Strategies to Support Learning of Gross Motor Tasks in Children with Autism Spectrum Disorder: A Scoping Review.

AIMS: Children with autism spectrum disorder (ASD) display motor difficulties that may impact social and communication interactions and participation in everyday activities. These difficulties may be related to a difference in the way they learn new skills. Therefore, strategies to support motor learning to optimize skill acquisition and retention may be beneficial. This scoping review described current motor learning strategies used to optimize acquisition, retention, transfer, and generalizability of motor tasks in children with ASD. METHODS: Three databases were searched from inception through 2021. Studies were included if they involved participants with ASD ≤ 18 years old, evaluated learning of a novel gross motor task, manipulated a motor learning variable, and were written in English. RESULTS: Twenty-two articles met eligibility criteria. Most articles examined strategies that manipulated the instruction of task, with few articles examining feedback or practice. Skill acquisition was the most represented motor learning outcome, with fewer studies examining retention, transfer, or generalizability. CONCLUSIONS: Positive results in 95% of the articles suggest that the use of support strategies to optimize motor learning is feasible and beneficial for children with ASD, and that modifications to instruction, feedback, and practice schedules should be considered in motor interventions.

Concurrent Validity of Two Standardized Measures of Gross Motor Function in Young Children with Autism Spectrum Disorder.

AIMS: This study provides information on how two standardized measures based on different theoretical frameworks can be used in collecting information on motor development and performance in 4- and 5-year-olds with autism spectrum disorder (ASD). The purpose of the study was to determine the concurrent validity of the Miller Function and Participation Scales (M-FUN) with the Peabody Developmental Motor Scales, Second Edition (PDMS-2) in young children with ASD. METHODS: The gross motor sections of the PDMS-2 and the M-FUN were administered to 22 children with ASD between the ages of 48 and 71 months. Concurrent validity between overall motor scores and agreement in identification of motor delay were assessed. RESULTS: A very strong correlation (Pearson's r =.851) was found between the M-FUN scale scores and the PDMS-2 gross motor quotients (GMQs). Strong agreement in identification of children with average motor skills and delayed motor skills at 1.5 standard deviations below the mean was also found. CONCLUSIONS: This study supports the concurrent validity of the M-FUN with the PDMS-2 for young children with ASD. While both tests provide information regarding motor delay, the M-FUN may provide additional information regarding the neurological profile of the child.

Relationships Between Gross Motor Skills and Social Function in Young Boys With Autism Spectrum Disorder.

PURPOSE: The purpose of this study was to examine the relationship between gross motor skills and social function in young boys with autism spectrum disorder. METHODS: Twenty-one children with autism spectrum disorder participated in the study. The Peabody Developmental Motor Scales Second Edition and the Miller Function and Participation Scales were used to assess gross motor skills. The Social Skills Improvement System Rating Scales was used to assess social function. RESULTS: Moderately high correlations were found between overall gross motor and social skills (r = 0.644) and between the core stability motor subtest and overall social skills (r = -0.672). Specific motor impairments in stability, motor accuracy, and object manipulation scores were predictive of social function. CONCLUSIONS: This study suggests that motor skills and social function are related in young boys with autism. Implications for physical therapy intervention are also discussed.

Parent and Adolescent Attitudes Toward a Virtual Nutrition Intervention for Adolescents with Autism Spectrum Disorder.

Objectives: This qualitative study examined acceptability, perceived benefits, and unintended consequences of a virtual implementation of an 8-week theory-driven nutrition intervention (BALANCE) for adolescents with autism spectrum disorder (ASD). Methods: Twenty-one parent interviews and six adolescent focus groups or interviews (n = 12; group size ranged 1-5) were conducted. Data were collected virtually via Microsoft Teams and analyzed for a priori and emergent themes. Results: The intervention was generally acceptable. Adolescents and parents reported that they were comfortable with the virtual format and the interactive group setting. Parents of adolescents 15 years and older emphasized the importance of autonomy/independence. Participants reported changes in adolescents' psychosocial determinants of dietary intake, including knowledge and self-efficacy, as well as diet changes (e.g., self-regulation). Conclusions: The virtual implementation of BALANCE was acceptable according to adolescents with ASD and their parents based on their reported perceptions and feelings about the intervention. The findings suggest that many adolescents with ASD may benefit from virtual group interventions. Quantitative research is needed to examine behavioral outcomes of the BALANCE intervention.

Feasibility of a virtual nutrition intervention for adolescents with autism spectrum disorder.

