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Background: Children with relapsed central nervous system (CNS tumors), neuroblastoma, sarcomas, and other rare solid tumors face poor outcomes. This prospective clinical trial examined the feasibility of combining genomic and transcriptomic profiling of tumor samples with a molecular tumor board (MTB) approach to make real‑time treatment decisions for children with relapsed/refractory solid tumors., Methods: Subjects were divided into three strata: stratum 1-relapsed/refractory neuroblastoma; stratum 2-relapsed/refractory CNS tumors; and stratum 3-relapsed/refractory rare solid tumors. Tumor samples were sent for tumor/normal whole-exome (WES) and tumor whole-transcriptome (WTS) sequencing, and the genomic data were used in a multi-institutional MTB to make real‑time treatment decisions. The MTB recommended plan allowed for a combination of up to 4 agents. Feasibility was measured by time to completion of genomic sequencing, MTB review and initiation of treatment. Response was assessed after every two cycles using Response Evaluation Criteria in Solid Tumors (RECIST). Patient clinical benefit was calculated by the sum of the CR, PR, SD, and NED subjects divided by the sum of complete response (CR), partial response (PR), stable disease (SD), no evidence of disease (NED), and progressive disease (PD) subjects. Grade 3 and higher related and unexpected adverse events (AEs) were tabulated for safety evaluation., Results: A total of 186 eligible patients were enrolled with 144 evaluable for safety and 124 evaluable for response. The average number of days from biopsy to initiation of the MTB-recommended combination therapy was 38 days. Patient benefit was exhibited in 65% of all subjects, 67% of neuroblastoma subjects, 73% of CNS tumor subjects, and 60% of rare tumor subjects. There was little associated toxicity above that expected for the MGT drugs used during this trial, suggestive of the safety of utilizing this method of selecting combination targeted therapy., Conclusions: This trial demonstrated the feasibility, safety, and efficacy of a comprehensive sequencing model to guide personalized therapy for patients with any relapsed/refractory solid malignancy. Personalized therapy was well tolerated, and the clinical benefit rate of 65% in these heavily pretreated populations suggests that this treatment strategy could be an effective option for relapsed and refractory pediatric cancers., Trial Registration: ClinicalTrials.gov, NCT02162732. Prospectively registered on June 11, 2014., (© 2024. The Author(s).)

