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PubMed2000

Analysis of cortical flow models in vivo.

Cortical flow, the directed movement of cortical F-actin and cortical organelles, is a basic cellular motility process. Microtubules are thought to somehow direct cortical flow, but whether they do so by stimulating or inhibiting contraction of the cortical actin cytoskeleton is the subject of debate. Treatment of Xenopus oocytes with phorbol 12-myristate 13-acetate (PMA) triggers cortical flow toward the animal pole of the oocyte; this flow is suppressed by microtubules. To determine how this suppression occurs and whether it can control the direction of cortical flow, oocytes were subjected to localized manipulation of either the contractile stimulus (PMA) or microtubules. Localized PMA application resulted in redirection of cortical flow toward the site of application, as judged by movement of cortical pigment granules, cortical F-actin, and cortical myosin-2A. Such redirected flow was accelerated by microtubule depolymerization, showing that the suppression of cortical flow by microtubules is independent of the direction of flow. Direct observation of cortical F-actin by time-lapse confocal analysis in combination with photobleaching showed that cortical flow is driven by contraction of the cortical F-actin network and that microtubules suppress this contraction. The oocyte germinal vesicle serves as a microtubule organizing center in Xenopus oocytes; experimental displacement of the germinal vesicle toward the animal pole resulted in localized flow away from the animal pole. The results show that 1) cortical flow is directed toward areas of localized contraction of the cortical F-actin cytoskeleton; 2) microtubules suppress cortical flow by inhibiting contraction of the cortical F-actin cytoskeleton; and 3) localized, microtubule-dependent suppression of actomyosin-based contraction can control the direction of cortical flow. We discuss these findings in light of current models of cortical flow.

Actins↗

PubMed1996

Personal risk taking and the spread of disease: beyond core groups.

Disease control efforts directed at human immunodeficiency virus are predicated on the need to reduce personal risk behaviors; that approach may not adequately reflect the complicated interplay between personal behaviors and the social setting in which they occur. Efforts to date, including the application of population ecology, the development of the core group hypothesis, and the use of compartment models to describe disease transmission, have aided in understanding the dynamics of transmission and have highlighted the relationship between personal risk taking and population risk. An area for further development is the application of the techniques of social network analysis to infectious disease spread. Initial work suggests that social structure may act as a barrier (or facilitator) in disease transmission and that the epidemiologic impact of a risky act varies with the social setting. The local context for risk behaviors has important implications for the dynamics of transmission.

HIV Infections↗

PubMed1995

Mobilizing a low-income African-American community around tobacco control: a force field analysis.

A statewide tobacco control campaign in California has been highly successful in reducing public exposure to the health hazards of secondhand smoke. Over 250 cities and counties in California have enacted local ordinances to regulate smoking in public places and workplaces. Although low-income people of color are disproportionately affected by the use of tobacco, the issue of regulating secondhand smoke tends to be a lower priority in communities that are confronted by other, more immediately pressing social justice issues, such as high rates of violence and lack of economic opportunity. This article describes the process undertaken by a county health department to mobilize a low-income African American community in a San Francisco Bay Area city to support a local ordinance mandating 100% smoke-free workplaces and restaurants. These efforts are more likely to succeed if health advocates (1) reframe issues in a context that acknowledges the political, economic, and social justice realities and strengths of the community; (2) organize within existing local networks and foster the integration of tobacco issues into the group's existing work; and (3) can defer their own agendas during times of community grieving and healing.

Advertising↗

PubMed2006

[Construction of urban green space ecosystem by using corridor network: a case study in west urban area of Dongying City, Shandong Province].

This paper discussed the ecological significance of urban green corridors network in urban green space ecosystem, analyzed the present status of green space ecosystem in the west urban area of Dongying in Shangdong Province, and figured out the ways of constructing urban green corridors network in this area to strengthen the linkage between its fragmented greenbelts, and between these greenbelts and rural natural environment. Through the construction of this network, the greenbelt area in the west urban area of Dongying would increase 1400 hm2, greenbelt area per capita would increase to 66 m2, and urban and rural greenbelts would be integrated into a whole system to serve the whole city, giving a powerful support to enhance the life quality of local people and the stability of urban ecosystem.

China↗

PubMed1994

Sleeping sickness and the central nervous system.

