The RCSLT would like to acknowledge the Research Priorities working group and DLD work stream for their involvement and support in developing and carrying out the program of activities with iDLD and assisting with data collection. The RCSLT would also like to extend acknowledgement and gratitude to all individuals who participated in the sessions and gave their views on research priorities for DLD.&#160;We would also like to sincerely thank Blossom House School staff and students for their participation in and facilitation of the filming of the video accompanying this article.

<ol>
	<li>. Briefing paper: Language Disorder with a specific focus on Developmental Language Disorder Available from: <a target="_blank" href="https://www.rcslt.org/-/media/Project/RCSLT/language-disorder-briefing-paper.pdf">https://www.rcslt.org/-/media/Project/RCSLT/language-disorder-briefing-paper.pdf</a> (2020)</li><li>Bishop, D. V. M., Snowling, M. J., Thompson, P. A., Greenhalgh, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=CATALISE-2+consortium.+Phase+2+of+CATALISE:+a+multinational+and+multidisciplinary+Delphi+consensus+study+of+problems+with+language+development:+Terminology.">CATALISE-2 consortium. Phase 2 of CATALISE: a multinational and multidisciplinary Delphi consensus study of problems with language development: Terminology.</a> J Child Psychol Psychiatry. 58, 1068-1080 (2017).</li><li>Lyons, R., Roulstone, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Well-being+and+resilience+in+children+with+speech+and+language+disorders.">Well-being and resilience in children with speech and language disorders.</a> Journal of Speech, Language and Hearing Research. 61, 324-344 (2018).</li><li>Durkin, K., Conti-Ramsden, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Language,+social+behaviour,+and+the+quality+of+friendships+in+adolescents+with+and+without+a+history+of+specific+language+impairment.">Language, social behaviour, and the quality of friendships in adolescents with and without a history of specific language impairment.</a> Child Development. 78 (5), 1441-1457 (2007).</li><li>Conti-Ramsden, G., Durkin, K., Toseeb, U., Botting, N., Pickles, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Education+and+employment+outcomes+of+young+adults+with+a+history+of+developmental+language+disorders.">Education and employment outcomes of young adults with a history of developmental language disorders.</a> International Journal of Language and Communication Disorders. 53 (2), 237-255 (2018).</li><li>. Standards of proficiency - Speech and language therapists Available from: <a target="_blank" href="https://www.hcpc-uk.org/resources/standards/standards-of-proficiency-speech-and-language-therapists/">https://www.hcpc-uk.org/resources/standards/standards-of-proficiency-speech-and-language-therapists/</a> (2020)</li><li>Law, J., Dennis, J. A., Charlton, J. J. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Speech+and+language+therapy+interventions+for+children+with+primary+speech+and/or+language+disorders.">Speech and language therapy interventions for children with primary speech and/or language disorders.</a> Cochrane Database Syst Rev. 1, (2017).</li><li>Ranson, M. K., Bennett, S. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Priority+setting+and+health+policy+and+systems+research.">Priority setting and health policy and systems research.</a> Health Res Policy Sys. 7 (1), 27 (2009).</li><li>Rugdan, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Setting+health+research+priorities+using+the+CHNRI+method:+IV.+Key+conceptual+advances.">Setting health research priorities using the CHNRI method: IV. Key conceptual advances.</a> J Glob Health. 6 (1), (2016).</li><li>Rowbotham, N. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adapting+the+James+Lind+Alliance+priority+setting+process+to+better+support+patient+participation:+an+example+from+cystic+fibrosis.">Adapting the James Lind Alliance priority setting process to better support patient participation: an example from cystic fibrosis.</a> Res Involv Engagem. 5 (24), (2019).</li><li>Chalmers, I., Atkinson, P., Fenton, M., Firkins, L., Crowe, S., Cowan, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tackling+treatment+uncertainties+together:+the+evolution+of+the+James+Lind+Initiative+(JLI),+2003-2013.">Tackling treatment uncertainties together: the evolution of the James Lind Initiative (JLI), 2003-2013.</a> J R Soc Med. 106 (12), 482-491 (2013).</li><li>Crowe, S., Fenton, M., Hall, M., Cowan, K., Chalmers, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patients',+clinicians'+and+the+research+communities'+priorities+for+treatment+research:+there+is+an+important+mismatch.">Patients', clinicians' and the research communities' priorities for treatment research: there is an important mismatch.</a> Res Involvem Engagem. 1 (2), (2015).</li><li>Tallon, D., Chard, J., Dieppe, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Relation+between+agendas+of+the+research+community+and+the+research+consumer.">Relation between agendas of the research community and the research consumer.</a> Lancet. 335, 2037-2040 (2000).</li><li>Madden, M., Morley, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Exploring+the+challenge+of+health+research+priority+setting+in+partnership:+reflections+on+the+methodology+used+by+the+James+Lind+Alliance+Pressure+Ulcer+Priority+Setting+Partnership.">Exploring the challenge of health research priority setting in partnership: reflections on the methodology used by the James Lind Alliance Pressure Ulcer Priority Setting Partnership.</a> Res Involv Engagem. 2 (12), (2016).</li><li>. NHS England's Research Needs Assessment 2018 by Strategy and Innovation Directorate Available from: <a target="_blank" href="https://www.england.nhs.uk/wp-content/uploads/2018/09/nhs-englands-research-needs-assessment-2018.pdf">https://www.england.nhs.uk/wp-content/uploads/2018/09/nhs-englands-research-needs-assessment-2018.pdf</a> (2020)</li><li>Elberse, J. E., Pittens, C. A., de Cock Buning, T., Broerse, J. