Constructing optimal designs for fitting pharmacokinetic models

We consider some computational issues that arise when searching for optimal designs for pharmacokinetic (PK) studies. Special factors that distinguish these are (i) repeated observations are taken from each subject and the observations are usually described by a nonlinear mixed model (NLMM), (ii) design criteria depend on the model fitting procedure, (iii) in addition to providing efficient parameter estimates, the design must also permit model checking, (iv) in practice there are several design constraints, (v) the design criteria are computationally expensive to evaluate and often numerical integration is needed and finally (vi) local optimisation procedures may fail to converge or get trapped at local optima.We review current optimal design algorithms and explore the possibility of using global optimisation procedures. We use these latter procedures to find some optimal designs.For multi-purpose designs we suggest two surrogate design criteria for model checking and illustrate their use.     

The social and demographic impact of the Southeast Asian Crisis of 1997–99

When an unexpected financial crisis overtook Southeast Asia in 1997 planners and policymakers feared that the economic difficulties would unwind two decades of remarkable economic and social development. Newspaper headlines spoke of massive increases in poverty, unemployment and malnutrition, and it was speculated that family planning programs would collapse and fertility would rise dramatically. Infant and child mortality and maternal mortality were also expected to increase. This paper briefly reviews the onset of the financial crisis as a background for assessing whether speculations about die demographic and social effects tallied with reality. It is found that these effects were neither as dramatic nor as easy to monitor as some of the public debate implied. The general lesson is that the most serious social and demographic problems were not so much the products of crisis as embedded in chronic weaknesses that had become entrenched in times of economic growth. The crisis exposed these weaknesses.     

Property Loss Estimation for Wind and Earthquake Perils

This article describes the development of a generic loss assessment methodology, which is applicable to earthquake and windstorm perils worldwide. The latest information regarding hazard estimation is first integrated with the parameters that best describe the intensity of the action of both windstorms and earthquakes on building structures, for events with defined average return periods or recurrence intervals. The subsequent evaluation of building vulnerability (damageability) under the action of both earthquake and windstorm loadings utilizes information on damage and loss from past events, along with an assessment of the key building properties (including age and quality of design and construction), to assess information about the ability of buildings to withstand such loadings and hence to assign a building type to the particular risk or portfolio of risks. This predicted damage information is then translated into risk-specific mathematical vulnerability functions, which enable numerical evaluation of the probability of building damage arising at various defined levels. By assigning cost factors to the defined damage levels, the associated computation of total loss at a given level of hazard may be achieved. This developed methodology is universal in the sense that it may be applied successfully to buildings situated in a variety of earthquake and windstorm environments, ranging from very low to extreme levels of hazard. As a loss prediction tool, it enables accurate estimation of losses from potential scenario events linked to defined return periods and, hence, can greatly assist risk assessment and planning.     

Innovation Management as a Post-Modern Phenomenon: The Outsourcing of Pharmaceutical R&D

The institutionalization of R&D by large, modern organizations is regarded as one of the most significant social and economic factors of the twentieth century. In recent years post-modern organizations have begun to replace bureaucratic control with market control. This approach is particularly attractive in the case of R&D employees who have been relatively successful in resisting direct managerial control. Government statistics are used to demonstrate that external R&D increased from 5% to 16% of internal R&D expenditure between 1989 and 1995. This trend is examined in the context of consolidation within the UK pharmaceutical industry, which has considerable implications for the sustainability of high-technology industry in the UK.     

Estimating conditional tail expectation with actuarial applications in view

We develop statistical inferential tools for estimating and comparing conditional tail expectation (CTE) functions, which are of considerable interest in actuarial science. In particular, we construct estimators for the CTE functions, develop the necessary asymptotic theory for the estimators, and then use the theory for constructing confidence intervals and bands for the functions. Both parametric and non-parametric approaches are explored. Simulation studies illustrate the performance of estimators in various situations. Results are obtained under minimal assumptions, and the general Vervaat process plays a crucial role in achieving these goals.     

Experiencing Work: Values, Attitudes, and Moods

This paper describes a model (the VAM model)which integrates three of the most significantdimensions of the work experience, work values,attitudes, and moods, into one overarching framework.The VAM model proposes that a rich and more completeunderstanding of the experience of work necessitates thesimultaneous consideration of work values, attitudes,and moods. After describing how work values, attitudes, and moods, each capture key aspects ofexperiencing work, we discuss three important dimensionsalong which they vary: time, dynamism, and focus. Thesedimensions underscore the need for the simultaneous consideration of values, attitudes, and moodsfor a fuller understanding of the work experience. Wethen describe how work values, attitudes, and moods havethe potential to influence each other. Finally, we discuss the implications of the VAM modelfor understanding important organizational outcomesincluding extra-role behavior, job performance, socialloafing, absenteeism, and turnover.     

The Protestant Ethic: Weber s Model and the Empirical Literature

Empirical research with regard to the Protestantethic is reviewed in relation to Weber s model of thepart a specifically religious ethos played in the riseof capitalism. Weber argued that Western legal and commercial changes were not in themselvesan adequate explanation. Essential also was the set ofvalues emphasized by ascetic Protestantism:self-discipline, hard work, the careful use of time, the reinvestment of one s gains, personal honesty,creative innovation, and faith in the rewards of a justGod. Empirical research has found positive correlationsbetween Protestant ethic values and internal locus of control (self-discipline), hard work,honesty, and belief in a just world. Findings withregard to the use of time and money are inconclusive.The relationship with creative innovation has not been examined. There is a need for empiricalstudy of the relationship between the Protestant ethicand personal religious orientation.     

Low-Income Mothers' Conversations About Emotions and Their Children's Emotional Competence

This study examined the linkage between low-income mothers' conversations about emotions and their children's understanding of emotion. Forty-five low-income preschoolers and their mothers were videotaped while viewing a wordless picture book designed to elicit talk about emotions. Three maternal and child emotional language behaviors were coded from the videotapes: (a) unelaborated comments about emotions; (b) explanations about the causes and consequences of emotions; and (c) empathy-related statements. The children's questions about emotions were also coded. In a separate interview, the preschoolers were administered tasks that assessed emotional expression knowledge, emotional situation knowledge, and emotional role-taking. The results revealed that emotional situation knowledge was positively predicted by mothers' empathy-related statements. Mothers' explanations about the causes and consequences of emotions were uniquely related to emotional role-taking ability. There were very few correlations between the mothers' and children's talk about emotions. Results are discussed in terms of the functional significance of mothers' emotional language for young children's emotional competence.     

Preparing the school-age child for adoption.

The development of an adoptive relationship for children who have been in the limbo of foster care is a continuous process. It is unrealistic to expect these families to live happily ever after. Agencies must begin developing regular services to meet the special needs of the families being created. To a large extent the issues that will have to be worked through relate to the stages of preparation outlined in this paper. Each stage in the child's growth may activate unresolved issues around the grief at the biological parents' rejection, confusion about identity or difficulty in working through problems. Future adoptive home recruitment must take this into account by providing training and other supports to families considering adopting the older child.     

Family-Enterprise Initiatives as a Response to Socioeconomic and Political Change in Eastern and Central Europe

It is argued that family business enterprises can be an adaptive response to the transformations that recently have characterized Eastern and Central Europe. Family-centered initiatives are important for sustainable socioeconomic development. In this article, a family-enterprise incubator scheme for the stimulation of family and socioeconomic development is discussed. This approach incorporates resources, services, and supports beyond those conventionally offered.