Paediatric sleep diagnostics in the 21st century: the era of "sleep-omics"?

Paediatric sleep diagnostics is performed using complex multichannel tests in specialised centres, limiting access and availability and resulting in delayed diagnosis and management. Such investigations are often challenging due to patient size (prematurity), tolerability, and compliance with "gold standard" equipment. Children with sensory/behavioural issues, at increased risk of sleep disordered breathing (SDB), often find standard diagnostic equipment difficult.SDB can have implications for a child both in terms of physical health and neurocognitive development. Potential sequelae of untreated SDB includes failure to thrive, cardiopulmonary disease, impaired learning and behavioural issues. Prompt and accurate diagnosis of SDB is important to facilitate early intervention and improve outcomes.The current gold-standard diagnostic test for SDB is polysomnography (PSG), which is expensive, requiring the interpretation of a highly specialised physiologist. PSG is not feasible in low-income countries or outwith specialist sleep centres. During the coronavirus disease 2019 pandemic, efforts were made to improve remote monitoring and diagnostics in paediatric sleep medicine, resulting in a paradigm shift in SDB technology with a focus on automated diagnosis harnessing artificial intelligence (AI). AI enables interrogation of large datasets, setting the scene for an era of "sleep-omics", characterising the endotypic and phenotypic bedrock of SDB by drawing on genetic, lifestyle and demographic information. The National Institute for Health and Care Excellence recently announced a programme for the development of automated home-testing devices for SDB. Scorer-independent scalable diagnostic approaches for paediatric SDB have potential to improve diagnostic accuracy, accessibility and patient tolerability; reduce health inequalities; and yield downstream economic and environmental benefits.

Reliability of Measures of Lower-Body Strength and Speed in Academy Male Adolescent Soccer Players.

ABSTRACT: Ferguson, J, Gibson, NV, Weston, M, and McCunn, R. Reliability of measures of lower body strength and speed in academy male adolescent soccer players. J Strength Cond Res 38(3): e96-e103, 2024-The Nordbord and ForceFrame represent a practical and time efficient means of assessing eccentric hamstring and isometric adductor strength in the large number of squads and players associated with youth soccer academies, yet measurement reliability in this population is unexamined. Therefore, over a period of 4 days, with no less than 24 hours and no more than 48 hours between trials, 37 players (age: 14.7 ± 0.8 years, stature: 168.7 ± 7.8 cm, mass: 57.7 ± 9.1 kg, and maturity offset: 0.8 ± 0.9 years) were assessed for eccentric hamstring strength (force, torque), isometric adductor strength (long and short lever positions), and 30-m sprint (5, 10, and 20-m splits), using the Nordbord, ForceFrame, and electronic timing gates, respectively, on 3 separate occasions. Relative reliability (intraclass correlation coefficient) was rated as good for all Nordbord (range: 0.86-0.89) and ForceFrame (0.78-0.85) measures and ranged from moderate (0.53) to excellent (0.93) for the speed measures, improving with increased distance. Absolute reliability (standard error of the measurement [%SEM]) ranged from 7 to 8% (Nordbord), 3 to 11% (ForceFrame), and 1 to 4% (sprints). Our data provide the first Nordbord and ForceFrame reliability estimates in adolescent soccer academy players. To interpret test sensitivity, practitioners are encouraged to interpret our estimates of absolute reliability against meaningful change values derived from personal experience and evidence-based knowledge and not against absolute or standardized thresholds.

Phase II trial of afatinib in patients with advanced urothelial carcinoma with genetic alterations in ERBB1-3 (LUX-Bladder 1).

BACKGROUND: Preclinical and early clinical data suggest that the irreversible ErbB family blocker afatinib may be effective in urothelial cancers harbouring ERBB mutations. METHODS: This open-label, phase II, single-arm trial (LUX-Bladder 1, NCT02780687) assessed the efficacy and safety of second-line afatinib 40 mg/d in patients with metastatic urothelial carcinoma with ERBB1-3 alterations. The primary endpoint was 6-month progression-free survival rate (PFS6) (cohort A); other endpoints included ORR, PFS, OS, DCR and safety (cohorts A and B). Cohort A was planned to have two stages: stage 2 enrolment was based on observed antitumour activity. RESULTS: Thirty-four patients were enroled into cohort A and eight into cohort B. In cohorts A/B, PFS6 was 11.8%/12.5%, ORR was 5.9%/12.5%, DCR was 50.0%/25.0%, median PFS was 9.8/7.8 weeks and median OS was 30.1/29.6 weeks. Three patients (two ERBB2-amplified [cohort A]; one EGFR-amplified [cohort B]) achieved partial responses. Stage 2 for cohort A did not proceed. All patients experienced adverse events (AEs), most commonly (any/grade 3) diarrhoea (76.2%/9.5%). Two patients (4.8%) discontinued due to AEs and one fatal AE was observed (acute coronary syndrome; not considered treatment-related). CONCLUSIONS: An exploratory biomarker analysis suggested that basal-squamous tumours and ERBB2 amplification were associated with superior response to afatinib. CLINICAL TRIAL REGISTRATION: NCT02780687.