Gliomas harboring oncogenic ROS1 alterations are uncommon and primarily described in infants. Our goal was to characterize the clinicopathological features and molecular signatures of the full spectrum of ROS1 fusion-positive gliomas across all age groups. Through a retrospective multi-institutional collaboration, we report a collection of unpublished ROS1 fusion gliomas along with the characterization and meta-analysis of new and published cases. A cohort of 32 new and 58 published cases was divided into the following 3 age groups: 19 infants, 40 pediatric patients, and 31 adults with gliomas. Tumors in infants and adults showed uniformly high-grade morphology; however, tumors in pediatric patients exhibited diverse histologic features. The GOPC::ROS1 fusion was prevalent (61/79, 77%) across all age groups, and 10 other partner genes were identified. Adult tumors showed recurrent genomic alterations characteristic of IDH wild-type glioblastoma, including the +7/-10/CDKN2A deletion; amplification of CDK4, MDM2, and PDGFRA genes; and mutations involving TERTp, TP53, PIK3R1, PIK3CA, PTEN, and NF1 genes. Infant tumors showed few genomic alterations, whereas pediatric tumors showed moderate genomic complexity. The outcomes were significantly poorer in adult patients. Although not statistically significant, tumors in infant and pediatric patients with high-grade histology and in hemispheric locations appeared more aggressive than tumors with lower grade histology or those in nonhemispheric locations. In conclusion, this study is the largest to date to characterize the clinicopathological and molecular signatures of ROS1 fusion-positive gliomas from infant, pediatric, and adult patients. We conclude that ROS1 likely acts as a driver in infant and pediatric gliomas and as a driver or codriver in adult gliomas. Integrated comprehensive clinical testing might be helpful in identifying such patients for possible targeted therapy., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Sonographers in the Western New South Wales Local Health District (WNSWLHD) reported a musculoskeletal pain prevalence rate of 95%. Participatory ergonomics, where workers are consulted about improving work conditions, was utilised to identify work-related musculoskeletal disorder (WMSD) risks and potential solutions. The aim of this study was to compare the prevalence of WMSD in a cohort of sonographers before and after implementation of ergonomic changes that were driven by recommendations from a participatory ergonomics approach., Methods: This observational mixed methods study analysed the impact of participatory ergonomic-driven interventions on changes on musculoskeletal pain in a cohort of sonographers employed within the WNSWLHD. A retrospective analysis of 10 sonographer WMSD pain surveys over five sites was completed, along with semi-structured interviews regarding which interventions were perceived as useful, which interventions were not implemented and any barriers to implementation., Results: Installation of patient monitors, use of ergonomic scanning techniques and job rotation were perceived as responsible for decreased musculoskeletal pain. Taking lunch breaks and microbreaks, use of antifatigue mats and having two sonographers perform mobile exams were not fully implemented. No interventions were perceived as responsible for increased pain., Conclusion: This small study provides preliminary evidence that a participatory ergonomics approach facilitated identification of occupation and site-specific risks for WMSD in the WNSWLHD, allowing implementation of ergonomic changes to be tailored to the workplace, resulting in a safer work environment for sonographers., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Background: Falls are a significant public health issue. There is strong evidence that exercise can prevent falls and the most effective programs are those that primarily involve balance and functional exercises, however uptake of such programs is low. Exercise prescribed during home visits by health professionals can prevent falls however this strategy would be costly to deliver at scale. We developed a new approach to teach home exercise through group-based workshops delivered by physiotherapists. The primary aim was to determine the effect of this approach on the rate of falls among older community-dwelling people over 12 months. Secondary outcomes included the proportion of people falling, fear of falling, physical activity, lower limb strength, balance and quality of life., Methods: A randomised controlled trial was conducted among community-dwelling people aged ≥65 in New South Wales, Australia. Participants were randomised to either the intervention group (exercise targeting balance and lower limb strength) or control group (exercise targeting upper limb strength)., Results: A total of 617 participants (mean age 73 years, +SD 6, 64% female) were randomly assigned to the intervention group (n = 307) or control group (n = 310). There was no significant between-group difference in the rate of falls (IRR 0.91, 95% CI 0.64 to 1.29, n = 579, p = 0.604) or the number of participants reporting one or more falls (IRR 0.99, 95% CI 0.76 to 1.29, n = 579, p = 0.946) during 12 month follow-up. A significant improvement in the intervention group compared to control group was found for fear of falling at 3, 6 and 12 months (mean difference 0.50, 95% CI 0.2 to 0.8, p = 0.004; 0.39, 95% CI 0.001 to 0.8, p = 0.049; 0.46, 95% CI 0.006 to 0.9, p = 0.047, respectively), and gait speed at 3 months (mean difference 0.09 s, 95% CI 0.003 to 0.19, p = 0.043). No statistically significant between-group differences were detected for the other secondary outcomes., Conclusions: There was no significant intervention impact on the rate of falls, but the program significantly reduced fear of falling and improved gait speed. Other exercise delivery approaches are needed to ensure an adequate intensity of balance and strength challenge and dose of exercise to prevent falls., (© 2022. The Author(s).)

The OncoScan CNV Plus Assay (OS+) is a single-nucleotide polymorphism microarray platform that can detect 74 hotspot somatic mutations (SMs) in nine genes via molecular inversion probes. We report validation of the SM component of OS+ using a cohort of pediatric high-grade brain tumor specimens. SM calls were generated from 46 brain tumor cases, most tested orthogonally via bidirectional Sanger sequencing. The initial calling algorithm result showed that 31 tumors were positive and 15 were negative for SM, with a total of 71 OS+ SM calls [28 high-confidence (HC) and 43 low-confidence (LC)]. Sanger sequencing was performed for 54 of the 71 calls (27 HC and 27 LC), as well as for 21 randomly selected hotspots across the 15 OS+ negative cases. HC calls (except EGFR) Sanger sequencing confirmed positive, negative calls confirmed negative, but none of the LC calls were Sanger-confirmed positive. An update of the OS+ algorithm resolved the LC calls, but of the 11 HC SM EGFR calls, Sanger sequencing confirmed only one. Two PTEN SM calls by OS+ in two separate cases were also negative per Sanger sequencing. We conclude that a majority of HC OS+ SM calls were accurate, except calls identified in EGFR and PTEN. Clinically, we report SMs identified by OS+ only after Sanger sequencing verification., (Copyright © 2021 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Deep learning (DL) is a widely applied mathematical modeling technique. Classically, DL models utilize large volumes of training data, which are not available in many healthcare contexts. For patients with brain tumors, non-invasive diagnosis would represent a substantial clinical advance, potentially sparing patients from the risks associated with surgical intervention on the brain. Such an approach will depend upon highly accurate models built using the limited datasets that are available. Herein, we present a novel genetic algorithm (GA) that identifies optimal architecture parameters using feature embeddings from state-of-the-art image classification networks to identify the pediatric brain tumor, adamantinomatous craniopharyngioma (ACP). We optimized classification models for preoperative Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and combined CT and MRI datasets with demonstrated test accuracies of 85.3%, 83.3%, and 87.8%, respectively. Notably, our GA improved baseline model performance by up to 38%. This work advances DL and its applications within healthcare by identifying optimized networks in small-scale data contexts. The proposed system is easily implementable and scalable for non-invasive computer-aided diagnosis, even for uncommon diseases.

