Explore the vast range of titles available.

Neurodevelopmental outcomes are impaired in survivors of critical congenital heart disease (CHD) in several developmental domains including motor, cognitive and sensory outcomes. These deficits can extend into the adolescent and early adulthood years. The cause of these neurodevelopmental impairments is multi-factorial and includes patient specific risk factors, cardiac anatomy and physiology as well as brain changes seen on MRI. Advances in imaging techniques have identified delayed brain development in the neonate with critical CHD as well as acquired brain injury. These abnormalities are seen even before corrective neonatal cardiac surgery. This review focuses on describing brain changes seen on MRI in neonates with CHD, risk factors for these changes and the association with neurodevelopmental outcome. There is an emerging focus on the impact of cardiovascular physiology on brain health and the complex heart-brain interplay that influences ultimate neurodevelopmental outcome in these patients. •Neurodevelopmental outcome is impaired in survivors of critical congenital heart disease.•Advances in neonatal brain imaging have identified delayed brain development beginning in the third trimester of fetal life.•Acquired brain injury is common in critical congenital heart disease.•The relationship between brain imaging abnormalities in CHD and neurodevelopmental outcome is complex.

We propose BrainNetCNN, a convolutional neural network (CNN) framework to predict clinical neurodevelopmental outcomes from brain networks. In contrast to the spatially local convolutions done in traditional image-based CNNs, our BrainNetCNN is composed of novel edge-to-edge, edge-to-node and node-to-graph convolutional filters that leverage the topological locality of structural brain networks. We apply the BrainNetCNN framework to predict cognitive and motor developmental outcome scores from structural brain networks of infants born preterm. Diffusion tensor images (DTI) of preterm infants, acquired between 27 and 46 weeks gestational age, were used to construct a dataset of structural brain connectivity networks. We first demonstrate the predictive capabilities of BrainNetCNN on synthetic phantom networks with simulated injury patterns and added noise. BrainNetCNN outperforms a fully connected neural-network with the same number of model parameters on both phantoms with focal and diffuse injury patterns. We then apply our method to the task of joint prediction of Bayley-III cognitive and motor scores, assessed at 18 months of age, adjusted for prematurity. We show that our BrainNetCNN framework outperforms a variety of other methods on the same data. Furthermore, BrainNetCNN is able to identify an infant's postmenstrual age to within about 2 weeks. Finally, we explore the high-level features learned by BrainNetCNN by visualizing the importance of each connection in the brain with respect to predicting the outcome scores. These findings are then discussed in the context of the anatomy and function of the developing preterm infant brain. •First deep convolutional neural network architecture designed for connectomes.•Novel convolutional layers for leveraging topological locality in brain networks.•Prediction of neurodevelopmental outcomes in preterm infants.•Visualization of brain connections learned to be important for prediction.

Extremely preterm babies are at increased risk of less than optimal neurodevelopment compared with their term-born counterparts. Optimising nutrition is a promising avenue to mitigate the adverse neurodevelopmental consequences of preterm birth. In this narrative review, we summarize current knowledge on how nutrition, and in particular, protein intake, affects neurodevelopment in extremely preterm babies. Observational studies consistently report that higher intravenous and enteral protein intakes are associated with improved growth and possibly neurodevelopment, but differences in methodologies and combinations of intravenous and enteral nutrition strategies make it difficult to determine the effects of each intervention. Unfortunately, there are few randomized controlled trials of nutrition in this population conducted to determine neurodevelopmental outcomes. Substantial variation in reporting of trials, both of nutritional intakes and of outcomes, limits conclusions from meta-analyses. Future studies to determine the effects of nutritional intakes in extremely preterm babies need to be adequately powered to assess neurodevelopmental outcomes separately in boys and girls, and designed to address the many potential confounders which may have clouded research findings to date. The development of minimal reporting sets and core outcome sets for nutrition research will aid future meta-analyses.