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patient+involvement+in+a+scientific+advisory+process:+setting+the+research+agenda+for+medical+products.">Patient involvement in a scientific advisory process: setting the research agenda for medical products.</a> Health Policy. 107, 231-242 (2012).</li><li>Harvey, N., Holmes, C. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nominal+group+technique:+An+effective+method+for+obtaining+group+consensus.">Nominal group technique: An effective method for obtaining group consensus.</a> Int J Nurs Pract. 18 (2), 188-194 (2012).</li><li>Fourie, R., Crowley, N., Oliviera, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Qualitative+Exploration+of+Therapeutic+Relationships+from+the+Perspective+of+Six+Children+Receiving+Speech-Language+Therapy.">A Qualitative Exploration of Therapeutic Relationships from the Perspective of Six Children Receiving Speech-Language Therapy.</a> Top Lang Disord. 31 (4), 310-324 (2011).</li><li>Snape, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Exploring+perceived+barriers,+drivers,+impacts+and+the+need+for+evaluation+of+public+involvement+in+health+and+social+care+research:+a+modified+Delphi+study.">Exploring perceived barriers, drivers, impacts and the need for evaluation of public involvement in health and social care research: a modified Delphi study.</a> BMJ Open. 4 (6), 004943 (2014).</li><li>Morris, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Setting+research+priorities+to+improve+the+health+of+children+and+young+people+with+neurodisability:+a+British+Academy+of+Childhood+Disability-James+Lind+Alliance+Research+Priority+Setting+Partnership.">Setting research priorities to improve the health of children and young people with neurodisability: a British Academy of Childhood Disability-James Lind Alliance Research Priority Setting Partnership.</a> BMJ open. 5 (1), (2015).</li><li>Pollock, A., St. George, B., Fenton, M., Crowe, S., Firkins, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+a+new+model+to+engage+patients+and+clinicians+in+setting+research+priorities.">Development of a new model to engage patients and clinicians in setting research priorities.</a> J Health Serv Res Policy. 19 (1), 12-18 (2014).</li><li>. RCSLT Position Paper: Inclusive communication and the role of speech and language therapy Available from: <a target="_blank" href="https://www.rcslt.org/members/delivering-quality-services/inclusive-communication/inclusive-communication-guidance#section-8">https://www.rcslt.org/members/delivering-quality-services/inclusive-communication/inclusive-communication-guidance#section-8</a> (2020)</li><li>Mander, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> The triangle of accessibility. Communication and Intellectual Disability Course Notes. , (2009).</li><li>. Royal College of Speech and Language Therapists. Research Priorities Available from: <a target="_blank" href="https://www.rcslt.org/members/research/research-priorities">https://www.rcslt.org/members/research/research-priorities</a> (2020)</li><li>Archibald, L. M. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Working+memory+and+language+learning:+A+review.">Working memory and language learning: A review.</a> Child Lang Teach Ther. 33 (1), 5-17 (2017).</li><li>Henry, L. A., Botting, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Working+memory+and+developmental+language+impairments.">Working memory and developmental language impairments.</a> Child Lang Teach Ther. 33 (1), 19-32 (2017).</li><li>Sowerbutts, A., Finer, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> DLD and Me: Supporting Children and Young People with Developmental Language Disorder. , (2019).</li><li>Socol, Y., Shaki, Y. Y., Yanovskiy, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interests,+Bias,+and+Consensus+in+Science+and+Regulation.">Interests, Bias, and Consensus in Science and Regulation.</a> Dose-Responnse. , (2019).</li><li>. Briefing notes for researchers: involving the public in NHS, public health and social care research Available from: <a target="_blank" href="https://www.invo.org.uk/wp-content/uploads/2014/11/9938_INVOLVE_Briefing_Notes_WEB.pdf">https://www.invo.org.uk/wp-content/uploads/2014/11/9938_INVOLVE_Briefing_Notes_WEB.pdf</a> (2020)</li><li>. UK standards for Public Involvement Available from: <a target="_blank" href="https://drive.google.com/file/d/1U-IJNJCfFepaAOruEhzz1TdLvAcHTt2Q/view">https://drive.google.com/file/d/1U-IJNJCfFepaAOruEhzz1TdLvAcHTt2Q/view</a> (2020)</li><li>Bunning, K., Steel, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Self-concept+in+young+adult+with+a+learning+disability+from+the+Jewish+community.">Self-concept in young adult with a learning disability from the Jewish community.</a> Br. J. Learn. Disabil. 35 (1), 43-49 (2007).</li><li>. Good Practice for Payment and Recognition Available from: <a target="_blank" href="https://www.invo.org.uk/good-practice-for-payment-and-recognition-things-to-consider/">https://www.invo.org.uk/good-practice-for-payment-and-recognition-things-to-consider/</a> (2020)</li><li>Gray-Burrows, K. A., Willis, T. A., Foy, R., Rathfelder, M., Bland, P., Chin, A., Hodgson, S., Ibegbuna, G., Prestwich, G., Samuel, K., Wood, L., Yaqoob, F., McEachan, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+patient+and+public+involvement+in+implementation+research:+a+consensus+study.">Role of patient and public involvement in implementation research: a consensus study.</a> BMJ quality &amp; safety. 27 (10), 858-864 (2018).</li><li>Blackburn, S., McLachlan, S., Jowett, S., Kinghorn, P., Gill, P., Higginbottom, A., Rhodes, C., Stevenson, F., Jinks, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+extent,+quality+and+impact+of+patient+and+public+involvement+in+primary+care+research:+a+mixed+methods+study.">The extent, quality and impact of patient and public involvement in primary care research: a mixed methods study.</a> Research Involvement and Engagement. 4 (16), (2018).</li></ol>

