Psychometric properties of inhibitory control measures among youth with Down syndrome.

BACKGROUND: Inhibitory control measures have been commonly used when assessing individuals with Down syndrome. However, minimal attention has been devoted to evaluating the appropriateness of specific assessments for use in this population, potentially leading to erroneous conclusions. This study aimed to examine the psychometric properties of measures of inhibitory control among youth with Down syndrome. We sought to examine the feasibility, presence of floor or practice effects, test-retest reliability, convergent validity and correlations with broader developmental domains of a set of inhibitory control tasks. METHODS: A sample of 97 youth with Down syndrome aged 6 to 17 years old participated in verbal and visuospatial tasks of inhibitory control including the Cat/dog Stroop, Neuropsychological Assessment Second Edition (NEPSY-II) Statue, National Institutes of Health (NIH) Toolbox Cognition Battery (TCB) Flanker, Leiter-3 Attention Sustained, and the Test of Attentional Performance for Children (KiTAP) Go/No-go and Distractibility subtests. Youth also completed standardised assessments of cognition and language, and caregivers completed rating scales. Psychometric properties on the tasks of inhibitory control were evaluated against a priori criteria. RESULTS: Apart from demonstrating negligible practice effects, adequate psychometric properties were not observed for any inhibitory control measure within the current sample's age range. One task with low working memory demands (NEPSY-II Statue) generally had better psychometric properties than the other tasks assessed. Subgroups of participants with an IQ greater than 30 and age more than 8 years were shown to be more likely to be able to complete the inhibition tasks. CONCLUSIONS: Findings suggest better feasibility for analogue tasks rather than computerised assessments of inhibitory control. Given the weak psychometrics of several common measures, future studies are required to evaluate other inhibitory control measures, specifically those with reduced working memory demands for youth with Down syndrome. Recommendations for use of the inhibitory control tasks among youth with Down syndrome are provided.

Diffusion tensor imaging findings in young children with benign external hydrocephalus differ from the normal population.

PURPOSE: To compare a pediatric population diagnosed with benign external hydrocephalus (BEH) to normal age-matched controls using diffusion tensor imaging (DTI) techniques. METHODS: We retrospectively identified 17 BEH patients by specific clinical and neuroimaging criteria. Fractional anisotropy (FA) and mean diffusivity (MD) values obtained from DTI scans were compared to a population of age-matched controls and group differences were examined by mixed model analysis. A longitudinal comparison was completed on a subset that underwent multiple scans (n = 8). RESULTS: In the genu of the corpus callosum (gCC), six of 15 BEH children had an FA value above the upper limit of 95% prediction interval, nine of 15 BEH children had MD values below the lower limit of 95% prediction interval. A similar trend applied to the other regions of interest (ROIs): splenium of the corpus callosum (sCC), ALIC, and PLIC. Statistical analysis demonstrated significant differences in FA within the gCC, sCC, and PLIC and in MD within the sCC between BEH patients and controls given (P = 0.05). No statistical differences were identified at any ROIs at the later scans. CONCLUSIONS: We found a significant increase in FA and decrease in MD in children with BEH compared with normal children in specific white matter (WM) ROIs, notably in the gCC and sCC; furthermore, in longitudinal comparison, DTI parameters normalized over time. The current study further demonstrates the ability of DTI to distinguish between subtle diffusion changes in periventricular white matter and establishes preliminary objective radiographic parameters for watchful observation of patients with BEH.

The Construction of a Predictive Composite Index for Decision-Making of CSF Diversion Surgery in Pediatric Patients following Prenatal Myelomeningocele Repair.

