Development and evaluation of the Capability, Opportunity, and Motivation to deliver Physical Activity in School Scale (COM-PASS).

BACKGROUND: Teachers are recognized as 'key agents' for the delivery of physical activity programs and policies in schools. The aim of our study was to develop and evaluate a tool to assess teachers' capability, opportunity, and motivation to deliver school-based physical activity interventions. METHODS: The development and evaluation of the Capability, Opportunity, and Motivation to deliver Physical Activity in School Scale (COM-PASS) involved three phases. In Phase 1, we invited academic experts to participate in a Delphi study to rate, provide recommendations, and achieve consensus on questionnaire items that were based on the Capability, Opportunity, and Motivation Behavior (COM-B) model. Each item was ranked on the degree to which it matched the content of the COM-B model, using a 5-point scale ranging from '1 = Poor match' to '5 = Excellent match'. In Phase 2, we interviewed primary and secondary school teachers using a 'think-aloud' approach to assess their understanding of the items. In Phase 3, teachers (n = 196) completed the COM-PASS to assess structural validity using confirmatory factor analysis (CFA). RESULTS: Thirty-eight academic experts from 14 countries completed three rounds of the Delphi study. In the first round, items had an average rating score of 4.04, in the second round 4.51, and in the third (final) round 4.78. The final tool included 14 items, which related to the six constructs of the COM-B model: physical capability, psychological capability, physical opportunity, social opportunity, reflective motivation, and automatic motivation. In Phase 2, ten teachers shared their interpretation of COM-PASS via a 20-min interview, which resulted in minor changes. In Phase 3, CFA of the 3-factor model (i.e., capability, opportunity, and motivation) revealed an adequate fit to the data (χ2 = 122.6, p < .001, CFI = .945, TLI = .924, RMSEA = .066). The internal consistencies of the three subscale scores were acceptable (i.e., capability: α = .75, opportunity: α = .75, motivation: α = .81). CONCLUSION: COM-PASS is a valid and reliable tool for assessing teachers' capability, opportunity, and motivation to deliver physical activity interventions in schools. Further studies examining additional psychometric properties of the COM-PASS are warranted.

Shorter Telomere Length Is Associated With Older Age, Poor Sleep Hygiene, and Orthopedic Injury, but Not Mild Traumatic Brain Injury, in a Cohort of Canadian Children.

BACKGROUND: Predicting recovery following pediatric mild traumatic brain injury (mTBI) remains challenging. The identification of objective biomarkers for prognostic purposes could improve clinical outcomes. Telomere length (TL) has previously been used as a prognostic marker of cellular health in the context of mTBI and other neurobiological conditions. While psychosocial and environmental factors are associated with recovery outcomes following pediatric mTBI, the relationship between these factors and TL has not been investigated. This study sought to examine the relationships between TL and psychosocial and environmental factors, in a cohort of Canadian children with mTBI or orthopedic injury (OI). METHODS: Saliva was collected at a postacute (median 7 days) timepoint following injury to assess TL from a prospective longitudinal cohort of children aged 8 to 17 years with either mTBI (n = 202) or OI (n = 90), recruited from 3 Canadian sites. Questionnaires regarding psychosocial and environmental factors were obtained at a postacute follow-up visit and injury outcomes were assessed at a 3-month visit. Univariable associations between TL and psychosocial, environmental, and outcome variables were assessed using Spearman's correlation. Further adjusted analyses of these associations were performed by including injury group, age, sex, and site as covariates in multivariable generalized linear models with a Poisson family, log link function, and robust variance estimates. RESULTS: After adjusting for age, sex, and site, TL in participants with OI was 7% shorter than those with mTBI (adjusted mean ratio = 0.93; 95% confidence interval, 0.89-0.98; P = .003). As expected, increasing age was negatively associated with TL (Spearman's r = -0.14, P = .016). Sleep hygiene at 3 months was positively associated with TL (adjusted mean ratio = 1.010; 95% confidence interval, 1.001-1.020; P = .039). CONCLUSION: The relationships between TL and psychosocial and environmental factors in pediatric mTBI and OI are complex. TL may provide information regarding sleep quality in children recovering from mTBI or OI; however, further investigation into TL biomarker validity should employ a noninjured comparison group.

