Feasibility of continuous non-invasive delivery of oxygen monitoring in cardiac surgical patients: a proof-of-concept preliminary study.

PURPOSE: Oxygen delivery (DO2) and its monitoring are highlighted to aid postoperative goal directed therapy (GDT) to improve perioperative outcomes such as acute kidney injury (AKI) after high-risk cardiac surgeries associated with multiple morbidities and mortality. However, DO2 monitoring is neither routine nor done postoperatively, and current methods are invasive and only produce intermittent DO2 trends. Hence, we proposed a novel algorithm that simultaneously integrates cardiac output (CO), hemoglobin (Hb) and oxygen saturation (SpO2) from the Edwards Life Sciences ClearSight System® and Masimo SET Pulse CO-Oximetry® to produce a continuous, real-time DO2 trend. METHODS: Our algorithm was built systematically with 4 components - machine interface to draw data with PuTTY, data extraction with parsing, data synchronization, and real-time DO2 presentation using a graphic-user interface. Hb readings were validated. RESULTS: Our algorithm was implemented successfully in 93% (n = 57 out of 61) of our recruited cardiac surgical patients. DO2 trends and AKI were studied. CONCLUSION: We demonstrated a novel proof-of-concept and feasibility of continuous, real-time, non-invasive DO2 monitoring, with each patient serving as their own control. Our study also lays the foundation for future investigations aimed at identifying personalized critical DO2 thresholds and optimizing DO2 as an integral part of GDT to enhance outcomes in perioperative cardiac surgery.

Enhanced recovery after surgery in pediatric urology: Current evidence and future practice.

PURPOSE: To offer an up-to-date appraisal of the current status of enhanced recovery after surgery (ERAS) protocols in pediatric urology and to provide a guide for the clinical urologist. MATERIALS AND METHODS: We performed a comprehensive literature search and scoping review on ERAS protocols in pediatric urology using Pubmed (from 1946), Cochrane library, and MEDLINE to December 2021 with the terms ''enhanced recovery'', ''protocolised care'', ''post-operative protocol", ''fast-track surgery'' and ''pediatric urology". Studies were excluded if they did not include perioperative intervention related to urological procedures, no full-text available and in non-English language. RESULTS: To date, eight clinical studies (involving 1153 patients) have been published on ERAS protocols in pediatric urology. The patients involved ranged from neonates to adolescents, and the urological procedures included bladder augmentation, the Mitrofanoff procedure, laparoscopic pyeloplasty, laparoscopic nephrectomy, hypospadias repair, etc. Multidisciplinary components such as surgical and anesthetic considerations have been employed in ERAS protocols. The length of hospital stay was significantly lower in the ERAS groups with earlier enteral feeding resumption and return of bowel function in pediatric urology patients. The implementation of ERAS protocols does not result in higher complication and readmission rates; instead, some studies have even demonstrated a significant reduction in complication occurrence. CONCLUSION: ERAS is novel to pediatric urology with a limited scale of published data in the literature. Initial clinical studies revealed that ERAS appears to be efficacious in the field of pediatric urology. Further prospective studies formulating a standardized multimodal protocol are encouraged to better understand key components of ERAS and incorporate ERAS into clinical practice to optimize surgical outcomes for pediatric urology procedures.

Effectiveness of a Self-Management Program to Improve Cognition and Quality of Life in Epilepsy: A Pragmatic, Randomized, Multicenter Trial.