Chronic African trypanosomiasis is associated with progressive behavioural deficits, for which there is a complex underlying central nervous system (CNS) pathology. This has been extensively studied in man and a range of experimental animals. An initial meningitis, which can occur quite early in the infection, is followed by a breakdown of the choroid plexus, movement of the parasite into certain localized brain areas, and subsequent encephalitis. The encephalitis consists of a chronic, widespread inflammation with perivascular infiltrations of B-cells, plasma cells, inactivated T-cells and macrophages. The blood-brain barrier is damaged and a vasogenic oedema ensues. Astrocytes and microglia become reactive and the cytokine/mediator network is perturbed. The alterations in some of these signalling substances, e.g. the prostaglandins, may induce some of the behavioural changes, e.g. the hypersomnia. The immunopathology in the CNS may be brought about by elevated levels of active substances in the cerebrospinal fluid, caused by parasite infection.

Animals↗

PubMed1997

Brefeldin A differently affects basal and prolactin-stimulated milk protein secretion in lactating rabbit mammary epithelial cells.

When lactating mammary epithelial cells were treated with prolactin in vitro, numerous small vesicles rapidly accumulated in the Golgi area, and secretion of milk proteins increased. The effects of brefeldin A on these intracellular events were investigated. As observed by electron microscopy, stacks of the median Golgi were not altered after incubation in the presence of 50 nM brefeldin A but were dissociated when the drug concentration was > or = 500 nM. Small vesicles did not accumulate in the Golgi area when mammary cells were incubated in medium containing both prolactin and brefeldin A, whatever the concentration of the latter. Immunofluorescence experiments showed that 50 nM brefeldin A did not modify the localization of the CTR 433 median Golgi protein, but it induced redistribution of trans-Golgi network-associated proteins such as TGN38, AP-1 adaptor and clathrin. These effects occurred in the presence of brefeldin A plus prolactin. Pulse-chase experiments showed that brefeldin A concentrations > or = 100 nM induced the intracellular accumulation of milk proteins, provoked the appearance of immature forms of caseins, and inhibited milk protein secretion. In contrast, concentrations of brefeldin A of < or = 50 nM did not affect basal casein secretion but inhibited the secretagogue effect of prolactin. These data show not only that several biochemical events in the transport of milk proteins which are sensitive to different brefeldin A concentrations occur in lactating mammary epithelial cells, but also that it is possible to inhibit a hormonal stimulus in a selective manner, while the machinery responsible for basal secretion is still active.

Animals↗

PubMed2002

Dynamics of brain activation during an explicit word and image recognition task: an electrophysiological study.

Recent brain imaging studies suggest that semantic processing of words and images may share a common neural network, although modality-specific activation can also be observed. Other studies using event-related potentials (ERPs) report that brain responses to words and images may already differ at approximately 150 ms following stimulus presentation. The question thus remains, which differences are due to perceptual categorization processes and which differences are due to the semantic ones? Using ERP recordings and spatio-temporal source localization analysis, we investigated the dynamics of brain activation during a recognition task. The stimuli consisted of a randomized set of verbal (words vs. non-words) and pictorial items (line drawings of objects vs. scrambled drawings). After each stimulus, subjects had to decide whether it corresponds to a recognizable word or objects. ERP map series were first analyzed in terms of segments of quasi-stable map topography using a cluster analysis. This showed that verbal and pictorial stimuli elicited different field patterns in two time segments between approximately 190-400 ms. Before and after this period, map patterns were similar between verbal and pictorial conditions indicating that the same brain structures were engaged during the early and late steps of processing. Source localization analysis of map segments corresponding to the P100 and the N150 components first showed activation of posterior bilateral regions and then of left temporo-posterior areas. During the period differentiating conditions, other patterns of activation, involving mainly left anterior and posterior regions for words and bilateral posterior regions for images, were observed. These findings suggest that, while sharing an initial common network, recognition of verbal and pictorial stimuli subsequently engage different brain regions during time periods generally allocated to the semantic processing of stimuli.

Acoustic Stimulation↗

PubMed2001

Standardization, analytical validation, and quality control of intermediate endpoint biomarkers.

