PLoS ONE plos plosone PLOS ONE 1932-6203 Public Library of Science San Francisco, CA USA 10.1371/journal.pone.0284738 PONE-D-22-05428 Research Article Medicine and health sciencesHealth careCaregivers Medicine and health sciencesClinical geneticsChromosomal disordersDown syndrome Medicine and health sciencesHealth careQuality of life Biology and life sciencesBioengineeringBiotechnologyMedical devices and equipmentAssistive technologies Engineering and technologyBioengineeringBiotechnologyMedical devices and equipmentAssistive technologies Medicine and health sciencesMedical devices and equipmentAssistive technologies Medicine and health sciencesHealth careQuality of lifeActivities of daily living Medicine and health sciencesMental health and psychiatryDementiaAlzheimer's disease Medicine and health sciencesNeurologyDementiaAlzheimer's disease Medicine and health sciencesMedical conditionsNeurodegenerative diseasesAlzheimer's disease Medicine and health sciencesNeurologyNeurodegenerative diseasesAlzheimer's disease Medicine and health sciencesMedical conditionsDisabilitiesIntellectual disability Medicine and health sciencesNeurologyIntellectual disability Computer and information sciencesSoftware engineeringComputer software Engineering and technologySoftware engineeringComputer software A feasibility study demonstrating that independence, quality of life, and adaptive behavioral skills can improve in children with Down syndrome after using assistive technology Improved Independence and Quality of Life in Children with Down syndrome Using Assistive Technology White Kaylin Investigation Methodology Project administration Supervision Writing – original draft 1 https://orcid.org/0000-0002-8899-2280 Han Samuel S. Conceptualization Data curation Investigation Methodology Project administration Supervision Writing – original draft Writing – review & editing 1 * Britton Angela Conceptualization Writing – original draft Writing – review & editing 2 ‡ Hendrix James Conceptualization Writing – original draft Writing – review & editing 2 ‡ Research and Development, MapHabit, Inc., Atlanta, Georgia, United States of America Scientific Research, LuMind IDSC Foundation, Burlington, Massachusetts, United States of America Carels Vanessa Editor PLoS ONE, UNITED STATES

We have read the journal’s policy and the authors of this manuscript have the following competing interests: Co-author, Kaylin White, MS, is a part-time consultant at MapHabit, Inc., the company that developed the assistive technology (the MapHabit System) that is used in this feasibility study. Ms. White receives compensation from MapHabit, Inc. Co-author, Samuel S. Han, B.A., is a part-time consultant at MapHabit, Inc., the company that developed the assistive technology (the MapHabit System) that is used in this feasibility study. Mr. Han receives compensation from MapHabit, Inc. The recruitment of subjects participating in the study was done independently of the authors, and carried out initially by the LuMind IDSC Foundation, a national support entity for families with Down syndrome. Statistical analyses of all data were carried out independently of the authors by a biostatistical resource department of an academic health center. Other than sharing the costs necessary to carry out the study, neither MapHabit, Inc., nor any MapHabit Inc. employees have any financial link to the LuMind IDSC Foundation, or to the independent biostatistical resource used in the study. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

‡ AB and JH also contributed equally to this work.

 * E-mail: shan@maphabit.com 24 5 2023 2023 18 5 e0284738 26 4 2022 5 4 2023 2023 White et al This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Enhancing independence and quality of life are key modifiable outcomes that are short- and long-term goals for children with Down syndrome and for their parents. Here we report the outcome of a 4-week feasibility study in a cohort of 26 children with Down Syndrome, 7–17 years old, who used an assistive technology approach that incorporated smart device software and step-by-step pictures (the MapHabit System). Parents reported improvements in children’s activities of daily living, quality of life, and independence. They recommended this technology to other families. This report and its findings underscore the feasibility of using assistive technology in children with Down syndrome within home and family settings. A limiting factor is whether participants who did not complete the study, and thus were not included in analyses, might have impacted the study outcomes. The current findings that assistive technology can be used successfully and effectively in family and home settings set the stage for more informative systematic studies using assistive technology for this population.

Trial registration: The clinical trial is registered with ClinicalTrials.gov

Registration number: NCT05343468

 http://dx.doi.org/10.13039/100000049 National Institute on Aging R43AG065081 http://dx.doi.org/10.13039/100014371 LuMind Research Down Syndrome Foundation MapHabit, Inc. This manuscript and supporting research were made possible in part by the National Institute on Aging of the National Institutes of Health under award number R43AG065081. This includes 33% ($15,000) funded with federal money and 66% ($30,000) non-government sources. Non-government sources include LuMind IDSC Foundation ($ 15,000) and in-kind donation by MapHabit, Inc. ($ 15,000). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of health. The funder MapHabit, Inc. had a role in the decision to publish the research. The funder LuMind IDSC foundation had no role in the conception and execution of the study. LuMind IDSC Foundation https://www.lumindidsc.org/s/1914/20/home.aspx?gid=2&pgid=61 MapHabit, Inc.: https://www.maphabit.com/ Data Availability The study data has been submitted for public availability at Dryad, a data repository: (DOI): doi:10.5061/dryad.12jm63z2w. Introduction

Down syndrome (DS) is a leading cause of intellectual disability. Prominent in the phenotype of individuals born with DS is developmentally impaired learning and memory emerging during the early part of their lifespan. Recently, there have been reports of considerable positive impact on quality of life in individuals with Alzheimer’s disease (AD) who have used assistive technology (AT) [1]. AT is usually defined as “any piece of equipment, or product system, whether acquired commercially, modified, or customized, that is used to increase, maintain, or improve functional capabilities of individuals with disabilities” [2]. The use of AT within AD communities has been associated with promoting independent living, engagement, enhanced ability to complete activities of daily living, and reduced stress for patients and caregivers [3–6].