The authors have no disclosures to state.

The protocol presented here reflects an experimental, novel approach to incorporating the views of iDLD/iDLDPC into a research priority setting exercise. In its development, it was considered that an important aspect of the protocol is the execution of Step 1 and 2 by a SLT with specialist skills in DLD, and who understands the individualized support needs of iDLD/iDLDPC. This aimed to support validity of the outputs, which subsequently influenced the next stages of the research priority setting process. The protocol directs execution of evidence-based support strategies for iDLD, which are aimed at priming the skills and understanding required for their full participation in the exercise. Moreover, the steps in the protocol can be modified, by the SLT, to the most suitable level for each individual. As experts in speech, language and communication needs, the role of the SLT in these steps is important to ensure the iDLD/iDLDPC has understood the concepts and can consequently express their opinion about them. Whilst the SLTs were required to be: (a) a DLD specialist and (b) familiar with the iDLD/iDLDPC, the impact of these requisites was not evaluated and so it is possible that these could be modified in future replications of the protocol. Nevertheless, such demand of expertise, resource and capacity is unlikely to be supplied in standard research priority setting protocols and it is valuable to explore solutions.
Presentation of this protocol may assist future projects in planning for and incorporating service-user input into their research priority setting. However, it is recognized that the protocol is likely to evolve; following a pilot of the protocol, some modifications were made. This largely included further refinement of the program of activities in Step 1. For example, in the pilot protocol, step 1.6 Consolidate and teach key concept of &#8216;speech, language and communication&#8217; was essentially omitted, but it was found that additional time needed to be spent consolidating these concepts for some iDLD/iDLDPC, therefore an activity was added in. It was also identified that adding in this step could have additional benefits for the iDLD/iDLDPC, since DLD is a relatively new diagnosis2. Participation may therefore offer iDLD/iDLDPC a unique opportunity to learn more about their diagnosis and what this means for them and others, in a world where there is limited diagnostic adjustment work or psychosocial support available28. It is likely that there may be other creative modifications that may enhance either the experience of participating for iDLD/iDLDPC, or the validity of the outputs. We anticipate that future iterations of the protocol could involve a greater focus on preparatory activities to ensure understanding of key concepts such as &#39;research&#39; and &#39;priorities&#39;, especially for younger iDLD. Reflections from carrying out the sessions with iDLD/iDLDPC suggested that some of the materials developed for this section (for example, Supplementary File H) caused a level of confusion and could be developed further, by changing the phrasing of the &#8216;research headlines&#8217; to be more fit-for-purpose.
While the aim was to develop an evidence-based protocol, there were challenges in doing so for some aspects. This applies to, for example, identifying a meaningful way to transform ratings of topics by iDLD/iDLDPC into the defined research area survey data. This necessitates a degree of pragmatism and judgement resulting from the absence of an accepted, robust approach. It is recognized that some elements of the protocol rely on consensus of the research group. This aligns with the approach taken in other methods, notably, the JLA PSPs17. While only small-scale in this protocol, consensus-making is a method which carries flaws in and of itself29. Going forward, it is possible a more reliable, valid and stringent way of transforming this data could be identified. Additionally, it is difficult to truly secure the fidelity of the protocol describing the program of activities. Supporting communication in iDLD should be personalized for the individual&#8217;s unique combination of strengths and needs2 and so given the heterogeneity of the population of iDLD, the protocol is likely to require ongoing adaptation.
While it is perceived that the protocol&#8217;s accommodation of individual needs is advantageous and suggests the protocol could be carried out with iDLD aged 7 years and above, it is acknowledged that in the context of traditional scientific rigor employing different approaches with different participants would be seen to compromise the reliability of the results. It is also difficult to ascertain the true extent to which iDLD/iDLDPC were able to access the exercise, and to which their ratings are valid and reliable. For some iDLD/iDLDPC, particularly those who are young or who have only recently learned about their diagnosis of DLD, obtaining a clear understanding of what this means for them presents a considerable challenge. A number of steps were taken to minimize these risks, such as repetition and consolidation activities. In future, measures could be taken to capture and evaluate this robustly: assessing the SLT&#8217;s confidence in each iDLD/iDLDPC&#8217;s understanding and authenticity of the ratings, or carrying out the protocol on a different day with the same iDLD/iDLDPC and comparing findings. Furthermore, the iDLDs that ended up participating were school-aged children, therefore while the protocol&#8217;s success may suggest it is useful for this age group, it may not be appropriate to generalize to adults with DLD. Future examination of this would be of interest.
While there is an increasing focus on inclusion of groups of individuals requiring different types and levels of support to access research involvement30 the extent to which adaptations are made for individuals with speech, language or communication needs is questionable. While PPI guidance tends to highlight the need for clear communication with patient groups (e.g., the UK PI Standards31) this is often oriented to ensuring the style of information or terminology given by professionals or researchers is accessible to the &#8216;layperson&#8217;. There is a fundamental gap in the guidance on how to create PPI protocols which are accessible to those who have communication difficulties. Some research proposes methods for engaging such populations in, for example, qualitative research32 that provides a useful backdrop to the methods presented here. However, it is possible research priority setting exercises present a unique challenge for people with communication difficulties given the abstract and metacognitive concepts of &#8216;research&#8217; and &#8216;research priorities&#8217;. This protocol describes one process which could be taken to address these challenges.
Whilst iDLD were presented a certificate of participation, iDLD and iDLDPC were not financially rewarded for their involvement in this protocol, contrary to good practice33. This was because the budget for such payment was not fully appreciated when the project was first conceived. Since this point, in 2014, a body of evidence has emerged further refining the role of patients and public in research34, particularly implementation research35, and the cost and consequences of PPI36. These include recommendations pertaining to the use of rewards, including financially incentivizing service-users which aims to also reduce power differentials and empower individuals, and demonstrate the value that researchers place on their time, commitment and expertise34. Whilst financial rewards were not offered, steps were taken to minimize potential burdens for iDLD/iDLDPC to participate. For example, the sessions were carried out in the SLT&#8217;s places of work, and where iDLDPC were already meeting or taking their children, and therefore no participants incurred expenses. SLTs carried out the program of activities for iDLD during school hours so there were no additional time pressures for iDLD, or for the iDLDPC to transport the child to and from the session. Furthermore, the SLTs met with iDLDPC just before or after their child&#8217;s regular &#8216;pick-up time&#8217; to minimize disruption to participants&#8217; schedules. For future replications of the protocol we would recommend iDLD/iDLDPC are involved in conversations about how they would like to be rewarded, in line with current guidance33.
The advantage of this protocol is that it provides an evidence-based framework for eliciting views from iDLD/iDLDPC on a complex topic, which could be replicated for multiple purposes. For example, for carrying out a subsequent DLD research priority setting exercise or for research priority setting exercises with people with other kinds of speech, language and communication needs. Importantly, it may also be used as a basis for involving iDLD/iDLDPC or similar populations in research in the broader sense.

