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W3MCSim: an online and reconfigurable Monte Carlo simulator for interactive probabilistic/statistical modeling.

We have implemented a Monte Carlo simulator (W3MCSim) as an Internet software tool, primarily for interactive use by students, educators, life and other physical scientists, as well as other practitioners of probabilistic and statistical modeling. Interested users download, install and run W3MCSim by visiting the application website. This application incorporates three freely available Microsoft web technologies, namely the Internet Explorer web browser, the Component Object Model software framework and the JScript web page script interpreter. We define the software architecture here, as a web application model, and show how incorporation of these technologies provides an efficient solution to W3MCSim software deployment. We demonstrate the usability and versatility of this simulator with three distinct tutorial examples: simulating the sum of six-sided dice, estimating intersection frequency in "Buffon's needle problem", and testing an animal experiment design model a priori. We also show how the program components can be reconfigured into other programs.

Computer Simulation↗

Perceptual evaluation of voice quality: review, tutorial, and a framework for future research.

The reliability of listeners' ratings of voice quality is a central issue in voice research because of the clinical primacy of such ratings and because they are the standard against which other measures are evaluated. However, an extensive literature review indicates that both intrarater and interrater reliability fluctuate greatly from study to study. Further, our own data indicate that ratings of vocal roughness vary widely across individual clinicians, with a single voice often receiving nearly the full range of possible ratings. No model or theoretical framework currently exists to explain these variations, although such a model might guide development of efficient, valid, and standardized clinical protocols for voice evaluation. We propose a theoretical framework that attributes variability in ratings to several sources (including listeners' backgrounds and biases, the task used to gather ratings, interactions between listeners and tasks, and random error). This framework may guide development of new clinical voice and speech evaluation protocols, ultimately leading to more reliable perceptual ratings and a better understanding of the perceptual qualities of pathological voices.

Adolescent↗

InSatDb: a microsatellite database of fully sequenced insect genomes.

InSatDb presents an interactive interface to query information regarding microsatellite characteristics per se of five fully sequenced insect genomes (fruit-fly, honeybee, malarial mosquito, red-flour beetle and silkworm). InSatDb allows users to obtain microsatellites annotated with size (in base pairs and repeat units); genomic location (exon, intron, up-stream or transposon); nature (perfect or imperfect); and sequence composition (repeat motif and GC%). One can access microsatellite cluster (compound repeats) information and a list of microsatellites with conserved flanking sequences (microsatellite family or paralogs). InSatDb is complete with the insects information, web links to find details, methodology and a tutorial. A separate 'Analysis' section illustrates the comparative genomic analysis that can be carried out using the output. InSatDb is available at www.cdfd.org.in/insatdb.

Animals↗

Combination of didactic lecture with problem-based learning sessions in physiology teaching in a developing medical college in Nepal.

Physiology teaching as an essential part of medical education faces tremendous criticism regarding curriculum design, methods of implementation, and application of knowledge in clinical practice. In the traditional method of medical education, physiology is taught in the first year and involves little interdisciplinary interaction. The Manipal College of Medical Sciences, Pokhara, Nepal (affiliated with the Kathmandu Univ.) started in 1994 and adopted an integrated curriculum drawn along the lines of the student-centered, problem-based, integrated, community-based, elective-oriented, and systematic (SPICES) medical curriculum. Here, physiology is taught for the first 2 yr of the 4.5-yr Bachelor of Medicine, Bachelor of Surgery course. Methodology adopted is as follows. For a particular topic, objectives are clearly defined and priority content areas are identified. An overview is given in a didactic lecture class to the entire batch of 100 students. Tutorial classes are conducted thereafter with smaller groups of students (25/batch) divided further into five subgroups of five students each. In these sessions, a problem is presented to the students as a focus for learning or as an example of what has just been taught. Each problem was accompanied with relevant questions to streamline the students' thought processes. A tutor is present throughout the session not as an instructor but as a facilitator of the learning process. A questionnaire sought students' opinion on the usefulness of this approach, relevance of the combination of problem-based learning (PBL) sessions and didactic lectures in understanding a particular topic and relating clinical conditions to basic mechanisms, and improvement of performance on the university final examination. The majority of the students opined that the combination of didactic lectures and PBL sessions was definitely beneficial regarding all the above-mentioned aspects of learning. The university results corroborated their opinion. Thus it may be considered that a judicious mixture of didactic lectures and PBL sessions is beneficial as a teaching module of physiology in medical schools.

Clinical Competence↗

PhysioBank, PhysioToolkit, and PhysioNet: components of a new research resource for complex physiologic signals.