What About the Little Ones? Systematic Review of Cognitive and Behavioral Outcomes Following Early TBI.

There is increasing empirical focus on the effects of early traumatic brain injuries (TBI; i.e., before the age of six years) on child development, but this literature has never been synthetized comprehensively. This systematic review aimed to document the cognitive, academic, behavioral, socio-affective, and adaptive consequences of early TBI. Four databases (Medline, PsycNET, CINAHL, PubMed) were systematically searched from 1990 to 2019 using key terms pertaining to TBI and early childhood. Of 12, 153 articles identified in the initial search, 43 were included. Children who sustain early TBI are at-risk for a range of difficulties, which are generally worse when injury is sustained at a younger age, injury severity is moderate to severe, and injury mechanisms are non-accidental. Early childhood is a sensitive period for the emergence and development of new skills and behaviors, and brain disruption during this time is not benign. Research, clinical management, intervention, and prevention efforts should be further developed with consideration of the unique characteristics of the early childhood period.

Development and evaluation of the perceived variety-support in physical education scale (PVSPES).

The provision of variety has been posited to influence motivation in physical education. Therefore, the aim of this 3-phase study was to design and evaluate a brief scale to assess ratings of variety-support in physical education. In Phase 1, 20 experts were invited to review the developed items of the Perceived Variety-Support in Physical Education (PVSPE) scale. In Phase 2, factorial validity of item responses was assessed in a sample of adolescents aged 12-14 years (n = 265). In Phase 3, test-retest reliability was determined over a one-week period (n = 100). A one-factor model resulted in "good" fit to the data (χ2(21) = 43.265, p < 0.001, CFI = 0.968, TLI = 0.952, RMSEA = 0.089; factor loading estimates showed that indicators were highly related to the factor (range: 0.60 to 0.93); and ICC was 0.98, 95% CI [0.97 to 0.98]. Our results provide initial evidence for the validity, measurement invariance, and test-retest reliability of scores derived from the VSPE scale for use with adolescents.

Cardiorespiratory fitness and accelerometer-determined physical activity following one year of free-living high-intensity interval training and moderate-intensity continuous training: a randomized trial.

BACKGROUND: Free-living adherence to high-intensity interval training (HIIT) has not been adequately tested. This randomized trial examined changes in cardiorespiratory fitness (CRF) and accelerometer-measured purposeful physical activity over 12 months of free-living HIIT versus moderate-intensity continuous training (MICT). METHODS: Ninety-nine previously low-active participants with overweight/obesity were randomly assigned to HIIT (n = 47) or MICT (n = 52). Both interventions were combined with evidence-based behaviour change counselling consisting of 7 sessions over 2 weeks. Individuals in HIIT were prescribed 10 X 1-min interval-based exercise 3 times per week (totalling 75 min) whereas individuals in MICT were prescribed 150 min of steady-state exercise per week (50 mins 3 times per week). Using a maximal cycling test to exhaustion with expired gas analyses, CRF was assessed at baseline and after 6 and 12 months of free-living exercise. Moderate-to-vigorous physical activity of 10+ minutes (MVPA10+) was assessed by 7-day accelerometry at baseline, 3, 6, 9, and 12 months. Intention to treat analyses were conducted using linear mixed models. RESULTS: CRF was improved over the 12 months relative to baseline in both HIIT (+ 0.15 l/min, 95% CI 0.08 to 0.23) and MICT (+ 0.11 l/min, 95% CI 0.05 to 0.18). Both groups improved 12-month MVPA10+ above baseline (HIIT: + 36 min/week, 95% CI 17 to 54; MICT: + 69 min/week, 95% CI 49 to 89) with the increase being greater (by 33 min, 95% CI 6 to 60) in MICT (between group difference, P = 0.018). CONCLUSION: Despite being prescribed twice as many minutes of exercise and accumulating significantly more purposeful exercise, CRF improvements were similar across 12 months of free-living HIIT and MICT in previously low-active individuals with overweight/obesity.

Modifiable factors related to life-space mobility in community-dwelling older adults: results from the Canadian Longitudinal Study on Aging.