While the etiology of cognitive decline due to AD is different than the cognitive deficits due to DS, there are similarities in phenotype characteristics [7]. The findings that the use of AT can assist and support adults with cognitive decline due to AD raise the straightforward question of whether children who have cognitive and behavioral impairments due to DS might also benefit from the use of AT, along with their caregivers. Importantly, the efficacy of AT in children with DS is an area of research that is still in its infancy and expanding with the rise of mobile device technology and its subsequent accessibility and familiarity [8]. In turn, continued empirical investigations of using AT among the DS community are needed. To address this need, the current study examined the feasibility of an AT as an intervention among children with DS. For the purpose of this study, we use the term feasibility to mean an assessment of a future randomized controlled trial evaluating the effect of an intervention” [9]. Here, we describe the findings from a feasibility study that used a simple pre-post intervention design to assess whether there was behavioral impact in a group of children with DS, ages 7–17, after using an AT for four weeks.

 Methods Clinical trial registration, consent, and enrollment Ethical approval and clinical trial registration

Advarra Institutional Review Board (IRB) served as the IRB of record (Pro00039611). The study is registered as a clinical trial with ClinicalTrials.gov (NCT05343468), a registry that meets the requirements of the International Committee of Medical Journal Editors (ICMJE). Registration for the study did not occur prior to participant enrollment due to the intervention being at the feasibility stage and the device not meeting the criteria for regulatory oversight by the Food and Drug Administration. The study underwent appropriate registration per the request that all forms of interventional studies be registered through an ICMJE-approved registry. The authors confirm that all ongoing and related trials for this intervention are registered.

 Recruitment, consent, and enrollment

Community outreach activities (social media, email, and web site posting) were performed by a Down syndrome research and resources organization based in the United States. Interested parties were directed from the organization channels to clinical coordinators of the study. Identified candidates completed the informed consent process, which included an electronic informed consent form that was filled out by the parent or legal guardian of the child with Down syndrome through a virtual meeting with a clinical coordinator. Informed consent forms were electronically signed, documented, and stored in REDCap, a research electronic data capture database. Assent forms were provided to the parents and legal guardians to explain the study and obtain consent from the children. The clinical coordinators worked with the families for the duration of the virtual study.

Parents or guardians are referred to here as “caregivers” and the enrolled children as “participants”. Caregivers completed all the assessments from which the findings were derived. Participants used the AT under the supervision of their caregiver throughout the duration of the study. Monetary compensation was provided to families for completing the requirements of the study. Eligibility criteria included the children being diagnosed with Down syndrome and being between the ages of 7 to 17. Additionally, participants were required to have internet access and be proficient in English. 72 families were assessed for eligibility. 18 of those families were excluded, with two of them not meeting inclusion criteria and the rest ultimately declining to participate. 54 participants began the intervention, with 23 of them lost after no contact from them during their participation and five participants who expressed no desire to continue. A total of 26 families fully completed the study (Table 1 and Fig 1). The study began recruitment and enrollment in September of 2020 and reached a primary completion date of June of 2021. The final study completion date was in August of 2021.

10.1371/journal.pone.0284738.g001 CONSORT participant flow diagram. 10.1371/journal.pone.0284738.t001 Participant demographics.
Variables Sample (n = 26)
Age
  Mean ± SD 11.5 ± 3.4
  Min-Max 7.0–17.0
Gender (%)
  Female 11 (42.3)
  Male 15 (57.7)
Race (%)
  White or Caucasian 20 (76.9)
  Hispanic or Latinx 3 (11.5)
  Black or African American 1 (3.8)
  Other 2 (7.7)

Description of the demographics of all participants included in the study. Spearman’s rank order correlation test was used for any correlations between demographic variables and assessment scores. No significant correlations were observed between any variables (all p values >1.0).

 The MapHabit system

Most AT that are dedicated to individuals with DS assist in teaching and reinforcing highly specific functional skills, such as memory, social inclusion, or labor [10–12]. Although these technologies each focus on particular skills, what is universal is the aim to support decision-making capacity, increase self-determination, and enhance self-esteem through daily activities in individuals with DS, all of which are factors that should be prioritized in AT development [8]. The MapHabit System (MHS) is a commercially available visual mapping software application that utilize visual, audio, and text media to create step-by-step visual guides—which are called maps—to assist individuals and their caregivers in structuring and accomplishing activities of daily living (ADLs) (Fig 2). The MHS has been shown to be effective in enhancing overall quality of life in individuals with AD [3–6]. The goal of the application is to develop and facilitate habits and routines using structured visual and auditory stimuli that can be customized by the user and can include educational and lesson-based material in addition to ADLs. This allows the user to engage in a wide range of functional skills, a unique aspect that differs from other AT that emphasize a specific set of functional skills. Moreover, the software application attempts to enhance the independence and confidence of their users [3–6], aligning with the tenants of AT mentioned above. The application was made available to families through compatible smartphones and tablets.

10.1371/journal.pone.0284738.g002 Example of a visual map.

An example of a visual map for an activity of daily living titled "Laundry", in which there are a total of 8 sequential steps guiding the user through a certain aspect of the activity. Each step appears individually and only progresses to the next step once the user interacts with the device’s touch screen. Once the user reaches the last step of the activity, the user is able to confirm that it has been successfully completed. The individual pictured in Fig 2 has provided written informed consent (as outlined in PLOS consent form) to publish their image alongside the manuscript. Republished under a CC BY license, with permission from MapHabit, Inc., original copyright 2022.

 Study design

Participants and caregivers were first trained on the use of the MHS by study coordinators in a single session, including discussing the most needed ADL maps for the participants and how to make and personalize their own maps. These training sessions were approximately one hour long. Caregivers were instructed to create and implement three visual maps for the participants, and to use the application at least 5 days per week. Caregivers were administered standardized assessment questionnaires before and after four weeks of using the MHS. This single-arm repeated measures design permitted us to obtain baseline measures and compare them with the post-intervention outcomes. All training and pre/post assessments between caregivers and the study coordinators were done remotely via virtual video calls.

