Search

The experimental demonstration of a fluidic, multiaxis thrust vectoring (MA TV) scheme is presented for a structurally fixed, afterburning nozzle referred to as the conformal fluidic nozzle (CFN). This concept for jet flow control features symmetric injection around the nozzle throat to provide throttling for jet area control and asymmetric injection to sub-sonically skew the sonic plane for jet vectoring. The conceptual development of the CFN was presented in a companion paper (Miller et al. [1]). In that study, critical design variables were shown to be the flap length and expansion area ratio of the nozzle, and the location, angle, and distribution of injected flow. Measures of merit were vectoring capability, gross thrust coefficient, and discharge coefficient. A demonstration of MATV was conducted on a 20 percent scale CFN test article across a range of nozzle pressure ratios (NPR), injector flow rates, and flow distributions. Both yaw and pitch vector angles of greater than 8 deg were obtained at NPR of 5.5. Yaw vector angles greater than 10 deg were achieved at lower NPR. Values of thrust coefficient for the CFN generally exceeded published measurements of shock-based vectoring methods. In terms of vectoring effectiveness (ratio of vector angle to percent injected flow), fluidic throat skewing was found to be comparable to shock-based vectoring methods. [DOI: 10.1115/1.1361109]

The article describes an iterative algorithm for sparcity enforcing near-field acoustical holography over a wide frequency range based on the application of an optimized pseudo-random array geometry. Topics discussed include the method called wideband holography (WBH) as an example of remote sensing. Also mentioned are WBH being tested by real measurements on a pair of two-way loudspeakers and a car engine as well as typical application areas, such as engines and gearboxes.

Background: Cellular senescence can have positive and negative effects on the body, including aiding in damage repair and facilitating tumor growth. Adamantinomatous craniopharyngioma (ACP), the most common pediatric sellar/suprasellar brain tumor, poses significant treatment challenges. Recent studies suggest that senescent cells in ACP tumors may contribute to tumor growth and invasion by releasing a senesecence-associated secretory phenotype. However, a detailed analysis of these characteristics has yet to be completed., Methods: We analyzed primary tissue samples from ACP patients using single-cell, single-nuclei, and spatial RNA sequencing. We performed various analyses, including gene expression clustering, inferred senescence cells from gene expression, and conducted cytokine signaling inference. We utilized LASSO to select essential gene expression pathways associated with senescence. Finally, we validated our findings through immunostaining., Results: We observed significant diversity in gene expression and tissue structure. Key factors such as NFKB, RELA, and SP1 are essential in regulating gene expression, while senescence markers are present throughout the tissue. SPP1 is the most significant cytokine signaling network among ACP cells, while the Wnt signaling pathway predominantly occurs between epithelial and glial cells. Our research has identified links between senescence-associated features and pathways, such as PI3K/Akt/mTOR, MYC, FZD, and Hedgehog, with increased P53 expression associated with senescence in these cells., Conclusions: A complex interplay between cellular senescence, cytokine signaling, and gene expression pathways underlies ACP development. Further research is crucial to understand how these elements interact to create novel therapeutic approaches for patients with ACP., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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.)

Children with relapsed/refractory (R/R) neuroblastoma (NB) and medulloblastoma (MB) have poor outcomes. We evaluated the efficacy of nifurtimox (Nfx) in a clinical trial for children with R/R NB and MB. Subjects were divided into three strata: first relapse NB, multiply R/R NB, and R/R MB. All patients received Nfx (30 mg/kg/day divided TID daily), Topotecan (0.75 mg/m 2 /dose, days 1-5) and Cyclophosphamide (250 mg/m 2 /dose, days 1-5) every 3 weeks. Response was assessed after every two courses using International Neuroblastoma Response Criteria and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. One hundred and twelve eligible patients were enrolled with 110 evaluable for safety and 76 evaluable for response. In stratum 1, there was a 53.9% response rate (CR + PR), and a 69.3% total benefit rate (CR + PR + SD), with an average time on therapy of 165.2 days. In stratum 2, there was a 16.3% response rate, and a 72.1% total benefit rate, and an average time on study of 158.4 days. In stratum 3, there was a 20% response rate and a 65% total benefit rate, an average time on therapy of 105.0 days. The most common side effects included bone marrow suppression and reversible neurologic complications. The combination of Nfx, topotecan and cyclophosphamide was tolerated, and the objective response rate plus SD of 69.8% in these heavily pretreated populations suggests that this combination is an effective option for patients with R/R NB and MB. Although few objective responses were observed, the high percentage of stabilization of disease and prolonged response rate in patients with multiply relapsed disease shows this combination therapy warrants further testing., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Objectives: To establish the reliability of a standardised ultrasound protocol to measure normal inferior glenohumeral capsule (IGHC) thickness and to investigate the effects of age, sex, hand dominance and angles of abduction on the thickness., Methods: IGHC images were obtained at 60 o , 90 o and 180 o abduction angles of 151 asymptomatic shoulders in supine position. Following the proposed guidelines, three sonographers blindly measured the IGHC thicknesses for intra- and interrater reliability assessments., Results: The intrarater reliability was excellent (intraclass correlation coefficient value = 0.95; 95% CI = 0.92-0.97). The interrater reliability was moderate (intraclass correlation coefficient value = 0.74; 95% CI = 0.60-0.83). The mean IGHC thickness values in mm ± SD at 60 o , 90 o and 180 o abduction angles for males were 3.3 ± 0.93, 3.0 ± 0.80 and 2.6 ± 0.55 and those for females were 2.7 ± 0.86, 2.4 ± 0.7 and 2.0 ± 0.56 respectively. Although males had thicker IGHC, the rate at which the thickness reduced with increased abduction was same in both males and females. Age and hand dominance had no effect., Conclusion: The normal IGHC thickness varies with sex and the abduction angle of the arm at which it is measured. A large variation of IGHC thickness exists in the normal population., Advances in Knowledge: The results of this study discourage the use of a single value of IGHC thickness and emphasise the importance of comparing the thickness of the symptomatic side to that of the asymptomatic side of the same subject at the same abduction level. The guidelines provided in this study can be used in clinical practice and in future research studies., Competing Interests: Competing interestsAuthors have no conflicts of interest to declare.

