The French multicentric molecular analysis platforms and personalized medicine trials MOST, MOST Plus and MEGAMOST.

BACKGROUND AND PURPOSE: In this manuscript we describe the academic French multicentric molecular analysis platforms including PROFILER, promoted by Centre Léon Berard, and the multicentric personalized medicine trials MOST, MOST Plus and MEGAMOST. PATIENTS/MATERIAL AND METHODS: MOST, MOST Plus and MEGAMOST comprise 14 cohorts with different targeted agents and immunotherapies. RESULTS AND INTERPRETATION: PROFILER has recruited 5,991 patients in 10 years, MOST and MOST Plus 875 patients since 2014 and MEGAMOST 172 patients since 2020, and are still ongoing. We provide a description of the local, national and international implications of these initiatives, and we review the results of the sorafenib and olaparib cohorts.

Cumulative Prenatal Risk Factors and Developmental Coordination Disorder in Young Children.

OBJECTIVES: To examine the effect of cumulative prenatal risk factors (RFs) on the presence of Developmental Coordination Disorder (DCD) in young children. METHODS: Participants (N = 589, 338 boys, Mage = 4.5 ± 0.5 years) were from a larger cohort study, the Coordination and Activity Tracking in Children (CATCH). Motor coordination was assessed using the Movement Assessment Battery for Children- 2nd Edition. Children were classified as at risk for DCD (DCDr) based on European Academy of Childhood Disability guidelines. RFs were obtained through a parent-completed survey. A multiple logistic regression was conducted to examine the effect of the RFs on DCD. RESULTS: Results showed that the odds of a child having DCDr are significantly higher with a greater total number of prenatal RFs, after adjustment for mother's age at child's birth, child's sex, child's age, marital status and total annual household income (OR = 1.48, p < 0.01). CONCLUSIONS: These findings warrant further investigation into the cumulative impact of multiple prenatal RFs and whether specific combinations of RFs might be more strongly linked to DCD than others. These results provide additional insight into possible causes and prevention of DCD.

Benefit of mechanical thrombectomy in acute ischemic stroke related to calcified cerebral embolus.

PURPOSE: Mechanical thrombectomies (MT) in patients with large vessel occlusion (LVO) related to calcified cerebral embolus (CCE) have been reported, through small case series, being associated with low reperfusion rate and worse outcome, compared to regular MT. The purpose of the MASC (Mechanical Thrombectomy in Acute Ischemic Stroke Related to Calcified Cerebral Embolus) study was to evaluate the incidence of CCEs treated by MT and the effectiveness of MT in this indication. METHODS: The MASC study is a retrospective multicentric (n = 37) national study gathering the cases of adult patients who underwent MT for acute ischemic stroke with LVO related to a CCE in France from January 2015 to November 2019. Reperfusion rate (mTICI ≥ 2B), complication rate and 90-day mRS were systematically collected. We then conducted a systematic review by searching for articles in PubMed, Cochrane Library, Embase and Google Scholar from January 2015 to March 2020. A meta-analysis was performed to estimate clinical outcome at 90 days, reperfusion rate and complications. RESULTS: We gathered data from 35 patients. Reperfusion was obtained in 57% of the cases. Good clinical outcome was observed in 28% of the patients. The meta-analysis retrieved 136 patients. Reperfusion and good clinical outcome were obtained in 50% and 29% of the cases, respectively. CONCLUSION: The MASC study found worse angiographic and clinical outcomes compared to regular thrombectomies. Individual patient-based meta-analysis including the MASC findings shows a 50% reperfusion rate and a 29% of good clinical outcome.

Physical activity in young children at risk for developmental coordination disorder.

