing additional studies [14–16], he argued that the mechanical stability of one’s body configuration during walking in the anterior direction is increased when forward center of mass velocity is reduced meaning that, everything else being equal, reducing walking speed will directly reduce the likelihood of a forward fall following a trip.

As this recent debate highlighted, there is currently no clear consensus on the various factors that interact to influence walking safety while wearing a mask and all involved in the described discussions agreed that systematic investigation of these issues is needed in order to move towards evidence-based recommendations. Since the risk of falling while wearing a mask is likely to be even greater in persons who already suffer from gait and balance impairments, especially those who are more reliant on vision [17], it is particularly urgent to address this issue in people with neurological diseases [18].

The first aim of this study is to investigate the effects of wearing a mask on objectively measured walking adaptability. Since perception and gait efficacy is known to have an influence on walking performance [19], the second aim of this study is to explore the relationships between wearing a face mask and gait efficacy and perceived safety. To address these aims, performance during a standardized test of walking adaptability (C-Gait) [20] on a VR-based treadmill (C-Mill+VR; Motek Medical, Amsterdam, The Netherlands) as well as during specific clinical tests (10-meter walk test (10MWT), Timed Up & Go test (TUG) and stair ambulation) will be measured with and without a face mask in 50 people with either Parkinson’s disease or multiple sclerosis, two populations at a greatly increased risk of falls [21, 22]. In addition, participants will be asked about their perceived performance and perceived safety during the tests with and without a mask. We will test the hypothesis of a potentially meaningful decline (indicated by a moderate to large effect size; see “Sample Size Calculation” below) in the C-Gait composite score (primary outcome as an objective measure of walking adaptability) as a result of wearing a face mask. We will supplement this with exploratory analyses of the C-Gait sub-scores to gain insight into specific walking adaptability tasks and with exploratory analyses of the 10MWT, the TUG test and the stair negotiation test for which we also tentatively test the hypothesis of a medium to large effect.

Methods

Recruitment & experimental procedures

Participants will be persons that were prescribed inpatient rehabilitation and will be recruited during their stay at the Neurological Rehabilitation Center "Godeshoehe". We aim to include 50 participants. However, the medical director, as well as the executing researcher in communication with the ethics committee, might decide to terminate recruiting in certain circumstances (e.g., changes in the pandemic situation). Only participants that fulfil the clinic’s standard aptitude checks for physical therapy and are not contraindicated (e.g. severe cognitive, visual or hearing impairment, > 135 kg bodyweight, > 2.00 meter body height, open skin lesion or bandage in the area of harness contact, ambulators with Functional Ambulation Categories (FAC) < 2, severe reduced bone density, spinal instability or unstable fractures, severe vascular disorders or cardiac abnormalities that affect the ability to exercise safely) with the use of the study`s main assessment tool (C-Mill) upon admission will be asked if they would be interested to participate in the study. In case they are principally interested, they will be informed verbally and in writing about the study by the study coordinator (ME) and the neuropsychology staff. Participants will be given detailed written study information, which has been approved by the ethics committee. If they agree to participate, they will have to provide their written informed consent for participation and data processing. The study has been approved by the ethics committee of the medical faculty of the University of Bonn (File-Nr.: 269/21) and was registered in the German Clinical Trial Register (Registration number: DRKS00030207). All study procedures will be in compliance with the declaration of Helsinki.

Data collection is planned to start in 12/2022 and end in 7/2023.

In the morning of the study measurement day, participants will undergo the C-Gait Test. The C-Gait walking test will be completed once with and once without an FFP2 face mask by each participant at two different difficulty levels, as defined based on the C-Gait decision algorithm by Timmermans et al. [20]. The order "mask/no mask" will be randomized per participant. Participants will be randomised to order 1 (wearing a face mask followed by not wearing a face mask) or order 2 (not wearing a face mask followed by wearing a face mask) by a paper lot that will be drawn from a sealed envelope by a person not related to the study. The lots will be prepared before participants’ enrollment. Therefore, the numbers 1 to 50 will be randomised into the two study conditions with randomizer.org. Thereafter, paper-lots indicating a number and group allocation will be prepared and sealed in an envelope.

The C-Gait test is a standardised test that is integrated into the diagnostic program of the C-Mill by Motek VR treadmill (Motek Medical, Amsterdam, The Netherlands). It lasts 20 minutes and includes a series of seven sub-tasks to test walking adaptability.

Before starting the actual test, approximately 3 minutes of treadmill familiarization will take place, during which each participant’s comfortable walking speed which will be determined according to Timmermans et al. [20] as follows: belt speed will be slowly increased (in steps of 0.1 km/h) until the participant reports it as comfortable. Subsequently, belt speed will be increased by 0.5 km/h followed by a stepwise decrease (0.1 km/h) until the participant reports it as comfortable again. These 2 indications of comfortable walking speed will then be averaged and taken to represent the participant’s comfortable belt speed, which will be used for all sub-tasks. In the afternoon of the same day, participants will undergo the 10MWT, the TUG and the stair negotiation test. After each test, participants will be asked some questions regarding their perceived performance and perceived safety during the test with and without a face mask (see below). Testing and intervention won’t be blinded, as the condition “mask/no mask”) will be obvious to the assessors.

