Charlatan philosopher and wise enchantress: Seduction and authority in eighteenth-century French discourses on happiness

In late 1757 Rousseau wrote a series of moral letters on happiness to Mme Sophie d'Houdetot. He distinguished himself and his teaching from the empty babble and hypocrisy prevalent in 'the century of philosophy and reason'. Philosophers were charlatans peddling happiness. This paper shows how Rousseau's critique of philosophy reworks the standard image of charlatans in the public square. It highlights a questioning and a gendering of reason implicit in the issue of credentials for teaching happiness. Against the dubious authority of the philosopher, Rousseau casts Sophie as the wise enchantress whose gentle influence inspires her tutor. He places moral authority outside the public square in a private, feminine domain. Rousseau's ideal woman cannot be a tainted charlatan like him. Yet the very opposition puts her in her place. (Author abstract)

Product performance and specification in new product development

This paper deals with product performance and specification in new product development. There are many different definitions of performance and specification in the literature. These are reviewed and a new classification scheme for product performance is proposed. The link between performance and specification is discussed in detail using a new model for the new product development process. The new model involves two stages, with each containing three main phases, and is useful for making decisions with regards to product performance and specification.

Standardising bull breeding soundness evaluations and reporting in Australia

There is substantial variation in bull breeding soundness evaluation procedures and reports in Australia; the situation is compounded by difficulties in interpretation and the validity of many reports. In an effort to overcome this, the scientific literature was reviewed [Fordyce G. In: Fordyce G, editor. Bull fertility: selection and management in Australia. Eight Mile Plains, Australia: Australian Cattle Vets; 2002] and the needs of stakeholders were considered in preparing a manual, Evaluating and Reporting Bull Fertility [Entwistle KW, Fordyce G. Evaluating and reporting bull fertility. Eight Mile Plains, Australia: Australian Cattle Vets; 2003.] that outlined standards for assessing and reporting bull breeding soundness. A new recording and reporting system, called Bull Reporter, is based on standards from this manual and groups bull fertility traits into five summary categories: Scrotum, Physical, Crush-side Semen, Sperm Morphology, and Serving. The client will generally select which categories they wish to have included in the evaluation to suit their specific purposes. While there is adequate room for comments, the veterinarian is not required to make an overall judgment of whether the bull has normal capacity to sire calves under natural mating management, but ensures the standards for each selected category are met. Professional, standardised, easy-to-read reports are produced either electronically [Entwistle KW, Fordyce G. Evaluating and reporting bull fertility. Eight Mile Plains, Australia: Australian Cattle Vets; 2003.] or manually. A bull owner or their agent signs the certificate to affirm that bulls have not undergone procedures to rectify faults which may have otherwise caused them to fail the standards. An accreditation system for assessing sperm morphology was established because of its demonstrated relationship with pregnancy rates and because of the difficulties in achieving consistent and accurate assessments among laboratories. It is considered that Bull Reporter is applicable to beef and dairy bulls across all levels of management, genotypes and environments throughout Australia, with substantial potential for application elsewhere in the world. Crown Copyright (c) 2006 Published by Elsevier Inc. All rights reserved.

A systematic review of successes and failures in home telehealth: preliminary results

We conducted a systematic review of the literature to identify studies in home telehealth that compared a home telehealth intervention with a non-telehealth standard/usual care alternative in terms of administrative changes, patient management decisions, patient outcomes, caregiver outcomes, economic impact or social impact on patients. A search of various databases produced 6643 references. Of these 769 papers were selected for more detailed investigation. These papers, combined with hand searching of relevant telehealth journals and cross-referencing of citations in identified publications, resulted in 138 papers referring to 130 projects for review. In this preliminary analysis we used a quality appraisal approach that took into account the study design. An additional analysis of patient numbers was then used to calculate a net evidence score. A large proportion of studies (80%) were randomised controlled trials. Only 22 projects (17%) reported economic data deemed to be sufficient for appraisal. Evidence exists for the clinical effectiveness of home telehealth in diabetes, the general area of mental health, high risk pregnancy monitoring, heart failure and cardiac disease.

Fixed wages and bonuses in agency contracts: the case of a continuous state space

In this paper, we extend the state-contingent production approach to principal–agent problems to the case where the state space is an atomless continuum. The approach is modelled on the treatment of optimal tax problems. The central observation is that, under reasonable conditions, the optimal contract may involve a fixed wage with a bonus for above-normal performance. This is analogous to the phenomenon of "bunching" at the bottom in the optimal tax literature.

A D-optimal designed population pharmacokinetic study of itraconazole capsules and solution in adults with cystic fibrosis

