Estimation of Metabolic Rate Constants in PBPK‐Models from Liver Slice Experiments: What Are the Experimental Needs?

A mechanistic model is presented describing the clearance of a compound in a precision-cut liver slice that is incubated in a culture medium. The problem of estimating metabolic rate constants in PBPK models from liver slice experiments is discussed using identifiability analysis. From the identifiability problem analysis, it appears that in addition to the clearance, the compound's free fraction in the slice and the diffusion rate of the exchange of the compound between culture medium and liver slice should be identified. In addition, knowledge of the culture medium volume, the slice volume, the compound's free fraction, and octanol-water-based partition between medium and slice is presupposed. The formal solution for identification is discussed from the perspective of experimental practice. A formally necessary condition for identification is the sampling of parent compound in liver slice or culture medium. However, due to experimental limitations and errors, sampling the parent compound in the slice together with additional sampling of metabolite pooled from the medium and the slice is required for identification in practice. Moreover, it appears that identification results are unreliable when the value of the intrinsic clearance exceeds the value of the diffusion coefficient, a condition to be verified a posteriori.     

A screening system for tardive dyskinesia: development and implementation.

1. Most diagnosed cases of tardive dyskinesia (TD) are mildly inconvenient to the patient, but some can be severe or life-threatening. The primary goal of intervention should be early identification of abnormal movements related to TD and the prescribing of an appropriate medication regimen. 2. Unless specific training occurs and a specific monitoring system is in place, TD movements may be missed. However, not all movements are necessarily related to TD. 3. Although screening and monitoring are valuable, nothing is more important than prevention. New medications must be developed that do not carry the risk of TD, and other approaches to treat TD must be developed.     

The analysis of incomplete data using stochastic covariates

In the development of many diseases there are often associated random variables which continuously reflect the progress of a subject towards the final expression of the disease (failure). At any given time these processes, which we call stochastic covariates, may provide information about the current hazard and the remaining time to failure. Likewise, in situations when the specific times of key prior events are not known, such as the time of onset of an occult tumour or the time of infection with HIV-1, it may be possible to identify a stochastic covariate which reveals, indirectly, when the event of interest occurred. The analysis of carcinogenicity trials which involve occult tumours is usually based on the time of death or sacrifice and an indicator of tumour presence for each animal in the experiment. However, the size of an occult tumour observed at the endpoint represents data concerning tumour development which may convey additional information concerning both the tumour incidence rate and the rate of death to which tumour-bearing animals are subject. We develop a stochastic model for tumour growth and suggest different ways in which the effect of this growth on the hazard of failure might be modelled. Using a combined model for tumour growth and additive competing risks of death, we show that if this tumour size information is used, assumptions concerning tumour lethality, the context of observation or multiple sacrifice times are no longer necessary in order to estimate the tumour incidence rate. Parametric estimation based on the method of maximum likelihood is outlined and is applied to simulated data from the combined model. The results of this limited study confirm that use of the stochastic covariate tumour size results in more precise estimation of the incidence rate for occult tumours.     

HIV-infected woman. Illness cognition assessment.

1. Special attention is particularly important in addressing the mental health needs of HIV-infected women. These needs may involve issues such as concerns about present or future pregnancy; child-rearing, often as single parents; poverty, illicit drug use or addiction; and the potential lack of support services. 2. Diagnosis of HIV infection in women may be overlooked, as the clinical signs that routinely trigger the suspicion of HIV illness in men are often interpreted to reflect depression or psychological factors, such as stress or overwork, rather than raise the suspicion of HIV infection in women. 3. Understanding a woman's illness cognition is an important component of designing strategies that can enhance coping. The picture a woman generates regarding her illness is a composite of her experiences and responses, and determines to a large extent what she will do in response to her illness.     

It takes two to tango: the integration of people with disabilities into society

The concept of integration is not well defined. It not known how people with disabilities experience integration. In this study qualitative methods were used. The aim of the article is to define a model of successful integration based on the perspectives of people with disabilities and people within their social environment. Integration consists of five elements: functioning ordinarily without receiving special attention, mixing with others that are not disabled, taking part in society, trying to realize one’s potential and directing one’s own life. Integration is obtained through a process of interaction between a person with a disability and society. This process is influenced by personal, societal and support factors. The individual with a disability and society have a mutual responsibility with respect to integration.     

The poverty of social control: explaining power in the historical sociology of the welfare state

The concept ‘social control’ has been criticised from a variety of quarters in recent years, particularly by historians and historical sociologists. However, it remains in common usage in sociological studies of welfare, deviance and social control. This paper shows, first, how this reliance on the concept of social control is rooted in a wider-ranging argument in social and political theory concerning the liberal-democratic fusion between the state and civil society, and that the lack of resolution of this argument is the foundation of the persistence of the concept social control in other areas of social inquiry, despite its repeated ‘falsification’. Second, the paper highlights the main arguments against the use of ‘social control’ in explaining social order, in particular the misunderstanding of class, culture and power which its use encourages, and the paper will conclude with a discussion of alternative ways of conceptualising the operation of power in contemporary societies.     

African American Migration to the North: New Evidence for the 1910s

The years between 1910 and 1920 witnessed the first wave of the "Great Migration" of African Americans to the North. This article uses new census data from the Integrated Public Use Microdata Series project to study self‐selection patterns in African American migration during this important decade. The results indicate that, contrary to contemporary accounts, migration rates rose at least as much among the literate as among the illiterate (and perhaps more), and migration increased more for married African Americans than for the unmarried.     

Bilingual Education Models in Latvia: A view from Belarus

In this article, we look at several issues relating to bilingual education in Latvia, as prescribed by the Latvian Ministry of Education and Science. We examine these issues from the perspective of the past and present situation in Belarus, Russia and the former Soviet Union. It is clear, in our view, that bilingual offers both advantages, but also various drawbacks if it is not implemented in an appropriate way. This applies to both the societal and the personal (cognitive level). Movement towards the dominant languages (in this case Latvian) needs to be viewed as a gradual process. Although each generation of newcomers might start with a passive knowledge of the dominant (second) language, this changes into a fluent grasp of the second language across generations. The original native language will lose its dominance in this process.