LAY ABSTRACT: Adolescents with autism spectrum disorder are at an increased risk of unhealthy eating behaviors and obesity compared to their typically developing peers. Many nutrition interventions for this population focus on improving autism spectrum disorder symptoms or managing weight rather than addressing participants' healthy eating self-efficacy. The purpose of this study was to examine a virtual implementation of a new intervention for adolescents with autism spectrum disorder, Bringing Adolescent Learners with Autism Nutrition and Culinary Education. We used fidelity checklists, engagement records, and field notes to measure implementation. We also examined the feasibility of assessing outcome measures, including a food frequency questionnaire (FFQ), psychosocial survey, height, and weight. We recruited adolescents with autism spectrum disorder aged 12-21 years. Six groups of 2-7 adolescents (27 total) participated in the intervention and pre-/post-intervention measurements. Bringing Adolescent Learners with Autism Nutrition and Culinary Education consisted of eight weekly lessons: exploring taste, flavor, and texture; mealtimes and rules; food groups and nutrients; moderation; beverages; cooking; well-being; sustaining healthy eating habits. The virtual implementation was feasible based on lesson attendance, participation, homework completion, fidelity, and prevalence of technical difficulties. Evaluation was also feasible based on response rate, completion, and data quality for the food frequency questionnaire, psychosocial survey, and height and weight measurements. Bringing Adolescent Learners with Autism Nutrition and Culinary Education may be used in virtual settings to reach diverse populations of adolescents with autism spectrum disorder. Future research is needed to evaluate the impact of Bringing Adolescent Learners with Autism Nutrition and Culinary Education on dietary behavior and obesity outcomes.

Pilot Study of a Virtual Nutrition Intervention for Adolescents and Young Adults With Autism Spectrum Disorder.

OBJECTIVE: Examine the impact of a virtual nutrition education program, Bringing Adolescent Learners with Autism Nutrition and Culinary Education (BALANCE), on dietary intake and psychosocial determinants of healthy eating in adolescents and young adults (AYA) with autism spectrum disorder (ASD). METHODS: A sample of AYA with ASD aged 12-21 years (n = 27; 6 groups of 2-7 adolescents) participated in BALANCE, a Social Cognitive Theory-based intervention, for eight 30-45-minute lessons. Outcomes were compared using a pre-post design and included dietary intake (assessed using a food frequency questionnaire) and psychosocial determinants of healthy eating (assessed by a validated survey). Wilcoxon signed-rank tests compared preintervention and postintervention medians with an alpha level of 0.05. RESULTS: Mean added sugar intake (P = 0.026) decreased, and behavioral strategies (P = 0.010), self-efficacy (P < 0.001), and outcome expectations (P = 0.009) improved. There was no difference in fruit or vegetable intake or other psychosocial determinants. CONCLUSIONS AND IMPLICATIONS: The BALANCE intervention may improve psychosocial determinants and dietary behaviors in AYA with ASD. Future virtual programs may incorporate more assistance and support to be accessible for AYA with ASD of varying severity levels.

The intersection of gross motor abilities and participation in children with autism spectrum disorder.

Many children with autism spectrum disorder (ASD) demonstrate movement difficulties in addition to problems with social communication and interactions, and repetitive or restrictive behaviors. The goal of early intervention for children with disabilities is to promote participation in routines and activities, but little is known about the role gross motor abilities contribute to participation for young children with ASD. The purpose of this study was to examine relationships between gross motor abilities and participation in preschool-aged children with ASD. Twenty-two children with ASD participated in the study. Gross motor skills were measured using the Peabody Developmental Motor Scales, Second Edition. Participation was measured using the Preschool Activity Card Sort. Children who had greater gross motor skills also demonstrated greater participation in self-care, high demand leisure, and social interaction activities. Results also identified activities that may be difficult for preschoolers with ASD. Findings suggest that early childhood intervention providers consider the impact of gross motor deficits within the context of participation in daily routines and activities.

Modernizing Clinical Trial Eligibility Criteria: Recommendations of the ASCO-Friends of Cancer Research Prior Therapies Work Group.