Background: Oral itraconazole (ITRA) is used for the treatment of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis (CF) because of its antifungal activity against Aspergillus species. ITRA has an active hydroxy-metabolite (OH-ITRA) which has similar antifungal activity. ITRA is a highly lipophilic drug which is available in two different oral formulations, a capsule and an oral solution. It is reported that the oral solution has a 60% higher relative bioavailability. The influence of altered gastric physiology associated with CF on the pharmacokinetics (PK) of ITRA and its metabolite has not been previously evaluated. Objectives: 1) To estimate the population (pop) PK parameters for ITRA and its active metabolite OH-ITRA including relative bioavailability of the parent after administration of the parent by both capsule and solution and 2) to assess the performance of the optimal design. Methods: The study was a cross-over design in which 30 patients received the capsule on the first occasion and 3 days later the solution formulation. The design was constrained to have a maximum of 4 blood samples per occasion for estimation of the popPK of both ITRA and OH-ITRA. The sampling times for the population model were optimized previously using POPT v.2.0.[1] POPT is a series of applications that run under MATLAB and provide an evaluation of the information matrix for a nonlinear mixed effects model given a particular design. In addition it can be used to optimize the design based on evaluation of the determinant of the information matrix. The model details for the design were based on prior information obtained from the literature, which suggested that ITRA may have either linear or non-linear elimination. The optimal sampling times were evaluated to provide information for both competing models for the parent and metabolite and for both capsule and solution simultaneously. Blood samples were assayed by validated HPLC.[2] PopPK modelling was performed using FOCE with interaction under NONMEM, version 5 (level 1.1; GloboMax LLC, Hanover, MD, USA). The PK of ITRA and OH‑ITRA was modelled simultaneously using ADVAN 5. Subsequently three methods were assessed for modelling concentrations less than the LOD (limit of detection). These methods (corresponding to methods 5, 6 & 4 from Beal[3], respectively) were (a) where all values less than LOD were assigned to half of LOD, (b) where the closest missing value that is less than LOD was assigned to half the LOD and all previous (if during absorption) or subsequent (if during elimination) missing samples were deleted, and (c) where the contribution of the expectation of each missing concentration to the likelihood is estimated. The LOD was 0.04 mg/L. The final model evaluation was performed via bootstrap with re-sampling and a visual predictive check. The optimal design and the sampling windows of the study were evaluated for execution errors and for agreement between the observed and predicted standard errors. Dosing regimens were simulated for the capsules and the oral solution to assess their ability to achieve ITRA target trough concentration (Cmin,ss of 0.5-2 mg/L) or a combined Cmin,ss for ITRA and OH-ITRA above 1.5mg/L. Results and Discussion: A total of 241 blood samples were collected and analysed, 94% of them were taken within the defined optimal sampling windows, of which 31% where taken within 5 min of the exact optimal times. Forty six per cent of the ITRA values and 28% of the OH-ITRA values were below LOD. The entire profile after administration of the capsule for five patients was below LOD and therefore the data from this occasion was omitted from estimation. A 2-compartment model with 1st order absorption and elimination best described ITRA PK, with 1st order metabolism of the parent to OH-ITRA. For ITRA the clearance (ClItra/F) was 31.5 L/h; apparent volumes of central and peripheral compartments were 56.7 L and 2090 L, respectively. Absorption rate constants for capsule (kacap) and solution (kasol) were 0.0315 h-1 and 0.125 h-1, respectively. Comparative bioavailability of the capsule was 0.82. There was no evidence of nonlinearity in the popPK of ITRA. No screened covariate significantly improved the fit to the data. The results of the parameter estimates from the final model were comparable between the different methods for accounting for missing data, (M4,5,6)[3] and provided similar parameter estimates. The prospective application of an optimal design was found to be successful. Due to the sampling windows, most of the samples could be collected within the daily hospital routine, but still at times that were near optimal for estimating the popPK parameters. The final model was one of the potential competing models considered in the original design. The asymptotic standard errors provided by NONMEM for the final model and empirical values from bootstrap were similar in magnitude to those predicted from the Fisher Information matrix associated with the D-optimal design. Simulations from the final model showed that the current dosing regimen of 200 mg twice daily (bd) would provide a target Cmin,ss (0.5-2 mg/L) for only 35% of patients when administered as the solution and 31% when administered as capsules. The optimal dosing schedule was 500mg bd for both formulations. The target success for this dosing regimen was 87% for the solution with an NNT=4 compared to capsules. This means, for every 4 patients treated with the solution one additional patient will achieve a target success compared to capsule but at an additional cost of AUD $220 per day. The therapeutic target however is still doubtful and potential risks of these dosing schedules need to be assessed on an individual basis. Conclusion: A model was developed which described the popPK of ITRA and its main active metabolite OH-ITRA in adult CF after administration of both capsule and solution. The relative bioavailability of ITRA from the capsule was 82% that of the solution, but considerably more variable. To incorporate missing data, using the simple Beal method 5 (using half LOD for all samples below LOD) provided comparable results to the more complex but theoretically better Beal method 4 (integration method). The optimal sparse design performed well for estimation of model parameters and provided a good fit to the data.

Comparing the conditions for small business and entrepreneurship in Sweden and Australia: Lessons for the European Charter for Small Enterprises

A growing body of literature is concerned with explaining cross-national performance of small business and entrepreneurs in advanced economies. This literature has considered a range of policy and institutional variables which create an environment supportive of small firms and entrepreneurial activities including macroeconomic variables such as taxation, labour market regulation, social security and income policy; regulatory factors such as establishment legislation, bankruptcy policy, administrative burdens, compliance costs, deregulation and competition policy; and cultural factors such as social and cultural norms that support entrepreneurship. However, this literature has not always distinguished between the policy environment of small firms operating in different industry sectors. The purpose of this paper is to examine the institutional and policy environment of small firms in knowledge intensive sectors. The characteristics of the business environment of particular relevance to knowledge intensive firms are somewhat different from the conditions for entrepreneurship and small business success more generally. This paper compares the science, technology and industry infrastructure of Australia, Denmark, Sweden with other OECD countries. The purpose of the paper is to identify cross-national differences in the business environment of small knowledge intensive firms. The paper seeks to explore whether particular institutional environments appear to be more supportive of small firms in knowledge intensive sectors.