Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response

Although the efficacy of methadone maintenance treatment (MMT) in opioid dependence disorder has been well established, the influence of methadone pharmacokinetics in dose requirement and clinical outcome remains controversial. The aim of this study is to analyze methadone dosage in responder and nonresponder patients considering pharmacogenetic and pharmacokinetic factors that may contribute to dosage adequacy. Opioid dependence patients (meeting Diagnostic and Statistical Manual of Mental Disorders, [4th Edition] criteria) from a MMT community program were recruited. Patients were clinically assessed and blood samples were obtained to determine plasma concentrations of (R,S)-, (R) and (S)- methadone and to study allelic variants of genes encoding CYP3A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19, and P-glycoprotein. Responders and nonresponders were defined by illicit opioid consumption detected in random urinalysis. The final sample consisted in 105 opioid dependent patients of Caucasian origin. Responder patients received higher doses of methadone and have been included into treatment for a longer period. No differences were found in terms of genotype frequencies between groups. Only CYP2D6 metabolizing phenotype differences were found in outcome status, methadone dose requirements, and plasma concentrations, being higher in the ultrarapid metabolizers. No other differences were found between phenotype and responder status, methadone dose requirements, neither in methadone plasma concentrations. Pharmacokinetic factors could explain some but not all differences in MMT outcome and methadone dose requirements.

Regional variability in the impact of human capital on regional growth

The first objective of this study is to furnish new evidence concerning the aggregate profitability of the accumulation of human capital. In addition to the traditional measure of the return to human capital, combining the information on its shadow price with the social cost of providing education allows us to confirm the profitability of human capital investments as a tool for promoting economic growth. The possibility of obtaining estimations of these effects for each Spanish region enables us to empirically evaluate the amount of heterogeneity across economies in the effects of human capital. As a second objective, we provide evidence on the indirect effect of human capital in making private capital investment more attractive. Among the main explanations for this process, we observe that higher worker skill levels enable higher returns to be extracted from investment in physical capital.

Dynamic patterns of flow in the workplace: characterizing within-individual variability using a complexity science approach

As a result of the growing interest in studying employee well-being as a complex process that portrays high levels of within-individual variability and evolves over time, this present study considers the experience of flow in the workplace from a nonlinear dynamical systems approach. Our goal is to offer new ways to move the study of employee well-being beyond linear approaches. With nonlinear dynamical systems theory as the backdrop, we conducted a longitudinal study using the experience sampling method and qualitative semi-structured interviews for data collection; 6981 registers of data were collected from a sample of 60 employees. The obtained time series were analyzed using various techniques derived from the nonlinear dynamical systems theory (i.e., recurrence analysis and surrogate data) and multiple correspondence analyses. The results revealed the following: 1) flow in the workplace presents a high degree of within-individual variability; this variability is characterized as chaotic for most of the cases (75%); 2) high levels of flow are associated with chaos; and 3) different dimensions of the flow experience (e.g., merging of action and awareness) as well as individual (e.g., age) and job characteristics (e.g., job tenure) are associated with the emergence of different dynamic patterns (chaotic, linear and random).

Effects of solar activity and climate variability on large floods in Switzerland

The paper presents the variability of major floods in Switzerland for the period 1800-2008 from a summer index (INU). The index is constructed from the damage caused by flooding, with the aim of establishing the possible influence of the solar and climate variability on the major floods. The coincidence of flood-rich periods with those observed in other regions of different climate and fluvial regimes suggests that climate forcings and changes in the general circulation of the atmosphere are those who govern the appearance of these high-frequency temporal clusters.