An erratum was issued for:&#160;<a href="https://www.jove.com/t/61267/involving-individuals-with-developmental-language-disorder-their">Involving Individuals with Developmental Language Disorder and their Parents/Carers in Research Priority Setting</a>. The tables in the Representative Results section were updated.

Erratum: Involving Individuals with Developmental Language Disorder and their Parents/Carers in Research Priority Setting

An erratum was issued for:&#160;<a href="https://www.jove.com/t/61267">Involving Individuals with Developmental Language Disorder and their Parents/Carers in Research Priority Setting</a>. The Authors section was updated from:
Katie E. Chadd1 
Amit A. Kulkarni1 
Lauren M. Longhurst1 
1Royal College of Speech and Language Therapists
to:
Katie E. Chadd1 
Amit A. Kulkarni1 
Lauren M. Longhurst1 
Mia Travlos2 
1Royal College of Speech and Language Therapists 
2Blossom House School

An erratum was issued for:&#160;<a href="https://www.jove.com/t/61267">Involving Individuals with Developmental Language Disorder and their Parents/Carers in Research Priority Setting</a>. The Authors section was updated.

Developmental language disorder (DLD) is a multifactorial, life-long condition characterized by difficulties with understanding and/or using language1. This can manifest in any or all areas of speech, language and communication (e.g., understanding instructions, word-finding, or joining a conversation)2. As a result, individuals with DLD (iDLD) are at increased risk of difficulties with their mental health3, relationships4, educational attainment and employment prospects5.
iDLD and their parents/carers (iDLDPC) are supported by speech and language therapists (SLTs) who are required to take an evidence-based approach to practice6. However, many gaps exist in the DLD evidence base7. Research priority setting exercises aim to address such situations, asking key stakeholders to consider what research is most urgently required8. Whilst some research priority setting approaches are focused on gathering &#39;expert opinion&#39; of researchers9, more recently, and within the UK context, such exercises are more typically carried out in research priority setting partnerships10. Born out of the movement for evidence-based practice11, research priority setting partnerships are designed to address the disconnect between the research agendas of academics, clinicians and users of health services12,13. Bringing together all key stakeholders, including service-users, to jointly decide upon research priorities offers theoretical and pragmatic benefits, improving the relevance, quality and impact of the process14. Additionally, involving service-users in research priority setting is a public and patient involvement (PPI) imperative within the UK&#39;s National Health Service15. It is therefore crucial that iDLD/iDLDPC are involved in research priority setting in this area.
There is no &#8220;gold standard method for health research &#8230; priority setting&#8221;14 but several approaches have been published. However, the communication challenges faced by iDLD/iDLDPC put them (or their opinions) at risk of being excluded via these methods. For example, the Dialogue Model relies entirely on in depth interviews with service-users16. Similarly, the James Lind Alliance Priority Setting Partnership (JLA PSP) approach17, which upholds itself on inclusion of all patient voices, would still present challenges for iDLD. The JLA PSP methodology utilizes Nominal Group Technique, requiring participants to independently &#8216;brainstorm&#8217; ideas, verbally express and then discuss them18. It is reasonable to assume the extent of meaningful involvement of iDLD/iDLDPC may be limited when using these approaches to research priority setting.
Another challenge in involving iDLD/iDLDPC in standardized protocols is that even if support was available, each individual will present a unique combination of strengths and needs in different aspects of language and communication1. Thus, one approach is unlikely to address the needs of everyone, putting some individuals at risk of exclusion. Here, a novel methodology is presented that embeds differentiated instruction and flexibility at its center. Perceived to be integral to the protocol is its delivery by specialist DLD SLTs with a detailed understanding of the iDLD/iDLDPC&#8217;s specific communication skills. This enhances reliability and assures quality as the SLT has: specialist knowledge, skills and experience working in DLD, and has already built a therapeutic relationship with the iDLD/iDLDPC19. This increases both the likelihood that the SLT can identify when the iDLD has understood and that the SLT can interpret the iDLD opinions accurately.
Resources and time are frequently cited as barriers to meaningful involvement of service-users in research20. Individuals with complex needs may be particularly disadvantaged. The British Academy of Childhood Disability state about their JLA PSP21: &#8220;our resources and time were insufficient to engage children and young people meaningfully&#8221; but that meaningful involvement could have been greater with &#8220;adequate resources&#8221; and &#8220;careful planning&#8221;. Pollock, St George, Fenton, Crowe &#38; Firkins22 adapted the JLA protocol in order to account for this additional demand on capacity and resources. Their &#8216;FREE TEA&#8217; model was implemented in a PSP for life after stroke. This offered an alternative, face-to-face method to yield data from service-users, which was considered to be much richer than that obtained through surveys. Additionally, Rowbotham et al.10 demonstrated success of online participation, which was imperative for the healthy involvement of people with cystic fibrosis (CF), in a CF JLA PSP. These innovative approaches demonstrate that when resources and time are used strategically, meaningful involvement is bolstered and the final output more reflective of service-user priorities.
It is well documented in the PPI literature that tokenism is common, which risks trivializing the impact and value of PPI20. This protocol describes a four-step process for meaningful involvement of iDLD/iDLDPC in a research priority setting exercise at multiple stages, reducing risk of tokenism:
Step 1: A program of activities for SLTs to carry out with iDLDs/iDLDPCs, aimed at developing their understanding of concepts related to research priorities; 
Step 2: An exercise for data collection on research priorities; 
Step 3: A method for data transformation to influence early stages of a research priority setting process; 
Step 4: A method for data transformation to influence late stages of a research priority setting process
To administer steps one and two, SLTs were recruited via advertisement in the organization&#8217;s general communications (for example, online forums). SLTs were required to be specialist DLD SLTs of UK band 6 (or above), and who had iDLD/iDLDPC on their caseload who they were familiar with and who could consent to participating. SLTs attended a 3 hour training session delivered by the research group (KC, AK, LL) to become familiar with the theoretical approach to the project, the program of activities and materials used. To maximize generalizability of the protocol, minimal exclusion criteria were specified for iDLD/iDLDPC participants. The expert SLTs formed consensus on the criteria that children in Key Stage 2 or above (7 years +) would be involved and would also allow iDLD with either suspected or confirmed DLD to participate. Selection of participants relied on the SLT&#8217;s clinical judgement of whether the iDLD/iDLDPC would be able to access the activities, even if suitable according to the inclusion criteria.
The program of activities, described in step 1 of the protocol uses an evidence-based inclusive communication approach, using tools and strategies to help iDLD understand and express themselves. Needs were planned for rather than reacted to and inclusive communication strategies were integrated consistently across the priority setting exercise, for example in forms, online communications and materials23. Activities were developed based upon the triangle of accessible support24, and addressed individual strengths and needs of the iDLD. The program includes optional activities and ones that can be implemented in different formats, which are to be selected by the specialist DLD SLT to tailor to the needs of iDLD/iDLDPC. This further recognizes the unique clinical skills, knowledge and experience of the SLT which optimize the iDLD&#8217;s communication capacity24. This component of the protocol is supported by materials found in the Supplementary Files.
The data collection activity described in step 2 of the protocol was based on 11 &#8216;topics&#8217; about DLD, which were associated with superordinate themes identified from a previous evaluation of professionals&#8217; &#8216;uncertainties&#8217; about DLD research25. iDLD/iDLDPC may experience greater difficulty with verbal reasoning26 therefore a topic-based approach was chosen over the presentation of many subordinate topics. Working memory may also be impaired in iDLD/iDLDPC27, thus in order to support iDLD/iDLDPC with decision-making, data was obtained via an individual-topic rating exercise followed by a comparative ranking exercise when appropriate.
Step 3 presents a data transformation process enabling iDLD/iDLDPC&#8217;s opinions on priorities to influence the early research priority setting process, by determining the types of topics that other stakeholders should discuss in the initial stages of the process. This was achieved by examining the average ratings by iDLD/iDLDPC&#8217;s on their perceived level of &#8216;priority&#8217; of the 11 DLD research topics (obtained from step 2) and forming consensus on whether there was sufficient agreement from participants on highly-rated (i.e., &#8216;prioritized&#8217;) topics. The aim of this evaluation was to inform which, if any, topics could be validly disregarded and not considered in the subsequent stages of the process, and which should be taken forward.
The final step describes use of the same data to transform survey data to further reflect iDLD/iDLDPC&#8217;s priorities and influence the final output. As part of the broader research priority setting process (beyond this protocol), defined research areas for DLD were developed by stakeholders, who subsequently voted for which areas they considered a priority via an online survey. Each defined research area was related to one of more of the topics that were previously rated by iDLD/iDLDPC. The iDLD/iDLDPC rating data was used to &#8216;boost&#8217; votes for the defined research areas associated with highly rated research topics.
This protocol is designed for those planning to set research priorities for DLD, who wish to meaningfully involve iDLD/iDLDPC. Access to specialist DLD SLTs and their clinical caseload of iDLD, and iDLDPC is required. It is designed to complement an overall research priority setting process collecting additional data, for example the topics of interest and defined research areas. A project group approach is recommended to allow for group decision-making. It may also be adaptable for use with iDLD/iDLDPC or different populations with speech, language and communication disorders, in other research activities.