Recommendations from Diabetes UK's 2022 diabetes and physical activity workshop.

AIMS: To describe the process and outputs of a workshop convened to identify key priorities for future research in the area of diabetes and physical activity and provide recommendations to researchers and research funders on how best to address them. METHODS: A 1-day research workshop was conducted, bringing together researchers, people living with diabetes, healthcare professionals, and members of staff from Diabetes UK to identify and prioritise recommendations for future research into physical activity and diabetes. RESULTS: Workshop attendees prioritised four key themes for further research: (i) better understanding of the physiology of exercise in all groups of people: in particular, what patient metabolic characteristics influence or predict the physiological response to physical activity, and the potential role of physical activity in beta cell preservation; (ii) designing physical activity interventions for maximum impact; (iii) promoting sustained physical activity across the life course; (iv) designing physical activity studies for groups with multiple long-term conditions. CONCLUSIONS: This paper outlines recommendations to address the current gaps in knowledge related to diabetes and physical activity and calls on the research community to develop applications in these areas and funders to consider how to stimulate research in these areas.

Subjective Measures of Workload and Sleep in Australian Army Recruits; Potential Utility as Monitoring Tools.

INTRODUCTION: Subjective measures may offer practitioners a relatively simple method to monitor recruit responses to basic military training (BMT). Yet, a lack of agreement between subjective and objective measures may presents a problem to practitioners wishing to implement subjective monitoring strategies. This study therefore aims to examine associations between subjective and objective measures of workload and sleep in Australian Army recruits. MATERIALS AND METHODS: Thirty recruits provided daily rating of perceived exertion (RPE) and differential RPE (d-RPE) for breathlessness and leg muscle exertion each evening. Daily internal workloads determined via heart rate monitors were expressed as Edwards training impulse (TRIMP) and average heart rate. External workloads were determined via global positioning system (PlayerLoadTM) and activity monitors (step count). Subjective sleep quality and duration was monitored in 29 different recruits via a customized questionnaire. Activity monitors assessed objective sleep measures. Linear mixed-models assessed associations between objective and subjective measures. Akaike Information Criterion assessed if the inclusion of d-RPE measures resulted in a more parsimonious model. Mean bias, typical error of the estimate (TEE) and within-subject repeated measures correlations examined agreement between subjective and objective sleep duration. RESULTS: Conditional R2 for associations between objective and subjective workloads ranged from 0.18 to 0.78, P < 0.01, with strong associations between subjective measures of workload and TRIMP (0.65-0.78), average heart rate (0.57-0.73), and PlayerLoadTM (0.54-0.68). Including d-RPE lowered Akaike Information Criterion. The slope estimate between objective and subjective measures of sleep quality was not significant. A trivial relationship (r = 0.12; CI -0.03, 0.27) was observed between objective and subjective sleep duration with subjective measures overestimating (mean bias 25 min) sleep duration (TEE 41 min). CONCLUSIONS: Daily RPE offers a proxy measure of internal workload in Australian Army recruits; however, the current subjective sleep questionnaire should not be considered a proxy measure of objective sleep measures.

A Phase I, Open-Label, Dose Confirmation, Escalation, and Expansion Trial of BI 1810631 as Monotherapy in Patients With Advanced or Metastatic Solid Tumors With HER2 Aberrations.