 Assessments

Caregivers completed the pre/post assessments of their participants using the Adaptive Behavior Assessment System Third Edition (ABAS-3) [13] to evaluate conceptual, social, and practical behavioral skills that are significant for day-to-day functioning [14]. Analyses were carried out using the ABAS-3 General Adaptive Composite (GAC), a final score that captures all three of an individual’s adaptive behavioral skills. At the end of the study, the ABAS-3 was re-administered to caregivers, along with two additional assessments. First, an 18-item quality-of-life questionnaire (QoL-18) that evaluates a range of participants’ behaviors, including mood, engagement, and memory at the end of the study compared to before the use of the MHS [3–5], which used a 5-point Likert scale format [15] where a higher score is better (5. Much better, 4. Better, 3. Not much change, 2. Worse, 1. Much worse). Secondly, a 2-item Satisfaction Scale (SS-2) that quantified caregivers’ endorsements to two survey questions: How satisfied were they with the MHS? Would they recommend MHS to others?

 Data analyses

All analyses were carried out independently by an academic university’s Department of Biostatistics, not connected with MapHabit, Inc. or any study authors. Statistical Product and Service Solutions (SPSS) statistics software, developed by International Business Machines Corporation (IBM), was used for all analyses. Paired group comparisons used the nonparametric Wilcoxon matched-pairs signed ranks test, and unpaired comparisons used the nonparametric Mann-Whitney test. All comparisons used 2-tail tests. For Quality-of-Life item analyses, the one-sample Wilcoxon test (also referred to as one-sample Wilcoxon signed-rank test) was used to compare scores against the null hypothesis (score of ‘3’).

 Results Demographics

Spearman’s rank order correlation test was used to analyze for any associations between the demographics of participants and their respective scores on the assessments. No correlations of significance were found between any of the participants’ demographic variables (Table 1) and scores on any the pre and post assessment variables (all p values > 1.0).

 ABAS-3

GAC1 refers to pre-scores. GAC2 refers to post-scores. The 26 participants obtained a median GAC2 score of 48.0 at the end of training, 5.5 points (8.5%) higher than their median GAC1 score of 42.5 (p = 0.0071; Table 2). Eighteen participants (69.2%) showed improved scores (GAC1 = 39.5; GAC2 = 53.0; (p = 0.001), while eight participants (30/7%) showed lower scores (GAC1 score = 47.5; GAC2 score = 40.5; p = 0.0078). There was no significant difference between the eighteen and eight participants in median GAC1 scores (18 participants = 39.5, 8 participants = 47.5, (p = 0.90)). For the pre-post comparisons, Wilcoxon matched pairs signed rank test was used. The Mann-Whitney U test was used to compare between groups.

10.1371/journal.pone.0284738.t002 ABAS-3 pre and post scores.
Group Median (IQR) p1
GAC1 GAC2
All (n = 26) 42.5 (25) 48.0 (27) <0.01
Improved (n = 18) 39.5 (31) 53.0 (32) <0.001
Decreased (n = 8) 47.5 (14) 40.5 (16) <0.01

Note: IQR indicates interquartile range

1 p values were calculated using the Wilcoxon matched pairs signed rank test; p<0.05 statistically significant; p<0.001 highly significant

 QOL-18

Scores for 13 of the 18 items reached statistical significance (i.e., they were significantly higher than the null hypothesis score of 3.0; p values of the one-sample Wilcoxon test ranged from < 0.05 to < 0.001; Fig 3). Five items had scores not significantly different from 3.0(all p values > 0.05).

10.1371/journal.pone.0284738.g003 Quality of life scores.

Average scores for the 26 participants on the 18-item Quality of Life questionnaire. Words on the left abbreviate the full question (e.g., ADL Ability: “Compared to before using the MapHabit System, is your child’s ability to complete activities of daily living now…”) and caregivers answered using the 5-point Likert scale that ranged from 1 = much worse to 5 = much better (see Methods).

 SS-2

The response scores of the 26 caregivers on each of the two questions were overwhelmingly positive with 20 caregivers (76.9%) “strongly agree” or “agree” in answers to both questions. Only two caregivers had negative responses to the two questions.

 Discussion ABAS-3

While the overall pre-post improvement between GAC1 and GAC2 scores was numerically small (Table 2), the level of statistical significance was high (p = 0.0071), even though not all participants showed improved GAC2 scores (see Results). Scores on the QOL-18 and the SS-2, likewise, reflected overall strong positive experiences. Taken together, these findings suggest that the pre-post difference on the ABAS-3 assessment, although numerically small, represented a meaningful and positive behavioral change.

 QOL-18

Thirteen of the 18 items were endorsed by caregivers as having significant positive changes (all p’s < 0.01), including items related to accomplishing ADLs as well as items focused on other behaviors and on emotions. Only five questions did not evidence change, (p’s > 0.05; Fig 3). Caregivers frequently and spontaneously commented on how the use of the MHS improved their own quality of life (e.g., reduced stress, caregiver burden) as well as that of their participants.

 SS-2

One of the challenges to the adoption of AT in various communities is simply ignorance of its availability [16]. The majorly positive responses to the experiences using the MHS by caregivers in the present study are encouraging. Enhancing communication and understanding of availability seems a small hurdle toward more universal use of AT.