AIM: To examine cross-sectional differences in patterns of daily physical activity accumulation between preschool children at risk for developmental coordination disorder (DCD) compared to typically developing children. METHOD: In total, 514 children (292 males, 222 females; 4-5y) were recruited as part of the Coordination and Activity Tracking in CHildren (CATCH) study. Motor competence was assessed using the Movement Assessment Battery for Children, Second Edition; children scoring ≤5th centile comprised the probable DCD group (pDCD, n=87), between the 6th and 16th centile were considered to be at risk for DCD (rDCD, n=149), and >16th centile were considered typically developing (n=278). Seven-day physical activity was measured using hip-worn accelerometers. Average daily intensity of activity, frequency, and duration of moderate-to-vigorous physical activity (MVPA) bouts, and triaxial activity counts per minute were determined. RESULTS: No differences in daily activity in any intensity or axis of movement were found among the three groups. However, young children with pDCD accumulated their MVPA in slightly shorter bouts compared to typically developing children. INTERPRETATION: Young children at risk for DCD are not yet in an activity deficit. This may be because of the low motor skill demands of play in this age group. Early motor interventions may be able to promote continued physical activity participation in children with DCD. WHAT THIS PAPER ADDS: Preschool children at risk for developmental coordination disorder (DCD) are not less active than their peers. Overall intensity and frequency of daily activity bouts are similar among motor groups. Children with probable DCD accumulate their activity in shorter bouts.

ACTIVIDAD FÍSICA EN NIÑOS PEQUEÑOS CON RIESGO DE TRASTORNO DEL DESARROLLO DE LA COORDINACIÓN: OBJETIVO: Examinar por medio de un corte transversal las diferencias en los patrones de actividad física entre los niños en edad preescolar con riesgo de trastorno del desarrollo de la coordinación (TDC) en comparación con niños con un desarrollo típico MÉTODO: En total, se reclutaron 514 niños (292 varones, 222 mujeres; de 4 y 5 años) como parte del estudio Coordinación y Seguimiento de Actividad en niños (CATCH). Las capacidades motrices se evaluaron utilizando el test MABC 2 (Movement Assessment Battery for Children). Los niños con puntaje ≤5 percentilo formaron el grupo con TDC probable (pTDC, n = 87), entre percentilos 6 y 16 se consideraron en riesgo de TDC (rTDC, n = 149), y > percentilo 16 se consideraron con desarrollo típico (o normal, n = 278). La actividad física a lo largo de siete días se midió utilizando acelerómetros portados en la cadera. Se determinó la intensidad diaria promedio de la actividad, la frecuencia y la duración de los momentos de actividad física moderada a intensa (MVPA), y los recuentos de actividad triaxial por minuto. RESULTADOS: No se encontraron diferencias en la actividad diaria en ninguna intensidad o eje de movimiento entre los tres grupos. Sin embargo, los niños pequeños con pTDC desarrollaron su MVPA (actividad física moderada a intensa) en episodios ligeramente más cortos en comparación con los niños con un desarrollo típico. INTERPRETACIÓN: Los niños pequeños en riesgo de TDC aún no presentan un déficit de actividad. Esto puede ser debido a las bajas exigencias motrices del juego en este grupo etario. Las intervenciones motoras tempranas pueden promover la participación en actividades físicas de los niños con TDC.

ATIVIDADE FÍSICA EM CRIANÇAS PEQUENAS COM RISCO DE TRANSTORNO DO DESENVOLVIMENTO DA COORDENAÇÃO: OBJETIVO: Observar as diferenças transversais nos padrões de acumulação de atividade física diária entre crianças na idade pré-escolar com risco de transtorno do desenvolvimento da coordenação (TDC) e crianças de desenvolvimento típico. MÉTODOS: Um total de 512 crianças (292 meninos, 222 meninas; de idade entre 4 e 5 anos) foram recrutadas como parte do estudo Acompanhamento da Coordenação e de Atividades de Crianças (Coordination and Activity Tracking in CHildren - CATCH). As competências motoras foram avaliadas por meio da Bateria de Avaliação do Movimento para Crianças (Movement Assessment Battery for Children - MABC) segunda edição. Crianças com pontuação abaixo do quinto percentil compunham o provável grupo com TDC (pDDC, n=87), entre o percentil 6 e 16 foram consideradas com risco de DDC (rTDC, n=149), e aquelas com pontuação acima do percentil 16 foram consideradas de desenvolvimento típico (n=278). A atividade física ao longo de 7 dias foi mensurada utilizando-se acelerômetros posicionados no quadril. Foram avaliadas a média de intensidade da atividade diária, frequência e duração das atividades físicas moderadas a vigorosas e contagem das atividades triaxiais por minuto. RESULTADOS: Não foram encontradas diferenças entre os três grupos avaliados para intensidade ou eixo de movimento. Entretanto, crianças do grupo pTDC acumularam suas atividades físicas moderadas a vigorosas em blocos ligeiramente mais curtos do que crianças de desenvolvimento típico. INTERPRETAÇÃO: Crianças mais novas com risco de TDC ainda não apresentam déficits de atividade física. Isso pode ser devido às baixas demandas motoras de brincar nessa faixa etária. Intervenções motoras precoces podem ser capazes de promover participação em atividades físicas continuada em crianças com TDC.