As modifications of the current protocol become necessary, they will be communicated within the research and the interdisciplinary clinical team as well as with the ethics committee (amendment) and the trial registration would be update accordingly.

Inclusion & exclusion criteria

Patients will be included or excluded from the study according to the following criteria.

Inclusion criteria

diagnosed either by the treating physician or by a neurologist with either Parkinson’s disease or multiple sclerosis
willing to provide informed consent
able to conduct the C-Gait Test
inpatient of the Neurological Rehabilitation Center "Godeshoehe"

Exclusion criteria

MOCA score < 17
other neurological or psychiatric illnesses that influence the ability to provide informed consent, understand the testing procedures, compromise safety during data collection or are known to influence motor functions
insufficient knowledge of German hindering the ability to follow instructions and tests
uncorrected visual or auditory impairments

Study outcomes

The C-Gait Test measures walking adaptability using seven different subtests of the C-Mill + VR treadmill. During the test, participants are secured via a harness and their comfortable walking speed is determined at the start of the test. This speed is maintained throughout all subtests (by the system). In this study, the same walking speed will be used for the test with and without a mask.

Instructions are given both via an integrated screen and by the therapists. The seven different subtests include: 1) goal-directed stepping, 2) tandem walking, 3) obstacle avoidance, 4) slalom walking, 5) walking with suddenly shifting obstacles and targets, 6) speed adaptations, 7) dual-task walking (verbal Stroop task). A video showing examples of these tasks from Timmermans et al. (2019) can be found in the supplementary material of this article (S1 Video). All seven subtests of the C-Gait will be conducted first with an easy (level 2 of 5) and then with a difficult level (level 4 of 5) of difficulty. For each level (lowest: 1, highest: 5) the individual subtasks (except the cognitive task) are increased in difficulty as follows: 1) goal directed stepping: increased randomization of step length and width; 2) obstacle avoidance: increased size of obstacles and decreased available response time; 3) slalom walking: increased sharpness of the curves; 4) speed adaption: faster changes in speed; 5) tandem walking: decreased walking-area-width; and 6) walking with suddenly shifting obstacles and targets: increased size of obstacles and decreased available response time. According to standardized criteria, performance for each item is scored 0–100%. A detailed description of the C-Gait is provided elsewhere [20]. Performance of the five subtests "goal-directed stepping", "tandem walking", "obstacle avoidance", "slalom walking" and "speed adaptations" will be measured by the proportion of steps during which the center of pressure under the foot is within the projected area during the mid-stance phase (extended by half of the foot size for goal-directed stepping and obstacle avoidance). In the "walking with suddenly shifting obstacles and targets" task, the weighted mean of correct steps and correctly avoided obstacles is calculated. The cognitive dual-task is scored as the percentage of correct answers in a verbal Stroop task. The primary endpoint of the study is the overall performance of the C-Gait Test (composite score, calculated as Mean C-Gait scores on high level + C-Gait score for the cognitive performance task). This outcome parameter will be compared per condition (1: with face mask, 2: without face mask). Additionally, and also to account for participants who do not complete the high difficulty level, secondary endpoints including performance of the seven C-Gait subtests (calculated as Difficulty level x 2 x Performance (%) / 100), as well as performance (duration) of the four field tests (10 Meter Walk test, Timed Up-and-Go test, Timed Up-and Go test in dual task (serial 3s starting from 100) and Stair ascent/Stair Descent) will be assessed.

Assessments

Sociodemographic and clinical data will be obtained by interview and self-report questionnaires. Motor testing will be performed by physiotherapists and/or exercise scientists with extended experience with the assessments in these patient groups. In case of any health issues (disease-related on unrelated) or any discomfort during testing, the assessments will be paused or terminated accordingly. Participants will be given the option to take breaks between tests whenever needed. All forms of adverse events during testing and intervention will be documented, reported (if necessary), communicated within the interdisciplinary team, and analyzed. Participants who experience culpably caused damage could assert a claim for compensation, which would be covered by the liability insurance of the rehabilitation center. Beside this there will be no additional insurance for participants. Insurance conditions are communicated to participants verbally and in the written study information.

The following assessments will be conducted:

Expanded Disability Status Scale (EDSS) (score) [23]
Activities-Specific Balance Confidence Scale (ABC) [24] (score)
C-Gait Test [20] (composite score)
- ○ goal-directed stepping task (score)
- ○ tandem walking task (score)
- ○ obstacle avoidance task (score)
- ○ slalom walking task (score)
- ○ walking with suddenly shifting obstacles and targets task (score)
- ○ speed adaptations task (score)
- ○ dual-task walking (% of the correct answer at a verbal Stroop task)
10-meter Walk Test (10MWT) [25] (time, (s))
Timed Up and Go Test (TUG) [26] (time, (s))
Timed Up and Go Test in dual-tasking (TUG+DT) [27]
Ascending/ descending stair test [28]
Tailored questionnaire assessing perceived performance and perceived safety during the tasks with and without a mask
- ○ How did you perform on the gait tests with versus without a mask?
- ○ How safe did you feel during the gait tests with versus without a mask during the gait tests with or without wearing a face mask?

