The accidental mentor: Australian rural nurses developing supportive relationships in the workplace.

INTRODUCTION: Like the fictional 'Accidental Tourist', an author who does not plan to write about travel, the accidental mentor is an experienced rural nurse who does not plan to be a mentor, and yet assumes that role with new or novice rural nurses as a result of them encountering a critical incident. Accidental mentoring is a short-term relationship that provides support for the new or novice nurse in managing the incident, while maintaining their level of confidence. This article describes the findings from a constructivist grounded theory study that examined Australian rural nurses' experiences of mentoring, including evidence for a new concept of mentoring - accidental mentoring. METHODS: Constructivist grounded theory is a research methodology that focuses on issues of importance for participants around an area of common interest - in this case Australian rural nurse mentoring. In this study, seven participants were interviewed, generating nine transcripts. These were analysed using a process of concurrent data generation and analysis. In addition, the literature regarding rural nurse workforce and mentoring was incorporated as a source of data, using collective frame analysis. RESULTS: Rural nurses live their work, which predisposes them to developing supportive relationships with new or novice rural nurses. Supportive relationships range from preceptoring, to accidental mentoring, mentoring and deep friendship, depending on the level of trust and engagement that is established between the partners and the amount of time they spend together. Accidental mentoring is a short-term relationship that is prompted by experienced rural nurses observing a new or novice rural nurse experiencing a critical incident. CONCLUSIONS: Findings are presented that illustrate a new concept of accidental mentoring not present in the current literature around nurse mentoring. A series of recommendations are included that suggest strategies for improved rural nurse retention as an outcome of recognising and developing such supportive relationships in the workplace. Strategies include: performance review and development processes that account for all forms of supportive relationships conducted in the workplace; recognising the importance of developing supportive relationships and allocating time for these; and continuing professional development designed to meet local needs for developing a culture of support in the workplace.

4-(Diphenylmethyl)-1-[(imino)methyl]piperidines as gastric antisecretory agents.

4-(Diphenylmethyl)-1-piperidinemethanimine (1) is a potent oral gastric antisecretory agent in rats but contains a strong anticholinergic component. Since a nonanticholinergic gastric antisecretory drug would be useful in the treatment of peptic ulcer disease, a program was initiated by us to find such an agent based on 1. Compound 1 contains structural elements common to the anticholinergics atropine and homatropine. Studies on the structure-activity relationships of these compounds and their derivatives have revealed certain modifications that diminish or abolish anticholinergic activity. The application of these modifications to the design of analogues of 1 afforded an antisecretory compound, 4-(diphenylmethyl)-1-[(octylimino)methyl]piperidine (3h, fenoctimine), which exhibited no anticholinergic activity. Fenoctimine is undergoing clinical trial as a gastric antisecretory drug.

Development of a pharmacophore model for histamine H3 receptor antagonists, using the newly developed molecular modeling program SLATE.

New molecular modeling tools were developed to construct a qualitative pharmacophore model for histamine H3 receptor antagonists. The program SLATE superposes ligands assuming optimum hydrogen bond geometry. One or two ligands are allowed to flex in the procedure, thereby enabling the determination of the bioactive conformation of flexible H3 antagonists. In the derived model, four hydrogen-bonding site points and two hydrophobic pockets available for binding antagonists are revealed. The model results in a better understanding of the structure-activity relationships of H3 antagonists. To validate the model, a series of new antagonists was synthesized. The compounds were designed to interact with all four hydrogen-bonding site points and the two hydrophobic pockets simultaneously. These ligands have high H3 receptor affinity, thereby illustrating how the model can be used in the design of new classes of H3 antagonists.

Role of the vagus nerves in anaphylaxis and histamine-induced bronchoconstrictions in guinea-pigs.

1. The effects of vagotomy on the respiratory responses of guinea-pigs to anaphylactic reactions and to intravenous injections of histamine acid phosphate are described.2. In spontaneously breathing guinea-pigs, vagotomy reduced by 50% or more the decreases in total lung conductance (bronchoconstriction) and the decreases in lung compliance, and almost abolished the rapid shallow breathing due to histamine.3. In paralysed, artificially ventilated guinea-pigs, vagotomy reduced by more than 33% the decreases in total lung conductance, but had little effect on the changes in lung compliance due to histamine.4. In paralysed, artificially ventilated guinea-pigs, vagotomy reduced by 75% the decrease in total lung conductance and halved the decrease in lung compliance due to anaphylaxis.5. We conclude that a vagal reflex is mainly responsible for the rapid shallow breathing due to histamine, and partly responsible for the bronchoconstrictions due to histamine and to anaphylaxis in guinea-pigs. We suggest that "lung irritant receptors" in the bronchial epithelium are the afferent end-organs involved.

Three-dimensional hydrogen-bond geometry and probability information from a crystal survey.

An extensive crystal survey of the Cambridge Structural Database has been carried out to provide hydrogen-bond data for use in drug-design strategies. Previous crystal surveys have generated 1D frequency distributions of hydrogen-bond distances and angles, which are not sufficient to model the hydrogen bond as a ligand-receptor interaction. For each hydrogen-bonding group of interest to the drug designer, geometric hydrogen-bond criteria have been derived. The 3D distribution of complementary atoms about each hydrogen-bonding group has been ascertained by dividing the space about each group into bins of equal volume and counting the number of observed hydrogen-bonding contacts in each bin. Finally, the propensity of each group to form a hydrogen bond has been calculated. Together, these data can be used to predict the potential site points with which a ligand could interact and therefore could be used in molecular-similarity studies, pharmacophore query searching of databases, or de novo design algorithms.

