66 research outputs found
Molecular and fossil evidence place the origin of cichlid fishes long after Gondwanan rifting.
Cichlid fishes are a key model system in the study of adaptive radiation, speciation and evolutionary developmental biology. More than 1600 cichlid species inhabit freshwater and marginal marine environments across several southern landmasses. This distributional pattern, combined with parallels between cichlid phylogeny and sequences of Mesozoic continental rifting, has led to the widely accepted hypothesis that cichlids are an ancient group whose major biogeographic patterns arose from Gondwanan vicariance. Although the Early Cretaceous (ca 135 Ma) divergence of living cichlids demanded by the vicariance model now represents a key calibration for teleost molecular clocks, this putative split pre-dates the oldest cichlid fossils by nearly 90 Myr. Here, we provide independent palaeontological and relaxed-molecular-clock estimates for the time of cichlid origin that collectively reject the antiquity of the group required by the Gondwanan vicariance scenario. The distribution of cichlid fossil horizons, the age of stratigraphically consistent outgroup lineages to cichlids and relaxed-clock analysis of a DNA sequence dataset consisting of 10 nuclear genes all deliver overlapping estimates for crown cichlid origin centred on the Palaeocene (ca 65-57 Ma), substantially post-dating the tectonic fragmentation of Gondwana. Our results provide a revised macroevolutionary time scale for cichlids, imply a role for dispersal in generating the observed geographical distribution of this important model clade and add to a growing debate that questions the dominance of the vicariance paradigm of historical biogeography
Analyzing Adherence to Prenatal Supplement: Does Pill Count Measure Up?
Objective. To determine if adherence as measured by pill count would show a significant association with serum-based measures of adherence.
Methods. Data were obtained from a prenatal vitamin D supplementation trial where subjects were stratified by race and randomized into three dosing groups: 400 (control), 2000, or 4000 IU vitamin D3/day. One measurement of adherence was obtained via pill counts remaining compared to a novel definition for adherence using serum 25-hydroxy-vitamin D (25-OH-D) levels (absolute change in 25(OH)D over the study period and the subject's steady-state variation in their 25(OH)D levels). A multivariate logistic regression model examined whether mean percent adherence by pill count was significantly associated with the adherence measure by serum metabolite levels.
Results. Subjects' mean percentage of adherence by pill count was not a significant predictor of adherence by serum metabolite levels. This finding was robust across a series of sensitivity analyses.
Conclusions. Based on our novel definition of adherence, pill count was not a reliable predictor of adherence to protocol, and calls into question how adherence is measured in clinical research. Our findings have implications regarding the determination of efficacy of medications under study and offer an alternative approach to measuring adherence of long half-life supplements/medications
A Retrospective Database Analysis of Neonatal Morbidities to Evaluate a Composite Endpoint for Use in Preterm Labor Clinical Trials
Objective To propose and assess a composite endpoint (CE) of neonatal benefit based on neonatal mortality and morbidities by gestational age (GA) for use in preterm labor clinical trials. Study Design A descriptive, retrospective analysis of the Medical University of South Carolina Perinatal Information System database was conducted. Neonatal morbidities were assessed for inclusion in the CE based on clinical significance/risk of childhood neurodevelopmental impairment, frequency, and association with GA in a mother– neonate linked cohort, comprising women with uncomplicated singleton pregnancies delivered at !24 weeks’ GA.
Results Among 17,912 mother–neonate pairs, neonates were at a risk of numerous severe but infrequent morbidities. Clinically important, predominantly rare events were combined into a CE comprising neonatal mortality and morbidities, which decreased in frequency with increasing GA. The highest CE frequency occurred at \u3c31 weeks. High frequency of respiratory distress syndrome, bronchopulmonary dysplasia, and sepsis drove the CE. Median length of hospital stay was longer at all GAs in those with the CE compared with those without.
Conclusions Descriptive epidemiological assessment and clinical input were used to develop a CE to measure neonatal benefit, comprising clinically meaningful outcomes. These empirical data and CE allowed trials investigating tocolytics to be sized appropriately
Circulating 25-Hydroxyvitamin D Levels in Fully Breastfed Infants on Oral Vitamin D Supplementation
Objective. To examine the effectiveness of oral vitamin D3 (400 IU) supplementation on the nutritional vitamin D status of breastfeeding infants.
Design. As part of a larger ongoing vitamin D RCT trial of lactating women, infants of mothers assigned to control
received 1 drop of 400 IU vitamin D3/day starting at one month of age. Infant 25(OH)D levels (mean ± S.D.) were measured by RIA at visits 1, 4, and 7.