Adamantinomatous craniopharyngioma (ACP) is a biologically benign but clinically aggressive lesion that has a significant impact on quality of life. The incidence of the disease has a bimodal distribution, with peaks occurring in children and older adults. Our group previously published the results of a transcriptome analysis of pediatric ACPs that identified several genes that were consistently overexpressed relative to other pediatric brain tumors and normal tissue. We now present the results of a transcriptome analysis comparing pediatric to adult ACP to identify biological differences between these groups that may provide novel therapeutic insights or support the assertion that potential therapies identified through the study of pediatric ACP may also have a role in adult ACP. Using our compiled transcriptome dataset of 27 pediatric and 9 adult ACPs, obtained through the Advancing Treatment for Pediatric Craniopharyngioma Consortium, we interrogated potential age-related transcriptional differences using several rigorous mathematical analyses. These included: canonical differential expression analysis; divisive, agglomerative, and probabilistic based hierarchical clustering; information theory based characterizations; and the deep learning approach, HD Spot. Our work indicates that there is no therapeutically relevant difference in ACP gene expression based on age. As such, potential therapeutic targets identified in pediatric ACP are also likely to have relvance for adult patients.

Objective: To investigate the influence of trunk and lower limb motion on electromyography (EMG) muscle activity and recruitment patterns around the shoulder., Design: Systematic review., Data Sources: MEDLINE, CINAHL, PEDro, AMED, PubMed, Cochrane Central Register of Controlled trials, Cochrane Database of Systematic reviews, SportsDiscuss and PROSPERO., Eligibility Criteria: Studies investigating both multiregional kinetic chain (KC) shoulder exercises and localised non-kinetic chain (nKC) shoulder exercises in healthy subjects under the same experimental conditions were included in this review., Results: KC exercises produced greater EMG activation levels in 5 of 11 studies for the lower trapezius. Of the remaining studies, five found no difference between the exercise types and one favoured nKC exercises. KC exercises produced greater EMG activation levels in 5 of 11 studies for the serratus anterior. Of the remaining studies, three reported the opposite and three found no significant difference between the exercise types. nKC exercises produced greater EMG activation in infraspinatus in three of four studies. KC exercises produced the lowest trapezius muscle ratios in all studies. Studies investigating the upper trapezius, middle trapezius, supraspinatus, subscapularis, biceps brachii, latifissimus dorsi, pectoralis major, deltoid, and trapezius and serratus anterior ratios showed inconsistency., Conclusion: This review found evidence that integrating the KC during shoulder rehabilitation may increase axioscapular muscle recruitment, produce lower trapezius muscle ratios and reduce the demands on the rotator cuff. Stepping appears preferable to squatting., Prospero Registration Number: CRD42015032557, 2015., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Shoulder Pain and Disability Index (SPADI) is a 13-item shoulder-specific patient-reported outcome measure (PROM). The English version is easy to use and has demonstrated excellent measurement properties for both clinical and research settings. The availability of the SPADI in Nepali would facilitate shoulder research and enhance management of patients with shoulder pain in Nepal. Therefore, the purpose of this study was to translate and cross-culturally adapt the SPADI into Nepali (SPADI-NP) and evaluate its measurement properties., Methods: The translation and adaptation process followed international guidelines. Participants completed SPADI-NP on two assessments (N = 150 at initial and 119 at follow-up assessment). A Nepali version of the Global Rating of Change score was completed at follow-up. Assessment of measurement properties included analysis of internal consistency (Cronbach's α), minimal detectable change (MDC) with standard error of measurement (SEM), test-retest reliability (intraclass correlation coefficient; ICC), validity (factor structure, construct using Pearson's correlation with the Disability of Arm and Hand [DASH]) and responsiveness (area under the curve; AUC) with minimal important change (MIC)., Results: Minor changes were integrated in the adaptation process to improve cultural relevance such as dress items. Items were largely loaded under two factors (pain and disability), internal consistencies were good for the pain construct (α = 0.82) and disability (α = 0.88) and test-retest reliability was excellent (pain = 0.89, disability = 0.96). MDC was 5.7 (out of 100) with SEM = 2.1. Strong associations with the DASH (r = 0.63 pain, r = 0.81 disability) demonstrated its construct validity. The AUC was 0.68 and MIC was 12.3 (out of 100)., Conclusion: The Nepali version of the SPADI demonstrated excellent reliability and validity. It can be used for the assessment of shoulder pain and disability in patients with shoulder pain in Nepal in both clinical practice and research.