 Conclusion

The findings observed in this study underscore the feasibility of using AT and it having a positive impact on behavioral outcomes in children with DS within family settings. Moreover, the findings set the stage for conducting systematic RCT studies to further evaluate the efficacy of AT. To underscore the latter point, the present feasibility study did identify methodological limitations that can inform future research of the MHS. First, a RCT would allow for a more systematic assessment of variables that could impact behavioral change. Second, eight participants showed no improvement on ABAS-3 scores, and it would be useful to explore what variables (e.g., parent engagement, grouping of participants based on various other behavioral phenotypes) might be linked to positive and negative outcomes. Third, our limited sample size prevented meaningful exploration of the effects of demographic variables such as age, gender, ethnicity, or additional intellectual disabilities, as well as more systematic subgroup analyses. A good example is the ABAS-3 scores of the 18 participants who reported improvement versus the 8 participants who did not. Retrospective power analysis revealed that in order to achieve a statistical power of 0.80 to detect a 95% confidence (p = 0.05), a total sample size of 30 would be required. Our recruited sample size (n = 26) for this current feasibility study was underpowered for stratification into subgroups and points to the important consideration that researchers must be prepared to devote considerable time and effort to obtain adequate levels of recruitment of Down syndrome families. Specifically, it will be important for future investigations to stratify participants with DS based on the severity of their intellectual disability. This specificity can allow a deeper understanding of this AT’s effectiveness in the outcomes that were observed here and address the wide range of intellectual or developmental disability that is observable in the DS community. In turn, such investigation can expand to observe if AT has a similar impact on other intellectual and developmental disability communities, such as families with autism. Fourthly, we acknowledge that 28 participants did not complete the study and resulted in incomplete data. This may have been due to the study having been taken place during the beginning of the COVID-19 pandemic and subsequent nationwide lockdowns in the United States. This was a time of uncertainty met with many challenges as families were navigating quarantine protocols, school shutdowns, and lifestyle changes, leading to the inability to continue with their participation in the study. Whether the incomplete participation of these subjects could have affected the study’s outcomes is another limiting factor. Lastly, the study was not designed to focus on caregiver stress or burden variables, and the impact of these variables will surely be useful to explore, as will having participants complete their own assessments.

Previously published work within this field explored the efficacy of assistive technology for children with Down Syndrome under the context of school learning or particular functional skills, but the current findings that assistive technology can be used successfully and effectively in family and home settings set the stage for more informative systematic studies. Overall, these findings are encouraging. The use of AT may provide important and effective interventions to help enhance overall quality of life and independence for children living with DS as well as their parents or caregivers. Moreover, as described in the Introduction, AT has experienced growing acceptance within the AD community as a useful intervention for helping maintain QOL and independence. The availability of a similar kind of effective intervention early in life in DS may prove advantageous for the well-being and continuity of care for the intellectual disability community.

 Supporting information Protocol of current study.

(DOCX)

 TREND statement checklist.

(DOC)

This manuscript and supporting research were made possible in part by the support and participation of families within the Down syndrome community. We thank Kevin Xu and Yanan Wang for assistance and validation of statistical analyses, Paolo Aguila for assistance with figure illustrations, and Matthew Golden and Stuart Zola, co-Founders of MapHabit, Inc., and Hampus Hillerstrom, President and CEO of Lumind IDSC Foundation for their support that enabled the undertaking of this study.

 References Klimova B, Valis M, Kuca K. Exploring assistive technology as a potential beneficial intervention tool for people with Alzheimer’s disease–a systematic review. Neuropsychiatric disease and treatment. 2018 Nov 16:3151–8. doi: 10.2147/NDT.S181849 30532546 Individuals with Disabilities Education Act 2004 (USA). https://sites.ed.gov/idea/statute-chapter-33/subchapter-i/1401/1/A Boatman F, Golden M, Jin J, Kim Y, Law S, Lu A, et al. Assistive technology: visual mapping combined with mobile software can enhance quality of life and ability to carry out activities of daily living in individuals with impaired memory. Technology and Health Care. 2020 Jan 1;28(2):121–8. doi: 10.3233/THC-191980 31796718 Kelleher J, Zola S, Cui X, Chen S, Gerber C, Parker MW, et al. Personalized visual mapping assistive technology to improve functional ability in persons with dementia: feasibility cohort study. JMIR aging. 2021 Oct 19;4(4):e28165. doi: 10.2196/28165 34269690 Parker MW, Davis C, White K, Johnson D, Golden M, Zola S. Reduced care burden and improved quality of life in African American family caregivers: Positive impact of personalized assistive technology. Technology and Health Care. 2022 Jan 1;30(2):379–87. doi: 10.3233/THC-213049 34334439 Han SS, White K, Cisek E. A Feasibility Study of Individuals Living at Home with Alzheimer’s Disease and Related Dementias: Utilization of Visual Mapping Assistive Technology to Enhance Quality of Life and Reduce Caregiver Burden. Clinical Interventions in Aging. 2022 Dec 31:1885–92. doi: 10.2147/CIA.S387255 36583148 Asim A, Kumar A, Muthuswamy S, Jain S, Agarwal S. Down syndrome: an insight of the disease. Journal of biomedical science. 2015 Dec;22(1):1–9. Krasniqi V, Zdravkova K, Dalipi F. Impact of assistive technologies to inclusive education and independent life of down syndrome persons: a systematic literature review and research agenda. Sustainability. 2022 Apr 13;14(8):4630. Eldridge SM, Lancaster GA, Campbell MJ, Thabane L, Hopewell S, Coleman CL, et al. Defining feasibility and pilot studies in preparation for randomised controlled trials: development of a conceptual framework. PloS one. 2016 Mar 15;11(3):e0150205. doi: 10.1371/journal.pone.0150205 26978655 Gomez J, Torrado JC, Montoro G. Using smartphones to assist people with Down syndrome in their labour training and integration: a case study. Wireless Communications and Mobile Computing. 2017 Dec 21;2017. Cuascota L, Guevara L, Cueva R, Tapia F, Guerrero G. Assistance application of people with cognitive disabilities in tasks for their social inclusion. In 2019 14th Iberian Conference on Information Systems and Technologies (CISTI) 2019 Jun 19 (pp. 1–7). IEEE. Hornero G, Conde D, Quilez M, Domingo S, Rodríguez MP, Romero B, et al. A wireless augmentative and alternative communication system for people with speech disabilities. IEEE Access. 2015 Aug 7;3:1288–97. Harrison PL, Oakland T. ABAS-3. Torrance: Western Psychological Services; 2015. Prokopiak A, Kirenko J. ABAS-3–an instrument for assessing adaptive skills in people with an intellectual disability. Hrvatska revija za rehabilitacijska istraživanja. 2020 Dec 23;56(2):154–68. McLeod S. Likert Scale Definition. Examples and Analysis| Simply Psychology. [(accessed on 15 March 2020)]. 2019. Copley J, Ziviani J. Barriers to the use of assistive technology for children with multiple disabilities. Occupational therapy international. 2004 Nov;11(4):229–43. doi: 10.1002/oti.213 15771212 10.1371/journal.pone.0284738.r001 Decision Letter 0 Verduci Lorena Staff Editor 2023 Lorena Verduci This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version 0