BACKGROUND AND OBJECTIVES: We conducted a multisite, pragmatic replication trial at 4 New England epilepsy centers to determine the effectiveness of Home-Based Self-Management and Cognitive Training Changes Lives (HOBSCOTCH) in a real-world setting and to assess feasibility of a virtual intervention. METHODS: HOBSCOTCH is an 8-session intervention addressing cognitive impairment and quality of life (QoL) for people with epilepsy (PWE). Participants were recruited from epilepsy centers in 4 states and block-randomized into the following groups: in-person HOBSCOTCH (H-IP), virtual HOBSCOTCH (H-V), and waitlist control. Outcome measures were assessed for all groups at baseline, 3 months, and 6 months; intervention groups received long-term follow-up at 9 and 12 months. RESULTS: A total of 108 participants were recruited, of whom 85 were included in this analysis (age at baseline 47.5 ± 11.5 years; 68% female). Participants completing the in-person intervention (H-IP) had a 12.4-point improvement in QoL score compared with controls (p < 0.001). Pairwise comparisons found a 6.2-point treatment effect for subjective cognition in the H-IP group (p < 0.001). There were no meaningful group differences in objective cognition or health care utilization at any time points and the treatment effect for QoL diminished by 6 months. The virtual intervention demonstrated feasibility but did not significantly improve outcomes compared with controls. Within-group analysis found improvements in QoL for both H-V and H-IP. DISCUSSION: This study replicated the effectiveness of the HOBSCOTCH program in improving QoL for PWE. The study was conducted prior to the COVID-19 pandemic, but the distance-delivered intervention may be particularly well-suited for the current environment. Future research will explore modifications designed to improve the efficacy of H-V and the sustainability of HOBSCOTCH's treatment effect. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov (NCT02394509). CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in-person HOBSCOTCH delivery improved subjective measures of cognition in persons with epilepsy.

Evaluation of replanning in intensity-modulated proton therapy for oropharyngeal cancer: Factors influencing plan robustness.

The head and neck (H&N) region is frequently replanned during intensity-modulated proton therapy (IMPT), but replanning disrupts clinical workflow and presents additional burden on patients. The purpose of this study was to establish a standard treatment planning approach to minimize H&N replanning by identifying a correlation between dosimetric variables and replan frequency. In a retrospective study of 27 bilateral oropharyngeal cancer patients treated with IMPT at a single institution, cases were evaluated using Fisher's exact tests and logistic regression for a significant relationship between replan frequency and the following variables: beam number, clinical target volume (CTV) coverage, presence of dental fillings, and robustness. The reason and timing for replan initiation, and patient immobilization was also recorded to identify trends. Results suggested that beam number, CTV coverage, presence of dental fillings, and the initial robustness curve on the high-dose CTV did not individually contribute to replanning frequency. Setup variation in the soft tissue of the neck was the most prominent reason for replanning. A lack of correlation between the number of replans and the studied dosimetric variables highlights the necessity of verification CT and adaptive replanning in IMPT of H&N cancer. Departments may therefore benefit from a methodical replan workflow. One development showing potential to enhance clinical replan processes is machine learning-based automatic adaptive replanning.

Sex Differences in Mathematics Anxiety and Attitudes: Concurrent and Longitudinal Relations to Mathematical Competence.

Sex differences in the strength of the relations between mathematics anxiety, mathematics attitudes and mathematics achievement were assessed concurrently in sixth grade (n = 1,091, 545 boys) and longitudinally from sixth- to seventh-grade (n = 190, 97 boys). Mathematics anxiety was composed of two facets, one associated with evaluations and the other for learning more generally. Girls had higher mathematics anxiety for evaluations than did boys (ds = -.30 to -.52), but not for mathematics learning. In sixth grade, the negative correlation between mathematical competence and mathematics anxiety for evaluations was stronger in girls than in boys. Longitudinally, higher mathematical competence in sixth grade was associated with lower mathematics anxiety for evaluations and better mathematics attitudes in seventh grade for girls but not for boys. The key finding is that adolescent girls' mathematics anxiety and their attitudes toward mathematics are more reflective of their actual mathematical competence than they are for boys. One implication is that relative to boys with low mathematics achievement, girls with low achievement are at higher risk of developing mathematics anxiety and poor attitudes toward mathematics.

Self-management practices associated with quality of life for adults with epilepsy.

Epilepsy self-management practices enhance a patient's competence and confidence in managing their chronic condition, which is assumed to lead to an improved quality of life (QoL). We analyzed the relationship between the Epilepsy Self-Management Scale (ESMS) responses and the Quality of Life in Epilepsy (QOLIE-31) scores. Baseline questionnaires from HOBSCOTCH, a self-management program for cognitive problems, were administered in four New England epilepsy centers on adults (n = 100) with epilepsy and subjective memory complaints. There was no correlation between overall self-management scores and overall quality-of-life scores; however, subscale analyses indicated that certain self-management practices were strongly correlated with the overall QOLIE-31 score. Specifically, improved ESMS lifestyle management was associated with an increased quality-of-life score (adjusted p < 0.01), while enhanced ESMS safety management practices were associated with a decreased overall quality-of-life score (adjusted p < 0.01). Our item-level analysis highlighted specific items within the ESMS safety management, ESMS lifestyle management, and ESMS information management subdomains that were significant predictors for QoL. Depression was also shown to be significantly correlated with the QOLIE-31 (p < 0.01). Our study suggests that an overemphasis on safety practices may negatively affect quality of life, while enhanced lifestyle management has positive effects. Furthermore, our finding that quality of life is greatly dependent on depressive symptoms underscores the importance of treating depression in epilepsy.