Standardized processes should be used in the identification and development of intermediate endpoint biomarkers (IEB) for the prediction of patient-specific disease outcomes. Using our own experiences, we outline some of our standardized processes. Using computer-assisted image analysis, we developed a new biomarker of genetic instability, termed quantitative nuclear grade (QNG). The QNG biomarker is derived using nuclear images analyzed from the tumor areas of Feulgen-stained 5-microm biopsy or radical prostatectomy tissue sections. From the variances of 41 to 60 different nuclear size, shape, and chromatin organization features, a QNG solution is computed using either logistic regression or artificial neural networks. QNG can then be used as an input for models that solve for a patient-specific probability to accurately predict disease outcomes. Preoperatively, QNG predicted both the pathologic stage and progression of prostate cancer using biopsies (P <0.0001). Postoperatively, QNG proved extremely valuable in the prediction of biochemical progression using radical prostatectomy specimens with more than 10 years of follow-up (P <0.0001). We also demonstrate the identification of novel, differentially expressed, prostate cancer genes using RNA fingerprinting methods and the clinical utility of testing for these genes in both blood and tissue samples. Also illustrated is the improvement of serum biomarker performance by combining molecular forms of PSA with new biomarkers. In conclusion, the development of new IEBs requires planning based upon an understanding of the molecular pathogenesis of disease. IEB selection and clinical evaluation should employ standardized methods of testing and validation, followed by publication. QNG is 1 example of a new, highly predictive, IEB for prostate cancer that has been developed using these processes.

Analysis of Variance↗

PubMed2002

The effects of diphenhydramine and SR142948A on periaqueductal gray neurons and on the interactions between the medial preoptic nucleus and the periaqueductal gray.

The midbrain periaqueductal gray contains both neurotensin type-1 and type-2 receptors. Behavioral studies have shown that the analgesic effect of neurotensin is mediated through its interaction with the type-2 receptors. These receptors specifically bind the type-1 histamine antagonist, levocabastine. Recently, it has been shown that another histamine-1 antagonist, diphenhydramine, blocks the analgesic effect of neurotensin. In addition, it has been shown that a non-peptide neurotensin antagonist, SR142948A, binds to both types of neurotensin receptors and blocks the analgesic effect of exogenously applied neurotensin. Major afferents to the periaqueductal gray arise from the medial preoptic nucleus of the hypothalamus. This region contains neurotensinergic neurons, and the expression of neurotensin mRNA in this region increases following cold-water swim stress that leads to opioid-independent analgesia. The goal of this study was to determine whether the responses of periaqueductal gray neurons to stimulation of the medial preoptic nucleus are modified by local injection of diphenhydramine and SR142948A. Because the cellular basis of the effects of diphenhydramine on periaqueductal gray neurons had not been reported, we also examined the effects of diphenhydramine on the baseline-firing rate and synaptic transmission using in vivo and in vitro methods. The results of the in vitro studies indicate that diphenhydramine concentrations above 500 nM significantly reduce the baseline firing of the periaqueductal gray neurons without a significant effect on the frequency of postsynaptic potentials. At concentrations below 100 nM, diphenhydramine has little effect on the baseline-firing rate but partially blocks the response to neurotensin. The results of the in vivo studies showed similar effects of diphenhydramine. At high concentrations it inhibited periaqueductal gray neurons, but at low concentrations it had no effect on the baseline-firing rate and it blocked the response to neurotensin and to medial preoptic nucleus stimulation. Unlike diphenhydramine, SR142948A had virtually no effect on the baseline-firing rate but blocked the response to neurotensin and to stimulation of the medial preoptic nucleus. It is concluded that: (1) SR142948A, at a dose that completely blocks the effect of exogenously applied neurotensin on periaqueductal gray neurons, has little effect on their baseline-firing rates. (2) Because of its effect on the baseline-firing rate, only low doses of diphenhydramine can be used as an antagonist of the neurotensin analgesic effect. (3) Responses of periaqueductal gray neurons to medial preoptic nucleus stimulation is, in part, mediated by a neurotensinergic network within the periaqueductal gray.

Adamantane↗

PubMed2006

Playing the game on the World Wide Web.

ISSUE ADDRESSED: 'Celebrate - do it Safely' is a project aimed at reducing youth alcohol-related harm on the Central Coast, New South Wales (NSW). The primary focus for 2003 was to use the world wide web and the website www.celebratesafely.com.au to raise awareness and reinforce the message of how to party safely to young people. METHODS: A creative, interactive website was set up to be a local and reliable source of information regarding the risks associated with alcohol misuse. It was supported by a steering committee with diverse representation from key organisations. Content pages and links were developed to ensure access to information and contact details were simple and comprehensive. Topics such as a safe party checklist, safe driving, safe sex and protection from violence were included. Games and competitions emphasised the safe party message with clever actions and graphics created within a virtual party environment. The website was promoted by distribution of postcards throughout the school network. Radio campaigning, plus display of posters and banners throughout the area, raised the profile in the wider community. Key rings were given to young people along with free 'mocktails' to reinforce the message of safe partying. RESULTS: There has been an increase in website hits from 758 in 2002 to more than 65,000 in 2003. Written feedback from young people suggests the content and format is well designed for the target group. CONCLUSIONS: Promoting the message of safe celebration on the world wide web is an effective way of raising awareness in a local community about safe partying.