All study data will be pseudonymised during data collection and anonymized during the data entry processes. Only anonymized data will be published, presented, and made available to other researchers. All data collection, handling, and processing will be according current regulations (General Data Protection Regulation, German Federal Data Protection Act, Health Data Protection Act of North Rhine Westfphalia (NRW) and the revised Declaration of Helsinki (current version from 2013)). The planned procedures were checked by the clinic’s data protection officer and were also submitted to the ethics committee. Participants are informed about data handling protocol in the written study description.

Sample size

As this is an unfunded study in a clinical setting, certain resource constraints have been taken into consideration when planning the sample size. Considering the researcher and laboratory time available for the study and the number of patients available within its intended study duration, we estimate that fifty participants can feasibly be included in the study.

As the C-Gait, and VR treadmill-based gait adaptability assessments are a recent development, there is limited data available in the literature to make an accurate prediction of the expected size of the effect of face masks on these outcomes. Similarly, clinically meaningful differences or changes in the intended primary outcome parameters have not yet been established, due to the novelty of the topic. Two studies have compared groups with well-established balance and mobility differences from which we can draw some insight. Chen et al. [29] compared people with Parkinson’s disease with and without freezing on the various subscales of the C-Gait and found differences with effect sizes (Cohen’s d) ranging from 0.43–0.92, with an average of 0.64. Timmermans et al. [20] compared the composite C-Gait scores between healthy adults (young and middle aged), healthy older adults, and older adults with balance and gait deficits. The effect sizes of the differences were 1.98 and 1.57 when comparing the healthy adults to the healthy older adults and older adults with balance and gait deficits, respectively, and a difference of d = 0.57 between the two older adult groups. Taken together, differences in C-Gait scores between groups with meaningful differences in mobility appear to be of medium to large magnitude. Therefore, if we were to observe medium or larger effect sizes for the difference in C-Gait scores between masked and unmasked assessments, we could infer that this change would be meaningful.

A sensitivity power analysis (S1 Fig) shows that with our feasible sample size, the analyses will have power of 0.8 to detect effect sizes of d = 0.4 and a power of 0.95 to detect effect sizes of d = 0.52, based on paired t-tests (within participants, mask vs. no mask). We believe that this, in combination with the various secondary parameters, will be sufficient to provide meaningful insight into the effect of face mask use on gait adaptability and mobility.

Planned analyses

Data will be analysed using Jamovi [30] by EG and CM who will be blinded to the groups after recruitment of all participants. Interim analyses are not planned. Sample description will be done via frequencies and corresponding percentages, medians (with minimum and maximum), or means (with standard deviations). To verify suitability of parametric statistics, Shapiro-Wilk normality tests will be run for each outcome variable. If data are not normally distributed, the first and third quartiles as summaries of the dispersion, will be provided. To test the hypothesis of a potentially meaningful decline (indicated by a moderate to large effect size) in the C-Gait composite score (primary outcome as an objective measure of walking adaptability), paired t-tests (in case data is normally distributed) or Wilcoxon signed-rank tests (in case the data is not normally distributed) will be applied. To address the secondary exploratory hypotheses of an effect of face masks on specific C-Gait subtests and on the clinical tests, the same statistical approach will be applied. The test statistics, the p values and the effect size calculated as Cohen’s d will be reported. Based on the limited literature described in our sample size justification above, we will treat effects larger than d = 0.57 as meaningful, though it is currently unknown if smaller effects would also be clinically important. For all, the significance level will be set at p < 0.05.

In case of missing data (e.g., due to measurement error or e.g., sudden illness or drop out) the respective participant will be excluded from that specific analysis, if complete data for others are available.

Timeline

Data collection is planned to start in 12/2022 and end in 7/2023.

Ethical approval and registration

The study was approved by the Ethics Committee of the University Bonn, Germany (269/21). The Study is registered in the German Register for Clinical Trials (Registration Number: DRKS00030207).

Supporting information

S1 Checklist. SPIRIT 2013 checklist: Recommended items to address in a clinical trial protocol and related documents*.

(DOC)

Click here for additional data file.^{(122KB, doc)}

S1 Video. Examples of the C-Gait task from Timmermans et al. (2019) [20].

(7Z)

Click here for additional data file.^{(56.5MB, 7z)}

S1 Fig. Results of the sensitivity analysis.

(TIF)

Click here for additional data file.^{(146.7KB, tif)}

S1 File

(DOCX)

Click here for additional data file.^{(398.4KB, docx)}

S2 File

(DOCX)

Click here for additional data file.^{(364.7KB, docx)}

Acknowledgments

We thank Professor Hans Karbe, Jochen Saliger, and Florian Wolf of the Neurological Rehabilitation Center Godeshoehe for their support in preparing this research project.

Data Availability

All relevant data from this study will be made available upon study completion.

Funding Statement

The author(s) received no specific funding for this work.