BACKGROUND AND PURPOSE: There is a wide range of clinical and radiographic factors affecting individual surgeons' ultimate decision for CSF diversion for pediatric patients following prenatal myelomeningocele repair. Our aim was to construct a composite index (CSF diversion surgery index) that integrates conventional clinical measures and neuroimaging biomarkers to predict CSF diversion surgery in these pediatric patients. MATERIALS AND METHODS: This was a secondary retrospective analysis of data from 33 patients with prenatal myelomeningocele repair (including 14 who ultimately required CSF diversion surgery). Potential independent variables, including the Management of Myelomeningocele Study Index (a dichotomized variable based on the shunt-placement criteria from the Management of Myelomeningocele Study), postnatal DTI measures (fractional anisotropy and mean diffusivity in the genu of the corpus callosum and the posterior limb of internal capsule), fronto-occipital horn ratio at the time of DTI, gestational ages, and sex, were evaluated using stepwise logistic regression analysis to identify the most important predictors. RESULTS: The CSF diversion surgery index model showed that the Management of Myelomeningocele Study Index and fractional anisotropy in the genu of the corpus callosum were significant predictors (P < .05) of CSF diversion surgery. The predictive value of the CSF diversion surgery index was also affected by fractional anisotropy in the posterior limb of the internal capsule and sex with marginal effect (.05

.10). The overall CSF diversion surgery index model fit the data well with statistical significance (eg, likelihood ratio: P < .001), with the performance (sensitivity = 78.6%; specificity = 86.5%, overall accuracy = 84.8%) superior to all individual indices in sensitivity and overall accuracy, and most of the individual indices in specificity. CONCLUSIONS: The CSF diversion surgery index model outperformed all single predictor models and, with additional validation, may potentially be developed and incorporated into a sensitive and robust clinical tool to assist clinicians in hydrocephalus management.

Differential patterns of brain activation over time in adolescents with and without attention deficit hyperactivity disorder (ADHD) during performance of a sustained attention task.

OBJECTIVE: Recent morphometric studies suggest that children with ADHD may demonstrate differential or delayed brain development compared with children without ADHD. This study examines the developmental course of brain activation patterns during the performance of an attention task. METHOD: Ten adolescents with ADHD and 14 healthy comparison adolescents performed a continuous performance task in an fMRI twice, one year apart. RESULTS: In the absence of performance differences, children with ADHD and healthy comparison subjects activated frontal-parietal regions while performing an attention task at initial testing. Children with ADHD appeared to require continued use of the right middle frontal gyrus during administration of testing one year apart while healthy comparison subjects did not activate this region at the time of the second testing. CONCLUSIONS: There appear to be developmental differences in brain activation patterns on an attentional task between ADHD and healthy controls. More research is needed for examining the longitudinal course of functional brain activation in children with ADHD.

Network-based Responses to the Psychomotor Vigilance Task during Lapses in Adolescents after Short and Extended Sleep.

Neuroimaging studies of the Psychomotor Vigilance Task (PVT) have revealed brain regions involved in attention lapses in sleep-deprived and well-rested adults. Those studies have focused on individual brain regions, rather than integrated brain networks, and have overlooked adolescence, a period of ongoing brain development and endemic short sleep. This study used functional MRI (fMRI) and a contemporary analytic approach to assess time-resolved peri-stimulus response of key brain networks when adolescents complete the PVT, and test for differences across attentive versus inattentive periods and after short sleep versus well-rested states. Healthy 14-17-year-olds underwent a within-subjects randomized protocol including 5-night spans of extended versus short sleep. PVT was performed during fMRI the morning after each sleep condition. Event-related independent component analysis (eICA) identified coactivating functional networks and corresponding time courses. Analysis of salient time course characteristics tested the effects of sleep condition, lapses, and their interaction. Seven eICA networks were identified supporting attention, executive control, motor, visual, and default-mode functions. Attention lapses, after either sleep manipulation, were accompanied by broadly increased response magnitudes post-stimulus and delayed peak responses in some networks. Well-circumscribed networks respond during the PVT in adolescents, with timing and intensity impacted by attentional lapses regardless of experimentally shortened or extended sleep.

Nephrotoxic Medications and Associated Acute Kidney Injury in Very Low Birth Weight Infants.