Adolescent↗

PubMed1992

Peptidergic neurotransmitters in the endocrine hypothalamus.

More than 20 neuropeptides have been localized in the endocrine hypothalamus. They may exert a neurohormonal effect on the pituitary or innervate other neurons (intranuclear, intrahypothalamic or extrahypothalamic) and act as neurotransmitters. Many of the hypothalamic neuropeptides are synthesized as inactive precursors that are activated by proteolysis during axonal transport from the cell body to the synapse. Studies in which the paraventricular nuclei were bilaterally destroyed have shown that the neuroendocrine cells in the hypothalamus show functional plasticity and cells that do not usually make detectable quantities of a particular neuropeptide may be activated to do so. Within the hypothalamic nuclei are dense networks of synaptic connections among neurons synthesizing the same or different neuropeptides. These local circuits may coordinate the activities of peptidergic neurons in a hypothalamic nucleus. Hypothalamic neurons project axons to the median eminence-pituitary stalk and the posterior pituitary, also to nuclei within the hypothalamus and to extrahypothalamic areas such as the lower brainstem. Peptidergic neurons in the hypothalamus can have combined neurohormonal and neurotransmitter activities mediated by axon terminals on portal capillaries and other hypothalamic nuclei. Double labelling immunohistochemistry has been used to demonstrate reciprocal connections between peptidergic neurons in the hypothalamus, such as those synthesizing growth hormone-releasing hormone and somatostatin.

Animals↗

PubMed1996

An unusual route to thermostability disclosed by the comparison of Thermus thermophilus and Escherichia coli inorganic pyrophosphatases.

The structures of Escherichia coli soluble inorganic pyrophosphatase (E-PPase) and Thermus thermophilus soluble inorganic pyrophosphatase (T-PPase) have been compared to find the basis for the superior thermostability of T-PPase. Both enzymes are D3 hexamers and crystallize in the same space group with very similar cell dimensions. Two rather small changes occur in the T-PPase monomer: a systematic removal of Ser residues and insertion of Arg residues, but only in the C-terminal part of the protein, and more long-range ion pairs from the C-terminal helix to the rest of the molecule. Apart from the first five residues, the three-dimensional structures of E-PPase and T-PPase monomers are very similar. The one striking difference, however, is in the oligomeric interactions. In comparison with an E-PPase monomer, each T-PPase monomer is skewed by about 1 A in the xy plane, is 0.3 A closer to the center of the hexamer in the z direction, and is rotated by approximately 7 degrees about its center of gravity. Consequently, there are a number of additional hydrogen bond and ionic interactions, many of which form an interlocking network that covers all of the oligomeric surfaces. The change can also be seen in local distortions of three small loops involved in the oligomeric interfaces. The complex rigid-body motion has the effect that the hexamer is more tightly packed in T-PPase: the amount of surface area buried upon oligomerization increases by 16%. The change is sufficiently large to account for all of the increased thermostability of T-PPase over E-PPase and further supports the idea that bacterial PPases, most active as hexamers or tetramers, achieve a large measure of their stabilization through oligomerization. Rigid-body motions of entire monomers to produce tighter oligomers may be yet another way in which proteins can be made thermophilic.

Amino Acid Sequence↗

PubMed1999

Neurovascular relationships in hippocampal slices: physiological and anatomical studies of mechanisms underlying flow-metabolism coupling in intraparenchymal microvessels.