Marginally specified generalized linear mixed models: a robust approach.

Longitudinal data modeling is complicated by the necessity to deal appropriately with the correlation between observations made on the same individual. Building on an earlier nonrobust version proposed by Heagerty (1999, Biometrics 55, 688-698), our robust marginally specified generalized linear mixed model (ROBMS-GLMM) provides an effective method for dealing with such data. This model is one of the first to allow both population-averaged and individual-specific inference. As well, it adopts the flexibility and interpretability of generalized linear mixed models for introducing dependence but builds a regression structure for the marginal mean, allowing valid application with time-dependent (exogenous) and time-independent covariates. These new estimators are obtained as solutions of a robustified likelihood equation involving Huber's least favorable distribution and a collection of weights. Huber's least favorable distribution produces estimates that are resistant to certain deviations from the random effects distributional assumptions. Innovative weighting strategies enable the ROBMS-GLMM to perform well when faced with outlying observations both in the response and covariates. We illustrate the methodology with an analysis of a prospective longitudinal study of laryngoscopic endotracheal intubation, a skill that numerous health-care professionals are expected to acquire. The principal goal of our research is to achieve robust inference in longitudinal analyses.

An automated method for predicting the positions of hydrogen-bonding atoms in binding sites.

Hydrogen bonds are the most specific, and therefore predictable of the intermolecular interactions involved in ligand-protein binding. Given the structure of a molecule, it is possible to estimate the positions at which complementary hydrogen-bonding atoms could be found. Crystal-survey data are used in the design of a program, HBMAP, that generates a hydrogen-bond map for any given ligand, which contains all the feasible positions at which a complementary atom could be found. On superposition of ligands, the overlapping regions of their maps represent positions of receptor atoms to which each molecule can bind. The certainty of these positions is increased by the incorporation of a larger number and diversity of molecules. In this work, superposition is achieved using the program HBMATCH, which uses simulated annealing to generate the correspondence between points from the hydrogen-bonding maps of the two molecules. Equivalent matches are distinguished on the basis of their steric similarity. The strategy is tested on a number of ligands for which ligand-protein complexes have been solved crystallographically, which allows validation of the techniques. The receptor atom positions of thermolysin are successfully predicted when the correct superposition is obtained.

Molecular surface-volume and property matching to superpose flexible dissimilar molecules.

Steric complementarity is a prerequisite for ligand-receptor recognition; this implies that drugs with a common receptor binding site should possess sterically similar binding surfaces. This principle is used as the basis for an automatic and unbiased method that superposes molecules. One molecule is rotated and translated to maximize the overlap between the two molecular surface volumes. A fast grid-based method is used to determine the extent of this overlap, and this is optimized using simulated annealing. Matches with high steric similarity scores are then sorted on the basis of both hydrogen-bond and electrostatic similarity between the matched molecules. Flexible molecules are treated as a set of rigid representative conformers. The algorithm has correctly predicted superpositions between a number of paris of molecules, according to crystallographic data from ligands that have been co-crystallized at common enzyme binding sites.

Activity of lung irritant receptors in pulmonary microembolism, anaphylaxis and drug-induced bronchoconstrictions.

1. Lung irritant receptors have been studied in rabbits by recording action potentials from single vagal nerve fibres. Some of the rabbits were bilaterally vagotomized, and some paralysed and artificially ventilated.2. The receptors gave rapidly adapting irregular discharges on inflation and deflation of the lungs. Many were stimulated by insufflation of ammonia vapour into the lungs, and some by passage of a fine catheter into the right bronchial tree. The fibres had conduction velocities in the range 3.6-25.8 m/sec.3. The receptors were strongly stimulated by intravenous injections of histamine acid phosphate, 25-100 mug/kg. The response was considerably reduced by previous injection of isoprenaline which also reduced the bronchoconstriction due to histamine.4. The receptors were stimulated by intravenous injections of isoprenaline, phenyl diguanide and micro-emboli, and by anaphylaxis induced in rabbits previously sensitized to egg albumin.5. The receptor responses could not be closely correlated in size with simultaneous changes in total lung resistance, lung compliance, tidal volume or breathing frequency.6. It is concluded that, in rabbits with intact vagus nerves, lung irritant receptors contribute to the reflex hyperpnoea and bronchoconstriction of the conditions studied.

SLATE: a method for the superposition of flexible ligands.

A novel program for the superposition of flexible molecules, SLATE, is presented. It uses simulated annealing to minimise the difference between the distance matrices calculated from the hydrogen-bonding and aromaticring properties of two ligands. A method for generating a molecular stack using multiple pairwise matches is illustrated. These stacks are used by the program DOH to predict the relative positions of receptor atoms that could form hydrogen bonds to two or more ligands in the dataset. The methodology has been applied to ligands binding to dihydrofolate reductase, thermolysin. H3 histamine receptors, alpha2 adrenoceptors and 5-HT1D receptors. When there are sufficient numbers and diversity of molecules in the dataset, the prediction of receptor-atom positions is applicable to compound design.