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Abstract: Children with acute lymphoblastic leukemia (ALL) often experience treatment-related neurocognitive deficits and significant pain. Pain may exacerbate these cognitive impairments. This study examined neuropathic pain and neurocognitive outcomes in survivors of childhood ALL treated with contemporary therapy on a clinical trial (NCT00137111). There were 345 survivors (45% female, M = 6.9 years at diagnosis) who completed neurocognitive assessments including measures of sustained attention, learning and memory, and parent ratings of attention during at least one of 4 time points: on-therapy (Induction and Reinduction), end of therapy, and 2 years post-therapy. At-risk performance was defined as a score at least 1SD below the age-adjusted mean. Data on neuropathic pain (events, duration, and severity according NCI Common Toxicity Criteria) and pharmacologic pain management (opioids and gabapentin) were ascertained. Results showed that 135 survivors (39%) experienced neuropathic pain during treatment. Compared with those without pain, survivors with pain had greater memory impairments at end of therapy (California Verbal Learning Test [CVLT]-Total, 24% vs 12%, P = 0.046). Within the pain group, survivors who experienced a greater number of pain events (CVLT-Total = -0.88, P = 0.023) and those who were treated with opioids (versus gabapentin) had poorer learning and memory performance (CVLT-Total = -0.73, P = 0.011; Short Delay = -0.57, P = 0.024; Long Delay = -0.62, P = 0.012; and Learning Slope = -0.45, P = 0.042) across time points. These are considered medium-to-large effects (SD = 0.45-0.88). Neuropathic pain may be a risk factor for learning problems after therapy completion, and treatment for pain with opioids may also adversely affect neurocognitive performance. Therefore, patients who experience pain may require closer monitoring and additional intervention for neurocognitive impairment. [ABSTRACT FROM AUTHOR]

This study examined changes in white matter microstructure and grey matter volume, cortical thickness, and cortical surface area before and after reading intervention. Participants included 22 average readers and 13 dyslexic readers (8–9 years old in third grade); the dyslexic readers were enrolled in reading intervention programs at their elementary school. Participants completed scans of diffusion tensor imaging and T1‐weighted MRI before and after 3 months of instruction. An a priori region of interest (ROI) analysis was used. Dyslexic readers, compared to average readers, showed higher mean diffusivity in white matter ROIs including bilateral inferior frontal, bilateral insula, left superior temporal, and right supramarginal gyri across time points. Dyslexic readers also had thicker cortex in left fusiform and bilateral supramarginal gyri; whereas, average readers had greater surface area in right fusiform across time. There were no significant changes in white or grey matter following intervention; however, mean diffusivity in the right hemisphere was associated with reading gains over time. White matter organization in the right hemisphere predicts reading changes, and dyslexic readers may have persistent differences in white and grey matter due to ongoing reading deficits. [ABSTRACT FROM AUTHOR]

Summary: Neurocognitive deficits in sickle cell disease (SCD) may impair adult care engagement. We investigated the relationship between neurocognitive functioning and socio‐environmental factors with healthcare transition outcomes. Adolescents aged 15–18 years who had neurocognitive testing and completed a visit with an adult provider were included. Transition outcomes included transfer interval from paediatric to adult care and retention in adult care at 12 and 24 months. Eighty adolescents (59% male, 64% HbSS/HbSβ0‐thalassaemia) were included. Mean age at adult care transfer was 18·0 (±0·3) years and transfer interval was 2·0 (±2·3) months. Higher IQ (P = 0·02; PFDR = 0·05) and higher verbal comprehension (P = 0·008; PFDR = 0·024) were associated with <2 and <6 month transfer intervals respectively. Better performance on measures of attention was associated with higher adult care retention at 12 and 24 months (P = 0·009; PFDR = 0·05 and P = 0·04; PFDR = 0·12 respectively). Transfer intervals <6 months were associated with smaller households (P = 0·02; PFDR = 0·06) and households with fewer children (P = 0·02; PFDR = 0·06). Having a working parent was associated with less retention in adult care at 12 and 24 months (P = 0·01; P = 0·02 respectively). Lower IQ, verbal comprehension, attention difficulties and environmental factors may negatively impact transition outcomes. Neurocognitive function should be considered in transition planning for youth with SCD. [ABSTRACT FROM AUTHOR]