BACKGROUND: BI 1810631 is a human HER2-selective tyrosine kinase inhibitor that covalently binds to both wild-type and mutated HER2 receptors, including exon 20 insertion mutations, whilst sparing EGFR signaling. This phase Ia/Ib, open-label, non-randomized study will determine the safety, maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of BI 1810631 in patients with HER2 aberration-positive solid tumors (NCT04886804). PATIENTS AND METHODS: In phase Ia, patients with histologically/cytologically confirmed HER2 aberration-positive advanced/metastatic solid tumors will receive BI 1810631 orally twice daily (BID) or once daily (QD) at escalating doses. Starting dose level is 15 mg BID; QD schedule will begin after one dose level above estimated therapeutic dose of BI 1810631 is determined safe by the Dose Escalation Committee. Dose escalation will continue until MTD/recommended phase II dose and preferred phase Ib schedule for each schedule is determined. In phase Ib, patients with HER2 tyrosine kinase domain (TKD) mutation-positive non-small cell lung cancer (NSCLC) who have previously received ≥1 line of systemic therapy will be enrolled initially, with possible inclusion of additional NSCLC cohorts in the future, including untreated patients. The primary endpoints will be MTD based on number of dose-limiting toxicities (DLTs)/number of patients with DLTs (phase Ia) and objective response (phase Ib). Secondary endpoints include PK parameters (phase Ia/Ib); duration of response, disease control, duration of disease control, and progression-free survival (phase Ib). CONCLUSIONS: BI 1810631 could be an effective and tolerable EGFR-sparing oral treatment for patients with HER2 mutation-positive NSCLC, including exon 20 insertion mutations. GOV IDENTIFIER: NCT04886804.

Injury incidence and burden differ between season phases in male academy football (soccer) players.

Adolescent elite-level footballers are exposed to unique physical and psychological stressors which may increase injury risk, with fluctuating injury prevalence and burden. This study investigates the patterns of injury incidence and burden from 2017 to 2020 within combined pre-, start-of-, mid- and end-of-season and school-holiday phases in U13-U18 Australian male academy players. Injury incidence rate and burden were calculated for medical attention (MA), full and partial time-loss (TL) and non-time-loss (non-TL) injuries. Injury rate ratios (IRR) for injury incidences were assessed using Generalised Linear Mixed Models, and 99% confidence intervals for injury burden differences between phases. MA and non-TL injury incidence rates were higher during pre-season (IRR 1.65, p = 0.01; IRR 2.08, p = 0.02, respectively), and mid-season showed a higher non-TL incidence rate (IRR 2.15, p = 0.02) and burden (69 days with injury/1000 hrs, CI 47-103) compared to end-of-season (25 days with injury/1000 hrs, CI 15-45). MA injury rates and partial TL injury burden were higher during school compared to holiday periods (IRR 0.6, p = 0.04; 61 partial days lost/1000 hrs, CI 35-104; 13 partial days lost/1000 hrs, CI 8-23). Season phase and return-to-school may increase injury risks for elite academy footballers, and considering these phases may assist in developing injury prevention systems.

Exploring the true burden of a time-loss injury: full vs partial time-loss in elite academy football (soccer).

In football, the number of days without full participation in training/competition is often used as a surrogate measure for time-loss (TL) caused by injury. However, injury management and return-to-play processes frequently include modified participation, which to date has only been recorded through self-reports. This study aims to demonstrate the differentiation between 'full' (no participation in team football) and 'partial' (reduced/modified participation in team football) burden. Injury and exposure data were collected from 118 male elite footballers (U13-U18) over 3 consecutive seasons according to the Football Consensus Statement. TL injury burden was calculated separately as the number of total, 'full' and 'partial' days lost per 1000 h of exposure. Injury burden (137.2 days lost/1000 h, 95% CI 133.4-141.0) was comprised of 23% (31.9 days lost/1000 h, 95% CI 30.1-33.8) partial TL and 77% (105.3 days lost/1000 h, 95% CI 102.0-108.6) full TL burden. Injuries of moderate severity (8-28 days lost) showed 40% of partial TL. TL injury incidence rate (6.6 injuries/1000 h, 95% CI 5.8-7.5), the number of severe injuries (16%), and the distribution of TL and non-TL injuries (56% and 44%) were comparable to other reports in elite youth footballers. Almost one-quarter of the TL injury burden showed that injured players were still included in some team football activities, which, for injuries with TL >7 days, was likely related to the return to play process. Therefore, reporting on partial TL provides insight into the true impact of injury on participation levels.

Recent advances in paediatric sleep disordered breathing.