Preterm infants are at risk for acute kidney injury (AKI) for multiple reasons. Reports on the frequency and timeline of iatrogenic renal insults and potential consequences are limited. Our objectives are to estimate the prevalence and timing of exposure to nephrotoxic medications, and assess the association of these nephrotoxic medications with AKI in preterm infants. We performed a retrospective chart review of infants <30 weeks postmenstrual age and/or <1500 g birth weight admitted to the neonatal intensive care units at Cincinnati Children's Hospital Medical Center and University of Cincinnati Medical Center from 2011 to 2014. We queried the electronic health record for exposures to nephrotoxic medications and/or radiologic contrast media and correlated to serum creatinine concentration proximate to the exposure. Using the Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria, we assessed the AKI rate associated with the exposures. The cohort included 276 preterm infants. 233 (84%) received nephrotoxicity-associated medications. Antibiotics were the most common type (80%). AKI occurred in 9% of infants and was associated with exposure to a nephrotoxic medication. In a forward stepwise logistical regression, birth weight (OR: 0.995 (95% CI: 0.991-0.998), p=0.004) and number of exposures (OR: 1.83 (95% CI: 1.33-2.53), p=0.0002) were predictive of AKI. Nephrotoxic medication exposure increased the odds of AKI in preterm and low birth weight infants. Future prospective surveillance through the electronic health record in addition to routine serum creatinine monitoring may reduce the rate of exposure and subsequent AKI.

Effect of method of defining the active patient population on measured immunization rates in predominantly Medicaid and non-Medicaid practices.

OBJECTIVE: To examine the effect of patient selection criteria on immunization practice assessment outcomes. METHODS: In 3 high- (50%-85%) and 7 low- (<25%) Medicaid pediatric practices in urban eastern Virginia, we assessed immunization rates of children 12 and 24 months old comparing the standard criteria (charts in the active files excluding those that documented the child moved or went elsewhere) with 3 alternative criteria for selecting active patients: 1) follow-up: the chart contained a complete immunization record or the patient was found to be active in the practice through follow-up contact by phone or mail; 2) seen in the past year: the chart indicated that the patient was seen in the practice in the past year; 3) consecutive: patients that were seen consecutively for any reason. RESULTS: Of the 1823 charts assessed in the high- and low-Medicaid practices, follow-up identified 61% and 83% as active patients; 78% and 95% were ever seen in the past year. At 24 months, mean practice immunization rates were lower for standard (70%) than all 3 alternative criteria (78%-86%). Immunization rate differences between standard and alternative criteria were greater in high- (17%-23%) than low-Medicaid practices (5%-13%). CONCLUSION: The standard for practice assessment should be based on a consistent definition of active patients as the immunization rate denominator.

DTI values in key white matter tracts from infancy through adolescence.

BACKGROUND AND PURPOSE: DTI is an advanced neuroimaging technique that allows in vivo quantification of water diffusion properties as surrogate markers of the integrity of WM microstructure. In our study, we investigated normative data from a large number of pediatric and adolescent participants to examine the developmental trends in DTI during this conspicuous WM maturation period. MATERIALS AND METHODS: DTI data in 202 healthy pediatric and adolescent participants were analyzed retrospectively. Fractional anisotropy and mean diffusivity values in the corpus callosum and internal capsule were fitted to an exponential regression model to delineate age-dependent maturational changes across the WM structures. RESULTS: The DTI metrics demonstrated characteristic exponential patterns of progression during development and conspicuous age-dependent changes in the first 36 months, with rostral WM tracts experiencing the highest slope of the exponential function. In contrast, the highest final FA and lowest MD values were detected in the splenium of the corpus callosum and the posterior limb of the internal capsule. CONCLUSIONS: Our analysis shows that the more caudal portions of the corpus callosum and internal capsule begin the maturation process earlier than the rostral regions, but the rostral regions develop at a more accelerated pace, which may suggest that rostral regions rely on development of more caudal brain regions to instigate their development. Our normative DTI can be used as a reference to study normal spatiotemporal developmental profiles in the WM and help identify abnormal WM structures in patient populations.

White matter microstructural abnormality in children with hydrocephalus detected by probabilistic diffusion tractography.