1 Sep 2022

PONE-D-22-05428

Independence, Quality of Life, and Adaptive Behavioral Skills Improved in Childrenwith Down Syndrome After Using Assistive Technology

PLOS ONE

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Co-author, Kaylin White, MS, is a part-time consultant at MapHabit, Inc., the company that developed the assistive technology (the MapHabit System) that is used in this feasibility study. Ms. White receives compensation from MapHabit, Inc.

Co-author, Samuel S. Han, B.A., is the Clinical Lead of MapHabit, Inc., the company that developed the assistive technology (the MapHabit System) that is used in this feasibility study. Mr. Han receives salary from MapHabit, Inc.

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5. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide.

6. Please include your full ethics statement in the ‘Methods’ section of your manuscript file. In your statement, please include the full name of the IRB or ethics committee who approved or waived your study, as well as whether or not you obtained informed written or verbal consent. If consent was waived for your study, please include this information in your statement as well.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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

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

Reviewer #1: Partly

**********

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

Reviewer #1: No

**********

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

**********

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

**********

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: The study aims to assess the significant behavioral impact of Assisted Technology on a group of children with Down Syndrome ages 7-17.

Comments

If it is a feasibility type of study, the word feasibility is to be added to the title.

Data analyses section is to be placed in the method section and not in the results section.

Line 115, the publisher name for the statistical software and its version to be stated. The level of statistical significance acceptance is to be stated.

Line 116-117, the use of the statistical tests for what comparison in the context of this study and the name of the correlation test is to be clearly stated.

Effect size could be employed to determine the effect of the intervention.

For a feasibility study, significance testing is not encouraged unless the sample size is properly/adequately powered (Line 166, 'limited sample size')

Results

The percentage figures are to be presented with at least one decimal point.

Line 117-119, Line 120-125, the data to be presented in table form.

Figure 2A could be presented in table form with median and IQR values rather than using a bar chart.

Line 122-123, the flow of the sentence requires improvement.

Line 124, ‘two subgroups participants’ to be revised. To state ‘there was no statistical difference between the 18 and 8 participants.'

Line 127, the name of the statistical test to be denoted in the Figure 2b footnote and in the data analyses section.

Figure 2a, statistical test to be denoted in the figure footnote. P value could be displayed on the figure rather than mentioned in the title.

Figure 2b, *, *** and dark line to be denoted in the Figure footnote.

CONSORT diagram to be revised and tweaked based on this study e.g. method, flow etc

Not all references comply with the journal format.

**********

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

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

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

Reviewer #1: No

**********

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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.

 10.1371/journal.pone.0284738.r002 Author response to Decision Letter 0 Submission Version 1

3 Nov 2022

Dear Dr. Verduci,

Thank you for giving us the opportunity to submit a revised draft of our manuscript previously titled “Independence, Quality of Life, and Adaptive Behavioral Skills Improved in Children with Down Syndrome After Using Assistive Technology” to PLOS ONE, now titled “A Feasibility Study Demonstrating that Independence, Quality of Life, and Adaptive Behavioral Skills Can Improve in Children with Down Syndrome After Using Assistive Technology” (see Reviewer Comment 1). We are grateful for the time and effort that you and the reviewer have dedicated in providing valuable feedback on our manuscript. We appreciate the insightful comments from you and the reviewer. We were able to incorporate changes to reflect the suggestions that were provided. Below are the point-by-point responses to the editor and reviewer’s comments and concerns:

Comments from Editor

Comment 1: Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming

Response: Thank you for this reminder. We have reviewed the manuscript and made changes that meet PLOS ONE’s style requirements.

Comment 2: Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information.

Response: We have added the details mentioned in the comment above into the Methods section of the revised manuscript.

Comment 3: We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form… Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement… Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

Response: We have removed the funding information from the Acknowledgements section and included our amended statements within our new cover letter.

Comment 4: Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: ""This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared. Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf.

Response: We confirm this does not alter our adherence to PLOS ONE policies on sharing data and materials. The updated Competing interests statement is included in our amended statements within our new cover letter.

Comment 5: We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide.

Response: We confirm the data availability statement upon acceptance.

Comment 6: Please include your full ethics statement in the ‘Methods’ section of your manuscript file. In your statement, please include the full name of the IRB or ethics committee who approved or waived your study, as well as whether or not you obtained informed written or verbal consent. If consent was waived for your study, please include this information in your statement as well.

Response: The full ethics statement has been included in the ‘Methods’ section of our manuscript file.

Comments from Reviewer

Comment 1: If it is a feasibility type of study, the word feasibility is to be added to the title.

Response: The title has been revised to address this comment.