This article reviews the latest evidence pertaining to childhood sleep disordered breathing (SDB), which is associated with negative neurobehavioural, cardiovascular and growth outcomes. Polysomnography is the accepted gold standard for diagnosing SDB but is expensive and limited to specialist centres. Simpler tests such as cardiorespiratory polygraphy and pulse oximetry are probably sufficient for diagnosing obstructive sleep apnoea (OSA) in typically developing children, and new data-processing techniques may improve their accuracy. Adenotonsillectomy is the first-line treatment for OSA, with recent evidence showing that intracapsular tonsillectomy results in lower rates of adverse events than traditional techniques. Anti-inflammatory medication and positive airway pressure respiratory support are not always suitable or successful, although weight loss and hypoglossal nerve stimulation may help in select comorbid conditions. Educational aims: To understand the clinical impact of childhood sleep disordered breathing (SDB).To understand that, while sleep laboratory polysomnography has been the gold standard for diagnosis of SDB, other diagnostic techniques exist with their own benefits and limitations.To recognise that adenotonsillectomy and positive pressure respiratory support are the mainstays of treating childhood SDB, but different approaches may be indicated in certain patient groups.

A Comprehensive Analysis of Injuries During Army Basic Military Training.

INTRODUCTION: The injury definitions and surveillance methods commonly used in Army basic military training (BMT) research may underestimate the extent of injury. This study therefore aims to obtain a comprehensive understanding of injuries sustained during BMT by employing recording methods to capture all physical complaints. MATERIALS AND METHODS: Six hundred and forty-six recruits were assessed over the 12-week Australian Army BMT course. Throughout BMT injury, data were recorded via (1) physiotherapy reports following recruit consultation, (2) a member of the research team (third party) present at physical training sessions, and (3) recruit daily self-reports. RESULTS: Two hundred and thirty-five recruits had ≥1 incident injury recorded by physiotherapists, 365 recruits had ≥1 incident injury recorded by the third party, and 542 recruits reported ≥1 injury-related problems via the self-reported health questionnaire. Six hundred twenty-one, six hundred eighty-seven, and two thousand nine hundred sixty-four incident injuries were recorded from a total of 997 physiotherapy reports, 1,937 third-party reports, and 13,181 self-reported injury-related problems, respectively. The lower extremity was the most commonly injured general body region as indicated by all three recording methods. Overuse accounted for 79% and 76% of documented incident injuries from physiotherapists and the third party, respectively. CONCLUSIONS: This study highlights that injury recording methods impact injury reporting during BMT. The present findings suggest that traditional injury surveillance methods, which rely on medical encounters, underestimate the injury profile during BMT. Considering accurate injury surveillance is fundamental in the sequence of injury prevention, implementing additional injury recording methods during BMT may thus improve injury surveillance and better inform training modifications and injury prevention programs.

Overnight sleeping heart rate variability of Army recruits during a 12-week basic military training course.

PURPOSE: This study aimed to quantify sleeping heart rate (HR) and HR variability (HRV) alongside circulating tumor necrosis factor alpha (TNFα) concentrations during 12-week Basic Military Training (BMT). We hypothesised that, despite a high allostatic load, BMT would increase cardiorespiratory fitness and HRV, while lowering both sleeping HR and TNFα in young healthy recruits. METHODS: Sixty-three recruits (18-43 years) undertook ≥ 2 overnight cardiac frequency recordings in weeks 1, 8 and 12 of BMT with 4 h of beat-to-beat HR collected between 00:00 and 06:00 h on each night. Beat-to-beat data were used to derive HR and HRV metrics which were analysed as weekly averages (totalling 8 h). A fasted morning blood sample was collected in the equivalent weeks for the measurement of circulating TNFα concentrations and predicted VO2max was assessed in weeks 2 and 8. RESULTS: Predicted VO2max was significantly increased at week 8 (+ 3.3 ± 2.6 mL kg-1 min-1; p < 0.001). Sleeping HR (wk1, 63 ± 7 b min-1) was progressively reduced throughout BMT (wk8, 58 ± 6; wk12, 55 ± 6 b min-1; p < 0.01). Sleeping HRV reflected by the root mean square of successive differences (RMSSD; wk1, 86 ± 50 ms) was progressively increased (wk8, 98 ± 50; wk12, 106 ± 52 ms; p < 0.01). Fasted circulating TNFα (wk1, 9.1 ± 2.8 pg/mL) remained unchanged at wk8 (8.9 ± 2.5 pg/mL; p = 0.79) but were significantly reduced at wk12 (8.0 ± 2.4 pg/mL; p < 0.01). CONCLUSION: Increased predicted VO2max, HRV and reduced HR during overnight sleep are reflective of typical cardiorespiratory endurance training responses. These results indicate that recruits are achieving cardiovascular health benefits despite the high allostatic load associated with the 12-week BMT.

