Neurodevelopmental outcome in perinatal asphyxia: prediction and measurement

The aim of this thesis was to improve our ability to predict and measure neurodevelopmental outcome in early childhood with particular reference to high-risk infants with perinatal asphyxia. Methods: 1) Promising umbilical cord blood biomarkers were analysed for ability to predict performance in the Bayley Scales of Infant and Toddler Development (Edition 3) at three years. 2) A retrospective cohort was analysed for performance of a low-risk cohort on the Bayley-3 at two years and compared to standardised scores. 3) A survey asked parents to report prevalence and quality of touch-screen usage in their toddlers. 4) Pilot testing of a novel cognitive assessment tool, the“Babyscreen App”, was performed on a prospective low risk cohort. The Babyscreen App was administered alongside the Bayley-3 at age 18 months to 2 years. Results: 1) IL-16 predicted severe outcome with an area under the ROC curve of 0.83 (p= Levels ≥ 514 pg/mL predicted a severe outcome with a sensitivity of 83% and a specificity of 81%. 2 metabolite models were tested. Model A predicted abnormal outcome with an area under ROC curve of 0.77, p<0.01. Model B was robust to predict both severe outcome (area under ROC curve of 0.92, p<0.01) and intact survival (0.80, p=0.01). 2) 240 two year olds were analysed for performance on the Bayley-3. Language and fine motor scores were significantly higher compared to U.S standardised norms, 109 ± 13 v. 100 ± 15 , p<0.001, and 11.5 ± 2 v. 10 ± 3, p<0.001 respectively. 3) For the examination of touch-screen usage in toddlers, 82 questionnaires were completed by parents of typically developing children aged 12 to 36 months. 71% of toddlers included had access to touch-screen devices for a median (IQR) of 15 (9-26) minutes per day. By 24 months the majority of children were able to swipe, unlock and actively look for touch-screen features. 4) 95 children underwent administration of the Babyscreen App and the Bayley-3. Significant medium sized correlations occurred between various measures of app performance and cognitive composite scores on the Bayley-3. Combined measures of overall app performance could predict cognitive scores less than 90 (1SD below the mean of our cohort) with an area under the ROC curve of 0.69 (0.55-0.83), p=0.02. Conclusion: This thesis has shown that novel biomarkers measured in umbilical cord blood at birth can predict neuro developmental outcome and that a novel touch-screen application can assess cognition in toddlers

Concurrent validity of a touchscreen application to detect early cognitive delay

OBJECTIVE: To explore the ability of an interactive screening tool to identify cognitive delay in children aged 18 to 24 months. DESIGN: Children were assessed using the Bayley Scale of Infant and Toddler Development-third edition (BSID-III) and a touchscreen measure of problem-solving (Babyscreen V.1.5). We examined the internal consistency and concurrent validity between the two measures. A BSID-III cognitive composite score (BSID-IIIcc) ≤1 SD below population mean was used to indicate a low average cognitive ability. RESULTS: 87 children with a mean (SD) age of 20.4 (1.3) months who experienced complications at delivery (n=53) and healthy age-matched controls (n=34) were included in the study. A moderate positive correlation between the BSID-IIIcc and the total number of tasks completed on the Babyscreen suggested reasonable concurrent validity (r=0.414, p90 (-1.08 (-1.5 to -0.46) vs 0.31 (-0.46 to 0.76); p=0.001). The area under the receiver operating characteristic curve for the prediction of a low normal BSID-IIIcc was 0.787 (CI 0.64 to 0.93). A BST z-score of <-0.44 yielded 82.4% sensitivity and 71.4% specificity in identifying children with cognitive delay. CONCLUSIONS: A touchscreen-based application has concurrent validity with the BSID-IIIcc and could be used to screen for cognitive delay at 18-24 months of age

Seizure burden and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy.