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			<td>Supporting resources</td>
			<td>Royal College of Speech and Language Therapists</td>
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involving individuals with developmental language disorder and their parents/carers in research priority setting

A protocol for involving individuals presenting with developmental language disorder (DLD) (iDLD) and their parents/carers (iDLDPC) in a research priority setting exercise is presented.
iDLD have difficulties with communication skills, such as understanding language, word-finding and discourse. Such difficulties mean existing research priority setting protocols are difficult for iDLD to access, since they require sophisticated communication skills. Thus, a novel protocol for involving iDLD in these exercises is warranted. The same protocol is recommended for use with iDLDPC, to ensure accessibility.
The protocol is presented in 4 steps. Step 1 describes a program of activities delivered by trained, specialist DLD speech and language therapists (SLTs) that prepares iDLD/iDLDPC for involvement. Step 2 outlines an approach to elicit iDLD/iDLDPC&#8217;s opinions on research priorities. Steps 3 and 4 describe methods to analyze and integrate this data at multiple stages of the research priority setting process.
9 trained specialist DLD SLTs delivered steps 1 and 2. 17 iDLDs and 25 iDLDPCs consented to involvement. Opinions from all participants were elicited, and this data was used to influence the process and output of the exercise.
An advantage of this protocol is its accommodation of the heterogeneity in support needs of iDLD/iDLDPC, through a menu of options, whilst also providing a structured framework. Due to the novelty of the protocol, the methods for data integration were developed by the research group. These are potential limitations of the protocol, and may bring the reliability and validity under scrutiny, which are yet to be tested.
This protocol enables meaningful involvement of iDLD/iDLDPC in&#160;research priority setting and could be utilized for people with other kinds of speech, language or communication needs. Further research should evaluate the effectiveness of the protocol and whether it can be adapted for involvement of such populations in other research studies.

Watch this Scientific Journal Video about Involving Individuals with Developmental Language Disorder and Their Parents/Carers in Research Priority Setting at JoVE.com

Involving Individuals with Developmental Language Disorder and Their Parents/Carers in Research Priority Setting

A protocol to enable individuals with developmental language disorder (DLD) and their parents/carers to meaningfully participate in a research priority setting exercise is established. The protocol includes a defined program of activities for data collection, and methods to incorporate this data into the broader research priority setting process.

A protocol for involving individuals presenting with developmental language disorder (DLD) (iDLD) and their parents/carers (iDLDPC) in a research priority ...

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3.4K Views.  Royal College of Speech and Language Therapists. A protocol to enable individuals with developmental language disorder (DLD) and their parents/carers to meaningfully participate in a research priority setting exercise is established. The protocol includes a defined program of activities for data collection, and methods to incorporate this data into the broader research priority setting process.

