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This paper contributes to empirical knowledge of citizen participation as a communicative event, by analyzing discursive tensions in interviews between civil servants and citizen-parents, that are part of a participatory process on how to mitigate violence in a suburban area in Sweden. Citizen participation events are increasingly initiated by public institutions in Western societies. Research, however, shows that goals of participatory processes often conflict with formal decision-making structures and institutional boundaries. Yet, how such tensions play out on the level of interaction is little researched. This study therefore analyzes discursive practices deployed by civil servants and how these construct characteristic tensions for the interviews. Three practices are identified: (1) pursuing the initial question, (2) cueing an institutional frame, and (3) epistemic positioning of the parents. These practices, being guided by an institutional agenda, create tensions both to the parents' lifeworld and for the ideals of the participatory method itself. [ABSTRACT FROM AUTHOR]

Local authorities in western societies increasingly initiate public participation processes despite criticism of these methods. To understand this development calls for in-depth studies of how the goals and values of public participation are articulated in practice. This paper analyzes the discursive legitimation strategies deployed by civil servants in twelve planning meetings for a participatory process aimed at mitigating violence in a Swedish suburb. The study draws on previous research on discursive legitimation, and presents the context-specific strategies of authorization, de-legitimation, cosmology and addressing of values. The analysis highlights that a core discursive tension in this practice arises from its need to seek mandate in the municipal structure, while the value discourses used to legitimize public participation build on a break from traditional bureaucracy. The study contributes to the broader literature on discursive legitimation in contemporary political contexts, with detailed empirical accounts of how a disputed practice is legitimized in interaction. [ABSTRACT FROM AUTHOR]

Background: Artemisinin-based combinations currently recommended for treatment of uncomplicated Plasmodium falciparum malaria in many countries of sub-Saharan Africa are substrates of CYP enzymes. The cytochrome enzyme system is responsible for metabolism of about 80-90% of clinically used drugs. It is, therefore, important to obtain the pharmacogenetics of the population in the region with respect to these combinations and thereby enable practitioners to predict treatment outcomes. The aim of this study was to detect and determine allelic frequencies of CYP2C8*2, CYP2C8*3, CYP3A4*1B, CYP3A5*3 and CYP2B6*6 variant alleles in a Tanzanian indigenous population. Methods: Genomic DNA extraction from blood obtained from 256 participants who escorted patients at Karume Health Centre in Mwanza Tanzania, was carried out using the Gene JET™ Genomic DNA purification kit (Thermo Scientific). Genotyping for the cytochrome P450 variant alleles was performed using predesigned primers. Amplification was done by PCR while differentiation between alleles was done by restriction fragment length polymorphism (PCR-RFLP) (for CYP2C8*2, CYP2C8*3) and sequencing (for CYP2B6*6, CYP3A5*3 and CYP3A4*1B). Results: CYP2C8*2, CYP2C8*3, CYP3A5*3, CYP3A4*1B and CYP2B6*6 variant allelic frequencies were found to be 19,10,16,78 and 36% respectively. Conclusion: Prevalence of CYP2C8*2, CYP3A5*3, CYP3A4*1B and CYP2B6*6 mutations in a Tanzanian population/ subjects are common. The impact of these point mutations on the metabolism of anti-malarial drugs, particularly artemisinin-based combinations, and their potential drug-drug interactions (DDIs) needs to be further evaluated. [ABSTRACT FROM AUTHOR]

Thyroid hormone (TH) deficiency during development causes severe and permanent neuronal damage, but the primary insult at the tissue level has remained unsolved. We have defined locomotor deficiencies in mice caused by a mutant thyroid hormone receptor α1 (TRα1) with potent aporeceptor activity attributable to reduced affinity to TH. This allowed identification of distinct functions that required either maternal supply of TH during early embryonic development or sufficient innate levels of hormone during late fetal development. In both instances, continued exposure to high levels of TH after birth and throughout life was needed. The hormonal dependencies correlated with severely delayed appearance of parvalbumin-immunoreactive GABAergic interneurons and increased numbers of calretinin-immunoreactive cells in the neocortex. This resulted in reduced numbers of fast spiking interneurons and defects in cortical network activity. The identification of locomotor deficiencies caused by insufficient supply of TH during fetal/perinatal development and their correlation with subtype-specific interneurons suggest a previously unknown basis for the neuronal consequences of endemic cretinism and untreated congenital hypothyroidism, and specifies TRα1 as the receptor isoform mediating these effects. [ABSTRACT FROM AUTHOR]

Abstract: The profound effects of thyroid hormone (TH) on heart development and function are mediated by the thyroid hormone receptors (TR) α1 and β1. While numerous patients with TRβ1 mutations have been identified, patients with similar mutations in TRα1 are yet to be discovered. Recently generated heterozygous mice with a dominant negative mutation in TRα1 (TRα1+/m mice) have normal TH levels, which may have hampered the discovery of patients with such mutations. We now measure intracellular Ca2+ and contraction in cardiomyocytes isolated from TRα1+/m mice and wildtype littermates (WT). TRα1+/m cardiomyocytes showed a phenotype similar to that in hypothyroidism with significant slowing of voltage-activated Ca2+ transients and contractions. Increased stimulation frequency (from 0.5 to 3 Hz) or β-adrenergic stimulation reduced the differences between TRα1+/m and WT cardiomyocytes. However, in TRα1+/m cells stimulation at 3 Hz gave a marked increase in diastolic Ca2+ and β-adrenergic stimulation triggered spontaneous Ca2+ release events during relaxation. Both TRα1+/m and WT cardiomyocytes responded to TH treatment by displaying a “hyperthyroid” phenotype with faster and larger Ca2+ transients and contractions. Excised TRα1+/m hearts showed an increased expression of phospholamban (PLB). In conclusion, isolated TRα1+/m cardiomyocytes display major dysfunctions with marked slowing of the Ca2+ transients and contractions. [Copyright &y& Elsevier]