Three-Dimensional Neurophenotyping of Adult Zebrafish Behavior

The use of adult zebrafish (Danio rerio) in neurobehavioral research is rapidly expanding. The present large-scale study applied the newest video-tracking and data-mining technologies to further examine zebrafish anxiety-like phenotypes. Here, we generated temporal and spatial three-dimensional (3D) reconstructions of zebrafish locomotion, globally assessed behavioral profiles evoked by several anxiogenic and anxiolytic manipulations, mapped individual endpoints to 3D reconstructions, and performed cluster analysis to reconfirm behavioral correlates of high- and low-anxiety states. The application of 3D swim path reconstructions consolidates behavioral data (while increasing data density) and provides a novel way to examine and represent zebrafish behavior. It also enables rapid optimization of video tracking settings to improve quantification of automated parameters, and suggests that spatiotemporal organization of zebrafish swimming activity can be affected by various experimental manipulations in a manner predicted by their anxiolytic or anxiogenic nature. Our approach markedly enhances the power of zebrafish behavioral analyses, providing innovative framework for high-throughput 3D phenotyping of adult zebrafish behavior

Adult zebrafish as a model organism for behavioural genetics

Recent research has demonstrated the suitability of adult zebrafish to model some aspects of complex behaviour. Studies of reward behaviour, learning and memory, aggression, anxiety and sleep strongly suggest that conserved regulatory processes underlie behaviour in zebrafish and mammals. The isolation and molecular analysis of zebrafish behavioural mutants is now starting, allowing the identification of novel behavioural control genes. As a result of this, studies of adult zebrafish are now helping to uncover the genetic pathways and neural circuits that control vertebrate behaviour

Molecular psychiatry of zebrafish

Due to their well-characterized neural development and high genetic homology to mammals, zebrafish (Danio rerio) have emerged as a powerful model organism in the field of biological psychiatry. Here, we discuss the molecular psychiatry of zebrafish, and its implications for translational neuroscience research and modeling central nervous system (CNS) disorders. In particular, we outline recent genetic and technological developments allowing for in vivo examinations, high-throughput screening and whole-brain analyses in larval and adult zebrafish. We also summarize the application of these molecular techniques to the understanding of neuropsychiatric disease, outlining the potential of zebrafish for modeling complex brain disorders, including attention-deficit/hyperactivity disorder (ADHD), aggression, post-traumatic stress and substance abuse. Critically evaluating the advantages and limitations of larval and adult fish tests, we suggest that zebrafish models become a rapidly emerging new field in modern molecular psychiatry research

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

Extension of the primary care research object model (PCROM) as clinical research information model (CRIM) for the “learning healthcare system”

Background: Patient data from general practices is already used for many types of epidemiological research and increasingly, primary care systems to facilitate randomized clinical trials. The EU funded project TRANSFoRm aims to create a “Learning Healthcare System” at a European level that is able to support all types of research using primary care data, to recruit patients and follow patients in clinical studies and to improve diagnosis and therapy. The implementation of such a Learning Healthcare System needs an information model for clinical research (CRIM), as an informational backbone to integrate aspects of primary care with clinical trials and database searches. Methods: Workflow descriptions and corresponding data objects of two clinical use cases (Gastro-Oesophageal Reflux Disease and Type 2 Diabetes) were described in UML activity diagrams. The components of activity diagrams were mapped to information objects of PCROM (Primary Care Research Object Model) and BRIDG (Biomedical Research Integrated Domain Group) and evaluated. The class diagram of PCROM was adapted to comply with workflow descriptions. Results: The suitability of PCROM, a primary care information model already used for clinical trials, to act as an information model for TRANSFoRm was evaluated and resulted in its extension with 14 new information object types, two extensions of existing objects and the introduction of two new high-ranking concepts (CARE area and ENTRY area). No PCROM component was redundant. Our result illustrates that in primary care based research an important but underestimated portion of research activity takes place in the area of care (e.g. patient consultation, screening, recruitment and response to adverse events). The newly introduced CARE area for care-related research activities accounts for this shift and includes Episode of Care and Encounter as two new basic elements. In the ENTRY area different aspects of data collection were combined, including data semantics for observations, assessment activities, intervention activities and patient reporting to enable case report form (CRF) based data collection combined with decision support. Conclusions Research with primary care data needs an extended information model that covers research activities at the care site which are characteristic for primary care based research and the requirements of the complicated data collection processes