BACKGROUND AND PURPOSE: Hydrocephalus is a severe pathologic condition in which WM damage is a major factor associated with poor outcomes. The goal of the study was to investigate tract-based WM connectivity and DTI measurements in children with hydrocephalus by using the probabilistic diffusion tractography method. MATERIALS AND METHODS: Twelve children with hydrocephalus and 16 age-matched controls were included in the study. Probabilistic diffusion tractography was conducted to generate tract-based connectivity distribution and DTI measures for the genu of the corpus callosum and the connectivity index. Tract-based summary measurements, including the connectivity index and DTI measures (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity), were calculated and compared between the 2 study groups. RESULTS: Tract-based summary measurement showed a higher percentage of voxels with lower normalized connectivity index values in the WM tracts in children with hydrocephalus. In the genu of the corpus callosum, the left midsegment of the corticospinal tract, and the right midsegment of the corticospinal tract, the normalized connectivity index value in children with hydrocephalus was found to be significantly lower (P < .05, corrected). The tract-based DTI measures showed that the children with hydrocephalus had significantly higher mean diffusivity, axial diffusivity, and radial diffusivity in the genu of the corpus callosum, left midsegment of the corticospinal tract, and right midsegment of corticospinal tract and lower fractional anisotropy in the genu of the corpus callosum (P < .05, corrected). CONCLUSIONS: The analysis of WM connectivity showed that the probabilistic diffusion tractography method is a sensitive tool to detect the decreased continuity in WM tracts that are under the direct influence of mechanical distortion and increased intracranial pressure in hydrocephalus. This voxel-based connectivity method can provide quantitative information complementary to the standard DTI summary measures.

Diffusion tensor imaging properties and neurobehavioral outcomes in children with hydrocephalus.

BACKGROUND AND PURPOSE: White matter structural alterations and the correlation with neuropsychological deficits in children with hydrocephalus have not been well investigated. In this prospective study, the objectives were the following: 1) to apply DTI to detect in vivo white matter alterations based on diffusion properties in children with acute hydrocephalus, 2) to quantify early neuropsychological deficits, and 3) to explore the correlation between potential neuropsychological deficits and abnormalities in functionally related white matter. MATERIALS AND METHODS: A total of 44 children, 24 with hydrocephalus and 20 controls, were enrolled in the study. DTI indices, FA, MD, AD, and RD, were evaluated in the gCC, sCC, PLIC, and ALIC. The ABAS-II was used as a broad screener of development, including conceptual, social, practical, and motor skills. The correlation between the Motor Scale and DTI indices in the PLIC was analyzed. RESULTS: DTI analyses showed that the gCC and sCC in children with hydrocephalus had lower FA and higher MD, driven by the increased RD with statistical significance (P < .05) or trend-level significance (P = .06). The PLIC and ALIC had significantly higher AD in children with hydrocephalus (P < .05). On the ABAS-II, parent ratings of general adaptive skills, conceptual skills, and motor skills were significantly lower in children with hydrocephalus (all at P < .05). The MD and RD values in the PLIC were found to have trend-level or significant correlation with the Motor Scale (P = .057, .041, respectively). CONCLUSIONS: DTI reveals alterations in the white matter structure in children with hydrocephalus with preliminary findings suggesting correlation with clinical motor deficits.

Anisotropic diffusion properties in infants with hydrocephalus: a diffusion tensor imaging study.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) can noninvasively detect in vivo white matter (WM) abnormalities on the basis of anisotropic diffusion properties. We analyzed DTI data retrospectively to quantify the abnormalities in different WM regions in children with hydrocephalus during early infancy. MATERIALS AND METHODS: Seventeen infants diagnosed with hydrocephalus (age range, 0.13-16.14 months) were evaluated with DTI and compared with 17 closely age-matched healthy children (age range, 0.20-16.11 months). Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity values in 5 regions of interest (ROIs) in the corpus callosum and internal capsule were measured and compared. The correlation between FA and age was also studied and compared by ROI between the 2 study groups. RESULTS: Infants with hydrocephalus had significantly lower FA, higher MD, and higher radial diffusivity values for all 3 ROIs in the corpus callosum, but not for the 2 ROIs in the internal capsule. In infants with hydrocephalus, the increase of FA with age during normal development was absent in the corpus callosum but was still preserved in the internal capsule. There was also a significant difference in the frequency of occurrence of abnormal FA values in the corpus callosum and internal capsule. CONCLUSIONS: This retrospective DTI study demonstrated significant WM abnormalities in infants with hydrocephalus in both the corpus callosum and internal capsule. The results also showed evidence that the impact of hydrocephalus on WM was different in the corpus callosum and internal capsule.

