How is leflunomide prescribed and used in Australia? analysis of prescribing and adverse effect reporting

Purpose To evaluate the use of leflunomide in the Australian community since introduction in 2000. Trends in adverse drug reaction (ADR) reporting were also studied. Methods Annual Australian prescription and dispensing statistics were analysed. Drug utilisation was estimated as defined daily doses (DDD)/1000 inhabitants/day. ADR data from the Therapeutic Goods Administration's Adverse Drug Reactions Advisory Committee (ADRAC) national monitoring system were compared with the World Health Organisation (WHO) Vigibase records. Results Leflunomide use in Australia (dispensing data) increased from 0.2 in 2000 to 0.4 DDD/1000 inhabitants/day in 2002. The same overall pattern was observed in the 'authority to prescribe' data. From 2000-2002, prescribing of the starter pack (3 x 100 mg loading dose plus 30 x 20 mg tablets) declined (down 74%); likewise for the 20mg (30 tablets) pack. Gradual increases were noted for the 10 mg (30 tablets) pack (up 40%). Approximately 135 reports, detailing about 370 individual ADR, were generated annually. Gastro-intestinal disorders predominated, accounting for 24% of reactions reported to ADRAC. Skin and appendages disorders constituted 14% of reported reactions. Deaths in leflunomide users were attributed to a combination of haematological and gastro-intestinal complications, but it was not possible to ascertain other medication usage or contributing factors. Trends observed with the ADRAC reports were consistent with the WHO database. Conclusions Leflunomide was the first registered DMARD in Australia in over a decade and its use has increased within the community. The ADR reports might have contributed to Australian rheumatologists gradually abandoning loading patients with high doses of leflunomide in favour of starting therapy at lower doses. Copyright (c) 2006 John Wiley & Sons, Ltd.

Interpretation of the temperature dependence of equilibrium and rate constants

The objective of this review is to draw attention to potential pitfalls in attempts to glean mechanistic information from the magnitudes of standard enthalpies and entropies derived from the temperature dependence of equilibrium and rate constants for protein interactions. Problems arise because the minimalist model that suffices to describe the energy differences between initial and final states usually comprises a set of linked equilibria, each of which is characterized by its own energetics. For example, because the overall standard enthalpy is a composite of those individual values, a positive magnitude for AHO can still arise despite all reactions within the subset being characterized by negative enthalpy changes: designation of the reaction as being entropy driven is thus equivocal. An experimenter must always bear in mind the fact that any mechanistic interpretation of the magnitudes of thermodynamic parameters refers to the reaction model rather than the experimental system For the same reason there is little point in subjecting the temperature dependence of rate constants for protein interactions to transition-state analysis. If comparisons with reported values of standard enthalpy and entropy of activation are needed, they are readily calculated from the empirical Arrhenius parameters. Copyright (c) 2006 John Wiley & Sons, Ltd.

Iron (Fe) bioavailability and the distribution of anti-Fe nutrition biochemicals in the unpolished, and bran fraction of five rice gei polished grain riotypes

Iron (Fe) bioavailability in unpolished, polished grain and bran fraction of five rice genotypes with a range of Fe contents was measured by in vitro digestion and cultured Caco-2 cells of cooked grain. There was a significant difference in Fe bioavailability among the five rice genotypes tested, in both the unpolished and polished grain. The range of Fe bioavailability variation in polished rice was much wider than that of unpolished, suggesting the importance of using Fe levels and bioavailability in polished rice grain as the basis for selecting high-Fe rice cultivars for both agronomic and breeding purposes. Milling and polishing the grain to produce polished (or white) rice increased Fe bioavailability in all genotypes. Iron bioavailability in polished rice was high in the UBON2 and Nishiki, intermediate in both IR68144 and KDML105, and low in CMU122. All genotypes had low bioavailability of Fe in bran fraction compared to unpolished and polished grain, except in CMU122. CMU122 contained the lowest level of bioavailable Fe in unpolished and polished grain and bran, because of the dark purple pericarp colored grain and associated tannin content. The level of bioavailable Fe was not significantly correlated with grain Fe concentration or grain phytate levels among these five genotypes tested. The negative relationship between Fe bioavailability and the levels of total extractable phenol was only observed in unpolished (r = -0.83**) and bran fraction (r = -0.50*). The present results suggested that total extractable phenol and tannin contents could also contribute to lowering bioavailability of Fe in rice grain, in addition to phytate. (c) 2006 Society of Chemical Industry

