Physiologically-based toxicokinetic (PBTK) models are widely used to quantify whole-body kinetics of various substances. However, since they attempt to reproduce anatomical structures and physiological events, they have a high number of parameters. Their identification from kinetic data alone is often impossible, and other information about the parameters is needed to render the model identifiable. The most commonly used approach consists of independently measuring, or taking from literature sources, some of the parameters, fixing them in the kinetic model, and then performing model identification on a reduced number of less certain parameters. This results in a substantial reduction of the degrees of freedom of the model. In this study, we show that this method results in final estimates of the free parameters whose precision is overestimated. We then compared this approach with an empirical Bayes approach, which takes into account not only the mean value, but also the error associated with the independently determined parameters. Blood and breath 2H8-toluene washout curves, obtained in 17 subjects, were analyzed with a previously presented PBTK model suitable for person-specific dosimetry. Model parameters with the greatest effect on predicted levels were alveolar ventilation rate QPC, fat tissue fraction VFC, blood-air partition coefficient Kb, fraction of cardiac output to fat Qa/co and rate of extrahepatic metabolism Vmax-p. Differences in the measured and Bayesian-fitted values of QPC, VFC and Kb were significant (p < 0.05), and the precision of the fitted values Vmax-p and Qa/co went from 11 ± 5% to 75 ± 170% (NS) and from 8 ± 2% to 9 ± 2% (p < 0.05) respectively. The empirical Bayes approach did not result in less reliable parameter estimates: rather, it pointed out that the precision of parameter estimates can be overly optimistic when other parameters in the model, either directly measured or taken from literature sources, are treated as known without error. In conclusion, an empirical Bayes approach to parameter estimation resulted in a better model fit, different final parameter estimates, and more realistic parameter precisions. 相似文献
This article introduces the Children’s Scales of Pleasure and Arousal as instruments to enable children to provide judgments of emotions they witness or experience along the major dimensions of affect. In two studies (Study 1: N = 160, 3–11 years and adults; Study 2: N = 280, 3–5 years and adults), participants used the scales to indicate the levels of pleasure or arousal they perceived in stylized drawings of facial expressions, in photographs of facial expressions, or in emotion labels. All age groups used the Pleasure Scale reliably and accurately with all three types of stimuli. All used the Arousal Scale with stylized faces and with facial expressions, but only 5-year-olds did so for emotion labels. 相似文献
While decades of academic research have consistently demonstrated a positive relationship between high school employment and adult earnings, the literature is empirically silent in regards to why this association exists. This study uses data from the National Longitudinal Survey of Youth 1997 (NLSY97) to examine the hypothesis that high school employment develops “marketable skills” in the form of occupation-specific human capital. By analyzing wage variation attributable to the commonality of skill portfolios across respondents’ high school and adult (age 20 and 23) occupations, this study fails to find consistent evidence that the types of skills utilized in high school employment are correlated with adult earnings. Within the framework of the human capital model, this would suggest that the positive, post-school economic gains of in-school work are largely attributable to increases in general human capital (e.g., workplace socialization, character building). 相似文献
In what ways might research on adolescence contribute to social justice? My 2014 Presidential Address identified strategies for social justice in our field. First, we need research that is conscious of biases, power, and privilege in science, as well as in our roles as scholars. Second, we need research that attends to inequities in lives of adolescents, and as scholars we need to question the ways that our research may unwittingly reinforce those inequalities. Third, we need research that attends to urgencies, that is, issues or conditions that influence adolescents’ well‐being which demand attention and action. I draw from a range of concepts and theoretical perspectives to make the case for a framework of social justice in research on adolescence. 相似文献
This study sought to understand the various roles music played for gay men who were members of the San Francisco Gay Men's Chorus, the world's first gay men's chorus. Specifically, it answers the following questions: What is the demographic profile of the chorus members? How has the chorus shaped or reflected social issues; how has the chorus shaped or reflected political issues; how has the music evolved over time?; How was the chorus impacted by the HIV/AIDS epidemic? Historical information for this study was gathered through eight interviews of original and long-time choral members as well as the current artistic director. Interviews were conducted in San Francisco at the San Francisco Gay Men's Chorus office, and additional data were derived from programs of previous choral concerts, two questionnaires (Internalized Homophobia Scale and Gay Chorus Questionnaire), and observations of choral rehearsals and concerts. As a follow-up to a previous study documenting the formation of the chorus in 1978-1982, this study historically documents the chorus's evolution from 1983 through 2003, emphasizing the chorus's impact on social and political issues, the musicality of the chorus, and the impact of HIV/AIDS on the chorus. 相似文献
Following an unprecedented boom, since 2008 Ireland has experienced a severe economic and labour market crisis. Considerable debate persists as to where the heaviest burden of the recession has fallen. Conventional measures of relative income poverty and inequality have a limited capacity to capture the impact of the recession in terms of social exclusion. This is exacerbated by a dramatic increase in the scale of debt problems including significant negative equity issues. Our analysis provides no evidence for individualization or class polarization of risk. Instead, while economic stress level is highly stratified in class terms in both boom and bust periods, the changing impact of class is highly contingent on life course stage. An income based classification showed that the affluent income class saw its advantage relative to the income poor class decline at the earliest stage of the life-course and remain stable across the rest of the life course. At the other end of the hierarchy, the income poor class experienced a relative improvement in their situation in the earlier life-course phase and no significant change at the later stages. For the remaining income classes, life-course stage was even more important. At the earliest stage the precarious class experienced some improvement in its situation while the outcomes for the middle classes remain unchanged. In the mid-life course the precarious and lower middle classes experienced disproportionate increases in their stress levels while at the later stage it is the combined middle classes that lost out. Additional effects over time relating to social class are restricted to the deteriorating situation of the petit bourgeoisie at the middle stage of the life-course. The pattern is clearly a good deal more complex than that suggested by conventional notions of ‘middle class squeeze’ and points to the distinctive challenges relating to welfare and taxation policy faced by governments in the Great Recession. 相似文献
This paper reports interest levels associated with twenty-three different phrasings of a request to leave a gift to charity in a will among 9964 survey respondents. Previous research suggests that a review of one’s life story may be an important component of bequest decision-making. Other findings suggest that mortality reminders may increase support for social norms and the pursuit of symbolic immortality. The attempts to reference symbolic immortality tested here were not effective. However, results supported avoiding extraneous death terms (“that will take effect at my death”) and using social norms (“many people like to leave a gift to charity in their wills”). The strongest support arose for the addition of the phrase “to support causes that have been important in their/your life/lives” to explain either the respondent’s or the social norm exemplars’ intent in making such a gift. Among common terms, “a gift to charity in your will” generated greater interest than substitute terms such as “bequest,” “leave a legacy” or “remember your favorite charities.”