Comparative Analysis Of Zebrafish And Planarian Model Systems For Developmental Neurotoxicity Screens Using An 87-Compound Library

There is a clear need to establish and validate new methodologies to more quickly and efficiently screen chemicals for potential toxic effects, particularly on development. The emergence of alternative animal systems for rapid toxicology screens presents valuable opportunities to evaluate how systems complement each other. In this article, we compare a chemical library of 87-compounds in two such systems, developing zebrafish and freshwater planarians, by screening for developmental neurotoxic effects. We show that the systems’ toxicological profiles are complementary to each other, with zebrafish yielding more detailed morphological endpoints and planarians more behavioral endpoints. Overall, zebrafish was more sensitive to this chemical library, yielding 86/87 hits, compared to 50/87 hits in planarians. The difference in sensitivity could not be attributed to molecular weight, Log Kow or the bioconcentration factor. Of the 87 chemicals, 28 had previously been evaluated in mammalian developmental neuro- (DNT), neuro- or developmental toxicity studies. Of the 28, 20 were hits in the planarian, and 27 were hits in zebrafish. Eighteen of the 28 had previously been identified as DNT hits in mammals and were highly associated with activity in zebrafish and planarian behavioral assays in this study. Only 1 chemical (out of 28) was a false negative in both zebrafish and planarian systems. Differences in endpoint coverage and system sensitivity illustrate the value of a dual systems approach to rapidly query a large chemical-bioactivity space and provide weight-of-evidence for prioritization of chemicals for further testing

Supporting Space Systems Design via Systems Dependency Analysis Methodology

The increasing size and complexity of space systems and space missions pose severe challenges to space systems engineers. When complex systems and Systems-of-Systems are involved, the behavior of the whole entity is not only due to that of the individual systems involved but also to the interactions and dependencies between the systems. Dependencies can be varied and complex, and designers usually do not perform analysis of the impact of dependencies at the level of complex systems, or this analysis involves excessive computational cost, or occurs at a later stage of the design process, after designers have already set detailed requirements, following a bottom-up approach. While classical systems engineering attempts to integrate the perspectives involved across the variety of engineering disciplines and the objectives of multiple stakeholders, there is still a need for more effective tools and methods capable to identify, analyze and quantify properties of the complex system as a whole and to model explicitly the effect of some of the features that characterize complex systems. This research describes the development and usage of Systems Operational Dependency Analysis and Systems Developmental Dependency Analysis, two methods based on parametric models of the behavior of complex systems, one in the operational domain and one in the developmental domain. The parameters of the developed models have intuitive meaning, are usable with subjective and quantitative data alike, and give direct insight into the causes of observed, and possibly emergent, behavior. The approach proposed in this dissertation combines models of one-to-one dependencies among systems and between systems and capabilities, to analyze and evaluate the impact of failures or delays on the outcome of the whole complex system. The analysis accounts for cascading effects, partial operational failures, multiple failures or delays, and partial developmental dependencies. The user of these methods can assess the behavior of each system based on its internal status and on the topology of its dependencies on systems connected to it. Designers and decision makers can therefore quickly analyze and explore the behavior of complex systems and evaluate different architectures under various working conditions. The methods support educated decision making both in the design and in the update process of systems architecture, reducing the need to execute extensive simulations. In particular, in the phase of concept generation and selection, the information given by the methods can be used to identify promising architectures to be further tested and improved, while discarding architectures that do not show the required level of global features. The methods, when used in conjunction with appropriate metrics, also allow for improved reliability and risk analysis, as well as for automatic scheduling and re-scheduling based on the features of the dependencies and on the accepted level of risk. This dissertation illustrates the use of the two methods in sample aerospace applications, both in the operational and in the developmental domain. The applications show how to use the developed methodology to evaluate the impact of failures, assess the criticality of systems, quantify metrics of interest, quantify the impact of delays, support informed decision making when scheduling the development of systems and evaluate the achievement of partial capabilities. A larger, well-framed case study illustrates how the Systems Operational Dependency Analysis method and the Systems Developmental Dependency Analysis method can support analysis and decision making, at the mid and high level, in the design process of architectures for the exploration of Mars. The case study also shows how the methods do not replace the classical systems engineering methodologies, but support and improve them

Ocular manifestations in Gorlin-Goltz syndrome

Background: Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome, is a rare genetic disorder that is transmitted in an autosomal dominant manner with complete penetrance and variable expressivity. It is caused in 85% of the cases with a known etiology by pathogenic variants in the PTCH1 gene, and is characterized by a wide range of developmental abnormalities and a predisposition to multiple neoplasms. The manifestations are multiple and systemic and consist of basal cell carcinomas in various regions, odontogenic keratocistic tumors and skeletal anomalies, to name the most frequent. Despite the scarce medical literature on the topic, ocular involvement in this syndrome is frequent and at the level of various ocular structures. Our study focuses on the visual apparatus and its annexes in subjects with this syndrome, in order to better understand how this syndrome affects the ocular system, and to evaluate with greater accuracy and precision the nature of these manifestations in this group of patients. Results: Our study confirms the presence of the commonly cited ocular findings in the general literature regarding the syndrome [hypertelorism (45.5%), congenital cataract (18%), nystagmus (9%), colobomas (9%)] and highlights strabismus (63% of the patients), epiretinal membranes (36%) and myelinated optic nerve fiber layers (36%) as the most frequent ophthalmological findings in this group of patients. Conclusions: The presence of characteristic and frequent ocular signs in the Gorlin- Goltz syndrome could help with the diagnostic process in subjects suspected of having the syndrome who do not yet have a diagnosis. The ophthalmologist has a role as part of a multidisciplinary team in managing these patients. The ophthalmological follow-up that these patients require, can allow, if necessary, a timely therapy that could improve the visual prognosis of such patients