Background: Patient-reported outcome measures (PROMs) are important tools in both clinical practice and research. However, no upper extremity PROM to assess physical disability is available in Nepali. The most commonly used and recommended questionnaire for the shoulder is the Disability of Arm, Shoulder and Hand (DASH). Therefore, the aim of the study was to translate and cross-culturally adapt the DASH into Nepali and determine its measurement properties., Methods: The translation and cultural adaptation process followed international standard procedures. The translated Nepali version of the questionnaire (DASH-NP) was completed by 156 patients with shoulder pain from three Nepali hospitals at an initial assessment and by 121 at follow-up. A Nepali version of Global Rating of Change (GROC-NP) was completed at follow-up to dichotomise improved and stable participants. Measurement properties testing included: internal consistency (Cronbach's alpha), test-retest reliability (Intraclass Correlation Coefficient, ICC), Minimal Detectable Change (MDC), construct validity - factor analysis, hypothesis testing with the Shoulder Pain and Disability Index (SPADI) (Pearson Correlation = r) and responsiveness - Area Under the Curve with minimal important change., Results: Significant adaptations such as changing measurement units, activities and terminology were incorporated to improve cultural relevance. Internal consistency (α = 0.92) and test-retest reliability (ICC = 0.97, 95% CI: 0.94-0.98, p < 0.001) were excellent. The MDC was 11 out of 100 points. There were moderate-high positive correlations with the SPADI pain and disability items (rs = 0.63 and 0.81, P < 0.001). Four factor solution was retrieved for the DASH-NP. The Area Under the Curve was 0.69 (95% CI: 0.57 - 0.81, p < 0.001) with minimal important change of 11.2/100 points., Conclusions: The Nepali translation of the DASH is comprehensible, easy to administer via self-report or interview. It is found to be a reliable, valid, and responsive measure in patients with shoulder pain in Nepal. The DASH-NP can be used to assess shoulder pain related disability in Nepal for clinical practice or research.

Introduction: Falling when older is a major public health issue. There is compelling evidence to show that specific exercise programs can reduce the risk and rate of falls in community-dwelling older people. Another major health issue for older people living in the community is upper limb dysfunction, including shoulder pain. Home-based exercise programs appeal to some older people, due to their convenience., Research Questions: This trial aims to determine the effectiveness and cost-effectiveness of a home-based lower limb exercise program compared with a home-based upper limb exercise program to prevent falls and upper limb dysfunction among community-dwelling people aged 65+ years., Design: Randomised, controlled trial., Participants and Setting: A total of 576 community-dwelling people will be recruited from the Illawarra and Shoalhaven regions of New South Wales, Australia., Intervention: Participants will be randomised to either a home-based lower limb exercise intervention or a home-based upper limb exercise intervention. The lower limb program is designed to improve balance and strength in the lower limbs. The upper limb program is designed to improve upper limb strength and mobility. Participants will attend three group-based instruction sessions to learn and progress the exercises, and will be instructed to perform the exercises three times per week at home for 12 months., Outcome Measures: The two primary outcomes will be fall rates, recorded with monthly calendars for a 12-month period, and upper limb dysfunction, measured with the Disability of the Arm, Shoulder and Hand questionnaire. Secondary outcomes will include: lower limb strength and balance; shoulder strength and mobility; physical activity; quality of life; attitudes to exercise; proportion of fallers; fear of falling; and health and community service use. The cost-effectiveness of both exercise programs from a health and community service provider perspective will be evaluated., Analysis: Negative binomial regression models will be used to estimate the between-group difference in fall rates. Modified Poisson regression models will be used to compare groups on dichotomous outcome measures. Linear regression models will be used to assess the effect of group allocation on the continuously scored measures, after adjusting for baseline scores. Two economic evaluations will be conducted: the first will assess cost-effectiveness of the lower limb program compared with the upper limb program; and the second will assess cost-effectiveness of the upper limb program compared with the lower limb program., Discussion: If effective, the trial will provide a model for both upper limb and lower limb exercise programs that can be performed at home and implemented at scale to community-dwelling older adults., (Copyright © 2017 Australian Physiotherapy Association. All rights reserved.)