NMR of conotoxins: structural features and an analysis of chemical shifts of post-translationally modified amino acids

Conotoxins are small conformationally constrained peptides found in the venom of marine snails of the genus Conus. They are usually cysteine rich and frequently contain a high degree of post-translational modifications such as C-terminal amidation, hydroxylation, carboxylation, bromination, epimerisation and glycosylation. Here we review the role of NMR in determining the three-dimensional structures of conotoxins and also provide a compilation and analysis of H-1 and C-13 chemical shifts of post-translationally modified amino acids and compare them with data from common amino acids. This analysis provides a reference source for chemical shifts of post-translationally modified amino acids. Copyright (C) 2006 John Wiley & Sons, Ltd.

Total and ileal digestible tryptophan contents of feedstuffs for broiler chickens

Reliable values of total and digestible tryptophan in components of feed formulation matrices are needed because tryptophan is often the third limiting amino acid in practical poultry diets. However, tryptophan is oxidatively destroyed during acid hydrolysis in routine amino acid analysis and its determination requires a separate analytical procedure. The variability in contents and apparent ileal digestibility for 6-week-old broiler chickens of tryptophan in 74 samples representing 24 feedstuffs are presented in this paper. The average ileal tryptophan digestibility coefficient in wheat was 0.83, in sorghum and triticale 0.75, maize 0.71, soybean meal 0.84, sunflower meal 0.81, canola meal 0.78 and cottonseed meal 0.75. Among the grain legumes, tryptophan in lupins was better digested than that in chickpeas, fababeans and field peas. Among the animal protein meals, the tryptophan digestibility coefficients in fish meal (0.77) and blood meal (0.84) were substantially higher than those in meat meal (0.64), meat-and-bone meal (0.63) and feather meal (0.52). Marked variations in tryptophan digestibility were also observed among samples of fish meal, meat-and-bone meal and meat meal, highlighting significant batch-to-batch differences. For most feedstuffs, considerable variability was observed in the tryptophan concentrations, but such variations were not reflected in digestibility coefficients. (c) 2006 Society of Chemical Industry.

Differentiation between and within groups: The influence of individualist and collectivist group norms

The power of individualist and collectivist group norms to influence intergroup and inter-individual differentiation was examined in three studies. Study I revealed that intergroup differentiation was lower when group norms prescribed individualism than when they prescribed collectivism. However inter-individual differentiation was higher when group norms endorsed individualism than when they promoted collectivism. In Studies 2 and 3 we found evidence for the moderating effect of group salience on the relationship between norms and differentiation. Specifically, the effect that individualist group norms reduced intergroup differentiation but enhanced inter-individual differentiation was more pronounced when group salience was high rather than low. This finding demonstrates that conformity to a group norm prescribing individualism influences the manner in which positive differentiation is expressed. The discussion focuses on the caveats of introducing individualist group norms when attempting to reduce intergroup differentiation. Copyright (c) 2006 John Wiley & Sons, Ltd.

Integration of ice-core, marine and terrestrial records for the Australian Last Glacial Maximum and Termination: a contribution from the OZ INTIMATE group

The degree to which Southern Hemisphere climatic changes during the end of the last glacial period and early Holocene (30-8 ka) were influenced or initiated by events occurring in the high latitudes of the Northern Hemisphere is a complex issue. There is conflicting evidence for the degree of hemispheric 'teleconnection' and an unresolved debate as to the principle forcing mechanism(s). The available hypotheses are difficult to test robustly, however, because the few detailed palaeoclimatic records in the Southern Hemisphere are widely dispersed and lack duplication. Here we present climatic and environmental reconstructions from across Australia, a key region of the Southern Hemisphere because of the range of environments it covers and the potentially important role regional atmospheric and oceanic controls play in global climate change. We identify a general scheme of events for the end of the last glacial period and early Holocene but a detailed reconstruction proved problematic. Significant progress in climate quantification and geochronological control is now urgently required to robustly investigate change through this period. Copyright (c) 2006 John Wiley & Sons, Ltd.

Conversation repair and adult cochlear implantation: A qualitative case study

Conversation breakdown and repair has been suggested to be a common site of the disability arising from acquired hearing impairment in adults. This qualitative case study reports on certain consequences of the use of general versus specific conversation repair initiators for the resolution of repair sequences. The 47 repair sequences analysed in this paper arose in a single 20-minute free and unstructured conversation between an adult bilateral cochlear implantee and his wife, audio-recorded in a clinic setting. The repairs analysed in this paper were undertaken in response to either general (n = 18) or specific (n = 29) repair requests. No difference was found in the number of turns taken to resolve repairs in response to general or specific repair requests. Qualitative analysis demonstrated that uttering the repair initiator in the immediate vicinity of the miscommunicated portion of talk provided the primary cue to the conversation partner about the location and the content of what had been misunderstood. These preliminary findings imply a change to rehabilitation counselling offered to familiar communication partners. Copyright © 2006 John Wiley & Sons, Ltd.