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PLoS One. doi: 10.1371/journal.pone.0286402.r001

Decision Letter 0

Eric R Anson

27 Jan 2023

PONE-D-22-24759A registered report of a crossover study on the effects of face masks on walking adaptability in people with Parkinson’s disease and multiple sclerosisPLOS ONE

Dear Dr. Giannouli,

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.

Overall this is an interesting and relevant manuscript. The reviewers have all raised some important points after reviewing this manuscript, but those should be easily addressed. Based on the existing literature about vision and walking considering the potential impact on the look ahead window the point about measuring head pitch during the walking task is important to address.

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PLOS ONE

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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: Yes

Reviewer #3: Partly

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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: No

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

**********

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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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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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.

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Reviewer #1: In this registered protocol report, the aim is to investigate the effects of mask-wearing on walking adaptability in people with Parkinson’s disease and Multiple Sclerosis. Gait measures with and without a mask will be collected and will be compared using t-tests or Wilcoxon signed-rank tests.

Minor revisions:

1- The standard statistical term for average is mean.

2- Line 300: In addition to frequencies, provide the corresponding percentage.

3- Line 300: Typically the first and third quartiles are provided as summaries of the dispersion when data is not not normally distributed.

Reviewer #2: This manuscript is about a registered report of a study that will investigate the influence of wearing a facial mask on several gait tests in Parkinson’s and Multiple Sclerosis patients. This is an interesting investigation because the facial mask causes a loss of part of the lower visual field, which can compromise gait adaptability and increase the risk of falls. This study is an initial response to the scientific debate raised regarding the recommendations that older adults should be given when wearing a face mask.

Although this study is well designed, there is no measure related to head pitch in the walking tasks. It would be relevant to add this parameter, especially for the c-mill walking tasks, as the participants may compensate for the loss of the lower visual field by pitching down the head to acquire the necessary visual information to perform the tasks successfully.

Also, no measure captures the amount of lower visual field loss due to mask-wearing. Some measures related to that would also help understand how the mask may affect gait performance.

Regarding the inclusion criteria, would the ability to walk independently without an aid device be a requirement to participate in this study? In addition, would Parkinson’s disease patients have a Hoehn and Yahr between 1 and 3? How about the Multiple Sclerosis patients – would you use a scale to define participants’ disability status?

Minor comments

- line 179: what does FAC mean?

- line 180: How will “severe reduced bone density” be assessed?

Reviewer #3: Dear authors,

I read your paper with interest and here I am writing some points for you.

Please doublecheck the writing of your paper.

The tense of presentation is different in sections.

You are talking about increasing the rate of falling because of wearing mask among patients with Parkinson or MS. Is it evidence based? Please let us know about published evidences in this regard.

Your test was done on a isolated walking area, treadmill. How you can compare it with walking in street or at home?? How you have considered the environmental parameters?

In potential significant section, you suddenly focus on older adults.

" fall risk took place recently after the Safe Exercise at Home website". I am not sure about the mechanism happened here. Maybe in the first session they have some difficulties, not in all the time. Home based exercises are simple and easy to do and there is not much mobility.

I got confused, because in some parts you talk about older adults and in some parts you talk about patients with Parkinson/MS. Please be careful. A patient with MS could be 25 years old, so you can not consider her as an older adult.

Then you give some evidence regarding younger adults.

There is not a consistency in your presentation in Introduction. In addition the novelty of work is not highlighted. It is not exactly in line with your main aim and target group.

Method section should be rewritten based on an standard format.

For example: However, the medical director, as well as the executing researcher in communication with the ethics committee, might decide to terminate recruiting in certain circumstances(e.g., changes in the pandemic situation).

Recruitment & Experimental Procedures is too long and messy.

In inclusion criteria, the what stage of MS is acceptable for you? This section needs to more accurate details. What about their medicines?

I think it is a protocol of study. Is it? Please double check your title.

Your figures are not clear. Are those necessary?

Once you answer to those general points, then I will be able review your paper accurately.

Good luck

**********

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

**********

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PLoS One. 2023 Jun 29;18(6):e0286402. doi: 10.1371/journal.pone.0286402.r002

Author response to Decision Letter 0

13 Mar 2023

Replies to the academic editor’s and reviewers’ comments

The authors would like to thank the editor and the reviewers for taking the time to read our work and for the helpful comments which will improve the manuscript. Some good points have been brought up and we appreciate the opportunity to clarify our research methodology. As you will see, we revised our manuscript taking into consideration the comments of the reviewers and the editor. Below you will find the concrete answers to each comment.

We will use abbreviations for persons with Parkinson’s disease (pwPD) and persons with multiple sclerosis (pwMS).

Below we include the editor and reviewer comments in italics, followed by our responses.

Academic editor

1. Based on the existing literature about vision and walking considering the potential impact on the look ahead window the point about measuring head pitch during the walking task is important to address.

• We thank the editor for highlighting this issue and agree that it is one of the most important points raised by the reviewers. Please see our response on this point to reviewer 2 below (comment 5). Note that we are specifically requesting the editor and reviewers’ opinions on the possibilities here, since the registered report format allows us this input before conducting the study.

