Parsimonious Higher-Order Hidden Markov Models for Improved Array-CGH Analysis with Applications to Arabidopsis thaliana

Array-based comparative genomic hybridization (Array-CGH) is an important technology in molecular biology for the detection of DNA copy number polymorphisms between closely related genomes. Hidden Markov Models (HMMs) are popular tools for the analysis of Array-CGH data, but current methods are only based on first-order HMMs having constrained abilities to model spatial dependencies between measurements of closely adjacent chromosomal regions. Here, we develop parsimonious higher-order HMMs enabling the interpolation between a mixture model ignoring spatial dependencies and a higher-order HMM exhaustively modeling spatial dependencies. We apply parsimonious higher-order HMMs to the analysis of Array-CGH data of the accessions C24 and Col-0 of the model plant Arabidopsis thaliana. We compare these models against first-order HMMs and other existing methods using a reference of known deletions and sequence deviations. We find that parsimonious higher-order HMMs clearly improve the identification of these polymorphisms. Moreover, we perform a functional analysis of identified polymorphisms revealing novel details of genomic differences between C24 and Col-0. Additional model evaluations are done on widely considered Array-CGH data of human cell lines indicating that parsimonious HMMs are also well-suited for the analysis of non-plant specific data. All these results indicate that parsimonious higher-order HMMs are useful for Array-CGH analyses. An implementation of parsimonious higher-order HMMs is available as part of the open source Java library Jstacs (www.jstacs.de/index.php/PHHMM)

Executive Function in Very Preterm Children at Early School Age

We examined whether very preterm (≤30 weeks gestation) children at early school age have impairments in executive function (EF) independent of IQ and processing speed, and whether demographic and neonatal risk factors were associated with EF impairments. A consecutive sample of 50 children (27 boys and 23 girls) born very preterm (mean age = 5.9 years, SD = 0.4, mean gestational age = 28.0 weeks, SD = 1.4) was compared to a sample of 50 age-matched full-term controls (23 girls and 27 boys, mean age = 6.0 years, SD = 0.6) with respect to performance on a comprehensive EF battery, assessing the domains of inhibition, working memory, switching, verbal fluency, and concept generation. The very preterm group demonstrated poor performance compared to the controls on all EF domains, even after partialing out the effects of IQ. Processing speed was marginally related to EF. Analyses with demographic and neonatal risk factors showed maternal education and gestational age to be related to EF. This study adds to the emerging body of literature showing that very preterm birth is associated with EF impairments

The effect of extremely preterm birth on attachment organization in late adolescence

Background Prior studies have examined the impact of preterm birth on the quality of the attachment relationship to the mother in infancy, but few have examined extremely preterm born infants and almost no data have been reported on prematurity and its impact on the attachment organization attained after childhood. Methods Thirty-nine adolescents born extremely preterm and 39 full-term born control participants were assessed with the Adult Attachment Interview. Results The prematurely born showed lower scores regarding measures of attachment security and, in particular, a higher proportion of insecure dismissive patterns. This difference seemed to be clear and persistent even when controlled for intelligence and socio-economic variables. Conclusions Because insecure attachment as well as prematurity may be considered as significant risk factors for developing psychopathology, they deserve careful attention in future research and clinical follow-ups

Electroencephalographic Response to Procedural Pain in Healthy Term Newborn Infants

The current study aimed to characterize changes in EEG-related measures after noxious stimuli in neonates, and to assess their potential utility as measures of pain and/or discomfort during neonatal intensive care.Seventy-two healthy term infants were investigated: Twenty-eight had a non skin-breaking pin-prick on the heel, randomized to receive either oral glucose (n=16) or water (n=12) before the stimulus. 21 infants were studied during a venous blood sample from the dorsum of the hand, 23 infants during a capillary heel stick. Behavioral pain responses were assessed with the Premature Infant Pain Profile (PIPP) scale. The stimulus evoked a significant increase in higher frequency components (10-30Hz) which also correlated to behavioral measures. The frontotemporal localization of the increased activity with frequency bands similar to electromuscular artifacts and the relation to behavioral measures confirmed that this activity corresponds to an increase in muscle tone. There was no change in frontal EEG asymmetry in any of the groups. The present results indicate that responses in cortical activity recorded by EEG are not useful for clinical assessment of infants' responses to noxious stimuli