Preschool deficits in cardinal knowledge and executive function contribute to longer-term mathematical learning disability.

In a preschool through first grade longitudinal study, we identified groups of children with persistently low mathematics achievement (n = 14) and children with low achievement in preschool but average achievement in first grade (n = 23). The preschool quantitative developments of these respective groups of children with mathematical learning disability (MLD) and recovered children and a group of typically achieving peers (n = 35) were contrasted, as were their intelligence, executive function, and parental education levels. The core characteristics of the children with MLD were poor executive function and delayed understanding of the cardinal value of number words throughout preschool. These compounded into even more substantive deficits in number and arithmetic at the beginning of first grade. The recovered group had poor executive function and cardinal knowledge during the first year of preschool but showed significant gains during the second year. Despite these gains and average mathematics achievement, the recovered children had subtle deficits with accessing magnitudes associated with numerals and addition combinations (e.g., 5 + 6 = ?) in first grade. The study provides unique insight into domain-general and quantitative deficits in preschool that increase risk for long-term mathematical difficulties.

Prescription patterns for routine EEG ordering in patients with intracranial hemorrhage admitted to a neurointensive care unit.

PURPOSE: To examine clinical factors, including established electroencephalography (EEG) consensus recommendations, that may influence EEG-prescription in critically-ill intracerebral hemorrhage (ICH) patients in the neurointensive care unit. METHODS: Retrospective analysis of 330 ICH patients admitted to a neurointensive care unit at an academic medical center between 01/2013-12/2015. We compared EEG prescription patterns with current EEG consensus recommendations, and employed univariate and multivariable logistic regression modeling to determine clinical variables associated with EEG ordering. RESULTS: Seventy-eight (41%) of 190 subjects underwent EEG in accordance with EEG-consensus guidelines, demonstrating an overall accuracy (probability that EEG prescription aligned with EEG consensus recommendations) of 64.6% (95%-CI59.1-69.7). Factors independently associated with EEG ordering included fulfillment of EEG consensus recommendations, lower admission Glasgow Coma Scale (GCS), and presence of clinical seizures. The unadjusted and adjusted C-statistics for fulfillment of consensus recommendations was 0.74 (95%-CI 0.69-0.80) and 0.85 (95%-CI 0.81-0.90), respectively. Among 83 subjects undergoing EEG (25.2%), EEG findings informed clinical decision-making in 50 patients (60%). CONCLUSIONS: EEG appeared underused in ICH, since <50% of patients who fulfilled guideline criteria underwent EEG. Prescription of EEG was related to factors beyond those included in consensus recommendations. Validation of our findings and their association with outcome is required.

Predicting Age of Becoming a Cardinal Principle Knower.

Children's first mathematics concept is their understanding of the quantities represented by number words (cardinal value), and the age at which they achieve this insight predicts their readiness for mathematics learning in school. We provide the first exploration of the factors that influence the age of becoming a cardinal principle knower (CPK), with a longitudinal study of 197 (94 boys) children from the beginning to the end of two years of preschool. Core symbolic and non-symbolic quantitative competencies at the beginning of preschool, as well as measures of intelligence, executive function, preliteracy skills, and parental education were used to predict timing of CPK status. Children who achieved early CPK status had higher IQ scores, knew more count words and numerals, and had a better intuitive understanding of relative quantity than their peers. Children who were delayed CPKs, in contrast, had deficits in executive function and poor preliteracy skills. The results add to our understanding of children's conceptual development in mathematics and have implications for the identification of at-risk children and design of interventions for them.

Children's early understanding of number predicts their later problem-solving sophistication in addition.