BACKGROUND: The most common methods for measuring mobility in older adulthood include performance-based tests, such as the Timed-Up-and-Go and gait speed. While these measures have strong predictive validity for adverse outcomes, they are limited to assessing what older adults do in standardized settings, rather than what they do in their daily life. Life-space mobility, which is the ability to move within environments that expand from one's home to the greater community, has been proposed as a more comprehensive measure of mobility. The aim of this study was to determine the association between modifiable factors and life-space mobility in older adults enrolled in the Canadian Longitudinal Study on Aging (CLSA). METHODS: Life-space mobility was measured using the Life Space Index (LSI). Explanatory factors included physical, psychosocial and cognitive determinants, as well as pain, fatigue, driving status, nutrition, body mass index, smoking status, and vision. To estimate the association between the LSI and explanatory variables, univariate and multivariable ordinary least squares regression analyses were performed. RESULTS: All adults 65 years and older (n = 12,646) were included in the analysis. Fifty percent were women and the mean age was 73.0 (SD5.7). The mean LSI score was 80.5, indicating that, on average, the sample was able to move outside of their neighborhood independently. All explanatory variables were significantly associated with the LSI except for balance and memory. The top 3 variables that explained the most variation in the LSI were driving, social support and walking speed. CONCLUSION: To our knowledge, this was the first study to examine the association between life-space mobility and a comprehensive set of modifiable factors that were selected based on a theoretical framework and existing research evidence. This study had two important messages. First, driving, social support and walking speed emerged as the most significant correlates of life-space mobility in older adults. Second, life-space mobility is multifactorial and interventions that are pragmatic in their design and testing are needed that consider the complexity involved. A multi-disciplinary approach to examining life-space mobility in older adults is needed to optimize opportunities for healthy aging and develop strategies that support mobility in older adulthood.

Moral reasoning and decision-making in adolescents who sustain traumatic brain injury.

Objective: Emerging evidence suggests that moral processes are disrupted by traumatic brain injury (TBI). The objective of this study was to explore moral reasoning (MR) and decision-making in adolescents with TBI, and to examine potential associations with global manifestations of social competence.Design: This retrospective, cross-sectional research design compared MR and decision-making in adolescents with mild TBI (n = 20), moderate-severe TBI (n = 23) and typically developing controls (n = 93).Methods: Participants completed a visual task of socio-moral reasoning (SoMoral) and the Index of Empathy for Children and Adolescents. Their parents completed questionnaires documenting their child's behavior (Child Behavior Checklist) and adaptive functioning (Adaptive Behavior Assessment System-Second Edition).Main results: Adolescents with both mild and moderate-severe TBI displayed more immature MR than typically developing peers. Participants with TBI also provided fewer socially adapted decisions. Closer inspection revealed that this difference was apparent only in the mild TBI group. No significant group differences were observed for empathy, behavior or adaptive skills.Conclusions: Sustaining TBI appears to affect adolescents' ability to provide mature moral justifications when faced with moral dilemmas representative of everyday social conflicts. These difficulties do not appear to be associated with behavior problems, reduced empathy, or adaptive functioning.

The contribution of social cognition in predicting social participation following moderate and severe TBI in youth.

Youth with moderate or severe traumatic brain injury (TBI) are at risk for reduced social participation after the injury, and the contribution of social cognition to these changes in functioning has been little studied. This study aimed to examine social participation and to measure the contribution of social and non-social cognitive functions to social participation impairment in youth (ages 12-21) who sustained moderate or severe TBI. Youth with TBI (n = 23) were compared to typically developing (TD) controls on self- and parent-rated social participation questionnaires. Direct testing of social cognition (mentalising, social knowledge, emotion recognition) and higher order cognitive abilities (intellectual abilities, attention and executive functions) was also conducted. Significant differences were found between the TBI participants and TD controls on social participation measures. Mentalising and problem-solving abilities revealed to be significant correlates of social participation as reported by youth with brain-injury and their parents. Overall, these results corroborate previous findings by showing that social participation is significantly reduced after TBI, and further shows that mentalising, which is not always considered during rehabilitation, is an important contributing factor. In addition to executive function measures, social cognition should therefore be systematically included in assessment following youth TBI for intervention and prevention purposes.

White matter microstructure predicts longitudinal social cognitive outcomes after paediatric traumatic brain injury: a diffusion tensor imaging study.