The newly inaugurated Research Resource for Complex Physiologic Signals, which was created under the auspices of the National Center for Research Resources of the National Institutes of Health, is intended to stimulate current research and new investigations in the study of cardiovascular and other complex biomedical signals. The resource has 3 interdependent components. PhysioBank is a large and growing archive of well-characterized digital recordings of physiological signals and related data for use by the biomedical research community. It currently includes databases of multiparameter cardiopulmonary, neural, and other biomedical signals from healthy subjects and from patients with a variety of conditions with major public health implications, including life-threatening arrhythmias, congestive heart failure, sleep apnea, neurological disorders, and aging. PhysioToolkit is a library of open-source software for physiological signal processing and analysis, the detection of physiologically significant events using both classic techniques and novel methods based on statistical physics and nonlinear dynamics, the interactive display and characterization of signals, the creation of new databases, the simulation of physiological and other signals, the quantitative evaluation and comparison of analysis methods, and the analysis of nonstationary processes. PhysioNet is an on-line forum for the dissemination and exchange of recorded biomedical signals and open-source software for analyzing them. It provides facilities for the cooperative analysis of data and the evaluation of proposed new algorithms. In addition to providing free electronic access to PhysioBank data and PhysioToolkit software via the World Wide Web (http://www.physionet. org), PhysioNet offers services and training via on-line tutorials to assist users with varying levels of expertise.

Databases as Topic↗

Micropatterned supported membranes as tools for quantitative studies of the immunological synapse.

In living cells, membrane receptors transduce ligand binding into signals that initiate proliferation, specialization, and secretion of signaling molecules. Spatial organization of such receptors regulates signaling in several key immune cell interactions. In the most extensively studied of these, a T cell recognizes membrane-bound antigen presented by another cell, and forms a complex junction called the "immunological synapse" (IS). The importance of spatial organization at the IS and the quantification of its effect on signaling remain controversial topics. Researchers have successfully investigated the IS using lipid bilayers supported on solid substrates as model antigen-presenting membranes. Recent technical developments have enabled micron- and nanometre-scale patterning of supported lipid bilayers (SLBs) and their application to immune cell studies with provocative results, including spatial mutation of the IS. In this tutorial review, we introduce the IS; discuss SLB techniques, including micropatterning; and discuss various methods used to perturb and quantify the IS.

Membranes, Artificial↗

Introducing problem-based learning in physiology in the conventional Indian medical curriculum.

BACKGROUND: Problem-based learning (PBL) is a widely acclaimed student-centred learning method. However, there are few reports of its use in the traditional lecture-practical-tutorial model of learning. We used PBL for teaching one module of Physiology to first-year medical undergraduate students who had no prior exposure to PBL. METHODS: One hundred first-year medical undergraduates enrolled in a medical college, which follows the traditional teaching-learning methods, participated in the exercise. The scheduled classes on 'Physiology of the thyroid gland' were converted into a PBL block to be covered over a week. An orientation of the teachers and students to PBL was done, clinical cases selected and tutor guides prepared before the actual PBL week. During the PBL week, students were exposed to small group discussions and Interactive resource sessions, and were given time for self-study. The PBL week concluded with a review session and evaluation of the PBL block using questionnaires. RESULTS: A comparison of the pre- and post-PBL questionnaire showed a clear preference for PBL over the conventional curriculum for the interactive resource sessions and group discussions. Both students and teachers found PBL rewarding. CONCLUSION: Implementation of PBL is feasible even in a traditional set-up despite limited resources, rigid time schedules and little interaction among various disciplines. We hope our experience would encourage other teachers to introduce appropriately modified PBL in their ongoing curriculum.

Education, Medical, Undergraduate↗

[E-learning in the education and training of physicians. Methods, results, evaluation].

E-learning has been established in the education and training of physicians in various types: linear sequential and hyper-textual forms of multimedia presentations and texts, tutorial systems and simulations. Case-based e-learning systems are of special importance in medicine because they allow for mediation of process and practical knowledge by presentation of authentic medical cases in a simulated environment. The integration into the medical education and advanced professional training is crucial for the long-term success of e-learning; in case-based systems this can be accomplished by blended learning approaches which combine elements of traditional teaching with e-learning. Learning management systems (LMS) support integration of traditional teaching and e-learning by serving as an organizational platform for content of teaching. Further, they provide means of communication for trainers and trainees, authoring tools, interactive components, course management and role-based sharing concept. The dissemination of e-learning can be fostered by attention to requirements and user analysis, early adoption to organizational structures, curricular integration and continuous cooperation with students. Summarized, didactic and organizational aspects determine the success of our own e-learning offers as well as they influence the general further development of e-learning more than technical features.