Previous studies suggest that the sophistication of the strategies children use to solve arithmetic problems is related to a more basic understanding of number, but they have not examined the relation between number knowledge in preschool and strategy choices at school entry. Accordingly, the symbolic and nonsymbolic quantitative knowledge of 134 children (65 boys) was assessed at the beginning of preschool and in kindergarten, and the sophistication of the strategies they used to solve addition problems was assessed at the beginning of first grade. Using a combination of Bayes and standard regression models, we found that children's understanding of the cardinal value of number words at the beginning of preschool predicted the sophistication of their strategy choices 3 years later, controlling for other factors. The relation between children's early understanding of cardinality and their strategy choices was mediated by their symbolic and nonsymbolic quantitative knowledge in kindergarten. The results suggest that sophisticated strategy choices emerge from children's developing understanding of the relations among numbers, in keeping with the overlapping waves model.

Attaching meaning to the number words: contributions of the object tracking and approximate number systems.

Children's understanding of the quantities represented by number words (i.e., cardinality) is a surprisingly protracted but foundational step in their learning of formal mathematics. The development of cardinal knowledge is related to one or two core, inherent systems - the approximate number system (ANS) and the object tracking system (OTS) - but whether these systems act alone, in concert, or antagonistically is debated. Longitudinal assessments of 198 preschool children on OTS, ANS, and cardinality tasks enabled testing of two single-mechanism (ANS-only and OTS-only) and two dual-mechanism models, controlling for intelligence, executive functions, preliteracy skills, and demographic factors. Measures of both OTS and ANS predicted cardinal knowledge in concert early in the school year, inconsistent with single-mechanism models. The ANS but not the OTS predicted cardinal knowledge later in the school year as well the acquisition of the cardinal principle, a critical shift in cardinal understanding. The results support a Merge model, whereby both systems initially contribute to children's early mapping of number words to cardinal value, but the role of the OTS diminishes over time while that of the ANS continues to support cardinal knowledge as children come to understand the counting principles.

Early Conceptual Understanding of Cardinality Predicts Superior School-Entry Number-System Knowledge.

We demonstrate a link between preschoolers' quantitative competencies and their school-entry knowledge of the relations among numbers (number-system knowledge). The quantitative competencies of 141 children (69 boys) were assessed at the beginning of preschool and throughout the next 2 years of preschool, as was their mathematics and reading achievement at the end of kindergarten and their number-system knowledge at the beginning of first grade. A combination of Bayes analyses and standard regressions revealed that the age at which the children had the conceptual insight that number words represent specific quantities (cardinal value) was strongly related to their later number-system knowledge and was more consistently related to broader mathematics than to reading achievement, controlling for intelligence, executive function, and parental education levels. The key implication is that it is not simply knowledge of cardinal value but the age of acquisition of this principle that is central to later mathematical development and school readiness.

Developmental Foundations of Children's Fraction Magnitude Knowledge.

The conceptual insight that fractions represent magnitudes is a critical yet daunting step in children's mathematical development, and the knowledge of fraction magnitudes influences children's later mathematics learning including algebra. In this study, longitudinal data were analyzed to identify the mathematical knowledge and domain-general competencies that predicted 8th and 9th graders' (n=122) knowledge of fraction magnitudes and its cross-grade gains. Performance on the fraction magnitude measures predicted 9th grade algebra achievement. Understanding and fluently identifying the numerator-denominator relation in 7th grade emerged as the key predictor of later fraction magnitudes knowledge in both 8th and 9th grades. Competence at using fraction procedures, knowledge of whole number magnitudes, and the central executive contributed to 9th but not 8th graders' fraction magnitude knowledge, and knowledge of whole number magnitude contributed to cross-grade gains. The key results suggest fluent processing of numerator-denominator relations presages students' understanding of fractions as magnitudes and that the integration of whole number and fraction magnitudes occurs gradually.

Predicting Children's Reading and Mathematics Achievement from Early Quantitative Knowledge and Domain-General Cognitive Abilities.