BACKGROUND: Deficits in social cognition may be among the most profound and disabling sequelae of paediatric traumatic brain injury (TBI); however, the neuroanatomical correlates of longitudinal outcomes in this domain remain unexplored. This study aimed to characterize social cognitive outcomes longitudinally after paediatric TBI, and to evaluate the use of sub-acute diffusion tensor imaging (DTI) to predict these outcomes. METHODS: The sample included 52 children with mild complex-severe TBI who were assessed on cognitive theory of mind (ToM), pragmatic language and affective ToM at 6- and 24-months post-injury. For comparison, 43 typically developing controls (TDCs) of similar age and sex were recruited. DTI data were acquired sub-acutely (mean = 5.5 weeks post-injury) in a subset of 65 children (TBI = 35; TDC = 30) to evaluate longitudinal prospective relationships between white matter microstructure assessed using Tract-Based Spatial Statistics and social cognitive outcomes. RESULTS: Whole brain voxel-wise analysis revealed significantly higher mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in the sub-acute TBI group compared with TDC, with differences observed predominantly in the splenium of the corpus callosum (sCC), sagittal stratum (SS), dorsal cingulum (DC), uncinate fasciculus (UF) and middle and superior cerebellar peduncles (MCP & SCP, respectively). Relative to TDCs, children with TBI showed poorer cognitive ToM, affective ToM and pragmatic language at 6-months post-insult, and those deficits were related to abnormal diffusivity of the sCC, SS, DC, UF, MCP and SCP. Moreover, children with TBI showed poorer affective ToM and pragmatic language at 24-months post-injury, and those outcomes were predicted by sub-acute alterations in diffusivity of the DC and MCP. CONCLUSIONS: Abnormal microstructure within frontal-temporal, limbic and cerebro-cerebellar white matter may be a risk factor for long-term social difficulties observed in children with TBI. DTI may have potential to unlock early prognostic markers of long-term social outcomes.

Effects of home-based exergaming on child social cognition and subsequent prediction of behavior.

The use of exergames may be one viable way to increase child physical activity, but investigation of its effects on motivation over time and prediction of adherence have seen little research attention. The purpose of this study was to compare the effect of two cycling exergame interventions (single-player, multi-player) among children aged 9-12 years on motivational variables (theory of planned behavior) and to explore whether these variables could predict objective assessment of playtime across 6 weeks. Sixty-nine insufficiently active children were recruited through advertisements within the community/schools and randomized to either the single play condition (n = 30) or multi-player condition (n = 39). Exergaming use was recorded objectively via game logs and motivational variables were assessed after a familiarization session, at 2 weeks, and at 4 weeks. Participants played the exergames M = 133.45 (SD = 81.27) minutes in week 1 to M = 77.23 (SD = 84.09) minutes in week 6. The two exergame conditions did not result in differences among theory of planned behavior variables (P > .05). Mean levels of these constructs declined across the first 4 weeks (P < .05), with the exception of injunctive norm. Positive bivariate associations (P < .05) between game play and perceived control (0-6 weeks), and intention (weeks 3-4 and weeks 5-6) were identified, but only affective attitude (assessed at week 2) predicted (P < .05) game play (3-4 weeks) in a multivariate examination of the theory of planned behavior model. The results demonstrate that social cognitive motives wane across time when exposed to repeated exergame play.

Prediction of adherence to a gluten-free diet using protection motivation theory among adults with coeliac disease.

BACKGROUND: Coeliac disease is a chronic autoimmune disease that requires strict adherence to a gluten-free diet. However, strict adherence to a gluten-free diet is difficult, with findings from a recent review suggesting that up to 42% of individuals with coeliac disease do not eat a strict gluten-free diet. METHODS: The present study aimed to examine psychosocial predictors of adherence (purposeful and accidental) to a gluten-free diet among adults with coeliac disease over a 1-month period. In this longitudinal study, 212 North American adults with coeliac disease completed online questionnaires at two time points, baseline and 1 month later. RESULTS: The results revealed that intentions partially mediated the effects of symptom severity, self-regulatory efficacy, planning and knowledge on purposeful gluten consumption. Intentions did not mediate the effects of severity, response cost, self-regulatory efficacy, planning and knowledge for accidental gluten consumption but, interestingly, self-regulatory efficacy directly predicted fewer accidental incidents of gluten-consumption. CONCLUSIONS: These findings delineate the differential psychological processes in understanding accidental and purposeful gluten consumption among adults with coeliac disease and emphasise the importance of bolstering self-regulatory efficacy beliefs to prevent accidental and purposeful consumption of gluten.