Altered brain development is evident in children born very preterm (24-32 weeks gestational age), including reduction in gray and white matter volumes, and thinner cortex, from infancy to adolescence compared to term-born peers. However, many questions remain regarding the etiology. Infants born very preterm are exposed to repeated procedural pain-related stress during a period of very rapid brain development. In this vulnerable population, we have previously found that neonatal pain-related stress is associated with atypical brain development from birth to term-equivalent age. Our present aim was to evaluate whether neonatal pain-related stress (adjusted for clinical confounders of prematurity) is associated with altered cortical thickness in very preterm children at school age. 42 right-handed children born very preterm (24-32 weeks gestational age) followed longitudinally from birth underwent 3-D T1 MRI neuroimaging at mean age 7.9 yrs. Children with severe brain injury and major motor/sensory/cognitive impairment were excluded. Regional cortical thickness was calculated using custom developed software utilizing FreeSurfer segmentation data. The association between neonatal pain-related stress (defined as the number of skin-breaking procedures) accounting for clinical confounders (gestational age, illness severity, infection, mechanical ventilation, surgeries, and morphine exposure), was examined in relation to cortical thickness using constrained principal component analysis followed by generalized linear modeling. After correcting for multiple comparisons and adjusting for neonatal clinical factors, greater neonatal pain-related stress was associated with significantly thinner cortex in 21/66 cerebral regions (p-values ranged from 0.00001 to 0.014), predominately in the frontal and parietal lobes. In very preterm children without major sensory, motor or cognitive impairments, neonatal pain-related stress appears to be associated with thinner cortex in multiple regions at school age, independent of other neonatal risk factors.

While spreading the gospel around the world through his signature crusades, internationally renowned evangelist Billy Graham maintained a visible and controversial presence in his native South, a region that underwent substantial political and economic change in the latter half of the twentieth century. In this period Graham was alternately a desegregating crusader in Alabama, Sunbelt booster in Atlanta, regional apologist in the national press, and southern strategist in the Nixon administration.Billy Graham and the Rise of the Republican Southconsiders the critical but underappreciated role of the noted evangelist in the creation of the modern American South. The region experienced two significant related shifts away from its status as what observers and critics called the \"Solid South\": the end of legalized Jim Crow and the end of Democratic Party dominance. Author Steven P. Miller treats Graham as a serious actor and a powerful symbol in this transition-an evangelist first and foremost, but also a profoundly political figure. In his roles as the nation's most visible evangelist, adviser to political leaders, and a regional spokesperson, Graham influenced many of the developments that drove celebrants and detractors alike to place the South at the vanguard of political, religious, and cultural trends. He forged a path on which white southern moderates could retreat from Jim Crow, while his evangelical critique of white supremacy portended the emergence of \"color blind\" rhetoric within mainstream conservatism. Through his involvement in the Eisenhower and Nixon administrations, as well as his deep social ties in the South, the evangelist influenced the decades-long process of political realignment. Graham's public life sheds new light on recent southern history in all of its ambiguities, and his social and political ethics complicate conventional understandings of evangelical Christianity in postwar America. Miller's book seeks to reintroduce a familiar figure to the narrative of southern history and, in the process, examine the political and social transitions constitutive of the modern South.

Emergency department (ED) to community (ED2C) programs, which redirect patients from the pediatric ED to community healthcare professionals represent a promising strategy to reduce the impact of non-urgent visits on the pediatric ED. Given an ED2C program's potential impact on various care professionals, we completed a qualitative study to explore key informants' attitudes and perceptions of pediatric ED2C programs. We conducted one-on-one semi-structured interviews with key informants in British Columbia, Canada. Participants included: pediatric ED staff - triage nurses and physicians; community professionals - pediatricians and family physicians; and health system leaders responsible for pediatric and emergency care in British Columbia. Interviews were recorded, transcribed verbatim, de-identified, and analyzed using reflexive thematic analysis within an interpretive description framework. A visual model was developed to depict key themes in attitudes and perceptions towards pediatric ED2C programs. We interviewed 24 participants: 6 community professionals, 11 pediatric ED professionals, and 7 healthcare leaders. Participants viewed the ED2C program as a valuable solution to address pediatric system strain provided that systemic barriers are addressed, and both emergency and community settings are equipped with adequate training and resources. Participants emphasized the need for clear guidelines on eligibility and operations to build confidence and enhance program effectiveness. Our findings suggest there is support for ED2C programs as a means to reduce the impact of non-urgent pediatric ED visits and strengthen community-based care. Successful implementation will require coordinated planning, resource investment, and clear operational frameworks.