Question: During isometric shoulder adduction in normal subjects, do the rotator cuff muscles activate more than other shoulder muscles? Are the activation patterns influenced by shoulder abduction angle or load?, Design: A within-participant, repeated measures experimental study., Participants: 15 healthy adults., Intervention: Participants performed an isometric adduction exercise at 30°, 60°, and 90° abduction in the scapular plane and at 25%, 50%, 75%, and 100% load., Outcome Measures: During the exercises, a combination of indwelling and surface electromyographic recordings were taken from 11 shoulder muscles: supraspinatus, infraspinatus, subscapularis, pectoralis major, teres major, latissimus dorsi, rhomboid major, serratus anterior, lower trapezius, upper trapezius, and deltoid., Results: At 100% load, mean rotator cuff activation levels were low (supraspinatus at 3% of its maximum voluntary contraction, infraspinatus 27%, and subscapularis 27%) and significantly less than the activation levels of rhomboid major (81%), latissimus dorsi (103%), and teres major (76%) (F₁₀,₁₄₀ = 15.5, p < 0.01). No significant difference in activity levels of the rotator cuff muscles were recorded when isometric adduction was performed at 30°, 60°, or 90° abduction (p > 0.89). Among the muscles activated above minimum levels (> 10% of maximum voluntary contraction), mean activation levels increased as load increased (F₃,₄₂ = 72.0, p < 0.01), Conclusion: Since isometric adduction in normal subjects does not produce moderate to high activation levels in any of the rotator cuff muscles tested, these results do not support the use of shoulder adduction to identify rotator cuff muscle dysfunction or strengthen the rotator cuff muscles.

Background and Purpose: The aim of this study was to evaluate the efficacy of a physical therapy approach to the treatment of shoulder pain. Subjects. Sixty-six volunteers with shoulder pain believed to be of local mechanical origin were randomly allocated to either a treatment group or a control group., Methods: Subjects in the treatment group received 1 month of physical therapy aimed at restoring function of their shoulder muscles. Subjects in the control group received no treatment. Outcome measurements of pain intensity, range of motion (ROM), isometric muscle force, functional impairment, and self-perception of improvement were obtained by blinded assessment., Results: Subjects in the treatment group showed improvement in pain-free abduction and flexion ROM, functional impairment, and self-perception of improvement. The control group deteriorated slightly over the experimental period in ROM and functional impairment measures., Conclusion and Discussion: These results suggest that the physical therapy approach used in this study is effective in improving shoulder function in subjects experiencing pain of mechanical origin. The results also provide little evidence of spontaneous recovery over a 1-month period.

A buckle force transducer, suitable for measuring forces in biological materials in situ, was investigated in order to establish its reliability as a force measuring instrument. Eleven separate materials varying in shape, size and mechanical properties, were tested. Each material was repeatedly loaded and unloaded. Calibration lines, relating the applied force and the output voltage, were calculated for each loading-unloading trial. For each material, deviations between trials were calculated as a percentage of the range of voltages recorded in the first trial of that material. These data were analysed to evaluate four parameters: test-retest reliability, the effect of skewed alignment, linearity of the instrument, and amount of hysteresis present. Results indicate that the buckle force transducer used is a highly reliable and consistent measuring instrument, which behaves in a linear manner and demonstrates acceptably small hysteresis. The implications for measuring forces in biological materials are discussed., (Copyright © 1993 Australian Physiotherapy Association. Published by . All rights reserved.)