Summary: Patients with sickle cell disease (SCD) are at increased risk for neurocognitive impairments. While disease‐modifying treatment, such as hydroxycarbamide (hydroxyurea), may decrease this risk, it has not been systematically investigated in children with SCD. We screened neurocognitive functioning in 103 adolescents with SCD (16–17 years, 50% female) and compared outcomes between patients with a history of exposure to hydroxycarbamide (n = 12 HbSC/HbSβ+ thalassaemia; n = 52 HbSS/HbSβ0 thalassaemia) and those never treated with hydroxycarbamide (n = 31 HbSC/HbSβ+ thalassaemia; n = 8 HbSS/HbSβ0 thalassaemia). Demographic distributions were similar between the groups. After adjusting for socioeconomic status, the hydroxycarbamide group had significantly higher scores on nonverbal IQ (HbSC/HbSβ thalassaemia: P = 0·036, effect size [d] = 0·65), reaction speed (HbSS/HbSβ0 thalassaemia: P = 0·002, d = 1·70), sustained attention (HbSS/HbSβ0 thalassaemia: P = 0·014, d = 1·30), working memory (HbSC/HbSβ+ thalassaemia: P = 0·034, d = 0·71) and verbal memory (HbSC/HbSβ+ thalassaemia: P = 0·038, d = 0·84) when compared to those who did not receive hydroxycarbamide. In patients with HbSS/HbSβ0 thalassaemia, longer treatment duration with hydroxycarbamide was associated with better verbal memory (P = 0·009) and reading (P = 0·002). Markers of hydroxycarbamide effect, including higher fetal haemoglobin (HbF), higher mean corpuscular volume (MCV) and lower white blood cell count (WBC), were associated with better verbal fluency (HbF: P = 0·014, MCV: P = 0·006, WBC: P = 0·047) and reading (MCV: P = 0·021, WBC: P = 0·037). Cognitive impairment may be mitigated by exposure to hydroxycarbamide in adolescents with SCD. [ABSTRACT FROM AUTHOR]

Early intervention is known to reduce reading disabilities; however, treatment response is variable, and some students have persistent deficits that require intensive supports. This study examined the immediate and 1-year outcomes of an individualized and intensive reading program for third grade students, which was delivered throughout the school day for an average of 189 hr of instruction over 3 months. These students' performances were compared with two comparison groups, including poor readers who received small group supports and good readers who did not have additional reading instruction. The intensive group showed an improvement in word recognition and decoding fluency immediately after the program and 1 year later, and there was a decrease in significant reading impairments from 62% before intervention to 35% at follow-up. Furthermore, baseline reading, spelling, phonological awareness, and rapid naming skills were predictive of persistent reading deficits at a later time point. Although improvements in reading skills were shown, a significant gap between poor and good readers persisted in the third and fourth grades. This study illustrates the importance of a tertiary intensive reading program, but also the need for continuing supports. [ABSTRACT FROM AUTHOR]

Children with poor reading skills have differences in brain function when compared to typically-developing readers, and there may also be changes in the brain following reading intervention. However, most functional imaging studies focus on phonological reading tasks with one level of task difficulty. The purpose of this study was to compare good and poor readers on functional magnetic resonance imaging (fMRI) tasks of orthography (spelling) and phonology (rhyming) before and after 3 months of school-based intervention. These tasks were also modulated by task difficulty based on printed word frequency. The results showed that primarily left hemisphere regions were activated for the spelling and rhyming tasks, and poor readers showed a pattern of increased activation in bilateral inferior frontal, bilateral insula, right parietal, and left cerebellum following intervention. Activity in left pars triangularis and right parietal regions were associated with gains in decoding skills. Intervention effects appeared across blocks of easy and difficult words, except for the right parietal cortex. In this region, poor readers had greater activity on the easy word blocks after intervention, which indicates that there was increased recruitment of the right parietal cortex for relatively easy words. These results indicate that effects of intervention may be more evident on phonological tasks in comparison to orthographic tasks, and some of these effects may be modulated by relative task difficulty. • Left hemisphere was primarily activated for orthographic and phonological reading. • Poor readers showed increased activity in frontal regions after intervention. • Brain activity before reading intervention was associated with gains in decoding. • Intervention effects were evident across blocks of easy and difficult words. [ABSTRACT FROM AUTHOR]