Evaluation of the revised Nipissing District Developmental Screening (NDDS) tool for use in general population samples of infants and children.

BACKGROUND: There is widespread interest in identification of developmental delay in the first six years of life. This requires, however, a reliable and valid measure for screening. In Ontario, the 18-month enhanced well-baby visit includes province-wide administration of a parent-reported survey, the Nipissing District Developmental Screening (NDDS) tool, to facilitate early identification of delay. Yet, at present the psychometric properties of the NDDS are largely unknown. METHOD: 812 children and their families were recruited from the community. Parents (most often mothers) completed the NDDS. A sub-sample (n = 111) of parents completed the NDDS again within a two-week period to assess test-retest reliability. For children 3 or younger, the criterion measure was the Bayley Scales of Infant Development, 3rd edition; for older children, a battery of other measures was used. All criterion measures were administered by trained assessors. Mild and severe delays were identified based on both published cut-points and on the distribution of raw scores. Sensitivity, specificity, positive and negative predictive values were calculated to assess agreement between tests. RESULTS: Test-retest reliability was modest (Spearman's rho = .62, p < 001). Regardless of the age of the child, the definition of delay (mild versus severe), or the cut-point used on the NDDS, sensitivities (from 29 to 68 %) and specificities (from 58 to 88 %) were poor to moderate. CONCLUSION: The modest test-retest results, coupled with the generally poor observed agreement with criterion measures, suggests the NDDS should not be used on its own for identification of developmental delay in community or population-based settings.

The Coordination and Activity Tracking in CHildren (CATCH) study: rationale and design.

BACKGROUND: Past studies have found that children with Developmental Coordination Disorder (DCD) engage in less physical activity than typically developing children. This "activity deficit" may result in children with DCD being less physically fit and more likely to be overweight or obese, potentially increasing later risk for poor cardiovascular health. Unfortunately, the majority of DCD research has been limited to cross-sectional designs, leading to questions about the complex relationship among motor ability, inactivity and health-related fitness. Of the few longitudinal studies on the topic, determining precedence amongst these factors is difficult because study cohorts typically focus on mid to late childhood. By this age, both decreased physical fitness and obesity are often established. The Coordination and Activity Tracking in CHildren (CATCH) study will examine the pathways connecting DCD, physical activity, physical fitness, and body composition from early to middle childhood. METHODS: The CATCH study is a prospective cohort study. We aim to recruit a cohort of 600 children aged 4 to 5 years (300 probable DCD [pDCD] and 300 controls) and test them once a year for 4 years. At Phase 1 of baseline testing, we assess motor skills, cognitive ability (IQ), basic anthropometry, flexibility and lower body muscle strength, while parents complete an interview and questionnaires regarding family demographics, their child's physical activity, and behavioural characteristics. Children who move on to Phase 2 (longitudinal cohort) have their body fat percentage, foot structure, aerobic and anaerobic fitness assessed. An accelerometer to measure physical activity is then given to the child and interested family members. The family also receives an accelerometer logbook and 3-day food dairy. At years 2 to 4, children in the longitudinal cohort will have all baseline assessments repeated (excluding the IQ test), and complete an additional measure of perceived self-efficacy. Parents will complete an ADHD index twice within the follow-up period. To assess the association between DCD, fitness and adiposity, our primary analysis will involve longitudinal growth models with fixed effects. DISCUSSION: The CATCH study will provide a clearer understanding of pathways between DCD and health-related fitness necessary to determine the types of interventions children with DCD require.

Does aneurysmal wall enhancement on vessel wall MRI help to distinguish stable from unstable intracranial aneurysms?