Interview with Marilyn K. Speedie

Dr. Marilyn K. Speedie was born and raised in Salem, Oregon. She earned her B.S. in pharmacy in 1970 and Ph.D. in medicinal chemistry and pharmacognosy in 1973, both from Purdue University. Before graduating, she became assistant professor of pharmacognosy at Oregon State University. She then moved, in 1975, to the University of Maryland to become assistant professor of pharmacognosy. Dr. Speedie was promoted to associate professor in 1980 and full professor in 1991. While at the University of Maryland, she also served as chairman of the Department of Biomedicinal Chemistry (1989-1993) and as chairman of the Department of Pharmaceutical Sciences (1993-1995). She then became dean and professor at the University of Minnesota College of Pharmacy, positions she held from 1996 to 2017. In addition to her university commitments, Dr. Speedie served for the American Association of Colleges of Pharmacy as president (2006-2007) and on the board of directors (2005-2008). She also served on the board of directors for the National Institute for Pharmaceutical Technology and Education (2007-2017) and two terms on the board of trustees for the United States Pharmacopeia (2010-2020).Dr. Speedie begins part one of her interview by describing her early life and educational background. She reflects on her undergraduate education at Purdue University, discussing her early experiences working in community pharmacies and her exposure to laboratory research. She briefly discusses her time in graduate school and reflects on her return to Oregon following graduation. She discusses her move to Baltimore, as well as her becoming assistant professor and department head at the University of Maryland. Dr. Speedie then reflects on being recruited to the University of Minnesota. She discusses the appeal of an administrative position, as well as her ongoing interest in teaching and research. She reflects on the chaotic state of the University of Minnesota College of Pharmacy upon her arrival, the mentorship she received, and the openness of the pharmacy profession to women. Dr. Speedie then discusses some of the College’s more famous research projects, including investigations into epilepsy, HIV, and opioids. She then details the founding of the Rural Health School and the impetus behind the Duluth expansion. She concludes by comparing revisions made to the College of Pharmacy curriculum in 1995 and 2013 and by reflecting on faculty responses to those changes. Dr. Speedie begins part two of her interview by offering some additional comments about curricular design and the contributions of specific people to that project. She then reflects on changes in pharmacy practice in the mid 2000s, describing the significance of medication therapy management (MTM), collaborative practice, and pharmaceutical care. She then discusses the changing status of the Pharm.D. degree. Dr. Speedie then reflects on the founding and vision behind the Doctor of Pharmacy Program for Practicing Pharmacists (DP4). She then describes the relationship between academic and practicing pharmacists and discusses Dr. Lawrence Weaver’s role in bridging these groups. She discusses the significance of the Center for Leading Health Care Change and the Academic Health Center (AHC). She briefly reflects on the difficulties involved with connecting the College of Pharmacy and Fairview Health Services and with securing physical space for the College. Dr. Speedie concludes by commenting on her position as the first female dean and on the future of pharmacy enrollments

Exploration of Classification Techniques as a Treatment Decision Support Tool for Patients with Uterine Fibroids

Uterine fibroids are benign growths in the uterus, for which there are several possible treatment options. Patients and physicians generally approach the decision process based on a combination of the patient's degree of discomfort, patient preferences, and physician practice patterns. In this paper, we examine the use of classification algorithms in combination with meta-learning algorithms as a decision support tool to facilitate more systematic fibroid treatment decisions. A model constructed from both Naive Bayes (with Adaboost) and J48 (with bagging) algorithms gave the best results and could be a useful tool to patients making this decision