Comment 2: Data analyses section is to be placed in the method section and not in the results section.

Response: The suggested change has been made in the manuscript.

Comment 3: Line 115, the publisher’s name for the statistical software and its version to be stated. The level of statistical significance acceptance is to be stated.

Response: The suggested additions have been made in the manuscript.

Comment 4: Line 116-117, the use of the statistical tests for what comparison in the context of this study and the name of the correlation test is to be clearly stated.

Response: The suggested additions have been made in the manuscript.

Comment 5: Effect size could be employed to determine the effect of the intervention.

Response: See Response to Comment 6, below.

Comment 6: For a feasibility study, significance testing is not encouraged unless the sample size is properly/adequately powered (Line 166, 'limited sample size')

Response: We have added a section to the discussion indicating that our study was underpowered for some analyses (e,g., further stratification of subject groups, effect size). Nevertheless, as we have indicated, the findings evidenced important behavioral outcomes to be further explored, as well as the need for researchers to be prepared to devote considerable resources to recruitment efforts and participant retention.

Comment 7: The percentage figures are to be presented with at least one decimal point.

Response: The suggested change has been made in the manuscript.

Comment 8: Line 117-119, Line 120-125, the data to be presented in table form.

Response: The suggested change has been made in the manuscript.

Comment 9: Figure 2A could be presented in table form with median and IQR values rather than using a bar chart.

Response: The suggested change has been made in the manuscript.

Comment 10: Line 122-123, the flow of the sentence requires improvement.

Response: The suggested clarification has been made in the manuscript.

Comment 11: Line 124, ‘two subgroups participants’ to be revised. To state ‘there was no statistical difference between the 18 and 8 participants.'

Response: The suggested revision has been made in the manuscript.

Comment 12: Line 127, the name of the statistical test to be denoted in the Figure 2b footnote and in the data analyses section.

Response: The suggested additions has been made in the manuscript and figure.

Comment 13: Figure 2a, statistical test to be denoted in the figure footnote. P value could be displayed on the figure rather than mentioned in the title.

Response: The suggested additions and changes have been made in the manuscript and figure.

Comment 14: Figure 2b, *, *** and dark line to be denoted in the Figure footnote.

Response: The suggested additions have been made in the figure.

Comment 15: CONSORT diagram to be revised and tweaked based on this study e.g., method, flow etc.

Response: We request that the CONSORT diagram that was previously submitted be removed. In PLOS ONE’s submission guidelines, the following statement is included: “Clinical trials must be reported according to the relevant reporting guidelines, i.e. CONSORT for randomized controlled trials, TREND for non-randomized trials, and other specialized guidelines as appropriate.” As our study is non-randomized, we believe the TREND statement checklist is appropriate. We have included a revised TREND statement in our resubmission.

Comment 16: Not all references comply with the journal format.

Response: We have adjusted the references to comply with the journal format.

We look forward to hearing from you in due time regarding our submission and to respond to any further questions and comments you may have.

Submitted filename: Response to Reviewers.docx

 10.1371/journal.pone.0284738.r003 Decision Letter 1 Cowley Hugh Staff Editor 2023 Hugh Cowley This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version 1

10 Jan 2023

PONE-D-22-05428R1A feasibility study demonstrating that independence, quality of life, and adaptive behavioral skills can improve in children with Down syndrome after using assistive technologyPLOS ONE

Dear Dr. Han,

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 see the reviewers' comments below. When revising your manuscript, please ensure you fully address each of the reviewers' comments; in particular, please provide a detailed response to Reviewer #3's comment regarding the evaluation of the study participants' intellectual disability, and to the comments regarding clarity and presentational structure from Reviewer #2.

Please submit your revised manuscript by Feb 20 2023 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,

Hugh Cowley

Staff Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

Reviewer #3: (No Response)

**********

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

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

Reviewer #1: Partly

Reviewer #2: Partly

Reviewer #3: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: No

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 #2: Yes

Reviewer #3: (No Response)

**********

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

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

Reviewer #1: Yes

Reviewer #2: No

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 Response)

Reviewer #2: Interesting and important study!

I appreciate reading the comments from the first reviewer and responses of the authors, which have improved the paper and made it clearer. Although I do have comments of my own.

Abstract: The term ’nationally’ implies a reader knows where the study is conducted. Consider naming the country instead.

Note: Personally, I find it difficult to use the framing “the first study on X”, because 1) How do you know that unless you have systematically searched the literature (as in a systematic review), 2) it puts a time stamp on the study, making it less interesting once another study on the same topic is published. It adds no scientific value, because there are thousands of studies that are first on a topic.

Introduction/Research question: I don’t generally approve revising the wording in a research question (although the question you have is very vague) but I think the term significant should not be stated in the question. Is that the ‘test’ you think would answer whether AT is feasible or not? Another statistical approach would also serve as equally good (eg., Bayesian statistics).

Introduction: I think the outline lacks a clear description of what is meant by feasibility of AT. There are no standards mentioned, conditions to be met (from models, theories, checklists) of what would count as a positive use of AT in everyday life. Additionally, there is little to no description of what kind of AT that is the focus of the study, and why you choose to study the MapHabit System over other technologies, and why the chosen technology may be a good fit for people with Down’s syndrome (other than resemblance to Alzheimer’s). Quality of life is also not mentioned.

With this being said, many of the points I have raised are presented in the Methods section, and I think the outline of the paper is a bit confusing. I would have preferred describing and provide the rationale for each construct/the feasibility take in the Introduction section, which would make the Method section follow more logically. I am not familiar with this standard/format or what it is called.

Method section

General: the Enrollment, consent, & clinical trial registration section would be a lot easier to read if there were subheadings.