One hundred children (44 boys) participated in a 3-year longitudinal study of the development of basic quantitative competencies and the relation between these competencies and later mathematics and reading achievement. The children's preliteracy knowledge, intelligence, executive functions, and parental educational background were also assessed. The quantitative tasks assessed a broad range of symbolic and nonsymbolic knowledge and were administered four times across 2 years of preschool. Mathematics achievement was assessed at the end of each of 2 years of preschool, and mathematics and word reading achievement were assessed at the end of kindergarten. Our goals were to determine how domain-general abilities contribute to growth in children's quantitative knowledge and to determine how domain-general and domain-specific abilities contribute to children's preschool mathematics achievement and kindergarten mathematics and reading achievement. We first identified four core quantitative competencies (e.g., knowledge of the cardinal value of number words) that predict later mathematics achievement. The domain-general abilities were then used to predict growth in these competencies across 2 years of preschool, and the combination of domain-general abilities, preliteracy skills, and core quantitative competencies were used to predict mathematics achievement across preschool and mathematics and word reading achievement at the end of kindergarten. Both intelligence and executive functions predicted growth in the four quantitative competencies, especially across the first year of preschool. A combination of domain-general and domain-specific competencies predicted preschoolers' mathematics achievement, with a trend for domain-specific skills to be more strongly related to achievement at the beginning of preschool than at the end of preschool. Preschool preliteracy skills, sensitivity to the relative quantities of collections of objects, and cardinal knowledge predicted reading and mathematics achievement at the end of kindergarten. Preliteracy skills were more strongly related to word reading, whereas sensitivity to relative quantity was more strongly related to mathematics achievement. The overall results indicate that a combination of domain-general and domain-specific abilities contribute to development of children's early mathematics and reading achievement.

Early numerical foundations of young children's mathematical development.

This study focused on the relative contributions of the acuity of the approximate number system (ANS) and knowledge of quantitative symbols to young children's early mathematical learning. At the beginning of preschool, 191 children (Mage=46 months) were administered tasks that assessed ANS acuity and explicit knowledge of the cardinal values represented by number words, and their mathematics achievement was assessed at the end of the school year. Children's executive functions, intelligence, and preliteracy skills and their parents' educational levels were also assessed and served as covariates. Both the ANS and cardinality tasks were significant predictors of end-of-year mathematics achievement with and without control of the covariates. As simultaneous predictors and with control of the covariates, cardinality remained significantly related to mathematics achievement, but ANS acuity did not. Mediation analyses revealed that the relation between ANS acuity and mathematics achievement was fully mediated by cardinality, suggesting that the ANS may facilitate children's explicit understanding of cardinal value and in this way may indirectly influence early mathematical learning.

Acuity of the approximate number system and preschoolers' quantitative development.

The study assessed the relations among acuity of the inherent approximate number system (ANS), performance on measures of symbolic quantitative knowledge, and mathematics achievement for a sample of 138 (64 boys) preschoolers. The Weber fraction (a measure of ANS acuity) and associated task accuracy were significantly correlated with mathematics achievement following one year of preschool, and predicted performance on measures of children's explicit knowledge of Arabic numerals, number words, and cardinal value, controlling for age, sex, parental education, intelligence, executive control, and preliteracy knowledge. The relation between ANS acuity, as measured by the Weber fraction and task accuracy, and mathematics achievement was fully mediated by children's performance on the symbolic quantitative tasks, with knowledge of cardinal value emerging as a particularly important mediator. The overall pattern suggests that ANS acuity facilitates the early learning of symbolic quantitative knowledge and indirectly influences mathematics achievement through this knowledge.

Quantitative deficits of preschool children at risk for mathematical learning disability.

The study tested the hypothesis that acuity of the potentially inherent approximate number system (ANS) contributes to risk of mathematical learning disability (MLD). Sixty-eight (35 boys) preschoolers at risk for school failure were assessed on a battery of quantitative tasks, and on intelligence, executive control, preliteracy skills, and parental education. Mathematics achievement scores at the end of 1 year of preschool indicated that 34 of these children were at high risk for MLD. Relative to the 34 typically achieving children, the at risk children were less accurate on the ANS task, and a one standard deviation deficit on this task resulted in a 2.4-fold increase in the odds of MLD status. The at risk children also had a poor understanding of ordinal relations, and had slower learning of Arabic numerals, number words, and their cardinal values. Poor performance on these tasks resulted in 3.6- to 4.5-fold increases in the odds of MLD status. The results provide some support for the ANS hypothesis but also suggest these deficits are not the primary source of poor mathematics learning.

Gray matter volumes and cognitive ability in the epileptogenic brain malformation of periventricular nodular heterotopia.