Experiments were carried out to investigate the functional and anatomical relationships between neuronal elements and cerebral microvessels in 300-350-microm thick coronal hippocampal slices maintained at 33-35 degrees C, obtained from 150-200 g male Wistar rats. Cerebral arterioles (9-22 microm in diameter) were visualized in situ and pre-constricted by 22.0+/-6.6% by the addition of the thromboxane A2 agonist U46619 (75 nM), to the bathing medium. The glutamate agonist N-methyl-D-aspartate (0.01-1 mM) produced a dose-related increase in luminal diameter of pre-constricted vessels. In the presence of 4 microM haemoglobin to scavenge nitric oxide from the extravascular environment of the slice, the increase in diameter evoked by 0.1 mM N-methyl-D-aspartate was significantly reduced from 17.5+/-4.6% to 4.8+/-1.7% indicating that N-methyl-D-aspartate-induced vasodilatation of cerebral microvessels is mediated via a mechanism which involves neuronally-derived nitric oxide. In a parallel anatomical study, beta-nicotinamide adenine dinucleotide phosphate-dependent diaphorase staining was used to reveal the enzyme nitric oxide synthase in vascular endothelium and neurons in slices. A small subpopulation (< 11 cells per slice) of darkly-stained multipolar neurons, 21-32 microm in diameter was observed to give rise to a dense network of fine diaphorase-reactive nerve fibres that ramified throughout the whole of the hippocampus and appeared to come into close apposition with arterioles. Morphometric analysis of the relationship between cerebral microvessels, beta-nicotinamide adenine dinucleotide phosphate, reduced form-dependent diaphorase-reactive neuronal elements and individual pyramidal layer neurons, identified by filling with biocytin, revealed that for a given point on a pyramidal layer neuron, the proximity of the nearest diaphorase-reactive nerve fibre was less than 10 microm, whilst the distance to the nearest arteriole (the smallest functional unit for controlling blood flow) was in excess of 70 microm. Such a distance would probably preclude diffusion of vasoactive metabolites in effective concentrations from the area of increased neuronal activity. We therefore propose that the diaphorase-reactive nerve network constitutes the functional link. It is possible that during periods of increased neuronal activity, spillover of glutamate from synapses may activate the diaphorase-reactive network. Release of nitric oxide from the network in the vicinity of local cerebral arterioles may then produce relaxation of the vascular smooth muscle, enabling increased blood flow into the capillary network supplying the region of increased metabolic activity. This study has shown that the process whereby increases in neuronal activity elicit a local change in cerebral blood flow remains functionally intact in hippocampal slice preparations. Nitric oxide of neuronal origin appears to be involved in mediating the coupling between neurons and cerebral arterioles. Stereological analysis of the relationship between neuronal and vascular elements within hippocampal slices suggested that a small subpopulation of nitric oxide synthase-containing neurons which give rise to a diffuse network of fine nitric oxide synthase-containing nerve fibres that lie in close apposition to cerebral arterioles may provide the anatomical substrate for coupling of blood flow to metabolism.

Animals↗

PubMed1998

A general procedure for locating and analyzing protein-binding sequence motifs in nucleic acids.

In the last decade, two tools, one drawn from information theory and the other from artificial neural networks, have proven particularly useful in many different areas of sequence analysis. The work presented herein indicates that these two approaches can be joined in a general fashion to produce a very powerful search engine that is capable of locating members of a given nucleic acid sequence family in either local or global sequence searches. This program can, in turn, be queried for its definition of the motif under investigation, ranking each base in context for its contribution to membership in the motif family. In principle, the method used can be applied to any binding motif, including both DNA and RNA sequence families, given sufficient family size.

Base Sequence↗

PubMed2000

Functional neuroimaging of visceral sensation.

The use of functional brain imaging techniques has led to considerable advances in our understanding of brain processing of human visceral sensation. The use of complementary techniques such as functional MRI, positron emission tomography, magnetoencephalography, and EEG has led to the identification of a network of brain areas that process visceral sensation. These studies suggest that unlike somatic sensation, which has an intense homuncular representation in the primary somatosensory cortex (SI), visceral sensation is primarily represented in the secondary somatosensory cortex, whereas representation in SI is vague. This difference could account for the poor localization of visceral sensation in comparison with somatic sensation. However, in a manner similar to that of somatic sensation, visceral sensation is represented in the paralimbic and limbic structures such as the insular, anterior cingulate, and prefrontal cortices. These areas are likely to mediate the affective and cognitive components of visceral sensation. Recent studies suggest that negative emotional factors such as fear, and cognitive factors such as attention can modulate the brain processing of visceral sensation in the insular and anterior cingulate cortices. In addition, alterations in the pattern of cortical processing of visceral sensation have been described in patients with functional gastrointestinal pain. It is likely that future research into the factors that modulate the brain processing of visceral sensation in health and disease are likely to improve further our understanding of the pathophysiology of functional visceral pain disorders.

Animals↗

PubMed2007

Phase resetting curves and oscillatory stability in interneurons of rat somatosensory cortex.