Video: Involving Individuals with Developmental Language Disorder and Their Parents/Carers in Research Priority Setting

Assessing Teratogenic Changes in a Zebrafish Model of Fetal Alcohol Exposure

Fetal alcohol syndrome (FAS) is a severe manifestation of embryonic exposure to ethanol. It presents with characteristic defects to the face and organs, including mental retardation due to disordered and damaged brain development. Fetal alcohol spectrum disorder (FASD) is a term used to cover a continuum of birth defects that occur due to maternal alcohol consumption, and occurs in approximately 4% of children born in the United States. With 50% of child-bearing age women reporting consumption of alcohol, and half of all pregnancies being unplanned, unintentional exposure is a continuing issue2. In order to best understand the damage produced by ethanol, plus produce a model with which to test potential interventions, we developed a model of developmental ethanol exposure using the zebrafish embryo. Zebrafish are ideal for this kind of teratogen study3-8. Each pair lays hundreds of eggs, which can then be collected without harming the adult fish. The zebrafish embryo is transparent and can be readily imaged with any number of stains. Analysis of these embryos after exposure to ethanol at different doses and times of duration and application shows that the gross developmental defects produced by ethanol are consistent with the human birth defect. Described here are the basic techniques used to study and manipulate the zebrafish FAS model.

In order to understand the molecular mechanisms of the ethanol-induced developmental damage, we have developed a zebrafish model of ethanol exposure and are exploring the physical, cellular, and genetic alterations that occur after ethanol exposure1. We then seek to find potential interventions and rapidly test them in this animal model.

Fetal alcohol syndrome (FAS) is a severe manifestation of embryonic exposure to ethanol. It presents with characteristic defects to the face and organs, ...

Portable Intermodal Preferential Looking (IPL): Investigating Language Comprehension in Typically Developing Toddlers and Young Children with Autism

One of the defining characteristics of autism spectrum disorder (ASD) is difficulty with language and communication.1 Children with ASD's onset of speaking is usually delayed, and many children with ASD consistently produce language less frequently and of lower lexical and grammatical complexity than their typically developing (TD) peers.6,8,12,23 However, children with ASD also exhibit a significant social deficit, and researchers and clinicians continue to debate the extent to which the deficits in social interaction account for or contribute to the deficits in language production.5,14,19,25
Standardized assessments of language in children with ASD usually do include a comprehension component; however, many such comprehension tasks assess just one aspect of language (e.g., vocabulary),5 or include a significant motor component (e.g., pointing, act-out), and/or require children to deliberately choose between a number of alternatives. These last two behaviors are known to also be challenging to children with ASD.7,12,13,16
We present a method which can assess the language comprehension of young typically developing children (9-36 months) and children with autism.2,4,9,11,22 This method, Portable Intermodal Preferential Looking (P-IPL), projects side-by-side video images from a laptop onto a portable screen. The video images are paired first with a 'baseline' (nondirecting) audio, and then presented again paired with a 'test' linguistic audio that matches only one of the video images. Children's eye movements while watching the video are filmed and later coded. Children who understand the linguistic audio will look more quickly to, and longer at, the video that matches the linguistic audio.2,4,11,18,22,26
This paradigm includes a number of components that have recently been miniaturized (projector, camcorder, digitizer) to enable portability and easy setup in children's homes. This is a crucial point for assessing young children with ASD, who are frequently uncomfortable in new (e.g., laboratory) settings. Videos can be created to assess a wide range of specific components of linguistic knowledge, such as Subject-Verb-Object word order, wh-questions, and tense/aspect suffixes on verbs; videos can also assess principles of word learning such as a noun bias, a shape bias, and syntactic bootstrapping.10,14,17,21,24 Videos include characters and speech that are visually and acoustically salient and well tolerated by children with ASD.

Portable Intermodal Preferential Looking IPL: Investigating Language Comprehension in Typically Developing Toddlers and Young Children with Autism

A reliable home-based way to assess the language comprehension of very young typically developing children, as well as those with autism, is described. The method analyzes children's eye gaze while viewing side-by-side images but hearing an audio that matches only one image. Stimuli are designed with young participants in mind.

One  of the defining characteristics of autism spectrum disorder (ASD) is difficulty  with language and communication.1  Children with ASD's onset of ...

Evaluation of Respiratory Muscle Activation Using Respiratory Motor Control Assessment (RMCA) in Individuals with Chronic Spinal Cord Injury

During breathing, activation of respiratory muscles is coordinated by integrated input from the brain, brainstem, and spinal cord. When this coordination is disrupted by spinal cord injury (SCI), control of respiratory muscles innervated below the injury level is compromised1,2 leading to respiratory muscle dysfunction and pulmonary complications. These conditions are among the leading causes of death in patients with SCI3. Standard pulmonary function tests that assess respiratory motor function include spirometrical and maximum airway pressure outcomes: Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1), Maximal Inspiratory Pressure (PImax) and Maximal Expiratory Pressure (PEmax)4,5. These values provide indirect measurements of respiratory muscle performance6. In clinical practice and research, a surface electromyography (sEMG) recorded from respiratory muscles can be used to assess respiratory motor function and help to diagnose neuromuscular pathology. However, variability in the sEMG amplitude inhibits efforts to develop objective and direct measures of respiratory motor function6. Based on a multi-muscle sEMG approach to characterize motor control of limb muscles7, known as the voluntary response index (VRI)8, we developed an analytical tool to characterize respiratory motor control directly from sEMG data recorded from multiple respiratory muscles during the voluntary respiratory tasks. We have termed this the Respiratory Motor Control Assessment (RMCA)9. This vector analysis method quantifies the amount and distribution of activity across muscles and presents it in the form of an index that relates the degree to which sEMG output within a test-subject resembles that from a group of healthy (non-injured) controls. The resulting index value has been shown to have high face validity, sensitivity and specificity9-11. We showed previously9 that the RMCA outcomes significantly correlate with levels of SCI and pulmonary function measures. We are presenting here the method to quantitatively compare post-spinal cord injury respiratory multi-muscle activation patterns to those of healthy individuals.