BACKGROUND AND PURPOSE: Arterial wall enhancement on vessel wall MRI was described in intracranial inflammatory arterial disease. We hypothesized that circumferential aneurysmal wall enhancement (CAWE) could be an indirect marker of aneurysmal wall inflammation and, therefore, would be more frequent in unstable (ruptured, symptomatic, or undergoing morphological modification) than in stable (incidental and nonevolving) intracranial aneurysms. METHODS: We prospectively performed vessel wall MRI in patients with stable or unstable intracranial aneurysms. Two readers independently had to determine whether a CAWE was present. RESULTS: We included 87 patients harboring 108 aneurysms. Interreader and intrareader agreement for CAWE was excellent (κ=0.85; 95% confidence interval, 0.75-0.95 and κ=0.90; 95% confidence interval, 0.83-0.98, respectively). A CAWE was significantly more frequently seen in unstable than in stable aneurysms (27/31, 87% versus 22/77, 28.5%, respectively; P<0.0001). Multivariate logistic regression, including CAWE, size, location, multiplicity of aneurysms, and daily aspirin intake, revealed that CAWE was the only independent factor associated with unstable status (odds ratio, 9.20; 95% confidence interval, 2.92-29.0; P=0.0002). CONCLUSIONS: CAWE was more frequently observed in unstable intracranial aneurysms and may be used as a surrogate of inflammatory activity in the aneurysmal wall.

Patient-specific academic detailing for smoking cessation: feasibility study.

OBJECTIVE: To describe and to determine the feasibility of a patient-specific academic detailing (PAD) smoking cessation (SC) program in a primary care setting. DESIGN: Descriptive cohort feasibility study. SETTING: Hamilton, Ont. PARTICIPANTS: Pharmacists, physicians, nurse practitioners, and their patients. INTERVENTIONS: Integrated pharmacists received basic academic detailing training and education on SC and then delivered PAD to prescribers using structured verbal education and written materials. Data were collected using structured forms. MAIN OUTCOME MEASURES: Five main feasibility criteria were generated based on Canadian academic detailing programs: PAD coordinator time to train pharmacists less than 40 hours; median time of SC education per pharmacist less than 20 hours; median time per PAD session less than 60 minutes for initial visit; percentage of prescribers receiving PAD within 3 months greater than 50%; and number of new SC referrals to pharmacists at 6 months more than 10 patients per 1.0 full-time equivalent (FTE) pharmacist (total of approximately 30 patients). RESULTS: Eight pharmacists (5.8 FTE) received basic academic detailing training and education on SC PAD. Forty-eight physicians and 9 nurse practitioners consented to participate in the study. The mean PAD coordinator training time was 29.1 hours. The median time for SC education was 3.1 hours. The median times for PAD sessions were 15 and 25 minutes for an initial visit and follow-up visit, respectively. The numbers of prescribers who had received PAD at 3 and 6 months were 50 of 64 (78.1%) and 57 of 64 (89.1%), respectively. The numbers of new SC referrals at 3 and 6 months were 11 patients per FTE pharmacist (total of 66 patients) and 34 patients per FTE pharmacist (total of 200 patients), respectively. CONCLUSION: This study met the predetermined feasibility criteria with respect to the management, resources, process, and scientific components. Further study is warranted to determine whether PAD is more effective than conventional academic detailing.

Are temporal artery temperatures accurate enough to replace rectal temperature measurement in pediatric ED patients?

OBJECTIVE: This study examined the accuracy of temporal artery and axillary temperatures compared with rectal temperatures in pediatric ED patients younger than 4 years. METHODS: A method-comparison study design was used to examine the agreement between a temporal artery or axillary thermometer and a nondisposable, rectal electronic thermometer, which is the clinical reference standard for temperature measurement in children. Temperatures were taken with each device in a convenience sample of stable, pediatric ED patients who were younger than 4 years. Bias and precision were calculated to quantify the differences between the 2 devices, as well as the percentage of temporal artery and axillary temperatures that were >±1.0°C and >±1.5°C higher or lower than the rectal temperature. RESULTS: A total of 52 pediatric ED patients were studied over a 10-month period. Bias and precision for the temporal artery and axillary devices were -0.46°C ± 0.50°C and -0.93°C ± 0.49°C, respectively. The percentage of temporal artery and axillary temperatures that were >±1.0°C and/or >±1.5°C above or below the clinical reference temperature were 15% and 6%, respectively, for the temporal artery thermometer and 39% and 14%, respectively, for the axillary thermometer. DISCUSSION: Bias and precision values for the temporal artery, but not the axillary temperature, were within the acceptable range set by experts to use as a noninvasive substitute for core body temperature measurements. If properly used by ED staff, temporal artery thermometers could be used to obtain temperature in pediatric patients younger than 4 years, thus avoiding physical and psychological discomfort for the child and parent associated with obtaining rectal thermometers.

