Mutual inhibition among neural command systems as a possible mechanism for behavioral choice in crayfish

Mutual inhibition among behavioral command systems frequently has been suggested as a possible mechanism for switching between incompatible behaviors. Several neural circuits in crayfish that mediate incompatible behaviors have been found to interact through inhibition; this accounts for increased stimulus threshold of one behavior (e.g., escape tailflip) during performance of others (eating, walking, defense). To determine whether mutual inhibition between command systems can provide a mechanism that produces adaptive behavior, I developed a model crayfish that uses this mechanism to govern its behavioral choices in a simulated world that contains a predator, a shelter, and a food source. The crayfish uses energy that must be replaced by eating while it avoids capture by the predator. The crayfish has seven command systems (FORAGE, EAT, DEFENSE, RETREAT, ESCAPE, SWIM, HIDE) that compete through mutual inhibition for control of its behavior. The model crayfish was found to respond to changing situations by making adaptive behavioral choices at appropriate times. Choice depends on internal and external stimuli, and on recent history, which determines the pattern of those stimuli. The model's responses are unpredictable: small changes in the initial conditions can produce unexpected patterns of behavior that are appropriate alternate responses to the stimulus conditions. Despite this sensitivity, the model is robust; it functions adaptively over a large range of internal and external parameter values.     

New South Wales Nurse Education Project

Abstract: The development of a teaching package for nurse educators on drug and alcohol problems is described and the contents of its 16 modules outlined.     

Predicting Survival after Trauma: a Comparison of TRISS and ASCOT in the Netherlands

Background: Evaluating the performance of a trauma system may be attempted by comparing outcome in different trauma populations. Controlling for injury severity is a necessity for such evaluations. We compare two current models for doing so: the “Trauma and Injury Severity Score” (TRISS) and “A Severity Characterization Of Trauma” (ASCOT). Material and Methods: This study of high-energy trauma victims took place in Leiden, the Netherlands, between 1993 and 1998. Using the Hosmer-Lemeshow (HL) test and receiver operator characteristic (ROC) analysis, the TRISS and ASCOT models were compared for calibration and discrimination. Results: 1,024 patients, with an average Injury Severity Score (ISS) of 13.5, were eligible for inclusion. Blunt trauma was the predominant cause of injuries. Both models gave accurate, though pessimistic, results in predicting the actual number of fatalities (n = 71). The HL test indicated a sufficient fit for the ASCOT model (p = 0.28) and an insufficient fit (p = 0.02) for TRISS. The ROC curves were nearly identical (0.97). Including age as a linear variable, instead of using the current age groups, resulted in an improved discriminative power of the models. Conclusions: The ASCOT model proved superior over TRISS in its accuracy to estimate of survival chances. This difference was most evident for victims with an estimated survival chance of 60–90%. Future national trauma researchers should therefore collect ASCOT data. Improved ASCOT models could be developed, with age as a linear variable. Received: April 25, 2002; revision accepted: September 17, 2002 Correspondence Address Prof. Arie B. van Vugt, MD, PhD, Department of General Surgery and Traumatology, Erasmus MC Rotterdam, Dr. Molewaterplein 40, Postbus 2040, 3000 CA Rotterdam, The Netherlands, Phone (+31/10) 463-5735, Fax -4757, e-mail: vanvugt@hlkd.azr.nl     

Reproductive toxicity studies with oxybutynin hydrochloride

Oxybutynin hydrochloride, an anti-cholinergic/anti-spasmodic agent, was examined for its effect on fertility and peri-post natal development in the rat and its embryotoxic potential in the rat and rabbit. In the rat effects on reproductive performance included a slight increase in the incidence of foetal malformations, extended gestation period and impaired post natal performance of offspring. These findings occurred at dosages clearly associated with maternal toxicity. Oxybutynin hydrochloride did not exert an effect on reproductive processes in the rat at lower dosages or on embryonic and foetal development in the rabbit.     

Multiattribute utility assessment of outcomes of treatment for head and neck cancer.