Inference procedures for assessing interobserver agreement among multiple raters.

We propose a new procedure for constructing inferences about a measure of interobserver agreement in studies involving a binary outcome and multiple raters. The proposed procedure, based on a chi-square goodness-of-fit test as applied to the correlated binomial model (Bahadur, 1961, in Studies in Item Analysis and Prediction, 158-176), is an extension of the goodness-of-fit procedure developed by Donner and Eliasziw (1992, Statistics in Medicine 11, 1511-1519) for the case of two raters. The new procedure is shown to provide confidence-interval coverage levels that are close to nominal over a wide range of parameter combinations. The procedure also provides a sample-size formula that may be used to determine the required number of subjects and raters for such studies.

A general goodness-of-fit approach for inference procedures concerning the kappa statistic.

The kappa statistic is frequently used as a measure of agreement among two or more raters. Although considerable research on statistical inferences for this statistic has been published for the case of two raters and a binary outcome, relatively little work has appeared on inference problems for the case of multiple raters and/or polytomous nominal outcome categories. In this paper we propose a new procedure for constructing inferences for the kappa statistic that may be applied to this general case. The procedure is based on a chi-square goodness-of-fit test as applied to the Dirichlet multinomial model, and is a natural extension of previously proposed procedures that apply to more restricted cases. A simulation study shows that the new procedure provides confidence interval coverage levels and type I error rates close to nominal over a wide range of parameter combinations. We also present a sample size formula which may be used to determine the required number of subjects and raters for a given number of outcome categories.

Fucosylated human milk oligosaccharides vary between individuals and over the course of lactation.

Specific human milk oligosaccharides, especially fucosylated neutral oligosaccharides, protect infants against specific microbial pathogens. To study the concentrations of individual neutral oligosaccharides during lactation, a total of 84 milk samples were obtained from 12 women at 7 time periods during weeks 1-49 postpartum. The neutral oligosaccharides from each sample were isolated, perbenzoylated, resolved, and quantified by reversed-phase high-performance liquid chromatography. The resultant oligosaccharide peaks, identified by co-elution with authentic standards and mass spectrometry, ranged in size from tri- to octasaccharides. The total concentration of oligosaccharides declined over the course of lactation; the mean concentration at 1 year was less than half that in the first few weeks postpartum. One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. In milk samples from the remaining 11 donors, fucosyloligosaccharides containing alpha1,2-linked fucose were prevalent, and their profiles were distinct from those of fucosyloligosaccharides devoid of alpha1,2-linked fucose. The ratio of alpha1,2-linked oligosaccharide concentrations to oligosaccharides devoid of alpha1,2-linked fucose changed during the first year of lactation from 5:1 to 1:1. Furthermore, the absolute and the relative concentrations of individual oligosaccharides varied substantially, both between individual donors and over the course of lactation for each individual. The patterns of milk oligosaccharides among individuals suggest the existence of many genotype subpopulations. This variation in individual oligosaccharide concentrations suggests that the protective activities of human milk could also vary among individuals and during lactation.

Pilot study of sunlight exposure and vitamin D status in Arab women of childbearing age

Vitamin D deficiency is common in Arab women, In a pilot study we investigated the effect of sun exposure at recommended levels on the vitamin D status of Arab women. Eight healthy Arab women of child-bearing age consented to expose their face, arms and hands for 15 minutes per day twice a week for 4 weeks within the privacy of their courtyard and to avoid changes in dietary vitamin D intake. Serum 25-hydroxyvitamin D [25[OH]] levels were measured pre- and post-intervention. Although vitamin D levels remained sub-optimal, median serum 25[OH]D levels were significantly higher post-intervention [23.0 nmol/L] than pre-intervention [17.6 nmol/L]. Extending sun exposure for more than 4 weeks should be investigated as part of strategies to improve vitamin D status in high-risk Arab women who lack outdoor sun exposure to the skin