Reviewer #1

2. The standard statistical term for average is mean

• Thank you for bringing this to our attention. We exchanged terms in L210.

3. Line 300: In addition to frequencies, provide the corresponding percentage.

• We will be happy to provide the corresponding percentage, as you suggested, since we agree this will enhance the value of information. We made changes accordingly see L293.

4. Line 300: Typically, the first and third quartiles are provided as summaries of the dispersion when data is not normally distributed.

• You are right, reporting the first and third quartiles as summaries of the dispersion when data is not normally distributed, is the standard procedure. Therefore, we will provide these. We added a sentence on that in the manuscript L295-295.

Reviewer #2

5. Although this study is well designed, there is no measure related to head pitch in the walking tasks. It would be relevant to add this parameter, especially for the c-mill walking tasks, as the participants may compensate for the loss of the lower visual field by pitching down the head to acquire the necessary visual information to perform the tasks successfully.

• Thank you very much for the compliments on our design. We agree that the possibility of pitching the head might be an expectable form of compensation that we should consider. In addition to the suggestion that this may allow participants to maintain their performance across conditions, we would also like to point out that increased forward head pitch may also have a negative effect on gait and balance due to the more anterior center of mass position that this will result in and could, therefore, also lead to a decline in performance. As this is an applied study in a clinical setting, we only have the resources and aim to investigate the overall outcome, not the specific mechanisms, since more detailed 3D motion capture will not be possible. In the clinical setting, we would suggest that the practically relevant result is initially whether or not the condition results in a reduction in performance. Should we find or not find a difference, future research can more precisely look into these changes with more appropriate, controlled setups. This being said, there would be a few options to gain some insight into this issue and given the registered report format, we would like to offer these ideas to the editor and reviewers before adjusting our protocol.

o Option 1: Add a 5-point visual Likert scale questionnaire asking participants to rate their head pitch while completing the task with the mask compared to without the mask (“I felt like I tilted my head forward more while wearing the mask: 1 Strongly disagree, 2 disagree, 3 neutral/not sure, 4 agree, 5 strongly agree.) This will not objectively measure head tilt, but will provide information on whether or not participants perceived a change in their head position to complete the task and this may indicate that changes did or did not take place. Moreover, add a 5-point Likert scale questionnaire asking the assessing researcher to rate the patients’ head tilt during each of the tasks.

o Option 2: Take video camera recordings of the trials from a standardized position relative to the C-Mill treadmill. Have two or three of the researchers rate the head tilt during each trial as described above for a more robust estimation and to check reliability of the procedure.

o Option 3: Take video recordings as described above and use 2D video analysis to label and track head tilt for a more objective outcome.

We would like to point out that while option 3 seems to be the most objective approach, none of the authors have expertise or experience in this type of analysis and it the accuracy will not be as high as it would be with 3D motion capture. Given the significant amount of time that will be needed to label and analyze the videos for this approach and the potentially limited accuracy, we are uncertain if this will really be a worthwhile approach. We would therefore be pleased to hear the opinions of the reviewers and editors on these approaches and what they would find acceptable for the study given the clinical setting and context.

6. Also, no measure captures the amount of lower visual field loss due to mask-wearing. Some measures related to that would also help understand how the mask may affect gait performance.

• Thank you for your advice on this aspect. Since this a first experimental study on that topic with limited resources, we are unfortunately not able to take all measures into account. Existing evidence suggests 9.5-13% of negative effect on visual-field test performance (1, 2), which could be reduced to 6% when fitting the superior border of the mask well to the person’s face (1). Therefore, in our study we will try to ensure a good fit of the mask. If we still find a deficit in performance while wearing the mask, it is likely that a small percentage of visual field loss was present. We will take this evidence into account, when interpreting our results.

7. Regarding the inclusion criteria, would the ability to walk independently without an aid device be a requirement to participate in this study? In addition, would Parkinson’s disease patients have a Hoehn and Yahr between 1 and 3? How about the Multiple Sclerosis patients – would you use a scale to define participants’ disability status?

• We would like to thank this reviewer for giving us the chance to clarify this. All pwPD and pwMS that are admitted in the clinic, in which the study will take place, undergo the following tests as part of the clinic`s standard procedures: standing with narrow stance and open eyes, standing with narrow stance and closed eyes and walking for 1 min. Patients who are able to perform these tests independently or with standby assistance, will be considered for our study. Based on existing clinical data, such persons are on average: pwPD with a Hoehn & Yahr stage 1-3 and pwMS with an EDSS of 0.0-4.0. We will record and report these stages of the participants in the descriptive results.

8. line 179: what does FAC mean?

• Sorry for not introducing this abbreviation. FAC means Functional Ambulation Categories (3-5) and refers to a scale rating peoples walking ability by five categories, where low scores indicate less ability to walk and higher scores more independent ambulation. (0: Non-functional ambulatory, 1: Ambulator, dependent on continuous physical assistance, 2: Ambulator, dependent on intermittent physical assistance, 3: Ambulator, dependent on supervision, 4: Ambulator, independent level surface only, 5: Ambulator, independent). We introduced the abbreviation in L127-128.