Evaluation of Respiratory Muscle Activation Using Respiratory Motor Control Assessment RMCA in Individuals with Chronic Spinal Cord Injury

The purpose of this publication is to present our original work on a multi-muscle surface electromyographic approach to quantitatively characterize respiratory muscle activation patterns in individuals with chronic spinal cord injury using vector-based analysis.

During breathing, activation of respiratory muscles is coordinated by integrated input from the brain, brainstem, and spinal cord. When this coordination ...

Utilizing Repetitive Transcranial Magnetic Stimulation to Improve Language Function in Stroke Patients with Chronic Non-fluent Aphasia

Transcranial magnetic stimulation (TMS) has been shown to significantly improve language function in patients with non-fluent aphasia1. In this experiment, we demonstrate the administration of low-frequency repetitive TMS (rTMS) to an optimal stimulation site in the right hemisphere in patients with chronic non-fluent aphasia. A battery of standardized language measures is administered in order to assess baseline performance. Patients are subsequently randomized to either receive real rTMS or initial sham stimulation. Patients in the real stimulation undergo a site-finding phase, comprised of a series of six rTMS sessions administered over five days; stimulation is delivered to a different site in the right frontal lobe during each of these sessions. Each site-finding session consists of 600 pulses of 1 Hz rTMS, preceded and followed by a picture-naming task. By comparing the degree of transient change in naming ability elicited by stimulation of candidate sites, we are able to locate the area of optimal response for each individual patient. We then administer rTMS to this site during the treatment phase. During treatment, patients undergo a total of ten days of stimulation over the span of two weeks; each session is comprised of 20 min of 1 Hz rTMS delivered at 90% resting motor threshold. Stimulation is paired with an fMRI-naming task on the first and last days of treatment. After the treatment phase is complete, the language battery obtained at baseline is repeated two and six months following stimulation in order to identify rTMS-induced changes in performance. The fMRI-naming task is also repeated two and six months following treatment. Patients who are randomized to the sham arm of the study undergo sham site-finding, sham treatment, fMRI-naming studies, and repeat language testing two months after completing sham treatment. Sham patients then cross over into the real stimulation arm, completing real site-finding, real treatment, fMRI, and two- and six-month post-stimulation language testing.

We explore the use of repetitive transcranial magnetic stimulation (rTMS) to improve language abilities in patients with chronic stroke and non-fluent aphasia. After identifying a site in the right frontal gyrus for each patient that responds optimally to stimulation, we target this site during ten days of rTMS treatment.

Transcranial magnetic stimulation (TMS) has been shown to significantly improve language function in patients with non-fluent aphasia1. In this ...

Implanting Glass Spinal Cord Windows in Adult Mice with Experimental Autoimmune Encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) in adult rodents is the standard experimental model for studying autonomic demyelinating diseases such as multiple sclerosis. Here we present a low-cost and reproducible glass window implantation protocol that is suitable for intravital microscopy and studying the dynamics of spinal cord cytoarchitecture with subcellular resolution in live adult mice with EAE. Briefly, we surgically expose the vertebrae T12-L2 and construct a chamber around the exposed vertebrae using a combination of cyanoacrylate and dental cement. A laminectomy is performed from T13 to L1, and a thin layer of transparent silicone elastomer is applied to the dorsal surface of the exposed spinal cord. A modified glass cover slip is implanted over the exposed spinal cord taking care that the glass does not directly contact the spinal cord. To reduce the infiltration of inflammatory cells between the window and spinal cord, anti-inflammatory treatment is administered every 2 days (as recommended by ethics committee) for the first 10 days after implantation. EAE is induced only 2-3 weeks after the cessation of anti-inflammatory treatment.
Using this approach we successfully induced EAE in 87% of animals with implanted windows and, using Thy1-CFP-23 mice (blue axons in dorsal spinal cord), quantified axonal loss throughout EAE progression. Taken together, this protocol may be useful for studying the recruitment of various cell populations as well as their interaction dynamics, with subcellular resolution and for extended periods of time. This intravital imaging modality represents a valuable tool for developing therapeutic strategies to treat autoimmune demyelinating diseases such as EAE.

We describe a method for implanting and maintaining glass windows over the exposed spinal cords of adult mice for studying experimental autoimmune encephalomyelitis. These windows provide chronic optical access to the spinal cord for monitoring cell dynamics at the subcellular level in live animals using two-photon microscopy.

Experimental autoimmune encephalomyelitis (EAE) in adult rodents is the standard experimental model for studying autonomic demyelinating diseases such as ...

Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study model. As the use of mouse models are often a vital step in preclinical drug discovery and drug development1-8, it is necessary to design a system to introduce drugs into mice in a uniform, reproducible manner. Ideally, the system should permit the collection of blood samples at regular intervals over a set time course. The ability to measure drug concentrations by mass-spectrometry, has allowed investigators to follow the changes in plasma drug levels over time in individual mice1, 9, 10. In this study, paclitaxel was introduced into transgenic mice as a continuous arterial infusion over three hours, while blood samples were simultaneously taken by retro-orbital bleeds at set time points. Carotid artery infusions are a potential alternative to jugular vein infusions, when factors such as mammary tumors or other obstructions make jugular infusions impractical. Using this technique, paclitaxel concentrations in plasma and tissue achieved similar levels as compared to jugular infusion. In this tutorial, we will demonstrate how to successfully catheterize the carotid artery by preparing an optimized catheter for the individual mouse model, then show how to insert and secure the catheter into the mouse carotid artery, thread the end of the catheter out through the back of the mouse&#8217;s neck, and hook the mouse to a pump to deliver a controlled rate of drug influx. Multiple low volume retro-orbital bleeds allow for analysis of plasma drug concentrations over time.

This method was developed with the goal of delivering a steady drug solution via the carotid artery, to assess the pharmacokinetics of novel drugs in mouse models.

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study ...