L54: Name the country

L115: You write: “This single-arm repeated measures design permitted the participants to serve as their own controls.” No, I don’t think the design allow for them being their own controls just because you measure pre- and post intervention (look up the designs in eg., Shadish, Cook and Campbell). Eg., in single subjects design you have multiple measurements to be able to observe a change more reliably bc a change in any of the measurements may be due to other reasons than the intervention. Consider removing that argument or provide a clearer description, number of measurement points etc.

L130-135: Provide rational of why you used non-parametric tests. They are less sensitive than parametric tests for observing change, for example.

Additionally: You write “1-sample t-test was used to compare scores against the null hypothesis (score of ‘3’). I am confused”. A one-sample t-test can be used to compare a point estimate (from your sample) to a fixed value. Consider explaining this more clearly, eg., if you test against the score 3. Also, in the results section you write: “one-sample Wilcoxon test”. Is this correct?

Method and Results

You have not mentioned the attrition or analysed what that meant for your conclusions. I think this is important because 23 participants were ‘lost’ and five expressed no desire to continue. The sample you have analysed are the ones that are ‘sufficiently satisfied’ because they fulfilled the trial, I guess. On the positive side, you analyse those that did not progress, but I think a general take is needed that includes all participants entering the study.

I think a conflict of interest statement should be added to the manuscript.

Explanation for the review questions with a 'No'

Q2, 3: If authors adress my comments these will be turned into a 'Yes'

Q5: Language is fine, but I have questions on the format/outline of the paper. If adequately met, this will also turn into a 'Yes'

Reviewer #3: This well written research paper focuses on the use of AT from children with DS - It is suggested authors to give more information about the evaluation of their intellectual disability; the results may differ according the severity

**********

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

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

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

Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Aspasia Serdari

**********

[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.

 10.1371/journal.pone.0284738.r004 Author response to Decision Letter 1 Submission Version 2

17 Feb 2023

Dear Mr. Cowley,

Thank you for giving us the opportunity to submit a revised manuscript titled “A feasibility study demonstrating that independence, quality of life, and adaptive behavioral skills can improve in children with Down syndrome after using assistive technology” to PLOS ONE. We are grateful for the additional time and effort that you and the reviewers have dedicated in providing valuable feedback on our initial revised manuscript. Below are the point-by-point responses to the reviewers’ comments and concerns:

Comments from Reviewer #2

Comment 1: “Abstract: The term ’nationally’ implies a reader knows where the study is conducted. Consider naming the country instead.”

Response: We agree with the reviewer that ‘nationally’ is vague for an international audience. We have replaced all mentions of the word to the specific country: United States of America.

Comment 2: “Personally, I find it difficult to use the framing ‘the first study on X’”

Response: We understand the reviewer’s caution with framing a study as the first to investigate on a particular subject. We have reframed the study as contributing to the expansion of research in an area that is still relatively new.

Comment 3: “I think the term significant should not be stated in the question”

Response: Following the reviewer’s suggestion, we have removed the word ‘significant’ to reserve its use for discussing statistical outcomes.

Comment 4: “Introduction: I think the outline lacks a clear description of what is meant by feasibility of AT…Additionally, there is little to no description of what kind of AT that is the focus of the study, and why you choose to study the MapHabit System”

Response: We have included additional details that define feasibility for the scope of our study and provided further rationale for using the MHS for the intervention.

Comment 5: “I would have preferred describing and provide the rationale for each construct/the feasibility take in the Introduction section”

Response: To clarify the structure of the manuscript, we have made changes in the Introduction. In addition, we included new subheadings to the Method section, as suggested by the reviewer in the next comment.

Comment 6: “Method section. General: the Enrollment, consent, & clinical trial registration section would be a lot easier to read if there were subheadings.”

Response: We have added subheadings to this section for better organization.

Comment 7: “L54: Name the country.”

Response: The country (USA) is now named in the manuscript. It is now located in line 78.

Comment 8: “L115…I don’t think the design allow for them being their own controls just because you measure pre- and post-intervention…Consider removing that argument or provide a clearer description, number of measurement points etc.”

Response: We appreciate the reviewer’s comment. The sentences were removed and replaced to be more straightforward: “permitted us to obtain baseline measures and compare them with the post-intervention outcomes”.

Comment 9: “L130-135: Provide rational of why you used non-parametric tests…Also, in the results section you write: ‘one-sample Wilcoxon test’. Is this correct”

Response:

We appreciate Reviewer #3’s discussion of the statistical aspects of the study. The Reviewer is correct, the test used for the analysis on line 136 should have been indicated as the Wilcoxon Signed Rank test, not the t-test. We have corrected the typo.

Additionally, Reviewer #3’s query about why nonparametric tests were used for the analyses (particularly for the QOL analysis) encouraged a second look. For the present study, the data sets were generated from relatively small samples (and possibly skewed data, because of the nature of the diagnosis of the participants). Accordingly, it was likely that our samples would yield scores from dependent measures that would depart from normality and potentially violate assumptions inherent to parametric tests (Seigel, 1956; Leech et al., 2002). Additionally, small sample sizes, as in the present study, will not cause the results derived from nonparametric analyses to be misleading to the extent that small sample sizes and outliers unduly can affect parametric tests (Hollander and Wolfe, 1973; McSeeney and Katz, 1978). Taking these points together, we feel confident our use of nonparametric tests in this study, including the QOL analysis, is appropriate, and we thank the Reviewer for the stimulating query.

Comment 10: “Method and Results. You have not mentioned the attrition or analysed what that meant for your conclusions.”

Response: We agree with the reviewer that the attrition of our participants is a limitation of the study. This may be explained by the study being too burdensome in the COVID-19 pandemic environment. We have added this point as a limitation in the Conclusion.

Comment 11: “I think a conflict-of-interest statement should be added to the manuscript.”

Response: Per the guidelines of PLOS ONE, a conflict-of-interest statement has already been submitted to PLOS ONE separately.