Genomic Analysis of Tumors from Patients with Glioblastoma with Long-Term Response to Afatinib.

Glioblastoma is an aggressive form of central nervous system tumor. Recurrence rates following primary therapy are high, and few second-line treatment options provide durable clinical benefit. Aberrations of the epidermal growth factor receptor (EGFR) gene are observed in up to 57% of glioblastoma cases and EGFR overexpression has been identified in approximately 60% of primary glioblastomas. In preclinical studies, afatinib, a second-generation ErbB blocker, inhibited cell proliferation in cells harboring mutations commonly found in glioblastoma. In two previous Phase I/II studies of afatinib plus temozolomide in patients with glioblastoma, limited efficacy was observed; however, there was notable benefit in patients with the EGFR variant III (EGFRvIII) mutation, EGFR amplification, and those with loss of phosphatase and tensin homolog (PTEN). This case series report details treatment histories of three long-term responders from these trials. Next-generation sequencing of tumor samples identified alterations in a number of cancer-related genes, including mutations in, and amplification of, EGFR. Tumor samples from all three patients shared favorable prognostic factors, eg O6-methylguanine-DNA methyl-transferase (MGMT) gene promoter methylation; however, negative prognostic factors were also observed, suggesting that these shared genetic features did not completely account for the favorable responses. The genetic profile of the tumor from Patient 1 showed clear differences from the other two tumors: lack of involvement of EGFR aberrations but with a mutation occurring in PTPN11. Preclinical studies showed that single-agent afatinib and temozolomide both separately inhibit the growth of tumors with a C-terminal EGFR truncation, thus providing further rationale for combining these two agents in the treatment of glioblastomas harboring EGFR aberrations. These findings suggest that afatinib may provide treatment benefit in patients with glioblastomas that harbor ErbB family aberrations and, potentially, other genetic aberrations. Further studies are needed to establish which patients with newly diagnosed/recurrent glioblastomas may potentially benefit from treatment with afatinib.

Chronicity of sleep restriction during Army basic military training.

OBJECTIVES: To investigate: (i) the chronicity and phasic variability of sleep patterns and restriction in recruits during basic military training (BMT); and (ii) identify subjective sleep quality in young adult recruits prior to entry into BMT. DESIGN: Prospective observational study. METHODS: Sleep was monitored using wrist-worn actigraphy in Army recruits (n = 57, 18-43 y) throughout 12-weeks of BMT. The Pittsburgh Sleep Quality Index (PSQI) was completed in the first week of training to provide a subjective estimate of pre-BMT sleep patterns. A mixed-effects model was used to compare week-to-week and training phase (Orientation, Development, Field, Drill) differences for rates of sub-optimal sleep (6-7 h), sleep restriction (≤6 h), and actigraphy recorded sleep measures. RESULTS: Sleep duration was 06:24 ±â€¯00:18h (mean ±â€¯SD) during BMT with all recruits experiencing sub-optimal sleep and 42% (n = 24) were sleep restricted for ≥2 consecutive weeks. During Field, sleep duration (06:06 ±â€¯00:36h) and efficiency (71 ±â€¯6%; p < 0.01) were reduced by 15-18 min (minimum - maximum) and 7-8% respectively; whereas, sleep latency (30 ±â€¯15 min), wake after sleep onset (121 ±â€¯23 min), sleep fragmentation index (41 ±â€¯4%) and average awakening length (6.5 ±â€¯1.6 min) were greater than non-Field phases (p < 0.01) by 16-18 min, 28-33 min, 8-10% and 2.5-3 min respectively. Pre-BMT global PSQI score was 5 ±â€¯3, sleep duration and efficiency were 7.4 ±â€¯1.3 h and 88 ±â€¯9% respectively. Sleep schedule was highly variable at pre-BMT (bedtime: 22:34 ±â€¯7:46 h; wake time: 6:59 ±â€¯1:42 h) unlike BMT (2200-0600 h). CONCLUSIONS: The chronicity of sub-optimal sleep and sleep restriction is substantial during BMT and increased training demands exacerbate sleep disruption. Exploration of sleep strategies (e.g. napping, night-time routine) are required to mitigate sleep-associated performance detriments and maladaptive outcomes during BMT.