Aim: To examine the relationship between electrographic seizures and long-term outcome in neonates with hypoxic-ischemic encephalopathy (HIE). Method: Full-term neonates with HIE born in Cork University Maternity Hospital from 2003 to 2006 (pre-hypothermia era) and 2009 to 2012 (hypothermia era) were included in this observational study. All had early continuous electroencephalography monitoring. All electrographic seizures were annotated. The total seizure burden and hourly seizure burden were calculated. Outcome (normal/abnormal) was assessed at 24 to 48 months in surviving neonates using either the Bayley Scales of Infant and Toddler Development, Third Edition or the Griffiths Mental Development Scales; a diagnosis of cerebral palsy or epilepsy was also considered an abnormal outcome. Results: Continuous electroencephalography was recorded for a median of 57.1 hours (interquartile range 33.5-80.5h) in 47 neonates (31 males, 16 females); 29 out of 47 (62%) had electrographic seizures and 25 out of 47 (53%) had an abnormal outcome. The presence of seizures per se was not associated with abnormal outcome (p=0.126); however, the odds of an abnormal outcome increased over ninefold (odds ratio [OR] 9.56; 95% confidence interval [95% CI] 2.43-37.67) if a neonate had a total seizure burden of more than 40 minutes (p=0.001), and eightfold (OR: 8.00; 95% CI: 2.06-31.07) if a neonate had a maximum hourly seizure burden of more than 13 minutes per hour (p=0.003). Controlling for electrographic HIE grade or treatment with hypothermia did not change the direction of the relationship between seizure burden and outcome. Interpretation: In HIE, a high electrographic seizure burden is significantly associated with abnormal outcome, independent of HIE severity or treatment with hypothermia

On religion and cultural policy: notes on the Roman Catholic Church

This paper argues that religious institutions have largely been neglected within the study of cultural policy. This is attributed to the inherently secular tendency of most modern social sciences. Despite the predominance of the ‘secularisation paradigm’, the paper notes that religion continues to promote powerful attachments and denunciations. Arguments between the ‘new atheists’, in particular, Richard Dawkins, and their opponents are discussed, as is Habermas’s conciliatory encounter with Joseph Ratzinger (later Pope Benedict XVI). The paper then moves to a consideration of the Roman Catholic Church as an agent of cultural policy, whose overriding aim is the promotion of ‘Christian consciousness’. Discussion focuses on the contested meanings of this, with reference to (1) the deliberations of Vatican II and (2) the exercise of theological and cultural authority by the Pope and the Congregation for the Doctrine of the Faith (CDF). It is argued that these doctrinal disputes intersect with secular notions of social and cultural policy and warrant attention outside the specialist realm of theological discourse

Chromosomal organization of biosynthetic gene clusters, including those of nine novel species, suggests plasticity of myxobacterial specialized metabolism

IntroductionNatural products discovered from bacteria provide critically needed therapeutic leads for drug discovery, and myxobacteria are an established source for metabolites with unique chemical scaffolds and biological activities. Myxobacterial genomes accommodate an exceptional number and variety of biosynthetic gene clusters (BGCs) which encode for features involved in specialized metabolism.MethodsIn this study, we describe the collection, sequencing, and genome mining of 20 myxobacteria isolated from rhizospheric soil samples collected in North America.ResultsNine isolates were determined to be novel species of myxobacteria including representatives from the genera Archangium, Myxococcus, Nannocystis, Polyangium, Pyxidicoccus, Sorangium, and Stigmatella. Growth profiles, biochemical assays, and descriptions were provided for all proposed novel species. We assess the BGC content of all isolates and observe differences between Myxococcia and Polyangiia clusters.DiscussionContinued discovery and sequencing of novel myxobacteria from the environment provide BGCs for the genome mining pipeline. Utilizing complete or near-complete genome sequences, we compare the chromosomal organization of BGCs of related myxobacteria from various genera and suggest that the spatial proximity of hybrid, modular clusters contributes to the metabolic adaptability of myxobacteria

Microcytosis is associated with low cognitive outcomes in healthy 2-year-olds in a high-resource setting

Fe deficiency in early childhood is associated with long-term consequences for cognitive, motor and behavioural development; however explorations in healthy children from low risk, high-resource settings have been limited. We aimed to explore associations between Fe status and neurodevelopmental outcomes in low risk, healthy 2-year-olds. This study was a secondary analysis of a nested case–control subgroup from the prospective, maternal-infant Cork Babies after Screening for Pregnancy Endpoints: Evaluating the Longitudinal Impact using Neurological and Nutritional Endpoints (BASELINE) Birth Cohort Study. At 2 years, serum ferritin, Hb and mean corpuscular volume (MCV) were measured and neurodevelopment was assessed using the Bayley Scales of Infant and Toddler Development (n 87). Five children had Fe deficiency (ferritin <12 µg/l) and no child had Fe deficiency anaemia (Hb<110 g/l+ferritin<12 µg/l). Children with microcytosis (MCV<74 fl, n 13) had significantly lower mean cognitive composite scores (88·5 (sd 13·3) v. 97·0 (sd 7·8), P=0·04, Cohen’s d effect size=0·8) than those without microcytosis. The ferritin concentration which best predicted microcytosis was calculated as 18·4 µg/l (AUC=0·87 (95% CI 0·75, 0·98), P<0·0001, sensitivity 92 %, specificity 75 %). Using 18·5 µg/l as a threshold, children with concentrations <18·5 µg/l had significantly lower mean cognitive composite scores (92·3 (sd 10·5) v. 97·8 (sd 8·1), P=0·012, Cohen’s d effect size=0·6) compared with those with ferritin ≥18·5 µg/l. All associations were robust after adjustment for potential confounding factors. Despite a low prevalence of Fe deficiency using current diagnostic criteria in this healthy cohort, microcytosis was associated with lower cognitive outcomes at 2 years. This exploratory study emphasises the need for re-evaluation of the diagnostic criteria for Fe deficiency in young children, with further research in adequately powered studies warranted