Good clinical practice is dependent on continuous audit. Most audits of head and neck cancer treatment planning have been subjective, with only 5-year survival rates being considered objectively. Improvements in clinical care require not only measurable goals that relate to patients'' perspectives, but also a means of assessing to what extent those goals have been met. In this context, 5-year survival rates are too crude to be useful, although they remain important for other reasons. Because a simple clinical objective measure of outcome applicable to head and neck cancer is not available, multiattribute assessment techniques were used to develop a clinically based scale for outcomes following treatment for head and neck cancer, with domains centred on social function, pain, physical appearance, eating and speech problems, nausea, donor site problems and shoulder function. Domains were weighted relative to each other; pain (mean weight 85) and social function (89) were considered most important followed by physical appearance (76), eating (76) and speech problems (74) A series of graded statements was constructed within each domain and scaled relative to each other. These components were also combined into an overall scale that will enable objective outcome assessment in this important area of medical care.     

Brevetoxins bind to multiple classes of sites in rat brain synaptosomes.

The brevetoxins (PbTx series), neurotoxins produced by the marine dinoflagellate Ptychodiscus brevis, cause dose-dependent activation of the voltage-sensitive sodium channel (VSSC). Saturation binding studies employing adult rat brain synaptosomes suggest the existence of a high affinity/low capacity (HA/LC) and a second, lower affinity/higher capacity (LA/HC) class of binding site. LIGAND analysis of saxitoxin and brevetoxin saturation binding data yields a statistically identical Bmax for the brevetoxin high affinity/low capacity (HA/LC) site (1.9 +/- 0.98 pmol/mg protein) and for saxitoxin (1.72 +/- 0.78 pmol/mg protein; P less than 0.001). The stoichiometry of HA/LC brevetoxin binding and saxitoxin binding approaches 1:1. Covalent modification of synaptosomes with a brevetoxin photoaffinity probe preferentially blocks the HA/LC binding site. Hill plots of saturation binding data yield a coefficient of 1.0 +/- 0.02, demonstrating a lack of cooperativity between brevetoxin binding site classes. Kd and Bmax for toxin binding are independent of membrane polarity, intimating that the observed low affinity/high capacity (LA/HC) binding characteristics are not due to modification of the HA/LC site, and strongly argue for the presence of multiple brevetoxin binding site classes. Half-maximal binding at the LA/HC site, and strongly argue for the presence of multiple brevetoxin binding site classes. Half-maximal binding at the LA/HC site occurs at concentration ranges for which the brevetoxins allosterically modulate binding of other natural toxins to their specific sites.     

The relationship between genetic and physical distances in the cloned a1-sh2 interval of the Zea mays L. genome.

A 470-kb segment from the long arm of chromosome 3 of Zea mays (inbred LH82), encompassing the a1-sh2 interval, was cloned as a yeast artificial chromosome. Comparison of the sizes of the restriction fragments generated from the cloned DNA fragment and from the DNA isolated from the maize inbred line LH82 established the colinearity of the a1-sh2 interval in these DNAs. By utilizing a chromosome fragmentation technique, a yeast artificial chromosome encompassing the a1-sh2 interval was separately fragmented at the a1 and sh2 loci. Comparison of the sizes of these fragmentation products established the physical distance between the a1 and sh2 loci to be 140 kb. Furthermore, these fragmentation experiments established the physical orientation of the a1 and sh2 genes relative to the maize centromere. The molecular cloning of the contiguous region between the a1 and sh2 loci made it possible to define the relationship between physical and genetic distances over a relatively large segment of the maize genome. In this interval, the relationship between physical and genetic distances is 1560 kb/centimorgan, which compares with 1460 kb/centimorgan for the entire maize genome, and 217 kb/centimorgan for a 1-kb segment within the a1 locus. Therefore, these findings are consistent with the hypothesis that genes per se are preferred sites for meiotic recombination rather than the hypothesis that genes reside in large recombinationally active segments of the genome.     

Recombinations defining centromeric and telomeric borders for the hereditary haemochromatosis locus.

Hereditary haemochromatosis (HFE) is a common inherited disorder, affecting approximately five per thousand white people of northern European descent. Genetic linkage and linkage disequilibrium studies indicate that the disease locus is tightly linked to HLA-A and D6S105. Recombination between HFE and HLA class I loci is known to be rare. We report here two pedigrees in which recombinations telomeric of HLA-A occurred. These recombinant events define new centromeric and telomeric borders for the HFE locus.