Reliability and Validity of a 6-Minute Yo-Yo Intermittent Endurance Test Level 2 in Subelite Part Time Male Soccer Players.

ABSTRACT: Gibson, N, Easton, C, Williams, M, McCunn, R, Gibson, NV. Reliability and validity of a 6-minute Yo-Yo Intermittent Endurance Test Level 2 in subelite part time male soccer players. J Strength Cond Res 36(4): 1011-1018, 2022-The aim of this study was to assess the reliability and relationship to maximal intermittent running performance of the 6-minute Yo-Yo Intermittent Endurance Test Level 2 (YYIET2), among subelite part time soccer players. Twenty male soccer players (15-22 years) completed three 6-minute YYIET2 trials with heart rate (HR), PlayerLoad, and rating of perceived exertion assessed during the protocol and HR and blood lactate assessed during 5 minutes of recovery. Subjects also completed a maximal version of the YYIET2 and the maximal Yo-Yo Intermittent Recovery Test Level 1 (YYIRT1) and 2 (YYIRT2). Heart rate at 4 and 6 minutes, PlayerLoad at 4 minutes, and HR recovery at 2, 3, 4, and 5 minutes during recovery from the 6-minute YYIET2 demonstrated little variance between tests. Correlations between variables measured during and after the 6-minute YYIET2 and distance covered in maximal tests ranged from r = 0.02 to -0.72. The 6-minute YYIET2 provides practitioners with a method of reliably assessing HR responses within subelite part time soccer players, although large correlations with maximal assessments suggest it can be used as a proxy measure for maximal intermittent running performance. Given its ease of administration and low time cost, the 6-minute YYIET2 offers practitioners a useful means of tracking training status and movement efficiency in players longitudinally.

Initial fitness, maturity status, and total training explain small and inconsistent proportions of the variance in physical development of adolescent footballers across one season.

To investigate how initial fitness, maturity status, and training time explain changes in physical performance across one season. Eighty-eight adolescent male footballers, representing four age categories (Under 15 [n = 12], Under 14 [n = 21], Under 13 [n = 25], Under 12 [n = 30]), were tested using physical performance tests (20 m sprint, change of direction, squat jump and yo-yo intermittent recovery test level 1 [YYIRTL1]) and maturity offset at the season start (Test 1) and end (Test 2). Multiple regression determined the proportion of variance in test score changes, explained by three predictor variables: initial fitness (i.e., Test 1), maturity offset change, and training time. With combined categories, predictor variables explained 0.051 to 0.297 of the variance in physical performance score changes. Analysing age categories separately, predictor variables explained 0.047 to 0.407 (20 m sprint), 0.202 to 0.626 (change of direction), 0.336 to 0.502 (squat jump), and 0.196 to 0.777 (YYIRTL1) of variance in test score changes. Of the limited differences in relative predictor contribution, Test 1 was the strongest predictor of test score change. Initial fitness, maturity status change, and training time explain small and inconsistent proportions of variance in adolescent footballers' physical development across one season.

Comprehensive analysis of the ErbB receptor family in pediatric nervous system tumors and rhabdomyosarcoma.

BACKGROUND: There is a paucity of knowledge regarding pediatric biomarkers, including the relevance of ErbB pathway aberrations in pediatric tumors. We investigated the occurrence of ErbB receptor aberrations across different pediatric malignancies, to identify patterns of ErbB dysregulation and define biomarkers suitable for patient enrichment in clinical studies. PROCEDURE: Tissue samples from 297 patients with nervous system tumors and rhabdomyosarcoma were analyzed for immunohistochemical expression or gene amplification of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). Exploratory analyses of HER3/HER4 expression, and mRNA expression of ErbB receptors/ligands (NanoString) were performed. Assay validation followed general procedures, with additional validation to address Clinical Laboratory Improvement Amendments (CLIA) requirements. RESULTS: In most tumor types, samples with high ErbB receptor expression were found with heterogeneous distribution. We considered increased/aberrant ErbB pathway activation when greater than or equal to two EGFR/HER2 markers were simultaneously upregulated. ErbB pathway dysregulation was identified in ∼20%-30% of samples for most tumor types (medulloblastoma/primitive neuroectodermal tumors 31.1%, high-grade glioma 27.1%, neuroblastoma 22.7%, rhabdomyosarcoma 23.1%, ependymoma 18.8%), 4.2% of diffuse intrinsic pontine gliomas, and no recurrent or refractory low-grade astrocytomas. In medulloblastoma/primitive neuroectodermal tumors and neuroblastoma, this was attributed mainly to high EGFR polysomy/HER2 amplification, whereas EGFR gene amplification was observed in some high-grade glioma samples. EGFR/HER2 overexpression was most prevalent in ependymoma. CONCLUSIONS: Overexpression and/or amplification of EGFR/HER2 were identified as potential enrichment biomarkers for clinical trials of ErbB-targeted drugs.