9. line 180: How will “severe reduced bone density” be assessed?

• Apologies for the confusion. Severe reduced bone density, spinal instability or unstable fractures, and severe vascular disorders or cardiac abnormalities that affect the ability to exercise safely are general contraindications according to the C-Mill manufacture manual. These will not be explicitly assessed in our study, but patients’ medical and anamnestic reports will serve as a source for this information. Patients with those contraindicators will not be eligible for participation in our study. We clarified this in L125-130.

Reviewer #3

10. Please doublecheck the writing of your paper. The tense of presentation is different in sections.

• This manuscript is a registered report protocol for a study that is not yet conducted (stage one being very similar to a typical protocol article).

11. You are talking about increasing the rate of falling because of wearing mask among patients with Parkinson or MS. Is it evidence based? Please let us know about published evidences in this regard.

• We would like to clarify, that we do not state that pwPD and pwMS fall more often because they wear a face mask. We provide evidence that occlusion of the lower visual field might increase the risk to stumble and eventually fall (6,7). We also highlighted that there is no clear consensus on the various factors that interact to influence walking safety while wearing a mask (8-20). Based on the discussed evidence, those persons who already suffer from impairments in balance and gait, being more dependent visual information (21) and already having an increased fall risk like pwPD (22) and pwMS (23) might have an even enhanced risk for falls when wearing a mask. We argue that it is therefore important to investigate this clinically in a neurological cohort, which is supported by (24). It is the aim of our study to further investigate this question within an inpatient clinical setting.

12. Your test was done on a isolated walking area, treadmill. How you can compare it with walking in street or at home?? How you have considered the environmental parameters?

• Our primary assessment will be done on a treadmill with virtual reality so we are able to reliably simulate environmental situations and obtain objective measurements of walking adaptability based on center of pressure data. As secondary outcomes, we will also assess typical clinical mobility parameters with and without wearing a face mask, that are commonly applied to draw conclusions on real life mobility (10 metre walk test, timed-up-and-go test, stair ascent and descent). Additionally, patients will be asked to reflect on their performance and safety with and without wearing a face mask. The subjective performance and safety perception might also be indicative for subjective fears/ carelessness related to patients’ mobility. We believe that this combination of tasks and outcomes is appropriate to address our aims.

13. In potential significant section, you suddenly focus on older adults.

• The ongoing debate only focused on older adults and we will add knowledge on persons with a neurological disease. We replaced “older adults” by “persons with and without a neurological disease” to enhance clarity, see L46.

14. " fall risk took place recently after the Safe Exercise at Home website". I am not sure about the mechanism happened here. Maybe in the first session they have some difficulties, not in all the time. Home based exercises are simple and easy to do and there is not much mobility.

• The citation you refer to in your comment needs to be considered as a whole: “A scientific debate regarding the recommendations that older adults should be given when wearing a face mask in order to minimize their fall risk took place recently after the Safe Exercise at Home website (endorsed by the Australian Physiotherapy Association) published recommendations for safe exercising in older adults in the COVID era.” We bring up this publication as it was the starting point for the scientific debate on what advice to give to older people for safe walking while wearing a face mask. This controversial debate shows that there is no clear consensus on the various factors that interact to influence walking safety while wearing a mask. Which for us was one of the reasons to look into that topic for persons who might be even more impaired in balance and gait, a neurological cohort.

15. I got confused, because in some parts you talk about older adults and in some parts you talk about patients with Parkinson/MS. Please be careful. A patient with MS could be 25 years old, so you cannot consider her as an older adult.

Then you give some evidence regarding younger adults.

There is not a consistency in your presentation in Introduction. In addition the novelty of work is not highlighted. It is not exactly in line with your main aim and target group.

• see our response to comment 11

16. Method section should be rewritten based on an standard format.

• Since this is a Stage 1 Registered Report manuscript, we have written and structured the manuscript based on both the PLOS One guidelines for this article format and other general guidelines for registered reports. Please note that these typically include much more a priori methodological and study design details in the interest of transparency and accurate preregistration of the approach to be taken.

17. Recruitment & Experimental Procedures is too long and messy.

• See our response to the previous comment.

18. In inclusion criteria, the what stage of MS is acceptable for you? This section needs to more accurate details. What about their medicines?

• See our response to comment 7.

19. I think it is a protocol of study. Is it? Please double check your title.

• This is a stage 1 registered report manuscript, which is indeed similar to a traditional protocol article. Since it is the stage 2 version that is eventually published, which includes results, discussion and conclusions, we will retain the current title to accommodate for the stage 2 version.

20. Your figures are not clear. Are those necessary?

• Thank you for your comment and question on our figures. These are the results of the sensitivity analysis. PLOS One author guidelines request sample size estimations in registered report. Considering your question, we will provide the figure in the supplement. Changes to the manuscript were made accordingly, see L284 and L436.