Working with Human Tissues for Translational Cancer Research

Medical research for human benefit is greatly impeded by the necessity for human tissues and subjects. However, upon obtaining consent for human specimens, precious samples must be handled with the greatest care in order to ensure integrity of organs, tissues, and cells to the highest degree. Unfortunately, tissue processing by definition requires extraction of tissues from the host, a change which can cause great cellular stress and have major repercussions on subsequent analyses. These stresses could result in the specimen being no longer representative of the site from which it was retrieved. Therefore, a strict protocol must be adhered to while processing these specimens to ensure representativeness. The desired assay(s) must also be taken into consideration in order to ensure that an optimal technique is used for sample processing. Outlined here is a protocol for tissue retrieval, processing and various analyses which may be performed on processed tissue in order to maximize downstream production from limited tissue samples.

Translational cancer research is dependent on extraction of human tissues. Much work has gone into optimizing extraction methods for ex vivo analysis. Here, we describe tissue processing methods allowing for maximal data output from limited samples.

Medical research for human benefit is greatly impeded by the necessity for human tissues and subjects. However, upon obtaining consent for human ...

Adapted Resistance Training Improves Strength in Eight Weeks in Individuals with Multiple Sclerosis

Hip weakness is a common symptom affecting walking ability in people with multiple sclerosis (MS). It is known that resistance strength training (RST) can improve strength in individuals with MS, however; it remains unclear the duration of RST that is needed to make strength gains and how to adapt hip strengthening exercises for individuals of varying strength using only resistance bands. This paper describes the methodology to set up and implement an adapted resistance strength training program, using resistance bands, for individuals with MS. Directions for pre- and post-strength tests to evaluate efficacy of the strength-training program are included. Safety features and detailed instructions outline the weekly program content and progression. Current evidence is presented showing that significant strength gains can be made within 8 weeks of starting a RST program. Evidence is also presented showing that resistance strength training can be successfully adapted for individuals with MS of varying strength with little equipment.

Hip weakness is a common symptom affecting walking ability in people with multiple sclerosis. Isolated muscle strengthening is a useful method to target specific weaknesses. This protocol describes a progressive resistance-training program using exercise bands to increase hip muscle strength.

Hip weakness is a common symptom affecting walking ability in people with multiple sclerosis (MS). It is known that resistance strength training (RST) can ...

Measuring Cardiac Autonomic Nervous System (ANS) Activity in Toddlers - Resting and Developmental Challenges

The autonomic nervous system (ANS) consists of two branches, the parasympathetic and sympathetic nervous systems, and controls the function of internal organs (e.g., heart rate, respiration, digestion) and responds to everyday and adverse experiences 1. ANS measures in children have been found to be related to behavior problems, emotion regulation, and health 2-7. Therefore, understanding the factors that affect ANS development during early childhood is important. Both branches of the ANS affect young children&#8217;s cardiovascular responses to stimuli and have been measured noninvasively, via external monitoring equipment, using valid and reliable measures of physiological change 8-11. However, there are few studies of very young children with simultaneous measures of the parasympathetic and sympathetic nervous systems, which limits understanding of the integrated functioning of the two systems. In addition, the majority of existing studies of young children report on infants&#8217; resting ANS measures or their reactivity to commonly used mother-child interaction paradigms, and less is known about ANS reactivity to other challenging conditions. We present a study design and standardized protocol for a non-invasive and rapid assessment of cardiac autonomic control in 18 month old children. We describe methods for continuous monitoring of the parasympathetic and sympathetic branches of the ANS under resting and challenge conditions during a home or laboratory visit and provide descriptive findings from our sample of 140 ethnically diverse toddlers using validated equipment and scoring software. Results revealed that this protocol can produce a range of&#160;physiological responses to both resting and developmentally challenging conditions, as indicated by changes in heart rate and indices of parasympathetic and sympathetic activity. Individuals demonstrated&#160;variability in resting levels, responses to challenges, and challenge reactivity, which provides additional evidence that this protocol is useful for the examination of ANS individual differences for toddlers.

Measuring Cardiac Autonomic Nervous System ANS Activity in Toddlers - Resting and Developmental Challenges

We describe the methods for continuous monitoring of the autonomic nervous system under resting and challenge conditions with 18 month old children. Results revealed that this protocol can produce meaningful physiological responses in both branches of the autonomic nervous system and elicit significant individual variability in patterns of responses.

The autonomic nervous system (ANS) consists of two branches, the parasympathetic and sympathetic nervous systems, and controls the function of internal ...

Ex vivo Live Imaging of Lung Metastasis and Their Microenvironment

Metastasis is a major cause for cancer-related morbidity and mortality. Metastasis is a multistep process and due to its complexity, the exact cellular and molecular processes that govern metastatic dissemination and growth are still elusive. Live imaging allows visualization of the dynamic and spatial interactions of cells and their microenvironment. Solid tumors commonly metastasize to the lungs. However, the anatomical location of the lungs poses a challenge to intravital imaging. This protocol provides a relatively simple and quick method for ex vivo live imaging of the dynamic interactions between tumor cells and their surrounding stroma within lung metastasis. Using this method, the motility of cancer cells as well as interactions between cancer cells and stromal cells in their microenvironment can be visualized in real time for several hours. By using transgenic fluorescent reporter mice, a fluorescent cell line, injectable fluorescently labeled molecules and/or antibodies, multiple components of the lung microenvironment can be visualized, such as blood vessels and immune cells. To image the different cell types, a spinning disk confocal microscope that allows long-term continuous imaging with rapid, four-color image acquisition has been used. Time-lapse movies compiled from images collected over multiple positions and focal planes show interactions between live metastatic and immune cells for at least 4 hr. This technique can be further used to test chemotherapy or targeted therapy. Moreover, this method could be adapted for the study of other lung-related pathologies that may affect the lung microenvironment.

Ex vivo Live Imaging of Lung Metastasis and Their Microenvironment

We describe a relatively simple method for ex vivo live imaging of the tumor cell-stroma interactions within lung metastasis, utilizing fluorescent reporters in mice. Using spinning-disk confocal microscopy, this technique enables visualization of live cells for at least 4 hr and could be adapted to study other inflammatory lung conditions.

Metastasis is a major cause for cancer-related morbidity and mortality. Metastasis is a multistep process and due to its complexity, the exact cellular ...