Indirect effects of the COVID-19 pandemic on paediatric healthcare use and severe disease: a retrospective national cohort study.

OBJECTIVES: To determine the indirect consequences of the COVID-19 pandemic on paediatric healthcare utilisation and severe disease at a national level following lockdown on 23 March 2020. DESIGN: National retrospective cohort study. SETTING: Emergency childhood primary and secondary care providers across Scotland; two national paediatric intensive care units (PICUs); statutory death records. PARTICIPANTS: 273 455 unscheduled primary care attendances; 462 437 emergency department attendances; 54 076 emergency hospital admissions; 413 PICU unplanned emergency admissions requiring invasive mechanical ventilation; and 415 deaths during the lockdown study period and equivalent dates in previous years. MAIN OUTCOME MEASURES: Rates of emergency care consultations, attendances and admissions; clinical severity scores on presentation to PICU; rates and causes of childhood death. For all data sets, rates during the lockdown period were compared with mean or aggregated rates for the equivalent dates in 2016-2019. RESULTS: The rates of emergency presentations to primary and secondary care fell during lockdown in comparison to previous years. Emergency PICU admissions for children requiring invasive mechanical ventilation also fell as a proportion of cases for the entire population, with an OR of 0.52 for likelihood of admission during lockdown (95% CI 0.37 to 0.73), compared with the equivalent period in previous years. Clinical severity scores did not suggest children were presenting with more advanced disease. The greatest reduction in PICU admissions was for diseases of the respiratory system; those for injury, poisoning or other external causes were equivalent to previous years. Mortality during lockdown did not change significantly compared with 2016-2019. CONCLUSIONS: National lockdown led to a reduction in paediatric emergency care utilisation, without associated evidence of severe harm.

Activation of the Gluteus Maximus During Performance of the Back Squat, Split Squat, and Barbell Hip Thrust and the Relationship With Maximal Sprinting.

ABSTRACT: Williams, MJ, Gibson, N, Sorbie, GG, Ugbolue, UC, Brouner, J, and Easton, C. Activation of the gluteus maximus during performance of the back squat, split squat, and barbell hip thrust and the relationship with maximal sprinting. J Strength Cond Res 35(1): 16-24, 2021-The purpose of this research was to compare muscle activation of the gluteus maximus and ground reaction force between the barbell hip thrust, back squat, and split squat and to determine the relationship between these outcomes and vertical and horizontal forces during maximal sprinting. Twelve, male, team sport athletes (age, 25.0 ± 4.0 years; stature, 184.1 ± 6.0 cm; body mass, 82.2 ± 7.9 kg) performed separate movements of the 3 strength exercises at a load equivalent to their individual 3 repetition maximum. The ground reaction force was measured using force plates and the electromyography (EMG) activity of the upper and lower gluteus maximus and was recorded in each leg and expressed as percentage of the maximum voluntary isometric contraction (MVIC). Subjects then completed a single sprint on a nonmotorized treadmill for the assessment of maximal velocity and horizontal and vertical forces. Although ground reaction force was lower, peak EMG activity in the gluteus maximus was higher in the hip thrust than in the back squat (p = 0.024; 95% confidence interval [CI] = 4-56% MVIC) and split squat (p = 0.016; 95% CI = 6-58% MVIC). Peak sprint velocity correlated with both anterior-posterior horizontal force (r = 0.72) and peak ground reaction force during the barbell hip thrust (r = 0.69) but no other variables. The increased activation of gluteus maximus during the barbell hip thrust and the relationship with maximal running speed suggests that this movement may be optimal for training this muscle group in comparison to the back squat and split squat.