Transformational teaching and adolescent physical activity: multilevel and mediational effects.

BACKGROUND: Regular physical activity is associated with a range of physical and psychological health benefits. In North America the majority of adolescents are insufficiently active. PURPOSE: The purpose of this study was to examine the prospective relationship between adolescents' perceptions of transformational leadership displayed by their school physical education teachers and their own physical activity behaviors, both with respect to within-class physical activity (WCPA) and also leisure time physical activity (LTPA). METHOD: The study used a prospective observational design. Using multilevel structural equation modeling (MSEM), we examined the extent to which adolescents' affective attitudes mediated the effects of teachers' behaviors on adolescents' physical activity responses. Two thousand nine hundred and forty-eight adolescents (M age = 14.33, SD = 1.00, N female = 1,641, 55.7 %) from 133 Grade 8-10 classes in British Columbia (Canada) provided ratings of their physical education teachers' behaviors midway through the school year. Two months later, students completed measures of affective attitudes, WCPA, and LTPA. RESULTS: The results indicated that adolescents' perceptions of transformational teaching explained significant variance in both WCPA and LTPA, and these effects were fully mediated by adolescents' affective attitudes (total indirect effect: b = 0.581, p < 0.001). CONCLUSION: The findings suggest that transformational leadership behaviors displayed by physical education teachers may be an important source of adolescent enjoyment of physical education as well as health-enhancing physical activity involvement within school and outside of school.

Motives for adherence to a gluten-free diet: a qualitative investigation involving adults with coeliac disease.

BACKGROUND: Currently , the only treatment for coeliac disease is life long adherence to a strict gluten-free diet. Strict adherence to a gluten-free diet is challenging, with recent reports suggesting that adherence rates range from 42% to 91%. The present study aimed to: (i) identify motives for adhering to a gluten-free diet and (ii) explore factors implicated in adherence and non-adherence behaviour in terms of accidental and purposeful gluten consumption among adults with coeliac disease. METHODS: Two hundred and three adults with coeliac disease completed an online questionnaire. Using a qualitative design, relationships were examined between reported adherence and motivation to follow a gluten-free diet, as well as the onset, duration and severity of symptoms. RESULTS: Feelings of desperation ('hitting rock bottom') and needing to gain or lose weight were associated with the strictest adherence to a gluten-free diet. Participants who accidentally consumed gluten over the past week developed symptoms the most quickly and reported the most pain over the past 6 months. Participants who consumed gluten on purpose over the past week reported a shorter duration of symptoms and less pain over the past 6 months. CONCLUSIONS: Hitting rock bottom and needing to gain or lose weight were factors associated with the strictest adherence, when considered in the context of both accidental and purposeful gluten consumption. Future research is warranted to develop resources to help people with coeliac disease follow a strict gluten-free diet.

A preliminary investigation of moral reasoning and empathy after traumatic brain injury in adolescents.

PRIMARY OBJECTIVE: Traumatic brain injury (TBI) sustained during childhood can affect a number of socio-cognitive skills; however, little attention has focused on the integrity of moral reasoning in the assessment of post-TBI social sequelae and the role of empathy and intelligence on moral maturity. RESEARCH DESIGN: In a quasi-experimental, cross-sectional research design, moral reasoning maturity and empathy in adolescents with mild-to-severe TBI (n = 25) were compared to typically-developing peers (n = 66). METHODS AND PROCEDURES: Participants were administered the So-Moral and So-Mature, tasks of socio-moral reasoning and maturity, the Index of Empathy for Children and Adolescents, the Wechsler Abbreviated Scale of Intelligence and a demographic questionnaire. MAIN OUTCOMES AND RESULTS: Participants with TBI had significantly lower levels of moral reasoning maturity. Further, adolescents with moderate-to-severe TBI had lower levels of empathy. Empathy correlated positively with moral reasoning abilities and, together with intellectual function, predicted a small, but significant proportion of moral reasoning outcome. CONCLUSIONS: Youth who sustained TBI during childhood have poorer moral reasoning abilities than their non-injured peers, potentially placing them at risk for poor social decision-making and socially maladaptive behaviour. This can have a significant impact on long-term social functioning.