Synchronous oscillations in neural activity are found over wide areas of the cortex. Specific populations of interneurons are believed to play a significant role in generating these synchronized oscillations through mutual synaptic and gap-junctional interactions. Little is known, though, about the mechanism of how oscillations are maintained stably by particular types of interneurons and by their local networks. To obtain more insight into this, we measured membrane-potential responses to small current-pulse perturbations during regular firing, to construct phase resetting curves (PRCs) for three types of interneurons: nonpyramidal regular-spiking (NPRS), low-threshold spiking (LTS), and fast-spiking (FS) cells. Within each cell type, both monophasic and biphasic PRCs were observed, but the proportions and sensitivities to perturbation amplitude were clearly correlated to cell type. We then analyzed the experimentally measured PRCs to predict oscillation stability, or firing reliability, of cells for a complex stochastic input, as occurs in vivo. To do this, we used a method from random dynamical system theory to estimate Lyapunov exponents of the simplified phase model on the circle. The results indicated that LTS and NPRS cells have greater oscillatory stability (are more reliably entrained) in small noisy inputs than FS cells, which is consistent with their distinct types of threshold dynamics.

Action Potentials↗

PubMed2003

Brain areas activated in fMRI during self-regulation of slow cortical potentials (SCPs).

In humans, surface-negative slow cortical potentials (SCPs) originating in the apical dendritic layers of the neocortex reflect synchronized depolarization of large groups of neuronal assemblies. They are recorded during states of behavioural or cognitive preparation and during motivational states of apprehension and fear. Surface positive SCPs are thought to indicate reduction of cortical excitation of the underlying neural networks and appear during behavioural inhibition and motivational inertia (e.g. satiety). SCPs at the cortical surface constitute summated population activity of local field potentials (LFPs). SCPs and LFPs may share identical neural substrates. In this study the relationship between negative and positive SCPs and changes in the BOLD signal of the fMRI were examined in ten subjects who were trained to successfully self-regulate their SCPs. FMRI revealed that the generation of negativity (increased cortical excitation) was accompanied by widespread activation in central, pre-frontal, and parietal brain regions as well as the basal ganglia. Positivity (decreased cortical excitation) was associated with widespread deactivations in several cortical sites as well as some activation, primarily in frontal and parietal structures as well as insula and putamen. Regression analyses revealed that cortical positivity was predicted with high accuracy by pallidum and putamen activation and supplementary motor area (SMA) and motor cortex deactivation, while differentiation between cortical negativity and positivity was revealed primarily in parahippocampal regions. These data suggest that negative and positive electrocortical potential shifts in the EEG are related to distinct differences in cerebral activation detected by fMRI and support animal studies showing parallel activations in fMRI and neuroelectric recordings.

Adult↗

PubMed2005

A Bayesian approach to generating tutorial hints in a collaborative medical problem-based learning system.

OBJECTIVES: Today a great many medical schools have turned to a problem-based learning (PBL) approach to teaching. While PBL has many strengths, effective PBL requires the tutor to provide a high degree of personal attention to the students, which is difficult in the current academic environment of increasing demands on faculty time. This paper describes intelligent tutoring in a collaborative medical tutor for PBL. The main contribution of our work is the development of representational techniques and algorithms for generating tutoring hints in PBL group problem solving, as well as the implementation of these techniques in a collaborative intelligent tutoring system, COMET. The system combines concepts from computer-supported collaborative learning with those from intelligent tutoring systems. METHODS AND MATERIALS: The system uses Bayesian networks to model individual student clinical reasoning, as well as that of the group. The prototype system incorporates substantial domain knowledge in the areas of head injury, stroke and heart attack. Tutoring in PBL is particularly challenging since the tutor should provide as little guidance as possible while at the same time not allowing the students to get lost. From studies of PBL sessions at a local medical school, we have identified and implemented eight commonly used hinting strategies. In order to evaluate the appropriateness and quality of the hints generated by our system, we compared the tutoring hints generated by COMET with those of experienced human tutors. We also compared the focus of group activity chosen by COMET with that chosen by human tutors. RESULTS: On average, 74.17% of the human tutors used the same hint as COMET. The most similar human tutor agreed with COMET 83% of the time and the least similar tutor agreed 62% of the time. Our results show that COMET's hints agree with the hints of the majority of the human tutors with a high degree of statistical agreement (McNemar test, p=0.652, kappa=0.773). The focus of group activity chosen by COMET agrees with that chosen by the majority of the human tutors with a high degree of statistical agreement (McNemar test, p=0.774, kappa=0.823). CONCLUSION: Bayesian network clinical reasoning models can be combined with generic tutoring strategies to successfully emulate human tutor hints in group medical PBL.

Artificial Intelligence↗