Results. The infant mean ± S.D. 25(OH)D at baseline was 16.0 ±9.3 ng/mL (range 1.0–40.8; n = 33); 24 (72.7%) had baseline levels <20 ng/mL (consistent with deficiency). The mean levels increased to 43.6 ±14.1 (range 18.2–69.7) at 4 months and remained relatively unchanged at month 7: 42.5 ±12.1 ng/mL (range 18.9–67.2). The change in values between 1 and 4 months and 1 and 7 months was statistically significant (P ≤ .0001), and despite a decrease in dose per kilogram, values were not significantly different between months 4 and 7 (P = .66).
Conclusions. Oral vitamin D3 supplementation as an oil emulsion was associated with significant and sustained increases in 25(OH)D from baseline in fully breastfeeding infants through 7 months
Parameter selection for and implementation of a web-based decision-support tool to predict extubation outcome in premature infants
BACKGROUND: Approximately 30% of intubated preterm infants with respiratory distress syndrome (RDS) will fail attempted extubation, requiring reintubation and mechanical ventilation. Although ventilator technology and monitoring of premature infants have improved over time, optimal extubation remains challenging. Furthermore, extubation decisions for premature infants require complex informational processing, techniques implicitly learned through clinical practice. Computer-aided decision-support tools would benefit inexperienced clinicians, especially during peak neonatal intensive care unit (NICU) census. METHODS: A five-step procedure was developed to identify predictive variables. Clinical expert (CE) thought processes comprised one model. Variables from that model were used to develop two mathematical models for the decision-support tool: an artificial neural network (ANN) and a multivariate logistic regression model (MLR). The ranking of the variables in the three models was compared using the Wilcoxon Signed Rank Test. The best performing model was used in a web-based decision-support tool with a user interface implemented in Hypertext Markup Language (HTML) and the mathematical model employing the ANN. RESULTS: CEs identified 51 potentially predictive variables for extubation decisions for an infant on mechanical ventilation. Comparisons of the three models showed a significant difference between the ANN and the CE (p = 0.0006). Of the original 51 potentially predictive variables, the 13 most predictive variables were used to develop an ANN as a web-based decision-tool. The ANN processes user-provided data and returns the prediction 0–1 score and a novelty index. The user then selects the most appropriate threshold for categorizing the prediction as a success or failure. Furthermore, the novelty index, indicating the similarity of the test case to the training case, allows the user to assess the confidence level of the prediction with regard to how much the new data differ from the data originally used for the development of the prediction tool. CONCLUSION: State-of-the-art, machine-learning methods can be employed for the development of sophisticated tools to aid clinicians' decisions. We identified numerous variables considered relevant for extubation decisions for mechanically ventilated premature infants with RDS. We then developed a web-based decision-support tool for clinicians which can be made widely available and potentially improve patient care world wide
A Second-Generation Device for Automated Training and Quantitative Behavior Analyses of Molecularly-Tractable Model Organisms
A deep understanding of cognitive processes requires functional, quantitative analyses of the steps leading from genetics and the development of nervous system structure to behavior. Molecularly-tractable model systems such as Xenopus laevis and planaria offer an unprecedented opportunity to dissect the mechanisms determining the complex structure of the brain and CNS. A standardized platform that facilitated quantitative analysis of behavior would make a significant impact on evolutionary ethology, neuropharmacology, and cognitive science. While some animal tracking systems exist, the available systems do not allow automated training (feedback to individual subjects in real time, which is necessary for operant conditioning assays). The lack of standardization in the field, and the numerous technical challenges that face the development of a versatile system with the necessary capabilities, comprise a significant barrier keeping molecular developmental biology labs from integrating behavior analysis endpoints into their pharmacological and genetic perturbations. Here we report the development of a second-generation system that is a highly flexible, powerful machine vision and environmental control platform. In order to enable multidisciplinary studies aimed at understanding the roles of genes in brain function and behavior, and aid other laboratories that do not have the facilities to undergo complex engineering development, we describe the device and the problems that it overcomes. We also present sample data using frog tadpoles and flatworms to illustrate its use. Having solved significant engineering challenges in its construction, the resulting design is a relatively inexpensive instrument of wide relevance for several fields, and will accelerate interdisciplinary discovery in pharmacology, neurobiology, regenerative medicine, and cognitive science
Demonstration of Ignition Radiation Temperatures in Indirect-Drive Inertial Confinement Fusion Hohlraums
Linear association between maternal age and spontaneous breech presentation in singleton pregnancies after 32 weeks gestation
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Maternal Prepregnant Body Mass Index and Weight Gain Related to Low Birth Weight in South Carolina
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