Peptide surfactants (Pepfactants) for switchable foams and emulsions

We have developed a series of sustainable peptide surfactants (Pepfactants) capable of stabilizing foams and emulsions in a stimuli-responsive manner, based on the reversible formation of a mechanically strong interfacial film. Under conditions where the interfacially adsorbed peptide forms a mechanically strong film state, foam or emulsion stabilization occurs as a direct result of the film strength. Under conditions where the interfacially adsorbed peptide forms a mobile detergent state, foam or emulsion stabilization is either reduced, or does not occur. Preformed foams or emulsions stabilized by Pepfactants undergo rapid phase coalescence when the film state is converted to the detergent state. Switching between film and detergent states is readily and reversibly achieved by a change in the bulk solution composition, such as a change in pH, or the addition or sequestering of metal ions. Copyright © 2007 Curtin University of Technology and John Wiley & Sons, Ltd.

Intergroup relations in action: questions asked about lesbian, gay and bisexual issues in diversity training

This paper focuses on the questions which heterosexual trainees ask about lesbian, gay and bisexual (LGB) experience within diversity training about LGB issues. Drawing on a data corpus of 162 questions asked by trainees in 13 tape-recorded training sessions, questions were coded into six categories: (1) general understanding questions; (2) questions about the trainer's life, experience and practices; (3) professional practice questions; (4) questions about lesbian and gay related legislation, policies and procedures; (5) questions about specific people and projects and (6) questions about the meanings, derivations and correct use of terms and symbols. Real questions are compared with the decontexualized questions (and answers to them) that are provided in training manuals and it is demonstrated that these questions differ markedly from how questions actually get asked and how they actually get answered. Recommendations are provided for improving training and the argument made for turning towards analyses of the real world in action, especially when considering intergroup relations. Copyright © 2008 John Wiley & Sons, Ltd.

Strategic groups, competitive groups and performance within the U.K. pharmaceutical industry:Improving our understanding of the competitive process

Strategic group research originated in the 1970s and a number of notable studies centered on the U.S. pharmaceutical industry. Results were, however, conflicting. This paper explores the nature of strategic groups in the U.K. pharmaceutical industry. The study confirms the presence of between six and eight strategic groups across the period studied, 1998-2002. The study also demonstrates a statistically significant relationship between these strategic groups and performance using three performance measures. The paper then compares strategic groups with competitive groups and concludes that the distinction is important and may explain the contradictory findings in earlier strategic group research. Copyright © 2007 John Wiley & Sons, Ltd.

Patterns of corporate governance and technical efficiency in Italian manufacturing

The purpose of this paper is to analyse the relationship between the corporate governance system and technical efficiency in Italian manufacturing. We use a non-parametric frontier technique (DEA) to derive technical efficiency measures for a sample of Italian firms taken from nine manufacturing industries. These measures are then related to the characteristics of the corporate governance system. Two of these characteristics turn out to have a positive impact on technical efficiency: the percentage of the company shares owned by the largest shareholder and the fact that a firm belongs to a pyramidal group. Interestingly, a trade-off emerges between these influences, in the sense that one is stronger in industries where the other is weaker. Copyright © 2007 John Wiley & Sons, Ltd.

Validating the organizational climate measure:links to managerial practices, productivity and innovation

This paper describes the development and validation of a multidimensional measure of organizational climate, the Organizational Climate Measure (OCM), based upon Quinn and Rohrbaugh's Competing Values model. A sample of 6869 employees across 55 manufacturing organizations completed the questionnaire. The 17 scales contained within the measure had acceptable levels of reliability and were factorially distinct. Concurrent validity was measured by correlating employees' ratings with managers' and interviewers' descriptions of managerial practices and organizational characteristics. Predictive validity was established using measures of productivity and innovation. The OCM also discriminated effectively between organizations, demonstrating good discriminant validity. The measure offers researchers a relatively comprehensive and flexible approach to the assessment of organizational members' experience and promises applied and theoretical benefits. Copyright © 2005 John Wiley & Sons, Ltd.