While ultrasound has become a preferred tool for musculoskeletal imaging, differing ultrasound findings that have been reported in patients with adhesive capsulitis can create confusion and misconceptions. This systematic review was aimed at summarizing all the ultrasound features currently described in the literature and providing a critical analysis of the sources to allow the readers to make a well-informed decision on the reliability of these features in the diagnosis of this condition. Databases were searched for original studies up to August 2021. Twenty-three studies were included. The QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool was used to assess the quality of each selected article. Fourteen ultrasound features were identified. A quality analysis of all ultrasound features was performed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) framework. All studies exhibited considerable heterogeneity in investigated ultrasound features and methodologies employed; therefore, meta-analysis was not considered to be appropriate. Hence, narrative synthesis was performed. The overall quality of each ultrasound outcome was found to be of "low" to "very low" level, and the generalisability of the results was also thought to be limited. Cautious interpretation and clinical correlation are recommended while applying these ultrasound features in clinical practice., Competing Interests: Conflict of interest disclosure We declare that no potential competing interests exist., (Copyright © 2022 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Context: The public health system faces unprecedented challenges due to the pandemic, racism, health inequity, and the politicization of public health. At all levels of the system, the workforce is experiencing distress, burnout, safety issues, and attrition. Public health is being challenged to demonstrate and justify its impact and value, while also leveraging opportunities for learning and system strengthening., Program: To explore the current state and identify opportunities to strengthen the public health system, the Region 7 Midwestern Public Health Training Center (MPHTC), with support from Engaging Inquiry, embarked on a distinctive type of systems analysis, called "dynamic systems mapping.", Implementation: This approach brought together diverse sectors of public health partners in the region to develop a rich contextual narrative and system-level understanding to highlight and align existing and emergent strengths, areas for growth, and tangible goals for the immediate- and long-term sustainability of local and regional health., Evaluation: Focus groups and workshops were conducted with diverse practitioners to identify upstream causes and downstream effects of 11 key forces driving system behavior. These focus groups resulted in the development of a visual map that MPHTC is utilizing to identify opportunities for leverage, develop strategies to maximize the potential impact of these leverage points, as well as facilitate continuous learning., Discussion: Public health utilization of systems mapping is a valuable approach to strengthening local and national system responses to current and future public health needs. Outcomes and lessons learned from the systems mapping process are discussed., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The Patient-Specific Functional Scale (PSFS), Disability of the Arm, Shoulder and Hand (DASH), Quick-DASH, and Shoulder Pain and Disability Index (SPADI) are frequently used instruments in shoulder functional assessment. They are available in Nepali and all but the PSFS has been validated for shoulder assessment. Therefore, the aim of this study was to validate the Nepali PSFS in shoulder pain patients and to compare validity, reliability, and responsiveness of all four instruments to provide a recommendation for their use., Method: Patients attending physiotherapy completed the Nepali PSFS at baseline and follow-up (1-3 weeks). It was tested for reliability using internal consistency (Cronbach's α), intraclass correlation coefficient (ICC), construct validity by hypothesis testing and responsiveness by anchor-based method using Area Under the Curve (AUC). The instruments were compared based on reported measurement properties and patients' preference., Results: 156 patients enrolled at baseline and 121 at follow-up. The PSFS showed sufficient reliability (α = 0.70, ICC = 0.82), construct validity (all three hypotheses met) and responsiveness (AUC = 0.83). Measurement property comparison demonstrated adequate reliability and validity, while PSFS was the most responsive instrument. Patients favoured the verbal rating scale of the DASH/Quick-DASH. The DASH had a lower completion rate for 'culturally sensitive' and 'uncommon' activities., Conclusion: The Nepali PSFS is a reliable, valid, and responsive instrument in shoulder functional assessment. The combined use of the Quick-DASH or SPADI with the PSFS is recommended for a comprehensive assessment of Nepali shoulder pain patients in clinical and research settings. They are shorter, more appropriate to the Nepali context and provide balanced self-evaluation., (© 2022. The Author(s).)