Previous studies have reported compromised reading ability in children with amblyopia. Standardized psychoeducational test norms have not been used; therefore, the practical consequences of poor reading ability, such as eligibility for reading supports at school, have not been assessed. Furthermore, several studies have used atypical reading conditions such as monocular or distant viewing. It is also not clear how amblyopia treatment impacts reading ability. Thus, the goal of this study was to use standardized tests to compare binocular reading performance in children treated for amblyopia to that of a large normative sample, as well as to the types of control groups used in previous studies. Children treated for strabismic or anisometropic amblyopia (N = 14) were compared to children treated for strabismus without amblyopia (N = 12) and to children with healthy vision (N = 39). Visual acuity, stereoacuity, interocular suppression, intellectual functioning, oral single-word reading (TOWRE-2), and oral paragraph reading (GORT-5) were assessed. The control group showed significantly higher single-word reading accuracy than the amblyopia and strabismus groups. However, mean performance for all groups was within the average range of the normative sample. While mean scores were in the average range, six children (four amblyopia, two strabismus) performed below average on the single-word reading task; four of these children also showed below average paragraph reading. Reading scores were not correlated with visual acuity in the patient groups. The results raise the possibility that both strabismus and amblyopia can disrupt reading ability, even following successful treatment, to an extent that might benefit from reading supports at school. [ABSTRACT FROM AUTHOR]

It has been suggested that slow and medium-to-fast speeds of motion may be processed by at least partially separate mechanisms. The purpose of this study was to establish the cortical areas activated during motion-defined form and global motion tasks as a function of speed, using functional magnetic resonance imaging. Participants performed discrimination tasks with random dot stimuli at high coherence, at coherence near their own thresholds, and for random motion. Stimuli were moving at 0.1 or 5 deg/s. In the motion-defined form task, lateral occipital complex, V5/MTþ and intraparietal sulcus showed greater activation by high or near-threshold coherence than by random motion stimuli; V5/MTþ and intraparietal sulcus demonstrated greater activation for 5 than 0.1 deg/s dot motion. In the global motion task, only high coherence stimuli elicited significant activation over random motion; this activation was primarily in nonclassical motion areas. V5/MTþ was active for all motion conditions and showed similar activation for coherent and random motion. No regions demonstrated speed-tuning effects for global motion. These results suggest that similar cortical systems are activated by slow- and medium-speed stimuli during these tasks in healthy adults. [ABSTRACT FROM AUTHOR]

There are some children who encounter unexpected reading difficulties in the fourth grade. This phenomenon has been described as late emerging reading disabilities (LERD). Using Grade 4 as a starting point, this study examined the reading development of 964 children between kindergarten and Grade 7. The results showed that 72.0% of children had typical reading performance in Grade 4, whereas there was 0.7% with poor word reading, 12.6% with poor reading comprehension, 2.5% with poor word reading and comprehension, and 12.2% with borderline performance. We also showed that there were similar proportions of children who had early versus late emerging reading difficulties; however, most of the late emerging poor readers recovered by Grade 7. Furthermore, our study showed that poor comprehenders showed poorer performance than typical readers on word reading, pseudoword decoding, and spelling between Grade 1 and Grade 7 and poorer performance on a working memory task in kindergarten. Overall, this study showed that most children recover from late emerging reading problems and that working memory may be an early indicator for reading comprehension difficulties. [ABSTRACT FROM AUTHOR]