Facilitating Gender-Affirming Nursing Encounters.

The purpose of this article is to highlight the essentials for facilitating gender-affirming nursing encounters for transgender, nonbinary, and other gender expansive (TNGE) people. The authors illustrate what constitutes as gender-affirming nursing encounters by characterizing gender-affirming approaches to conducting and documenting a nursing assessment and describing techniques to overcome institutional-level challenges that may hinder a nurse's ability to establish gender-affirming therapeutic relationships with TNGE people. The authors also provide strategies that nurses can use to improve their health care organization and interprofessional collaborative practice to create psychologically and physically safe health care spaces for TNGE people.

Comparing the experiences of rural and urban family caregivers of the terminally ill.

INTRODUCTION: There are many challenges in delivering rural health services; this is particularly true for the delivery of palliative care. Previous work has identified consistent themes around end-of-life care, including caregiver burden in providing care, the importance of informal care networks and barriers imposed by geography. Despite these well-known barriers, few studies have explored the experience of palliative care in rural settings. The purpose of the present study was to compare the experiences of rural family caregivers actively providing end-of-life care to the experiences of their urban counterparts. METHODS: Caregivers' perceived health status, the experience of burden in caregiving, assessment of social supports and the pattern of formal care used by the terminally ill were explored using a consistent and standardized measurement approach. A cross-sectional survey study was conducted with 100 informal caregivers (44 rural, 56 urban) actively providing care to a terminally ill patient recruited from a publicly funded community agency located in northeastern Ontario, Canada. The telephone-based survey included questions assessing: (i) caregiver perceived burden (14-item instrument based on the Caregiver's Burden Scale in End-of-Life Care [CBS-EOLC]); (ii) perceived social support (modified version of the Multidimensional Scale of Perceived Social Support [MSPSS] consisting of 12 items); and (iii) functional status of the care recipient (assessed using the Eastern Collaborative Oncology Group performance scale). RESULTS: Rural and urban caregivers were providing care to recipients with similar functional status; the majority of care recipients were either capable of all self-care or experiencing some limitation in self-care. No group differences were observed for caregiver perceived burden: both rural and urban caregivers reported low levels of burden (CBS-EOLC score of 26.5 [SD=8.1] and 25.0 [SD=9.2], respectively; p=0.41). Urban and rural caregivers also reported similarly high levels of social support (mean MSPSS total score of 4.3 [SD=0.7] and 4.1 [SD=0.8], respectively; p=0.40). Although caregivers across both settings reported using a comparable number of services (rural 4.8 [SD=1.9] vs urban 4.5 [SD=1.8]; p=0.39), the types of services used differed. Rural caregivers reported greater use of family physicians (65.1% vs 40.7%; p=0.02), emergency room visits (31.8% vs 13.0%; p=0.02) and pharmacy services (95.3% vs 70.4%; p=0.002), while urban caregivers reported greater use of caregiver respite services (29.6% vs 11.6%; p=0.03). CONCLUSION: Through the use of standardized tools, this study explored the experiences of rural informal family caregivers providing palliative care in contrast to the experiences of their urban counterparts. The results of the present study suggest that while there are commonalities to the caregiving experience regardless of setting, key differences also exist. Thus, location is a factor to be considered when implementing palliative care programs and services.

Bifurcation geometry remodelling of vessels in de novo and growing intracranial aneurysms: a multicenter study.