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).)

Calibration of neuromusculoskeletal models using functional tasks is performed to calculate subject-specific musculotendon parameters, as well as coefficients describing the shape of muscle excitation and activation functions. The objective of the present study was to employ a neuromusculoskeletal model of the shoulder driven entirely from muscle electromyography (EMG) to quantify the influence of different model calibration strategies on muscle and joint force predictions. Three healthy adults performed dynamic shoulder abduction and flexion, followed by calibration tasks that included reaching, head touching as well as active and passive abduction, flexion and axial rotation, and submaximal isometric abduction, flexion and axial rotation contractions. EMG data were simultaneously measured from 16 shoulder muscles using surface and intramuscular electrodes, and joint motion evaluated using video motion analysis. Muscle and joint forces were calculated using subject-specific EMG-driven neuromusculoskeletal models that were uncalibrated and calibrated using (i) all calibration tasks (ii) sagittal plane calibration tasks, and (iii) scapular plane calibration tasks. Joint forces were compared to published instrumented implant data. Calibrating models across all tasks resulted in glenohumeral joint force magnitudes that were more similar to instrumented implant data than those derived from any other model calibration strategy. Muscles that generated greater torque were more sensitive to calibration than those that contributed less. This study demonstrates that extensive model calibration over a broad range of contrasting tasks produces the most accurate and physiologically relevant musculotendon and EMG-to-activation parameters. This study will assist in development and deployment of subject-specific neuromusculoskeletal models., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: To examine the measurement properties of the Nepali version of the Quick-Disabilities of the Arm, Shoulder and Hand (QuickDASH-NP)., Materials and Methods: The Nepali DASH and Shoulder Pain and Disability Index (SPADI) were completed at baseline assessment, and again at follow-up with the Nepali Global Rating of Change (GROC-NP) score. The 11 items of the QuickDASH-NP were extracted from the DASH and tested for confirmatory factory analysis (CFA), exploratory factor analysis (EFA), internal consistency (α), item-total correlation (ITC), test-retest reliability (ICC), measurement errors, hypothesis testing (correlation with DASH and SPADI) and responsiveness (effect size-ES, standardised response mean-SRM)., Results: A total of 156 participants completed questionnaires at baseline and 121 at follow-up with all questionnaires valid (no participant leaving more than one question blank). CFA suggested a poor fit for the single-factor model. The EFA demonstrated two factors with acceptable internal consistency (α = 0.79 and 0.75) for each factor. The test-retest reliability was excellent (ICC = 0.94; 95%CI:0.92-0.98), correlation was positive and very strong with the DASH-NP (r = 0.96) and strong with the SPADI-NP (r = 0.81). The Standard Error of Measurement was 2.83 and Smallest Detectable Change 7.84/100. The ES and SRM were moderate to high., Conclusions: The QuickDASH-NP is reliable, valid, and able to detect change in shoulder symptoms among Nepali participants. It offers a short, easy to complete self-reporting tool for clinical use and research., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.)

The aim of this systematic review was to summarise the effects of ergonomics interventions on work-related upper limb musculoskeletal pain and dysfunction, and on productivity in sonographers, surgeons and dentists. A total of 31 studies were included. All studies reported effects on upper limb pain. Nine studies reported effects on dysfunction and only two studies reported effects on productivity. Moderately strong evidence in reducing upper limb pain was found for instigation of microbreaks into long duration surgical procedures, and the use of wider, lighter handles in dental instruments. Moderate evidence was also found for use of prismatic glasses and favourable positioning in reducing upper limb pain. Weak, inconsistent or no evidence was found for all other ergonomics interventions in reducing upper limb pain and dysfunction and increasing productivity. The lack of high quality research, particularly in sonographers and in the outcome of productivity, should be addressed. Practitioner summary: This systematic review investigates the effectiveness of ergonomics interventions on upper limb pain, dysfunction and productivity in sonographers, dentists and surgeons. Instigation of microbreaks during long duration procedures and the use of wider, lighter instrument handles were most effective in reducing upper limb work-related pain. Abbreviations: ANOVA: analysis of variance; CLS: conventional laparoscopic surgery; DMAIC: define, measure, analyze, improve and control; GRADE: grading of recommendations, assessment, development and evaluations; HD: high definition; PRISMA: preferred reporting items for systematic reviews and meta-analyses; PROSPERO: The International Prospective Register of Systematic Reviews; RCT: randomised control trial; SILS: single incision laparoscopic surgery; VITOM: video telescopic operative microscope; WNSWLHD: Western New South Wales Local Health District; WMSD: work related musculoskeletal disorder.