Abstract: The current study examined auditory processing deficits in dyslexia using a dichotic pitch stimulus and functional MRI. Cortical activation by the dichotic pitch task occurred in bilateral Heschl’s gyri, right planum temporale, and right superior temporal sulcus. Adolescents with dyslexia, relative to age-matched controls, illustrated greater activity in left Heschl’s gyrus for random noise, less activity in right Heschl’s gyrus for all auditory conditions, and less activity in right superior temporal sulcus for a dichotic melody. Subsequent analyses showed that these group differences were attributable to dyslexic readers who performed poorly on the psychophysical task. Furthermore, behavioral performance on phonological reading was correlated to activity from dichotic conditions in right Heschl’s gyrus and right superior temporal sulcus. It is postulated that these differences between reader groups is primarily due to a noise exclusion deficit shown previously in dyslexia. [Copyright &y& Elsevier]

PURPOSE: To investigate the relationship between systemic cytokines, the complement factor H (CFH) Y402H polymorphism, drusen load, and subfoveal choroidal thickness in patients with dry age-related macular degeneration (AMD). DESIGN: Cross-sectional study. METHODS: Forty-four dry AMD patients under care of the Retina Service at the University of British Columbia were enrolled. Drusen load was measured with an automated software algorithm in spectral-domain optical coherence tomography; subfoveal choroidal thickness was measured manually using enhanced depth imaging. Bio-Plex suspension assays (Bio-Rad Laboratories) were used to analyze cytokines in plasma and CFH Y402H was genotyped. Statistical analyses included analysis of covariance and Pearson correlation, corrected for multiple comparisons. RESULTS: The levels of 3 of 4 studied cytokines were significantly different among patients with CC, CT, or TT variants of the CFH Y402H polymorphism (P < .01). Patients with the at-risk CC variant had higher systemic levels of interleukin-6, interleukin-18, and tumor necrosis factor a than those with the CT variants, the TT variant, or both (P < .01). Interleukin-1b did not reach significance (P = .02), but did demonstrate a consistent trend. No correlation was found between plasma cytokines and drusen load or choroidal thickness (all P>.15). CONCLUSIONS: The elevated systemic levels of selected proinflammatory cytokines, including those representing products of inflammasome activation, were associated with the CC at-risk variant of the Y402H polymorphism and suggest that genetic factors regulate the inflammatory status in dry AMD patients. Our data support the central role of inflammation in the pathogenesis of AMD and provide further evidence of a systemic involvement in AMD etiology. [ABSTRACT FROM AUTHOR]

Abstract: We determined the effect of dot speed on the typical and atypical development of motion-defined form perception. Monocular motion coherence thresholds for orientation discrimination of motion-defined rectangles were determined at slow (0.1deg/s), medium (0.9deg/s) and fast (5.0deg/s) dot speeds. First we examined typical development from age 4 to 31years. We found that performance was most immature at the slow speed and in the youngest group of children (4–6years). Next we measured motion-defined form perception in the amblyopic and fellow eyes of patients with amblyopia. Deficits were found in both eyes and were most pronounced at the slow speed. These results demonstrate the importance of dot speed to the development of motion-defined form perception. Implications regarding sensitive periods and the neural correlates of motion-defined form perception are discussed. [Copyright &y& Elsevier]

A single experiment is reported in which we provide a novel analysis of eye movements during visual search to disentangle the contributions of unattended guidance and focal target processing to visual search performance. This technique is used to examine the controversial claim that unattended affective faces can guide attention during search. Results indicated that facial expression influences how efficiently the target was fixated for the first time as a function of set size. However, affective faces did not influence how efficiently the target was identified as a function of set size after it was first fixated. These findings suggest that, in the present context, facial expression can influence search before the target is attended and that the present measures are able to distinguish between the guidance of attention by targets and the processing of targets within the focus of attention. [ABSTRACT FROM AUTHOR]