The effects of exercise intensity on the cortisol response to a subsequent acute psychosocial stressor.

OBJECTIVE: The aim of this experimental study was to determine the extent to which the intensity of a single 30 min bout of exercise alters the salivary cortisol (sCort) response to a subsequently induced acute psychosocial stressor. The study further aimed to elucidate a physiological mechanism through which exercise intensity exerts stress-mitigating effects. METHODS: Eighty-three healthy men (Mage = 21.04 SD = 2.89) were randomly assigned to exercise on a treadmill at either 30%, 50% or 70% of their heart rate reserve (HRR) for 30 min and then underwent the Trier Social Stress Test 45 min later. sCort was measured repeatedly throughout and following the exercise bout and stressor task. RESULTS: ANCOVA and Multilevel Growth Curve Analysis determined that vigorous (70% HRR) exercise elicited dampened sCort responses to the stressor task, marked by lower total sCort levels, diminished sCort reactivity, and faster recovery to baseline values, as compared to less intense exercise. Moreover, exercise elicited a sCort response in proportion to the intensity at which it was performed, and this exercise-associated HPA-axis response was inversely proportional to the sCort response to the subsequent stressor task. CONCLUSIONS: This study revealed that exercise-intensity dampens the HPA-axis stress response in a dose-dependent manner, with evidence that the cortisol released from exercising intensely suppresses the subsequent cortisol response to a psychosocial stressor.

The PARENT model: a pathway approach for understanding parents' role after early childhood mild traumatic brain injury.

OBJECTIVE: Mild traumatic brain injury (mTBI or "concussion") is a highly prevalent health condition in children, and those under the age of 6 years have the highest rate of Emergency Department presentation for suspected head injuries. The outcome of mTBI is determined by a range of child (injury, biological, functional) and environmental (socio-economic status, parent, family) factors. The aim of this work is to present evidence supporting the central role of parental and familial factors in pediatric mTBI recovery, and to illustrate ways in which parental factors can especially influence the outcome of early mTBI, defined as injuries sustained by infants, toddlers and preschoolers. METHOD: The manuscript first presents a topical review of empirical studies providing evidence that family functioning and parental factors such as their mental or affective state, parenting style, and the quality of their interactions with their child, are affected by and determine the course of recovery after pediatric mTBI. Then, a pathway approach and conceptual model are proposed to illustrate probable scenarios associated with how parents detect and react to their child's post-concussive symptoms and changes in behavior after early mTBI. CONCLUSION: The "Perception, Attribution, and Response after Early Non-inflicted Traumatic Brain Injury" (PARENT) model suggests that parental roles and factors are especially influential in the context of early brain injuries, and that parents' ability to perceive, attribute and respond to the symptoms experienced by their child in a well-adjusted and adaptive manner critically sets the direction and rhythm of the early mTBI recovery process.

Effects of Aerobic Exercise Training on Daily Psychological Processes in Family Caregivers: Secondary Analyses of a Randomized Controlled Trial.

The aim of this study was to examine the effects of a 24-week aerobic exercise training program on daily psychological processes and occurrence of stressors in a group of previously physically underactive family caregivers of patients with dementia. As part of the Fitness, Aging, and STress (FAST) randomized controlled trial, 68 participants (F = 55; M = 13) were randomized to either a staff-supported, 24-week aerobic training (N = 34) program or waitlist control (N = 34) group. Approximately 2 weeks prior to randomization, ecological momentary assessments were completed 6 times per day for 7 days and again in the 24th week of the trial to assess exposure to levels of momentary positive affect, negative affect, rumination, control, and the occurrence of stressors throughout the day. These secondary analyses with data from 56 of the participants revealed that the intervention group showed a significantly larger increase in daily positive affect and perceptions of control compared to control participants over the course of the intervention. A treatment effect was also found for negative affect and rumination, whereby both decreased to a greater extent in the intervention group when compared with participants in the control condition. The 24-week aerobic training program had significant impacts on daily psychological processes in family caregivers, deepening our understanding of the robust effects of exercise on mental health.

