Defining the correctness of a diagnosis: differential judgments and expert knowledge.

Approaches that use a simulated patient case to study and assess diagnostic reasoning usually use the correct diagnosis of the case as a measure of success and as an anchor for other measures. Commonly, the correctness of a diagnosis is determined by the judgment of one or more experts. In this study, the consistency of experts' judgments of the correctness of a diagnosis, and the structure of knowledge supporting their judgments, were explored using a card sorting task. Seven expert pediatricians were asked to sort into piles the diagnoses proposed by 119 individuals who had worked through a simulated patient case of Haemophilus influenzae Type B (HIB) meningitis. The 119 individuals had varying experience levels. The expert pediatricians were asked to sort the proposed diagnoses by similarity of content, and then to order the piles based on correctness, relative to the known correct diagnosis (HIB meningitis). Finally, the experts were asked to judge which piles contained correct or incorrect diagnoses. We found that, contrary to previous studies, experts shared a common conceptual framework of the diagnostic domain being considered and were consistent in how they categorized the diagnoses. However, similar to previous studies, the experts differed greatly in their judgment of which diagnoses were correct. This study has important implications for understanding expert knowledge, for scoring performance on simulated or real patient cases, for providing feedback to learners in the clinical setting, and for establishing criteria that define what is correct in studies of diagnostic error and diagnostic reasoning.

Developmental downregulation of P2X3 receptors in motoneurons of the compact formation of the nucleus ambiguus.

Motoneurons of the compact division of the nucleus ambiguus (cNA) are the final output neurons of the swallowing pattern generator. Thus, their normal function is critical to neonatal survival. To explore the role of purinergic signaling in modulating the excitability of these motoneurons during development, immunohistochemical and whole-cell recording techniques were used to characterize expression patterns of ionotropic P2X receptors and the effects of ATP on cNA motoneurons. Medullary slices containing the cNA were prepared from neonatal (P0-4) and juvenile (P15-21) rats. In neonatal cNA motoneurons, local application of 1 mM ATP produced a large (-133 +/- 17 pA; n = 78), desensitizing, inward current that was mimicked by 1 mM alpha,beta meATP and 2meSATP, and inhibited by the P2 antagonist, PPADS (5 microM), and the P2X3 antagonist, A-317481 (0.1-1 mM). In juvenile cNA motoneurons, 1 mM ATP produced negligible currents, while 10 mM ATP produced small (-59 +/- 14 pA; n = 42), primarily non-desensitizing currents. Immunohistochemistry demonstrated that in the neonate, the expression of P2X3 was robust, P2X2 and P2X5 moderate, P2X4 and P2X6 weak, and P2X1 absent. In the juvenile cNA, only low levels of P2X5 and P2X6 labeling were detected. These data indicate that P2X receptors in cNA motoneurons are profoundly downregulated during the first two postnatal weeks, and suggest a role for the purinoceptor system, particularly P2X3 receptors, in the control of esophageal motor networks during early postnatal periods.

Expression of Phox2 transcription factors and induction of the dopaminergic phenotype in primary sensory neurons.

Cell-type-specific transcription factors may regulate phenotypic diversity by conferring selective responsiveness to relatively nonspecific environmental cues. To test this hypothesis, we examined whether the homeodomain transcription factors Phox2a/2b play a role in activity-dependent expression of the dopaminergic phenotype using petrosal ganglion (PG) sensory neurons as a model. The timing of Phox2a/2b expression is precisely correlated with the ability of PG neurons to express the dopamine-synthesizing enzyme, tyrosine hydroxylase (TH), in response to depolarizing stimuli. Phox2a/2b expression is highest at embryonic day 16.5, when virtually all PG neurons exhibit activity-dependent TH induction, and subsequently falls in parallel with the loss of activity-dependent TH induction. Expression is maintained, however, in all dopaminergic neurons. Physiologic stimulation of PG neurons in vivo induces TH expression exclusively in Phox2a/2b(+) cells. Our data suggest that constitutive expression of Phox2a/2b defines the potential of neurons to become dopaminergic in response to membrane depolarization during a critical window of phenotypic plasticity.