References

1. Boxrud, C. A., Householder, N. A., Kim, D. K., Kugler, K. M., Harris, C. S., Benjamin, B. P., Panrudkevich, A. H., & Bahadur, G. G. (2023). Inferior altitudinal visual loss and mask-wearing practices: A case series. Indian journal of ophthalmology, 71(2), 657–660. https://doi.org/10.4103/ijo.IJO_934_22

2. Gómez Mariscal, M., Muñoz-Negrete, F. J., Muñoz-Ramón, P. V., Aguado Casanova, V., Jaumandreu, L., & Rebolleda, G. (2022). Avoiding mask-related artefacts in visual field tests during the COVID-19 pandemic. The British journal of ophthalmology, 106(7), 947–951. https://doi.org/10.1136/bjophthalmol-2020-318408

3. Holden, M. K., Gill, K. M., & Magliozzi, M. R. (1986). Gait assessment for neurologically impaired patients. Standards for outcome assessment. Physical therapy, 66(10), 1530–1539. https://doi.org/10.1093/ptj/66.10.1530

4. Holden, M. K., Gill, K. M., Magliozzi, M. R., Nathan, J., & Piehl-Baker, L. (1984). Clinical gait assessment in the neurologically impaired. Reliability and meaningfulness. Physical therapy, 64(1), 35–40. https://doi.org/10.1093/ptj/64.1.35

5. Marks, D. (2011). Gehfähigkeit: Functional Ambulation Categories (FAC). In Schädler, S., Kool, J., Lüthi, H., Marks, D., Oesch, P., Pfeffer, A., Wirz, M. Assessments in der Neurorehabilitation. Band 1: Neurologie, 3rd Ed. Bern, Hans Huber Verlag

6. Buckley JG, Timmis MA, Scally AJ, Elliott DB. When Is Visual Information Used to Control Locomotion When Descending a Kerb? PLoS One [Internet]. 2011 [cited 2021 Sep 10];6(4):e19079. Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0019079

7. Rietdyk S, Rhea CK. The effect of the visual characteristics of obstacles on risk of tripping and gait parameters during locomotion. Ophthalmic Physiol Opt [Internet]. 2011 May 1 [cited 2021 Sep 10];31(3):302–10. Available fr

8. Association AP. Mask up and look down | Safe Exercise at Home [Internet]. 2021 [cited 2021 Sep 12]. Available from: https://www.safeexerciseathome.org.au/mask-up-and-look-down

9. Kal EC, Young WR, Ellmers TJ. Face masks, vision, and risk of falls. BMJ [Internet]. 2020 Oct 28 [cited 2020 Nov 2];371:m4133. Available from: https://www.bmj.com/lookup/doi/10.1136/bmj.m4133

10. Kal EC, Young WR, Ellmers TJ. Authors’ response to: “Face masks and risk of falls – a vision for personalised advice and timing?” by Callisaya et al. BMJ. 2020;

11. Curzon-Jones BT, Hollands MA. Route previewing results in altered gaze behaviour, increased self-confidence and improved stepping safety in both young and older adults during adaptive locomotion. Exp Brain Res 2018 2364 [Internet]. 2018 Feb 13 [cited 2021 Sep 12];236(4):1077–89. Available from: https://link.springer.com/article/10.1007/s00221-018-5203-9

12. Ellmers TJ, Cocks AJ, Young WR. Evidence of a Link Between Fall-Related Anxiety and High-Risk Patterns of Visual Search in Older Adults During Adaptive Locomotion. Journals Gerontol Ser A [Internet]. 2020 Apr 17 [cited 2021 Sep 12];75(5):961–7. Available from: https://academic.oup.com/biomedgerontology/article/75/5/961/5541624

13. Callisaya ML, Hill K, Hill A-M, Mackintosh S, Said CM, Sherrington C, et al. Face masks and risk of falls – a vision for personalised advice and timing? BMJ. 2020;(4):8–10.

14. Marigold DS, Patla AE. Visual information from the lower visual field is important for walking across multi-surface terrain. Exp Brain Res 2008 1881 [Internet]. 2008 Mar 6 [cited 2021 Sep 12];188(1):23–31. Available from: https://link.springer.com/article/10.1007/s00221-008-1335-7

15. Latt MD, Hylton AE, Menz B, Victor AE, Fung S, Lord SR. Walking speed, cadence and step length are selected to optimize the stability of head and pelvis accelerations.

16. Huijben B, van Schooten KS, van Dieën JH, Pijnappels M. The effect of walking speed on quality of gait in older adults. Gait Posture. 2018 Sep 1;65:112–6.

17. McCrum C. Walking slower increases anterior stability to a trip: a consideration for face masks and falls risk. BMJ. 2020;1–2.

18. Pavol MJ, Owings TM, Foley KT, Grabiner MD. Gait Characteristics as Risk Factors for Falling From Trips Induced in Older Adults. Journals Gerontol Ser A [Internet]. 1999 Nov 1 [cited 2021 Sep 12];54(11):M583–90. Available from: https://academic.oup.com/biomedgerontology/article/54/11/M583/544811

19. Süptitz F, Karamanidis K, Catalá MM, Brüggemann GP. Symmetry and reproducibility of the components of dynamic stability in young adults at different walking velocities on the treadmill. J Electromyogr Kinesiol. 2012 Apr 1;22(2):301–7.