PURPOSE: Restrictive eligibility criteria induce differences between clinical trial and "real-world" treatment populations. Restrictions based on prior therapies are common; minimizing them when appropriate may increase patient participation in clinical trials. EXPERIMENTAL DESIGN: A multi-stakeholder working group developed a conceptual framework to guide evaluation of prevailing practices with respect to using prior treatment as selection criteria for clinical trials. The working group made recommendations to minimize restrictions based on prior therapies within the boundaries of scientific validity, patient centeredness, distributive justice, and beneficence. RECOMMENDATIONS: (i) Patients are eligible for clinical trials regardless of the number or type of prior therapies and without requiring a specific therapy prior to enrollment unless a scientific or clinically based rationale is provided as justification. (ii) Prior therapy (either limits on number and type of prior therapies or requirements for specific therapies before enrollment) could be used to determine eligibility in the following cases: a) the agents being studied target a specific mechanism or pathway that could potentially interact with a prior therapy; b) the study design requires that all patients begin protocol-specified treatment at the same point in the disease trajectory; and c) in randomized clinical studies, if the therapy in the control arm is not appropriate for the patient due to previous therapies received. (iii) Trial designers should consider conducting evaluation separately from the primary endpoint analysis for participants who have received prior therapies. CONCLUSIONS: Clinical trial sponsors and regulators should thoughtfully reexamine the use of prior therapy exposure as selection criteria to maximize clinical trial participation.See related commentary by Giantonio, p. 2369.

The Interdependence of Motor and Social Skill Development: Influence on Participation.

Participation is a major outcome area for physical therapists serving young children with disabilities. Contemporary models of disability such as the International Classification of Function, developmental theories such as the system perspective, and evidence-based early childhood practices recognize the interdependence of developmental domains, and suggest that change in 1 area of development influences change in another. Physical therapy provided in naturally occurring activities and routines, considered the preferred service delivery method, promotes participation of young children with disabilities. Research indicates that: (1) children develop skills, become independent, and form relationships through participation; and (2) with developing skills, children can increasingly participate. The purpose of this Perspective article is to synthesize the literature examining the relationship between motor skill development and the social interaction dimension of participation in young children. Current research examining the influence of motor skill development on social interactions in children with autism spectrum disorder will be discussed, exemplifying the interdependence of developmental domains. Implications for physical therapist practice and recommendations for future research are provided.

Promoting Scientist-Advocate Collaborations in Cancer Research: Why and How.

Advocates bring unique and important viewpoints to the cancer research process, ensuring that scientific and medical advances are patient-centered and relevant. In this article, we discuss the benefits of engaging advocates in cancer research and underscore ways in which both the scientific and patient communities can facilitate this mutually beneficial collaboration. We discuss how to establish and nurture successful scientist-advocate relationships throughout the research process. We review opportunities that are available to advocates who want to obtain training in the evaluation of cancer research. We also suggest practical solutions that can strengthen communication between scientists and advocates, such as introducing scientist-advocate interactions at the trainee level. Finally, we highlight the essential role social media can play in disseminating patient-supported cancer research findings to the patient community and in raising awareness of the importance of promoting cancer research. Our perspective offers a model that Georgetown Breast Cancer Advocates have found effective and which could be one option for those interested in developing productive, successful, and sustainable collaborations between advocates and scientists in cancer research. Cancer Res; 78(20); 5723-8. ©2018 AACR.

Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Clinical Practice Guideline Focused Update.

Purpose To update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. Methods An Expert Panel conducted targeted systematic literature reviews guided by a signals approach to identify new, potentially practice-changing data that might translate to revised practice recommendations. Results The Expert Panel reviewed phase III trials that evaluated adjuvant capecitabine after completion of standard preoperative anthracycline- and taxane-based combination chemotherapy by patients with early-stage breast cancer HER2-negative breast cancer with residual invasive disease at surgery; the addition of 1 year of adjuvant pertuzumab to combination chemotherapy and trastuzumab for patients with early-stage, HER2-positive breast cancer; and the use of neratinib as extended adjuvant therapy for patients after combination chemotherapy and trastuzumab-based adjuvant therapy with early-stage, HER2-positive breast cancer. Recommendations Patients with early-stage HER2-negative breast cancer with pathologic, invasive residual disease at surgery following standard anthracycline- and taxane-based preoperative therapy may be offered up to six to eight cycles of adjuvant capecitabine. Clinicians may add 1 year of adjuvant pertuzumab to trastuzumab-based combination chemotherapy in patients with high-risk, early-stage, HER2-positive breast cancer. Clinicians may use extended adjuvant therapy with neratinib to follow trastuzumab in patients with early-stage, HER2-positive breast cancer. Neratinib causes substantial diarrhea, and diarrhea prophylaxis must be used. Additional information can be found at www.asco.org/breast-cancer-guidelines .

Selection of Optimal Adjuvant Chemotherapy Regimens for Human Epidermal Growth Factor Receptor 2 (HER2) -Negative and Adjuvant Targeted Therapy for HER2-Positive Breast Cancers: An American Society of Clinical Oncology Guideline Adaptation of the Cancer Care Ontario Clinical Practice Guideline.