Altered hippocampal morphology and reduced volumes have been found in children born preterm compared to full-term. Stress inhibits neurogenesis in the hippocampus, and neonatal stress/noxious stimulation in rodent pups are associated with long-term alterations in hippocampal volumes. We have previously shown reduced cortical thickness and cerebellar volumes in relation to more exposure to pain-related stress of neonatal invasive procedures in children born very preterm. We have reported targeted gene-by-pain environment interactions that contribute to long-term brain development and outcomes in this population. We now aim to determine whether exposure to pain-related stress (adjusted for clinical factors and genotype) differentially impacts regional structures within the limbic system and thalamus, and investigate relationships with outcomes in very preterm children. Our study included 57 children born very preterm (<32 weeks GA) followed longitudinally from birth who underwent 3-D T1 MRI neuroimaging at ∼8 years. Hippocampal subfields and white matter tracts, thalamus and amygdala were automatically segmented using the MAGeT Brain algorithm. The relationship between those subcortical brain volumes (adjusted for total brain volume) and neonatal invasive procedures, gestational age (GA), illness severity, postnatal infection, days of mechanical ventilation, number of surgeries, morphine exposure, and genotype ( , and ) was examined using constrained principal component analysis. We found that neonatal clinical factors and genotypes accounted for 46% of the overall variance in volumes of hippocampal subregions, tracts, basal ganglia, thalamus and amygdala. After controlling for clinical risk factors and total brain volume, greater neonatal invasive procedures was associated with lower volumes in the amygdala and thalamus ( = 0.0001) and an interaction with genotype predicted smaller hippocampal subregional volume ( = 0.0001). More surgeries, days of ventilation, and lower GA were also related to smaller volumes in various subcortical regions ( < 0.002). These reduced volumes were in turn differentially related to poorer cognitive, visual-motor and behavioral outcomes. Our findings highlight the complexity that interplays when examining how exposure to early-life stress may impact brain development both at the structural and functional level, and provide new insight on possible novel avenues of research to discover brain-protective treatments to improve the care of children born preterm.

ObjectivesTo assess the association of head circumference (HC) <10th percentile at birth and discharge from the neonatal intensive care unit (NICU) with neurodevelopment in very preterm (24–32 weeks’ gestational age) neonates, and to compare the association of HC and total cerebral volume (TCV) with neurodevelopmental outcomes.DesignIn a prospective cohort, semiautomatically segmented TCV and manually segmented white matter injury (WMI) volumes were obtained. Multivariable regressions were used to study the association of HC and TCV with neurodevelopmental outcomes, accounting for birth gestational age, WMI and postnatal illness.SettingParticipants born in 2006–2013 at British Columbia Women’s Hospital were recruited.Patients168 neonates had HC measurements at birth and discharge and MRI at term-equivalent age (TEA). 143 children were assessed at 4.5 years.Main outcome measuresMotor, cognitive and language outcomes at 4.5 years were assessed using the Movement Assessment Battery for Children Second Edition (M-ABC) and Wechsler Preschool and Primary Scale of Intelligence Third Edition Full Scale IQ (FSIQ) and Verbal IQ (VIQ).ResultsSmall birth HC was associated with lower M-ABC and FSIQ scores. In children with small birth HC, small discharge HC was associated with lower M-ABC, FSIQ and VIQ scores, while normal HC at discharge was no longer associated with adverse outcomes. HC strongly correlated with TCV at TEA. TCV did not correlate with outcomes.ConclusionsSmall birth HC is associated with poorer neurodevelopment, independent of postnatal illness and WMI. Normalisation of HC during NICU care appears to moderate this risk.