Periventricular nodular heterotopia (PNH) is a brain malformation clinically characterized by the triad of epilepsy, normal intelligence, and dyslexia. We investigated the structure-function relationship between cerebral volumes and cognitive ability in this disorder by studying 12 subjects with PNH and 6 controls using volumetric analysis of high-resolution anatomical MRI and neuropsychological testing. Total cerebral volumes and specific brain compartment volumes (gray matter, white matter, and cerebrospinal fluid) in subjects with PNH were comparable to those in controls. There was a negative correlation between heterotopic gray matter volume and cortical gray matter volume. Cerebral and cortical volumes in PNH did not correlate with Full Scale IQ, unlike in normal individuals. Our findings support the idea that heterotopic nodules contain misplaced neurons that would normally have migrated to the cortex, and suggest that structural correlates of normal cognitive ability may be different in the setting of neuronal migration failure.

Essential and opposing roles of zebrafish beta-catenins in the formation of dorsal axial structures and neurectoderm.

In Xenopus, Wnt signals and their transcriptional effector beta-catenin are required for the development of dorsal axial structures. In zebrafish, previous loss-of-function studies have not identified an essential role for beta-catenin in dorsal axis formation, but the maternal-effect mutation ichabod disrupts beta-catenin accumulation in dorsal nuclei and leads to a reduction of dorsoanterior derivatives. We have identified and characterized a second zebrafish beta-catenin gene, beta-catenin-2, located on a different linkage group from the previously studied beta-catenin-1, but situated close to the ichabod mutation on LG19. Although the ichabod mutation does not functionally alter the beta-catenin-2 reading frame, the level of maternal beta-catenin-2, but not beta-catenin-1, transcript is substantially lower in ichabod, compared with wild-type, embryos. Reduction of beta-catenin-2 function in wild-type embryos by injection of morpholino antisense oligonucleotides (MOs) specific for this gene (MO2) results in the same ventralized phenotypes as seen in ichabod embryos, and administration of MO2 to ichabod embryos increases the extent of ventralization. MOs directed against beta-catenin-1 (MO1), by contrast, had no ventralizing effect on wild-type embryos. beta-catenin-2 is thus specifically required for organizer formation and this function is apparently required maternally, because the ichabod mutation causes a reduction in maternal transcription of the gene and a reduced level of beta-catenin-2 protein in the early embryo. A redundant role of beta-catenins in suppressing formation of neurectoderm is revealed when both beta-catenin genes are inhibited. Using a combination of MO1 and MO2 in wild-type embryos, or by injecting solely MO1 in ichabod embryos, we obtain expression of a wide spectrum of neural markers in apparently appropriate anteroposterior pattern. We propose that the early, dorsal-promoting function of beta-catenin-2 is essential to counteract a later, dorsal- and neurectoderm-repressing function that is shared by both beta-catenin genes.

The zebrafish gene map defines ancestral vertebrate chromosomes.

Genetic screens in zebrafish (Danio rerio) have identified mutations that define the roles of hundreds of essential vertebrate genes. Genetic maps can link mutant phenotype with gene sequence by providing candidate genes for mutations and polymorphic genetic markers useful in positional cloning projects. Here we report a zebrafish genetic map comprising 4073 polymorphic markers, with more than twice the number of coding sequences localized in previously reported zebrafish genetic maps. We use this map in comparative studies to identify numerous regions of synteny conserved among the genomes of zebrafish, Tetraodon, and human. In addition, we use our map to analyze gene duplication in the zebrafish and Tetraodon genomes. Current evidence suggests that a whole-genome duplication occurred in the teleost lineage after it split from the tetrapod lineage, and that only a subset of the duplicates have been retained in modern teleost genomes. It has been proposed that differential retention of duplicate genes may have facilitated the isolation of nascent species formed during the vast radiation of teleosts. We find that different duplicated genes have been retained in zebrafish and Tetraodon, although similar numbers of duplicates remain in both genomes. Finally, we use comparative mapping data to address the proposal that the common ancestor of vertebrates had a genome consisting of 12 chromosomes. In a three-way comparison between the genomes of zebrafish, Tetraodon, and human, our analysis delineates the gene content for 11 of these 12 proposed ancestral chromosomes.