BACKGROUND: Geometrical parameters, including arterial bifurcation angle, tortuosity, and arterial diameters, have been associated with the pathophysiology of intracranial aneurysm (IA) formation. The aim of this study was to investigate whether these parameters were present before or if they resulted from IA formation and growth. METHODS: Patients from nine academic centers were retrospectively identified if they presented with a de novo IA or a significant IA growth on subsequent imaging. For each patient, geometrical parameters were extracted using a semi-automated algorithm and compared between bifurcations with IA formation or growth (aneurysmal group), and their contralateral side without IA (control group). These parameters were compared at two different times using univariable models, multivariable models, and a sensitivity analysis with paired comparison. RESULTS: 46 patients were included with 21 de novo IAs (46%) and 25 significant IA growths (54%). The initial angle was not different between the aneurysmal and control groups (129.7±42.1 vs 119.8±34.3; p=0.264) but was significantly wider at the final stage (140.4±40.9 vs 121.5±34.1; p=0.032), with a more important widening of the aneurysmal angle (10.8±15.8 vs 1.78±7.38; p=0.001). Variations in other parameters were not significant. These results were confirmed by paired comparisons. CONCLUSION: Our study suggests that wider bifurcation angles that have long been deemed causal factors for IA formation or growth may be secondary to IA formation at pathologic bifurcation sites. This finding has implications for our understanding of IA formation pathophysiology.

Impact of Repeated Clot Retrieval Attempts on Infarct Growth and Outcome After Ischemic Stroke.

OBJECTIVE: To determine whether the association between increasing number of clot retrieval attempts (CRA) and unfavorable outcome is due to an increase in emboli to new territory (ENT) and greater infarct growth (IG) in successfully recanalized patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). METHODS: Data were extracted from 2 pooled multicentric prospective registries of consecutive patients with anterior AIS-LVO treated with mechanical thrombectomy (MT) between January 2016 and 2019. Patients with pretreatment and 24-hour posttreatment diffusion-weighted imaging (DWI) achieving successful recanalization, defined as expanded Thrombolysis in Cerebral Infarction Scale score of 2B, 2C, or 3, were included. ENT were assessed and IG was measured by voxel-based segmentation after DWI coregistration. Associations between number of CRA, ENT, IG, and 3-month outcome were analyzed. RESULTS: Four hundred nineteen patients achieving successful recanalization were included. ENT occurrence was strongly correlated with increasing CRA (ρ = 0.73, p = 10-4). In multivariable linear analysis, IG was independently associated with CRA (ß = 1.6 per retrieval attempt, 95% confidence interval [CI] 0.97-9.74, p = 0.03) and ENT (ß = 2.7 [95% CI 1.21-4.1], p = 0.03). Unfavorable functional outcome (3-month modified Rankin Scale score >2) increased with each additional CRA. IG was an independent predictor of unfavorable outcome (odds ratio 1.05 [95% CI 1.02-1.07] per 1-mL IG increase, p = 10-4) in binary logistic regression analysis. CONCLUSIONS: Increasing number of CRA in acute stroke is correlated with an increased ENT rate and increased IG volume, affecting functional outcome even when successful recanalization is achieved. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, for patients with acute stroke undergoing successful recanalization, an increasing number of CRA is associated with poorer functional outcome.

Molecular profile to guide personalized medicine in adult patients with primary brain tumors: results from the ProfiLER trial.