PURPOSE: A Cancer Care Ontario (CCO) guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer including adjuvant targeted therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancers was identified for adaptation. METHODS: The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for adapting clinical practice guidelines developed by other organizations. The CCO guideline was reviewed for developmental rigor and content applicability. RESULTS: On the basis of the content review of the CCO guideline, the ASCO Panel agreed that, in general, the recommendations were clear and thorough and were based on the most relevant scientific evidence, and they presented options that will be acceptable to patients. However, for some topics addressed in the CCO guideline, the ASCO Panel formulated a set of adapted recommendations on the basis of local context and practice beliefs of the Panel members. RECOMMENDATIONS: Decisions regarding adjuvant chemotherapy regimens should take into account baseline recurrence risk, toxicities, likelihood of benefit, and host factors such as comorbidities. In high-risk HER2-negative populations with excellent performance status, anthracycline- and taxane-containing regimens are the standard of care. Docetaxel and cyclophosphamide for four cycles is an acceptable non-anthracycline regimen. In high-risk HER2-positive disease, sequential anthracycline and taxanes administered concurrently with trastuzumab or docetaxel, carboplatin, and trastuzumab for six cycles are recommended. An alternative regimen in a lower-risk, node-negative, HER2-positive population is paclitaxel and trastuzumab once per week for 12 cycles. Trastuzumab should be given for 1 year. Platinum salts should not be routinely administered in the adjuvant triple-negative population until survival efficacy data become available.

ERα-XPO1 Cross Talk Controls Tamoxifen Sensitivity in Tumors by Altering ERK5 Cellular Localization.

Most breast cancer deaths occur in women with recurrent, estrogen receptor (ER)-α(+), metastatic tumors. There is a critical need for therapeutic approaches that include novel, targetable mechanism-based strategies by which ERα (+) tumors can be resensitized to endocrine therapies. The objective of this study was to validate a group of nuclear transport genes as potential biomarkers to predict the risk of endocrine therapy failure and to evaluate the inhibition of XPO1, one of these genes as a novel means to enhance the effectiveness of endocrine therapies. Using advanced statistical methods, we found that expression levels of several of nuclear transport genes including XPO1 were associated with poor survival and predicted recurrence of tamoxifen-treated breast tumors in human breast cancer gene expression data sets. In mechanistic studies we showed that the expression of XPO1 determined the cellular localization of the key signaling proteins and the response to tamoxifen. We demonstrated that combined targeting of XPO1 and ERα in several tamoxifen-resistant cell lines and tumor xenografts with the XPO1 inhibitor, Selinexor, and tamoxifen restored tamoxifen sensitivity and prevented recurrence in vivo. The nuclear transport pathways have not previously been implicated in the development of endocrine resistance, and given the need for better strategies for selecting patients to receive endocrine modulatory reagents and improving therapy response of relapsed ERα(+) tumors, our findings show great promise for uncovering the role these pathways play in reducing cancer recurrences.

A cytoplasmic substrate of mitogen-activated protein kinase is responsible for estrogen receptor-alpha down-regulation in breast cancer cells: the role of nuclear factor-kappaB.

Estrogen receptor alpha (ERalpha) negative breast tumors often present with enhanced expression and/or activation of growth factor receptors, resulting in increased growth factor signaling and hyperactivation of MAPK (ERK1 and ERK2). We have pre-viously shown that ERalpha(+) MCF-7 cells with elevated growth factor signaling lose expression of ERalpha without any ligand-independent transcriptional activation, and this is a reversible effect attributable to ERK1/2 hyperactivation. Here, we show that down-regulation of ERalpha is not mediated by a specific ERK-1 vs. ERK-2 substrate. Despite up-regulated activator protein-1 activity in response to ERK1/2 activation, and in ERalpha(-) and hormone-independent breast cancers, we find that increased activator protein-1 activity is not responsible for ERalpha down-regulation. Interestingly, our findings implicate a cytoplasmic substrate of ERK1/2. However, RSK1, the best-characterized cytoplasmic ERK1/2 substrate, does not down-regulate ERalpha in our models. On the other hand, inhibition of nuclear factor-kappaB (which is linked to chemoresistance in cancer in general and has elevated activity in hormone-independent and ERalpha- breast cancer) significantly enhances ERalpha activity, suggesting that indirect elevation in nuclear factor-kappaB activity (due to hyperactive ERK1/2) is at least partially responsible for ERalpha down-regulation in these cell line models.