Computer-Assisted Instruction↗

Cell++--simulating biochemical pathways.

MOTIVATION: With the generation of a wealth of information, detailing cellular components, their functions and interactions, there is a growing need for the development of new computational tools capable of interpreting these data within spatial and dynamic contexts. Here, we introduce Cell++, a novel stochastic simulation environment with the capacity to study a wide variety of biochemical processes within a spatial context. RESULTS: Focusing on three case studies, we highlight the potential impact of spatial organization in the evolution and engineering of signaling and metabolic pathways. In addition to altering signaling and metabolic efficiency, simulations also demonstrated features consistent with the phenomenon of metabolic channeling. AVAILABILITY: Cell++ is licensed under the GNU general public license (GPL) and has been successfully implemented under Linux and IRIX operating systems. Source code together with a simple tutorial is available at http://www.compsysbio.org/CellSim/.

Biochemistry↗

Helping family physicians improve their cardiac auscultation skills with an interactive CD-ROM.

INTRODUCTION: There have been few studies of the cardiac auscultation skills of residents and family physicians. This study assessed a group of family physicians' cardiac auscultation skills and use of a computerized self-instructional program to improve these skills. METHODS: Forty-two volunteer family physicians participated in an initial assessment of cardiac auscultation skills using test recordings of 12 common heart sounds. They were provided with a CD-ROM instructional program and were asked to devote 15 hours of self-study to the program and to return in 9 months for reassessment. RESULTS: The 42 family physicians in the initial assessment identified 39% of the heart sounds. Twenty-one returned for reassessment and showed significant improvement. Their initial mean score was 4.3 of 12 (35%), and their final mean score was 8.0 of 12 (67%). They found the CD-ROM program to be a valuable resource. The feature most liked was the unlimited opportunity to review sounds, cases, and tutorials. Most frequent problems related to computer access or skills. Eleven respondents reported using the program to resolve patient problems in their clinical practices. DISCUSSION: The cardiac auscultation skills of a group of volunteer family physicians showed low initial scores that improved significantly after self-study with a CD-ROM instructional program. The program was a valuable self-instructional aid, and physicians used it as a resource in clinical practice. However, only 50% of the initial group completed the self-study and returned for final assessment. Providing more support and assistance in the initial phase, especially with computer use, may enable completion of similar computerized self-study programs.

CD-ROM↗

Human papillomavirus. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Cervical squamous cell carcinomas, adenocarcinomas and their precursors are caused by the human papillomavirus (HPV). Although HPV appears to be essential to the transformation of these epithelial cells, it is not sufficient, and a variety of cofactors and molecular events must take place between when an HPV infection occurs and a cervical cancer or its precursor develops. This review examines the data supporting these contentions, briefly outlines the molecular events that occur, considers the epidemiology and natural history of the disease, and details the implications of using HPV detection and typing in both clinical management and population-based screening programs. CONSENSUS POSITION: 1. Based on the available molecular, clinical and epidemiologic data, a subset of HPVs are unequivocally the etiologic agents for cervical cancers and their precursors. 2. Different mucosotropic HPVs have varying neoplastic potential. However, the great majority of cervical HPVs have oncogenic potential. Since oncogenic HPV-induced epithelial transformation to a high grade lesion or cancer is rare relative to the rate of infection, the term high risk is discouraged. 3. HPV's interaction with host cells has two principal biologic consequences: a) All anogenital HPVs induce low grade squamous lesions, which are the morphologic correlate of a productive infection. b) Rarely, HPVs induce a proliferative epithelial phenotype that pathologists recognize as a high grade lesion and that is the proximate cytohistologic precursor of invasive cervical carcinoma. 4. HPV biology and issues of practical clinical management should be reflected in the classification systems used for cytologic and histologic diagnosis. ONGOING ISSUES: The molecular identification of HPVs (HPV testing) potentially may be very useful for primary screening or secondary triage of patients with certain lesions. However, the technology available to the practicing clinician is still evolving. Optimization of type spectrum, sensitivity, specificity and ease of use is under development. Data regarding these factors as well as a clear cost benefit analysis are sparse or pending in several large trials. Until such data are available, caution in clinical implementation of HPV testing is warranted.

Adenocarcinoma↗

Effects of tutor expertise on student performance in relation to prior knowledge and level of curricular structure.