Immunohistochemistry and recent molecular technologies progressively guided access to personalized anti-tumoral therapies. We explored the feasibility, efficacy, and the impact of molecular profiling in patients with advanced brain tumors. This multicentric prospective trial ProfiLER enrolled patients with primary brain tumors, who have been pre-treated with at least one line of anti-cancer treatment, and for whom molecular profiles had been achieved using next-generation sequencing and/or comparative genomic hybridization on fresh or archived samples from tumor, relapse, or biopsies. A molecular tumor board weekly analyzed results and proposed molecular-based recommended therapy (MBRT). From February 2013 to December 2015, we enrolled 141 patients with primary brain tumor and analyzed 105 patients for whom tumor genomic profiles had been achieved. Histology mainly identified glioblastoma (N = 46, 44%), low-grade glioma (N = 26, 25%), high-grade glioma (N = 12, 11%), and atypical and anaplastic meningioma (N = 8, 8%). Forty-three (41%) patients presented at least one actionable molecular alteration. Out of 61 alterations identified, the most frequent alterations occurred in CDKN2A (N = 18), EGFR (N = 12), PDGFRa (N = 8), PTEN (N = 8), CDK4 (N = 7), KIT (N = 6), PIK3CA (N = 5), and MDM2 (N = 3). Sixteen (15%) patients could not be proposed for a MBRT due to early death (N = 5), lack of available clinical trials (N = 9), or inappropriate results (N = 2). Only six (6%) of the 27 (26%) patients for whom a MBRT had been proposed finally initiated MBRT (everolimus (N = 3), erlotinib (N = 1), ruxolitinib (N = 1), and sorafenib (N = 1)), but discontinued treatment for toxicity (N = 4) or clinical progression (N = 2). High-throughput sequencing in patients with brain tumors may be routinely performed, especially when macroscopic surgery samples are available; nevertheless delays should be reduced. Criteria for clinical trial enrollment should be reconsidered in patients with brain tumors, and a panel of genes specifically dedicated to neurologic tumors should be developed to help decision-making in clinical practice.

The Association Between PLAYfun and Physical Activity: A Convergent Validation Study.

Purpose: The purpose of this study was to examine the convergent validity of the PLAYfun tool, a physical literacy-based measure of movement competence, by examining its association with objectively measured physical activity in a sample of children and youth. Method: Participants included 110 children between the ages of seven to 14 years attending a stratified random sample of 27 afterschool programs across the province of Ontario, Canada. The PLAYfun tool was administered to the participants on one occasion at their afterschool program and then they were asked to wear a pedometer for seven consecutive days to measure their physical activity levels. A series of multiple linear regression models were used to examine the association between PLAYfun scores and physical activity, while controlling for age, sex, and time of year (season) in which the data were collected. Results: On its own, the PLAYfun average score accounted for close to 13% of the variance in physical activity, R = .36, R2 = .13, p < .001. The PLAYfun average score was also a significant independent predictor of physical activity, b (SE) = 145.98 (53.46), p < .01, when controlling for age, sex, and season in which the data were collected, R2 = .30, F (4, 105) = 11.04, p < .001. Conclusion: Results from the present study indicate that the PLAYfun tool is a significant predictor of objectively measured physical activity, supporting the convergent validity of the tool.

Investigating the Association Between Exposure to Second Hand Smoke in utero and Developmental Coordination Disorder.

Background: Developmental coordination disorder (DCD) and attention-deficit hyperactivity disorder (ADHD) are highly comorbid in children. There is evidence linking second hand smoke (SHS) exposure in utero to ADHD; however, it's relation to DCD is unknown. The purpose of this study was to examine the effect of SHS exposure in utero in children with and without DCD. Methods: This study was a cross-sectional examination of 122 children from the District School Board of Niagara (72 males, 50 females, M age = 12.9 years) who were part of a larger, prospective cohort study. Participants were assessed for motor proficiency and intelligence and were screened for symptoms of ADHD using the Bruininks-Oseretsky Test of Motor Proficiency-Short Form, the Kaufman Brief Intelligence Inventory, 2nd edition, and the Conners' Parent Rating Scales-Revised: Short Form, respectively. Parent questionnaires were used to determine SHS exposure in utero as either yes or no. Multinomial logistic regression was used to examine the relationship between SHS exposure and DCD risk. Results: Children exposed to SHS in utero were significantly more likely to be at high risk for DCD than children who were not (OR = 3.33, p = 0.004), and children exposed to SHS in utero were more likely to be at moderate risk for DCD in the presence (OR = 3.57, p = 0.025) or absence of ADHD (OR = 2.38, p = 0.042). However, statistical adjustment for birth weight, socioeconomic status, age, and sex reduced this effect to non-significance in the moderate risk group. Conclusion: Results suggest exposure to SHS during pregnancy increases the chances of a child developing high risk DCD. While SHS exposure may increase DCD risk with and without ADHD, this effect may be explained by covariates and confounding factors. Further study is needed to examine the mechanisms linking SHS exposure in utero to motor coordination problems in children.

Identifying Quiescent Stem Cells in Hair Follicles.