Flexible modeling improves assessment of prognostic value of C-reactive protein in advanced non-small cell lung cancer.

BACKGROUND: C-reactive protein (CRP) is gaining credibility as a prognostic factor in different cancers. Cox's proportional hazard (PH) model is usually used to assess prognostic factors. However, this model imposes a priori assumptions, which are rarely tested, that (1) the hazard ratio associated with each prognostic factor remains constant across the follow-up (PH assumption) and (2) the relationship between a continuous predictor and the logarithm of the mortality hazard is linear (linearity assumption). METHODS: We tested these two assumptions of the Cox's PH model for CRP, using a flexible statistical model, while adjusting for other known prognostic factors, in a cohort of 269 patients newly diagnosed with non-small cell lung cancer (NSCLC). RESULTS: In the Cox's PH model, high CRP increased the risk of death (HR=1.11 per each doubling of CRP value, 95% CI: 1.03-1.20, P=0.008). However, both the PH assumption (P=0.033) and the linearity assumption (P=0.015) were rejected for CRP, measured at the initiation of chemotherapy, which kept its prognostic value for approximately 18 months. CONCLUSION: Our analysis shows that flexible modeling provides new insights regarding the value of CRP as a prognostic factor in NSCLC and that Cox's PH model underestimates early risks associated with high CRP.

Cognitive, behavioural and adaptive profiles of children with glutaric aciduria type I detected through newborn screening.

BACKGROUND: Glutaric aciduria type I (GA I) is an autosomal recessive disorder of lysine and tryptophan metabolism due to a deficiency in glutaryl-CoA dehydrogenase activity. Recent reports suggest that early diagnosis through newborn screening and initiation of preventive therapy result in improved functional outcome; however, detailed neuropsychological profiles of children with GA I are seldom reported and thus the impact of the disease on cognition, motor abilities and behaviour remains uncertain. METHOD: We present detailed neuropsychological profiles of three children who were diagnosed with GA I through newborn screening and treated from early age, and one asymptomatic patient diagnosed through cascade screening. A comprehensive battery of standardized tests was administered including measures of intellectual function, attention/memory, executive function, motor skills, speech/language, as well as behavioural and adaptive skills. RESULTS: The results reveal overall average cognitive outcomes; however, subtle, but significant, fine motor and articulation deficits were observed. The results are discussed with regard to potential links between fine motor deficits and speech impairments in children with GA I. Such difficulties can impact on the child's ability to engage in academic, leisure and daily activities. CONCLUSIONS: These findings highlight the importance of in-depth assessments of all aspects of neuropsychological function in patients with GA I and provide a basis for future neuropsychological assessment in similar groups of children. In spite of relatively preserved overall functioning, using a broad range of sensitive cognitive and motor measures facilitates the detection of subtle deficits, and allows for planning of early and adequate therapeutic interventions.

Cognitive and social profiles in two patients with cobalamin C disease.

Cobalamin C (cblC) disease, an inborn error of vitamin B(12) metabolism, results in neurometabolic, neurochemical and neuroanatomical changes. Little is known of the long-term effects of the disorder on cognition and behaviour in children. Here, the complete neuropsychological profiles of two 12-year-old girls with cblC disease are presented. The two girls were tested longitudinally with standardized neuropsychological tests including intellectual ability, attention and memory, as well as executive, adaptive and behavioural function. The results indicate the presence of intellectual dysfunction, attention problems, and concerns with behavioural aspects of executive function. Both patients demonstrated a pattern of decreasing intellectual function over time, which may reflect a growing developmental gap in comparison with their same age peers. These impairments are in contrast to the relatively spared verbal expression and comprehension abilities, as well as strengths in sociability. The findings highlight a pattern of neuropsychological strengths and weaknesses that may distinguish cblC disease from other inborn errors of metabolism. Overt sociability such as observed in these two patients may actually mask underlying cognitive deficits because the patients appear to function at a more advanced level than that reflected by quantitative assessment of intellectual and cognitive functioning. This is of clinical and functional importance and suggests that accurate determination of cognitive, adaptive and social abilities necessitates an in-depth and broad evaluation. The presence of significant intellectual and cognitive deficits also underscores the need to document and monitor cognitive development in children with cblC disease and to consider remediative and adaptive learning strategies.