PURPOSE: To test whether there are effects of tutor expertise on student performance under conditions of curricular materials that have low or high levels of structure and that are poorly or well matched to students' levels of prior knowledge. METHOD: The study was conducted in 1994-95 at the medical school of the University of Limburg. The data set used for analysis included 135 tutorial groups (with ten to 12 students per group), 119 tutors (each running only one group per unit), and 15 units in four curriculum years. The analysis was conducted at the level of tutorial groups since a tutor's level of expertise might differ for distinct units. Tutors were asked to judge their levels of expertise related to the cases discussed, based on which a distinction was made between expert and non-expert tutors. The degrees of structure of curricular materials and students' levels of prior knowledge were rated by the students. Using analyses of variance, students' scores on end-of-unit tests (each with about 150 true-false items) were compared for groups led by expert and non-expert tutors under conditions of low and high levels of structure and low and high levels of prior knowledge. RESULTS: No difference was found between the test scores of groups led by expert and non-expert tutors. The interaction effects between expertise and structure and expertise and prior knowledge also turned out to be not statistically significant. CONCLUSION: The results suggest that expert tutors do not compensate for lack of curricular structure or students' lack of prior knowledge. This finding is not consistent with that of a recent study that expert tutors do compensate for lack of structure and lack of prior knowledge. This discrepancy may be accounted for by a much smaller range within which the structuredness of the curriculum and students' levels of prior knowledge varied in the present study compared with the previous study. An implication might be that faculty should put their efforts into designing structured curricula that are well matched to students' levels of prior knowledge instead of selecting hyper-expert tutors.

Curriculum↗

[An example of simulation for a better understanding of PK/PD relationship of antibiotics].

The interpretation of PK/PD indices is specific to each class of antibiotics. In order to illustrate this, we developed a multidisciplinary tutorial program based on simulation of clinical cases. Three drugs were included in this software: tobramycin, vancomycin and azithromycin. From the dosage regimen proposed by the user, the model simulates a plotting of antibiotic plasma concentrations vs. time (tobramycin, vancomycin and azithromycin) and tissue concentrations (azithromycin). Peak and trough concentrations are calculated at steady-state. A commentary is provided to evaluate the efficacy of treatment and to assist the user in improving his prescription of tobramycin or vancomycin. T(> MIC) (time the concentration remains above the MIC) and AUC(24) (area under the concentration-time curve) are calculated in plasma and tissues for azithromycin. In order to create a link between theoretical pharmacokinetics and clinical practice, we propose this model as a simulation of antibiotic monitoring. We put the emphasis on interactivity and simulation, leading to applied reasoning and decision making. It illustrates (i) the influence of pharmacokinetic parameters, location of infection and bactericidal kinetics on the use of three different classes of antibiotics, (ii) the role of route of administration, dosing and intervals between administrations on therapeutic response and (iii) the influence of erratic administrations on clinical efficacy.

Anti-Bacterial Agents↗

Teaching sexual history taking to health care professionals in primary care.

OBJECTIVES: Although it is accepted that history taking is central to correct diagnosis, little work has been undertaken on the development of sexual history taking, particularly in a primary care context where sexual health may not occur to the patient. Embarrassment is recognized as one major problem. This paper reports on a series of teaching interventions designed to help primary health care professionals (doctors and nurses) to identify and deal effectively with sexual health issues in the consultation. METHODS: 141 participants took part in nine different courses, with 114 returning evaluations. All courses involved tutorial teaching on clinical and ethicolegal issues and role play with trained professional role-players; some involved video-based dramatizations to particularize principles in context. During role play sessions, which were followed by detailed, contextualized feedback, clinical issues, attitudinal issues (e.g. articulating a sense of personal embarrassment, and the risk of stereotyping), and ethicolegal issues were all discussed, as were examples of words and phrases which participants were invited to try out. OUTCOMES: The overall quality of the courses was rated by participants, on average, at 89.95 (maximum 100), and the relevance of the topic at 91.40. Free text comments centred on the power of the training as a consciousness raiser, on the need to alter communication strategies, the need to change existing clinical practice and the value of role play as a methodology. Interactive courses on sexual health are highly acceptable to participants.

Clinical Competence↗

The applications of capture-recapture models to epidemiological data.