Intrinsic Motivation Systems for Autonomous Mental Development

Exploratory activities seem to be intrinsically rewarding for children and crucial for their cognitive development. Can a machine be endowed with such an intrinsic motivation system? This is the question we study in this paper, presenting a number of computational systems that try to capture this drive towards novel or curious situations. After discussing related research coming from developmental psychology, neuroscience, developmental robotics, and active learning, this paper presents the mechanism of Intelligent Adaptive Curiosity, an intrinsic motivation system which pushes a robot towards situations in which it maximizes its learning progress. This drive makes the robot focus on situations which are neither too predictable nor too unpredictable, thus permitting autonomous mental development.The complexity of the robot’s activities autonomously increases and complex developmental sequences self-organize without being constructed in a supervised manner. Two experiments are presented illustrating the stage-like organization emerging with this mechanism. In one of them, a physical robot is placed on a baby play mat with objects that it can learn to manipulate. Experimental results show that the robot first spends time in situations which are easy to learn, then shifts its attention progressively to situations of increasing difficulty, avoiding situations in which nothing can be learned. Finally, these various results are discussed in relation to more complex forms of behavioral organization and data coming from developmental psychology. Key words: Active learning, autonomy, behavior, complexity, curiosity, development, developmental trajectory, epigenetic robotics, intrinsic motivation, learning, reinforcement learning, values

Discovering Communication

What kind of motivation drives child language development? This article presents a computational model and a robotic experiment to articulate the hypothesis that children discover communication as a result of exploring and playing with their environment. The considered robotic agent is intrinsically motivated towards situations in which it optimally progresses in learning. To experience optimal learning progress, it must avoid situations already familiar but also situations where nothing can be learnt. The robot is placed in an environment in which both communicating and non-communicating objects are present. As a consequence of its intrinsic motivation, the robot explores this environment in an organized manner focusing first on non-communicative activities and then discovering the learning potential of certain types of interactive behaviour. In this experiment, the agent ends up being interested by communication through vocal interactions without having a specific drive for communication

Monitoring and Assessing the Use of External Quality Review Organizations to Improve Services for Young Children: A Toolkit for State Medicaid Agencies

Assesses the extent to which states use external quality review organizations in studying the quality of preventive and developmental services for young children enrolled in Medicaid, and provides guidance on determining their scope of work

Schülerbewertungen von Unterricht an weiterführenden Schulen: Welche Faktoren hängen mit der lehrerseitigen Nützlichkeitswahrnehmung von Unterrichtsevaluationen zusammen?

This study builds on and contributes to work about the use of student evaluation of teacher performance. Although many studies have examined multiple forms of teacher evaluation, not much has been written about high school teachers’ perception of the usefulness of evaluations performed anonymously by students. This article provides additional insight by exploring factors contributing to Norwegian high school teachers’ perceptions of the usefulness of evaluations. Structural equation modelling indicates that perceptions of the developmental purposes of the evaluation process and of clear communication from the school leadership, as well as acknowledgement of the students’ ability to evaluate, are associated with teachers’ perceptions of the usefulness of the evaluation. Student ratings are often used for administrative purposes and tend to be underutilized for developmental purposes. Our findings suggest that feedback from student ratings can be useful in improving teaching practices by providing high school teachers with constructive feedback with which to improve the quality of their teaching. (DIPF/Orig.)Die vorliegende Studie leistet einen Beitrag zur Forschung über den Einsatz von Schülerbefragungen zur Unterrichtsevaluation. Wenngleich zahlreiche Studien vielfältige Formen der Lehrerevaluation untersucht haben, ist über die lehrerseitige Nützlichkeitswahrnehmung von anonymen Unterrichtsbewertungen durch Schülerinnen und Schüler wenig bekannt. Der vorliegende Artikel beleuchtet diese Thematik, indem Faktoren für den wahrgenommenen Nutzen von Evaluationen bei Lehrkräften weiterführender Schulen in Norwegen untersucht werden. Strukturgleichungsmodelle deuten darauf hin, dass die Wahrnehmung eines Entwicklungsziels beim Evaluationsprozess, eine klare Kommunikation der Schulleitung sowie die Anerkennung der Beurteilungsfähigkeit von Schülerinnen und Schülern mit der von Lehrkräften wahrgenommenen Nützlichkeit der Evaluation zusammenhängen. Schülerbewertungen dienen oftmals zu administrativen Zwecken und werden hingegen für entwicklungsorientierte Ziele bislang zu wenig genutzt. Unsere Befunde legen nahe, dass Schülerbewertungen einen Nutzen für die Unterrichtsentwicklung an weiterführenden Schulen haben können, indem sie Lehrkräften konstruktive Rückmeldungen zur Verbesserung ihrer Lehrpraxis bereitstellen. (DIPF/Orig.