Leadership Competencies for Digital Transformation : Evidence from Multiple Cases

Digital transformation (DT) is disrupting industrial organizations, which require significant changes in their properties to remain competitive. This calls for strong leadership to drive this transformation. However, what leadership competencies are required to lead DT impactfully is unclear. Therefore, we seek to identify the key leadership competencies by employing a qualitative, grounded theory approach. By conducting interviews of ten DT experts from two hardcore industrial organizations, we highlight five key leadership competencies that industrial organizations need to develop in their leaders: digital vision, digital knowledge, failing fast, empowerment, and managing diverse teams. The results of this study will help industrial organizations to strategically prepare their leadership for the requirements of DT.©2020 Springer. This is a post-peer-review, pre-copyedit version of an article published in Advances in Human Factors, Business Management and Leadership: Proceedings of the AHFE 2020 Virtual Conferences on Human Factors, Business Management and Society, and Human Factors in Management and Leadership, July 16-20, 2020, USA. The final authenticated version is available online at: http://dx.doi.org/0.1007/978-3-030-50791-6_11.fi=vertaisarvioitu|en=peerReviewed

Stable U(IV) Complexes Form at High-Affinity Mineral Surface Sites

Uranium (U) poses a significant contamination hazard to soils, sediments, and groundwater due to its extensive use for energy production. Despite advances in modeling the risks of this toxic and radioactive element, lack of information about the mechanisms controlling U transport hinders further improvements, particularly in reducing environments where UIV predominates. Here we establish that mineral surfaces can stabilize the majority of U as adsorbed UIV species following reduction of UVI. Using X-ray absorption spectroscopy and electron imaging analysis, we find that at low surface loading, UIV forms inner-sphere complexes with two metal oxides, TiO2 (rutile) and Fe3O4 (magnetite) (at <1.3 U nm–2 and <0.037 U nm–2, respectively). The uraninite (UO2) form of UIV predominates only at higher surface loading. UIV–TiO2 complexes remain stable for at least 12 months, and UIV–Fe3O4 complexes remain stable for at least 4 months, under anoxic conditions. Adsorbed UIV results from UVI reduction by FeII or by the reduced electron shuttle AH2QDS, suggesting that both abiotic and biotic reduction pathways can produce stable UIV–mineral complexes in the subsurface. The observed control of high-affinity mineral surface sites on UIV speciation helps explain the presence of nonuraninite UIV in sediments and has important implications for U transport modeling

What Drives Home Bias? Evidence from Fund Managers' Views

A survey of fund managers reveals home bias for these sophisticated investors in an unrestricted setting. Proximity, perceived informational advantage and higher expected returns are confirmed as accompanying factors. In addition, the home bias of equity managers is also related to institutional, informational and behavioral characteristics. The perceived informational advantage does not seem to be valid. Multivariate analyses indicate that home bias is mainly related to relative return optimism, non-fundamental information and peculiar behavior towards risk. We interpret these as characteristics of less than fully rational behavior. It is consistently found that this pattern does not apply to bond managers.Eine Befragung von Fondsmanagern offenbart die Heimatverzerrung (sog. Home Bias) dieser erfahrenen Investoren in unbegrenzten Rahmenbedingungen. Nähe, empfundene Informationsvorteile und höhere erwartete Renditen werden als Begleitumstände bestätigt. Zusätzlich ist der Home Bias von Aktienfondsmanagern mit institutionellen und informatorischen Gegebenheiten sowie mit bestimmten Verhaltensmustern verbunden. Der empfundene Informationsvorteil scheint sich jedoch nicht zu bewahrheiten. Multivariate Analysen zeigen, dass der Home Bias hauptsächlich mit relativem Renditeoptimismus, der Nutzung nicht-fundamentaler Informationen und besonderem Risikoverhalten verbunden ist. Wir interpretieren diese Eigenschaften als unvollkommen rationales Verhalten. Konsistent zeigt sich, dass dieses Muster nicht für Rentenfondsmanager gilt