Capture-recapture methodology, originally developed for estimating demographic parameters of animal populations, has been applied to human populations. This tutorial reviews various closed capture-recapture models which are applicable to ascertainment data for estimating the size of a target population based on several incomplete lists of individuals. Most epidemiological approaches merging different lists and eliminating duplicate cases are likely to be biased downwards. That is, the final merged list misses those who are in the population but were not ascertained in any of the lists. If there are no matching errors, then the duplicate information collected from a capture-recapture experiment can be used to estimate the number of missed under proper assumptions. Three approaches and their associated estimation procedures are introduced: ecological models; log-linear models, and the sample coverage approach. Each approach has its unique way of incorporating two types of source dependencies: local (list) dependence and dependence due to heterogeneity. An interactive program, CARE (for capture-recapture) developed by the authors is demonstrated using four real data sets. One set of data deals with infection by the acute hepatitis A virus in an outbreak in Taiwan; the other three sets are ascertainment data on diabetes, spina bifida and infants' congenital anomaly discussed in the literature. These data sets provide examples to show the usefulness of the capture-recapture method in correcting for under-ascertainment. The limitations of the methodology and some cautionary remarks are also discussed.

Adult↗

On the relationship between group functioning and study success in problem-based learning.

INTRODUCTION: In problem-based learning (PBL), discussion in the tutorial group plays a central role in stimulating student learning. Problems are the principal input for stimulating discussion. The quality of discussion is assumed to influence student learning and, in the end, study success. AIMS: To investigate the relationships between aspects of group functioning and study success. METHODS: First-year medical students (n = 116), forming 12 PBL groups, completed a 21-item questionnaire on various aspects of a PBL session. At the end of the unit, a course examination was administered. Scales were constructed and reliability analyses conducted. RESULTS: Group functioning and case quality were strongly correlated with students' grades in a course examination. Further, students' perceptions of group functioning, case quality and the quality of their own contribution were linked strongly with each other. CONCLUSIONS: Group functioning, case quality and study success are associated with each other in PBL. The interaction between these aspects of PBL in promoting learning calls for further investigation.

Adult↗

Thermoregulatory responses to RF energy absorption.

This white paper combines a tutorial on the fundamentals of thermoregulation with a review of the current literature concerned with physiological thermoregulatory responses of humans and laboratory animals in the presence of radio frequency (RF) and microwave fields. The ultimate goal of research involving whole body RF exposure of intact organisms is the prediction of effects of such exposure on human beings. Most of the published research on physiological thermoregulation has been conducted on laboratory animals, with a heavy emphasis on laboratory rodents. Because their physiological heat loss mechanisms are limited, these small animals are very poor models for human beings. Basic information about the thermoregulatory capabilities of animal models relative to human capability is essential for the appropriate evaluation and extrapolation of animal data to humans. In general, reliance on data collected on humans and nonhuman primates, however fragmentary, yields a more accurate understanding of how RF fields interact with humans. Such data are featured in this review, including data from both clinic and laboratory. Featured topics include thermal sensation, human RF overexposures, exposures attending magnetic resonance imaging (MRI), predictions based on simulation models, and laboratory studies of human volunteers. Supporting data from animal studies include the thermoregulatory profile, response thresholds, physiological responses of heat production and heat loss, intense or prolonged exposure, RF effects on early development, circadian variation, and additive drug-microwave interactions. The conclusion is inescapable that humans demonstrate far superior thermoregulatory ability over other tested organisms during RF exposure at, or even above current human exposure guidelines.

Animals↗

Taxonomic colouring of phylogenetic trees of protein sequences.

BACKGROUND: Phylogenetic analyses of protein families are used to define the evolutionary relationships between homologous proteins. The interpretation of protein-sequence phylogenetic trees requires the examination of the taxonomic properties of the species associated to those sequences. However, there is no online tool to facilitate this interpretation, for example, by automatically attaching taxonomic information to the nodes of a tree, or by interactively colouring the branches of a tree according to any combination of taxonomic divisions. This is especially problematic if the tree contains on the order of hundreds of sequences, which, given the accelerated increase in the size of the protein sequence databases, is a situation that is becoming common. RESULTS: We have developed PhyloView, a web based tool for colouring phylogenetic trees upon arbitrary taxonomic properties of the species represented in a protein sequence phylogenetic tree. Provided that the tree contains SwissProt, SpTrembl, or GenBank protein identifiers, the tool retrieves the taxonomic information from the corresponding database. A colour picker displays a summary of the findings and allows the user to associate colours to the leaves of the tree according to any number of taxonomic partitions. Then, the colours are propagated to the branches of the tree. CONCLUSION: PhyloView can be used at http://www.ogic.ca/projects/phyloview/. A tutorial, the software with documentation, and GPL licensed source code, can be accessed at the same web address.

Algorithms↗