Ventilatory responses of healthy subjects to intravenous combinations of morphine and oxycodone under imposed hypercapnic and hypoxaemic conditions

Aims Previous isobolographic analysis revealed that coadministration of morphine and oxycodone produces synergistic antinociception in laboratory rodents. As both opioids can produce ventilatory depression, this study was designed to determine whether their ventilatory effects were synergistic when coadministered to healthy human subjects. Methods A placebo-controlled, randomized, crossover study was performed in 12 male volunteers. Ventilatory responses to hypoxaemia and hypercapnia were determined from 1-h intravenous infusions of saline ('placebo'), 15 mg morphine sulphate (M), 15 mg oxycodone hydrochloride (O), and their combination in the dose ratios of 1 : 2, 1 : 1, 2 : 1. Drug and metabolite concentrations in serial peripheral venous blood samples were measured by high-performance liquid chromatography-MS/MS. Results 'Placebo' treatment was without significant ventilatory effects. There were no systematic differences between active drug treatments on either the slopes or intercepts of the hypoxaemic and hypercapnia ventilation responses. During drug treatment, the mean minute ventilation at PETCO2 = 55 mmHg (V-E55) decreased to 74% of the subjects' before treatment values (95% confidence interval 62, 87), 68% (57, 80), 69% (59, 79), 68% (63, 73), and 61% (52, 69) for M15, M10/O5, M7.5/O7.5, M5/O10 and O15, respectively. Recovery was more prolonged with increasing oxycodone doses, corresponding to its greater potency and lower clearance compared with morphine. Conclusions Although adverse ventilatory effects of these drugs were found as expected, no unexpected or disproportionate effects of any of the morphine and oxycodone treatments were found that might impede their use in combination for pain management.

GANN: Genetic algorithm neural networks for the detection of conserved combinations of features in DNA

Background: The multitude of motif detection algorithms developed to date have largely focused on the detection of patterns in primary sequence. Since sequence-dependent DNA structure and flexibility may also play a role in protein-DNA interactions, the simultaneous exploration of sequence-and structure-based hypotheses about the composition of binding sites and the ordering of features in a regulatory region should be considered as well. The consideration of structural features requires the development of new detection tools that can deal with data types other than primary sequence. Results: GANN ( available at http://bioinformatics.org.au/gann) is a machine learning tool for the detection of conserved features in DNA. The software suite contains programs to extract different regions of genomic DNA from flat files and convert these sequences to indices that reflect sequence and structural composition or the presence of specific protein binding sites. The machine learning component allows the classification of different types of sequences based on subsamples of these indices, and can identify the best combinations of indices and machine learning architecture for sequence discrimination. Another key feature of GANN is the replicated splitting of data into training and test sets, and the implementation of negative controls. In validation experiments, GANN successfully merged important sequence and structural features to yield good predictive models for synthetic and real regulatory regions. Conclusion: GANN is a flexible tool that can search through large sets of sequence and structural feature combinations to identify those that best characterize a set of sequences.

Grammatical sensitivity: Its origins and potential contribution to early word reading skill

A three-phase longitudinal study examined the origins of grammatical sensitivity and its usefulness as a predictor of early word-level reading. At about 4 years of age, children were given a range of language and cognitive tests. One year later, the children were given a further series of language and cognitive tests, this time including grammatical sensitivity, phonological sensitivity, and nonword repetition. Another year later, word-level reading achievement was assessed. Overall, grammatical sensitivity and phonological sensitivity were more firmly grounded in earlier language ability than in cognitive ability. Phonological sensitivity and nonword repetition showed reliable predictive associations with subsequent word reading skills. Grammatical sensitivity did not. (c) 2005 Elsevier Inc. All rights reserved.

Neuromuscular-skeletal constraints on the acquisition of skill in a discrete torque production task

The organisation of the human neuromuscular-skeletal system allows an extremely wide variety of actions to be performed, often with great dexterity. Adaptations associated with skill acquisition occur at all levels of the neuromuscular-skeletal system although all neural adaptations are inevitably constrained by the organisation of the actuating apparatus (muscles and bones). We quantified the extent to which skill acquisition in an isometric task set is influenced by the mechanical properties of the muscles used to produce the required actions. Initial performance was greatly dependent upon the specific combination of torques required in each variant of the experimental task. Five consecutive days of practice improved the performance to a similar degree across eight actions despite differences in the torques required about the elbow and forearm. The proportional improvement in performance was also similar when the actions were performed at either 20 or 40% of participants' maximum voluntary torque capacity. The skill acquired during practice was successfully extrapolated to variants of the task requiring more torque than that required during practice. We conclude that while the extent to which skill can be acquired in isometric actions is independent of the specific combination of joint torques required for target acquisition, the nature of the kinetic adaptations leading to the performance improvement in isometric actions is influenced by the neural and mechanical properties of the actuating muscles.

Employee recognition as a management skill: Considering the effects of team efficacy

Recognising and rewarding good performance is an important managerial skill as it is vital for employee motivadon. To gain a better understanding on how recognidon exerts its infiuence, the purpose of the current study is twofold: firsdy, to invesdgate whether recognition (or the lack of it) is a relevant issue with the staff of a large Australian pharmacy. Secondly, to our best knowledge the present study is the first to shed light onto the nature and funcdon of recognidon by invesdgadng its underlying processes. Drawing from goal setdng, social cognidve and attribution theory, a model in which recognidon from the manger predicts employee outcomes is developed. It predicts that managerial recognidon will infiuence employee well-being direcdy and indirecdy by its impact on team efficacy. Data from the pharmacy staff is qualitadvely and quandtadvely analysed. Qualitadve analysis suggests that recognidon is a major modvator for the pharmacy staff. Addidonally it is found that employees who receive recognidon from their manager have posidve percepdons about their work groups, and in turn experience high levels of well-being. Implicadons and Hmitadons of the current study, as well as avenues for future research are discussed.

A multilevel analysis of BIS sensitivity and negative affect during skill acquisition

This Study examined the muldlevel reladonships among negadve affect Behavioural Inhibidon System (BIS) Sensidvit)' and performance. It also invesdgated whether the reladonship among these variables changed across pracdce. Pardcipants performed muldple trials of a simulated air traffic control task, A single measure of BIS was taken before pracdce, while negadve affect and performance were measured at repeated intervals. As expected, negadve affect was detrimental to performance at both a between-person and withinperson level, BIS was also found to be detrimental to performance. Contrary' to expectadons, the reladonship between BIS and performance was not mediated by overall levels of negadve affect. As predicted, the effects of overall levels of negadve affect and BIS strengthened across pracdce as pardcipants gained task knowledge and skill. The findings of this study are interpreted using resource allocadon theor}' and the implicadons for skiU acquisidon discussed.