Comments from Reviewer #3

Comment 12: This well written research paper focuses on the use of AT from children with DS - It is suggested authors to give more information about the evaluation of their intellectual disability; the results may differ according the severity.

Response: We believe that the reviewer’s point is a very important one, and further reinforces the importance of this feasibility study. Further studies that are more systematic, such as randomized controlled trials, will allow for more conclusive findings and the ability to stratify the participants by intellectual or developmental disability severity. The present study did not have sufficient power or number of participants. We have added this point as a limitation to our conclusions.

Sincerely,

Samuel S. Han

Clinical Lead

MapHabit, Inc., Atlanta, GA 30308

shan@maphabit.com

Tel: 207-991-1955

References

Hollander, M., & Wolfe, D. A. (1973). Nonparametric Statistical Methods (Wiley Series In Probability And Mathematical Statistics). Wiley.

Leech, N. L., & Onwuegbuzie, A. J. (2002). A Call for Greater Use of Nonparametric Statistics.

McSweeney, M., & Katz, B. M. (1978). Nonparametric statistics: Use and nonuse. Perceptual and Motor Skills, 46(3_suppl), 1023-1032.

Messick, S. (1957). Nonparametric Statistics for the Behavioral Sciences. Sidney Siegel. McGraw-Hill, New York, 1956. 312 pp. $6.50. Science, 126(3267), 266-266.

Submitted filename: Response to Reviewers.docx

 10.1371/journal.pone.0284738.r005 Decision Letter 2 Zimmerman Steve Staff Editor 2023 Steve Zimmerman This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version 2

6 Mar 2023

PONE-D-22-05428R2A feasibility study demonstrating that independence, quality of life, and adaptive behavioral skills can improve in children with Down syndrome after using assistive technologyPLOS ONE

Dear Dr. Han,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

The manuscript has been evaluated by three reviewers, and their comments are available below.

Although reviewer 3 is now satisfied with the revised manuscript, reviewers 1 and 2 still have some requests for clarification.Reviewer 1 requests some minor language edits with reference to the Wilcoxon test, and reviewer 2 would like additional detail regarding their earlier requests.Could you please revise the manuscript to carefully address the concerns raised?

Please submit your revised manuscript by Apr 20 2023 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,

Steve Zimmerman, PhD

Associate 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.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

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Reviewer #1: Partly

Reviewer #2: Partly

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: (No Response)

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Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

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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. 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: Line 154, Line 177 and Figure 2, the name for one-sample Wilcoxon test or one-sample Wilcoxon signed-rank test to be standardised or alternatively one-sample Wilcoxon test (also referred as one-sample Wilcoxon signed-rank test) to be indicated.

Reviewer #2: I cannot see h0w you have addressed some of the concerns I raised. Responses for comment 4 and 5 say you have added rationale and descriptions in the manuscript, which I cannot find. Also, the attrition is only mentioned as a limitation but no one knows how these participants' scores would have altered the conclusions. Still, the abstract does not mention this uncertainty.

Reviewer #3: (No Response)

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Aspasia Serdari, Assoc Professor of child Psychiatry, Medical School, DUTH

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 10.1371/journal.pone.0284738.r006 Author response to Decision Letter 2 Submission Version 3

22 Mar 2023

Dear Dr. Zimmerman,

Thank you for giving us the opportunity to submit a revised manuscript titled “A feasibility study demonstrating that independence, quality of life, and adaptive behavioral skills can improve in children with Down syndrome after using assistive technology” to PLOS ONE. We are grateful for the additional time and effort that you and the reviewers have dedicated in providing valuable feedback that will enhance the manuscript. Below are the point-by-point responses to the reviewers’ comments and concerns:

Comments from Reviewer #1

Comment 1: Line 154, Line 177 and Figure 2, the name for one-sample Wilcoxon test or one-sample Wilcoxon signed-rank test to be standardised or alternatively one-sample Wilcoxon test (also referred as one-sample Wilcoxon signed-rank test) to be indicated.

Response: We thank the reviewer for noting the inconsistency of naming the statistical analysis. We have clarified this by following the reviewer’s suggestion: “one-sample Wilcoxon test (also referred to as one-sample Wilcoxon signed-rank test)”.

Comments from Reviewer #2

Comment 1.A: I cannot see how you have addressed some of the concerns I raised. Responses for comment 4 and 5 say you have added rationale and descriptions in the manuscript, which I cannot find.

Response: We believe comment 4 and 5 from the previous review have been addressed in the last rendition of the manuscript, seen in the Introduction (line 38-40; 48-50; 53-54) and Methods (line 100-105; 109-115).

Comment 1.B: Also, the attrition is only mentioned as a limitation, but no one knows how these participants' scores would have altered the conclusions. Still, the abstract does not mention this uncertainty.

Response: We appreciate the reviewer noting the potential limitation of the incompletions seen in participation. We have clarified this as a limitation that could have affected the outcomes that we reported. This has also been addressed in the abstract.

Submitted filename: Response to Reviewers.docx

 10.1371/journal.pone.0284738.r007 Decision Letter 3 Carels Vanessa Staff Editor 2023 Vanessa Carels This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version 3

10 Apr 2023

A feasibility study demonstrating that independence, quality of life, and adaptive behavioral skills can improve in children with Down syndrome after using assistive technology

PONE-D-22-05428R3

Dear Dr. Han,

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,

Vanessa Carels

Staff Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

 10.1371/journal.pone.0284738.r008 Acceptance letter Carels Vanessa Staff Editor 2023 Vanessa Carels This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

15 May 2023

PONE-D-22-05428R3

A feasibility study demonstrating that independence, quality of life, and adaptive behavioral skills can improve in children with Down syndrome after using assistive technology

Dear Dr. Han:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Vanessa Carels

Staff Editor

PLOS ONE