20. McCrum C, Willems P, Karamanidis K, Meijer K. Stability-normalised walking speed: A new approach for human gait perturbation research. J Biomech. 2019 Apr 18;87:48–53.

21. Yakubovich S, Israeli-Korn S, Halperin O, Yahalom G, Hassin-Baer S, Zaidel A. Visual self-motion cues are impaired yet overweighted during visual–vestibular integration in Parkinson’s disease. Brain Commun [Internet]. 2020 Jan 1 [cited 2021 Sep 10];2(1). Available from: https://academic.oup.com/braincomms/article/2/1/fcaa035/5814201

22. Nilsagard Y, Gunn H, Freeman J, Hoang P, Lord S, Mazumder R, et al. Falls in people with MS - An individual data meta-analysis from studies from Australia, Sweden, United Kingdom and the United States. Mult Scler J [Internet]. 2015 Jan 14 [cited 2021 Nov 30];21(1):92–100. Available from: https://journals.sagepub.com/doi/10.1177/1352458514538884

23. Homann B, Plaschg A, Grundner M, Haubenhofer A, Griedl T, Ivanic G, et al. The impact of neurological disorders on the risk for falls in the community dwelling elderly: a case-controlled study. BMJ Open [Internet]. 2013 Nov 1 [cited 2021 Nov 30];3(11):e003367. Available from: https://bmjopen.bmj.com/content/3/11/e003367

24. Klatt BN, Anson ER. Navigating Through a COVID-19 World: Avoiding Obstacles. J Neurol Phys Ther [Internet]. 2021 Jan 1 [cited 2021 Mar 30];45(1):36–40. Available from: https://journals.lww.com/10.1097/NPT.0000000000000338

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PLoS One. doi: 10.1371/journal.pone.0286402.r003

Decision Letter 1

Eric R Anson

16 May 2023

A registered report of a crossover study on the effects of face masks on walking adaptability in people with Parkinson’s disease and multiple sclerosis

PONE-D-22-24759R1

Dear Dr. Giannouli,

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,

Eric R. Anson

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

Reviewer #3: 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?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

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 relating to the statistical aspects of the manuscript have been adequately addressed.

Reviewer #2: I want to thank the authors for thoughtfully revising the manuscript. I understand the limitations of clinical studies like this regarding using a 3D motion analysis system to assess head pitch angle. I liked that the authors proposed three different options to introduce simple measures of head motion. I agree with the authors that option 3 is the most objective, whereas, in my opinion, option 1 is the most subjective. I would go with options 2 or 3. For option 3, you do not need to analyze the entire time series. You could measure head tilt at foot contact. This should be sufficient to get a reasonable estimate of changes due to mask-wearing. As a suggestion, you could try the software Kinovea (https://www.kinovea.org/).

Reviewer #3: Dear authors,

Many thanks for your valuable submission.

You have done my comments accurately and I am happy about this revised version.

Kind regards

**********

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

**********

PLoS One. doi: 10.1371/journal.pone.0286402.r004

Acceptance letter

Eric R Anson

16 Jun 2023

PONE-D-22-24759R1

A registered report of a crossover study on the effects of face masks on walking adaptability in people with Parkinson’s disease and multiple sclerosis

Dear Dr. Giannouli:

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.

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Kind regards,

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on behalf of

Dr. Eric R. Anson

Academic Editor

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 Checklist. SPIRIT 2013 checklist: Recommended items to address in a clinical trial protocol and related documents*.

(DOC)

Click here for additional data file.^{(122KB, doc)}

S1 Video. Examples of the C-Gait task from Timmermans et al. (2019) [20].

(7Z)

Click here for additional data file.^{(56.5MB, 7z)}

S1 Fig. Results of the sensitivity analysis.

(TIF)

Click here for additional data file.^{(146.7KB, tif)}

S1 File

(DOCX)

Click here for additional data file.^{(398.4KB, docx)}

S2 File

(DOCX)

Click here for additional data file.^{(364.7KB, docx)}

Attachment

Submitted filename: Response to Reviewers.docx

Click here for additional data file.^{(27.9KB, docx)}

Data Availability Statement

All relevant data from this study will be made available upon study completion.

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PERMALINK

A registered report of a crossover study on the effects of face masks on walking adaptability in people with Parkinson’s disease and multiple sclerosis

Mareike Eschweiler

Christopher McCrum

Eleftheria Giannouli

Roles

Abstract

Background

Methods

Potential significance

Trial registration

Background

Methods

Recruitment & experimental procedures

Inclusion & exclusion criteria

Inclusion criteria

Exclusion criteria

Study outcomes

Assessments

Sample size

Planned analyses

Timeline

Ethical approval and registration

Supporting information

Acknowledgments

Data Availability

Funding Statement

References

Decision Letter 0

Eric R Anson

Roles

Author response to Decision Letter 0

Decision Letter 1

Eric R Anson

Roles

Acceptance letter

Eric R Anson

Roles

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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