ObjectiveTo determine whether severe retinopathy of prematurity (ROP) is associated with (1) abnormal white matter maturation and (2) neurodevelopmental outcomes at 18 months’ corrected age (CA) compared with neonates without severe ROP.DesignWe conducted a prospective longitudinal cohort of extremely preterm neonates born 24–28 weeks’ gestational age recruited between 2006 and 2013 with brain MRIs obtained both early in life and at term-equivalent age. Severe ROP was defined as ROP treated with retinal laser photocoagulation. Using diffusion tensor imaging and tract-based spatial statistics (TBSS), white matter maturation was assessed by mean fractional anisotropy (FA) in seven predefined regions of interest. Neurodevelopmental outcomes were assessed with Bayley Scales of Infant and Toddler Development-III (Bayley-III) composite scores at 18 months’ CA. Subjects were compared using Fisher’s exact, Kruskal-Wallis and generalised estimating equations.SettingFamilies were recruited from the neonatal intensive care unit at BC Women’s Hospital.PatientsOf 98 extremely preterm neonates (median: 26.0 weeks) assessed locally for ROP, 19 (19%) had severe ROP and 83 (85%) were assessed at 18 months’ CA.ResultsSevere ROP was associated with lower FA in the posterior white matter, and with decreased measures of brain maturation in the optic radiations, posterior limb of the internal capsule (PLIC) and external capsule on TBSS. Bayley-III cognitive and motor scores were lower in infants with severe ROP.ConclusionsSevere ROP is associated with maturational delay in the optic radiations, PLIC, external capsule and posterior white matter, housing the primary visual and motor pathways, and is associated with poorer cognitive and motor outcomes at 18 months’ CA.

Proton (1H) magnetic resonance spectroscopy (MRS) is a non‐invasive imaging technique that can be used to assess brain metabolism. Establishing reference levels of fetal brain metabolites in a translatable preclinical model is crucial for identifying subtle deviations from normal cerebral development. Herein, we developed a 1H‐MRS protocol for fetal sheep across three gestational periods (109 ± 2, 120 ± 5 and 139 ± 2 days gestation; term is 150 days gestation). Using this protocol, we established reference metabolic levels using recommended 1H‐MRS data analysis techniques. Objectives included adapting protocols for reliable metabolite detection despite the challenges of fetal 1H‐MRS, applying the protocol at multiple gestational ages, using recommended processing techniques and comparing two analysis software packages for robustness. MRI scans were performed on a 3 T Siemens clinical system (Magnetom Skyra, Siemens Healthineers, Germany) while the ewe was ventilated. 1H‐MRS was performed using a point‐resolved spectroscopy sequence at an echo time of 135 ms and a voxel size of 15 mm × 15 mm × 15 mm, gated to maternal respiration. We showed that TARQUIN metabolite level estimates had a significantly higher Cramér–Rao lower bound uncertainty compared with LCModel in N‐acetyl aspartate and choline, with differences in fit quality, while also underestimating metabolites. LCModel was then used to determine reference levels for N‐acetyl aspartate, choline, creatine and lactate across three gestational time points in late gestation. Our findings demonstrate the feasibility and reproducibility of non‐invasive fetal sheep brain 1H‐MRS. The study highlights the importance of objective criteria for accurate data interpretation, providing insights into fetal brain development and potential non‐invasive applications for earlier detection of poor neurodevelopmental outcomes. What is the central question of this study? Can proton magnetic resonance spectroscopy (1H‐MRS) be used reliably to assess cerebral metabolism non‐invasively in a preclinical fetal sheep model throughout gestation, and what is the most robust analysis method for fetal sheep data? What is the main finding and its importance? This study established a preclinical fetal sheep 1H‐MRS protocol capable of measuring cerebral metabolites non‐invasively. LCModel was shown to provide more robust fetal data analysis than TARQUIN, and reference metabolite levels were defined throughout late gestation. These findings support the use of 1H‐MRS as a non‐invasive tool for assessing fetal brain metabolism in preclinical models.