Hair follicle stem cells (HFSCs) are noted for their relative quiescence and therefore can be distinguished from other cells by their differential history of cell division. Replicating cells can be labeled by pulsing the animals repeatedly with 5-bromo-2'-deoxyuridine (BrdU) or tritiated thymidine ([3H]TdR), thymidine analogs that get incorporated into DNA during DNA synthesis. Because dividing cells dilute the label after each cell division, frequently dividing cells will lose the label over time while slow cycling cells will retain the label and thus are termed label retaining cells (LRCs). [3H]TdR can be visualized by autoradiography and BrdU can be detected by immunofluorescence with anti-BrdU antibodies. Alternatively, a well-established tet-regulatable transgenic mouse model can be used to express histone H2B-GFP in epithelial proliferative cells and their dilution and retention of the GFP signal can be followed. In this chapter, we detail the steps to perform BrdU pulse-chase and H2B-GFP pulse-chase experiments to identify quiescent cells in the hair follicle.

Health-related Fitness in Preschool Children with and without Motor Delays.

PURPOSE: School-age children with developmental coordination disorder (DCD) have poor health-related fitness (HRF), but little is known about when these deficits emerge. The purpose of this study was to determine if 4- and 5-yr-old children who meet the criteria for DCD exhibit poorer HRF compared with typically developing (TD) children, and if this relationship is mediated by vigorous physical activity (VPA) engagement. METHODS: Five hundred and ninety-two children participated (age, 5.0 ± 0.6 yr) from the Coordination and Activity Tracking in CHildren study. Motor skills were assessed using the Movement Assessment Battery for Children-2, with groups defined as having DCD (≤5th percentile), at risk for DCD (6th-16th percentile), and TD (>16th percentile). Measures of body composition included body mass index, waist circumference, and body fat percentage. Musculoskeletal fitness assessments included standing long jump distance, as well as peak and mean power assessed using a 30-s Wingate protocol on a pediatric cycle ergometer. Time to exhaustion on a progressive, treadmill test was used to determine aerobic fitness. Flexibility and VPA were assessed using a sit-and-reach test and 7-d accelerometry, respectively. RESULTS: Children in the DCD group had the poorest musculoskeletal and aerobic fitness, whereas TD children had the highest. No differences in body composition among groups were found. Daily VPA was similar among groups and did not explain HRF differences. CONCLUSIONS: Preschool children with DCD have decreased anaerobic and aerobic fitness compared with TD children; however, VPA and body composition seem to be less affected by DCD in the early years. Early motor interventions may be able to improve fitness and reduce the risk of hypoactivity and obesity as children with DCD get older.

A Construct Validation Study of PLAYfun.

INTRODUCTION: Physical Literacy Assessment for Youth (PLAYfun) is a measure of motor competence, comprehension, and confidence which is part of a suite of scales used to assess physical literacy in children and youth; however, its measurement properties have not been reported in the published literature. The purpose of this study is to examine the factor structure of PLAYfun, in addition to variations in PLAYfun subscale results by age and sex. METHOD: In this study, we use a sample of children and youth 7 to 14 yr of age (n = 215) to test a proposed factor structure for the motor competence component of PLAYfun and to examine age and sex differences in subscale and total scores. The initial (n = 128) and secondary (n = 98) samples were drawn from a stratified (by geographic region), random sample of 27 after-school programs from a larger pool of 400 programs across the province of Ontario. Seven research assistants were initially trained on the administration of PLAYfun and rated a small pilot sample of 10 children. These trained assessors then assessed the full sample. RESULTS: Interrater agreement was very good (intraclass correlation, 0.87). The hypothesized five-factor structure of the scale was found to have an acceptable fit to the data (root mean square error of approximation, 0.055; 90% confidence interval, 0.03-0.075; comparative fit index, 0.95; Tucker-Lewis Index, 0.94). In general, PLAYfun scores increased with age as developmentally expected. There were few sex differences across skills, but girls did not perform as well as boys on upper and lower body object control skills. CONCLUSIONS: The factor structure and patterns of results by age and sex support PLAYfun as a measure of motor competence. Continued evaluation of the tool and other subscales of PLAY is required.